syedzayyan/paper_mill_benchmark huggingface dataset:
Performance of Janus kinase inhibitors in psoriatic arthritis with axial involvement in indirect comparison with ankylosing spondylitis: a retrospective analysis from pooled data.

And objective as the well-acknowledged autoimmune disease, janus kinase (jak) is thought to play important roles in the progression of tissue injury in spondyloarthropathy.From a current perspective, jak inhibitors could be applied to both psoriatic arthritis (ps a) and ankylosing spondylitis (as).Nonetheless, it is reasonable to doubt whether ps a and as differentially respond to jak inhibitors.Methods different databases were searched for full-text publication based on inclusion and exclusion criteria.For data-pooling, a fixed-effect model was applied if heterogeneity was not detected.All results of the analysis were illustrated as forest plots.Publication bias was assessed using begg's adjusted rank correlation test.The standard mean difference (smd) was calculated in continuous variables.The pooled odds ratio was calculated in categorical variables.Results nine clinical studies were finally included with a 3-month follow-up.The efficacy and safety of jak inhibitors were comprehensively investigated.Jak inhibitors were proved to be effectively improving disease condition within 3 months (12 weeks) in both ps a and as.Besides, psoriasis-related dermal lesions could also be improved by jak inhibitors.Dose-dependent effects suggested that higher dose tofacitinib could bring not only a higher level of treatment response but also more safety concerns.Conclusion jak inhibitors were proved to be effective in improving arthritis symptoms and enhancing the quality of life in both ps a and as patients.Compared with as, jak inhibitors seemed to perform better in ps a treatment.However, the frequency of adverse events ps a and as in comparison with the placebo group showed no difference.Higher dose of tofacitinib could attain better treatment response without increasing adverse events in short-term follow-up.Key points • jak inhibitors were proved to be effective in improving arthritis symptoms and enhancing the quality of life in both ps a and as patients.• compared with as, jak inhibitors seemed to perform better in ps a treatment.• the frequency of adverse events ps a and as in comparison with the placebo group showed no difference.• higher dose of tofacitinib could attain better treatment response without increasing adverse events in short-term follow-up.

Journal: Clinical rheumatology (2021)
Publication types: Journal Article
Hierarchical Self-Assembly of Adhesive and Conductive Gels with Anion-Coordinated Triple Helicate Junctions.

The fabrication of anion-coordinated assemblies into functional soft materials remains a major challenge.To this end, four c2-symmetric anion-binding ligands equipped with ortho-phenylene-bridged bis(urea) and amine or amide ends were designed, which generated a2l3triple helical architectures upon self-assembly with phosphate ions.Hierarchical intermolecular hydrogen bonds among the terminal amine/amide groups and urea moieties resulted in the formation of functional gels.The obtained gels were further applied for conductive adhesion between different surfaces, displaying excellent flexibility and selective wettability.The viscoelastic gels constructed from anion-coordinated assemblies described in this work represent the first example of a new class of anion-coordination-driven smart materials.

Journal: Angewandte Chemie (International ed. in English) (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Novel pyrazolo[3,4-d]pyrimidines as dual Src/Bcr-Abl kinase inhibitors: Synthesis and biological evaluation for chronic myeloid leukemia treatment.

The bcr-abl tyrosine kinase (tk) is the molecular hallmark of chronic myeloid leukemia (cml).Src is another tk kinase whose involvement in cml was widely demonstrated.Small molecules active as dual src/bcr-abl inhibitors emerged as effective targeted therapies for cml and a few compounds are currently in clinical use.In this study, we applied a target-oriented approach to identify a family of pyrazolo[3,4-d]pyrimidines as dual src/bcr-abl inhibitors as anti-leukemia agents.Considering the high homology between src and bcr-abl, in-house src inhibitors 8a-l and new analogue compounds 9a-n were screened as dual src/bcr-abl inhibitors.The antiproliferative activity on k562 cml cells and the adme profile were determined for the most promising compounds.Molecular modeling studies elucidated the binding mode of the inhibitors into the bcr-abl (wt) catalytic pocket.Compounds 8j and 8k showed nanomolar activities in enzymatic and cellular assays, together with favorable adme properties, emerging as promising candidates for cml therapy.Finally, derivatives 9j and 9k, emerging as valuable inhibitors of the most aggressive bcr-abl mutation, t315i, constitute a good starting point in the search for compounds able to treat drug-resistant forms of cml.Overall, this study allowed us to identify more potent compounds than those previously reported by the group, marking a step forward in searching for new antileukemic agents.

Journal: Bioorganic chemistry (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Outcomes of single- and two-stage revision total knee arthroplasty for chronic periprosthetic joint infection : long-term outcomes of changing clinical practice in a specialist centre.

S single-stage revision total knee arthroplasty (r tka) is gaining popularity in treating chronic periprosthetic joint infections (pjis).We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage r tka for chronic pji.Methods a retrospective comparative cohort study of all r tkas for chronic pji between 1 april 2003 and 31 december 2018 was undertaken using prospective databases.Patients with acute infections were excluded; r tkas were classified as single-stage, stage 1, or stage 2 of two-stage revision.The primary outcome measure was failure to eradicate or recurrent infection.Variables evaluated for failure by regression analysis included age, bmi, american society of anesthesiologists grade, infecting organisms, and the presence of a sinus.Patient survivorship was also compared between the groups.Results a total of 292 consecutive first-time r tkas for chronic pji were included: 82 single-stage (28.1%); and 210 two-stage (71.9%) revisions.The mean age was 71 years (27 to 90), with 165 females (57.4%), and a mean bmi of 30.9 kg/m2(20 to 53).Significantly more patients with a known infecting organism were in the single-stage group (93.9% vs 80.47%; p = 0.004).The infecting organism was identified preoperatively in 246 cases (84.2%).At a mean follow-up of 6.3 years (2.0 to 17.6), the failure rate was 6.1% in the single-stage, and 12% in the two-stage groups.All failures occurred within four years of treatment.The presence of a sinus was an independent risk factor for failure (odds ratio (or) 4.97; 95% confidence interval (ci) 1.593 to 15.505; p = 0.006), as well as age > 80 years (or 5.962; 95% ci 1.156 to 30.73; p = 0.033).The ten-year patient survivorship rate was 72% in the single-stage group compared with 70.5% in the two-stage group.This difference was not significant (p = 0.517).Conclusion single-stage r tka is an effective strategy with a high success rate comparable to two-stage approach in appropriately selected patients.Cite this article:bone joint j2021;103-b(8):1373-1379.

Journal: The bone & joint journal (2021)
Publication types: Comparative Study;Journal Article
Longitudinal studies examining the impact of prenatal and subsequent episodes of maternal depression on offspring antisocial behaviour.

Maternal depression is associated with adverse child outcomes including antisocial behaviour (asb).Prospective longitudinal studies have focused on the timing and cumulative exposure to maternal depression to further delineate the association and mechanisms of effect.The objective of this systematic review was to synthesise and evaluate the findings of longitudinal studies of maternal depression and offspring antisocial behaviour.Three databases were searched (psychinfo, web of science, and medline).Twenty of 5936 studies met inclusion criteria.Study quality was assessed using the critical appraisal skills programme criteria [critical appraisal skills programme (2017) casp (cohort observation checklist).].Results of individual studies were highly varied, using diverse analytical approaches and not all studies explored the independent effects of different episodes.Only three studies examined hypothesised mechanisms.Prenatal, postnatal, and later episodes of depression were all predictive of antisocial outcomes.One particular time period of depression exposure did not emerge as more predictive of offspring asb than another.However, measures of maternal depression after the perinatal period were limited and typically included a one-off assessment of mothers' depressive symptoms that was concurrent to the assessment of offspring asb.When cumulative exposure to maternal depression and specific timing effects were measured within the same study it was cumulative exposure that conferred the greatest risk for offspring asb-particularly when this exposure began during the perinatal period.Findings are discussed in terms of limitations in the literature and highlight the need for future research to examine the biological and environmental mechanisms that underpin associations between maternal depression and offspring antisocial behaviour during different stages of development.

Journal: European child & adolescent psychiatry (2021)
Publication types: Journal Article;Review
Could environmental effect overcome genetic? A chemometric study on wheat volatiles fingerprint.

A deeper knowledge of the causes of volatile organic compounds (vocs) variance in wheat is crucial for quality improvement and control of its derivatives.The vocs profile of common and durum wheat kernels grown in different fields sited at different altitudes over two years was analysed and 149 compounds were identified by gas chromatography-mass spectrometry.Principal component analysis evidenced that the year of cultivation was the highest source of vocs variance.The effects of wheat origin, as described by the cultivation site, its elevation, and species were further investigated by pls-da, that permitted to correctly classify wheat of different origin on the basis of its vocs profile.The importance of the different effects was investigated by multidimensional test and resulted: year of cultivation > field of cultivation > species > altitude.Findings suggest that environmental conditions are more important than species in the determination of the vocs variance of wheat.

Journal: Food chemistry (2022)
Publication types: Journal Article
Computational Approaches Towards Kinases as Attractive Targets for Anticancer Drug Discovery and Development.

One of the major goals of computational chemists is to determine and develop the pathways for anticancer drug discovery and development.In recent past, high performance computing systems elicited the desired results with little or no side effects.The aim of the current review is to evaluate the role of computational chemistry in ascertaining kinases as attractive targets for anticancer drug discovery and development.Methods research related to computational studies in the field of anticancer drug development is reviewed.Extensive literature on achievements of theorists in this regard has been compiled and presented with special emphasis on kinases being the attractive anticancer drug targets.Results different approaches to facilitate anticancer drug discovery include determination of actual targets, multi-targeted drug discovery, ligand-protein inverse docking, virtual screening of drug like compounds, formation of di-nuclear analogs of drugs, drug specific nano-carrier design, kinetic and trapping studies in drug design, multi-target qsar (quantitative structure activity relationship) model, targeted co-delivery of anticancer drug and si rna, formation of stable inclusion complex, determination of mechanism of drug resistance, and designing drug like libraries for the prediction of drug-like compounds.Protein kinases have gained enough popularity as attractive targets for anticancer drugs.These kinases are responsible for uncontrolled and deregulated differentiation, proliferation, and cell signaling of the malignant cells which result in cancer.Conclusion interest in developing drugs through computational methods is a growing trend, which saves equally the cost and time.Kinases are the most popular targets among the other for anticancer drugs which demand attention.3d-qsar modelling, molecular docking, and other computational approaches have not only identified the target-inhibitor binding interactions for better anticancer drug discovery but are also designing and predicting new inhibitors, which serve as lead for the synthetic preparation of drugs.In light of computational studies made so far in this field, the current review highlights the importance of kinases as attractive targets for anticancer drug discovery and development.

Journal: Anti-cancer agents in medicinal chemistry (2019)
Publication types: Journal Article;Review
Disrupted presynaptic nectin1-based neuronal adhesion in the entorhinal-hippocampal circuit contributes to early-life stress-induced memory deficits.

The cell adhesion molecule nectin3 and its presynaptic partner nectin1 have been linked to early-life stress-related cognitive disorders, but how the nectin1-nectin3 system contributes to stress-induced neuronal, circuit, and cognitive abnormalities remains to be studied.Here we show that in neonatally stressed male mice, temporal order and spatial working memories, which require the medial entorhinal cortex (mec)-ca1 pathway, as well as the structural integrity of ca1 pyramidal neurons were markedly impaired in adulthood.These cognitive and structural abnormalities in stressed mice were associated with decreased nectin levels in entorhinal and hippocampal subregions, especially reduced nectin1 level in the mec and nectin3 level in the ca1.Postnatal suppression of nectin1 but not nectin3 level in the mec impaired spatial memory, whereas conditional inactivation of nectin1 from mec excitatory neurons reproduced the adverse effects of early-life stress on mec-dependent memories and neuronal plasticity in ca1.Our data suggest that early-life stress disrupts presynaptic nectin1-mediated interneuronal adhesion in the mec-ca1 pathway, which may in turn contribute to stress-induced synaptic and cognitive deficits.

Journal: Translational psychiatry (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Health Services Use Among Jailed Women with Alcohol Use Disorders.

Correctional facilities now house unprecedented numbers of women with complex treatment needs.This investigation applied the behavioral model for vulnerable populations to study 168 jailed women with alcohol use disorders.It described the sample's predisposing (age, race, victimization), enabling (health insurance), and need (self-reported medical, substance use, and mental health problems) factors and examined associations of these factors with pre-incarceration services utilization.Most participants had clinically significant levels of depression and ptsd symptoms, most took psychiatric medications, and most had been victimized.Participants reported considerable health services utilization.Younger, black, and uninsured women utilized fewer medical and mental health services.Drug use was associated with less use of medical services, but more use of alcohol and drug services.High rates of health services use support the need for integrated, ongoing care for substance-using women before, during, and after incarceration.

Journal: The journal of behavioral health services & research (2019)
Publication types: Journal Article;Randomized Controlled Trial;Research Support, N.I.H., Extramural;Research Support, U.S. Gov't, Non-P.H.S.
A Longitudinal Analysis of Disability-Related Interpersonal Violence and Some Implications for Violence Prevention Work.

This article explores the extent to which disabled individuals experience interpersonal violence due to victimization.Data on people injured by violence were collated directly from the accident and emergency units in hospitals.High frequency daily data were obtained from computerized records of 26 major accident and emergency departments in london for each day throughout the year of 2016.The final sample consisted of 408,000 observations.A fundamental distinction of our research lies in applying the generalized method of moments system panel estimator to our sample.This makes our empirical estimates robust to endogeneity and joint determination unlike previous empirical research in this area.Data analysis provides strong evidence confirming the victimization of people with disabilities and the necessity to focus on disability equality in violence prevention work.

Journal: Journal of interpersonal violence (2021)
Publication types: Journal Article
A Time-Course-Based Estimation of the Human Medial Olivocochlear Reflex Function Using Clicks.

The auditory efferent system, especially the medial olivocochlear reflex (mocr), is implicated in both typical auditory processing and in auditory disorders in animal models.Despite the significant strides in both basic and translational research on the mocr, its clinical applicability remains under-utilized in humans due to the lack of a recommended clinical method.Conventional tests employ broadband noise in one ear while monitoring change in otoacoustic emissions (oaes) in the other ear to index efferent activity.These methods, (1) can only assay the contralateral mocr pathway and (2) are unable to extract the kinetics of the reflexes.We have developed a method that re-purposes the same oae-evoking click-train to also concurrently elicit bilateral mocr activity.Data from click-train presentations at 80 d b pe spl at 62.5 hz in 13 young normal-hearing adults demonstrate the feasibility of our method.Mean mocr magnitude (1.7 d b) and activation time-constant (0.2 s) are consistent with prior mocr reports.The data also suggest several advantages of this method including, (1) the ability to monitor memr, (2) obtain both magnitude and kinetics (time constants) of the mocr, (3) visual and statistical confirmation of mocr activation.

Journal: Frontiers in neuroscience (2021)
Publication types: Journal Article
The Impact of the COVID-19 Lockdown on the Cognitive Functions in Persons with Intellectual and Developmental Disabilities.

The main objective of the research was to compare the cognitive functioning of a sample of persons with idd (intellectual and developmental disabilities) before the pandemic (2019) and after the pandemic (2020 and 2021), and to analyse the impact according to age and level of idd impairment.The participants were 92 persons with idd, of whom 43 were female (46.7%).The mean age in 2019 was 47.07 years (sd = 6.78).All the participants were living with family members.The camcog-ds test from camdex was used to assess the cognitive functions.The results indicate a worsening in cognitive functions (attention-concentration, abstract thought, language, and praxis) after lockdown, in both the total group of participants and the mild-moderate impairment group, and in both age groups.In the severely affected group, we found an improvement in the cognitive functions assessed after lockdown.These results are similar to those found in people with dementia and in the general ageing population.Results were discussed in relation to the consequences of isolation in people with idd, as well as providing guidelines for future pandemic situations.

Journal: International journal of environmental research and public health (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Editors' roundup: October 2022.

This commentary constitutes the october edition of the 'editors' roundup'-a multi-author omnibus of personal recommendations to interesting biophysics-related articles contributed by members of the editorial boards of leading international biophysics journals.The present commentary contains contributions from progress in biochemistry and biophysics (an official journal of the biophysical society of china), european biophysics journal (the official journal of the european biophysical societies association), biophysical reviews (the official iupab journal), and biophysics (an official journal of the russian academy of sciences).This edition of the editors' roundup also contains a new section from an editor at large who has provided selections from a number of journals on a single thematic topic.

Journal: Biophysical reviews (2022)
Publication types: Journal Article
Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation.

Dot1 (disruptor of telomeric silencing-1), the histone h3 lysine 79 (h3k79) methyltransferase, is conserved throughout evolution, and its deregulation is found in human leukemias.Here, we provide evidence that acetylation of histone h4 allosterically stimulates yeast dot1 in a manner distinct from but coordinating with histone h2b ubiquitination (h2bub).We further demonstrate that this stimulatory effect is specific to acetylation of lysine 16 (h4k16ac), a modification central to chromatin structure.We provide a mechanism of this histone cross-talk and show that h4k16ac and h2bub play crucial roles in h3k79 di- and trimethylation in vitro and in vivo.These data reveal mechanisms that control h3k79 methylation and demonstrate how h4k16ac, h3k79me, and h2bub function together to regulate gene transcription and gene silencing to ensure optimal maintenance and propagation of an epigenetic state.

Journal: Science (New York, N.Y.) (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural
The Optofluidic Light Cage - On-Chip Integrated Spectroscopy Using an Antiresonance Hollow Core Waveguide.

Emerging applications in spectroscopy-related bioanalytics demand for integrated devices with small geometric footprints and fast response times.While hollow core waveguides principally provide such conditions, currently used approaches include limitations such as long diffusion times, limited light-matter interaction, substantial implementation efforts, and difficult waveguide interfacing.Here, we introduce the concept of the optofluidic light cage that allows for fast and reliable integrated spectroscopy using a novel on-chip hollow core waveguide platform.The structure, implemented by 3d nanoprinting, consists of millimeter-long high-aspect-ratio strands surrounding a hollow core and includes the unique feature of open space between the strands, allowing analytes to sidewise enter the core region.Reliable, robust, and long-term stable light transmission via antiresonance guidance was observed while the light cages were immersed in an aqueous environment.The performance of the light cage related to absorption spectroscopy, refractive index sensitivity, and dye diffusion was experimentally determined, matching simulations and thus demonstrating the relevance of this approach with respect to chemistry and bioanalytics.The presented work features the optofluidic light cage as a novel on-chip sensing platform with unique properties, opening new avenues for highly integrated sensing devices with real-time responses.Application of this concept is not only limited to absorption spectroscopy but also includes raman, photoluminescence, or fluorescence spectroscopy.Furthermore, more sophisticated applications are also conceivable in, e.g., nanoparticle tracking analysis or ultrafast nonlinear frequency conversion.

Journal: Analytical chemistry (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't