syedzayyan/paper_mill_benchmark huggingface dataset:
The zinc-binding motif in tankyrases is required for the structural integrity of the catalytic ADP-ribosyltransferase domain.

Tankyrases are adp-ribosylating enzymes that regulate many physiological processes in the cell and are considered promising drug targets for cancer and fibrotic diseases.The catalytic adp-ribosyltransferase domain of tankyrases contains a unique zinc-binding motif of unknown function.Recently, this motif was suggested to be involved in the catalytic activity of tankyrases.In this work, we set out to study the effect of the zinc-binding motif on the activity, stability and structure of human tankyrases.We generated mutants of human tankyrase (tnks) 1 and tnks2, abolishing the zinc-binding capabilities, and characterized the proteins biochemically and biophysicallyin vitro.We further generated a crystal structure of tnks2, in which the zinc ion was oxidatively removed.Our work shows that the zinc-binding motif in tankyrases is a crucial structural element which is particularly important for the structural integrity of the acceptor site.While mutation of the motif rendered tnks1 inactive, probably due to introduction of major structural defects, the tnks2 mutant remained active and displayed an altered activity profile compared to the wild-type.

Journal: Open biology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
The development and validation of an obstetric triage acuity index: a mixed-method study.

There is uncertainty about the applicability of developed country triage scales in the developing population.Objective to develop and validate an obstetric triage scale in iran.Methods this exploratory sequential mixed-method study was conducted on experienced gynecologists, emergency medicine, midwives, and nurses as evaluators, and pregnant or parturient women as sample.Development of obstetric triage acuity index was done using qualitative study and literature review.Thirty-two evaluators in two rounds evaluated the clinical impact score, content validity ratio, and content validity index.The tool performance was compared with a standard reference in 415 women.The association of urgency levels with hospitalization, resource utilization, and emergency department length of stay were assessed in 599 women.Five midwives independently double-triaged 234 convenience women to estimate inter-rater reliability.Results out of 191 items in the initial draft, 9 (4.7%) items in the face validity, 33 (18.1%) in the first, and 5 (3.2%) in the second content validity round were removed because not meeting the expected thresholds.Nine items added based on evaluators' suggestions.Finally, total items had a kappa above 0.74, and s-cvi/ave, s-cvi/ua were 0.99 and 0.86, respectively.There was a significant correlation between the two tools (r= 0.661,p< 0).Level 1 mothers had a higher chance of using ≥ 2 resources (or = 16.4, 95% ci = 2.06-129.98) and hospitalization (or = 18.0, 95% ci = 3.96-81.51) compared to the level 5, after adjusting for gestational age/postpartum, and referral method.Sensitivity, specificity, and accuracy of the scale in predicting hospitalization were 74.8% (95% ci = 69.73-79.49), 80.8% (95% ci = 73.60-86.74), and 76.7% (72.67-80.48), respectively.The over and under-triage rates were 6.1% and 17.1%, respectively.The absolute agreement inter-raters was 86.8%, and the linear weighted kappa was 0.86 (95% ci = 0.81-0.91).Conclusion the designed ob triage scale showed good validity and reliability in the tertiary teaching hospital.Studying this tool at lower levels, non-educational, and public hospitals are recommended for external validity testing.

Journal: The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians (2022)
Publication types: Journal Article
Regeneration in distantly related species: common strategies and pathways.

While almost all animals are able to at least partially replace some lost parts, regeneration abilities vary considerably across species.Here we study gene expression patterns in distantly related species to investigate conserved regeneration strategies.To this end, we collect from the literature transcriptomic data obtained during the regeneration of three species (hydra magnipapillata, schmidtea mediterranea,and apostichopus japonicus), and compare them with gene expression during regeneration in vertebrates and mammals.This allows us to identify a common set of differentially expressed genes and relevant shared pathways that are conserved across species during the early stage of the regeneration process.We also find a set of differentially expressed genes that in mammals are associated to the presence of macrophages and to the epithelial-mesenchymal transition.This suggests that features of the sophisticated wound healing strategy of mammals are already observable in earlier emerging metazoans.

Journal: NPJ systems biology and applications (2018)
Publication types: Journal Article
In vitro and in vivo studies of the native isolates of nematophagous fungi from China against the larvae of trichostrongylides.

To screen potential nematophagous fungi candidates for the biological control of parasitic nematodes in livestock, in vitro and in vivo studies of the native isolates of nematophagous fungi against the larvae of trichostrongylides were conducted.The in vitro predatory activity of 16 native nematophagous fungal isolates on the larvae of trichostrongylides in sheep feces was assessed.In the ten isolates of duddingtonia flagrans, the reduction percentage for the infective larvae (l3) of trichostrongylus colubriformis ranged from 57.21 to 99.83%, and that of haemonchus contortus ranged from 62.12 to 99.88%.The analysis of the same assay on five isolates of arthrobotrys superba and one isolate of a.Cookedickinson (monacrosporium cystosporum) showed comparable results with those for d.Flagrans.To determine the excretion time of fungal isolates in feces after oral administration, d.Flagrans (sdh035) were studied in vivo in sheep and rabbits.Results showed that the tested fungal isolates existed in sheep feces from 12 to 72 h after fungal treatment, and the fungal excretion in rabbit feces occurred at 4 h, reached a peak at 10 h, and declined gradually 18 h after oral administration.All the native fungal isolates were assessed after passing through the gastrointestinal tract of sheep.Treatment with isolates of d.Flagrans significantly reduced the number of developing larvae in the feces, and the efficacies ranged from 55.15 to 98.82%.One out of the five isolates of a.Superba and a.Cookedickinson (bs002) survived after passing through the gastrointestinal tract, and the l3 reduction rates were 83.79 and 81.33%, respectively.Results of the present study provide information about the in vitro predatory activity of nematophagous fungi from china on the l3 of trichostrongylides and their ability to pass through the gastrointestinal tract before administering them for biocontrol.

Journal: Journal of basic microbiology (2017)
Publication types: Journal Article
Cryopreservation did not affect sperm DNA methylation levels of genes related to fertilization and embryonic development of cynomolgus macaque (Macaca fascicularis).

Dna methylation alters gene expression in numerous biological processes, including embryonic development.It is little known about the effect of cryopreservation on sperm dna methylation.The present study has investigated whether cryopreservation causes abnormal dna methylation in cynomolgus macaque sperm for five critical genes that includes the maternally imprinted gene (snrpn), genes associated with male infertility (hspa1l, mthfr) and genes involved in embryonic development (tet3, lztr1).Our results showed that sperm motility, the percentage of acrosomal integrity, dna integrity and mitochondrial membrane potential were decreased after cryopreservation either being frozen with penetrating cryoprotectant, glycerol (gly) or ethylene glycol (eg), compared to fresh sperm (p = 0.000), but the methylation patterns of the five target genes from cynomolgus macaque sperm samples were not affected after cryopreservation as evaluated by the bisulfite sequencing pcr (bsp) method.The data indicates that the current protocol for sperm cryopreservation of cynomolgus macaque is safe in terms of dna methylation levels in these genes related to critical sperm functions.

Journal: Cryobiology (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Impact of different laminae open angles on axial symptoms after expansive open-door laminoplasty.

The present study is a retrospective study.axial symptoms are frequently encountered complication after laminoplasty.Some studies have reported the influencing factors and preventive measures of axial symptoms after laminoplasty.However, impact of different laminae open angles on the postoperative axial symptoms remains unclear.the objective of the present study was to explore the effect of different laminae open angles on postoperative axial symptoms and to discuss the possible mechanisms of the impact of different open angles on axial symptoms.we retrospectively analyzed 124 patients with multilevel cervical compression myelopathy who were treated with expansive open-door laminoplasty from february 2012 to january 2015.The operational level ranged from c3-c7 in all patients.The laminae open angles at the c4, c5, and c6 levels were measured 1 week postoperative.The mean value was taken for statistical analysis.The patients were divided into 2 groups, group a (open angles .05).At 2 weeks and 6 months after surgery, there was significant difference in axial symptoms between the 2 groups (p .05).in different angles of the lamina open-door, incidence of axial symptoms has statistically difference between the 2 groups.When the lamina open-door angles are <40°, there are not only ensure adequate spinal cord decompression but reduces the incidence of early and midterm postoperative axial pain.

Journal: Medicine (2018)
Publication types: Journal Article;Observational Study
Association between anticholinergic drug burden and mortality in older people: a systematic review.

The purpose of the study is to conduct a systematic review of studies examining the association between anticholinergic burden and mortality in older individuals.Methods a literature search was performed to identify relevant studies, using medline, embase, psyc info and central, from january 1990 to december 2018.We included studies of patients with a mean age of 65 years or older where the anticholinergic burden was estimated using anticholinergic risk assessment tools, and associations between anticholinergic load and mortality were investigated.The primary outcome of interest was the association between anticholinergic burden and mortality.Results twenty-seven studies were included.These were three cross-sectional, one nested case-control and 23 prospective or retrospective cohort studies.Most studies were determined to be of good quality.A total of 15 studies reported a positive correlation between anticholinergic burden and mortality, while the remaining 10 studies did not report a significant association.Eighteen out of 27 studies (80%) had a short follow-up period of 1 year or less.Among the five high-quality studies that met all the domains of the quality assessment criteria, four showed a positive association.Conclusion the variation in results could relate to the quality of the studies, follow-up period, anticholinergic risk assessment tool used and the study setting.Sixty-three percent (n = 17) of all the included studies, but almost all of the high-quality studies with an extended follow-up, reported a positive correlation between anticholinergic burden and mortality.Further high-quality research, using standardized measures and with adequate follow-up periods, is required to confirm the relationship between anticholinergic burden and mortality.

Journal: European journal of clinical pharmacology (2020)
Publication types: Journal Article;Meta-Analysis;Systematic Review
COVID-19 associated diabetes mellitus: A review.

A significantly higher rate of new-onset diabetes in many coronavirus disease 2019 (covid-19) patients is a frequently observed phenomenon.The resultant hyperglycemia is known to influence the clinical outcome, thereby increasing the cost of treatment and stay in hospital.This will also affect the post-hospitalization recuperation.It has been observed that new-onset diabetes in covid-19 patients is associated with considerable increase in morbidity and may be associated with increased mortality in some cases.This mini-review focuses on the possible causes to understand how covid-19-related diabetes develops, various associated risk factors, and possible mechanism to understand the natural history of the disease process, clinical outcome, associated morbidities and various treatment options in the mana-gement of post covid-19 diabetes.A literature search was performed in pub med and other online database using appropriate keywords.A total of 80 articles were found, among which, 53 of the most relevant were evaluated/ analyzed and relevant data were included.The studies show that patients who have had severe acute respiratory syndrome coronavirus 2 infection leading to development of covid-19 may manifest not only with new-onset diabetes but also worsening of pre-existing diabetes.Cytopathic effect and autoimmune destruction of insulin-secreting pancreatic beta cells, cytokine storm during the active phase of infection causing impaired insulin secretion and resistance, drug-induced hyperglycemia, undetected pre-existing hyperglycemia/diabetic condition, and stress-induced impairment of glucose metabolism are some of the possible potential mechanisms of covid-19-associated new-onset diabetes mellitus.Many studies published in recent times have found a significantly higher rate of new-onset diabetes mellitus in many covid-19 patients.Whether it is an inflammatory or immune-mediated response, direct effect of virus or combination of these is unclear.The resultant hyperglycemia is known to influence the clinical outcome and has been associated with considerable increase in morbidity and increased mortality in some cases.

Journal: World journal of diabetes (2022)
Publication types: Journal Article;Review
Environmental surveillance of Legionella pneumophila in hot water systems of hotels in Morocco.

Environmental monitoring of legionella in hot water systems of hotels in morocco was performed during the period from january 2016 to april 2018.A total of 149 water samples from 118 different hotels were analyzed.Methods a total of 149 water samples from 118 different hotels were analyzed.Possible risk factors were prospectively recorded, and data were analyzed in connection with building and plumbing systems characteristics.Data about building and risk factors were collected through a questionnaire survey.Results out of the 149 samples, 77(51.7%) were positive for l.Pneumophila.Serological typing of the isolates revealed that 54 (70.1%) are l.Pneumophila serogroup 2-15 and 23 (29.9%) are l.Pneumophila serogroup 1.56.8% of all buildings were colonized by l.Pneumophila.Counts were over 1,000 cfu/l in 44%.Contamination was strongly correlated with temperature in the circulation, the age of the premise plumbing and the size of the building.Conclusions the results showed a relevant exposure to l.Pneumophila in the community and the identified risk factors can serve as indicators for risk assessment and relevant actions.

Journal: Journal of water and health (2021)
Publication types: Journal Article
Therapeutic efficacy of lenvatinib as third-line treatment after regorafenib for unresectable hepatocellular carcinoma progression.

Multiple molecular agents have been developed for treating unresectable hepatocellular carcinoma.This study aimed to elucidate the clinical efficacy of sequential treatment with lenvatinib after regorafenib failure.Methods from june 2017 to october 2020, 63 patients with child-pugh a and treated with regorafenib followed by sorafenib were enrolled (median age 71 years, 52 men, barcelona clinic liver cancer b:c = 23:40).They were divided into two groups, those treated with lenvatinib after regorafenib treatment (r-l group, n = 47) and those who did not receive lenvatinib after regorafenib (non-r-l group, n = 16).Prognostic factors were retrospectively analyzed after adjustment with inverse probability weighting.Results serum albumin level at the start of regorafenib and reasons for discontinuation of regorafenib were significantly different between the r-l and non-r-l groups, whereas the albumin-bilirubin score, child-pugh class, and tumor burden were not.Progression-free survival was also not significantly different (median 4.1 vs.3.8 months, p = 0.586).As for overall survival, the r-l group showed better prognosis after introducing regorafenib and after introducing sorafenib, following inverse probability weighting adjustment (mst 19.7 vs.10.3 months, 33.8 vs.15.3 months, p -2.27) at the start of regorafenib (hr 2.074, p = 0.041) and the presence of lenvatinib treatment after regorafenib failure (hr 0.355, p = 0.004) were found to be significant prognostic factors in cox proportional hazards multivariate analysis, after inverse probability weighting adjustment.Conclusion these results show that lenvatinib is a good sequential treatment option after progression under regorafenib therapy in unresectable hepatocellular carcinoma patients with better hepatic reserve function.

Journal: Hepatology research : the official journal of the Japan Society of Hepatology (2021)
Publication types: Journal Article
Comparative Analysis and Phylogenetic Relationships ofCeriopsSpecies (Rhizophoraceae) andAvicennia lanata(Acanthaceae): Insight into the Chloroplast Genome Evolution between Middle and Seaward Zones of Mangrove Forests.

Ceriops and avicennia are true mangroves in the middle and seaward zones of mangrove forests, respectively.The chloroplast genomes of ceriops decandra, ceriops zippeliana, and ceriops tagal were assembled into lengths of 166,650, 166,083 and 164,432 bp, respectively, whereas avicennia lanata was 148,264 bp in length.The gene content and gene order are highly conserved among these species.The chloroplast genome contains 125 genes in a.Lanata and 129 genes in ceriops species.Three duplicate genes (rpl2, rpl23, and trn m-cau) were found in the ir regions of the three ceriops species, resulting in expansion of the ir regions.The rpl32 gene was lost in c.Zippeliana, whereas the inf a gene was present in a.Lanata.Short repeats (<40 bp) and a lower number of ssrs were found in a.Lanata but not in ceriops species.The phylogenetic analysis supports that all ceriops species are clustered in rhizophoraceae and a.Lanata is in acanthaceae.In a search for genes under selective pressures of coastal environments, the rps7 gene was under positive selection compared with non-mangrove species.Finally, two specific primer sets were developed for species identification of the three ceriops species.Thus, this finding provides insightful genetic information for evolutionary relationships and molecular markers in ceriops and avicennia species.

Journal: Biology (2022)
Publication types: Journal Article
One-dimensional Lieb-Oxford bounds.

We investigate and prove lieb-oxford bounds in one dimension by studying convex potentials that approximate the ill-defined coulomb potential.A lieb-oxford inequality establishes a bound of the indirect interaction energy for electrons in terms of the one-body particle density ρψof a wave function ψ.Our results include modified soft coulomb potential and regularized coulomb potential.For these potentials, we establish lieb-oxford-type bounds utilizing logarithmic expressions of the particle density.Furthermore, a previous conjectured form ixc(ψ)≥-c1∫rρψ(x)2dx is discussed for different convex potentials.

Journal: The Journal of chemical physics (2020)
Publication types: Journal Article
Nedd8-Activating Enzyme Is a Druggable Host Dependency Factor of Human and Mouse Cytomegalovirus.

Human cytomegalovirus causes diseases in individuals with insufficient immunity.Cytomegaloviruses exploit the ubiquitin proteasome pathway to manipulate the proteome of infected cells.The proteasome degrades ubiquitinated proteins.The family of cullin ring ubiquitin ligases (crl) regulates the stability of numerous important proteins.If the cullin within the crl is modified with nedd8 ("neddylated"), the crl is enzymatically active, while crls lacking nedd8 modifications are inactive.The nedd8-activating enzyme (nae) is indispensable for neddylation.By binding to nae and inhibiting neddylation, the drug mln4924 (pevonedistat) causes crl inactivation and stabilization of crl target proteins.We showed that mln4924 elicits potent antiviral activity against cytomegaloviruses, suggesting that nae might be a druggable host dependency factor (hdf).However, mln4924 is a nucleoside analog related to amp, and the antiviral activity of mln4924 may have been influenced by off-target effects in addition to nae inhibition.To test if nae is indeed an hdf, we assessed the novel nae inhibitor tas4464 and observed potent antiviral activity against mouse and human cytomegalovirus.Additionally, we raised an mln4924-resistant cell clone and showed that mln4924 as well as tas4464 lose their antiviral activity in these cells.Our results indicate that nae, the neddylation process, and crls are druggable hdfs of cytomegaloviruses.

Journal: Viruses (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Fetal therapies and trials for lysosomal storage diseases: a survey of attitudes of parents and patients.

Lysosomal storage diseases (lsds) are inherited metabolic disorders that may lead to severe multi-organ disease.Current erts are limited by anti-drug antibodies, the blood-brain barrier, and early disease onset and progression before ert is started.We have opened a phase i clinical trial of enzyme replacement therapy (ert) for fetuses with lsds (nct04532047).We evaluated the attitudes of parents and patients with lsds towards fetal clinical trials and therapies.Methods a multidisciplinary team designed a survey which was distributed by five international patient advocacy groups.We collected patients' demographic, diagnostic, and treatment information.Associations between respondent characteristics and attitudes towards fetal therapies/trials were analyzed using multivariate ordinal logistic regression.Results the survey was completed by 181 adults from 19 countries.The majority of respondents were mothers from the united states.The most common diseases were mps1 (26%), mps3 (19%), and infantile-onset pompe (14%).Most patients (88%) were diagnosed after birth, at a median of 21 months.Altogether, 65% of participating patients and children of participants had received ert, 27% a stem cell transplant, and 4% gene therapy.We found that half (49%) of respondents were unlikely to terminate a future affected pregnancy, 55% would enroll in a phase i clinical trial for fetal ert, and 46% would enroll in a fetal gene therapy trial.Respondents who received postnatal ert were significantly more likely enroll in a trial for fetal ert or gene therapy (ert or 4.48, 95% ci 2.13-9.44, p < 0.0001; gene therapy or 3.03, 95% ci 1.43-6.43, p = 0.0038).Respondents who used clinicaltrials.gov as a main source of information were more likely to choose to participate in a fetal trial (ert or 2.43, 95% ci 1.18-5.01, p = 0.016; gene therapy or 2.86, 95% ci 1.27-6.46, p = 0.011).Conclusions familiarity with postnatal ert increased respondents' likelihood of pursuing fetal therapies.Families who use clinicaltrials.gov may be more receptive to innovative fetal treatments.The patient community has a favorable attitude towards fetal therapy; over half of respondents would enroll in a phase i clinical trial to assess the safety and efficacy of fetal ert.

Journal: Orphanet journal of rare diseases (2022)
Publication types: Journal Article;Research Support, N.I.H., Extramural