syedzayyan/paper_mill_benchmark huggingface dataset:
Microbial and genetic-based framework identifies drug targets in inflammatory bowel disease.

Rationale:with increasing incidence and prevalence of inflammatory bowel disease (ibd), it has become one of the major public health threats, and there is an urgent need to develop new therapeutic agents.Although the pathogenesis of ibd is still unclear, previous research has provided evidence for complex interplays between genetic, immune, microbial, and environmental factors.Here, we constructed a gene-microbiota interaction-based framework to discover ibd biomarkers and therapeutics.methods:we identified candidate biomarkers for ibd by analyzing the publicly available transcriptomic and microbiome data from ibd cohorts.Animal models of ibd and diarrhea were established.The inflammation-correlated microbial and genetic variants in gene knockout mice were identified by 16s r rna sequences and pcr array.We performed bioinformatic analysis of microbiome functional prediction and drug repurposing.Our validation experiments with cells and animals confirmed anti-inflammatory properties of a drug candidate.results:we identified the dna-sensing enzyme cyclic gmp-amp synthase (c gas) as a potential biomarker for ibd in both patients and murine models.C gas knockout mice were less susceptible to dss-induced colitis.C gas-associated gut microbiota and host genetic factors relating to ibd pathogenesis were also identified.Using a computational drug repurposing approach, we predicted 43 candidate drugs with high potency to reverse colitis-associated gene expression and validated that brefeldin-a mitigates inflammatory response in colitis mouse model and colon cancer cell lines.conclusions:by integrating computational screening, microbiota interference, gene knockout techniques, andin vitroandin vivovalidation, we built a framework for predicting biomarkers and host-microbe interaction targets and identifying repurposing drugs for ibd, which may be tested further for clinical application.This approach may also be a tool for repurposing drugs for treating other diseases.

Journal: Theranostics (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural;Research Support, Non-U.S. Gov't
Identification of clinical trait-related small RNA biomarkers with weighted gene co-expression network analysis for personalized medicine in endocervical adenocarcinoma.

Endocervical adenocarcinoma (eac) is an aggressive type of endocervical cancer.At present, molecular research on eac mainly focuses on the genome and m rna transcriptome, the investigation of small rnas in eac has not been fully described.Here, we systematically explored small rnas in 14 eac patients with different subtypes using small rna sequencing.Mi rnas and t rna-derived rnas (t drs) accounted for the majority of mapped reads and the total number of mi rnas and t drs maintained a relative balance.To explore the correlations between small rnas expression and eac with different clinical characteristics, we performed the weighted gene co-expression network analysis (wgcna) and screened for hub small rnas.From the key modules, we identified 9 small rnas that were significantly related to clinical characteristics in eac patients.Gene ontology and pathway analyses revealed that these molecules were involved in the pathogenesis of eac.Our work provided new insights into eac pathogenesis and successfully identified several small rnas as candidate biomarkers for diagnosis and prognosis of eac.

Journal: Aging (2021)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Validation of questionnaire-reported chest wall abnormalities with a telephone interview in Swiss childhood cancer survivors.

Chest wall abnormalities are a poorly studied complication after treatment for childhood cancer.Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors.Methods we investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (swiss childhood cancer survivor study) with a questionnaire survey.We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors.Results forty-eight of 2382 (95%ci 2-3%) survivors reported a chest wall abnormality.Risk factors were older age at cancer diagnosis (16-20 years; or 2.5, 95%ci 1.0-6.1), lymphoma (or 3.8, 95%ci 1.2-11.4), and central nervous system tumors (or 9.5, 95%ci 3.0-30.1) as underlying disease, and treatment with thoracic radiotherapy (or 2.0, 95%ci 1.0-4.2), surgery to the chest (or 4.5, 95%ci 1.8-11.5), or chemotherapy (or 2.9, 95%ci 1.0-8.1).The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%).Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors.Conclusion it is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Journal: BMC cancer (2021)
Publication types: Journal Article
Long-Term Antitumor CD8+T Cell Immunity Induced by Endogenously Engineered Extracellular Vesicles.

We developed an innovative method to induce antigen-specific cd8+t cytotoxic lymphocyte (ctl) immunity based on in vivo engineering of extracellular vesicles (evs).This approach employs a dna vector expressing a mutated hiv-1 nef protein (nefmut) deprived of the anti-cellular effects typical of the wild-type isoform, meanwhile showing an unusual efficiency of incorporation into evs.This function persists even when foreign antigens are fused to its c-terminus.In this way, nefmuttraffics large amounts of antigens fused to it into evs spontaneously released by the recipient cells.We previously provided evidence that mice injected with a dna vector expressing the nefmut/hpv16-e7 fusion protein developed an e7-specific ctl immune response as detected 2 weeks after the second immunization.Here, we extended and optimized the anti-hpv16 cd8+t cell immune response induced by the endogenously engineered evs, and evaluated the therapeutic antitumor efficacy over time.We found that the co-injection of dna vectors expressing nefmutfused with e6 and e7 generated a stronger anti-hpv16 immune response compared to that observed in mice injected with the single vectors.When hpv16-e6 and -e7 co-expressing tumor cells were implanted before immunization, all mice survived at day 44, whereas no mice injected with either void or nefmut-expressing vectors survived until day 32 after tumor implantation.A substantial part of immunized mice (7 out of 12) cleared the tumor.When the cured mice were re-challenged with a second tumor cell implantation, none of them developed tumors.Both e6- and e7-specific cd8+t immunities were still detectable at the end of the observation time.We concluded that the immunity elicited by engineered evs, besides counteracting and curing already developed tumors, was strong enough to guarantee the resistance to additional tumor attacks.These results can be of relevance for the therapy of both metastatic and relapsing tumors.

Journal: Cancers (2021)
Publication types: Journal Article
Understanding opportunities and challenges with telemedicine-delivered buprenorphine during the COVID-19 pandemic.

Introduction opioid use disorder (oud) is a debilitating illness that remains a serious public health issue in the united states.Use of telemedicine to deliver medications for the treatment of oud (moud) was limited until the confluence of the covid-19 and opioid addiction epidemics in spring 2020.Starting in spring 2020, the department of veterans health affairs (vha) transitioned from in-person to mostly telemedicine-delivered oud care to reduce covid-19 transmission among veterans and providers.To gain a nuanced understanding of provider perspectives on moud care delivery using telemedicine, we conducted semi-structured interviews with vha providers who were using telehealth to deliver moud care.Methods we conducted semi-structed zoom interviews with va clinicians at nine va medical centers (vamcs) in eight states.Potential study participants were identified as providers who were involved in referrals and provision of buprenorphine treatment for chronic pain and opioid addiction.Audio-recordings of all interviews were transcribed and entered into atlas.Ti qualitative analysis software.The study team analyzed the transcripts for major themes related to tele-prescribing practices for buprenorphine.Results twenty-three va providers participated in the study, representing 32% of all providers invited to participate in the study.The research team identified the following four themes: (1) covid-19 spurred a seismic shift in oud treatment; (2) video calls provided a rare window into veterans' lives; (3) providers experienced numerous challenges to virtual visits; and (4) providers wrestled with paternalism and trust.Conclusions the pandemic accelerated the movement toward harm reduction approaches.Prior to the pandemic, stringent requirements existed for patients receiving moud care.Providers in this study reflected on the need for these requirements (e.g., in-person visits, toxicology screens) and how reducing this monitoring implied more trust in patients' autonomous decisions.Providers' observation that videoconferencing offered them a window into patients' lives may offer some ways to improve rapport, and research should explore how best to incorporate the additional information conveyed in virtual visits.

Journal: Journal of substance abuse treatment (2022)
Publication types: Journal Article
Solvent-Dependent Photophysical Properties of a Semiconducting One-Dimensional Silver Cluster-Assembled Material.

Unraveling the total structure of the atom-precise silver cluster-assembled materials (cams) is extremely significant to elucidating the structure-property correlation, but it is a very challenging task.Herein, a new silver cam is synthesized by a facile synthetic pathway with a unique distorted elongated square-bipyramid-based ag11core geometry.The core is protected by two different kinds of the surface protecting ligands (adamantanethiolate and trifluoroacetate) and connected through a bidentate organic linker.The crystallographic data show that this material embraces a one-dimensional periodic structure that orchestrates by various noncovalent interactions to build a thermally stable supramolecular assembly.Further characterization confirms its n-type semiconducting property with an optical band gap of 1.98 e v.The impact of an adamantanethiol-protected silver core on the optical properties of this type of periodic framework is analyzed by the uv-vis absorbance and emission phenomena.Theoretical calculations predicted that the occupied states are majorly contributed by ag-s.Solvent-dependent photoluminescence studies proved that a polar solvent can significantly perturb the metal thiolate and thiolate-centered frontier molecular orbitals that are involved in the electronic transitions.

Journal: Inorganic chemistry (2021)
Publication types: Journal Article
Content and Evaluation of the Benefits of Effective Exercise for Older Adults With Knee Pain Trial Physiotherapist Training Program.

To explore whether participating in the benefits of effective exercise for knee pain (beep) trial training program increased physiotherapists' self-confidence and changed their intended clinical behavior regarding exercise for knee pain in older adults.Design before/after training program evaluation.Physiotherapists were asked to complete a questionnaire before the beep trial training program, immediately after, and 12 to 18 months later (postintervention delivery in the beep trial).The questionnaire included a case vignette and associated clinical management questions.Questionnaire responses were compared over time and between physiotherapists trained to deliver each intervention within the beep trial.Setting primary care.Participants physiotherapists (n=53) who completed the beep trial training program.Interventions not applicable.Main outcome measures self-confidence in the diagnosis and management of knee pain in older adults; and intended clinical behavior measured by a case vignette and associated clinical management questions.Results fifty-two physiotherapists (98%) returned the pretraining questionnaire, and 44 (85%) and 39 (74%) returned the posttraining and postintervention questionnaires, respectively.Posttraining, self-confidence in managing older adults with knee pain increased, and intended clinical behavior regarding exercise for knee pain in older adults appeared more in line with clinical guidelines.However, not all positive changes were maintained in the longer-term.Conclusions participating in the beep trial training program increased physiotherapists' self-confidence and changed their intended clinical behavior regarding exercise for knee pain, but by 12 to 18 months later, some of these positive changes were lost.This suggests that brief training programs are useful, but additional strategies are likely needed to successfully maintain changes in clinical behavior over time.

Journal: Archives of physical medicine and rehabilitation (2017)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Relationship between Intraoperative Hypotension, Defined by Either Reduction from Baseline or Absolute Thresholds, and Acute Kidney and Myocardial Injury after Noncardiac Surgery: A Retrospective Cohort Analysis.

How best to characterize intraoperative hypotension remains unclear.Thus, the authors assessed the relationship between myocardial and kidney injury and intraoperative absolute (mean arterial pressure [map]) and relative (reduction from preoperative pressure) map thresholds.Methods the authors characterized hypotension by the lowest map below various absolute and relative thresholds for cumulative 1, 3, 5, or 10 min and also time-weighted average below various absolute or relative map thresholds.The authors modeled each relationship using logistic regression.The authors further evaluated whether the relationships between intraoperative hypotension and either myocardial or kidney injury depended on baseline map.Finally, the authors compared the strength of associations between absolute and relative thresholds on myocardial and kidney injury using c statistics.Results map below absolute thresholds of 65 mm hg or relative thresholds of 20% were progressively related to both myocardial and kidney injury.At any given threshold, prolonged exposure was associated with increased odds.There were no clinically important interactions between preoperative blood pressures and the relationship between hypotension and myocardial or kidney injury at intraoperative mean arterial blood pressures less than 65 mm hg.Absolute and relative thresholds had comparable ability to discriminate patients with myocardial or kidney injury from those without.Conclusions the associations based on relative thresholds were no stronger than those based on absolute thresholds.Furthermore, there was no clinically important interaction with preoperative pressure.Anesthetic management can thus be based on intraoperative pressures without regard to preoperative pressure.

Journal: Anesthesiology (2017)
Publication types: Journal Article
Trunk kinematic, kinetic, and neuro-muscular response to foot center of pressure translation along the medio-lateral foot axis during gait.

Footwear devices that shift foot center of pressure (cop), thereby impacting lower-limb biomechanics to produce clinical benefit, have been studied regarding degenerative diseases of knee and hip joints, exhibiting evidence of clinical success.Ability to purposefully affect trunk biomechanics has not been investigated for this type of footwear.Fifteen healthy young male subjects underwent gait and electromyography analysis using a biomechanical device that shifts cop via moveable convex elements attached to the shoe sole.Analyses were performed in three cop configurations for pairwise comparison: (1) neutral (control) (2) laterally deviated, and (3) medially deviated.Sagittal and frontal-plane pelvis and spine kinematics, external oblique activity, and frontal and transverse-plane lumbar moments were affected by medio-lateral cop shift.Transverse-plane trunk kinematics, activity of the lumbar longissimus, latissimus dorsi, rectus abdominus, and quadratus lumborum, and sagittal-plane lumbar moment, were not significantly impacted.Two linear mixed effects models assessed predictive impact of (i) cop location, and (ii) trunk kinematics and neuromuscular activity, on the significant lumbar moment parameters.The cop was a significant predictor of all modeled frontal and transverse-plane lumbar moment parameters, while pelvic and spine rotation, and lumbar longissimus activity were significant predictors of one frontal-plane lumbar moment parameter.Model results suggest that, although trunk biomechanics and muscle activity were altered by cop shift, cop offset influences lumbar kinetics directly, or via lower-limb changes not assessed in this study, but not by means of alteration of trunk kinematics or muscle activity.Further study may reveal implications in treatment of low back pain.

Journal: Journal of biomechanics (2019)
Publication types: Journal Article
A case of a mobile choroid plexus cyst presenting with different types of obstructive hydrocephalus.

Although it is well known that most choroid plexus cysts (cpcs) are asymptomatic, previous studies have reported that they can infrequently cause progressive hydrocephalus along with their increasing sizes.Among those cases, some patients needed cyst fenestration or cerebrospinal fluid (csf) diversion to recover neurological deterioration.Meanwhile, some cpcs revealed spontaneous resolution, and in rare cases, they developed re-accumulation.Some reports have described series of radiological findings about their changes in location.Case description we present a 47-year-old male with cpc manifesting obstructive hydrocephalus.Radiological findings of the lateral and the third ventricles changed along with their different obstructive points, leading to their own symptoms.Because the patient's symptoms were not resolved completely, he underwent endoscopic fenestration for the cyst at the third ventricle.We could perform near-total resection, resulting in recovery of normal csf flow.Postoperatively, the size of the ventricles decreased, with histological confirmation of a cpc.His symptoms resolved clearly without any complications.Conclusions it seems quite unusual that shift of the cpc location in the ventricle systems could induce not only different types of hydrocephalus but also their own symptoms.We need to consider that the location of cpcs might change when patients present with fluctuating symptoms over time.

Journal: Surgical neurology international (2018)
Publication types: Case Reports;Journal Article
Spatial-temporal pattern of land use conflict in China and its multilevel driving mechanisms.

Land use conflict describes the incoordination of land use structure when meeting the diverse human demands under the deterioration of natural environment, which is a sensitive indicator of human-environmental interaction.The increased demand for different land use types due to rapid population growth and urbanization in china places tremendous pressure on limited land resources, which raises great concerns about land use conflict.To solve them, nation-scale assessment is essential, but such kind of research is still lacking due to the high data requirements.Here we drew on the conceptual framework of ecological risk assessment and the theories in landscape ecology, and developed a methodology to derive the spatio-temporal patterns of land use conflict in china from 2001 to 2017.We then used multilevel regression model to identify the driving factors of land use conflict at different levels.The results showed that the areas with strong land use conflict had a higher frequency of land use change, indicating that our model based on the framework of ecological risk assessment could effectively measure land use conflict.Land use conflict showed significant differences between two sides of the hu huanyong line, an important division line of population density and socio-economic background.The main types of land use conflict in china included the strong competition between the use of cultivated land and grassland, the rapid expansion of construction land and the high risk of desertification.Among the driving forces, population density had a positive impact on land use conflict at the upper level, and altitude had a negative impact at the bottom level.Our research provides essential information to solve land use conflict through scientific land use planning and management and further to achieve the sustainable use of land resources.

Journal: The Science of the total environment (2021)
Publication types: Journal Article
Mechanisms Involved in the Stimulatory and Inhibitory Effects of 5-Hydroxytryptamine on Vagal Mechanosensitive Afferents in Rat Lung.

Mechanosensitive vagal afferents in the lung, rapidly and slowly adapting receptors (rars and sars, respectively), play an important role in eliciting the reflexes that regulate the normal airway function.A profound bronchoconstrictive effect of 5-hydroxytryptamine (5-ht) has been extensively reported in various animal species, but its influence on the sar and rar activity is not known.This study investigated the effect of 5-ht on these receptors, and the possible mechanisms involved.Single-fiber activities of these afferents were measured in anesthetized, open-chest, and mechanically ventilated rats.Our results showed that intravenous injection of 5-ht evoked a consistent and pronounced stimulation of phasic rars.In contrast, 5-ht generated an inconsistent and paradoxical action on sars: no effect in 29% (5 of 17) of the sars; stimulation in 35% (6 of 17); and inhibition in the remainder.These responses of both rars and sars to 5-ht were reproducible and dose-dependent.After the injection of a high dose of 5-ht (16 μg/kg), the receptor responses slowly reached a peak (after ∼8 s) and returned toward the baseline in ∼20 s, accompanied by a consistent increase in total pulmonary resistance and a decrease in dynamic lung compliance in a temporal pattern very similar to the increased receptor activity.When these changes in lung mechanics induced by 5-ht were prevented by pretreatment with salbutamol, a β2adrenergic receptor agonist, the delayed responses of both rars and sars to 5-ht were also abolished, except that the immediate stimulatory effect on a subset of rars, the silent rars, was not affected.In conclusion, 5-ht generated a delayed stimulatory effect on rars and a paradoxical effect on sars, which resulted primarily from the 5-ht-induced changes in mechanical properties of the lung.

Journal: Frontiers in physiology (2022)
Publication types: Journal Article