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We observed stronger tilt aftereffects in PSZ compared to HC, but no difference in negative afterimages. Stronger tilt aftereffects were related to more severe negative symptoms. These data suggest oversensitivity to recent regularities, in the form of stronger visual adaptation, at cortical, but not subcortical, levels in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).Based on the structures of isoxaflutole (IFT) and N-isobutyl-N-(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (i.e., a multitarget drug design strategy). A total of 27 N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides were prepared from 5-cyclopropylisoxazole-4-carboxylic acid and substituted benzylamines, and their structures were confirmed by NMR and MS. Laboratory bioassays indicated that I-26 showed 100% inhibition against Portulaca oleracea and Abutilon theophrasti at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds). A strong growth inhibition was observed, but a typical bleaching phenomenon of IFT could not be observed in the Petri dish assay. I-05 displayed excellent postemergence herbicidal activity against Echinochloa crusgalli and A. theophrasti at a rate of 150 g/ha, and bleaching symptoms were observed in the leaves of treated weeds. The bleaching effect of Chlamydomonas reinhardtii treated by I-05 could be reversed by adding homogentisate. Enzymatic bioassays indicated that I-05 could not inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, but II-05, an isoxazole ring-opening product of I-05, could inhibit HPPD activity with an EC50 value of 1.05 μM, similar to that of mesotrione (with an EC50 value of 1.35 μM). Detailed discussion about observed herbicidal symptoms is provided in the Results and Discussion section. This investigation provided a proof-of-concept foundation that a multitarget drug design strategy could be applied in agrochemical research.An efficient [3 + 2] cycloaddition of in situ generated nitrile imines with enamides has been established. https://www.selleckchem.com/screening/kinase-inhibitor-library.html A wide range of functionalized pyrazoline derivatives (53 examples) were obtained in moderate to good yields (up to 96%) under very mild conditions. This protocol features broad substrate scope, good functional group tolerance, and operational simplicity. Practical transformation of the products into useful pyrazoles via a one-pot process and the scalability of this protocol highlight the utility of this synthetic methodology.Transition-metal dichalcogenide heterostructures are an emergent platform for novel many-body states from exciton condensates to nanolasers. However, their exciton dynamics are difficult to disentangle due to multiple competing processes with time scales varying over many orders of magnitude. Using a configurable nano-optical cavity based on a plasmonic scanning probe tip, the radiative (rad) and nonradiative (nrad) relaxation of intra- and interlayer excitons is controlled. Tuning their relative rates in a WSe2/MoSe2 heterobilayer over 6 orders of magnitude in tip-enhanced photoluminescence spectroscopy reveals a cavity-induced crossover from nonradiative quenching to Purcell-enhanced radiation. Rate equation modeling with the interlayer charge transfer time as a reference clock allows for a comprehensive determination from the long interlayer exciton (IX) radiative lifetime τIXrad = (94 ± 27) ns to the 5 orders of magnitude faster competing nonradiative lifetime τIXnrad = (0.6 ± 0.2) ps. This approach of nanocavity clock spectroscopy is generally applicable to a wide range of excitonic systems with competing decay pathways.One of the major applications of generative models for drug discovery targets the lead-optimization phase. During the optimization of a lead series, it is common to have scaffold constraints imposed on the structure of the molecules designed. Without enforcing such constraints, the probability of generating molecules with the required scaffold is extremely low and hinders the practicality of generative models for de novo drug design. To tackle this issue, we introduce a new algorithm, named SAMOA (Scaffold Constrained Molecular Generation), to perform scaffold-constrained in silico molecular design. We build on the well-known SMILES-based Recurrent Neural Network (RNN) generative model, with a modified sampling procedure to achieve scaffold-constrained generation. We directly benefit from the associated reinforcement learning methods, allowing to design molecules optimized for different properties while exploring only the relevant chemical space. We showcase the method's ability to perform scaffold-constrained generation on various tasks designing novel molecules around scaffolds extracted from SureChEMBL chemical series, generating novel active molecules on the Dopamine Receptor D2 (DRD2) target, and finally, designing predicted actives on the MMP-12 series, an industrial lead-optimization project.Inorganic nanomaterials are often depicted as rigid structures whose shape is permanent. However, forces that are ordinarily considered weak can exert sufficient stress at the nanoscale to drive mechanical deformation. Here, we leverage van der Waals (VdW) interactions to mechanically reshape inorganic nanostructures from planar to curvilinear. Modified plate deformation theory shows that high-aspect-ratio two-dimensional particles can be plastically deformed via VdW forces. Informed by this finding, silver nanoplates were deformed over spherical iron oxide template particles, resulting in distinctive bend contour patterns in bright-field (BF) transmission electron microscopy (TEM) images. High-resolution TEM images of deformed areas reveal the presence of highly strained bonds in the material. Finally, we show that the distance between two nearby template particles allows for the engineering of several distinct curvilinear morphologies. This work challenges the traditional view of nanoparticles as static objects and introduces methods for postsynthetic mechanical shape control.
We observed stronger tilt aftereffects in PSZ compared to HC, but no difference in negative afterimages. Stronger tilt aftereffects were related to more severe negative symptoms. These data suggest oversensitivity to recent regularities, in the form of stronger visual adaptation, at cortical, but not subcortical, levels in schizophrenia. (PsycInfo Database Record (c) 2021 APA, all rights reserved).Based on the structures of isoxaflutole (IFT) and N-isobutyl-N-(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (i.e., a multitarget drug design strategy). A total of 27 N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides were prepared from 5-cyclopropylisoxazole-4-carboxylic acid and substituted benzylamines, and their structures were confirmed by NMR and MS. Laboratory bioassays indicated that I-26 showed 100% inhibition against Portulaca oleracea and Abutilon theophrasti at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds). A strong growth inhibition was observed, but a typical bleaching phenomenon of IFT could not be observed in the Petri dish assay. I-05 displayed excellent postemergence herbicidal activity against Echinochloa crusgalli and A. theophrasti at a rate of 150 g/ha, and bleaching symptoms were observed in the leaves of treated weeds. The bleaching effect of Chlamydomonas reinhardtii treated by I-05 could be reversed by adding homogentisate. Enzymatic bioassays indicated that I-05 could not inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, but II-05, an isoxazole ring-opening product of I-05, could inhibit HPPD activity with an EC50 value of 1.05 μM, similar to that of mesotrione (with an EC50 value of 1.35 μM). Detailed discussion about observed herbicidal symptoms is provided in the Results and Discussion section. This investigation provided a proof-of-concept foundation that a multitarget drug design strategy could be applied in agrochemical research.An efficient [3 + 2] cycloaddition of in situ generated nitrile imines with enamides has been established. https://www.selleckchem.com/screening/kinase-inhibitor-library.html A wide range of functionalized pyrazoline derivatives (53 examples) were obtained in moderate to good yields (up to 96%) under very mild conditions. This protocol features broad substrate scope, good functional group tolerance, and operational simplicity. Practical transformation of the products into useful pyrazoles via a one-pot process and the scalability of this protocol highlight the utility of this synthetic methodology.Transition-metal dichalcogenide heterostructures are an emergent platform for novel many-body states from exciton condensates to nanolasers. However, their exciton dynamics are difficult to disentangle due to multiple competing processes with time scales varying over many orders of magnitude. Using a configurable nano-optical cavity based on a plasmonic scanning probe tip, the radiative (rad) and nonradiative (nrad) relaxation of intra- and interlayer excitons is controlled. Tuning their relative rates in a WSe2/MoSe2 heterobilayer over 6 orders of magnitude in tip-enhanced photoluminescence spectroscopy reveals a cavity-induced crossover from nonradiative quenching to Purcell-enhanced radiation. Rate equation modeling with the interlayer charge transfer time as a reference clock allows for a comprehensive determination from the long interlayer exciton (IX) radiative lifetime τIXrad = (94 ± 27) ns to the 5 orders of magnitude faster competing nonradiative lifetime τIXnrad = (0.6 ± 0.2) ps. This approach of nanocavity clock spectroscopy is generally applicable to a wide range of excitonic systems with competing decay pathways.One of the major applications of generative models for drug discovery targets the lead-optimization phase. During the optimization of a lead series, it is common to have scaffold constraints imposed on the structure of the molecules designed. Without enforcing such constraints, the probability of generating molecules with the required scaffold is extremely low and hinders the practicality of generative models for de novo drug design. To tackle this issue, we introduce a new algorithm, named SAMOA (Scaffold Constrained Molecular Generation), to perform scaffold-constrained in silico molecular design. We build on the well-known SMILES-based Recurrent Neural Network (RNN) generative model, with a modified sampling procedure to achieve scaffold-constrained generation. We directly benefit from the associated reinforcement learning methods, allowing to design molecules optimized for different properties while exploring only the relevant chemical space. We showcase the method's ability to perform scaffold-constrained generation on various tasks designing novel molecules around scaffolds extracted from SureChEMBL chemical series, generating novel active molecules on the Dopamine Receptor D2 (DRD2) target, and finally, designing predicted actives on the MMP-12 series, an industrial lead-optimization project.Inorganic nanomaterials are often depicted as rigid structures whose shape is permanent. However, forces that are ordinarily considered weak can exert sufficient stress at the nanoscale to drive mechanical deformation. Here, we leverage van der Waals (VdW) interactions to mechanically reshape inorganic nanostructures from planar to curvilinear. Modified plate deformation theory shows that high-aspect-ratio two-dimensional particles can be plastically deformed via VdW forces. Informed by this finding, silver nanoplates were deformed over spherical iron oxide template particles, resulting in distinctive bend contour patterns in bright-field (BF) transmission electron microscopy (TEM) images. High-resolution TEM images of deformed areas reveal the presence of highly strained bonds in the material. Finally, we show that the distance between two nearby template particles allows for the engineering of several distinct curvilinear morphologies. This work challenges the traditional view of nanoparticles as static objects and introduces methods for postsynthetic mechanical shape control.0 Commenti 0 condivisioni 6 Views 0 AnteprimaEffettua l'accesso per mettere mi piace, condividere e commentare! -
Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19.
To identify predictors of superinfections in COVID-19.
Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections.
Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfectiond immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.Thyrolipoma and thymolipoma are rare neoplasms of the thyroid gland and thymus, respectively. Their simultaneous occurrence is exceptional. Up to now, only 2 cases have been reported in literature in 1966 and in 1997. For the first time, we report the occurrence of both neoplasms associated with myasthenia gravis in a 64-year-old woman. The value of this case report lies not only in the fact that it allows us to speculate on the presence of a syndrome but also because a complete radiological work-up (computed tomography scanner, magnetic resonance imaging, Positron emission tomography (PET) with fluorodeoxyglucose (FDG)) is reported.
Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93 1265-1270) is the most used score.
We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients.
The 8- and the 28-sites scores were highly inter-related (Spearman's ρ = 0.93, P < 0.001), and their concordance index was fairly good (k = 0.79, 95% confidence interval 0.74-0.84). https://www.selleckchem.com/products/BMS-790052.html During a mean follow-up of 3 years, 112 patients died, and 129 experienced a CV event. At univariate and multivariate analysis, both scores were associated with mortality (P ≤ 0.01) and CV events (P ≤ 0. be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and tion of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.
Numerous studies have shown the association between eosinophilia and clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). But the evidences are lack of consensus.
The aim of this meta-analysis was to conduct a pooled analysis of outcome comparing eosinophilic (EOS) AECOPD and non-EOS AECOPD patients.
We included PubMed, EMBASE, Web of Science, and Cochrane databases up to 2020 to retrieve articles. Randomized controlled trials and quasi-experimental studies about patients with and without EOS AECOPD in terms of in-hospital mortality, length of hospital stay, comorbidities, forced expiratory volume in 1 s (FEV1), gender, and BMI were included preclinical studies, review articles, editorials, commentaries, conference abstracts, and book chapters were excluded. The methodologic assessment of studies was performed with the Newcastle-Ottawa Scale and Cochran scale. Comprehensive Rev Man 5 was used for the statistical analysis.
Twenty-one studies with 18,041 patients fulfilled the inclusion criteria and were used in this meta-analysis.
Bacterial and fungal superinfections may complicate the course of hospitalized patients with COVID-19. To identify predictors of superinfections in COVID-19. Prospective, observational study including patients with COVID-19 consecutively admitted to the University Hospital of Pisa, Italy, between 4 March and 30 April 2020. Clinical data and outcomes were registered. Superinfection was defined as a bacterial or fungal infection that occurred ≥48 h after hospital admission. A multivariate analysis was performed to identify factors independently associated with superinfections. Overall, 315 patients with COVID-19 were hospitalized and 109 episodes of superinfections were documented in 69 (21.9%) patients. The median time from admission to superinfection was 19 days (range 11-29.75). Superinfections were caused by Enterobacterales (44.9%), non-fermenting Gram-negative bacilli (15.6%), Gram-positive bacteria (15.6%) and fungi (5.5%). Polymicrobial infections accounted for 18.3%. Predictors of superinfectiond immunomodulant drugs should be carefully selected. Infection control rules must be reinforced.Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.Thyrolipoma and thymolipoma are rare neoplasms of the thyroid gland and thymus, respectively. Their simultaneous occurrence is exceptional. Up to now, only 2 cases have been reported in literature in 1966 and in 1997. For the first time, we report the occurrence of both neoplasms associated with myasthenia gravis in a 64-year-old woman. The value of this case report lies not only in the fact that it allows us to speculate on the presence of a syndrome but also because a complete radiological work-up (computed tomography scanner, magnetic resonance imaging, Positron emission tomography (PET) with fluorodeoxyglucose (FDG)) is reported. Lung ultrasound (US) reliably estimates lung water and it is increasingly applied in clinical practice in dialysis patients. A semi-quantitative US score summing up the US-B lines (an equivalent of B lines in the standard chest X-ray) at 28 sites in the intercostal spaces (Jambrik et al. Usefulness of ultrasound lung comets as a non-radiologic sign of extravascular lung water. Am J Cardiol 2004; 93 1265-1270) is the most used score. We compared the prognostic performance for death, and cardiovascular (CV) events of the 28-sites US score with a score restricted to eight sites in a cohort of 303 haemodialysis (HD) patients. The 8- and the 28-sites scores were highly inter-related (Spearman's ρ = 0.93, P < 0.001), and their concordance index was fairly good (k = 0.79, 95% confidence interval 0.74-0.84). https://www.selleckchem.com/products/BMS-790052.html During a mean follow-up of 3 years, 112 patients died, and 129 experienced a CV event. At univariate and multivariate analysis, both scores were associated with mortality (P ≤ 0.01) and CV events (P ≤ 0. be completed just in ∼3 min, the 8-sites score requires only ∼1.30 min, and it is, therefore, better suited for application in everyday clinical practice in HD units.Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and tion of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges. Numerous studies have shown the association between eosinophilia and clinical outcomes of patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). But the evidences are lack of consensus. The aim of this meta-analysis was to conduct a pooled analysis of outcome comparing eosinophilic (EOS) AECOPD and non-EOS AECOPD patients. We included PubMed, EMBASE, Web of Science, and Cochrane databases up to 2020 to retrieve articles. Randomized controlled trials and quasi-experimental studies about patients with and without EOS AECOPD in terms of in-hospital mortality, length of hospital stay, comorbidities, forced expiratory volume in 1 s (FEV1), gender, and BMI were included preclinical studies, review articles, editorials, commentaries, conference abstracts, and book chapters were excluded. The methodologic assessment of studies was performed with the Newcastle-Ottawa Scale and Cochran scale. Comprehensive Rev Man 5 was used for the statistical analysis. Twenty-one studies with 18,041 patients fulfilled the inclusion criteria and were used in this meta-analysis.0 Commenti 0 condivisioni 1 Views 0 Anteprima -
Wafer-level probing of photonic integrated circuits is key to reliable process control and efficient performance assessment in advanced production workflows. In recent years, optical probing of surface-coupled devices such as vertical-cavity lasers, top-illuminated photodiodes, or silicon photonic circuits with surface-emitting grating couplers has seen great progress. In contrast to that, wafer-level probing of edge-emitting devices with hard-to-access vertical facets at the sidewalls of deep-etched dicing trenches still represents a major challenge. In this paper, we address this challenge by introducing a novel concept of optical probes based on 3D-printed freeform coupling elements that fit into deep-etched dicing trenches on the wafer surface. Exploiting the design freedom and the precision of two-photon laser lithography, the coupling elements can be adapted to a wide variety of mode-field sizes. We experimentally demonstrate the viability of the approach by coupling light to edge-emitting waveguides on different integration platforms such as silicon photonics (SiP), silicon nitride (TriPleX), and indium phosphide (InP). Achieving losses down to 1.9 dB per coupling interface, we believe that 3D-printed coupling elements represent a key step towards highly reproducible wafer-level testing of edge-coupled photonic integrated circuits.A limiting factor in organic solar cells (OSCs) is the incomplete absorption in the thin absorber layer. One concept to enhance absorption is to apply an optical cavity design. In this study, the performance of an OSC with cavity is evaluated. By means of a comprehensive energy yield (EY) model, the improvement is demonstrated by applying realistic sky irradiance, covering a wide range of incidence angles. https://www.selleckchem.com/products/molidustat-(bay85-3934).html The relative enhancement in EY for different locations is found to be 11-14% compared to the reference device with an indium tin oxide front electrode. The study highlights the improved angular light absorption as well as the angular robustness of an OSC with cavity.Subwavelength grating (SWG) waveguides have been shown to provide enhanced light-matter interaction resulting in superior sensitivity in integrated photonics sensors. Narrowband integrated optical filters can be made by combining SWG waveguides with evanescently coupled Bragg gratings. In this paper, we assess the sensing capabilities of this novel filtering component with rigorous electromagnetic simulations. Our design is optimized for an operating wavelength of 1310 nm to benefit from lower water absorption and achieve narrower bandwidths than at the conventional wavelength of 1550 nm. Results show that the sensor achieves a sensitivity of 507 nm/RIU and a quality factor of 4.9 × 104, over a large dynamic range circumventing the free spectral range limit of conventional devices. Furthermore, the intrinsic limit of detection, 5.1 × 10-5 RIU constitutes a 10-fold enhancement compared to state-of-the-art resonant waveguide sensors.Polarization aberrations exist in almost all astronomical telescopes. Polarization aberrations would bring about asymmetric apodization in the exit pupil, leading to asymmetric PSFs. The shape of PSFs is critical to telescopes that are used to detect weak gravitational lensing (WGL) in the universe. In this paper, polarization aberrations and their connections with PSF ellipticity in an unobscured off-axis space telescope are analyzed. Together with the Jones pupil, cumulative diattenuation and retardance maps of the telescope are obtained via polarization ray tracing. Due to asymmetric apodization caused by polarization aberrations, the ellipticities of all four PSF components are found to be greater than zero. The PSF ellipticity of the telescope over the full FOV is obtained. Results show that polarization aberrations change PSF ellipticity in different degrees at different FOVs. The maximum variance of PSF ellipticity induced by polarization aberrations is 7.5e-3 and the average value is 2.7e-3. In addition, interpolation errors of PSF ellipticity would also be affected by polarization aberrations. It is found that there are 405 FOV points (about 4% of all FOV points involved in the calculations) whose variances of interpolation errors caused by polarization aberrations are greater than 1.4e-4. According to the results shown in this paper, polarization aberrations of telescopes play a significant role in WGL measurements.Multifocal structured illumination microscopy (MSIM) can rapidly retrieve 3D structures of thick samples by using multi-spot excitation and detection. Although numerous super-resolution (SR) and optical sectioning (OS) methods have been introduced in this field, the existing OS-SR method in MSIM still has the difficulty in rejecting deep defocused light, which may lead to strong background signal in the retrieved results. To this end, an enhanced OS-SR method is proposed to simultaneously achieve the desired OS capability and significant resolution improvement in MSIM. The enhanced OS-SR image is obtained by combining the standard deviation image with the conventional OS-SR image in the frequency domain. The validity of the proposed method is demonstrated by simulation and experimental results.In this work, a new recognition method of orbital angular momentum (OAM) is proposed. The method combines mode recognition and the wavefront sensor-less (WFS-less) adaptive optics (AO) by utilizing a jointly trained convolutional neural network (CNN) with the shared model backbone. The CNN-based AO method is implicitly applied in the system by providing additional mode information in the offline training process and accordingly the system structure is rather concise with no extra AO components needed. The numerical simulation result shows that the proposed method can improve the recognition accuracy significantly in different conditions of turbulence and can achieve similar performance compared with AO-combined methods.We propose a scheme of high-speed physical key distribution based on dispersion-shift-keying chaos synchronization in two semiconductor lasers without external feedback (response lasers), which are driven by a common external-cavity semiconductor laser (drive laser). In this scheme, the dispersion introduces a laser field beating-induced nonlinear transformation to the outputs of drive laser and renders the correlation elimination between the drive and response lasers improving the security of key distribution. Moreover, the commonly driven lasers without external feedback constitute an open-loop synchronization configuration and yield a short synchronization recovery time of a subnanosecond supporting the implementation of high-speed key distribution. With these two merits, we numerically demonstrate a 1.2 Gb/s secure key distribution with a bit error ratio below 3.8×10-3.
Wafer-level probing of photonic integrated circuits is key to reliable process control and efficient performance assessment in advanced production workflows. In recent years, optical probing of surface-coupled devices such as vertical-cavity lasers, top-illuminated photodiodes, or silicon photonic circuits with surface-emitting grating couplers has seen great progress. In contrast to that, wafer-level probing of edge-emitting devices with hard-to-access vertical facets at the sidewalls of deep-etched dicing trenches still represents a major challenge. In this paper, we address this challenge by introducing a novel concept of optical probes based on 3D-printed freeform coupling elements that fit into deep-etched dicing trenches on the wafer surface. Exploiting the design freedom and the precision of two-photon laser lithography, the coupling elements can be adapted to a wide variety of mode-field sizes. We experimentally demonstrate the viability of the approach by coupling light to edge-emitting waveguides on different integration platforms such as silicon photonics (SiP), silicon nitride (TriPleX), and indium phosphide (InP). Achieving losses down to 1.9 dB per coupling interface, we believe that 3D-printed coupling elements represent a key step towards highly reproducible wafer-level testing of edge-coupled photonic integrated circuits.A limiting factor in organic solar cells (OSCs) is the incomplete absorption in the thin absorber layer. One concept to enhance absorption is to apply an optical cavity design. In this study, the performance of an OSC with cavity is evaluated. By means of a comprehensive energy yield (EY) model, the improvement is demonstrated by applying realistic sky irradiance, covering a wide range of incidence angles. https://www.selleckchem.com/products/molidustat-(bay85-3934).html The relative enhancement in EY for different locations is found to be 11-14% compared to the reference device with an indium tin oxide front electrode. The study highlights the improved angular light absorption as well as the angular robustness of an OSC with cavity.Subwavelength grating (SWG) waveguides have been shown to provide enhanced light-matter interaction resulting in superior sensitivity in integrated photonics sensors. Narrowband integrated optical filters can be made by combining SWG waveguides with evanescently coupled Bragg gratings. In this paper, we assess the sensing capabilities of this novel filtering component with rigorous electromagnetic simulations. Our design is optimized for an operating wavelength of 1310 nm to benefit from lower water absorption and achieve narrower bandwidths than at the conventional wavelength of 1550 nm. Results show that the sensor achieves a sensitivity of 507 nm/RIU and a quality factor of 4.9 × 104, over a large dynamic range circumventing the free spectral range limit of conventional devices. Furthermore, the intrinsic limit of detection, 5.1 × 10-5 RIU constitutes a 10-fold enhancement compared to state-of-the-art resonant waveguide sensors.Polarization aberrations exist in almost all astronomical telescopes. Polarization aberrations would bring about asymmetric apodization in the exit pupil, leading to asymmetric PSFs. The shape of PSFs is critical to telescopes that are used to detect weak gravitational lensing (WGL) in the universe. In this paper, polarization aberrations and their connections with PSF ellipticity in an unobscured off-axis space telescope are analyzed. Together with the Jones pupil, cumulative diattenuation and retardance maps of the telescope are obtained via polarization ray tracing. Due to asymmetric apodization caused by polarization aberrations, the ellipticities of all four PSF components are found to be greater than zero. The PSF ellipticity of the telescope over the full FOV is obtained. Results show that polarization aberrations change PSF ellipticity in different degrees at different FOVs. The maximum variance of PSF ellipticity induced by polarization aberrations is 7.5e-3 and the average value is 2.7e-3. In addition, interpolation errors of PSF ellipticity would also be affected by polarization aberrations. It is found that there are 405 FOV points (about 4% of all FOV points involved in the calculations) whose variances of interpolation errors caused by polarization aberrations are greater than 1.4e-4. According to the results shown in this paper, polarization aberrations of telescopes play a significant role in WGL measurements.Multifocal structured illumination microscopy (MSIM) can rapidly retrieve 3D structures of thick samples by using multi-spot excitation and detection. Although numerous super-resolution (SR) and optical sectioning (OS) methods have been introduced in this field, the existing OS-SR method in MSIM still has the difficulty in rejecting deep defocused light, which may lead to strong background signal in the retrieved results. To this end, an enhanced OS-SR method is proposed to simultaneously achieve the desired OS capability and significant resolution improvement in MSIM. The enhanced OS-SR image is obtained by combining the standard deviation image with the conventional OS-SR image in the frequency domain. The validity of the proposed method is demonstrated by simulation and experimental results.In this work, a new recognition method of orbital angular momentum (OAM) is proposed. The method combines mode recognition and the wavefront sensor-less (WFS-less) adaptive optics (AO) by utilizing a jointly trained convolutional neural network (CNN) with the shared model backbone. The CNN-based AO method is implicitly applied in the system by providing additional mode information in the offline training process and accordingly the system structure is rather concise with no extra AO components needed. The numerical simulation result shows that the proposed method can improve the recognition accuracy significantly in different conditions of turbulence and can achieve similar performance compared with AO-combined methods.We propose a scheme of high-speed physical key distribution based on dispersion-shift-keying chaos synchronization in two semiconductor lasers without external feedback (response lasers), which are driven by a common external-cavity semiconductor laser (drive laser). In this scheme, the dispersion introduces a laser field beating-induced nonlinear transformation to the outputs of drive laser and renders the correlation elimination between the drive and response lasers improving the security of key distribution. Moreover, the commonly driven lasers without external feedback constitute an open-loop synchronization configuration and yield a short synchronization recovery time of a subnanosecond supporting the implementation of high-speed key distribution. With these two merits, we numerically demonstrate a 1.2 Gb/s secure key distribution with a bit error ratio below 3.8×10-3.0 Commenti 0 condivisioni 1 Views 0 Anteprima -
Disrupting the canonical TGFβ-pathway in Smad2;3ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3ScxCre/Alk6null) recapitulated many features of the Smad4ScxCre contracture phenotype, suggesting that joint contracture in Smad4ScxCre mutants is caused by disruption of BMP signaling. Overall, these results establish a model of murine postnatal joint contracture and a role for BMP signaling in tendon elongation and extracellular matrix accumulation.
Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI.
A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n= 170), an internal test cohort (ITC, n= 73), and an external test cohort (ETC, n= 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).
EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy .770 vs .755, P= .355; sensitivity .792 vs .767, P= .183; specificity .745 vs .742, P= .931) but better than the junior endoscopists (accuracy .770 vs .728, P< .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P< .05).
EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.
EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.Congenital aniridia is caused by heterozygous mutations in the PAX6 gene. In this disease, congenital iris and foveal hypoplasia is associated with juvenile onset cataract, glaucoma, and corneal keratopathy. In rodents, Pax6 mutations result in a congenital reduction in ocular size that is not typically described in human aniridia. Here, the ocular morphometry of aniridia patients is compared with the lens phenotype of Pax6+/tm1/Pgr **** to reveal whether there are species differences in Pax6 regulation of lens development and homeostasis. Ultrasound biometry (UBM) revealed that eleven percent of aniridia patients exhibited mild microphthalmia while the anterior chamber depth of aniridic eyes was significantly reduced from 6 months of age onward. Although aniridic lens thickness was normal from birth, it was significantly decreased in aniridic lenses older than 30. Notably, 86% of aniridic lenses exhibited cataractous changes in this cohort. In addition, a significant proportion of aniridia patients develop lens subluxation as they age associated with reduced lens diameter as measured by anterior segment optical coherence tomography (AS-OCT). Analysis of young adult Pax6+/tm1/Pgr mouse lenses by micro-computed tomography (microCT), bright field and dark field imaging revealed that they are reduced in size but did not exhibit overt cataracts at this age. Overall, this study reveals that congenital microphthalmia as assessed by axial length, or microphakia, as assessed by lens thickness, are not typical in human aniridia, although these are primary manifestations of Pax6 mutations in ****, suggesting that PAX6 regulates some aspects of lens development differently between these species.
We aimed to determine the mean glucose thresholds to increase the risk of left ventricular diastolic dysfunction (LVDD) and whether visit-to-visit variability of fasting plasma glucose (FPG) and glycated hemoglobin (A1C) could independently increase the risk in a cohort with serial echocardiography.
This was a 3.5-year (range, 0.5-8.3) retrospective longitudinal cohort study of 3025 adults (age, 55.15 ± 7.6 years; without diabetes, n = 2755) with LV ejection fraction > 50% by serial echocardiography between 2006 and 2016. Mean, standard of deviation (SD) and coefficient of variation (CV) of FPG and A1C obtained from three consecutive measurements preceding the first echocardiography. The definition of LVDD in this study was primarily based on early peak mitral inflow velocity and early diastolic mitral annulus motion velocity.
LVDD developed in 611/3025 subjects (20.2%). https://www.selleckchem.com/products/ldc195943-imt1.html Cox proportional hazard models showed increased adjusted hazard ratios (HRs) for incident LVDD in the highest quartile of FPG-mean (HR 1.76, 95% confidence interval [CI]; 1.36-2.30), FPG-SD (HR 1.63, 95% CI; 1.27-2.09), FPG-CV (HR 1.47, 95% CI; 1.15-1.89), and A1C-mean (HR 1.83, 95% CI; 1.41-2.38) versus the lowest quartile, which was consistent even in subjects without diabetes. Mean glucose thresholds for the increased risk were below the lower limits for pre-diabetes.
In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD.
In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD.Amyloid precursor protein (APP) is a transmembrane precursor protein that is widely expressed in the central nervous system and peripheral tissues in the liver and pancreas, adipose tissue, and myotubes. APP can be cleaved by proteases in two different ways to produce a variety of short peptides, each with different physiological properties and functions. APP peptides generated by non-amyloidogenic processing can positively influence metabolism, while the peptides produced by amyloidogenic processing have the opposite effects. Here, we summarize the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues. In addition, abnormal expression and function of APP and APP-derived peptides are associated with metabolic diseases, such as type 2 diabetes, obesity, non-alcoholic fatty liver disease, and cardiovascular disease, and cancers. Pharmacological intervention of APP function or reduction of the production of peptides derived from amyloidogenic processing may be effective strategies for the prevention and treatment of Alzheimer's disease, and they may also provide new guidance for the treatment of metabolic diseases.
Disrupting the canonical TGFβ-pathway in Smad2;3ScxCre mutants did not result in joint contractures. Conversely, disrupting the BMP pathway by targeting BMP receptors (Alk3ScxCre/Alk6null) recapitulated many features of the Smad4ScxCre contracture phenotype, suggesting that joint contracture in Smad4ScxCre mutants is caused by disruption of BMP signaling. Overall, these results establish a model of murine postnatal joint contracture and a role for BMP signaling in tendon elongation and extracellular matrix accumulation. Narrow-band imaging with magnifying endoscopy (ME-NBI) has shown advantages in the diagnosis of early gastric cancer (EGC). However, proficiency in diagnostic algorithms requires substantial expertise and experience. In this study, we aimed to develop a computer-aided diagnostic model for EGM (EGCM) to analyze and assist in the diagnosis of EGC under ME-NBI. A total of 1777 ME-NBI images from 295 cases were collected from 3 centers. These cases were randomly divided into a training cohort (n= 170), an internal test cohort (ITC, n= 73), and an external test cohort (ETC, n= 52). EGCM based on VGG-19 architecture (Visual Geometry Group [VGG], Oxford University, Oxford, UK) with a single fully connected 2-classification layer was developed through fine-tuning and validated on all cohorts. Furthermore, we compared the model with 8 endoscopists with varying experience. Primary comparison measures included accuracy, area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). EGCM acquired AUCs of .808 in the ITC and .813 in the ETC. Moreover, EGCM achieved similar predictive performance as the senior endoscopists (accuracy .770 vs .755, P= .355; sensitivity .792 vs .767, P= .183; specificity .745 vs .742, P= .931) but better than the junior endoscopists (accuracy .770 vs .728, P< .05). After referring to the results of EGCM, the average diagnostic ability of the endoscopists was significantly improved in terms of accuracy, sensitivity, PPV, and NPV (P< .05). EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists. EGCM exhibited comparable performance with senior endoscopists in the diagnosis of EGC and showed the potential value in aiding and improving the diagnosis of EGC by endoscopists.Congenital aniridia is caused by heterozygous mutations in the PAX6 gene. In this disease, congenital iris and foveal hypoplasia is associated with juvenile onset cataract, glaucoma, and corneal keratopathy. In rodents, Pax6 mutations result in a congenital reduction in ocular size that is not typically described in human aniridia. Here, the ocular morphometry of aniridia patients is compared with the lens phenotype of Pax6+/tm1/Pgr mice to reveal whether there are species differences in Pax6 regulation of lens development and homeostasis. Ultrasound biometry (UBM) revealed that eleven percent of aniridia patients exhibited mild microphthalmia while the anterior chamber depth of aniridic eyes was significantly reduced from 6 months of age onward. Although aniridic lens thickness was normal from birth, it was significantly decreased in aniridic lenses older than 30. Notably, 86% of aniridic lenses exhibited cataractous changes in this cohort. In addition, a significant proportion of aniridia patients develop lens subluxation as they age associated with reduced lens diameter as measured by anterior segment optical coherence tomography (AS-OCT). Analysis of young adult Pax6+/tm1/Pgr mouse lenses by micro-computed tomography (microCT), bright field and dark field imaging revealed that they are reduced in size but did not exhibit overt cataracts at this age. Overall, this study reveals that congenital microphthalmia as assessed by axial length, or microphakia, as assessed by lens thickness, are not typical in human aniridia, although these are primary manifestations of Pax6 mutations in mice, suggesting that PAX6 regulates some aspects of lens development differently between these species. We aimed to determine the mean glucose thresholds to increase the risk of left ventricular diastolic dysfunction (LVDD) and whether visit-to-visit variability of fasting plasma glucose (FPG) and glycated hemoglobin (A1C) could independently increase the risk in a cohort with serial echocardiography. This was a 3.5-year (range, 0.5-8.3) retrospective longitudinal cohort study of 3025 adults (age, 55.15 ± 7.6 years; without diabetes, n = 2755) with LV ejection fraction > 50% by serial echocardiography between 2006 and 2016. Mean, standard of deviation (SD) and coefficient of variation (CV) of FPG and A1C obtained from three consecutive measurements preceding the first echocardiography. The definition of LVDD in this study was primarily based on early peak mitral inflow velocity and early diastolic mitral annulus motion velocity. LVDD developed in 611/3025 subjects (20.2%). https://www.selleckchem.com/products/ldc195943-imt1.html Cox proportional hazard models showed increased adjusted hazard ratios (HRs) for incident LVDD in the highest quartile of FPG-mean (HR 1.76, 95% confidence interval [CI]; 1.36-2.30), FPG-SD (HR 1.63, 95% CI; 1.27-2.09), FPG-CV (HR 1.47, 95% CI; 1.15-1.89), and A1C-mean (HR 1.83, 95% CI; 1.41-2.38) versus the lowest quartile, which was consistent even in subjects without diabetes. Mean glucose thresholds for the increased risk were below the lower limits for pre-diabetes. In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD. In terms of mean glycemia, LVDD may be initiated in the earliest diabetic continuum, and such changes could be measurable within several years. Visit-to-visit variability of FPG, but not that of A1C, predicted accelerated development of LVDD.Amyloid precursor protein (APP) is a transmembrane precursor protein that is widely expressed in the central nervous system and peripheral tissues in the liver and pancreas, adipose tissue, and myotubes. APP can be cleaved by proteases in two different ways to produce a variety of short peptides, each with different physiological properties and functions. APP peptides generated by non-amyloidogenic processing can positively influence metabolism, while the peptides produced by amyloidogenic processing have the opposite effects. Here, we summarize the regulatory effects of APP and its cleavage peptides on metabolism in the central nervous system and peripheral tissues. In addition, abnormal expression and function of APP and APP-derived peptides are associated with metabolic diseases, such as type 2 diabetes, obesity, non-alcoholic fatty liver disease, and cardiovascular disease, and cancers. Pharmacological intervention of APP function or reduction of the production of peptides derived from amyloidogenic processing may be effective strategies for the prevention and treatment of Alzheimer's disease, and they may also provide new guidance for the treatment of metabolic diseases.0 Commenti 0 condivisioni 5 Views 0 Anteprima -
https//github.com/dDipankar/DeepPTM.
https//github.com/dDipankar/DeepPTM.Mapping protein-protein interactions at a proteome scale is critical to understanding how cellular signaling networks respond to stimuli. Since eukaryotic genomes encode thousands of proteins, testing their interactions one-by-one is a challenging prospect. High-throughput yeast-two hybrid (Y2H) assays that employ next-generation sequencing to interrogate complementary DNA (cDNA) libraries represent an alternative approach that optimizes scale, cost and effort. We present NGPINT, a robust and scalable software to identify all putative interactors of a protein using Y2H in batch culture. NGPINT combines diverse tools to align sequence reads to target genomes, reconstruct prey fragments and compute gene enrichment under reporter selection. Central to this pipeline is the identification of fusion reads containing sequences derived from both the Y2H expression plasmid and the cDNA of interest. To reduce false positives, these fusion reads are evaluated as to whether the cDNA fragment forms an in-frame translational fusion with the Y2H transcription factor. NGPINT successfully recognized 95% of interactions in simulated test runs. As proof of concept, NGPINT was tested using published data sets and it recognized all validated interactions. NGPINT can process interaction data from any biosystem with an available genome or transcriptome reference, thus facilitating the discovery of protein-protein interactions in model and non-model organisms.
The forskolin-induced swelling (FIS) assay has become the preferential assay to predict the efficacy of approved and investigational CFTR-modulating drugs for individuals with cystic fibrosis (CF). https://www.selleckchem.com/products/en460.html Currently, no standardized quantification method of FIS data exists thereby hampering inter-laboratory reproducibility.
We developed a complete open-source workflow for standardized high-content analysis of CFTR function measurements in intestinal organoids using raw microscopy images as input. The workflow includes tools for (i) file and metadata handling; (ii) image quantification and (iii) statistical analysis. Our workflow reproduced results generated by published proprietary analysis protocols and enables standardized CFTR function measurements in CF organoids.
All workflow components are open-source and freely available the htmrenamer R package for file handling https//github.com/hmbotelho/htmrenamer; CellProfiler and ImageJ analysis scripts/pipelines https//github.com/hmbotelho/FIS_image_analysis; the Organoid Analyst application for statistical analysis https//github.com/hmbotelho/organoid_analyst; detailed usage instructions and a demonstration dataset https//github.com/hmbotelho/FIS_analysis. Distributed under GPL v3.0.
Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online.
Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online.
To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings.
The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests.
Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category.
Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.
Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders.
The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience.
Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute).
Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as **** as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients.
Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.
Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.
https//github.com/dDipankar/DeepPTM. https//github.com/dDipankar/DeepPTM.Mapping protein-protein interactions at a proteome scale is critical to understanding how cellular signaling networks respond to stimuli. Since eukaryotic genomes encode thousands of proteins, testing their interactions one-by-one is a challenging prospect. High-throughput yeast-two hybrid (Y2H) assays that employ next-generation sequencing to interrogate complementary DNA (cDNA) libraries represent an alternative approach that optimizes scale, cost and effort. We present NGPINT, a robust and scalable software to identify all putative interactors of a protein using Y2H in batch culture. NGPINT combines diverse tools to align sequence reads to target genomes, reconstruct prey fragments and compute gene enrichment under reporter selection. Central to this pipeline is the identification of fusion reads containing sequences derived from both the Y2H expression plasmid and the cDNA of interest. To reduce false positives, these fusion reads are evaluated as to whether the cDNA fragment forms an in-frame translational fusion with the Y2H transcription factor. NGPINT successfully recognized 95% of interactions in simulated test runs. As proof of concept, NGPINT was tested using published data sets and it recognized all validated interactions. NGPINT can process interaction data from any biosystem with an available genome or transcriptome reference, thus facilitating the discovery of protein-protein interactions in model and non-model organisms. The forskolin-induced swelling (FIS) assay has become the preferential assay to predict the efficacy of approved and investigational CFTR-modulating drugs for individuals with cystic fibrosis (CF). https://www.selleckchem.com/products/en460.html Currently, no standardized quantification method of FIS data exists thereby hampering inter-laboratory reproducibility. We developed a complete open-source workflow for standardized high-content analysis of CFTR function measurements in intestinal organoids using raw microscopy images as input. The workflow includes tools for (i) file and metadata handling; (ii) image quantification and (iii) statistical analysis. Our workflow reproduced results generated by published proprietary analysis protocols and enables standardized CFTR function measurements in CF organoids. All workflow components are open-source and freely available the htmrenamer R package for file handling https//github.com/hmbotelho/htmrenamer; CellProfiler and ImageJ analysis scripts/pipelines https//github.com/hmbotelho/FIS_image_analysis; the Organoid Analyst application for statistical analysis https//github.com/hmbotelho/organoid_analyst; detailed usage instructions and a demonstration dataset https//github.com/hmbotelho/FIS_analysis. Distributed under GPL v3.0. Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online. Supplementary information and a stepwise guide for software installation and data analysis for training purposes are available at Bioinformatics online. To summarize cases submitted to the 2019 Society for Hematopathology/European Association for Haematopathology Workshop under the category of myeloid/lymphoid neoplasms with eosinophilia and PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 rearrangements, focusing on recent updates and relevant practice findings. The cases were summarized according to their respective gene rearrangement to illustrate the spectrum of clinical, laboratory, and histopathology manifestations and to explore the appropriate molecular genetic tests. Disease presentations were heterogeneous, including myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDSs), MDS/MPN, acute myeloid leukemia, acute B- or T-lymphoblastic lymphoma/acute lymphoblastic lymphoma (ALL/LBL), or mixed-lineage neoplasms. Frequent extramedullary involvement occurred. Eosinophilia was common but not invariably present. With the advancement of RNA sequencing, cryptic rearrangements were recognized in genes other than PDGFRA. Additional somatic mutations were more frequent in the FGFR1-rearranged cases. Cases with B-ALL presentations differed from Philadelphia-like B-ALL by the presence of an underlying MPN. Cases with FLT3 and ABL1 rearrangements could be potential candidates for future inclusion in this category. Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders. Accurate diagnosis and classification of this category of myeloid/lymphoid neoplasms has important therapeutic implications. With the large number of submitted cases, we expand our understanding of these rare neoplasms and improve our ability to diagnose these genetically defined disorders. The aim of this multisite quality improvement study was to evaluate patients' experiences with the patient-centered pathology (PCP) consultation program and to determine whether PCP enhanced their care experience. Patients were invited to attend PCP consultations to review their pathology report and slides and have their questions answered by the pathologist privately, with the option to attend the appointment with family members or friends for support. A patient experience questionnaire (PEQ) was administered to patients, who participated voluntarily in the PCP, and survey data were collected and stored in REDCap. Statistical analysis was performed using SAS 9.4 (SAS Institute). Sixty-seven patients (95.5% female) aged 18 to 84 years across 4 institutions completed the PEQ. Overall, 58% and 15.8% of patients had breast and brain tumors, respectively, and 59.7% of tumors were newly diagnosed. Most patients thought it was important for them to learn as much as they could about their health condition. However, the majority of patients reported some degree of difficulty learning about their health condition based on written information, despite 97% having completed high school and/or further education. The majority of patients rated their pathologist as "excellent" across communication metrics. Ultimately, 100% of respondents were satisfied, found their visits to be useful, and would recommend the PCP to other patients. Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically. Patients found that personalized clinical encounters with pathologists improved their understanding of their health condition and their satisfaction with their care experience. Patients thought pathologists communicated respectfully, effectively, and empathetically.0 Commenti 0 condivisioni 1 Views 0 Anteprima -
The popularity of E-Cigarettes is increasing. Besides addiction and pulmonary health damage, reports of burn injuries from e-cigarette explosions are also increasing. Mostly, explosions of e-cigarettes are attributed to its lithium-ion battery. Due to increasing cases and missing guidelines we want to present three cases of our hospital and publish recommendations for the management of burn injuries caused by e-cigarette explosions.
Three cases of e-cigarette explosions which occurred between 2016 and 2019, are presented.
All three e-cigarette explosions occurred in the trouser pockets. Two patients were male one patient was female. The age ranged from 24 to 64 years, the burned total body surface area (TBSA) from 3 % to 12.5 %. All three patients required skin grafting and the length of stay in hospital ranged from five to eleven days.
In the synopsis of recent literature, we recommend the following management of burns due to e-cigarette explosions. The guidelines of the Advanced Trauma Life Support should be followed, signs of an inhalation trauma should be checked and litmus test should be performed prior to irrigation with aqueous solutions to prevent exothermic reactions with remaining metals. If litmus test shows alkali pH wounds should be irrigated by mineral oil.
In the synopsis of recent literature, we recommend the following management of burns due to e-cigarette explosions. The guidelines of the Advanced Trauma Life Support should be followed, signs of an inhalation trauma should be checked and litmus test should be performed prior to irrigation with aqueous solutions to prevent exothermic reactions with remaining metals. If litmus test shows alkali pH wounds should be irrigated by mineral oil.Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroavailable for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.BACKGROUND AND STUDY AIM Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. METHODS This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. RESULTS In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). https://www.selleckchem.com/products/ap-3-a4-enoblock.html Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02-1.08]), good access (OR 3.58 [1.94-9.59]), complete submucosal lifting (OR 2.28 [1.36-3.90]), en bloc resection (OR 5.75 [1.48-22.39]), and serrated histology (OR 2.74 [1.35-5.56]). CONCLUSIONS Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding.
Hirschsprung's disease (HSCR) is congenital aganglionosis affecting the hindgut and presents with constipation. Surgical pull-through is the current standard treatment but causes morbidity. Per-rectal endoscopic myotomy is a novel third-space endoscopy technique for treating short-segment (SS)-HSCR.
Retrospective study of SS-HSCR patients diagnosed on history, contrast enema, rectal biopsies, and anorectal manometry, and treated by PREM. The aganglionic segment was mapped before PREM was performed using third-space endoscopy principles. Stool frequency and laxative usage before and after PREM were compared.
Nine patients (age 7.5 [± 5.2] years; 7 male) underwent PREM during a 4-year period. Mean aganglionic segment length was 6.3 cm, mean procedure time 96.1 minutes, and mean length of hospital stay 2.5 days. Median follow-up was 17 months (range 9-58 months). Stool frequency was 1/4.4 days before vs. 1/1.2 days after PREM (
= 0.0004). Mean laxative usage was 5.4 units of laxative (UL) before vs. 0.4 UL after PREM (
= 0.
The popularity of E-Cigarettes is increasing. Besides addiction and pulmonary health damage, reports of burn injuries from e-cigarette explosions are also increasing. Mostly, explosions of e-cigarettes are attributed to its lithium-ion battery. Due to increasing cases and missing guidelines we want to present three cases of our hospital and publish recommendations for the management of burn injuries caused by e-cigarette explosions. Three cases of e-cigarette explosions which occurred between 2016 and 2019, are presented. All three e-cigarette explosions occurred in the trouser pockets. Two patients were male one patient was female. The age ranged from 24 to 64 years, the burned total body surface area (TBSA) from 3 % to 12.5 %. All three patients required skin grafting and the length of stay in hospital ranged from five to eleven days. In the synopsis of recent literature, we recommend the following management of burns due to e-cigarette explosions. The guidelines of the Advanced Trauma Life Support should be followed, signs of an inhalation trauma should be checked and litmus test should be performed prior to irrigation with aqueous solutions to prevent exothermic reactions with remaining metals. If litmus test shows alkali pH wounds should be irrigated by mineral oil. In the synopsis of recent literature, we recommend the following management of burns due to e-cigarette explosions. The guidelines of the Advanced Trauma Life Support should be followed, signs of an inhalation trauma should be checked and litmus test should be performed prior to irrigation with aqueous solutions to prevent exothermic reactions with remaining metals. If litmus test shows alkali pH wounds should be irrigated by mineral oil.Long-term oxygen therapy is of great importance both for reducing mortality and for improving performance in patients with chronic lung diseases. The prerequisites for Long-term oxygen therapy are adequate diagnostics and clearly defined indication. A causal distinction into chronic hypoxaemic and hypercapnic respiratory failure is reasonable, from which the differential indication for non-invasive ventilation results.The revised guideline covers the diagnostics and indication of chronic lung and heart diseases, the role of oxygen in terminal illness and gives a detailed description of available oxygen devices. The guideline is intended to help avoid undersupply, oversupply and false prescriptions. Furthermore, the chapter "Postacute Oxygen Therapy" discusses the procedure, relevant in everyday life, but not yet clearly defined, for prescribing oxygen therapy for the home at the end of an inpatient stay. Another important point, the correct prescription of mobile oxygen systems, is also presented in the guideline. This document is a revised version of the guideline for longterm oxygen therapy and replaces the version of 2008.Seizures are the most common neurological emergency in the neonates, and this age group has the highest incidence of seizures compared with any other period of life. The author provides a narrative review of recent advances in the genetics of neonatal epilepsies, new neonatal seizure classification system, diagnostics, and treatment of neonatal seizures based on a comprehensive literature review (MEDLINE using PubMED and OvidSP vendors with appropriate keywords to incorporate recent evidence), personal practice, and experience. Knowledge regarding various systemic and postzygotic genetic mutations responsible for neonatal epilepsy has been exploded in recent times, as well as better delineation of clinical phenotypes associated with rare neonatal epilepsies. An International League Against Epilepsy task force on neonatal seizure has proposed a new neonatal seizure classification system and also evaluated the specificity of semiological features related to particular etiology. Although continuous video electroavailable for the management of neonatal seizures, institutional guidelines should be formed based on a consensus of local experts to mitigate wide variability in the treatment and to facilitate early diagnosis and treatment.BACKGROUND AND STUDY AIM Delayed bleeding is a common adverse event following endoscopic mucosal resection (EMR) of large colorectal polyps. Prophylactic clip closure of the mucosal defect after EMR of nonpedunculated polyps larger than 20 mm reduces the incidence of severe delayed bleeding, especially in proximal polyps. This study aimed to evaluate factors associated with complete prophylactic clip closure of the mucosal defect after EMR of large polyps. METHODS This is a post hoc analysis of the CLIP study (NCT01936948). All patients randomized to the clip group were included. Main outcome was complete clip closure of the mucosal resection defect. The defect was considered completely closed when no remaining mucosal defect was visible and clips were less than 1 cm apart. Factors associated with complete closure were evaluated in multivariable analysis. RESULTS In total, 458 patients (age 65, 58 % men) with 494 large polyps were included. Complete clip closure of the resection defect was achieved for 338 polyps (68.4 %); closure was not complete for 156 (31.6 %). https://www.selleckchem.com/products/ap-3-a4-enoblock.html Factors associated with complete closure in adjusted analysis were smaller polyp size (odds ratio 1.06 for every millimeter decrease [95 % confidence interval 1.02-1.08]), good access (OR 3.58 [1.94-9.59]), complete submucosal lifting (OR 2.28 [1.36-3.90]), en bloc resection (OR 5.75 [1.48-22.39]), and serrated histology (OR 2.74 [1.35-5.56]). CONCLUSIONS Complete clip closure was not achieved for almost one in three resected large nonpedunculated polyps. While stable access and en bloc resection facilitate clip closure, most factors associated with clip closure are not modifiable. This highlights the need for alternative closure options and measures to prevent bleeding. Hirschsprung's disease (HSCR) is congenital aganglionosis affecting the hindgut and presents with constipation. Surgical pull-through is the current standard treatment but causes morbidity. Per-rectal endoscopic myotomy is a novel third-space endoscopy technique for treating short-segment (SS)-HSCR. Retrospective study of SS-HSCR patients diagnosed on history, contrast enema, rectal biopsies, and anorectal manometry, and treated by PREM. The aganglionic segment was mapped before PREM was performed using third-space endoscopy principles. Stool frequency and laxative usage before and after PREM were compared. Nine patients (age 7.5 [± 5.2] years; 7 male) underwent PREM during a 4-year period. Mean aganglionic segment length was 6.3 cm, mean procedure time 96.1 minutes, and mean length of hospital stay 2.5 days. Median follow-up was 17 months (range 9-58 months). Stool frequency was 1/4.4 days before vs. 1/1.2 days after PREM ( = 0.0004). Mean laxative usage was 5.4 units of laxative (UL) before vs. 0.4 UL after PREM ( = 0.0 Commenti 0 condivisioni 6 Views 0 Anteprima -
8%) females. The median BMI was 29.14±52 kg/m<sup>2</sup>. The median operative time was 80±25 minutes. There were no intraoperative complications or conversions to open surgery. Patients began a fluid diet on the first postoperative day and were discharged after a median hospital stay of 3±1.87 days. In a median follow-up of 36 months, we did not observe any recurrences.
Transabdominal laparoscopic approach with primary closure of the diaphragmatic defect is a viable approach for the repair of Morgagni hernia. In our experience, the use of laparoscopic transabdominal suture fixed to the fascia allowed the closure of the defect laparoscopically with minimal tension on the repairs.
Transabdominal laparoscopic approach with primary closure of the diaphragmatic defect is a viable approach for the repair of Morgagni hernia. In our experience, the use of laparoscopic transabdominal suture fixed to the fascia allowed the closure of the defect laparoscopically with minimal tension on the repairs.
Aim of this study was to assess whether the reduction in the number of tackers maintains a similar recurrence rate and to subsequently evaluate whether this reduction associated with fibrin adhesive (FA) influences postsurgical pain after laparoscopic ventral hernia repair (LVHR) at 5 years follow-up.
Fifty patients with ventral hernia (intervention group) underwent to LVHR with the double crown (DC) technique with a decrease in the number of tackers, each tacker being separated by about 3 cm associated with FA to seal the spaces between them. Data obtained from intervention group were compared to data obtained from a historical series of 50 patients (control group) undergoing LVHR using DC technique with tackers at 1 cm each other.
No statistically significant differences were found between groups about patients' characteristics. Mean hospital stay was 2 days. Statistically significant differences were observed about hospital stay between both groups U-Mann-Whitney ([UMW] =345, P=0) being higher in the control group. Statistically significant difference was observed in the postoperative pain evaluated by the visual analogical scale (VAS) score, having 95% of patients in the control group with VAS less than or equal to 7 compared to 4.55 in the intervention group. Recurrence rate was 4.1% for the control group versus 4.2% in the intervention group.
The reduction of metallic tackers associated with FA does not present statistically significant differences in the recurrence rate in comparison to conventional DC technique. In the intervention group a reduction in postoperative pain and hospital stay were observed.
The reduction of metallic tackers associated with FA does not present statistically significant differences in the recurrence rate in comparison to conventional DC technique. In the intervention group a reduction in postoperative pain and hospital stay were observed.
Incisional hernia still represents the most frequent late complication of abdominal surgery. https://www.selleckchem.com/products/valemetostat-ds-3201.html After a direct repair, in literature is reported a recurrence rate ranging from 31 to 49%, meanwhile after a prosthetic repair such values were **** lower, with a recurrence rate up to 10%. The sites of prosthetic placement in the abdominal wall are premusculo-aponeurotic (onlay, or Chevrel technique), retromuscular-prefascial and preperitoneal (Rives technique, Stoppa technique), whereas intraperitoneal insertion can be done with open or laparoscopic surgery. The aim of this study was to evaluate the immediate and late postoperative results in patients treated with a Chevrel technique for ventral incisional hernia.
A retrospective review was conducted on the medical records of patients undergoing ventral hernia repair between January 2008 and December 2018 at the Emergency Surgery Unit of the Careggi University Hospital in Florence.
Between January 2008 and December 2018 at the Emergency Surgery Unit of the Car satisfactory in both immediate and late follow-up; moreover this technique is safe and easy to perform.
Most of the objections to the Chevrel procedure focus on the parietal complications and risk of infection. Chevrel procedure cannot be considered an obsolete intervention, in our series, results were very satisfactory in both immediate and late follow-up; moreover this technique is safe and easy to perform.
The technical evolution of hernia repair has brought to the introduction of laparoscopy in this field. The most common laparoscopic techniques are transabdominal preperitoneal (TAPP) repair and totally extraperitoneal (TEP) repair. Indirect comparisons between TAPP and TEP have raised questions as to which is the superior approach in improving patient outcomes; however, there is still a scarcity of data directly comparing these laparoscopic approaches. The aim of this report is to offer a retrospective comparison between the two techniques with a long-term follow-up.
This study is a retrospective comparative study, comparing TEP and TAPP in the treatment of groin hernias. All patients undergoing laparoscopic hernia repair from 2015 and 2020 at a large UK Hospital Trust with tertiary referral center, were considered as eligible for inclusion. The primary endpoint was rate of successful surgery defined as absence of recurrence and chronic pain at the end of the follow-up. Secondary endpoints were conversionon, and experience.The internationalized segment of manuscripts on surgery published in top-rated journals indexed in the Web of Science Core Collection (WoS CC) was analyzed. Presence of national publications in surgical journals of different quartiles was estimated. It was shown that 59.6% of surgical articles of Russian authors, indexed in the WoS CC, were published in high-ranking journals (Q1 and Q2). The number of such articles has been increased by more than 3 times (from 23 in 2010 to 86 in 2018) on the background of no growth in the fourth quartile. We formed a rating of national educational and academic organizations, which have made the greatest contribution to a portfolio of publications on surgery, indexed in Q1-Q2 quartiles of WoS CC, as well as in the segment of highly cited publications.
8%) females. The median BMI was 29.14±52 kg/m<sup>2</sup>. The median operative time was 80±25 minutes. There were no intraoperative complications or conversions to open surgery. Patients began a fluid diet on the first postoperative day and were discharged after a median hospital stay of 3±1.87 days. In a median follow-up of 36 months, we did not observe any recurrences. Transabdominal laparoscopic approach with primary closure of the diaphragmatic defect is a viable approach for the repair of Morgagni hernia. In our experience, the use of laparoscopic transabdominal suture fixed to the fascia allowed the closure of the defect laparoscopically with minimal tension on the repairs. Transabdominal laparoscopic approach with primary closure of the diaphragmatic defect is a viable approach for the repair of Morgagni hernia. In our experience, the use of laparoscopic transabdominal suture fixed to the fascia allowed the closure of the defect laparoscopically with minimal tension on the repairs. Aim of this study was to assess whether the reduction in the number of tackers maintains a similar recurrence rate and to subsequently evaluate whether this reduction associated with fibrin adhesive (FA) influences postsurgical pain after laparoscopic ventral hernia repair (LVHR) at 5 years follow-up. Fifty patients with ventral hernia (intervention group) underwent to LVHR with the double crown (DC) technique with a decrease in the number of tackers, each tacker being separated by about 3 cm associated with FA to seal the spaces between them. Data obtained from intervention group were compared to data obtained from a historical series of 50 patients (control group) undergoing LVHR using DC technique with tackers at 1 cm each other. No statistically significant differences were found between groups about patients' characteristics. Mean hospital stay was 2 days. Statistically significant differences were observed about hospital stay between both groups U-Mann-Whitney ([UMW] =345, P=0) being higher in the control group. Statistically significant difference was observed in the postoperative pain evaluated by the visual analogical scale (VAS) score, having 95% of patients in the control group with VAS less than or equal to 7 compared to 4.55 in the intervention group. Recurrence rate was 4.1% for the control group versus 4.2% in the intervention group. The reduction of metallic tackers associated with FA does not present statistically significant differences in the recurrence rate in comparison to conventional DC technique. In the intervention group a reduction in postoperative pain and hospital stay were observed. The reduction of metallic tackers associated with FA does not present statistically significant differences in the recurrence rate in comparison to conventional DC technique. In the intervention group a reduction in postoperative pain and hospital stay were observed. Incisional hernia still represents the most frequent late complication of abdominal surgery. https://www.selleckchem.com/products/valemetostat-ds-3201.html After a direct repair, in literature is reported a recurrence rate ranging from 31 to 49%, meanwhile after a prosthetic repair such values were much lower, with a recurrence rate up to 10%. The sites of prosthetic placement in the abdominal wall are premusculo-aponeurotic (onlay, or Chevrel technique), retromuscular-prefascial and preperitoneal (Rives technique, Stoppa technique), whereas intraperitoneal insertion can be done with open or laparoscopic surgery. The aim of this study was to evaluate the immediate and late postoperative results in patients treated with a Chevrel technique for ventral incisional hernia. A retrospective review was conducted on the medical records of patients undergoing ventral hernia repair between January 2008 and December 2018 at the Emergency Surgery Unit of the Careggi University Hospital in Florence. Between January 2008 and December 2018 at the Emergency Surgery Unit of the Car satisfactory in both immediate and late follow-up; moreover this technique is safe and easy to perform. Most of the objections to the Chevrel procedure focus on the parietal complications and risk of infection. Chevrel procedure cannot be considered an obsolete intervention, in our series, results were very satisfactory in both immediate and late follow-up; moreover this technique is safe and easy to perform. The technical evolution of hernia repair has brought to the introduction of laparoscopy in this field. The most common laparoscopic techniques are transabdominal preperitoneal (TAPP) repair and totally extraperitoneal (TEP) repair. Indirect comparisons between TAPP and TEP have raised questions as to which is the superior approach in improving patient outcomes; however, there is still a scarcity of data directly comparing these laparoscopic approaches. The aim of this report is to offer a retrospective comparison between the two techniques with a long-term follow-up. This study is a retrospective comparative study, comparing TEP and TAPP in the treatment of groin hernias. All patients undergoing laparoscopic hernia repair from 2015 and 2020 at a large UK Hospital Trust with tertiary referral center, were considered as eligible for inclusion. The primary endpoint was rate of successful surgery defined as absence of recurrence and chronic pain at the end of the follow-up. Secondary endpoints were conversionon, and experience.The internationalized segment of manuscripts on surgery published in top-rated journals indexed in the Web of Science Core Collection (WoS CC) was analyzed. Presence of national publications in surgical journals of different quartiles was estimated. It was shown that 59.6% of surgical articles of Russian authors, indexed in the WoS CC, were published in high-ranking journals (Q1 and Q2). The number of such articles has been increased by more than 3 times (from 23 in 2010 to 86 in 2018) on the background of no growth in the fourth quartile. We formed a rating of national educational and academic organizations, which have made the greatest contribution to a portfolio of publications on surgery, indexed in Q1-Q2 quartiles of WoS CC, as well as in the segment of highly cited publications.0 Commenti 0 condivisioni 1 Views 0 Anteprima -
Catheter ablation is effective in reducing atrial fibrillation (AF), but the association of ablation for AF with quality of life is unclear.
To evaluate whether the procedural outcome of ablation for AF is associated with quality of life (QOL) measures.
This was a prespecified secondary analysis of the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation-Part II (STAR AF II) prospective randomized clinical trial, which compared 3 strategies for ablation of persistent AF. This analysis included 549 of the 589 patients enrolled in the trial who underwent ablation. Enrollment occurred at 35 centers in Europe, Canada, Australia, China, and Korea from November 2010 to July 2012. Data for the current study were analyzed on December 11, 2019.
Patients underwent AF ablation with 1 of 3 ablation strategies (1) pulmonary vein isolation (PVI), (2) PVI plus complex fractionated electrograms, or (3) PVI plus linear lesions.
Quality of life was assessed at baseline and at 6, 12, and 18 months afternt QOL improvement occurred in all 3 study arms and regardless of AF recurrence, defined as AF episodes lasting more than 30 seconds for no recurrence, mean (SD) PCS increased from 66.5 (20.9) to 79.1 (19.4) and MCS from 35.3 (8.7) to 37.7 (7.7); for recurrence, mean (SD) PCS increased from 70.2 (20.4) to 86.4 (16.8) and MCS from 35.3 (8.6) to 37.1 (7.4) (P < .05 for all). When outcome was defined by AF burden reduction, in patients with less than 70% reduction in AF burden, the increase in PCS was significantly less than in those with greater than 70% reduction, and only 3 of 8 subscales showed significant improvement.
In this secondary analysis, decreases in AF burden after ablation for AF were significantly associated with improvements in QOL. Quality of life changes were significantly associated with the percentage of AF burden reduction after ablation.
ClinicalTrials.gov Identifier NCT01203748.
ClinicalTrials.gov Identifier NCT01203748.
Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China.
To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system.
A decision tree for a simulated cohort population of 15 000 000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years).
Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.
To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.The COVID-19 (coronavirus disease 2019) pandemic has underscored the critical need for all countries to strengthen their health data and information systems and ensure the routes the data travel, from submission to use, are unobstructed. Timely, credible, reliable, and actionable data are key to ensuring that political decisions are data driven and facilitate understanding, monitoring, and forecasting. https://www.selleckchem.com/products/eft-508.html To ensure that critical decisions related to the wider health and socioeconomic effects of this pandemic are data driven, each country needs to develop or enhance a national data governance plan that includes a clear coordination mechanism, well-defined and documented data processes (manual or electronic), the exchange of data, and a data culture to empower users. In addition, countries should now more than ever invest and enhance their data and health information systems to ensure that all decisions are data driven and that they are prepared for what is next.The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B-G039927 and EPS15L1-lncOR7C2-1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial-both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2'-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells.
Catheter ablation is effective in reducing atrial fibrillation (AF), but the association of ablation for AF with quality of life is unclear. To evaluate whether the procedural outcome of ablation for AF is associated with quality of life (QOL) measures. This was a prespecified secondary analysis of the Substrate and Trigger Ablation for Reduction of Atrial Fibrillation-Part II (STAR AF II) prospective randomized clinical trial, which compared 3 strategies for ablation of persistent AF. This analysis included 549 of the 589 patients enrolled in the trial who underwent ablation. Enrollment occurred at 35 centers in Europe, Canada, Australia, China, and Korea from November 2010 to July 2012. Data for the current study were analyzed on December 11, 2019. Patients underwent AF ablation with 1 of 3 ablation strategies (1) pulmonary vein isolation (PVI), (2) PVI plus complex fractionated electrograms, or (3) PVI plus linear lesions. Quality of life was assessed at baseline and at 6, 12, and 18 months afternt QOL improvement occurred in all 3 study arms and regardless of AF recurrence, defined as AF episodes lasting more than 30 seconds for no recurrence, mean (SD) PCS increased from 66.5 (20.9) to 79.1 (19.4) and MCS from 35.3 (8.7) to 37.7 (7.7); for recurrence, mean (SD) PCS increased from 70.2 (20.4) to 86.4 (16.8) and MCS from 35.3 (8.6) to 37.1 (7.4) (P < .05 for all). When outcome was defined by AF burden reduction, in patients with less than 70% reduction in AF burden, the increase in PCS was significantly less than in those with greater than 70% reduction, and only 3 of 8 subscales showed significant improvement. In this secondary analysis, decreases in AF burden after ablation for AF were significantly associated with improvements in QOL. Quality of life changes were significantly associated with the percentage of AF burden reduction after ablation. ClinicalTrials.gov Identifier NCT01203748. ClinicalTrials.gov Identifier NCT01203748. Congenital cytomegalovirus infection (cCMVi) is one of the most common infections associated with childhood hearing loss. Prevention and mitigation of cCMVi-related hearing loss will require an increase in newborn screening, which is not yet available in China. To estimate the cost-effectiveness of newborn screening strategies for cCMVi from the perspective of the Chinese health care system. A decision tree for a simulated cohort population of 15 000 000 live births was developed to compare the costs and health effects of 3 mutually exclusive interventions (1) no screening, (2) targeted screening using CMV polymerase chain reaction assay for newborns who fail a universal hearing screening, and (3) universal screening for CMV among all newborns. Markov diagrams were used to evaluate the lifetime horizon (76 years). Cost, hearing-related health outcomes, and incremental cost-effectiveness ratios (ICERs) were estimated based on a direct medical costs perspective. Costs and ICERs were reported in 2018 US considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries. To achieve cost-effectiveness and best health outcomes, universal screening could be considered for the Chinese population. While the results are specific to China, the model may easily be adapted for other countries.The COVID-19 (coronavirus disease 2019) pandemic has underscored the critical need for all countries to strengthen their health data and information systems and ensure the routes the data travel, from submission to use, are unobstructed. Timely, credible, reliable, and actionable data are key to ensuring that political decisions are data driven and facilitate understanding, monitoring, and forecasting. https://www.selleckchem.com/products/eft-508.html To ensure that critical decisions related to the wider health and socioeconomic effects of this pandemic are data driven, each country needs to develop or enhance a national data governance plan that includes a clear coordination mechanism, well-defined and documented data processes (manual or electronic), the exchange of data, and a data culture to empower users. In addition, countries should now more than ever invest and enhance their data and health information systems to ensure that all decisions are data driven and that they are prepared for what is next.The majority of the human genome encodes long noncoding RNA (lncRNA) genes, critical regulators of various cellular processes, which largely outnumber protein-coding genes. However, lncRNA-involved fusions have not been surveyed and characterized yet. Here, we present a systematic study of the lncRNA fusion landscape across cancer types and identify >30 000 high-confidence tumor-specific lncRNA fusions (using 8284 tumor and 6946 normal samples). Fusions positively correlated with DNA damage and cancer stemness and were specifically low in microsatellite instable (MSI)-High or virus-infected tumors. Moreover, fusions distribute differently among cancer molecular subtypes, but with shared enrichment in tumors that are microsatellite stable (MSS), with high somatic copy number alterations (SCNA), and with poor survival. Importantly, we find a potentially new mechanism, mediated by enhancer RNAs (eRNA), which generates secondary fusions that form densely connected fusion networks with many fusion hubs targeted by FDA-approved drugs. Finally, we experimentally validate functions of two tumor-promoting chimeric proteins derived from mRNA-lncRNA fusions, KDM4B-G039927 and EPS15L1-lncOR7C2-1. The EPS15L1 fusion protein may regulate (Gasdermin E) GSDME, critical in pyroptosis and anti-tumor immunity. Our study completes the fusion landscape in cancers, sheds light on fusion mechanisms, and enriches lncRNA functions in tumorigenesis and cancer progression.Nucleic acid therapeutics (NATs) have proven useful in promoting the degradation of specific transcripts, modifying gene expression, and regulating mRNA splicing. In each situation, efficient delivery of nucleic acids to cells, tissues and intracellular compartments is crucial-both for optimizing efficacy and reducing side effects. Despite successes in NATs, our understanding of their cellular uptake and distribution in tissues is limited. Current methods have yielded insights into distribution of NATs within cells and tissues, but the sensitivity and resolution of these approaches are limited. Here, we show that nanoscale secondary ion mass spectrometry (NanoSIMS) imaging can be used to define the distribution of 5-bromo-2'-deoxythymidine (5-BrdT) modified antisense oligonucleotides (ASO) in cells and tissues with high sensitivity and spatial resolution. This approach makes it possible to define ASO uptake and distribution in different subcellular compartments and to quantify the impact of targeting ligands designed to promote ASO uptake by cells.0 Commenti 0 condivisioni 9 Views 0 Anteprima -
While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan-Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening. A representative sample of Belgian adults was asked about their contact behaviour from mid-April to the beginning of August, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of [Formula see text] with respect to pre-pandemic data. During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. From the end of May to the end of July , the estimated reproduction number has a median value larger than one, although with a wide dispersion. Estimated [Formula see text] fell below one again at the beginning of August. We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19.We propose a novel class of mixed fluctuations with different orientations and fractal scaling features as a model for anisotropic two-dimensional (2D) trajectories hypothesized to appear in complex systems. Furthermore, we develop the oriented fractal scaling component analysis (OFSCA) to decompose such mixed fluctuations into the original orientation components. In the OFSCA, the original orientations are detected based on the principle that the original angles are orthogonal to the angles with the minimum and maximum scaling exponents of the mixed fluctuations. In our approach, the angle-dependent scaling properties are estimated using the Savitzky-Golay-filter-based detrended moving-average analysis (DMA), which has a higher detrending order than the conventional moving-average-filter-based DMA. To illustrate the OFSCA, we demonstrate that the numerically generated time-series of mixed fractional Gaussian noise (fGn) processes with non-orthogonal orientations and different scaling exponents is successfully decomposed into the original fGn components. We demonstrate the existence of oriented components in the 2D trajectories by applying OFSCA to real-world time-series, such as human postural fluctuations during standing and seismic ground acceleration during the great 2011 Tohoku-oki earthquake.Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). https://www.selleckchem.com/products/fluorofurimazine.html We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR less then 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process 'receptor-mediated endocytosis', and 52 TMPRSS2-correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0-2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.
While the effectiveness of baricitinib was similar regardless of whether patients had a history of only one or multiple targeted DMARDs use, patients with previous use of non-TNF inhibitors or JAK inhibitors showed lower rates of improvement in DAS28-CRP. The overall retention rate for baricitinib was 86.5% at 24 weeks, as estimated by Kaplan-Meier analysis. The discontinuation rate due to adverse events was 6.5% at 24 weeks. Baricitinib significantly improved RA disease activity in clinical practice. Baricitinib was significantly more effective when used as a first-line targeted DMARDs.The COVID-19 pandemic has shown how a newly emergent communicable disease can lay considerable burden on public health. To avoid system collapse, governments have resorted to several social distancing measures. In Belgium, this included a lockdown and a following period of phased re-opening. A representative sample of Belgian adults was asked about their contact behaviour from mid-April to the beginning of August, during different stages of the intervention measures in Belgium. Use of personal protection equipment (face masks) and compliance to hygienic measures was also reported. We estimated the expected reproduction number computing the ratio of [Formula see text] with respect to pre-pandemic data. During the first two waves (the first month) of the survey, the reduction in the average number of contacts was around 80% and was quite consistent across all age-classes. The average number of contacts increased over time, particularly for the younger age classes, still remaining significantly lower than pre-pandemic values. From the end of May to the end of July , the estimated reproduction number has a median value larger than one, although with a wide dispersion. Estimated [Formula see text] fell below one again at the beginning of August. We have shown how a rapidly deployed survey can measure compliance to social distancing and assess its impact on COVID-19 spread. Monitoring the effectiveness of social distancing recommendations is of paramount importance to avoid further waves of COVID-19.We propose a novel class of mixed fluctuations with different orientations and fractal scaling features as a model for anisotropic two-dimensional (2D) trajectories hypothesized to appear in complex systems. Furthermore, we develop the oriented fractal scaling component analysis (OFSCA) to decompose such mixed fluctuations into the original orientation components. In the OFSCA, the original orientations are detected based on the principle that the original angles are orthogonal to the angles with the minimum and maximum scaling exponents of the mixed fluctuations. In our approach, the angle-dependent scaling properties are estimated using the Savitzky-Golay-filter-based detrended moving-average analysis (DMA), which has a higher detrending order than the conventional moving-average-filter-based DMA. To illustrate the OFSCA, we demonstrate that the numerically generated time-series of mixed fractional Gaussian noise (fGn) processes with non-orthogonal orientations and different scaling exponents is successfully decomposed into the original fGn components. We demonstrate the existence of oriented components in the 2D trajectories by applying OFSCA to real-world time-series, such as human postural fluctuations during standing and seismic ground acceleration during the great 2011 Tohoku-oki earthquake.Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). https://www.selleckchem.com/products/fluorofurimazine.html We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. ACE2 was in a module of 681 co-expressed genes; 10 genes with moderate-high correlation with ACE2 (r > 0.3, FDR less then 0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 31 of these genes were enriched in the gene ontology biologic process 'receptor-mediated endocytosis', and 52 TMPRSS2-correlated genes had known interactions with drug compounds. Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may accelerate the development of COVID-19 therapeutics.Liver iron excess is observed in several chronic liver diseases and is associated with the development of hepatocellular carcinoma (HCC). However, apart from oxidative stress, other cellular mechanisms by which excess iron may mediate/increase HCC predisposition/progression are not known. HCC pathology involves epithelial to mesenchymal transition (EMT), the basis of cancer phenotype acquisition. Here, the effect of excess iron (holo-transferrin 0-2 g/L for 24 and 48 h) on EMT biomarkers in the liver-derived HepG2 cells was investigated. Holo-transferrin substantially increased intracellular iron. Unexpectedly, mRNA and protein expression of the epithelial marker E-cadherin either remained unaltered or increased. The mRNA and protein levels of metastasis marker N-cadherin and mesenchymal marker vimentin increased significantly. While the mRNA expression of EMT transcription factors SNAI1 and SNAI2 increased and decreased, respectively after 24 h, both factors increased after 48 h. The mRNA expression of TGF-β (EMT-inducer) showed no significant alterations. In conclusion, data showed direct link between iron and EMT. Iron elevated mesenchymal and metastatic biomarkers in HepG2 cells without concomitant decrement in the epithelial marker E-cadherin and altered the expression of the key EMT-mediating transcription factors. Such studies can help identify molecular targets to devise iron-related adjunctive therapies to ameliorate HCC pathophysiology.0 Commenti 0 condivisioni 8 Views 0 Anteprima
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