syedzayyan/paper_mill_benchmark huggingface dataset:
Hypoxia-inducible factor-prolyl hydroxylase inhibitor ameliorates myopathy in a mouse model of chronic kidney disease.

Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (ckd), for which no curative therapy exists.Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of ckd models.Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting ckd-associated myopathy.Hypoxia-inducible factor (hif)-prolyl hydroxylase inhibitor (hif-phi) stabilizes hif and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from ckd models.Here, we assessed whether pharmacological activation of hif by mk-8617 (mk), a novel orally active hif-phi, improves ckd-associated myopathy.Mice were divided into sham or ckd groups, and ckd mice were subdivided into ckd + vehicle or mk treatment groups (1.5, 5, or 12.5 mg/kg for 12 wk).In ckd mice, skeletal muscle mass, mitochondrial amount, and exercise capacity decreased compared with sham mice.Compared with the ckd + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) doses of mk, but not the high dose (12.5 mg/kg), significantly restored these changes and was accompanied by incremental increases in hif-1α.Furthermore, increased capillary density and area were observed in a mk dose-dependent manner, which is likely related to an improved vegf response in the skeletal muscle of ckd mice.In addition, macrophage and proinflammatory cytokines, including monocyte chemoattractant protein 1, tnf-α, and il-6, significantly increased in the high-dose mk group.These results indicate that hif-phi provides a potential therapeutic strategy to improve ckd-associated myopathy.

Journal: American journal of physiology. Renal physiology (2019)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Hole Hopping through Cytochrome P450.

High-potential iron-oxo species are intermediates in the catalytic cycles of oxygenase enzymes.They can cause heme degradation and irreversible oxidation of nearby amino acids.We have proposed that there are protective mechanisms in which hole hopping from oxidized hemes through tryptophan/tyrosine chains generates a surface-exposed amino-acid oxidant that could be rapidly disarmed by reaction with cellular reductants.In investigations of cytochrome p450bm3, we identified trp96 as a critical residue that could play such a protective role.This trp is cation-π paired with arg398 in 81% of mammalian p450s.Here we report on the effect of the trp/arg cation-π interaction on trp96 formal potentials as well as on electronic coupling strengths between trp96 and the heme both for wild type cytochrome p450 and selected mutants.Mutation of arg398 to his, which decreases the trp96 formal potential, increases trp-heme electronic coupling; however, surprisingly, the rate of phototriggered electron transfer from a ru-sensitizer (through trp96) to the p450bm3heme was unaffected by the arg398his mutation.We conclude that trp96 has moved away from arg398, suggesting that the protective mechanism for p450s with this trp-arg pair is conformationally gated.

Journal: The journal of physical chemistry. B (2020)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't;Research Support, U.S. Gov't, Non-P.H.S.
Information-Driven Docking for TCR-pMHC Complex Prediction.

T cell receptor (tcr) recognition of peptides presented by major histocompatibility complex (mhc) molecules is a fundamental process in the adaptive immune system.An understanding of this recognition process at the molecular level is crucial for tcr based therapeutics and vaccine design.The broad nature of tcr diversity and cross-reactivity presents a challenge for traditional structural resolution.Computational modelling of tcr-p mhc complexes offers an efficient alternative.This study compares the ability of four general-purpose docking platforms (clus pro, light dock, zdock and haddock) to make use of varying levels of binding interface information for accurate tcr-p mhc modelling.Each platform was tested on an expanded benchmark set of 44 tcr-p mhc docking cases.In general, haddock is shown to be the best performer.Docking strategy guidance is provided to obtain the best models for each platform for future research.The tcr-p mhc docking cases used in this study can be downloaded from benchmark.

Journal: Frontiers in immunology (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Pyrazol-1-yl-propanamides as SARD and Pan-Antagonists for the Treatment of Enzalutamide-Resistant Prostate Cancer.

We report herein the design, synthesis, and pharmacological characterization of a library of novel aryl pyrazol-1-yl-propanamides as selective androgen receptor degraders (sards) and pan-antagonists that exert broad-scope ar antagonism.Pharmacological evaluation demonstrated that introducing a pyrazole moiety as the b-ring structural element in the common a-ring-linkage-b-ring nonsteroidal antiandrogens' general pharmacophore allowed the development of a new scaffold of small molecules with unique sard and pan-antagonist activities even compared to our recently published af-1 binding sards such as ut-155 (9) and ut-34 (10).Novel b-ring pyrazoles exhibited potent ar antagonist activities, including promising distribution, metabolism, and pharmacokinetic properties, and broad-spectrum ar antagonist properties, including potentin vivoantitumor activity.26awas able to induce an 80% tumor growth inhibition of xenografts derived from the enzalutamide-resistant (enz-r) vca p cell line.These results represent an advancement toward the development of novel ar antagonists for the treatment of enz-r prostate cancer.

Journal: Journal of medicinal chemistry (2020)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Factors Associated with Knowledge, Attitudes, and Prevention towards HIV/AIDS among Adults 15-49 Years in Mizoram, North East India: A Cross-Sectional Study.

Despite a campaign of effective educational interventions targeting knowledge, attitudes, and prevention, human immunodeficiency-virus/acquired immune deficiency syndrome (hiv/aids) continues to be a significant public health issue in india, with mizoram reporting the highest hiv/aids cases in 2018-2019.In this study, we extracted mizoram state from the national family health survey fourth series (nfhs-4) 2015-2016 datasets and investigated factors associated with respondents' knowledge, attitudes, and prevention towards hiv/aids.The sample included 3555 adults aged 15-49 years residing in mizoram, north-east india.Respondents who reported having ever heard of hiv/aids was 98%.Multivariate analysis indicated that the probability of having inadequate knowledge of hiv/aids was higher among those with no schooling, who were illiterate, of non-christian faiths, belonging to backward tribes or caste, from poor households, and those who lived in rural areas, not exposed to media.The odds of mother-to-child transmission (pmtct) of hiv/aids transmission was high among females (aor = 3.12, 95% ci 2.34-4.16), respondents aged 35-39 years (aor = 1.74, 95% ci 1.05-2.87) and those belonging to other backward class.The hiv/aids knowledge of respondents was found to be encouraging as the majority (98%) were considered to have a good level of understanding of the condition.An educational intervention to reduce the number of adults 15-49 years infected with hiv/aids in mizoram should target those from low socioeconomic groups, those from non-christian religions, and those from other backward classes.

Journal: International journal of environmental research and public health (2021)
Publication types: Journal Article
Higher intake of coagulase-negative staphylococci from maternal milk promotes gut colonization with mecA-negative Staphylococcus epidermidis in preterm neonates.

We aimed to determine factors associated with gut colonization of preterm neonates with coagulase-negative staphylococci (co ns) from maternal milk (mm).Study design co ns isolated from weekly collected stool and mm of hospitalized preterm (n = 49) and healthy term neonates (n = 20) were genotyped.Colonization-related factors were determined by cox proportional hazards regression.Result gut colonization with mec a-negative staphylococcus epidermidis from mm was less prevalent (40.8% vs.95%) and delayed (median age 15.5 vs.2 days) in preterm compared with term neonates.Enhanced colonization was associated with higher intake of co ns from mm (hazard ratio (95% confidence interval) 1.006 (1.00-1.01) for 106colony-forming units), lower proportion of mec a-positive predominant nicu strains in gut (0.09 (0.01-0.49) for 1%) and lower incidence of late-onset co ns sepsis (5% vs.34% in those without colonization).Conclusion enteral feeding with larger proportion of unpasteurized mm and limiting spread of predominant strains may promote colonization with co ns from mm.

Journal: Journal of perinatology : official journal of the California Perinatal Association (2018)
Publication types: Journal Article;Observational Study;Research Support, Non-U.S. Gov't
Therapeutic interventions for spinal muscular atrophy: preclinical and early clinical development opportunities.

Introduction spinal muscular atrophy (sma) is an autosomal recessive neurodegenerative neuromuscular disease that presents primarily in children.Abnormalities in the smn1gene cause reduced levels of the survival motor neuron (smn) protein, while a second gene,smn2, produces low levels of functional smn protein.Currently available drugs do not cure, so a significant unmet need remains for patients treated after symptom onset.Areas covered drugs available in the clinic, investigational agents and key questions for researchers are discussed.A pragmatic search of the literature was performed to identify therapies in late stages of preclinical, or in early stages of clinical development.This list was compared to the cure sma pipeline for completeness.Drugs approved for indications that have potential for impact for sma were included.These drugs target the primary deficiency in smn protein or other pathways involved in sma pathophysiology that are not smn-protein dependent.Expert opinion children treated after the onset of symptoms continue to have significant disability.Given the heterogeneity of the population phenotype evidenced by variable response to initial therapy, age at treatment onset and the need to demonstrate added value beyond approved therapeutics, the clinical development of new drugs will be challenging.

Journal: Expert opinion on investigational drugs (2021)
Publication types: Journal Article;Review
Impact of the substrate composition on enhanced biological phosphorus removal during formation of aerobic granular sludge.

Performance of enhanced biological phosphorus removal (ebpr) is often investigated with simple synthetic wastewater containing volatile fatty acids (vfas).In this study, various (fermentable) substrates, individually and in mixtures, were examined during the application of a granulation strategy.In addition, the microbial community and n2o formation were monitored.Sludge densification was observed in all systems.Stable ebpr, associated with the presence of accumulibacter and an anaerobic p-release up to 21.9 mg po43--p.g vss-1, was only obtained when vfas were present as sole substrate or in mixture.Systems fed with vfas were strongly related to the formation of n2o (maximum of 6.25% relative to the total available nitrogen).A moderate anaerobic dissolved organic carbon (doc) uptake was observed when amino acids (64.27 ± 3.08%) and glucose (75.39 ± 5.79%) as sole carbon source were applied.The substrate/species-specific enrichment of burkholderiaceae and saccharimonadaceae respectively, resulted in unstable ebpr in those systems.

Journal: Bioresource technology (2021)
Publication types: Journal Article
Synthesis and Nanoarchitectonics of Novel Squaraine Derivatives for Organic Photovoltaic Devices.

Necessary advancements in the area of organic photovoltaic (opv) devices include the upgrade of power conversion efficiencies (pce) and stability.One answer to these demands lies in the research into new absorbers.Here, we focus on the development of new small molecule absorbers from the group of squaraines (sqs).These modular absorbers can be applied as donors in organic solar cells and have the ability to utilize a broad range of solar radiation if blended with suitable acceptors.In order to allow for the compatibility and favorable organization of donor and acceptor in the absorber layer, we intend to optimize the structure of the sq by varying the groups attached to the squaric acid core.For that purpose, we accordingly developed a well-suited synthesis route.The novel alkyl- and benzyl-substituted aryl aminosquaraines were synthesized through an improved and eco-friendly procedure.Special emphasis was placed on optimizing the amination reaction to obtain initial precursors in the synthesis of squaraine, avoiding hitherto common catalytic processes.All sq precursors and sq products were completely described.The derived sqs were additionally characterized in thin-film configuration using cyclic voltammetry and uv-vis spectroscopy and then processed to prepare self-standing bulk heterojunction (bhj) thin films in conjunction with fullerene-based electron acceptors, which were characterized via profilometry.The comparison between sq and bhj solutions and thin films, using atomic force microscopy and uv-vis spectroscopy, revealed differences in susceptibility for the organization and orientation of the constituting domains.

Journal: Nanomaterials (Basel, Switzerland) (2022)
Publication types: Journal Article
Whole-genome sequence of a putative pathogenic Bacillus sp. strain SD-4 isolated from cattle feed.

S the present study describes the draft genome sequence of a novel bacillus sp.Strain sd-4 isolated from animal feed.The study aims to get a deeper insight into antimicrobial resistance and secondary metabolite biosynthetic gene clusters (bgcs) and the association between them.Methods the strain sd-4 was preliminarily evaluated for antibacterial activities, motility, biofilm formation, and enterotoxin production using in vitro assays.The genome of strain sd-4 was sequenced using the illumina hi seq 2500 platform with paired-end reads.The reads were assembled and annotated using spades and pgap, respectively.The genome was further analysed using several bioinformatics tools, including tygs, anti smash, rast, plasmid finder, vfdb, virulence finder, card, pathogen finder, mobile element finder, island viewer, and crisprfinder.Results in vitro assays showed that the strain is motile, synthesises biofilm, and produces an enterotoxin and antibacterial metabolites.The genome analysis revealed that the strain sd-4 carries antimicrobial resistance genes (args), virulence factors, and beneficial secondary metabolite bgcs.Further genome analysis showed interesting genome architectures containing several mobile genetic elements, including two plasmid replicons (rep us22 and rep20), five prophages, and at least four genomic islands (gis), including one listeria pathogenicity island lipi-1.Moreover, the strain sd-4 is identified as a putative human pathogen.Conclusion the genome of strain sd-4 harbours several bgcs coding for biologically active metabolites.It also contains antimicrobial resistance genes and is identified as a potential human pathogen.These results can be used to better comprehend antibiotic resistance in environmental bacteria that are not influenced by human intervention.

Journal: Journal of global antimicrobial resistance (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A Method for Contraction Force Measurement of hiPSC-Derived Engineered Cardiac Tissues.

Engineered cardiac tissue (ect) derived from human induced pluripotent stem cells (i pscs) can replicate human heart in vitro and be applied to drug discovery and heart disease models.The contraction force of ect is an important indicator of its function and of the disease phenotype.Here we describe a construction method of ect using the flexcell®tissue train®culture system and a contraction force measurement method based on the frank-starling law.

Journal: Methods in molecular biology (Clifton, N.J.) (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Smoking, telomere length and lung function decline: a longitudinal population-based study.

Telomere shortening is associated with copd and impaired lung function in cross-sectional studies, but there is no longitudinal study.We used data from 448 participants recruited as part of the french follow-up of the european community respiratory health survey.We found no relationship between telomere length at baseline and fev1decline after 11 years of follow-up.However, heavy smoking was associated with an accelerated fev1decline in individuals with short telomeres, but not in subjects with longer telomeres (p for interaction p=0.08).Our findings suggest that short telomere length in peripheral leucocytes might be a marker for increased susceptibility to the effect of smoking.

Journal: Thorax (2018)
Publication types: Letter
Advanced Care Planning and End-of-life Outcomes in Hematopoietic Stem Cell Transplant Patients.

/purpose this integrative review addresses whether the presence and timing of advanced care planning (acp) with or without a palliative care (pc) consultation affect place of death and use of high-intensity medical care at end-of-life (eol) in adolescent and young adult and adult cancer patients receiving hematopoietic stem cell transplant (hsct) therapy.Methods and results a literature search was completed in the scopus and pub med databases.The search was not restricted by date but was restricted to english language.A total of 1,616 articles were found, and after exclusion of duplicates and irrelevance, 79 articles were available to review.After reviewing inclusion and exclusion criteria, 9 articles related to acp with hsct were found, and 4 were eliminated after further review, resulting in 5 viable articles for review related to eol outcomes.Eol outcomes reviewed were place of death and high-intensity medical care.Factors noted to influence these measures included the presence or absence of acp, the timing of acp, and pc consultation.Overall survival also emerged as an eol outcome affected by acp.Conclusion although there have been many barriers identified to acp discussions in the hsct population, the findings from the integrative literature review support the use of early acp with patients who have hematologic malignancies undergoing hsct to address patient eol goals and reduce healthcare utilization at the eol.The data also suggest that identification of patients who would most benefit from early engagement in acp may positively impact outcomes.

Journal: The American journal of hospice & palliative care (2021)
Publication types: Journal Article;Review
Influences on Skeletal Health and Bone Mineralization in Children.

Bone is in its most active formation phase of mineralization in the pediatric and adolescent population.Peak bone mass is achieved around the late teens to early 20s.Deficient bone mineralization and decreased peak bone mass acquisition predispose an individual to childhood fractures or lifelong fracture risk.Adolescent fragility or stress fractures should prompt a secondary evaluation for the causes of a low bone mineral content, the root of a fracture.The purpose of this article is to review published literature that discusses the risk factors associated with a decreased bone mineral content in children from birth to the age of peak bone mass.The article also includes a public health planning model for pediatric osteoporosis.

Journal: Orthopedic nursing (2022)
Publication types: Journal Article
SparkEC: speeding up alignment-based DNA error correction tools.

In recent years, huge improvements have been made in the context of sequencing genomic data under what is called next generation sequencing (ngs).However, the dna reads generated by current ngs platforms are not free of errors, which can affect the quality of downstream analysis.Although error correction can be performed as a preprocessing step to overcome this issue, it usually requires long computational times to analyze those large datasets generated nowadays through ngs.Therefore, new software capable of scaling out on a cluster of nodes with high performance is of great importance.Results in this paper, we present spark ec, a parallel tool capable of fixing those errors produced during the sequencing process.For this purpose, the algorithms proposed by the cloud ec tool, which is already proved to perform accurate corrections, have been analyzed and optimized to improve their performance by relying on the apache spark framework together with the introduction of other enhancements such as the usage of memory-efficient data structures and the avoidance of any input preprocessing.The experimental results have shown significant improvements in the computational times of spark ec when compared to cloud ec for all the representative datasets and scenarios under evaluation, providing an average and maximum speedups of 4.9[formula: see text] and 11.9[formula: see text], respectively, over its counterpart.Conclusion as error correction can take excessive computational time, spark ec provides a scalable solution for correcting large datasets.Due to its distributed implementation, spark ec speed can increase with respect to the number of nodes in a cluster.Furthermore, the software is freely available under gplv3 license and is compatible with different operating systems (linux, windows and mac os).

Journal: BMC bioinformatics (2022)
Publication types: Journal Article
Physician Voices on ECHO Autism India-Evaluation of a Telementoring Model for Autism in a Low-Middle Income Country.

S training pediatricians in low- and middle-income countries (lmics) in early diagnosis and comprehensive management of autism spectrum disorder (asd) is crucial to ensure optimal developmental outcomes for a substantial number of children with asd in this region.This study evaluates the relevance and effectiveness of an evidence-based telementoring model extension for community healthcare outcomes (echo) autism in increasing pediatricians' access to best-practice care for children with asd in lmic contexts.Methods echo autism was launched by a ‟hub" team of multidisciplinary asd experts at a child development center in mumbai, india.The culturally modified model included 13 biweekly sessions conducted annually using video-conferencing technology.Sessions combined expert-delivered didactics and facilitated case-based discussions on best-practice methods in screening, diagnosing, and managing autism and its comorbidities.Sixty-two physicians, including 59 pediatricians across 2 cohorts (2019-2020), participated in the mixed-methods study to evaluate participants' reactions, knowledge, behaviors, and impact on children and families.Results participants represented a broad geographic reach across india (n = 47) and other lmics (n = 15).Both quantitative and qualitative data revealed high levels of participant satisfaction and improved knowledge and self-efficacy in asd diagnosis and management.Qualitative themes highlighted the adult-learning processes of echo autism that participants considered novel and beneficial, such as reflective discussions, respectful mentoring, having a parent as ‟expert," and cultural relevance, alongside changes in practice behaviors.Conclusion echo autism clinics facilitated by local experts in lmics can improve access to early diagnosis and evidence-based, comprehensive management for children with asd and their families by positively influencing pediatricians' knowledge, attitudes, and practice behaviors.

Journal: Journal of developmental and behavioral pediatrics : JDBP (2022)
Publication types: Journal Article