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  • 1 vs. 30.9±10.9 Kg) compared to those with optimal PIFR. There were no significant differences between the two PIFR groups by gender, race, history of coronary artery disease, congestive heart failure, hypertension or functional scores. Each kilogram increase in HGS was associated with 0.50 (95%CI 0.18-0.89, p = 0.003) L/min increase in PIFR. We did not observe an association between PIFR and 30 or 90-day readmission rates. CONCLUSION We found a significant association between HGS and PIFR in hospitalized patients with acute exacerbations of COPD. Whether interventions aimed at increasing skeletal muscle strength also result in improvement in PIFR remains unclear and need further study.Patients diagnosed with coronary heart disease should follow lifestyle recommendations that can reduce their cardiovascular risk (e.g., avoid smoking). However, some patients fail to follow these recommendations and engage in unhealthy behavior. With the aim to identify psychosocial factors that characterize patients at high risk of repeated cardiovascular events, we investigated the relationship between social support, mental health (coping, self-esteem, and perceived stress), and unhealthy behavior. We conducted a cross-sectional study of 419 patients recently diagnosed with coronary heart disease (myocardial infarction or angina) who participated in the National Health Survey in Spain (2018). Unhealthy behaviors were defined according to the European Guidelines on cardiovascular disease prevention. Only 1% of patients reported no unhealthy behaviors, with 11% reporting one, 40% two, 35% three, and 13% four or more unhealthy behaviors. In multiple regression controlling for demographic and traditional risk factors, mental health was the only significant psychosocial factor, doubling the odds of accumulated unhealthy behaviors, OR(high vs. low) = 2.03, 95% CI [1.14, 3.64]. https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html Mental health was especially strongly related to unhealthy behavior among patients with obesity, OR(high vs. low) = 3.50, 95% CI [1.49, 8.45]. The relationship between mental health and unhealthy behaviors suggests that a large proportion of patients may not adhere to lifestyle recommendations not because they purposefully choose to do so, but because they lack coping skills to maintain the recommended healthy behaviors. Low mental well-being may be especially detrimental for behavior change of patients with obesity.Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.PURPOSE The purpose was to explore the exercise behavior of the Taiwanese population during leisure time and to examine the gender differences in related influential factors. METHODS The Leisure Time and Sport Questionnaire (LTSQ) conducted by the Academia Sinica in 2007 was used for analysis. Participants were drawn from the Taiwanese population aged over 18 years old. Multinomial logistic regression models were used to test the association between the frequency of exercise and related factors in all the participants, male, and female participants, respectively. RESULTS In the total 2,147 participants, 47.8% reported they regularly exercised, 34.1% irregularly exercised, and 18.1% never exercised. There were no significant gender differences in the frequency of exercise, but a significant gender difference was found in the types of exercise most often practiced. Participants in one of following conditions, over 65 and under 40 years old, living in the city, having higher education levels, having a spouse or partner, enjoying exercise, feeling worthwhile to spend money on exercise, and not having to take care of others, were more likely to be engaged in regular exercise in the total population. The "enjoyment" in exercise was a significant influential factor for both sexes. Women were more likely to exercise regularly if they were aged 40-64 years old compared with those over 65 years old, have lower self-rated health scores, felt it was more worthwhile to spend money on exercise and did not have to care for another, whereas men who have higher education level and did not feel a lack of time were more likely to exercise regularly. CONCLUSIONS There are gender differences in regular exercise behavior during leisure time and related influential factors among Taiwanese adults. The findings of the present study can be used when designing gender-specific health promotion programs.
    1 vs. 30.9±10.9 Kg) compared to those with optimal PIFR. There were no significant differences between the two PIFR groups by gender, race, history of coronary artery disease, congestive heart failure, hypertension or functional scores. Each kilogram increase in HGS was associated with 0.50 (95%CI 0.18-0.89, p = 0.003) L/min increase in PIFR. We did not observe an association between PIFR and 30 or 90-day readmission rates. CONCLUSION We found a significant association between HGS and PIFR in hospitalized patients with acute exacerbations of COPD. Whether interventions aimed at increasing skeletal muscle strength also result in improvement in PIFR remains unclear and need further study.Patients diagnosed with coronary heart disease should follow lifestyle recommendations that can reduce their cardiovascular risk (e.g., avoid smoking). However, some patients fail to follow these recommendations and engage in unhealthy behavior. With the aim to identify psychosocial factors that characterize patients at high risk of repeated cardiovascular events, we investigated the relationship between social support, mental health (coping, self-esteem, and perceived stress), and unhealthy behavior. We conducted a cross-sectional study of 419 patients recently diagnosed with coronary heart disease (myocardial infarction or angina) who participated in the National Health Survey in Spain (2018). Unhealthy behaviors were defined according to the European Guidelines on cardiovascular disease prevention. Only 1% of patients reported no unhealthy behaviors, with 11% reporting one, 40% two, 35% three, and 13% four or more unhealthy behaviors. In multiple regression controlling for demographic and traditional risk factors, mental health was the only significant psychosocial factor, doubling the odds of accumulated unhealthy behaviors, OR(high vs. low) = 2.03, 95% CI [1.14, 3.64]. https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html Mental health was especially strongly related to unhealthy behavior among patients with obesity, OR(high vs. low) = 3.50, 95% CI [1.49, 8.45]. The relationship between mental health and unhealthy behaviors suggests that a large proportion of patients may not adhere to lifestyle recommendations not because they purposefully choose to do so, but because they lack coping skills to maintain the recommended healthy behaviors. Low mental well-being may be especially detrimental for behavior change of patients with obesity.Financial barriers are a major obstacle to accessing maternal health care services in low-resource settings. In Madagascar, less than half of live births are attended by skilled health staff. Although mobile money-based savings and payment systems are often used to pay for a variety of services, including health care, data on the implications of a dedicated mobile money wallet restricted to health-related spending during pregnancy-a mobile health wallet (MHW)-are not well understood. In cooperation with the Madagascan Ministry of Health, this study aims to elicit the perceptions, experiences, and recommendations of key stakeholders in relation to a MHW amid a pilot study in 31 state-funded health care facilities. We conducted a two-stage qualitative study using semi-structured in-depth interviews with stakeholders (N = 21) representing the following groups community representatives, health care providers, health officials and representatives from phone provider companies. Interviews were conducted in Atsimondrano and Renivohitra districts, between November and December of 2017. Data was coded thematically using inductive and deductive approaches, and found to align with a social ecological model. Key facilitators for successful implementation of the MHW, include (i) close collaboration with existing communal structures and (ii) creation of an incentive scheme to reward pregnant women to save. Key barriers to the application of the MHW in the study zone include (i) disruption of informal benefits for health care providers related to the current cash-based payment system, (ii) low mobile phone ownership, (iii) illiteracy among the target population, and (iv) failure of the MHW to overcome essential access barriers towards institutional health care services such as fear of unpredictable expenses. The MHW was perceived as a potential solution to reduce disparities in access to maternal health care. To ensure success of the MHW, direct demand-side and provider-side financial incentives merit consideration.PURPOSE The purpose was to explore the exercise behavior of the Taiwanese population during leisure time and to examine the gender differences in related influential factors. METHODS The Leisure Time and Sport Questionnaire (LTSQ) conducted by the Academia Sinica in 2007 was used for analysis. Participants were drawn from the Taiwanese population aged over 18 years old. Multinomial logistic regression models were used to test the association between the frequency of exercise and related factors in all the participants, male, and female participants, respectively. RESULTS In the total 2,147 participants, 47.8% reported they regularly exercised, 34.1% irregularly exercised, and 18.1% never exercised. There were no significant gender differences in the frequency of exercise, but a significant gender difference was found in the types of exercise most often practiced. Participants in one of following conditions, over 65 and under 40 years old, living in the city, having higher education levels, having a spouse or partner, enjoying exercise, feeling worthwhile to spend money on exercise, and not having to take care of others, were more likely to be engaged in regular exercise in the total population. The "enjoyment" in exercise was a significant influential factor for both sexes. Women were more likely to exercise regularly if they were aged 40-64 years old compared with those over 65 years old, have lower self-rated health scores, felt it was more worthwhile to spend money on exercise and did not have to care for another, whereas men who have higher education level and did not feel a lack of time were more likely to exercise regularly. CONCLUSIONS There are gender differences in regular exercise behavior during leisure time and related influential factors among Taiwanese adults. The findings of the present study can be used when designing gender-specific health promotion programs.
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  • Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients.

    All patients (n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75mg of ASA per day in a single antiplatelet therapy for 3months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed.

    There was a significant reduction in 24-h BP and blood pressure at night in the ASA group evening group compared with the ASA morning group and the control group.

    The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.
    The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.Cutaneous melanoma is known to be one of the most dangerous skin cancers because of its metastatic functions. Today, it is essential to investigate specific biomarkers for the target treatment in many diseases including cancers. DJ-1 protein, also known as Parkinson disease 7, has various functions associated with cancer progression including cell survival and migration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates the PI3K/AKT signaling pathway and its mutations have been reported to frequently occur in many cancers such as thyroid, breast and skin. Recently, DJ-1 has been identified as a negative regulator of PTEN in many human cancer cells. However, the impacts and relationship of DJ-1 and PTEN have not been studied yet in melanoma. To confirm the expression of DJ-1 and PTEN in melanoma compared to normal skin tissues and find out functions of DJ-1 in melanoma cells, Western blot analysis and immunohistochemical staining were used. Transfection of G361 cells with DJ-1-specific small interfering RNA was performed to figure out the roles of DJ-1 and the relationship between DJ-1 and PTEN in melanoma cells. In our study, the DJ-1 protein was significantly increased with loss of PTEN protein in melanoma compared to that in normal skin. Inhibition of DJ-1 in G361 cells induced apoptosis, and suppressed cell survival and migration. Furthermore, suppression of DJ-1 in G361 cells increased the expression of cleaved caspase-3, cleaved PARP, Bax, p53, and Daxx as well as PTEN, while it decreased expression of survivin, caspase-3, and PARP. Also, downregulated DJ-1 inhibited phosphorylation of AKT in G361 cells. Collectively, DJ-1 overexpression could affect the proliferative and invasive capabilities of melanoma cells via regulating the PTEN/AKT pathway and apoptosis-related proteins. This study suggests that DJ-1 may be a potential target for the treatment of melanoma.
    To discuss and summarize the latest evidence on imaging techniques in giant cell arteritis (GCA) and Takayasu arteritis (TAK). This is a report on the performance of ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET), and other emerging imaging techniques in diagnosis, outcome prediction, and monitoring of disease activity.

    Imaging techniques have gained an important role for diagnosis of large vessel vasculitides (LVV). As signs of vasculitis, US, MRI, and CT show a homogeneous arterial wall thickening, which is mostly concentric. PET displays increased FDG uptake in inflamed artery walls. US is recommended as the initial imaging modality in GCA. MRI and PET/CT may also detect vasculitis of temporal arteries. For TAK, MRI is recommended as the first imaging modality as it provides a good overview without radiation. Extracranial LVV can be confirmed by all four modalities. In addition, MRI and PET/CT provide consisterview without radiation. Extracranial LVV can be confirmed by all four modalities. In addition, MRI and PET/CT provide consistent examination of the aorta and its branches. New techniques such as contrast-enhanced ultrasound, PET/MRI, and auxiliary methods such as "computer-assisted quantitative analysis" have emerged and need to be further validated. Imaging has partly replaced histology for confirming LVV. Provided experience and adequate training, US, MRI, CT, or PET provide excellent diagnostic accuracy. Imaging results need to complement history and clinical examination. https://www.selleckchem.com/products/sd-208.html Ongoing studies are evaluating the role of imaging for monitoring and outcome measurement.Stable and efficient hydrocarbon degrading microbial consortia were developed from a refinery sludge through nitrate amendment for their application in enhanced bioremediation of petroleum contaminated waste. Nitrate induced biostimulation of refinery sludge resulted in increased abundance of hydrocarbon degrading Rhodocyclaceae, Xanthomonadaceae, Syntrophaceae and Comamonadaceae members. Repeated subculturing of nitrate stimulated communities in crude oil supplemented basal medium was done under aerobic and anaerobic conditions. Aerobically enriched consortia (composed of Pseudomonadaceae, Pseudoxanthomonadaceae and unclassified Comamonadaceae) showed their ability to utilize alkanes, aromatics and crude oil as growth substrates. Anaerobically enriched consortium was predominated by Bacillaceae, Pseudomonadaceae, Xanthomonadaceae, Porphyromonadaceae and Comamonadaceae members. Anaerobic consortium was found to be relatively less efficient in terms of TPH (total petroleum hydrocarbons) degradation compared to its aerobic counterpart.
    Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients. All patients (n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75mg of ASA per day in a single antiplatelet therapy for 3months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed. There was a significant reduction in 24-h BP and blood pressure at night in the ASA group evening group compared with the ASA morning group and the control group. The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA. The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.Cutaneous melanoma is known to be one of the most dangerous skin cancers because of its metastatic functions. Today, it is essential to investigate specific biomarkers for the target treatment in many diseases including cancers. DJ-1 protein, also known as Parkinson disease 7, has various functions associated with cancer progression including cell survival and migration. Phosphatase and tensin homolog (PTEN) is a tumor suppressor that regulates the PI3K/AKT signaling pathway and its mutations have been reported to frequently occur in many cancers such as thyroid, breast and skin. Recently, DJ-1 has been identified as a negative regulator of PTEN in many human cancer cells. However, the impacts and relationship of DJ-1 and PTEN have not been studied yet in melanoma. To confirm the expression of DJ-1 and PTEN in melanoma compared to normal skin tissues and find out functions of DJ-1 in melanoma cells, Western blot analysis and immunohistochemical staining were used. Transfection of G361 cells with DJ-1-specific small interfering RNA was performed to figure out the roles of DJ-1 and the relationship between DJ-1 and PTEN in melanoma cells. In our study, the DJ-1 protein was significantly increased with loss of PTEN protein in melanoma compared to that in normal skin. Inhibition of DJ-1 in G361 cells induced apoptosis, and suppressed cell survival and migration. Furthermore, suppression of DJ-1 in G361 cells increased the expression of cleaved caspase-3, cleaved PARP, Bax, p53, and Daxx as well as PTEN, while it decreased expression of survivin, caspase-3, and PARP. Also, downregulated DJ-1 inhibited phosphorylation of AKT in G361 cells. Collectively, DJ-1 overexpression could affect the proliferative and invasive capabilities of melanoma cells via regulating the PTEN/AKT pathway and apoptosis-related proteins. This study suggests that DJ-1 may be a potential target for the treatment of melanoma. To discuss and summarize the latest evidence on imaging techniques in giant cell arteritis (GCA) and Takayasu arteritis (TAK). This is a report on the performance of ultrasound (US), magnetic resonance imaging (MRI), computed tomography (CT), 18F-fluorodeoxyglucose positron emission tomography (18-FDG-PET), and other emerging imaging techniques in diagnosis, outcome prediction, and monitoring of disease activity. Imaging techniques have gained an important role for diagnosis of large vessel vasculitides (LVV). As signs of vasculitis, US, MRI, and CT show a homogeneous arterial wall thickening, which is mostly concentric. PET displays increased FDG uptake in inflamed artery walls. US is recommended as the initial imaging modality in GCA. MRI and PET/CT may also detect vasculitis of temporal arteries. For TAK, MRI is recommended as the first imaging modality as it provides a good overview without radiation. Extracranial LVV can be confirmed by all four modalities. In addition, MRI and PET/CT provide consisterview without radiation. Extracranial LVV can be confirmed by all four modalities. In addition, MRI and PET/CT provide consistent examination of the aorta and its branches. New techniques such as contrast-enhanced ultrasound, PET/MRI, and auxiliary methods such as "computer-assisted quantitative analysis" have emerged and need to be further validated. Imaging has partly replaced histology for confirming LVV. Provided experience and adequate training, US, MRI, CT, or PET provide excellent diagnostic accuracy. Imaging results need to complement history and clinical examination. https://www.selleckchem.com/products/sd-208.html Ongoing studies are evaluating the role of imaging for monitoring and outcome measurement.Stable and efficient hydrocarbon degrading microbial consortia were developed from a refinery sludge through nitrate amendment for their application in enhanced bioremediation of petroleum contaminated waste. Nitrate induced biostimulation of refinery sludge resulted in increased abundance of hydrocarbon degrading Rhodocyclaceae, Xanthomonadaceae, Syntrophaceae and Comamonadaceae members. Repeated subculturing of nitrate stimulated communities in crude oil supplemented basal medium was done under aerobic and anaerobic conditions. Aerobically enriched consortia (composed of Pseudomonadaceae, Pseudoxanthomonadaceae and unclassified Comamonadaceae) showed their ability to utilize alkanes, aromatics and crude oil as growth substrates. Anaerobically enriched consortium was predominated by Bacillaceae, Pseudomonadaceae, Xanthomonadaceae, Porphyromonadaceae and Comamonadaceae members. Anaerobic consortium was found to be relatively less efficient in terms of TPH (total petroleum hydrocarbons) degradation compared to its aerobic counterpart.
    0 Commenti 0 condivisioni 52 Views 0 Anteprima

  • Artificial calcium influx by an ionophore did not induce major changes in the accumulation of astaxanthin, nor in the transcript levels, but amplified the response of crtR-b to nsPEFs at 25 ns, while decreased in 50 ns treatment. When Ca2+ influx was inhibited by GdCl3, the transcript of psy and bkt 1 were decreased for both 25 ns and 50 ns treatments, while crtR-b exhibited an obvious increase for the 25 ns treatment. We interpret these data in a working model, where nsPEFs permeabilise plasma and chloroplast membrane depending on pulse duration leading to a differential release of plastid retrograde signaling to the nucleus.Barrett's esophagus (BE) predisposes for the malignant condition of esophageal adenocarcinoma (EAC). Since BE patients have few or no symptoms, most of these patients are not identified and not included in surveillance programs. These BE patients are at risk of developing advanced-stage EAC. At present, non-invasive tests to identify BE patients from the general population are lacking. We and others showed that Bone Morphogenetic Protein 4 (BMP4), and other BMPs are upregulated in BE. We aimed to determine if circulating BMPs can be identified and used as blood biomarkers to identify BE patients at high risk in the general population. https://www.selleckchem.com/products/jib-04.html In this study, we could detect the different BMPs in the blood of 112 BE patients and 134 age- and sex-matched controls. Concentration levels of BMP2, BMP4, and BMP5 were elevated in BE patients, with BMP2 and BMP5 significantly increased. BMP5 remained significant after multivariate analysis and was associated with an increased risk for BE with an OR of 1.49 (p value 0.01). Per log (pg/mL) of BMP5, the odds of having BE increased by 50%. Future optimization and validation studies might be needed to prove its utility as a non-invasive method for the detection of BE in high-risk populations and screening programs.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These enzymes are widely distributed among plants and bacteria. Previously, we have described for the first time RIP genes in mosquitoes belonging to the Culicidae family. We showed that these genes are derived from a single event of horizontal gene transfer (HGT) from a prokaryotic donor. Mosquito RIP genes are evolving under purifying selection, strongly suggesting that these toxins have acquired a functional role. In this work, we show the existence of two RIP encoding genes in the genome of the whitefly Bemisia tabaci, a hemiptera species belonging to the Aleyrodidae family distantly related to mosquitoes. Contamination artifacts were ruled out analyzing three independent B. tabaci genome databases. In contrast to mosquito RIPs, whitefly genes harbor introns and according to transcriptomic evidence are transcribed and spliced. Phylogeny and the taxonomic distribution strongly support that whitefly RIP genes are derived from an independent HGT event from a plant source. These results, along with our previous description of RIPs in Diptera, suggest that the acquired genes are functional in these insects and confer some fitness advantage.Cataract is the leading cause of blindness worldwide but the mechanisms involved in the process of cataractogenesis are not yet fully understood. Two most prevalent types of age-related cataracts are nuclear (N) and cortical (C) cataracts. A common environmental factor in most age-related cataracts is believed to be oxidative stress. The lens epithelium, the first physical and biological barrier in the lens, is build from lens epithelial cells (LECs). LECs are important for the maintenance of lens transparency as they control energy production, antioxidative mechanisms and biochemical transport for the whole lens. The purpose of this study is to characterize compounds in LECs originated from N and C cataracts, by using the synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy, in order to understand the functional importance of their different bio-macromolecules in cataractogenesis. We used the SR-FTIR microspectroscopy setup installed on the beamline MIRAS at the Spanish synchrotron light source ALBA, where measurements were set to achieve single cell resolution, with high spectral stability and high photon flux. The results showed that protein aggregation in form of fibrils was notably pronounced in LECs of N cataracts, while oxidative stress and the lipids peroxidation were more pronounced in LECs of C cataracts.Previous studies have shown that it is possible to nutritionally program gilthead seabream offspring through fish oil (FO) replacement by vegetable oils (VO) in the broodstock diet, to improve their ability to grow fast when fed low fish meal (FM) and FO diets during grow-out phase. However, in those studies broodstock performance was reduced by the VO contained diet. Therefore, the present study aimed to determine if it is possible to replace FO by a mixture of FO and rapeseed oil (RO) with a specific fatty acid profile in broodstock diets, without altering gilthead seabream broodstock reproductive performance. Besides, the study also aimed to evaluate the reproductive performance of broodstock with different expression of fatty acid desaturase 2 gene (fads2) a key enzyme in synthesis of long chain polyunsaturated fatty acids. For that purpose, broodfish having either a high (HD) or low (LD) expression of fads2 were fed for three months during the spawning season with two diets containing different fatty acid profiles and their effects on reproductive hormones, fecundity, sperm and egg quality, egg biochemical composition and fads2 expression were studied. The results showed that blood fads2 expression in females, which tended to be higher than in males, was positively related to plasma 17β-estradiol levels. Moreover, broodstock with high blood fads2 expression showed a better reproductive performance, in terms of fecundity and sperm and egg quality, which was correlated with female fads2 expression. Our data also showed that it is feasible to reduce ARA, EPA and DHA down to 0.43, 6.6 and 8.4% total fatty acids, respectively, in broodstock diets designed to induce nutritional programming effects in the offspring without adverse effects on spawning quality. Further studies are being conducted to test the offspring with low FM and FO diets along life span.
    Artificial calcium influx by an ionophore did not induce major changes in the accumulation of astaxanthin, nor in the transcript levels, but amplified the response of crtR-b to nsPEFs at 25 ns, while decreased in 50 ns treatment. When Ca2+ influx was inhibited by GdCl3, the transcript of psy and bkt 1 were decreased for both 25 ns and 50 ns treatments, while crtR-b exhibited an obvious increase for the 25 ns treatment. We interpret these data in a working model, where nsPEFs permeabilise plasma and chloroplast membrane depending on pulse duration leading to a differential release of plastid retrograde signaling to the nucleus.Barrett's esophagus (BE) predisposes for the malignant condition of esophageal adenocarcinoma (EAC). Since BE patients have few or no symptoms, most of these patients are not identified and not included in surveillance programs. These BE patients are at risk of developing advanced-stage EAC. At present, non-invasive tests to identify BE patients from the general population are lacking. We and others showed that Bone Morphogenetic Protein 4 (BMP4), and other BMPs are upregulated in BE. We aimed to determine if circulating BMPs can be identified and used as blood biomarkers to identify BE patients at high risk in the general population. https://www.selleckchem.com/products/jib-04.html In this study, we could detect the different BMPs in the blood of 112 BE patients and 134 age- and sex-matched controls. Concentration levels of BMP2, BMP4, and BMP5 were elevated in BE patients, with BMP2 and BMP5 significantly increased. BMP5 remained significant after multivariate analysis and was associated with an increased risk for BE with an OR of 1.49 (p value 0.01). Per log (pg/mL) of BMP5, the odds of having BE increased by 50%. Future optimization and validation studies might be needed to prove its utility as a non-invasive method for the detection of BE in high-risk populations and screening programs.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Ribosome inactivating proteins (RIPs) are RNA N-glycosidases that depurinate a specific adenine residue in the conserved sarcin/ricin loop of 28S rRNA. These enzymes are widely distributed among plants and bacteria. Previously, we have described for the first time RIP genes in mosquitoes belonging to the Culicidae family. We showed that these genes are derived from a single event of horizontal gene transfer (HGT) from a prokaryotic donor. Mosquito RIP genes are evolving under purifying selection, strongly suggesting that these toxins have acquired a functional role. In this work, we show the existence of two RIP encoding genes in the genome of the whitefly Bemisia tabaci, a hemiptera species belonging to the Aleyrodidae family distantly related to mosquitoes. Contamination artifacts were ruled out analyzing three independent B. tabaci genome databases. In contrast to mosquito RIPs, whitefly genes harbor introns and according to transcriptomic evidence are transcribed and spliced. Phylogeny and the taxonomic distribution strongly support that whitefly RIP genes are derived from an independent HGT event from a plant source. These results, along with our previous description of RIPs in Diptera, suggest that the acquired genes are functional in these insects and confer some fitness advantage.Cataract is the leading cause of blindness worldwide but the mechanisms involved in the process of cataractogenesis are not yet fully understood. Two most prevalent types of age-related cataracts are nuclear (N) and cortical (C) cataracts. A common environmental factor in most age-related cataracts is believed to be oxidative stress. The lens epithelium, the first physical and biological barrier in the lens, is build from lens epithelial cells (LECs). LECs are important for the maintenance of lens transparency as they control energy production, antioxidative mechanisms and biochemical transport for the whole lens. The purpose of this study is to characterize compounds in LECs originated from N and C cataracts, by using the synchrotron radiation-based Fourier Transform Infrared (SR-FTIR) microspectroscopy, in order to understand the functional importance of their different bio-macromolecules in cataractogenesis. We used the SR-FTIR microspectroscopy setup installed on the beamline MIRAS at the Spanish synchrotron light source ALBA, where measurements were set to achieve single cell resolution, with high spectral stability and high photon flux. The results showed that protein aggregation in form of fibrils was notably pronounced in LECs of N cataracts, while oxidative stress and the lipids peroxidation were more pronounced in LECs of C cataracts.Previous studies have shown that it is possible to nutritionally program gilthead seabream offspring through fish oil (FO) replacement by vegetable oils (VO) in the broodstock diet, to improve their ability to grow fast when fed low fish meal (FM) and FO diets during grow-out phase. However, in those studies broodstock performance was reduced by the VO contained diet. Therefore, the present study aimed to determine if it is possible to replace FO by a mixture of FO and rapeseed oil (RO) with a specific fatty acid profile in broodstock diets, without altering gilthead seabream broodstock reproductive performance. Besides, the study also aimed to evaluate the reproductive performance of broodstock with different expression of fatty acid desaturase 2 gene (fads2) a key enzyme in synthesis of long chain polyunsaturated fatty acids. For that purpose, broodfish having either a high (HD) or low (LD) expression of fads2 were fed for three months during the spawning season with two diets containing different fatty acid profiles and their effects on reproductive hormones, fecundity, sperm and egg quality, egg biochemical composition and fads2 expression were studied. The results showed that blood fads2 expression in females, which tended to be higher than in males, was positively related to plasma 17β-estradiol levels. Moreover, broodstock with high blood fads2 expression showed a better reproductive performance, in terms of fecundity and sperm and egg quality, which was correlated with female fads2 expression. Our data also showed that it is feasible to reduce ARA, EPA and DHA down to 0.43, 6.6 and 8.4% total fatty acids, respectively, in broodstock diets designed to induce nutritional programming effects in the offspring without adverse effects on spawning quality. Further studies are being conducted to test the offspring with low FM and FO diets along life span.
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  • Idiopathic cryptoglandular fistula-in-ano is a common pathological condition. Fistula-in-ano has been managed by a number of surgical techniques, and there is still no consensus regarding the management of this condition. Surgical techniques aim to treat and cure the fistula-in-ano with minimal risk of recurrence or complications, and to maintain patient continence. This article discusses the evidence available to inform the management of idiopathic cryptoglandular fistula-in-ano, and problems that surgeons face because of the lack of high-quality evidence.Hypoxaemia is a common presentation in critically ill patients, with the potential for severe harm if not addressed appropriately. This review provides a framework to guide the management of any hypoxaemic patient, regardless of the clinical setting. Key steps in managing such patients include ascertaining the severity of hypoxaemia, the underlying diagnosis and implementing the most appropriate treatment. Oxygen therapy can be delivered by variable or fixed rate devices, and non-invasive ventilation; if patients deteriorate they may require tracheal intubation and mechanical ventilation. Early critical care team involvement is a key part of this pathway. Specialist treatments for severe hypoxaemia can only be undertaken on an intensive care unit and this field is developing rapidly as trial results become available. It is important that each new scenario is approached in a structured manner with an open diagnostic mind and a clear escalation plan.Hydronephrosis is diagnosed more often with the increased availability of computed tomography and ultrasound scanning. Hydronephrosis is an important consideration in patients with abdominal or pelvic pathology as progressive dilation of the upper urinary tract can lead to acute kidney injury and, if not corrected, permanent nephron loss. This article explores how to approach an adult patient with hydronephrosis, encompassing aetiology, clinical presentation, diagnosis and management.Epidural analgesia is a key component in the management of inpatient pain relief, particularly in surgical and trauma patients, and those with comorbidities. When used appropriately epidurals can decrease a patient's opiate consumption, as well as reducing the risk of adverse cardiorespiratory outcomes. https://www.selleckchem.com/products/oligomycin-a.html To non-anaesthetists, or those not versed in their usage, epidurals can appear complex and intimidating, and the potential complications, although rare, can be catastrophic if not picked up on in a timely fashion. This article demystifies the epidural for hospital clinicians, looking at the anatomy and pharmacology, helping to identify patients who may benefit from epidural analgesia, highlighting some common pitfalls and questions posed by nursing staff, and providing a framework via which junior clinicians can detect, manage and appropriately escalate epidural-related problems and complications. Epidural analgesia is an invasive and high-risk intervention; as such it should always be managed by a multidisciplinary team, including anaesthesia and acute pain services.Management of anticoagulation has become a hot topic in the last decade. Health-care professionals are encountering increasing number of patients diagnosed with a thromboembolic episode, probably as a result of heightened awareness. In addition, the recognition that hospital-acquired thrombosis causes substantial mortality has led to an emphasis on appropriate thromboprophylaxis in all patients deemed at risk of thrombosis. However, the use of anticoagulants for both treatment and prophylaxis of thrombosis can pose a challenge in individuals who are obese. There are no detailed studies in this area and as such the dosing and monitoring of anticoagulants in these individuals can be problematic.Polypharmacy and multimorbidity are both currently rising. The number of medicines taken is the single biggest predictor of adverse drug events. Deprescribing is an approach to managing polypharmacy and reducing adverse outcomes. Multiple international evidence-based guidelines are emerging to promote discontinuation of high-risk medications, and use of alternative medical and non-pharmacological management. This review outlines the evidence base behind deprescribing, and suggests some pragmatic approaches to decision making around medication review.The significance of early diagnosis for melanoma prognosis and survival cannot be understated. The public health benefits of melanoma prevention and detection have driven advances in diagnostics for skin cancer, particularly in the field of artificial intelligence. Evaluating the benefits and limitations of artificial intelligence in dermatology is paramount to its future development and clinical application.It is important for physicians to be aware of stroke warning syndromes because, although rare, there is a high associated risk of subsequent ischaemic infarction. Stroke warning syndromes present as stereotypical, recurrent transient episodes of focal neurological deficit, in the absence of cortical signs, occurring within a short period of time. They are broadly divided into two main subtypes, based on vascular territory capsular warning syndrome and pontine warning syndrome. The exact underlying pathophysiology related to stroke warning syndromes is incompletely established, but proposed pathophysiological hypotheses for cerebral hypoperfusion include micro-atherosclerosis (cerebral small vessel disease) and haemodynamic instability (e.g. hypotension). Atherosclerotic disease involving small perforating arteries in the anterior circulation (e.g. lenticulostriatal arteries) gives rise to capsular warning syndrome and subsequent risk of capsular infarcts. Conversely, involvement of the posterior circulation pontine perforator arteries gives rise to pontine warning syndrome, which can result in paramedian pontine infarcts. Although the evidence is limited, recommended treatment modalities include permissive hypertension, intravenous recombinant tissue plasminogen activator, dual antiplatelet therapy and statins.The impact of hospital-acquired pneumonia and the pressure to reduce unnecessary antibiotic prescribing has lead to the publication of prescribing guidelines from the National Institute for Health and Care Excellence. This editorial gives an overview of the guidelines and emphasises the need for more high-quality evidence to inform decision making in this group of patients.
    Idiopathic cryptoglandular fistula-in-ano is a common pathological condition. Fistula-in-ano has been managed by a number of surgical techniques, and there is still no consensus regarding the management of this condition. Surgical techniques aim to treat and cure the fistula-in-ano with minimal risk of recurrence or complications, and to maintain patient continence. This article discusses the evidence available to inform the management of idiopathic cryptoglandular fistula-in-ano, and problems that surgeons face because of the lack of high-quality evidence.Hypoxaemia is a common presentation in critically ill patients, with the potential for severe harm if not addressed appropriately. This review provides a framework to guide the management of any hypoxaemic patient, regardless of the clinical setting. Key steps in managing such patients include ascertaining the severity of hypoxaemia, the underlying diagnosis and implementing the most appropriate treatment. Oxygen therapy can be delivered by variable or fixed rate devices, and non-invasive ventilation; if patients deteriorate they may require tracheal intubation and mechanical ventilation. Early critical care team involvement is a key part of this pathway. Specialist treatments for severe hypoxaemia can only be undertaken on an intensive care unit and this field is developing rapidly as trial results become available. It is important that each new scenario is approached in a structured manner with an open diagnostic mind and a clear escalation plan.Hydronephrosis is diagnosed more often with the increased availability of computed tomography and ultrasound scanning. Hydronephrosis is an important consideration in patients with abdominal or pelvic pathology as progressive dilation of the upper urinary tract can lead to acute kidney injury and, if not corrected, permanent nephron loss. This article explores how to approach an adult patient with hydronephrosis, encompassing aetiology, clinical presentation, diagnosis and management.Epidural analgesia is a key component in the management of inpatient pain relief, particularly in surgical and trauma patients, and those with comorbidities. When used appropriately epidurals can decrease a patient's opiate consumption, as well as reducing the risk of adverse cardiorespiratory outcomes. https://www.selleckchem.com/products/oligomycin-a.html To non-anaesthetists, or those not versed in their usage, epidurals can appear complex and intimidating, and the potential complications, although rare, can be catastrophic if not picked up on in a timely fashion. This article demystifies the epidural for hospital clinicians, looking at the anatomy and pharmacology, helping to identify patients who may benefit from epidural analgesia, highlighting some common pitfalls and questions posed by nursing staff, and providing a framework via which junior clinicians can detect, manage and appropriately escalate epidural-related problems and complications. Epidural analgesia is an invasive and high-risk intervention; as such it should always be managed by a multidisciplinary team, including anaesthesia and acute pain services.Management of anticoagulation has become a hot topic in the last decade. Health-care professionals are encountering increasing number of patients diagnosed with a thromboembolic episode, probably as a result of heightened awareness. In addition, the recognition that hospital-acquired thrombosis causes substantial mortality has led to an emphasis on appropriate thromboprophylaxis in all patients deemed at risk of thrombosis. However, the use of anticoagulants for both treatment and prophylaxis of thrombosis can pose a challenge in individuals who are obese. There are no detailed studies in this area and as such the dosing and monitoring of anticoagulants in these individuals can be problematic.Polypharmacy and multimorbidity are both currently rising. The number of medicines taken is the single biggest predictor of adverse drug events. Deprescribing is an approach to managing polypharmacy and reducing adverse outcomes. Multiple international evidence-based guidelines are emerging to promote discontinuation of high-risk medications, and use of alternative medical and non-pharmacological management. This review outlines the evidence base behind deprescribing, and suggests some pragmatic approaches to decision making around medication review.The significance of early diagnosis for melanoma prognosis and survival cannot be understated. The public health benefits of melanoma prevention and detection have driven advances in diagnostics for skin cancer, particularly in the field of artificial intelligence. Evaluating the benefits and limitations of artificial intelligence in dermatology is paramount to its future development and clinical application.It is important for physicians to be aware of stroke warning syndromes because, although rare, there is a high associated risk of subsequent ischaemic infarction. Stroke warning syndromes present as stereotypical, recurrent transient episodes of focal neurological deficit, in the absence of cortical signs, occurring within a short period of time. They are broadly divided into two main subtypes, based on vascular territory capsular warning syndrome and pontine warning syndrome. The exact underlying pathophysiology related to stroke warning syndromes is incompletely established, but proposed pathophysiological hypotheses for cerebral hypoperfusion include micro-atherosclerosis (cerebral small vessel disease) and haemodynamic instability (e.g. hypotension). Atherosclerotic disease involving small perforating arteries in the anterior circulation (e.g. lenticulostriatal arteries) gives rise to capsular warning syndrome and subsequent risk of capsular infarcts. Conversely, involvement of the posterior circulation pontine perforator arteries gives rise to pontine warning syndrome, which can result in paramedian pontine infarcts. Although the evidence is limited, recommended treatment modalities include permissive hypertension, intravenous recombinant tissue plasminogen activator, dual antiplatelet therapy and statins.The impact of hospital-acquired pneumonia and the pressure to reduce unnecessary antibiotic prescribing has lead to the publication of prescribing guidelines from the National Institute for Health and Care Excellence. This editorial gives an overview of the guidelines and emphasises the need for more high-quality evidence to inform decision making in this group of patients.
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  • an important component of patient selection for advanced heart failure therapies. Addressing these specific components may help improve access to advanced therapies and post-LVAD outcomes.Determination of circadian phase is required to diagnose and treat circadian abnormalities, but the measurement of dim light melatonin onset (DLMO), the most common phase marker, is laborious. As sleep timing reflects circadian phase, measurement of sleep markers (e.g., sleep onset, sleep midpoint, sleep offset) provides a simple way to estimate DLMO. The study aim was to compare methods to estimate DLMO from markers derived from the Pittsburgh Sleep Quality Index (PSQI), Munich Chronotype Questionnaire (MCTQ), sleep diaries, and actigraphy. PSQI, MCTQ, and 1 week of diary and actigraphy data were collected from 72 (36 f, 36 m) healthy adults aged 23.1 (± 3.6) y prior to a laboratory sleep study. Saliva samples were collected hourly in dim light during the second evening of the study. The sleep markers most strongly associated with DLMO from each source were PSQI onset, MCTQ average midpoint, 7-d diary midpoint, and 7-d actigraphy midpoint. https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html Estimates of DLMO as a fixed interval before the sleep marker exhibited proportional bias. DLMO estimated from regression models based on sleep midpoint from 7 d of diary or 7 d of actigraphy showed the narrowest limits of agreement with measured DLMO without proportional bias (±1.8 h and ±1.9 h, respectively). Our findings indicate none of the methods provided precise estimates of DLMO from sleep markers. The best estimates were from linear regressions on sleep midpoints from 7 d of diary or actigraphy, and these estimates of DLMO may be suitable for limited research purposes.Aim To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). ResultsABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR] 1.8; 95% CI 1.3-2.7; p = 0.0019), PFS (HR 2.0; 95% CI 1.4-2.9; p less then 0.0001) and PFI (HR 1.9; 95% CI 1.4-2.8; p = 0.0002) compared with those in low-risk group. Conclusion The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI.
    For human papilloma virus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset.

    Retrospective cohort study.

    National Cancer Database (NCDB).

    We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression.

    In therapeutic NDs (n = 1935), the following proportions of positive LNs were found level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31;
    = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18;
    < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected.

    For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III.

    4.
    4.
    Surgical resection is the mainstay of treatment for spheno-orbital meningiomas. The Sonopet® is an ultrasonic aspirator device that provides several advantages over the traditional standard suction techniques and bone drill, including decreased collateral soft tissue damage, more precise bone removal and a clearer operative field. The purpose of the study was to examine the treatment outcomes of Sonopet®-assisted resection of spheno-orbital meningiomas.

    A retrospective chart review was conducted in seven patients with spheno-orbital meningioma in a single institution who underwent surgical resection with the Sonopet®. Pre-operative and post-operative data included the assessment of visual acuity, relative afferent pupillary defect (RAPD), Ishihara score, proptosis, fundus examination, computerised visual fields and the presence or absence of diplopia, headache, and other neuro-ophthalmic complications.

    Nine Sonopet®-assisted procedures were performed on seven patients. Post-operatively, 89% of cases had stabilization or improvement of visual acuity and colour vision, whilst 29% had improved visual fields with the remainder being stable. Proptosis improved in all patients. Five of nine cases (44%) had new post-operative cranial nerve palsies, of which 75% were transient. One patient had tumour recurrence after 14months, requiring further tumour resection and radiotherapy.

    Sonopet®-assisted resection of spheno-orbital meningiomas has comparable outcomes of visual improvement and complication rates to traditional resection techniques. Longer periods of post-operative observation and follow-up are recommended to observe long-term benefits.
    Sonopet®-assisted resection of spheno-orbital meningiomas has comparable outcomes of visual improvement and complication rates to traditional resection techniques. Longer periods of post-operative observation and follow-up are recommended to observe long-term benefits.
    an important component of patient selection for advanced heart failure therapies. Addressing these specific components may help improve access to advanced therapies and post-LVAD outcomes.Determination of circadian phase is required to diagnose and treat circadian abnormalities, but the measurement of dim light melatonin onset (DLMO), the most common phase marker, is laborious. As sleep timing reflects circadian phase, measurement of sleep markers (e.g., sleep onset, sleep midpoint, sleep offset) provides a simple way to estimate DLMO. The study aim was to compare methods to estimate DLMO from markers derived from the Pittsburgh Sleep Quality Index (PSQI), Munich Chronotype Questionnaire (MCTQ), sleep diaries, and actigraphy. PSQI, MCTQ, and 1 week of diary and actigraphy data were collected from 72 (36 f, 36 m) healthy adults aged 23.1 (± 3.6) y prior to a laboratory sleep study. Saliva samples were collected hourly in dim light during the second evening of the study. The sleep markers most strongly associated with DLMO from each source were PSQI onset, MCTQ average midpoint, 7-d diary midpoint, and 7-d actigraphy midpoint. https://www.selleckchem.com/products/pd-1-pd-l1-inhibitor-2.html Estimates of DLMO as a fixed interval before the sleep marker exhibited proportional bias. DLMO estimated from regression models based on sleep midpoint from 7 d of diary or 7 d of actigraphy showed the narrowest limits of agreement with measured DLMO without proportional bias (±1.8 h and ±1.9 h, respectively). Our findings indicate none of the methods provided precise estimates of DLMO from sleep markers. The best estimates were from linear regressions on sleep midpoints from 7 d of diary or actigraphy, and these estimates of DLMO may be suitable for limited research purposes.Aim To define the impact of polymorphisms in genes involved in platinum-taxane and estrogen activity in the outcome of platinum-based treated ovarian cancer patients (OCP). Patients & Methods Two hundred and thirty OCP were analyzed for 124 germ-line polymorphisms to generate a prognostic score for overall survival (OS), progression-free survival (PFS) and platinum-free interval (PFI). ResultsABCG2 rs3219191D>I, UGT1A rs10929302G>A and UGT1A rs2741045T>C polymorphisms were significantly associated with all three parameters (OS, PFS and PFI) and were used to generate a score. Patients in high-risk group had a poorer OS (hazard ratio [HR] 1.8; 95% CI 1.3-2.7; p = 0.0019), PFS (HR 2.0; 95% CI 1.4-2.9; p less then 0.0001) and PFI (HR 1.9; 95% CI 1.4-2.8; p = 0.0002) compared with those in low-risk group. Conclusion The prognostic-score including polymorphisms involved in drug and estrogen pathways stratifies OCP according to OS, PFS and PFI. For human papilloma virus-associated oropharynx squamous cell carcinoma (HPV+ OPSCC), we evaluated the distribution of neck-level lymph node (LN) metastasis, based on postsurgical histopathology, and the incidence of and risk factors for occult LN metastases, as these patterns need clarification for this newer cancer subset. Retrospective cohort study. National Cancer Database (NCDB). We analyzed 2358 patients in the NCDB with HPV+ OPSCC who underwent neck dissection (ND) from 2010 to 2015. Incidence and distribution of LN metastases were calculated for neck levels I to V. Variables associated with occult LN metastasis were assessed by multivariate logistic regression. In therapeutic NDs (n = 1935), the following proportions of positive LNs were found level I, 9.0% (n = 175); level II, 81.0% (n = 1568); level III, 29.6% (n = 573); level IV, 11.9% (n = 230); and level V, 4.9% (n = 95). In elective NDs (n = 423), occult-positive LNs were found in 35.8% (n = 152), with the following proportions by level level I, 3.3% (n = 14); level II, 26.9% (n = 114); level III, 8.7% (n = 37); level IV, 4.0% (n = 17); and level V, 0.2% (n = 1). The presence of occult LNs was independently associated with a Charlson-Deyo score of 1 (odds ratio, 2.26; 95% CI, 1.18-4.31; = .014) and lymphovascular invasion (odds ratio, 5.91; 95% CI, 3.21-11.18; < .001). Occult LN metastases were not significantly associated with pT classification, primary site, or number of LNs resected. For HPV+ OPSCC, occult nodal disease is common. Therapeutic NDs should encompass at least levels II, III, and IV and possibly I, whereas elective NDs could possibly encompass levels II and III. 4. 4. Surgical resection is the mainstay of treatment for spheno-orbital meningiomas. The Sonopet® is an ultrasonic aspirator device that provides several advantages over the traditional standard suction techniques and bone drill, including decreased collateral soft tissue damage, more precise bone removal and a clearer operative field. The purpose of the study was to examine the treatment outcomes of Sonopet®-assisted resection of spheno-orbital meningiomas. A retrospective chart review was conducted in seven patients with spheno-orbital meningioma in a single institution who underwent surgical resection with the Sonopet®. Pre-operative and post-operative data included the assessment of visual acuity, relative afferent pupillary defect (RAPD), Ishihara score, proptosis, fundus examination, computerised visual fields and the presence or absence of diplopia, headache, and other neuro-ophthalmic complications. Nine Sonopet®-assisted procedures were performed on seven patients. Post-operatively, 89% of cases had stabilization or improvement of visual acuity and colour vision, whilst 29% had improved visual fields with the remainder being stable. Proptosis improved in all patients. Five of nine cases (44%) had new post-operative cranial nerve palsies, of which 75% were transient. One patient had tumour recurrence after 14months, requiring further tumour resection and radiotherapy. Sonopet®-assisted resection of spheno-orbital meningiomas has comparable outcomes of visual improvement and complication rates to traditional resection techniques. Longer periods of post-operative observation and follow-up are recommended to observe long-term benefits. Sonopet®-assisted resection of spheno-orbital meningiomas has comparable outcomes of visual improvement and complication rates to traditional resection techniques. Longer periods of post-operative observation and follow-up are recommended to observe long-term benefits.
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  • Continuous and robust monitoring of physiological signals is essential in improving the diagnosis and management of cardiovascular and respiratory diseases. The state-of-the-art systems for monitoring vital signs such as heart rate, heart rate variability, respiration rate, and other hemodynamic and respiratory parameters use often bulky and obtrusive systems or depend on wearables with limited sensing methods based on repetitive properties of the signals rather than the morphology. Moreover, multiple devices and modalities are typically needed for capturing various vital signs simultaneously. In this paper, we introduce ImpediBands small-sized distributed smart bio-impedance (Bio-Z) patches, where the communication between the patches is established through the human body, eliminating the need for electrical wires that would create a common potential point between sensors. We use ImpediBands to collect instantaneous measurements from multiple locations over the chest at the same time. We propose a blind source separation (BSS) technique based on the second-order blind identification (SOBI) followed by signal reconstruction to extract heart and lung activities from the Bio-Z signals. Using the separated source signals, we demonstrate the performance of our system via providing strong confidence in the estimation of heart and respiration rates with low RMSE (HRRMSE = 0.579 beats per minute, RRRMSE = 0.285 breaths per minute), and high correlation coefficients (rHR = 0.948, rRR = 0.921).This paper proposes novel methods for making embryonic bio-inspired hardware efficient against faults through self-healing, fault prediction, and fault-prediction assisted self-healing. The proposed self-healing recovers a faulty embryonic cell through innovative usage of healthy cells. Through experimentations, it is observed that self-healing is effective, but it takes a considerable amount of time for the hardware to recover from a fault that occurs suddenly without forewarning. To get over this problem of delay, novel deep learning-based formulations are proposed for fault predictions. The proposed self-healing technique is then deployed along with the proposed fault prediction methods to gauge the accuracy and delay of embryonic hardware. The proposed fault prediction and self-healing methods have been implemented in VHDL over FPGA. The proposed fault predictions achieve high accuracy with low training time. The accuracy is up to 99.36% with the training time of 2.16 min. The area overhead of the proposed self-healing method is 34%, and the fault recovery percentage is 75%. To the best of our knowledge, this is the first such work in embryonic hardware, and it is expected to open a new frontier in fault-prediction assisted self-healing for embryonic systems.Photoacoustic imaging (PAI), an emerging imaging technique, exploits the merits of both optical and ultrasound imaging, equipped with optical contrast and deep penetration. Typical linear PAI relies on a nanosecond laser pulse to induce photoacoustic signals. To construct a multi-wavelength PAI system, a multi-wavelength nano-second laser source is required, which greatly increases the cost of the PAI system. However, according to the nonlinear photoacoustic effect, the amplitude of the photoacoustic signals will vary with different base temperatures of the tissue. Therefore, using continuous-wave lasers with different wavelengths to induce different temperature variations at the same point of the tissue, and then using a single-wavelength pulsed laser to induce photoacoustic signals has been an alternative method to achieve multi-wavelength PAI. https://www.selleckchem.com/products/nb-598.html In this paper, based on the nonlinear photoacoustic effect, we developed a continuous-wave multi-wavelength laser source to cut down the cost of the conventional multi-wavelength PAI system. The principle will be introduced firstly, followed by qualitative and quantitative experiments.This paper presents an 8-channel energy-efficient analog front-end (AFE) for neural recording, with improvements in power supply rejection ratio (PSRR) and dynamic range. The input stage in the low noise amplifier (LNA) adopts low voltage supply (0.35 V) and current-reusing to achieve ultralow power. To maintain a high PSRR performance while using such a low-voltage supply, a replica-biasing scheme is proposed to generate a stable bias current for the input stage of the LNA despite large supply interference. By exploiting the signal characteristics in the tetrode recording, an averaged local field potential (A-LFP) servo loop is introduced to extend the dynamic range without consuming too **** extra power and chip area. The A-LFP signal is generated by integrating the four-channel PGA outputs from the same tetrode. Furthermore, the outputs of the programmable gain amplifier (PGA) are level shifted to bias the input nodes of the amplifier through large pseudo resistors, thus increase the maximum output range without distortion under the low-voltage supply. The proof-of-concept prototype is fabricated in a 65 nm CMOS process. Each recording channel including an LNA and a PGA occupies 0.04 mm 2 and consumes 340 nW from the 0.35 V and 0.7 V supply. Each A-LFP servo loop, which is shared by four recording channels, occupies 0.04 mm 2 and consumes 190 nW. The maximum gain of the AFE is 54 dB, and the input-referred noise is 6.7 μV over the passband from 0.5 Hz to 6.5 kHz. Measurement also shows that the 0.35 V replica-biasing input stage can tolerate a large interferer up to 200 mVpp with a PSRR of 74 dB, which has been improved to 110 dB with a silicon respin that shields critical wires in the layout.The evaluation of toxic effects of nanoparticles (NPs) has become an important aspect of Nanotechnology research in the 21st century. The present investigation deals with the green synthesis of biogenic zinc oxide nanoparticles (ZnO-NPs) using Bryophyllum pinnatum leaves, their characterization and evaluation of acute oral toxicity in Wistar rats. The characterization of synthesized ZnO-NPs revealed maximum absorbance at 307 nm on UV-Vis spectrophotometric analysis, NTA showed mean size of particles and mode of the particles distribution as 128.2 nm and 12.6 nm, respectively. Zeta potential was found to be -0.369 mV. The absorbance shown by FTIR at 3469, 1644, 1355 and 887 cm-1 indicates the involvement of biomolecules that are accountable for capping and stabilization of ZnO-NPs. The XRD assessment further demonstrated the crystalline nature of the ZnO-NP. The TEM analysis of the synthesized ZnO-NPs revealed the presence of spherical NPs with the mean size of 3.7 nm. The acute oral toxicity evaluation in rat showed an approximate median lethal dose to be more than 2000 mg/kg body weight.
    Continuous and robust monitoring of physiological signals is essential in improving the diagnosis and management of cardiovascular and respiratory diseases. The state-of-the-art systems for monitoring vital signs such as heart rate, heart rate variability, respiration rate, and other hemodynamic and respiratory parameters use often bulky and obtrusive systems or depend on wearables with limited sensing methods based on repetitive properties of the signals rather than the morphology. Moreover, multiple devices and modalities are typically needed for capturing various vital signs simultaneously. In this paper, we introduce ImpediBands small-sized distributed smart bio-impedance (Bio-Z) patches, where the communication between the patches is established through the human body, eliminating the need for electrical wires that would create a common potential point between sensors. We use ImpediBands to collect instantaneous measurements from multiple locations over the chest at the same time. We propose a blind source separation (BSS) technique based on the second-order blind identification (SOBI) followed by signal reconstruction to extract heart and lung activities from the Bio-Z signals. Using the separated source signals, we demonstrate the performance of our system via providing strong confidence in the estimation of heart and respiration rates with low RMSE (HRRMSE = 0.579 beats per minute, RRRMSE = 0.285 breaths per minute), and high correlation coefficients (rHR = 0.948, rRR = 0.921).This paper proposes novel methods for making embryonic bio-inspired hardware efficient against faults through self-healing, fault prediction, and fault-prediction assisted self-healing. The proposed self-healing recovers a faulty embryonic cell through innovative usage of healthy cells. Through experimentations, it is observed that self-healing is effective, but it takes a considerable amount of time for the hardware to recover from a fault that occurs suddenly without forewarning. To get over this problem of delay, novel deep learning-based formulations are proposed for fault predictions. The proposed self-healing technique is then deployed along with the proposed fault prediction methods to gauge the accuracy and delay of embryonic hardware. The proposed fault prediction and self-healing methods have been implemented in VHDL over FPGA. The proposed fault predictions achieve high accuracy with low training time. The accuracy is up to 99.36% with the training time of 2.16 min. The area overhead of the proposed self-healing method is 34%, and the fault recovery percentage is 75%. To the best of our knowledge, this is the first such work in embryonic hardware, and it is expected to open a new frontier in fault-prediction assisted self-healing for embryonic systems.Photoacoustic imaging (PAI), an emerging imaging technique, exploits the merits of both optical and ultrasound imaging, equipped with optical contrast and deep penetration. Typical linear PAI relies on a nanosecond laser pulse to induce photoacoustic signals. To construct a multi-wavelength PAI system, a multi-wavelength nano-second laser source is required, which greatly increases the cost of the PAI system. However, according to the nonlinear photoacoustic effect, the amplitude of the photoacoustic signals will vary with different base temperatures of the tissue. Therefore, using continuous-wave lasers with different wavelengths to induce different temperature variations at the same point of the tissue, and then using a single-wavelength pulsed laser to induce photoacoustic signals has been an alternative method to achieve multi-wavelength PAI. https://www.selleckchem.com/products/nb-598.html In this paper, based on the nonlinear photoacoustic effect, we developed a continuous-wave multi-wavelength laser source to cut down the cost of the conventional multi-wavelength PAI system. The principle will be introduced firstly, followed by qualitative and quantitative experiments.This paper presents an 8-channel energy-efficient analog front-end (AFE) for neural recording, with improvements in power supply rejection ratio (PSRR) and dynamic range. The input stage in the low noise amplifier (LNA) adopts low voltage supply (0.35 V) and current-reusing to achieve ultralow power. To maintain a high PSRR performance while using such a low-voltage supply, a replica-biasing scheme is proposed to generate a stable bias current for the input stage of the LNA despite large supply interference. By exploiting the signal characteristics in the tetrode recording, an averaged local field potential (A-LFP) servo loop is introduced to extend the dynamic range without consuming too much extra power and chip area. The A-LFP signal is generated by integrating the four-channel PGA outputs from the same tetrode. Furthermore, the outputs of the programmable gain amplifier (PGA) are level shifted to bias the input nodes of the amplifier through large pseudo resistors, thus increase the maximum output range without distortion under the low-voltage supply. The proof-of-concept prototype is fabricated in a 65 nm CMOS process. Each recording channel including an LNA and a PGA occupies 0.04 mm 2 and consumes 340 nW from the 0.35 V and 0.7 V supply. Each A-LFP servo loop, which is shared by four recording channels, occupies 0.04 mm 2 and consumes 190 nW. The maximum gain of the AFE is 54 dB, and the input-referred noise is 6.7 μV over the passband from 0.5 Hz to 6.5 kHz. Measurement also shows that the 0.35 V replica-biasing input stage can tolerate a large interferer up to 200 mVpp with a PSRR of 74 dB, which has been improved to 110 dB with a silicon respin that shields critical wires in the layout.The evaluation of toxic effects of nanoparticles (NPs) has become an important aspect of Nanotechnology research in the 21st century. The present investigation deals with the green synthesis of biogenic zinc oxide nanoparticles (ZnO-NPs) using Bryophyllum pinnatum leaves, their characterization and evaluation of acute oral toxicity in Wistar rats. The characterization of synthesized ZnO-NPs revealed maximum absorbance at 307 nm on UV-Vis spectrophotometric analysis, NTA showed mean size of particles and mode of the particles distribution as 128.2 nm and 12.6 nm, respectively. Zeta potential was found to be -0.369 mV. The absorbance shown by FTIR at 3469, 1644, 1355 and 887 cm-1 indicates the involvement of biomolecules that are accountable for capping and stabilization of ZnO-NPs. The XRD assessment further demonstrated the crystalline nature of the ZnO-NP. The TEM analysis of the synthesized ZnO-NPs revealed the presence of spherical NPs with the mean size of 3.7 nm. The acute oral toxicity evaluation in rat showed an approximate median lethal dose to be more than 2000 mg/kg body weight.
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  • r hospital admission. These estimates for (dis) utility could be used in the calculations of effectiveness on economic evaluations, especially when discrete event simulations are the employed modelling technique.
    Knowing the impact of hospitalisation on health-related quality of life is particularly relevant for informing cost-effectiveness studies designed to assess health technologies aimed at reducing hospital admissions. Through using patient-level data it was possible to estimate the variation in utilities before and after the average hospitalisation and for hospitalisations due to the most common causes for hospital admission. These estimates for (dis) utility could be used in the calculations of effectiveness on economic evaluations, especially when discrete event simulations are the employed modelling technique.
    Individuals with diabetes mellitus have difficulty solving problems in meaningful occupations and have similar difficulties with self-care regimens. We examined the effects of an occupation-based intervention supported with problem-solving therapy in individuals with type 2 diabetes mellitus on participation in and satisfaction with meaningful occupations, diabetes-related psychosocial self-efficacy, preferred coping strategies and individual well-being.

    This study was planned as a single-blind, randomised controlled study with a 3-month follow-up involving 67 adults with type 2 diabetes. The Canadian Occupational Performance Measure, Diabetes Empowerment Scale, Brief COPE and five-item World Health Organisation Well-Being Index were used. This programme included evaluations, diabetes education, and problem-solving therapy. The intervention was conducted for 6 weeks, and each weekly session lasted approximately 60 min. Differences between groups were analysed using the Mann-Whitney U test, and the Friedmaful occupation can be used to lead to a meaningful and quality life for individuals with type 2 diabetes mellitus.

    ClinicalTrials.gov Identifier NCT03783598 . Retrospectively Registered. First Posted-December 21, 2018, Last Update Posted-February 18, 2020.
    ClinicalTrials.gov Identifier NCT03783598 . Retrospectively Registered. First Posted-December 21, 2018, Last Update Posted-February 18, 2020.
    Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF).

    This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study.

    Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy.

    Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.
    Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy.
    We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS.

    Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAF
    -mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause.

    RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage ****disease an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM).
    Psychological flexibility is considered a fundamental aspect of health. It includes six interrelated facets 1) cognitive defusion, 2) acceptance, 3) contact with the present moment, 4) self-as-context, 5) values, and 6) committed action. To gain further insight into psychological flexibility and its effects on health, reliable and valid instruments to assess all facets are needed. Committed action is one facet that is understudied. https://www.selleckchem.com/products/dmog.html A long and short version of a validated measure (CAQ and CAQ-8) have been developed in English. Currently, there are no German versions of the CAQ. Aim of this study is to validate German-language versions of these in a chronic pain population.

    The CAQ instructions and items were translated and evaluated in a chronic pain population (N= 181). Confirmatory factor analysis and Mokken scale analysis were conducted to evaluate the German questionnaires. Correlations with health outcomes, including quality of life (SF-12), physical and emotional functioning (MPI, BPI, PHQ-9, GAD-7), pain intensity, and with other facets of psychological flexibility (CPAQ, FAH-II) were investigated for convergent validity purposes.
    r hospital admission. These estimates for (dis) utility could be used in the calculations of effectiveness on economic evaluations, especially when discrete event simulations are the employed modelling technique. Knowing the impact of hospitalisation on health-related quality of life is particularly relevant for informing cost-effectiveness studies designed to assess health technologies aimed at reducing hospital admissions. Through using patient-level data it was possible to estimate the variation in utilities before and after the average hospitalisation and for hospitalisations due to the most common causes for hospital admission. These estimates for (dis) utility could be used in the calculations of effectiveness on economic evaluations, especially when discrete event simulations are the employed modelling technique. Individuals with diabetes mellitus have difficulty solving problems in meaningful occupations and have similar difficulties with self-care regimens. We examined the effects of an occupation-based intervention supported with problem-solving therapy in individuals with type 2 diabetes mellitus on participation in and satisfaction with meaningful occupations, diabetes-related psychosocial self-efficacy, preferred coping strategies and individual well-being. This study was planned as a single-blind, randomised controlled study with a 3-month follow-up involving 67 adults with type 2 diabetes. The Canadian Occupational Performance Measure, Diabetes Empowerment Scale, Brief COPE and five-item World Health Organisation Well-Being Index were used. This programme included evaluations, diabetes education, and problem-solving therapy. The intervention was conducted for 6 weeks, and each weekly session lasted approximately 60 min. Differences between groups were analysed using the Mann-Whitney U test, and the Friedmaful occupation can be used to lead to a meaningful and quality life for individuals with type 2 diabetes mellitus. ClinicalTrials.gov Identifier NCT03783598 . Retrospectively Registered. First Posted-December 21, 2018, Last Update Posted-February 18, 2020. ClinicalTrials.gov Identifier NCT03783598 . Retrospectively Registered. First Posted-December 21, 2018, Last Update Posted-February 18, 2020. Frailty results in a high risk for disability, hospitalization, and mortality. This study aimed to investigate perioperative details of frail patients who underwent pancreatectomy and whether frailty can be a predictive factor of postoperative complications, especially of clinically relevant postoperative pancreatic fistula (CR-POPF). This retrospective study included patients who underwent pancreatectomy in our hospital between August 2016 and March 2019. The patients were divided into frail and pre-/non-frail groups. The diagnostic criteria were based on the Japanese version of the Cardiovascular Health Study. Of 93 patients, 11 (11.8%) and 82 (88.2%) were frail and pre-/non-frail patients, with median ages of 82 and 72 years, respectively (p = 0.041). Postoperative complications (Clavien-Dindo ≧ IIIa) were found in 8 and 32 patients (p = 0.034), CR-POPF in 3 and 13 patients (p = 0.346), and postoperative hospital stays were 21 and 17 days (p = 0.041), respectively. On multivariate analysis, frailty was an independent predictive factor (odds ratio [OR] 5.604, 95.0% confidence interval [CI] 1.002-30.734; p = 0.047) of postoperative complications (Clavien-Dindo ≧ IIIa) after pancreaticoduodenectomy. On multivariate analysis, a soft pancreas (OR 5.696, 95.0% CI 1.142-28.149; p = 0.034) was an independent and significant predictive factor of CR-POPF after pancreaticoduodenectomy. Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy. Frailty may be a useful predictive factor of postoperative complications in patients undergoing pancreaticoduodenectomy. We sought to identify patient subgroups with distinct postprogression overall survival (ppOS) outcomes and investigate the impact of original treatment assignment and initial postprogression treatment (ppRx) on ppOS. Recursive partitioning analysis (RPA) was performed to model relationships between prespecified covariates and ppOS in patients with BRAF -mutated metastatic melanoma who had experienced progressive disease (PD) following treatment with cobimetinib plus vemurafenib, vemurafenib monotherapy, or dacarbazine in the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Prognostic subgroups identified by RPA were then applied to pooled treatment cohorts. The primary endpoint was ppOS, defined as time from first PD to death from any cause. RPA identified baseline lactate dehydrogenase (LDH), baseline disease stage, Eastern Cooperative Oncology Group performance status at PD, and ppRx as significant prognostic factors for ppOS. Median ppOS was longest in patients with normal baseline LDH, stage M1c disease an independent prognostic factor for improved overall survival following progression regardless of original treatment. Trial registration The trials included in this analysis are registered with ClinicalTrials.gov NCT00949702 (BRIM-2), NCT01006980 (BRIM-3), NCT01271803 (BRIM-7), and NCT01689519 (coBRIM). Psychological flexibility is considered a fundamental aspect of health. It includes six interrelated facets 1) cognitive defusion, 2) acceptance, 3) contact with the present moment, 4) self-as-context, 5) values, and 6) committed action. To gain further insight into psychological flexibility and its effects on health, reliable and valid instruments to assess all facets are needed. Committed action is one facet that is understudied. https://www.selleckchem.com/products/dmog.html A long and short version of a validated measure (CAQ and CAQ-8) have been developed in English. Currently, there are no German versions of the CAQ. Aim of this study is to validate German-language versions of these in a chronic pain population. The CAQ instructions and items were translated and evaluated in a chronic pain population (N= 181). Confirmatory factor analysis and Mokken scale analysis were conducted to evaluate the German questionnaires. Correlations with health outcomes, including quality of life (SF-12), physical and emotional functioning (MPI, BPI, PHQ-9, GAD-7), pain intensity, and with other facets of psychological flexibility (CPAQ, FAH-II) were investigated for convergent validity purposes.
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  • Notably, the increase of base substitutions in the homologous recombination-deficient Rad51 mutant, specifically dependent on the Polζ translesion polymerase, yields COSMIC signature 3 observed in BRCA1/BRCA2-mutant breast cancer tumors. Furthermore, "mutome" analyses in highly polymorphic diploids and single-cell bottleneck lineages revealed a diverse spectrum of loss-of-heterozygosity (LOH) signatures characterized by interstitial and terminal chromosomal events resulting from interhomolog mitotic cross-overs. Following the appearance of heterozygous mutations, the strong stimulation of LOHs in the rad27/FEN1 and tsa1/PRDX1 backgrounds leads to fixation of homozygous mutations or their loss along the lineage. Overall, these mutomes and their trajectories provide a mechanistic framework to understand the origin and dynamics of genome variations that accumulate during clonal evolution.Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the **** needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.Mechanistic understanding of DNA recombination in the Cre-loxP system has largely been guided by crystallographic structures of tetrameric synaptic complexes. Those studies have suggested a role for protein conformational dynamics that has not been well characterized at the atomic level. We used solution nuclear magnetic resonance (NMR) spectroscopy to discover the link between intrinsic flexibility and function in Cre recombinase. Transverse relaxation-optimized spectroscopy (TROSY) NMR spectra show the N-terminal and C-terminal catalytic domains (CreNTD and CreCat) to be structurally independent. Amide 15N relaxation measurements of the CreCat domain reveal fast-timescale dynamics in most regions that exhibit conformational differences in active and inactive Cre protomers in crystallographic tetramers. However, the C-terminal helix αN, implicated in assembly of synaptic complexes and regulation of DNA cleavage activity via trans protein-protein interactions, is unexpectedly rigid in free Cre. Chemical shift perturbations and intra- and intermolecular paramagnetic relaxation enhancement (PRE) NMR data reveal an alternative autoinhibitory conformation for the αN region of free Cre, wherein it packs in cis over the protein DNA binding surface and active site. Moreover, binding to loxP DNA induces a conformational change that dislodges the C terminus, resulting in a cis-to-trans switch that is likely to enable protein-protein interactions required for assembly of recombinogenic Cre intasomes. https://www.selleckchem.com/products/ici-118551-ici-118-551.html These findings necessitate a reexamination of the mechanisms by which this widely utilized gene-editing tool selects target sites, avoids spurious DNA cleavage activity, and controls DNA recombination efficiency.Shigella is a major cause of moderate to severe diarrhea largely affecting children ( less then 5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or fustrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.Kathy Shair works in the field of Epstein-Barr virus (EBV)-associated cancers, with emphasis on nasopharyngeal carcinoma (NPC). In this mSphere of Influence article, she reflects on how the paper "Efficient replication of Epstein-Barr virus in stratified epithelium in vitro" by Temple et al. (R. M. Temple, J. Zhu, L. Budgeon, N. D. Christensen, et al., Proc Natl Acad Sci U S A 11116544-16549, 2014, https//doi.org/10.1073/pnas.1400818111) has influenced her work on EBV molecular pathogenesis in the nasopharynx by highlighting the importance of using three-dimensional (3-D) culture models to study epithelial infection.
    Notably, the increase of base substitutions in the homologous recombination-deficient Rad51 mutant, specifically dependent on the Polζ translesion polymerase, yields COSMIC signature 3 observed in BRCA1/BRCA2-mutant breast cancer tumors. Furthermore, "mutome" analyses in highly polymorphic diploids and single-cell bottleneck lineages revealed a diverse spectrum of loss-of-heterozygosity (LOH) signatures characterized by interstitial and terminal chromosomal events resulting from interhomolog mitotic cross-overs. Following the appearance of heterozygous mutations, the strong stimulation of LOHs in the rad27/FEN1 and tsa1/PRDX1 backgrounds leads to fixation of homozygous mutations or their loss along the lineage. Overall, these mutomes and their trajectories provide a mechanistic framework to understand the origin and dynamics of genome variations that accumulate during clonal evolution.Molecular and genomic surveillance systems for bacterial pathogens currently rely on tracking clonally evolving lineages. By contrast, plasmids are usually excluded or analyzed with low-resolution techniques, despite being the primary vectors of antibiotic resistance genes across many key pathogens. Here, we used a combination of long- and short-read sequence data of Klebsiella pneumoniae isolates (n = 1,717) from a European survey to perform an integrated, continent-wide study of chromosomal and plasmid diversity. This revealed three contrasting modes of dissemination used by carbapenemase genes, which confer resistance to last-line carbapenems. First, blaOXA-48-like genes have spread primarily via the single epidemic pOXA-48-like plasmid, which emerged recently in clinical settings and spread rapidly to numerous lineages. Second, blaVIM and blaNDM genes have spread via transient associations of many diverse plasmids with numerous lineages. Third, blaKPC genes have transmitted predominantly by stable association with one successful clonal lineage (ST258/512) yet have been mobilized among diverse plasmids within this lineage. We show that these plasmids, which include pKpQIL-like and IncX3 plasmids, have a long association (and are coevolving) with the lineage, although frequent recombination and rearrangement events between them have led to a complex array of mosaic plasmids carrying blaKPC Taken altogether, these results reveal the diverse trajectories of antibiotic resistance genes in clinical settings, summarized as using one plasmid/multiple lineages, multiple plasmids/multiple lineages, and multiple plasmids/one lineage. Our study provides a framework for the much needed incorporation of plasmid data into genomic surveillance systems, an essential step toward a more comprehensive understanding of resistance spread.Mechanistic understanding of DNA recombination in the Cre-loxP system has largely been guided by crystallographic structures of tetrameric synaptic complexes. Those studies have suggested a role for protein conformational dynamics that has not been well characterized at the atomic level. We used solution nuclear magnetic resonance (NMR) spectroscopy to discover the link between intrinsic flexibility and function in Cre recombinase. Transverse relaxation-optimized spectroscopy (TROSY) NMR spectra show the N-terminal and C-terminal catalytic domains (CreNTD and CreCat) to be structurally independent. Amide 15N relaxation measurements of the CreCat domain reveal fast-timescale dynamics in most regions that exhibit conformational differences in active and inactive Cre protomers in crystallographic tetramers. However, the C-terminal helix αN, implicated in assembly of synaptic complexes and regulation of DNA cleavage activity via trans protein-protein interactions, is unexpectedly rigid in free Cre. Chemical shift perturbations and intra- and intermolecular paramagnetic relaxation enhancement (PRE) NMR data reveal an alternative autoinhibitory conformation for the αN region of free Cre, wherein it packs in cis over the protein DNA binding surface and active site. Moreover, binding to loxP DNA induces a conformational change that dislodges the C terminus, resulting in a cis-to-trans switch that is likely to enable protein-protein interactions required for assembly of recombinogenic Cre intasomes. https://www.selleckchem.com/products/ici-118551-ici-118-551.html These findings necessitate a reexamination of the mechanisms by which this widely utilized gene-editing tool selects target sites, avoids spurious DNA cleavage activity, and controls DNA recombination efficiency.Shigella is a major cause of moderate to severe diarrhea largely affecting children ( less then 5 years old) living in low- and middle-income countries. Several vaccine candidates are in development, and controlled human infection models (CHIMs) can be useful tools to provide an early assessment of vaccine efficacy and potentially support licensure. A lyophilized strain of S. sonnei 53G was manufactured and evaluated to establish a dose that safely and reproducibly induced a ≥60% attack rate. Samples were collected pre- and postchallenge to assess intestinal inflammatory responses, antigen-specific serum and mucosal antibody responses, functional antibody responses, and memory B cell responses. Infection with S. sonnei 53G induced a robust intestinal inflammatory response as well as antigen-specific antibodies in serum and mucosal secretions and antigen-specific IgA- and IgG-secreting B cells positive for the α4β7 gut-homing marker. There was no association between clinical disease outcomes and systemic or fustrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.Kathy Shair works in the field of Epstein-Barr virus (EBV)-associated cancers, with emphasis on nasopharyngeal carcinoma (NPC). In this mSphere of Influence article, she reflects on how the paper "Efficient replication of Epstein-Barr virus in stratified epithelium in vitro" by Temple et al. (R. M. Temple, J. Zhu, L. Budgeon, N. D. Christensen, et al., Proc Natl Acad Sci U S A 11116544-16549, 2014, https//doi.org/10.1073/pnas.1400818111) has influenced her work on EBV molecular pathogenesis in the nasopharynx by highlighting the importance of using three-dimensional (3-D) culture models to study epithelial infection.
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  • We studied avian development in 49 to 153 species of temperate and tropical New World passerine birds to determine how growth rates, and incubation and nestling periods, varied in relation to other life-history traits. We collected growth data and generated unbiased mass and tarsus growth rate estimates (mass n = 92 species, tarsus n = 49 species), and measured incubation period (n = 151) and nestling period (n = 153), which we analyzed with respect to region, egg mass, adult mass, clutch size, parental care type, nest type, daily nest predation rate (DMR), and nest height. We investigated covariation of life-history and natural-history attributes with the four development traits after controlling for phylogeny. Species in our lowland tropical sample grew 20% (incubation period), 25% (mass growth rate), and 26% (tarsus growth rate) more slowly than in our temperate sample. Nestling period did not vary with respect to latitude, which suggests that tropical songbirds fledge in a less well-developed state than tharacteristics of each region influence physiological processes of passerines, and thus, how they can shape the evolution of life histories. While development traits clearly vary with respect to latitude, trait distributions overlap broadly. Life-history and natural history associations differ for each development trait, which suggests that unique selective pressures or constraints influence the evolution of each trait.Leishmania species are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenic Leishmania spp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and the Leishmania proteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representing L. braziliensis, L. panamensis and L. guyanensis species. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. "Total Protein Approach" and "Proteomic Ruler" were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Ouchange with identifier PXD017696.Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR 1.75, 95% CI 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR 1.15, 95% CI 1.03, 1.29), low maternal education ( less then 10 years, RR 1.14, 95% CI 1.03, 1.26), initiating complementary foods before 3 months (RR 1.10, 95% CI 1.01, 1.20), and malnutrition (RR 0.91, 95% CI 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery.
    The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation.

    We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. https://www.selleckchem.com/products/ABT-869.html DHS included maternally-repo32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries.

    Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.
    Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.The human body generates a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design vaccines for highly mutable pathogens such as influenza and HIV. BCR diversity is induced by naturally occurring combinatorial "V(D)J" rearrangement, mutation, and selection processes. Most current methods for BCR sequence analysis focus on separately modeling the above processes. Statistical phylogenetic methods are often used to model the mutational dynamics of BCR sequence data, but these techniques do not consider all the complexities associated with B cell diversification such as the V(D)J rearrangement process. In particular, standard phylogenetic approaches assume the DNA bases of the progenitor (or "naive") sequence arise independently and according to the same distribution, ignoring the complexities of V(D)J rearrangement. In this paper, we introduce a novel approach to Bayesian phylogenetic inference for BCR sequences that is based on a phylogenetic hidden Markov model (phylo-HMM).
    We studied avian development in 49 to 153 species of temperate and tropical New World passerine birds to determine how growth rates, and incubation and nestling periods, varied in relation to other life-history traits. We collected growth data and generated unbiased mass and tarsus growth rate estimates (mass n = 92 species, tarsus n = 49 species), and measured incubation period (n = 151) and nestling period (n = 153), which we analyzed with respect to region, egg mass, adult mass, clutch size, parental care type, nest type, daily nest predation rate (DMR), and nest height. We investigated covariation of life-history and natural-history attributes with the four development traits after controlling for phylogeny. Species in our lowland tropical sample grew 20% (incubation period), 25% (mass growth rate), and 26% (tarsus growth rate) more slowly than in our temperate sample. Nestling period did not vary with respect to latitude, which suggests that tropical songbirds fledge in a less well-developed state than tharacteristics of each region influence physiological processes of passerines, and thus, how they can shape the evolution of life histories. While development traits clearly vary with respect to latitude, trait distributions overlap broadly. Life-history and natural history associations differ for each development trait, which suggests that unique selective pressures or constraints influence the evolution of each trait.Leishmania species are responsible for a broad spectrum of diseases, denominated Leishmaniasis, affecting over 12 million people worldwide. During the last decade, there have been impressive efforts for sequencing the genome of most of the pathogenic Leishmania spp. as well as hundreds of strains, but large-scale proteomics analyses did not follow these achievements and the Leishmania proteome remained mostly uncharacterized. Here, we report a comprehensive comparative study of the proteomes of strains representing L. braziliensis, L. panamensis and L. guyanensis species. Proteins extracted by SDS-mediated lysis were processed following the multi-enzyme digestion-filter aided sample preparation (FASP) procedure and analysed by high accuracy mass spectrometry. "Total Protein Approach" and "Proteomic Ruler" were applied for absolute quantification of proteins. Principal component analysis demonstrated very high reproducibility among biological replicates and a very clear differentiation of the three species. Ouchange with identifier PXD017696.Culture-independent diagnostics have revealed a larger burden of Shigella among children in low-resource settings than previously recognized. We further characterized the epidemiology of Shigella in the first two years of life in a multisite birth cohort. We tested 41,405 diarrheal and monthly non-diarrheal stools from 1,715 children for Shigella by quantitative PCR. To assess risk factors, clinical factors related to age and culture positivity, and associations with inflammatory biomarkers, we used log-binomial regression with generalized estimating equations. The prevalence of Shigella varied from 4.9%-17.8% in non-diarrheal stools across sites, and the incidence of Shigella-attributable diarrhea was 31.8 cases (95% CI 29.6, 34.2) per 100 child-years. The sensitivity of culture compared to qPCR was 6.6% and increased to 27.8% in Shigella-attributable dysentery. Shigella diarrhea episodes were more likely to be severe and less likely to be culture positive in younger children. Older age (RR 1.75, 95% CI 1.70, 1.81 per 6-month increase in age), unimproved sanitation (RR 1.15, 95% CI 1.03, 1.29), low maternal education ( less then 10 years, RR 1.14, 95% CI 1.03, 1.26), initiating complementary foods before 3 months (RR 1.10, 95% CI 1.01, 1.20), and malnutrition (RR 0.91, 95% CI 0.88, 0.95 per unit increase in weight-for-age z-score) were risk factors for Shigella. There was a linear dose-response between Shigella quantity and myeloperoxidase concentrations. The burden of Shigella varied widely across sites, but uniformly increased through the second year of life and was associated with intestinal inflammation. Culture missed most clinically relevant cases of severe diarrhea and dysentery. The key metric for monitoring the progress of deworming programs in controlling soil-transmitted helminthiasis (STH) is national drug coverage reported to the World Health Organization (WHO). There is increased interest in utilizing geographically-disaggregated data to estimate sub-national deworming coverage and equity, as well as gender parity. The Demographic and Health Surveys (DHS) offer a potential source of sub-national data. This study aimed to compare deworming coverage routinely reported to WHO and estimated by DHS in pre-school aged children to inform global STH measurement and evaluation. We compared sub-national deworming coverage in pre-school aged children reported to WHO and estimated by DHS aligned geospatially and temporally. We included data from Burundi (2016-2017), Myanmar (2015-2016), and the Philippines (2017) based on data availability. WHO provided data on the date and sub-national coverage per mass drug administration reported by Ministries of Health. https://www.selleckchem.com/products/ABT-869.html DHS included maternally-repo32 of 40 districts). National deworming coverage from DHS estimates were similar by gender within countries. Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data. Agreement of deworming coverage reported to WHO and estimated by DHS data was heterogeneous across countries, varying from broadly compatible in Burundi to largely discrepant in Myanmar. DHS data could complement deworming data reported to WHO to improve data monitoring practices and serve as an independent sub-national source of coverage data.The human body generates a diverse set of high affinity antibodies, the soluble form of B cell receptors (BCRs), that bind to and neutralize invading pathogens. The natural development of BCRs must be understood in order to design vaccines for highly mutable pathogens such as influenza and HIV. BCR diversity is induced by naturally occurring combinatorial "V(D)J" rearrangement, mutation, and selection processes. Most current methods for BCR sequence analysis focus on separately modeling the above processes. Statistical phylogenetic methods are often used to model the mutational dynamics of BCR sequence data, but these techniques do not consider all the complexities associated with B cell diversification such as the V(D)J rearrangement process. In particular, standard phylogenetic approaches assume the DNA bases of the progenitor (or "naive") sequence arise independently and according to the same distribution, ignoring the complexities of V(D)J rearrangement. In this paper, we introduce a novel approach to Bayesian phylogenetic inference for BCR sequences that is based on a phylogenetic hidden Markov model (phylo-HMM).
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