syedzayyan/paper_mill_benchmark huggingface dataset:
Cigar Use Progression Among New Cigar Initiators: A Two-Part Growth Curve Analysis Among a Youth and Young Adult Cohort.

Introduction youth and young adults (yyas) are at high risk of cigar use.This study's objective was to examine progression and sociodemographic differences in current cigar use and frequency among new cigar initiators.Aims and methods we conducted a two-part latent growth model among a nationally representative cohort of cigar initiators (aged 15-25) to examine 24-month trajectories of current cigar use and frequency (n = 1483).The cohort was recruited via address-based sampling with online data collection from 2014 to 2019 and surveyed approximately every 6 months.Results the unconditional odds of current cigar use (ie, past 30-day use) within 6 months of initiation was 0.72 (95% confidence interval: 0.63, 0.82), corresponding to a probability of 42%.The odds of current use among recent cigar initiates declined 6 months after initiation and was followed by a stabilization in use over time.Among continued users, frequency (# days used in past 30 days) increased linearly over time but remained low (3.47 days/months at 24 months).Younger individuals, non-hispanic african americans, those with lower subjective financial status, and current users of cigarettes, other tobacco products and/or marijuana were at highest risk within 6 months of initiation.Males, younger users, and current cigarette smokers had the highest risk for cigar progression over time.Conclusions this study is the first to examine longitudinal cigar use patterns among yya cigar initiators.Findings emphasize the need for research across the cigar use spectrum and the importance of interventions targeted by age, stage of use, cigarette, other tobacco, and marijuana use and key sociodemographics to interrupt use pathways.Implications this study is the first to examine progression of cigar use among yyas who have newly initiated cigars.Results show a high probability of current cigar use within 6 months of initiation followed by a rapid decline and stabilization over time.Frequency increases among those who continue using cigars.Males, younger users, and current cigarette smokers had the highest risk for cigar progression over time.Findings emphasize the need for targeting interventions by age, stage of use, cigarette, other tobacco, and marijuana use and key sociodemographics to interrupt use pathways.

Journal: Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Bifidobacterium longumCECT 7894 Improves the Efficacy of Infliximab for DSS-Induced ColitisviaRegulating the Gut Microbiota and Bile Acid Metabolism.

Recent evidence suggests that the changes in gut microbiota and its metabolites could predict the clinical response of anti-tumor necrosis factor (tnf) agents, such as infliximab (ifx).However, whether manipulation of the gut microbiota can enhance the efficacy of anti-tnf agents remains unclear.Here, we aim to evaluate the effect of a probiotic strain,bifidobacterium longum(b.Longum) cect 7894, on ifx efficacy for dextran sulfate sodium (dss)-induced colitis in mice and attempt to explore the potential involved mechanisms.methods:c57bl/6 mice were treated with phosphate-buffered saline (pbs) or b.Longum cect 7894 (5 × 108cfu/day) once daily by gavage for 5 days and subsequently induced acute colitis by 3% (w/v) dss in drinking water.The efficacies of ifx combined with or without b.Longum cect 7894 were assessed by weight loss, fecal consistency, colon length, and histopathological changes.Immunohistochemistry (ihc) was used to examine the expression of tight junction proteins (tjps) in colonic tissues.The microbiota composition was characterized through 16 s r rna gene sequencing.Fecal bile acids (bas) levels were analyzed by targeted metabolomics.results:b.Longum cect 7894 improved the efficacy of ifx for dss-induced colitis as evidenced by decreased weight loss, disease activity index (dai) scores, colon length shortening, histological damage, increased zo-1, and occludin expressions as compared with mice that received ifx only.b.Longum cect 7894 modified the composition and structure of the gut microbiota community in dss-induced colitis mice.b.Longum cect 7894 increased the relative abundances of genera bifidobacterium,blautia,butyricicoccus,clostridium,coprococcus,gemmiger, and parabacterioides, and reduced the relative abundances of bacteria genera enterococcusand pseudomonas.Furthermore,b.Longum cect 7894 changed the bas metabolism by increasing the abundance of secondary bas, such asa-mca,ß-mca, lca, cdca, udca, hca, iso lca, isoallo lca.The covariance analysis revealed the upregulated secondary bas were positively associated with the increased abundance of bacteria that contained bile salt hydrolases (bsh) and 7α-dehydroxylases genes.conclusion:b.Longum cect 7894 improved the efficacy of ifx for dss-induced colitisviaregulating the gut microbiota composition and bile acid metabolism.Probiotics supplementation may provide a possibility to improve the clinical response of anti-tnf agents in ibd management.

Journal: Frontiers in pharmacology (2022)
Publication types: Journal Article
Circular RNA circ-PLCD1 functions as a tumor suppressor in non-small cell lung cancer by inactivation of PI3K/AKT signaling pathway.

Circular rnas (circ rnas) are emerging as crucial regulators in tumorigenesis and aggressive progression.However, their biological roles in non-small cell lung cancer (nsclc) remain largely unknown.Here, by performing circ rna high throughput sequencing in 4 paired nsclc and normal tissues, we found a nsclc-associated circ rna, circ-plcd1, which was evidently downregulated in nsclc tissues and cell lines.Circ-plcd1 was transcriptionally activated by tumor-inhibiting protein p53, and exogenous expression of circ-plcd1 inhibited nsclc cell proliferation, invasion and induced apoptosis.Mechanistically, circ-plcd1 acted as a competitive endogenous rna (ce rna) to sponge mi r-375 and mi r-1179 and elevate pten, a well-known inhibitor of oncogenic pi3k/akt signaling, thereby repressing nsclc tumorigenesis.Importantly, we also identified this ce rna regulatory axis of circ-plcd1/mi r-375/mi r-1179/pten in vivo by establishing a xenograft tumor model.Clinically, nsclc patients with low circ-plcd1 expression had larger tumor size, later clinical stage and shorter survival time than those with high circ-plcd1 expression.Altogether, our findings reveal the important tumor suppressive role of circ-plcd1 in nsclc, reactivation of this circ rna may be considered as a novel therapeutic avenue for patient with nsclc.

Journal: Human cell (2022)
Publication types: Journal Article
Euler common spatial patterns for EEG classification.

The technique of common spatial patterns (csp) is a widely used method in the field of feature extraction of electroencephalogram (eeg) signals.Motivated by the fact that a cosine distance can enlarge the distance between samples of different classes, we propose the euler csp (e-csp) for the feature extraction of eeg signals, and it is then used for eeg classification.The e-csp is essentially the conventional csp with the euler representation.It includes the following two stages: each sample value is first mapped into a complex space by using the euler representation, and then the conventional csp is performed in the euler space.Thus, the e-csp is equivalent to applying the euler representation as a kernel function to the input of the csp.It is computationally as straightforward as the csp.However, it extracts more discriminative features from the eeg signals.Extensive experimental results illustrate the discrimination ability of the e-csp.

Journal: Medical & biological engineering & computing (2022)
Publication types: Journal Article
The Management of Substance Use Disorders: Synopsis of the 2021 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

Description in august 2021, leadership within the u.s.Department of veterans affairs (va) and u.s.Department of defense (do d) approved a joint clinical practice guideline (cpg) for the management of substance use disorders (suds).This synopsis summarizes key recommendations.Methods in march 2020, the va/do d evidence-based practice work group assembled a team to update the 2015 va/do d clinical practice guideline for the management of substance use disorders that included clinical stakeholders and conformed to the national academy of medicine's tenets for trustworthy cpgs.The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 35 recommendations for care using the grade (grading of recommendations assessment, development and evaluation) system.This synopsis presents the recommendations that were believed to be the most clinically impactful.Recommendations the scope of the cpg is broad; however, this synopsis focuses on key recommendations for the management of alcohol use disorder, use of buprenorphine in opioid use disorder, contingency management, and use of technology and telehealth to manage patients remotely.

Journal: Annals of internal medicine (2022)
Publication types: Journal Article;Research Support, U.S. Gov't, Non-P.H.S.
Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice.

Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation.Objectives this study aimed to screen and identify placentation-disrupting chemicals in commonly used organophosphate flame retardants (opfrs) and, if identified, to investigate potential adverse effects on placentation in relation to adverse pregnancy outcomes and metabolic disorder in offspring in mice.Methods we devised a high-throughput immunofluorescence screening assay based on human trophoblast organoids and used it to screen opfrs that inhibit the proliferation of organoids.One identified chemical was assessed for its effects on placentation by evaluating villous cytotrophoblasts, syncytiotrophoblasts, and extravillous trophoblasts using immunofluorescence and a mitochondrial stress test after 2 d of exposure.A 10-d exposure study was further performed to observe the dynamic effect of the opfr on the structure of the organoids.Rna-sequencing and western blotting experiments were performed to explore the associated pathways, and a potential binding protein was identified by immunoprecipitation andin vitrokinase activity assays.Animal studies were performed to determine whether the findings in organoids could be replicated in mice and to observe adverse pregnancy outcomes.Results the proliferation of organoids exposed to three aryl-opfrs was significantly lower than the proliferation of control organoids.Further analysis demonstrated that one such chemical, 2-ethylhexyl-diphenyl phosphate (ehdpp), disrupted placentation in organoids.Mechanistically, ehdpp interfered with insulin-like growth factor 1 receptor (igf1r) to inhibit aerobic respiration.Mice exposed to ehdpp at a physiological human concentrations exhibited immature and mature placental disorders, which correlated with fetal growth restriction, implantation failure, stillbirth, and impaired glucose tolerance.Conclusions the human trophoblast organoid model showed that the commonly used opfrs disrupted placentation via igf1r, indicating that its use may contribute to adverse pregnancy outcomes and metabolic disorders in offspring.

Journal: Environmental health perspectives (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
New methodology of TMB assessment from tissue and liquid biopsy in NSCLC.

Immunotherapy has dramatically influenced and changed therapeutical approach in non-small cell lung cancer (nsclc) in recent five years.Even though we can reach long-term response to this treatment in approximately 20% of patients with nsclc, we are still not able to identify this cohort of patients based on predictive biomarkers.In our study we have focused on tumor mutation burden (tmb), one of the potential biomarkers which could predict effectiveness of check-point inhibitors, but has several limitations, especially in multiple approaches to tmb quantification and ununiform threshold.We determined the value of tmb in tumor tissue (t tmb) and blood (b tmb) in 20 patients with early stage nsclc using original custom gene panel lmb_tmb1.We evaluated various possibilities of tmb calculation and concluded that tmb should be counted from both somatic non-synonymous and synonymous mutations.Considering various factors, we established cut-offs of t tmb in/excluding hla genes as ≥22 mut/mb and 12 mut/mb respectively, and cut-offs of b tmb were defined as ≥21 mut/mb and ≥5 mut/mb, respectively.We also observed trend in correlation of somatic mutations in hla genes with overall survival of patients.

Journal: PloS one (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Raloxifene is a Female-specific Proteostasis Therapeutic in the Spinal Cord.

Several neurodegenerative disorders are characterized by proteasome dysfunctions leading to protein aggregations and pathogenesis.Since we showed that estrogen receptor alpha (erα) activates the proteasome, drugs able to stimulate erα in the central nervous system (cns) could hold potential for therapeutic intervention.However, the transcriptional effects of selective estrogen receptor modulators (serms), such as tamoxifen and raloxifene, can be tissue specific.A direct comparison of the effects of different serms on gene transcription in the cns has never been performed.Here, we report an rna-seq analysis of the spinal cord treated with estrogen, tamoxifen, or raloxifene.We find stark serm and sex-specific differences in gene expression profiles in the spinal cord.Notably, raloxifene, but not estrogen or tamoxifen, modulates numerous deubiquitinating enzymes, proteasome subunits and assembly factors, and these effects translate into decreased protein aggregates.In the sod1-g93a mouse model of amyotrophic lateral sclerosis, we found that even a low dose of raloxifene causes a significant decrease in mutant sod1 aggregates in the spinal cord, accompanied by a delay in the decline of muscle strength in females, but not in males.These results strongly indicate serm-selective as well as sex-specific effects, and emphasize the importance of sex as a biological variable to be considered for the careful selection of specific serm for use in clinical trials for neurodegenerative diseases.

Journal: Endocrinology (2021)
Publication types: Journal Article;Research Support, N.I.H., Extramural
A new access to diazaphospholesviacycloaddition-cycloreversion reactions on triazaphospholes.

A novel bis-cf3-substituted diazaphosphole was synthesized selectively from hexafluoro-2-butyne and a 3h-1,2,3,4-triazaphosphole derivative.The [4+2] cycloaddition and subsequent cycloreversion reaction under elimination of pivaloyl nitrile affords the product in high yield.The heterocycle coordinatesviathe phosphorus atom to a w(co)5-fragment and shows stronger π-accepting properties than the triazaphosphole.

Journal: Chemical communications (Cambridge, England) (2022)
Publication types: Journal Article
Substance Use and Violent Victimization: Evidence from a Cohort of >82,000 Patients Treated for Alcohol and Drug Use Disorder in Denmark.

Although the association between substance use and violence has been well established, knowledge on predictors for violent victimization of individuals treated for alcohol use disorder (aud) or drug use disorder (dud) is lacking.Using goldstein's tripartite conceptual framework, this study examines the relationship between substance use and violent victimization.Data were derived from national registers on persons aged between 15 and 75 years, living in denmark, and admitted for aud or dud treatment during 2006-2016 (n= 82,767).Rates of new incidence of violent victimization were estimated per 10,000 person years for the patient cohort, and for an age- and gender-matched control group of 492,397 people with no history of treatment for drug and alcohol problems.The incidence of victimization for the aud/dud sample was 145.6 per 10,000 person years and 5.4 per 10,000 person years for the comparison cohort.Results of multivariate cox regression on specific types of substance use supported goldstein's psychopharmacological and economic compulsive models of victimization, but not the systemic model.Gender-stratified results showed that the use of cannabis and methadone was associated with victimization in women treated for aud and dud.Patients with a non-western background were more likely to experience victimization than danish patients.The study highlights the strong association between substance use disorder and victimization, and the important role that service providers play in addressing the high levels of victimization experienced by patients with aud or dud.

Journal: Journal of interpersonal violence (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
Analysis of patient-specific NF1 variants leads to functional insights for Ras signaling that can impact personalized medicine.

We have created a panel of 29 nf1 variant complementary dnas (c dnas) representing missense variants, many with clinically relevant phenotypes, in-frame deletions, splice variants, and nonsense variants.We have determined the functional consequences of the variants, assessing their ability to produce mature neurofibromin and restore ras signaling activity in nf1 null (-/-) cells.C dnas demonstrate variant-specific differences in neurofibromin protein levels, suggesting that some variants lead to neurofibromatosis type 1 (nf1) gene or protein instability or enhanced degradation.When expressed at high levels, some variant proteins are still able to repress ras activity, indicating that the nf1 phenotype may be due to low protein abundance.In contrast, other variant proteins are incapable of repressing ras activity, indicating that some do not functionally engage ras and stimulate gtpase activity.We observed that effects on protein abundance and ras activity can be mutually exclusive.These assays allow us to categorize variants by functional effects, may help to classify variants of unknown significance, and may have future implications for more directed therapeutics.

Journal: Human mutation (2022)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A toxin-binding alkaline phosphatase fragment synergizes Bt toxin Cry1Ac against susceptible and resistant Helicoverpa armigera.

Evolution of resistance by insects threatens the continued success of pest control using insecticidal crystal (cry) proteins from the bacterium bacillus thuringiensis (bt) in sprays and transgenic plants.In this study, laboratory selection with cry1ac yielded five strains of cotton bollworm, helicoverpa armigera, with resistance ratios at the median lethal concentration (lc50) of activated cry1ac ranging from 22 to 1700.Reduced activity and reduced transcription of an alkaline phosphatase protein that binds cry1ac was associated with resistance to cry1ac in the four most resistant strains.A cry1ac-binding fragment of alkaline phosphatase from h.Armigera (ha alp1f) was not toxic by itself, but it increased mortality caused by cry1ac in a susceptible strain and in all five resistant strains.Although synergism of bt toxins against susceptible insects by toxin-binding fragments of cadherin and aminopeptidase n has been reported previously, the results here provide the first evidence of synergism of a bt toxin by a toxin-binding fragment of alkaline phosphatase.The results here also provide the first evidence of synergism of a bt toxin by any toxin-binding peptide against resistant insects.

Journal: PloS one (2015)
Publication types: Journal Article;Research Support, Non-U.S. Gov't
A Pharmacometric Model to Predict Chemotherapy-Induced Myelosuppression and Associated Risk Factors in Non-Small Cell Lung Cancer.

Chemotherapy often induces severe neutropenia due to the myelosuppressive effect.While predictive pharmacokinetic (pk)/pharmacodynamic (pd) models of absolute neutrophil count (anc) after anticancer drug administrations have been developed, their deployments to routine clinics have been limited due to the unavailability of pk data and sparseness of pd (or anc) data.Here, we sought to develop a model describing temporal changes of anc in non-small cell lung cancer patients receiving (i) combined chemotherapy of paclitaxel and cisplatin and (ii) granulocyte colony stimulating factor (g-csf) treatment when needed, under such limited circumstances.Maturation of myelocytes into blood neutrophils was described by transit compartments with negative feedback.The k-pd model was employed for drug effects with drug concentration unavailable and the constant model for g-csf effects.The fitted model exhibited reasonable goodness of fit and parameter estimates.Covariate analyses revealed that anc decreased in those without diabetes mellitus and female patients.Using the final model obtained, an r shiny web-based application was developed, which can visualize predicted anc profiles and associated risk of severe neutropenia for a new patient.Our model and application can be used as a supportive tool to identify patients at the risk of grade 4 neutropenia early and suggest dose reduction.

Journal: Pharmaceutics (2022)
Publication types: Journal Article
A pragmatic evaluation of the primary school Be Active After-School Activity Programme (Be Active ASAP).

The period after school represents an opportunity to engage children in physical activity (pa) programmes in schools.The purpose of this study was to evaluate the effect of an afterschool programme, delivered in schools, on children's participation in and attitudes to pa.Ten schools took part in this non-randomized controlled trial (five experimental and five control schools).Experimental schools participated in an after-school programme delivered by teachers and parents for 50 min per week.Outcome measures included device-measured pa, self-report youth pa behaviour and parental perceptions of the school environment.Measurements took place at baseline, and mean follow-up was at 10 weeks.Data were collected from 196 participants, with a mean age of 8.1 ± 0.8 years.Mean daily minutes of moderate-to-vigorous physical activity (mvpa) for the entire sample at baseline was 69.9 ± 23.3.While both groups presented a decline in mvpa levels, there was a significant difference in the change from baseline to follow-up (p = 0.043) of min/day mvpa between the control group (-13.2 ± 23.9) and the experimental group (-0.9 ± 25.2).This programme may help maintain mvpa levels, with children exposed to the intervention experiencing a significantly lower decline in mvpa than their control counterparts.

Journal: Health education research (2022)
Publication types: Controlled Clinical Trial;Journal Article;Research Support, Non-U.S. Gov't