syedzayyan/paper_mill_benchmark huggingface dataset:
Hepatitis C virus genotype 4 resistance and subtype demographic characterization of patients treated with ombitasvir plus paritaprevir/ritonavir.

Hepatitis c virus (hcv) genotype 4 (gt4) is genetically diverse, with 17 confirmed subtypes, and comprises approximately 13% of infections worldwide.In this study, we identified gt4 subtypes by phylogenetic analysis, assessed differences in patient demographics across gt4 subtypes, examined baseline sequence variability among subtypes and the potential impact on treatment outcome, and analyzed the development of viral resistance in patients who received a regimen of ombitasvir (nonstructural protein 5a [ns5a] inhibitor) plus ritonavir-boosted paritaprevir (ns3/4a inhibitor) with or without ribavirin (rbv) for the treatment of hcv gt4 infection.Phylogenetic analysis of hcv ns3/4a, ns5a, and ns5b nucleotide sequences identified 7 subtypes (4a, 4b, 4c, 4d, 4f, 4g/4k, and 4o) among 132 patient samples.Subtype prevalence varied by country, and the distributions of patient birth cohort and race were significantly different across gt4 subtypes 4a, 4d, and non-4a/4d.Baseline amino acid variability was detected in ns5a across gt4 subtypes but had no impact on treatment outcome.Three patients experienced virologic failure and were infected with subtype 4d, and the predominant resistance-associated variants at the time of failure were d168v in ns3 and l28v in ns5a.Overall, high response rates were observed among patients infected with 7 hcv gt4 subtypes, with no impact of baseline variants on treatment outcome.Gt4 subtype distribution in this study differed based on patient demographics and geography.

Journal: Antimicrobial agents and chemotherapy (2015)
Publication types: Clinical Trial, Phase II;Journal Article;Randomized Controlled Trial
Loneliness and Mental Health: The Mediating Effect of Perceived Social Support.

Social connectedness is a fundamental human need.The evolutionary theory of loneliness (etl) predicts that a lack of social connectedness has long-term mental and physical health consequences.Social support is a potential mechanism through which loneliness influences health.The present cross-sectional study examined the relationship between loneliness and mental health, and the mediating effects of social support in a dutch adult sample (n = 187, age 20 to 70).The health variables included in the study are anxiety, depression, somatic symptoms as measured by the scl-90, and the dsm-5 diagnosis somatic symptom disorder.The results indicated that social support partially mediated the relationship between loneliness and anxiety, depression, and somatic symptoms.These results indicate that social support partially explains the relationship between loneliness and physical and mental health issues.The relationship between loneliness and being diagnosed with somatic symptom disorder was not mediated by social support.This suggests that the mechanisms through which loneliness relates to either somatic symptoms or somatic symptom disorder are different.

Journal: International journal of environmental research and public health (2021)
Publication types: Journal Article
Chiral supramolecular polymers.

As an active branch within the field of supramolecular polymers, chiral supramolecular polymers (sps) are an excellent benchmark to generate helical structures that can clarify the origin of homochirality in nature or help determine new exciting functionalities of organic materials.Herein, we highlight the most utilized strategies to build up chiral sps by using chiral monomeric units or external stimuli.Selected examples of transfer of asymmetry, in which the point or axial chirality contained by the monomeric units is efficiently transferred to the supramolecular scaffold yielding enantioenriched helical structures, will be presented.The importance of the thermodynamics and kinetics associated with those processes is stressed, especially the influence that parameters such as the helix reversal and mismatch penalties exert on the achievement of amplification of asymmetry in co-assembled systems will also be considered.Remarkable examples of breaking symmetry, in which chiral supramolecular polymers can be attained from achiral self-assembling units by applying external stimuli like stirring, solvent or light, are highlighted.Finally, the specific and promising applications of chiral supramolecular polymers are presented with recent relevant examples.

Journal: Chemical Society reviews (2023)
Publication types: Journal Article;Review
Access to and experience of education for children and adolescents with cancer: a scoping review protocol.

Cancer diagnosis in childhood or adolescence impacts significantly on school attendance, experience and educational outcomes.While there is longstanding recognition in clinical practice that these effects span the whole illness trajectory and continue beyond treatment completion, further clarity is required on the specific barriers and facilitators to education during cancer treatment and beyond, as well as on the experiences of children and adolescents across the full range of education settings (hospital, home, virtual, original school of enrolment), in order to determine which interventions are successful in improving access and experience from their perspective.The aim of this review is to identify what is known from the existing literature about access to and experience of education for children and adolescents with cancer during and post treatment.Methods we have planned a scoping literature review searching the following databases from inception onwards: medline (ovid), embase and embase classic, web of science core collection, education resources index, sociological abstracts, apa psyc info, scopus, cinahl plus, emcare and the cochrane library.In addition, dare, conference abstracts, key journals, and institutional websites will be searched.Arksey and o'malley's six-step process will be followed, including a consultation exercise.Studies, reports and policies from any country providing care and treatment for children and adolescents with cancer published in english will be considered eligible for inclusion.Two reviewers will independently screen all citations, full-text articles and abstract data.A narrative summary of findings will be conducted.Data analysis will involve quantitative (e.g., frequencies) and qualitative (e.g., content and thematic analysis) methods.Discussion this is a timely examination given the increased incidence of childhood cancer, more intensive treatment regimens and improved survival rates for childhood cancer.The inclusion of a substantive consultation exercise with families and professionals will provide an important opportunity to examine the scoping review outputs.Findings will assist the childhood cancer community in developing a comprehensive evidence-based understanding of a significant associated bio-psychosocial impact of cancer diagnosis and treatment and will form the first step towards developing effective interventions and policies to mitigate identified detrimental effects.Systematic review registration open science framework (osf/io/yc4wt).

Journal: Systematic reviews (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Clinical Features, Inpatient Trajectories and Frailty in Older Inpatients with COVID-19: A Retrospective Observational Study.

Introduction we describe the clinical features and inpatient trajectories of older adults hospitalized with covid-19 and explore relationships with frailty.Methods this retrospective observational study included older adults admitted as an emergency to a university hospital who were diagnosed with covid-19.Patient characteristics and hospital outcomes, primarily inpatient death or death within 14 days of discharge, were described for the whole cohort and by frailty status.Associations with mortality were further evaluated using cox proportional hazards regression (hazard ratio (hr), 95% confidence interval).Results 214 patients (94 women) were included of whom 142 (66.4%) were frail with a median clinical frailty scale (cfs) score of 6.Frail compared to nonfrail patients were more likely to present with atypical symptoms including new or worsening confusion (45.1% vs.20.8%,p< 0.001) and were more likely to die (66% vs.16%,p= 0.001).Older age, being male, presenting with high illness acuity and high frailty were independent predictors of death and a dose-response association between frailty and mortality was observed (cfs 1-4: reference; cfs 5-6: hr 1.78, 95% ci 0.90, 3.53; cfs 7-8: hr 2.57, 95% ci 1.26, 5.24).Conclusions clinicians should have a low threshold for testing for covid-19 in older and frail patients during periods of community viral transmission, and diagnosis should prompt early advanced care planning.

Journal: Geriatrics (Basel, Switzerland) (2021)
Publication types: Journal Article
Critical Role for Macrophages in the Developmental Programming of Pancreatic β-Cell Area in Offspring of Hypertensive Pregnancies.

Preeclampsia is a pregnancy-specific complication with long-term negative outcomes for offspring, including increased susceptibility to type 2 diabetes (t2d) in adulthood.In a rat reduced uteroplacental perfusion pressure (rupp) model of chronic placental ischemia, maternal hypertension in conjunction with intrauterine growth restriction mimicked aspects of preeclampsia and resulted in female embryonic day 19 (e19) offspring with reduced β-cell area and increased β-cell apoptosis compared with offspring of sham pregnancies.Decreased pancreatic β-cell area persisted to postnatal day 13 (pd13) in females and could influence whether t2d developed in adulthood.Macrophage changes also occurred in islets in t2d.Therefore, we hypothesized that macrophages are crucial to reduction in pancreatic β-cell area in female offspring after chronic placental ischemia.Macrophage marker cd68 m rna expression was significantly elevated in e19 and pd13 islets isolated from female rupp offspring compared with sham.Postnatal injections of clodronate liposomes into female rupp and sham offspring on pd2 and pd9 significantly depleted macrophages compared with injections of control liposomes.Depletion of macrophages rescued reduced β-cell area and increased β-cell proliferation and size in rupp offspring.Our studies suggest that the presence of macrophages is important for reduced β-cell area in female rupp offspring and changes in macrophages could contribute to development of t2d in adulthood.

Journal: Diabetes (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural
Idelalisib immune-related toxicity is associated with improved treatment response.

Idelalisib is associated with increased occurrence of immune-related adverse events (ir aes).Clinical observations suggest a correlation between immune checkpoint inhibitor-induced ir aes and survival outcomes in patients with solid tumors; however, this relationship in hematologic malignancies is not well understood.In a post hoc analysis of 3 registrational trials, we explored the relationship between grade ≥3 diarrhea/colitis and alanine/aspartate transaminase (alt/ast) elevation incidences and efficacy endpoints in patients with indolent non-hodgkin lymphoma (i nhl), follicular lymphoma (fl), and chronic lymphocytic leukemia treated with idelalisib.Grade ≥3 diarrhea/colitis was associated with higher overall response rate (orr) and longer progression-free survival (pfs) for all subgroups.Grade ≥3 alt/ast elevations were associated with improved duration of response and overall survival for all subgroups and improved orr and pfs for patients with fl or i nhl.Our analysis in hematologic malignancies showed a trend correlating idelalisib-induced grade ≥3 ir aes with improved efficacy.

Journal: Leukemia & lymphoma (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Recombinant Unique Cartilage Matrix-associated Protein Potentiates Osteogenic Differentiation and Mineralization of MC3T3-E1 Cells.

The relative balance of osteoblasts in bone formation and osteoclasts in bone resorption is crucial for maintaining bone health.With age, this balance between osteoblasts and osteoclasts is broken, resulting in bone loss.Anabolic drugs are continuously being developed to counteract this low bone mass.Recombinant proteins are used as biotherapeutics due to being relatively easy to produce on a large scale and are cost-effective through various expression systems.This study aimed to develop a recombinant protein that would positively impact osteoblast differentiation and mineralized nodule formation using unique cartilage matrix-associated protein (ucma).Methods a recombinant glutathione-s-transferase (gst)-ucma fusion protein was generated in an e.coli system, and purified by affinity chromatography.Mc3t3-e1 osteoblast cells and osterix (osx)-knockdown stable cells were cultured for 14 days to investigate osteoblast differentiation and nodule formation in the presence of the recombinant gst-ucma protein.The differentiated cells were assessed by alizarin red s staining and quantitative pcr of the osteoblast differentiation marker osteocalcin.In addition, cell viability in the presence of the recombinant gst-ucma protein was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (mtt) assay and cell adhesion assay.Results the isolation of both purified recombinant gst-only and gst-ucma proteins were confirmed at 26 k da and 34 k da, respectively, by coomassie staining and western blot analysis.Neither dose-dependent nor time-dependent presence of recombinant gst-ucma affected mc3t3-e1 cell viability.However, mc3t3-e1 cell adhesion to the recombinant gst-ucma protein increased dose-dependently.Osteoblast differentiation and nodule formation were promoted in both mc3t3-e1 osteoblast cells and osxknockdown stable cells when cultured in the presence of recombinant gst-ucma protein.Conclusion a recombinant gst-ucma protein induces osteogenic differentiation and mineralization, suggesting its potential use as an anabolic drug to increase low bone mass in osteoporotic patients.

Journal: Current molecular medicine (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Unravelling the interplay of ecological processes structuring the bacterial rare biosphere.

Most ecological communities harbor many rare species (i.e., the rare biosphere), however, relatively little is known about how distinct ecological processes structure their existence.Here, we used spatiotemporal data on soil bacterial communities along a natural ecosystem gradient to model the relative influences of assembly processes structuring the rare and common biospheres.We found a greater influence of homogeneous selection (i.e., imposed by spatiotemporally constant variables) mediating the assembly of the rare biosphere, whereas the common biosphere was mostly governed by variable selection (i.e., imposed by spatial and/or temporal fluctuating variables).By partitioning the different types of rarity, we found homogeneous selection to explain the prevalence of permanently rare taxa, thus suggesting their persistence at low abundances to be restrained by physiological traits.Conversely, the dynamics of conditionally rare taxa were mostly structured by variable selection, which aligns with the ability of these taxa to switch between rarity and commonness as responses to environmental spatiotemporal variations.Taken together, our study contributes to the establishment of a link between conceptual and empirical developments in the ecology of the soil microbial rare biosphere.Besides, this study provides a framework to better understand, model, and predict the existence and dynamics of microbial rare biospheres across divergent systems and scales.

Journal: ISME communications (2022)
Publication types: Journal Article
Anti-MDA5 Antibody-positive Dermatomyositis with Rapidly Progressive Interstitial Pneumonia Presenting with Nephrotic Syndrome during Treatment with Corticosteroids and Cyclosporine.

A 50-year-old japanese woman with anti-melanoma differentiation-associated gene 5 antibody (anti-mda5 antibody)-positive dermatomyositis presenting with rapidly progressive interstitial pneumonia was treated with corticosteroids and cyclosporine.She developed nephrotic syndrome during the treatment regimen with corticosteroids and cyclosporine.A kidney biopsy revealed a thrombotic microangiopathy (tma) glomerular lesion.Anti-mda5 antibody-positive dermatomyositis is prone to severe interstitial lung disease (ild) and is often exacerbated and refractory to treatment.Renal symptoms might be due to tma of the kidney, and this may be a sign that more intensive treatment is needed.Patients sometimes develop acute kidney injury, which may be due to the tma.

Journal: Internal medicine (Tokyo, Japan) (2022)
Publication types: Case Reports;Journal Article
Population Attributable Fraction of Early Age of Onset of Alcohol Use in Alcohol Abuse and Dependence: A 3-Year Follow-Up Study in University Students.

We aimed to determine the risk factors and associated population attributable fractions (pafs) for the age of onset of alcohol use and also to identify protective factors.Methods we analyzed follow-up data collected between autumn 2011 and spring 2016 (n= 5170) from the first two cohorts (2011, 2012) of the spit for science tmproject.The dependent variables were alcohol abuse and dependence, and the independent variables were age of drinking onset, residence, ethnicity, religiosity, sexual orientation and work status.We determined the odds ratios (or) using multilevel logistic regression for repeated measures in spssv.20.Results the early onset of alcohol use was associated with an increased risk of alcohol abuse and dependence among females (or = 14.98; or = 11.83) and males (or = 7.41; or = 6.24).The pafs for the early onset of alcohol use in alcohol abuse and dependence were respectively 80.9% and 71.7% in females and 71.0% and 63.5% in males.Among females, being white (or = 1.58; or = 1.51), living off-campus (or = 1.73; or = 2.76) and working full-time (or = 1.69; or = 1.78) were also risk factors.Strong religious beliefs were found to protect males from alcohol abuse (or = 0.58), while same-gender sexual orientation increased the risk among females (or = 2.09).Conclusion delaying the age of onset by one year would reduce alcohol abuse among young adults.

Journal: International journal of environmental research and public health (2020)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
A Multicenter Clinical Phase II Study of FOLFOXIRI Plus Bevacizumab as First-line Therapy in Patients With Metastatic Colorectal Cancer: QUATTRO Study.

Folfoxiri (fluorouracil, folinate, oxaliplatin, and irinotecan) plus bevacizumab improved progression-free survival (pfs) and overall survival in patients with metastatic colorectal cancer (m crc), compared with folfiri (fluorouracil, folinate, and irinotecan) plus bevacizumab, but significantly increased the incidences of adverse events.The efficacy and safety profiles of folfoxiri plus bevacizumab in ethnic asian patients have not been established yet.Patients and methods this study was an open-label, single-arm, multi-centered phase ii prospective clinical trial in patients with m crc who received folfoxiri plus bevacizumab.The primary endpoint was the pfs rate at 10 months.Secondary endpoints included overall survival, response rate, and safety.Results a total of 69 patients received folfoxiri plus bevacizumab as induction therapy and were assessed for efficacy and safety.The pfs rate at 10 months was 75.2% and the median pfs was 13.3 months.Complete response and partial response were achieved in 2 (2.9%) and 47 patients (69.1%), respectively.Grade 3 and 4 adverse events with incidence rates exceeding 20% were neutropenia (72.5%), hypertension (34.8%), leucopenia (33.3%), and febrile neutropenia (21.7%).Significantly more patients with grade 4 neutropenia had single-heterozygous ugt1a1*1/*6 or *1/*28 (46.2%) than ugt1a1 wild-type genotype (*1/*1) (13.3%) (p = .004).Conclusions folfoxiri plus bevacizumab is considered an effective first-line regimen that improves the outcome of patients with m crc regardless of ethnicity.In asian patients, utmost attention should be paid to the possible onset of severe neutropenia or febrile neutropenia attributed to different types of ugt1a1*6 and *28 polymorphism, when folfoxiri plus bevacizumab is administered.

Journal: Clinical colorectal cancer (2018)
Publication types: Clinical Trial, Phase II;Journal Article;Multicenter Study;Research Support, Non-U.S. Gov't
Implications of multimorbidity on healthcare utilisation and work productivity by socioeconomic groups: Cross-sectional analyses of Australia and Japan.

Multimorbidity, the presence of 2 or more non-communicable diseases (ncds), is a major contributor to inequalities of health in australia and japan.We use nationally representative data to examine (i) the relationships between multimorbidity with healthcare utilisation and productivity loss and (ii) whether these relationships differed by socioeconomic groups.Methods cross-sectional analyses using the household, income, and labour dynamics in australia (hilda) and the japanese study of aging and retirement (jstar) surveys.We examined 6,382 (hilda) and 3,503 (jstar) adults aged ≥50 years.We applied multivariable regression, logistic and negative binomial models.Results prevalence of multimorbidity was overall 38.6% (46.0%, 36.1%, 28.9% amongst those in the lowest, middle and highest education group, respectively) in australia, and 28.4% (33.9%, 24.6%, 16.6% amongst those in the lowest, middle and highest education group, respectively) in japan.In australia and japan, more ncds was associated with greater healthcare utilisation.In australia and japan, more ncds was associated with higher mean number of sick leave days amongst the employed and lower odds of being employed despite being in the labour force.The association between multimorbidity and lower retirement age was found in australia only.Conclusion having more ncds pose significant economic burden to the health system and wider society in australia and japan.Targeted policies are critical to improve financial protection, especially for lower income groups who are more likely to have multiple ncds.These individuals incur both high direct and indirect costs, which lead to a greater risk of impoverishment.

Journal: PloS one (2020)
Publication types: Journal Article;Research Support, Non-U.S. Gov't