Miracle-dz/UniFAR-FTUs huggingface dataset:
Association of Aspirin with Hepatocellular Carcinoma and Liver-Related Mortality.

BACKGROUND More information is needed about the long-term effects of low-dose aspirin (≤160 mg) on incident hepatocellular carcinoma, liver-related mortality, and gastrointestinal bleeding in persons with chronic hepatitis B or hepatitis C virus infection. METHODS Using nationwide Swedish registries, we identified all adults who received a diagnosis of chronic hepatitis B or hepatitis C from 2005 through 2015 and who did not have a history of aspirin use (50,275 patients). Patients who were starting to take low-dose aspirin (14,205 patients) were identified by their first filled prescriptions for 90 or more consecutive doses of aspirin. We constructed a propensity score and applied inverse probability of treatment weighting to balance baseline characteristics between groups. Using Cox proportional-hazards regression modeling, we estimated the risk of hepatocellular carcinoma and liver-related mortality, accounting for competing events. RESULTS With a median of 7.9 years of follow-up, the estimated cumulative incidence of hepatocellular carcinoma was 4.0% among aspirin users and 8.3% among nonusers of aspirin (difference, -4.3 percentage points; 95% confidence interval [CI], -5.0 to -3.6; adjusted hazard ratio, 0.69; 95% CI, 0.62 to 0.76). This inverse association appeared to be duration-dependent; as compared with short-term use (3 months to <1 year), the adjusted hazard ratios were 0.90 (95% CI, 0.76 to 1.06) for 1 to less than 3 years of use, 0.66 (95% CI, 0.56 to 0.78) for 3 to less than 5 years of use, and 0.57 (95% CI, 0.42 to 0.70) for 5 or more years of use. Ten-year liver-related mortality was 11.0% among aspirin users and 17.9% among nonusers (difference, -6.9 percentage points [95% CI, -8.1 to -5.7]; adjusted hazard ratio, 0.73 [95% CI, 0.67 to 0.81]). However, the 10-year risk of gastrointestinal bleeding did not differ significantly between users and nonusers of aspirin (7.8% and 6.9%, respectively; difference, 0.9 percentage points; 95% CI, -0.6 to 2.4). CONCLUSIONS In a nationwide study of patients with chronic viral hepatitis in Sweden, use of low-dose aspirin was associated with a significantly lower risk of hepatocellular carcinoma and lower liver-related mortality than no use of aspirin, without a significantly higher risk of gastrointestinal bleeding. (Funded by the National Institutes of Health and others.).
Analysis of Natural Gas Using a Portable Hollow-Core Photonic Crystal Coupled Raman Spectrometer

The low accessibility of natural gas fields and transporting pipelines requires portable online analyzers of the composition of natural gas, ensuring nearly chromatographic precision and capable of in situ analysis of a wide range of gases, including infrared-inactive ones (hydrogen, oxygen, nitrogen, chlorine). We have developed an express method of gas analysis meeting all the requirements for analysis of natural gas and its derivative mixtures using a portable 532 nm Raman spectrometer rigidly connected to a hollow-core crystal photonic fiber.
Long-Term Outcomes of Postpartum Psychosis: A Systematic Review and Meta-Analysis.

OBJECTIVE There is limited information on the longitudinal disease course after first-onset postpartum psychosis (PP). Some women will experience severe affective episodes outside the postpartum period, while for other women their vulnerability to mania and psychosis may be restricted to the postpartum period. This meta-analysis estimates the risk of recurrence after first-onset PP. DATA SOURCES A computerized literature search was conducted using Embase, MEDLINE, Web of Science, PsycINFO, Cochrane Central, PubMed, and Google Scholar (first 100 hits) combining key terms regarding longitudinal studies of first-onset PP from inception through May 9, 2019. Two levels of screening were used on 2,807 citations. STUDY SELECTION A total of 6 English-language articles including patients with a first-onset PP within 1 year after childbirth and a minimum follow-up period of 18 months or more after the index episode were included in the quantitative analysis. DATA EXTRACTION The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines were used for data extraction, and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines were used to independently assess the quality of the included studies. The primary outcome was recurrence, defined as any subsequent psychiatric episode after first-onset PP. RESULTS Six studies and 645 patients could be included in the quantitative analyses; follow-up periods were 11-26 years. Of these patients, 279 did not experience subsequent severe episodes outside the postpartum period. Meta-analysis using random-effect estimation resulted in a weighted estimate of 43.5% (95% CI, 37.7% to 49.4%). CONCLUSIONS In this meta-analysis, more than 40% of women were classified as having "isolated postpartum psychosis," which could be considered a distinct diagnostic category with a more favorable prognosis. The remaining women had severe non-puerperal psychiatric episodes during longitudinal follow-up.
Development of Gut-Selective Pan-Janus Kinase Inhibitor TD-1473 for Ulcerative Colitis: A Translational Medicine Programme

Abstract Background and Aims Oral systemic pan-Janus kinase [JAK] inhibition is effective for ulcerative colitis [UC] but is limited by toxicities. We describe preclinical to clinical translation of TD-1473—an oral gut-selective pan-JAK inhibitor—from in vitro characterization through a Phase 1b study in patients with UC. Methods TD-1473 JAK inhibition potency was evaluated in vitro; plasma pharmacokinetics, safety and efficacy were assessed in mice. In a first-time-in-human study, plasma pharmacokinetics and safety were assessed after single and multiple [14 days] ascending doses administered orally to healthy subjects. The Phase 1b study randomized patients with moderately to severely active UC to receive once-daily oral TD-1473 20, 80 or 270 mg, or placebo for 28 days. Plasma and colonic tissue concentrations were measured; safety was assessed; and efficacy was evaluated by UC clinical parameters, disease-surrogate biomarkers, endoscopy, histology and colonic tissue JAK signalling. Results TD-1473 exhibited potent pan-JAK inhibitory activity in vitro. Oral TD-1473 administration to mice achieved high, biologically active colonic tissue concentrations with low plasma exposure and decreased oxazolone-induced colitis activity without reducing blood cell counts vs placebo. TD-1473 administration in healthy human subjects and patients with UC yielded low plasma exposure and was generally well tolerated; treatment in patients with UC resulted in biologically active colonic tissue concentrations and descriptive trends toward reduced clinical, endoscopic and histological disease activity vs placebo. Conclusion Gut-selective pan-JAK inhibition with TD-1473 administration resulted in high intestinal vs plasma drug exposure, local target engagement, and trends toward reduced UC disease activity. [Clinicaltrials.gov NCT02657122, NCT02818686]
Proteomic and transcriptomic profiling of Pten gene‐knockout mouse model of prostate cancer

The prostate‐specific phosphatase and tensin homolog deleted on chromosome 10 (Pten) gene‐conditional knockout (KO) mouse carcinogenesis model is highly desirable for studies of prostate cancer biology and chemoprevention due to its close resemblance of primary molecular defect and many histopathological features of human prostate cancer including androgen response and disease progression from prostatic intraepithelial neoplasia to invasive adenocarcinoma. Here, we profiled the proteome and transcriptome of the Pten‐KO mouse prostate tumors for global macromolecular expression alterations for signaling changes and biomarker signatures.
Treatment Outcomes of Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis in Patients Over Age 75 Years: A Meta-Analysis

Background: The benefits of treating anti-neutrophil cytoplasmic autoantibody-associated vasculitis (AAV) in advancing age remains unclear with most published studies defining elderly as ≥65 years. This study aims to determine outcomes of induction immunosuppression in patients aged ≥75 years. Methods: A cohort of patients aged ≥75 years with a diagnosis of AAV between 2006 and 2018 was constructed from 2 centres. Follow-up was to 2 years or death. Analysis included multivariable Cox regression to compare mortality and end-stage renal disease (ESRD) based on receipt of induction immunosuppression therapy with either cyclophosphamide or rituximab. A systematic review of outcome studies was subsequently undertaken amongst this patient group through Pubmed, Cochrane and Embase databases from inception until October 16, 2019. Results: Sixty-seven patients were identified. Mean age was 79 ± 2.9 years and 82% (n = 55) received induction immunosuppression. Following systematic review, 4 studies were eligible for inclusion, yielding a combined total of 290 patients inclusive of our cohort. The aggregated 1-year mortality irrespective of treatment was 31% (95% CI 25–36%). Within our cohort, induction immunosuppression therapy was associated with a significantly lower 2-year mortality risk (hazard ratio [HR] 0.29 [95% CI 0.09–0.93]). The pooled HR by meta-analysis confirmed this with a significant risk reduction for death (HR 0.31 [95% CI 0.16–0.57], I2 = 0%). Treated patients had a lower pooled rate of ESRD, but was not statistically significant (HR 0.71 [95% CI 0.15–3.35]). Conclusion: This meta-analysis suggests that patients ≥75 years with AAV do benefit from induction immunosuppression with a significant survival benefit. Age alone should not be a limiting factor when considering treatment.
Can we reduce conduction disturbances following transcatheter aortic valve replacement?

ABSTRACT Introduction: Transcatheter aortic valve replacement (TAVR) has been demonstrated to be a good alternative to surgery for treating severe aortic stenosis (AS) across the whole range of surgical risk patients. Whereas most periprocedural TAVR complications have significantly decreased over time, conduction disturbances remain high. Approaches to decrease this shortcoming are under continuous investigation. Areas covered: Overview of the actual evidence regarding conduction disturbances in the TAVR setting, focusing on modifiable factors. PubMed and Embase databases were used for literature search. Expert opinion: Several factors have been associated with an increased risk of conduction disturbances post-TAVR, and some of them may be modifiable. While some transcatheter valve systems have been associated with higher rates of conduction disturbances, additional randomized data are needed to draw definite conclusions about newer generation transcatheter valve systems. Nowadays, good hemodynamic valve function can be obtained without excessive valve oversizing, which has been associated with an increased risk of conduction disturbances in some studies. Also, contemporary data regarding valve implantation depth and new anatomical landmarks such as membranous septum length have provided valuable insights for procedural planning. Finally, homogenization of the management of conduction abnormalities post-TAVR should be emphasized to allow a better understanding and generalization of available evidence.
Anxiety sensitivity in relation to cigarette smoking and other substance use in African American smokers.

Anxiety sensitivity (AS)-fearfulness of anxiety symptoms-has been implicated in the etiology of emotional disorders (e.g., depressive and anxiety disorders) and linked to cigarette smoking and other substance use (SU). However, studies examining AS in relation to SU primarily have been conducted with racially/ethnically heterogeneous or mostly European American samples. Hence, this cross-sectional study involving secondary analysis of baseline data focused on investigating associations of AS with cigarette smoking and other SU in a sample of 630 non-treatment-seeking African American smokers (37.3% female; M age = 49.6 years; M cigarettes smoked per day = 15.4). After screening out individuals with non-nicotine substance dependence, participants reported their demographics, AS, dysphoria symptoms (i.e., depression and anxiety symptoms), and SU. In regression analyses controlling for dysphoria symptoms, age, education level, income level, and years of regular smoking, AS was positively associated with tobacco withdrawal severity (β = .12, p = .007), overall smoking motives (β = .17, p < .001), alcohol use problems (β = .12, p = .005), and other (non-nicotine, nonalcohol) SU problems (β = .16, p < .001). Though lacking the passage of time between assessments needed to provide strong evidence of mediation, unplanned analyses further revealed indirect associations of AS with several SU variables through dysphoria symptoms. Current findings are consistent with those found in prior samples and suggest that AS is similarly related to SU in African Americans, who may benefit from interventions that have been helpful in improving AS, dysphoria symptoms, and SU in other groups. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
Study on physical fitness factors affecting race-class of Korea racing cyclists

The purpose of this study is to compare and analyze the difference of isokinetic muscle functions, anaerobic capabilities, pedaling power and maximum strength according to race-class of Korea racing cyclists. The participants in this study were 57 racing cyclist candidates who graduated from the Korea racing school. One year after graduation, we confirmed race-class of candidates and they were divided into three groups: the first-class racer group (FC, n=14), second-class racer group (SC, n=29), third-class racer group (TC, n=14). The isokinetic muscle strength of trunk and knee flexion/extension was measured using HUMAC NORM and basic physical strength such as squat and bench press was analyzed by Ariel device. As results of this study, % Fat (percentage of body fat) in FC group was the lowest compared to other groups. Isokinetic knee flexion strength was higher in FC group than SC and TC racer groups. Peak and average pedaling power as well as maximum muscle strength were significantly higher in FC group than in other groups. Our findings suggest new evidence that pedaling power and isokinetic muscle strength might be closely associated with race-class of Korea racing cyclists.
FT-IR Spectroscopy is a New Option for Outbreak Investigation: A Retrospective Analysis of an ESBL-producing Klebsiella pneumoniae Outbreak in a Neonatal Intensive Care Unit.

The IR Biotyper is a new automated typing system based on Fourier-transform infrared (FT-IR) spectroscopy that gives results within 4 hours. We aimed: 1) to use the IR Biotyper to retrospectively analyze an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in a neonatal intensive care unit and to compare results to BOX-PCR and whole genome sequencing (WGS) as the gold standard; and 2) to assess how the cut-off values used to define clusters affect the discriminatory power of the IR Biotyper. The sample consisted of 18 isolates from 14 patients. Specimens were analyzed in the IR Biotyper using the default analysis settings and spectra were analyzed using OPUS 7.5 software. The software contains a feature that automatically proposes a cut-off value to define clusters; the cut-off value defines up to which distance the spectra are considered to be in the same cluster. By FT-IR, the outbreak represented 1 dominant clone, 1 secondary clone, and several unrelated clones. FT-IR results, using the cut-off value generated by the accompanying software after 4 replicates, were concordant with WGS for all but 1 isolate. BOX-PCR was under-discriminatory compared to the other two methods. Using the cut-off value generated after 12 replicates, the results of FT-IR and WGS were completely concordant. The FT-IR Biotyper can achieve the same typeability and discriminatory power as genome-based methods. However, to attain this high performance requires either previous, strain-dependent, knowledge about the optimal technical parameters to be used or validation by a second method.
Ecological prediction at macroscales using big data: Does sampling design matter?

Although ecosystems respond to global change at regional to continental scales (i.e., macroscales), model predictions of ecosystem responses often rely on data from targeted monitoring of a small proportion of sampled ecosystems within a particular geographic area. In this study, we examined how the sampling strategy used to collect data for such models influences predictive performance. We subsampled a large and spatially-extensive dataset to investigate how macroscale sampling strategy affects prediction of ecosystem characteristics in 6,784 lakes across a 1.8 million km2 area. We estimated model predictive performance for different subsets of the dataset to mimic three common sampling strategies for collecting observations of ecosystem characteristics: random sampling design, stratified random sampling design, and targeted sampling. We found that sampling strategy influenced model predictive performance such that (1) stratified random sampling designs did not improve predictive performance compared to simple random sampling designs and (2) although one of the scenarios that mimicked targeted (non-random) sampling had the poorest performing predictive models, the other targeted sampling scenarios resulted in models with similar predictive performance to that of the random sampling scenarios. Our results suggest that although potential biases in datasets from some forms of targeted sampling may limit predictive performance, compiling existing spatially-extensive datasets can result in models with good predictive performance that may inform a wide range of science questions and policy goals related to global change.
Dendritic cells dictate responses to PD-L1 blockade cancer immunotherapy

DCs are critical cellular targets of PD-L1 blockade in cancer treatment. Checkpoint musical chairs Anti–PD-1 or PD-L1 antibodies can reinvigorate antitumor immunity in a subset of patients with cancer. To better understand the mechanisms behind successful therapy, Mayoux et al. characterized various ligands on the surface of dendritic cells (DCs). PD-L1 on DCs can bind B7.1 on the same cell, potentially preventing PD-1 ligation on T cells or B7.1 ligation of its partner CD28. They saw that PD-L1 was expressed in excess of B7.1, likely preventing T cell stimulation through these two pathways. Patients with a high DC signature before treatment were more likely to respond to PD-L1 blockade. These results reveal that in cis interactions on DCs have immunological and likely clinical consequences for checkpoint blockade therapy. PD-L1/PD-1 blocking antibodies have demonstrated therapeutic efficacy across a range of human cancers. Extending this benefit to a greater number of patients, however, will require a better understanding of how these therapies instigate anticancer immunity. Although the PD-L1/PD-1 axis is typically associated with T cell function, we demonstrate here that dendritic cells (DCs) are an important target of PD-L1 blocking antibody. PD-L1 binds two receptors, PD-1 and B7.1 (CD80). PD-L1 is expressed much more abundantly than B7.1 on peripheral and tumor-associated DCs in patients with cancer. Blocking PD-L1 on DCs relieves B7.1 sequestration in cis by PD-L1, which allows the B7.1/CD28 interaction to enhance T cell priming. In line with this, in patients with renal cell carcinoma or non–small cell lung cancer treated with atezolizumab (PD-L1 blockade), a DC gene signature is strongly associated with improved overall survival. These data suggest that PD-L1 blockade reinvigorates DC function to generate potent anticancer T cell immunity.
Augmenting Safety Planning With Text Messaging Support for Adolescents at Elevated Suicide Risk: Development and Acceptability Study

Background Suicide is the second leading cause of death among adolescents. A critical need exists for developing promising interventions for adolescents after psychiatric hospitalization who are at a high risk of experiencing repeated suicidal behaviors and related crises. The high-risk period following psychiatric hospitalization calls for cost-effective and scalable continuity of care approaches to support adolescents’ transition from inpatient care. Text messages have been used to improve a wide range of behavioral and health outcomes and may hold promise as an accessible continuity of care strategy for youth at risk of suicide. Objective In this study of 40 adolescents at elevated suicide risk, we report on the iterative development and acceptability of a text-based intervention designed to encourage adaptive coping and safety plan adherence in the high-risk period following psychiatric hospitalization. Methods Adolescents (aged 13-17 years) who were hospitalized because of last-month suicide attempts or last-week suicidal ideation took part in either study phase 1 (n=25; 19/25, 76% female), wherein message content was developed and revised on the basis of feedback obtained during hospitalization, or study phase 2 (n=15; 11/15, 73% female), wherein text messages informed by phase 1 were further tested and refined based on feedback obtained daily over the course of a month after discharge (n=256 observations) and during an end-of-study phone interview. Results Quantitative and qualitative feedback across the 2 study phases pointed to the acceptability of text-based support. Messages were seen as having the potential to be helpful with the transition after hospitalization, with adolescents indicating that texts may serve as reminders to use coping strategies, contribute to improvement in mood, and provide them with a sense of encouragement and hope. At the same time, some adolescents expressed concerns that messages may be insufficient for all teens or circumstances. In phase 2, the passage of time did not influence adolescents’ perception of messages in the month after discharge (P=.74); however, there were notable daily level associations between the perception of messages and adolescents’ affect. Specifically, higher within-person (relative to adolescents’ own average) anger was negatively related to liking text messages (P=.005), whereas within-person positive affect was associated with the perception of messages as more helpful (P=.04). Conclusions Text-based support appears to be an acceptable continuity of care strategy to support adolescents’ transition after hospitalization. The implications of study findings are discussed. Future work is needed to evaluate the impact of text-based interventions on suicide-related outcomes.