syedzayyan/paper_mill_benchmark huggingface dataset:
Hexokinase 2 is a transcriptional target and a positive modulator of AHR signalling.

The aryl hydrocarbon receptor (ahr) regulates the expression of numerous genes in response to activation by agonists including xenobiotics.Although it is well appreciated that environmental signals and cell intrinsic features may modulate this transcriptional response, how it is mechanistically achieved remains poorly understood.We show that hexokinase 2 (hk2) a metabolic enzyme fuelling cancer cell growth, is a transcriptional target of ahr as well as a modulator of its activity.Expression of hk2 is positively regulated by ahr upon exposure to agonists both in human cells and in mice lung tissues.Conversely, over-expression of hk2 regulates the abundance of many proteins involved in the regulation of ahr signalling and these changes are linked with altered ahr expression levels and transcriptional activity.Hk2 expression also shows a negative correlation with ahr promoter methylation in tumours, and these tumours with high hk2 expression and low ahr methylation are associated with a worse overall survival in patients.In sum, our study provides novel insights into how ahr signalling is regulated which may help our understanding of the context-specific effects of this pathway and may have implications in cancer.

Journal: Nucleic acids research (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
Downregulation of microRNA-302b-3p relieves oxygen-glucose deprivation/re-oxygenation induced injury in murine hippocampal neurons through up-regulating Nrf2 signaling by targeting fibroblast growth factor 15/19.

Micro rnas have emerged as critical mediators of cerebral ischaemia/reperfusion injury.Recent studies have demonstrated that micro rna-302b-3p (mi r-302b-3p) plays an important role in regulating apoptosis and oxidative stress in various cells.However, whether mi r-302b-3p is involved in regulating cerebral ischaemia/reperfusion injury-induced neuronal apoptosis and oxidative stress remains unknown.In the present study, we explored the potential function and molecular mechanism of mi r-302b-3p in oxygen-glucose deprivation/re-oxygenation (ogd/r)-induced neuronal injury, using an in vitro model of cerebral ischaemia/reperfusion injury.We found that mi r-302b-3p expression was up-regulated by ogd/r treatment in neurons.The inhibition of mi r-302b-3p improved cell viability, and reduced apoptosis and the production of reactive oxygen species, showing a protective effect against ogd/r-induced injury.Interestingly, mi r-302b-3p was shown to target and modulate murine fibroblast growth factor 15 (fgf15).Moreover, our results showed that mi r-302b-3p down-regulation contributed to the promotion of nuclear factor erythroid 2-related factor 2 (nrf2)/antioxidant response element (are)-mediated antioxidant signaling associated with the inactivation of glycogen synthase kinase-3β.However, the knockdown of fgf15 significantly reversed the mi r-302b-3p inhibition-mediated protective effect in ogd/r-treated neurons.Overall, these results demonstrated that mi r-302b-3p inhibition confers a neuroprotective effect in ogd/r-treated neurons by up-regulating nrf2/are antioxidant signaling via targeting fgf15, providing a novel target for neuroprotection in cerebral ischaemia/reperfusion injury.

Journal: Chemico-biological interactions (2019)
Publication types: Journal Article
Six month nonunion tibial diaphysis osteotomy treated with conventional pulsed therapeutic ultrasound: a case report.

A large tibial defect significantly increases the chances of nonunion fractures, changes in the quality of life, and pain.Tibial osteotomy with a large gap size is an unfavorable condition to complete healing.Purpose to describe the treatment of a complex case of a six-month nonunion tibial diaphysis osteotomy using conventional pulsed ultrasound therapy (cput).Case description a 46-year-old man, 1.65 m tall, weighing 63 kg, and homeless was diagnosed with a nonunion tibial diaphysis fracture and underwent osteotomy of the tibial diaphysis with an opening gap and external fixation with circular rings and thin wires (ilizarov).An interdisciplinaty approach including social work, nutrition, and physiotherapy including exercise reconditioning was initiated over a period of two years.After six months of nonunion following a tibial osteotomy, cput was used with a frequency of 1 mhz, duty cycle of 20%, spatially averaged temporally averaged (sata) intensity of 0.1 w/cm2, frequency of 100 hz, 20 min of duration, for 2-3 times for 20 weeks.Outcomes there was an improvement in the amount of bone in the fracture gap with a total restoration of function, resolution of pain, and gait without crutches after 35 sessions of cput.Conclusion an interdisciplinary approach including mechanical stimulus from cput assisted in the healing process in a patient with chronic tibial osteotomy nonunion.

Journal: Physiotherapy theory and practice (2022)
Publication types: Case Reports;Journal Article
Whole-genome sequencing analysis and CRISPR genotyping of rare antibiotic-resistant Salmonella enterica serovars isolated from food and related sources.

For decades, salmonella typhimurium and salmonella enteritidis have prevailed in several countries as agents of salmonellosis outbreaks.In brazil, the largest exporter of poultry meat, relatively little attention has been paid to infrequent serovars.Here, we report the emergence and characterization of rare serovars isolated from food and related sources collected between 2014 and 2016 in brazil.Twenty-two salmonella enterica isolates were analyzed through the use of whole-genome sequencing (wgs) and clustered regularly interspaced short palindromic repeats (crispr) genotyping.These isolates were classified into 10 infrequent serovars, including s.Abony, s.Isangi, s.Rochdale, s.Saphra, s.Orion, s.Ouakam, s.Grumpensis, s.Carrau, s.Abaetetuba, and s.Idikan.The presence of six antimicrobial resistance (amr) genes, qnr b19, bla cmy-2, tet a, aac(6')-iaa, sul2 and fos a7, which encode resistance to quinolones, third-generation cephalosporin, tetracycline, aminoglycoside, sulfonamide and fosfomycin, respectively, were confirmed by wgs.All s.Isangi harbored qnr b19 with conserved genomic context across strains, while s.Abony harbored bla cmy-2.Twelve (54.5%) strains displayed chromosomal mutations in par c (thr57→ser).Most serovars were classified as independent lineages, except s.Abony and s.Abaetetuba, which phylogenetically nested with salmonella strains from different countries.Crispr analysis revealed that the spacer content was strongly correlated with serovar and multi-locus sequence type for all strains, independently confirming the observed phylogenetic patterns, and highlighting the value of crispr-based genotyping for salmonella.These findings add valuable information to the epidemiology of s.Enterica in brazil, where the emergency of antibiotic-resistant salmonella continues to evolve.

Journal: Food microbiology (2021)
Publication types: Journal Article
Role of endoplasmic reticulum stress in impaired neonatal lung growth and bronchopulmonary dysplasia.

Myeloperoxidase (mpo), oxidative stress (os), and endoplasmic reticulum (er) stress are increased in the lungs of rat pups raised in hyperoxia, an established model of bronchopulmonary dysplasia (bpd).However, the relationship between os, mpo, and er stress has not been examined in hyperoxia rat pups.We treated sprague-dawley rat pups with tunicamycin or hyperoxia to determine this relationship.Er stress was detected using immunofluorescence, transcriptomic, proteomic, and electron microscopic analyses.Immunofluorescence observed increased er stress in the lungs of hyperoxic rat bpd and human bpd.Proteomic and morphometric studies showed that tunicamycin directly increased er stress of rat lungs and decreased lung complexity with a bpd phenotype.Previously, we showed that hyperoxia initiates a cycle of destruction that we hypothesized starts from increasing os through mpo accumulation and then increases er stress to cause bpd.To inhibit er stress, we used tauroursodeoxycholic acid (tudca), a molecular chaperone.To break the cycle of destruction and reduce os and mpo, we used n-acetyl-lysyltyrosylcysteine amide (kyc).The fact that tudca improved lung complexity in tunicamycin- and hyperoxia-treated rat pups supports the idea that er stress plays a causal role in bpd.Additional support comes from data showing tudca decreased lung myeloid cells and mpo levels in the lungs of tunicamycin- and hyperoxia-treated rat pups.These data link os and mpo to er stress in the mechanisms mediating bpd.Kyc's inhibition of er stress in the tunicamycin-treated rat pup's lung provides additional support for the idea that mpo-induced er stress plays a causal role in the bpd phenotype.Er stress appears to expand our proposed cycle of destruction.Our results suggest er stress evolves from os and mpo to increase neonatal lung injury and impair growth and development.The encouraging effect of tudca indicates that this compound has the potential for treating bpd.

Journal: PloS one (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't;Research Support, N.I.H., Extramural
A mixed methods study to assess the impact of COVID-19 on maternal, newborn, child health and nutrition in fragile and conflict-affected settings.

The impacts of covid-19 are unprecedented globally.The pandemic is reversing decades of progress in maternal, newborn, child health and nutrition (mnchn), especially fragile and conflict-affected settings (fcas) whose populations were already facing challenges in accessing basic health and nutrition services.This study aimed to investigate the collateral impact of covid-19 on funding, services and mnchn outcomes in fcas, as well as adaptations used in the field to continue activities.Methods a scoping review of peer-reviewed and grey literature published between 1st march 2020-31st january 2021 was conducted.We analysed 103 publications using a narrative synthesis approach.39 remote semi-structured key informant interviews with humanitarian actors and donor staff within 12 fcas were conducted between october 2020 and february 2021.Thematic analysis was undertaken independently by two researchers on interview transcripts and supporting documents provided by key informants, and triangulated with literature review findings.Results funding for mnchn has been reduced or suspended with increase in cost of continuing the same activities, and diversion of mnchn funding to covid-19 activities.Disruption in supply and demand of interventions was reported across different settings which, despite data evidence still being missing, points towards likely increased maternal and child morbidity and mortality.Some positive adaptations including use of technology and decentralisation of services have been reported, however overall adaptation strategies have been insufficient to equitably meet additional challenges posed by the pandemic, and have not been evaluated for their effectiveness.Conclusions covid-19 is further exacerbating negative women's and children's health outcomes in fcas.Increased funding is urgently required to re-establish mnchn activities which have been deprioritised or halted.Improved planning to sustain routine health services and enable surge planning for emergencies with focus on the community/service users throughout adaptations is vital for improved mnchn outcomes in fcas.

Journal: Conflict and health (2022)
Publication types: Journal Article
Development and Implementation of a Longitudinal Global Acute Care and Systems Strengthening Program.

Increasing access to safe, timely, and affordable acute care in low- and middle-income countries is a worldwide priority.Longitudinal curricula on systems of acute care have not been previously described.Objectives the authors aimed to develop a novel four-year longitudinal curriculum for medical students addressing systems development across multiple acute care specialties.Methods the authors followed kern's six-step framework for curriculum design.After review of literature, a group of medical students and school of medicine faculty conducted a targeted needs assessment.Foundational goals and objectives were adapted from the 39 interprofessional global health competencies by the consortium of universities for global health.Educational strategies include didactic sessions, workshops, journal clubs, preceptorships, and community outreach.Clinical years include specialty-specific emphases, guided junior-level discussions, and a capstone project.Yearly swot and kirkpatrick model analyses served as program evaluation.Findings the curriculum council approved the program in july 2019.During the first cycle, the program matriculated 30 students from classes of 2023 (14) and 2022 (16).The first year produced 11 interactive sessions, 6 journal clubs, and 10 seminars led by 31 faculty and guest speakers; 29/30 students completed requirements; 87 evaluations reflected 4.57/5 content satisfaction and 4.73/5 instructor satisfaction.The 2023 cohort reported improved understanding of session objectives (3.13/5 vs.3.82/5, p = 0.03).Free-text feedback led to implementation of pre-reading standardization and activity outlines.Conclusion the program was well-received and successfully implemented.It meets the needs of graduating medical students interested in leading global health work.This novel student-faculty collaborative model could be applied at other institutions seeking to provide students with a foundation in global acute care.

Journal: Annals of global health (2021)
Publication types: Journal Article
Interactions of Colorectal Cancer, Dietary Fats, and Polymorphisms of Arachidonate Lipoxygenase and Cyclooxygenase Genes: A Literature Review.

Genetics and dietary factors play important roles in the development of colorectal cancer (crc).However, the underlying mechanisms of the interactions between crc, gene polymorphisms, and dietary fat are unclear.This review study investigated the effects of polymorphisms of arachidonate lipoxygenase (alox) and cyclooxygenase (cox) genes in the association between crc and dietary fat.Methods all the related papers published from 2000 to 2022 were collected from different databases such as pub med, science direct, scopus, and cochran using related keywords such as colorectal cancer,alox,cox, polymorphism, and dietary fat.Non-english and unrelated documents were excluded.Results some single-nucleotide polymorphisms (snps) in the aloxand coxgenes, such as rs2228065, rs6413416, and rs4986832 in the aloxgene, and rs689465 in the coxgene may play significant roles in the association between the risk of crc and dietary fats.Snps of alox and cox genes may influence the effects of dietary fatty acids on the risk of crc.Conclusion some polymorphisms of the aloxand coxgenes may have important roles in the effects of dietary fat on the risk of crc.If future studies confirm these results, dietary recommendations for preventing colorectal cancer may be personalized based on the genotype of the aloxand coxgenes.

Journal: Frontiers in oncology (2022)
Publication types: Journal Article;Review
Optofluidic Particle Manipulation Platform with Nanomembrane.

We demonstrate a method for fabricating and utilizing an optofluidic particle manipulator on a silicon chip that features a 300 nm thick silicon dioxide membrane as part of a microfluidic channel.The fabrication method is based on etching silicon channels and converting the walls to silicon dioxide through thermal oxidation.Channels are encapsulated by a sacrificial polymer which fills the length of the fluid channel by way of spontaneous capillary action.The sacrificial material is then used as a mold for the formation of a nanoscale, solid-state, silicon dioxide membrane.The hollow channel is primarily used for fluid and particle transport but is capable of transmitting light over short distances and utilizes radiation pressure for particle trapping applications.The optofluidic platform features solid-core ridge waveguides which can direct light on and off of the silicon chip and intersect liquid channels.Optical loss values are characterized for liquid and solid-core structures and at interfaces.Estimates are provided for the optical power needed to trap particles of various sizes.

Journal: Micromachines (2022)
Publication types: Journal Article
The cascade of care for latent tuberculosis infection in congregate settings: A national cohort analysis, Korea, 2017-2018.

In 2017, korea implemented a nationwide project to screen and treat latent tuberculosis infection (ltbi) in high-risk for transmission public congregate settings.We aimed to assess programme success using a cascade of care framework.Materials and methods we undertook a cohort study of people from three congregate settings screened between march 2017 and december 2018: (1) first-grade high school students, (2) employees of educational institutions, (3) employees of social welfare facilities.We report percentages of participants with ltbi completing each step in the cascade of care model.Poisson regression models were used to determine factors associated with not visiting clinics, not initiating treatment, and not completing treatment.Results among the 96,439 participants who had a positive interferon-gamma release assay result, the percentage visiting clinics for further assessment, to initiate treatment, and who then completed treatment were 50.7, 34.7, and 28.9%, respectively.Compared to those aged 20-34 years, individuals aged < 20 years and aged ≥ 65 years were less likely to visit clinics, though more likely to complete treatment once initiated.Using public health centres rather than private hospitals was associated with people "not initiating treatment" (adjusted risk ratio [a rr], 3.72; 95% confidence interval [ci], 3.95-3.86).Nine-month isoniazid monotherapy therapy was associated with "not completing treatment," compared to 3-month isoniazid and rifampin therapy (a rr, 1.28; 95% ci, 1.16-1.41).Conclusion among participants with ltbi from three congregate settings, less than one third completed treatment.Age, treatment centre, and initial regimen were important determinants of losses to care through the cascade.

Journal: Frontiers in medicine (2022)
Publication types: Journal Article
DWV 3C Protease Uncovers the Diverse Catalytic Triad in Insect RNA Viruses.

Deformed wing virus (dwv) is the most prevalent iflavirus that is infecting honey bees worldwide.However, the mechanisms of its infection and replication in host cells are poorly understood.In this study, we analyzed the structure and function of dwv 3c protease (3cpro), which is necessary for the cleavage of the polyprotein to synthesize mature viral proteins.Thus, it is one of the nonstructural viral proteins essential for the replication.We found that the 3cpros of dwv and picornaviruses share common enzymatic properties, including sensitivity to the same inhibitors, such as rupintrivir.The predicted structure of dwv 3cproby alpha fold2, the predicted rupintrivir binding domain, and the protease activities of mutant proteins revealed that it has a cys-his-asn catalytic triad.Moreover, 3cpros of other iflaviruses and dicistrovirus appear to contain asn, ser, asp, or glu as the third residue of the catalytic triad, suggesting diversity in insect rna viruses.Both precursor 3cprowith rna-dependent rna polymerase and mature 3cproare present in dwv-infected cells, suggesting that they may have different enzymatic properties and functions.Dwv 3cprois the first 3cprocharacterized among insect rna viruses, and our study uncovered both the common and unique characteristics among 3cpros of picornavirales.Furthermore, it would be possible to use the specific inhibitors of dwv 3cproto control dwv infection in honey bees in future.importancethe number of managed honey bee (apis mellifera) colonies has considerably declined in many developed countries in the recent years.Deformed wing virus (dwv) vectored by the mites is the major threat to honey bee colonies and health.To give insight into the mechanism of dwv replication in the host cells, we studied the structure-function relationship of 3c protease (3cpro), which is necessary to cleave a viral polyprotein at the specific sites to produce the mature proteins.We found that the overall structure, some inhibitors, and processing of 3cproare shared between picornavirales; however, there is diversity in the catalytic triad.Dwv 3cprois the first viral protease characterized among insect rna viruses and reveals the evolutionary history of 3cproamong picornavirales.Furthermore, dwv 3cproinhibitors identified in our study could also be applied to control dwv in honey bees in future.

Journal: Microbiology spectrum (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Unraveling the Abnormal Molecular Mechanism of Suicide Inhibition of Cytochrome P450 3A4.

Suicide inhibition of the cyp3a4 enzyme by a drug inactivates the enzyme in the drug biotransformation process and often shows safety concerns about the drug.Despite extensive experimental studies, the abnormal molecular mechanism of a suicide inhibitor that forms a covalent bond with the residue far away from the catalytically active center of cyp3a4 inactivating the enzyme remains elusive.Here, the authors used molecular simulation approaches to study in detail how diquinone methide (dqr), the metabolite product of raloxifene, unbinds from cyp3a4 and inactivates the enzyme at the atomistic level.The results clearly indicate that in one of the intermediate states formed in its unbinding process, dqr covalently binds to cys239, a residue far away from the catalytically active center of cyp3a4, and hinders the substrate from entering or leaving the enzyme.This work therefore provides an unprecedented way of clarifying the abnormal mechanism of suicide inhibition of the cyp3a4 enzyme.

Journal: Journal of chemical information and modeling (2022)
Publication types: Journal Article
Dietary intake of patients with inflammatory bowel disease aligns poorly with traditional Mediterranean diet principles.

Previous research has shown that individuals with inflammatory bowel disease avoid specific food items, such as fibre rich foods, in order to manage symptoms.Dietary fibre and the traditional mediterranean diet are both associated with reduced mucosal and systemic inflammation, gut barrier integrity, and microbiota diversity.There is limited data on the diet composition of individuals with inflammatory bowel disease.The aim of this study was to evaluate how it compares to the traditional mediterranean diet and national dietary guidelines.Methods outpatients with inflammatory bowel disease were recruited to the study between february and august 2019.Demographic and medical information was obtained for consenting participants.All participants completed a dietary assessment of usual intake (24-h diet recall and 17-point ready reckoner) from which a mediterranean diet adherence score was calculated.Dietary intake of core food groups was compared to the recommended number of serves outlined in the australian guide to healthy eating.Results 100 participants were recruited.The mean mediterranean diet adherence score was 5.1 ± 1.3 (maximum 14 points), 4% of participants scored ≥9 (commonly agreed criteria for mediterranean diet adherence).Participants also consumed considerably less grains and vegetables than national dietary guidelines recommendations.Conclusions the diet of outpatients with inflammatory bowel disease did not align with mediterranean diet characteristics.Participants consumed significantly less grains and vegetables than national guidelines, suggesting a low fibre intake.These findings suggest that dietary interventions focusing on improving the diet of individuals with inflammatory bowel disease to align with mediterranean diet characteristics are warranted.

Journal: Nutrition & dietetics : the journal of the Dietitians Association of Australia (2022)
Publication types: Journal Article