Miracle-dz/UniFAR-FTUs huggingface dataset:
Do antihypertensive drugs really have antitumor effects? Baseline differences in hypertensive and non-hypertensive patients with advanced pancreatic cancer

Although the antitumor effects of antihypertensive drugs for patients with advanced pancreatic cancer (APC) have been investigated, their efficacy remains unclear. Previous studies suggest that hypertensive (HT) patients with APC are significantly older than non-HT patients with APC, and that other major baseline differences in patient characteristics which may affect prognosis exist between HT and non-HT patients. It is also possible that antihypertensive drugs lack antitumor activity. Therefore, we herein retrospectively investigated the baseline differences between HT and non-HT patients with APC. From January 2015 to April 2020, 56 patients with APC received nab-paclitaxel plus gemcitabine as first-line chemotherapy at Higashiosaka City Medical Center (Higashiosaka, Japan). Of these 56 patients, 30 were diagnosed with hypertension (HT group); the remaining 26 did not have hypertension (non-HT group). Differences between the two groups were compared and prognostic factors were evaluated. Patients in the HT group had significantly less sarcopenia, a significantly larger body mass index, were significantly older, and significantly more likely to have a regular doctor and primary site in the body and tail of the pancreas than those in the non-HT group. Although no significant difference was found in the treatment response, patients in the HT group were significantly more likely to move to second-line chemotherapy than those in the non-HT group. Survival curves showed that median overall survival (OS) in the HT group was significantly longer (10.5 months) than in the non-HT group (6.8 months, P = .04). Multivariate analysis did not identify the use of antihypertensive drugs as an independent prognostic factor of OS. We identified key baseline differences in the characteristics of APC patients with and without HT, suggesting that major selection bias could occur when investigating the efficacy of antihypertensive drugs in all populations. Therefore, it is possible that antihypertensive drugs lack antitumor activity. To determine the true efficacy of antihypertensive drugs for APC, HT, and non-HT patients in another population should be investigated, or a prospective, randomized, controlled trial conducted that is stratified by HT or non-HT status.
PROM1, CXCL8, RUNX1, NAV1 and TP73 genes as independent markers predictive of prognosis or response to treatment in two cohorts of high-grade serous ovarian cancer patients

Considering the vast biological diversity and high mortality rate in high-grade ovarian cancers, identification of novel biomarkers, enabling precise diagnosis and effective, less aggravating treatment, is of paramount importance. Based on scientific literature data, we selected 80 cancer-related genes and evaluated their mRNA expression in 70 high-grade serous ovarian cancer (HGSOC) samples by Real-Time qPCR. The results were validated in an independent Northern American cohort of 85 HGSOC patients with publicly available NGS RNA-seq data. Detailed statistical analyses of our cohort with multivariate Cox and logistic regression models considering clinico-pathological data and different TP53 mutation statuses, revealed an altered expression of 49 genes to affect the prognosis and/or treatment response. Next, these genes were investigated in the validation cohort, to confirm the clinical significance of their expression alterations, and to identify genetic variants with an expected high or moderate impact on their products. The expression changes of five genes, PROM1, CXCL8, RUNX1, NAV1, TP73, were found to predict prognosis or response to treatment in both cohorts, depending on the TP53 mutation status. In addition, we revealed novel and confirmed known SNPs in these genes, and showed that SNPs in the PROM1 gene correlated with its elevated expression.
Optimization of peripheral blood volume for in silico reconstitution of the human B‐cell receptor repertoire

B cells recognize antigens via membrane‐expressed B‐cell receptors (BCR) and antibodies. Similar human BCR sequences are frequently found at a significantly higher frequency than that theoretically calculated. Patients infected with SARS‐CoV2 and HIV or with autoimmune diseases share very similar BCRs. Therefore, in silico reconstitution of BCR repertoires and identification of stereotypical BCR sequences related to human pathology have diagnostic potential. Furthermore, monitoring changes of clinically significant BCR sequences and isotype conversion has prognostic potential. For BCR repertoire analysis, peripheral blood (PB) is the most convenient source. However, the optimal human PB volume for in silico reconstitution of the BCR repertoire has not been studied in detail. Here, we sampled 5, 10, and 20 mL PB from the left arm and 40 mL PB from the right arm of two volunteers, reconstituted in silico PB BCR repertoires, and compared their composition. In both volunteers, PB sampling over 20 mL resulted in slight increases in functional unique sequences (FUSs) or almost no increase in repertoire diversity. All FUSs with a frequency above 0.08% or 0.03% in the 40 mL PB BCR repertoire were detected even in the 5 mL PB BCR repertoire from each volunteer. FUSs with a higher frequency were more likely to be found in BCR repertoires from reduced PB volume, and those coexisting in two repertoires showed a statistically significant correlation in frequency irrespective of sampled anatomical site. The correlation was more significant in higher‐frequency FUSs. These observations support the potential of BCR repertoire analysis for diagnosis.
Automatic CD30 scoring method for whole slide images of primary cutaneous CD30+ lymphoproliferative diseases

Aims Deep-learning methods for scoring biomarkers are an active research topic. However, the superior performance of many studies relies on large datasets collected from clinical samples. In addition, there are fewer studies on immunohistochemical marker assessment for dermatological diseases. Accordingly, we developed a method for scoring CD30 based on convolutional neural networks for a few primary cutaneous CD30+ lymphoproliferative disorders and used this method to evaluate other biomarkers. Methods A multipatch spatial attention mechanism and conditional random field algorithm were used to fully fuse tumour tissue characteristics on immunohistochemical slides and alleviate the few sample feature deficits. We trained and tested 28 CD30+ immunohistochemical whole slide images (WSIs), evaluated them with a performance index, and compared them with the diagnoses of senior dermatologists. Finally, the model’s performance was further demonstrated on the publicly available Yale HER2 cohort. Results Compared with the diagnoses by senior dermatologists, this method can better locate the tumour area and reduce the misdiagnosis rate. The prediction of CD3 and Ki-67 validated the model’s ability to identify other biomarkers. Conclusions In this study, using a few immunohistochemical WSIs, our model can accurately identify CD30, CD3 and Ki-67 markers. In addition, the model could be applied to additional tumour identification tasks to aid pathologists in diagnosis and benefit clinical evaluation.
The effect of time on task, sleep deprivation, and time of day on simulated driving performance

Abstract Sleep deprivation and time of day have been shown to play a critical role in decreasing ability to sustain attention, such as when driving long distances. However, a gap in the literature exists regarding external factors, such as workload. One way to examine workload is via modulating time on task. This study investigated the combined effect of sleep deprivation, time of day, and time on task as a workload factor on driving performance. Twenty-one participants (18–34 years, 10 females) underwent 62 h of sleep deprivation within a controlled laboratory environment. Participants received an 8-h baseline and 9.5-h recovery sleep. Every 8 h, participants completed a Psychomotor Vigilance Task (PVT), Karolinska Sleepiness Scale (KSS), 30-min monotonous driving task and NASA-Task Load Index (TLX). Driving variables examined were lane deviation, number of crashes, speed deviation and time outside the safe zone. Workload was measured by comparing two 15-min loops of the driving track. A mixed model ANOVA revealed significant main effects of day and time of day on all driving performance measures (p < .001). There was a significant main effect of workload on lane deviation (p < .05), indicating that a longer time on task resulted in greater lane deviation. A significant main effect of day (p < .001) but not time of day for the NASA-TLX, PVT and KSS was found. Time on task has a significant further impact on driving performance and should be considered alongside sleep deprivation and time of day when implementing strategies for long-distance driving.
Understanding the role of sex on outcomes for the cancer patient undergoing treatment with immune checkpoint inhibitors: a scoping review protocol

Introduction Immune checkpoint inhibitors (ICIs) have changed the treatment landscape for multiple cancer types. Sex plays an important role in both the development of cancer as well as the functioning of the immune system. Though a difference in response to immune therapy is emerging between men and women it is unclear how this difference affects cancer outcomes and what the potential underlying mechanisms are for those effects. The objective of this study is to describe the influence that sex has on the outcomes experienced by cancer patients on ICI therapy and to identify and analyse any knowledge gaps in the field. Method and analysis The framework for this methodology was guided by the Joanna Briggs Institute Manual for Evidence Synthesis. The search and review will be conducted from January 2022 to June 2022. Two independent researchers will screen titles and abstracts followed by full-text screening for manuscript inclusion. Full length studies published between 2010 and December 2021 found in PubMed, Cochrane, CINAHL, and Scopus describing the influence of sex differences on cancer outcomes in patients treated with ICIs will be included. After data are extracted it will be summarised for presentation. Ethics and dissemination The findings of this scoping review will be published in a peer-reviewed journal. The results will be used to inform future studies on the potential differential impacts of ICIs. All data are from published openly accessible sources and therefore no ethical clearance is necessary.
Cumulative environmental risk in early life is associated with mental disorders in childhood

Abstract Background No single environmental factor is a necessary or sufficient cause of mental disorder; multifactorial and transdiagnostic approaches are needed to understand the impact of the environment on the development of mental disorders across the life course. Method Using linked multi-agency administrative data for 71 932 children from the New South Wales Child Developmental Study, using logistic regression, we examined associations between 16 environmental risk factors in early life (prenatal period to <6 years of age) and later diagnoses of mental disorder recorded in health service data (from age 6 to 13 years), both individually and summed as an environmental risk score (ERS). Results The ERS was associated with all types of mental disorder diagnoses in a dose–response fashion, such that 2.8% of children with no exposure to any of the environmental factors (ERS = 0), compared to 18.3% of children with an ERS of 8 or more indicating exposure to 8 or more environmental factors (ERS ⩾ 8), had been diagnosed with any type of mental disorder up to age 13–14 years. Thirteen of the 16 environmental factors measured (including prenatal factors, neighbourhood characteristics and more proximal experiences of trauma or neglect) were positively associated with at least one category of mental disorder. Conclusion Exposure to cumulative environmental risk factors in early life is associated with an increased likelihood of presenting to health services in childhood for any kind of mental disorder. In many instances, these factors are preventable or capable of mitigation by appropriate public policy settings.
The Inequitable Burden of the COVID-19 Pandemic Among Marginalized Older Workers in the United States: An Intersectional Approach

Abstract Objectives The COVID-19 pandemic has profoundly affected the lives of people globally, widening long-standing inequities. We examined the COVID-19 pandemic’s impact on employment conditions by race/ethnicity, gender, and educational attainment and the association between such conditions and well-being in older adults in the United States. Methods Using data from the Health and Retirement Study respondents interviewed between May 2020 and May 2021 when they were ≥55 years of age, we examined intersectional patterns in COVID-19-related changes in employment conditions among 4,107 participants working for pay at the start of the pandemic. We also examined the compounding nature of changes in employment conditions and their association with financial hardship, food insecurity, and poor self-rated health. Results Relative to non-Hispanic White men with greater than high school education (>HS), Black and Latinx men and women were more likely to experience job loss irrespective of education; among those who did not experience job loss, men with ≤HS reporting Black, Latinx, or “other” race were >90% less likely to transition to remote work. Participants who experienced job loss with decreased income or continued in-person employment with decreased income/shift changes had greater prevalence of financial hardship, food insecurity, and poor/fair self-rated health than others. Discussion The impact of COVID-19 on employment conditions is inequitably patterned and is associated with financial hardship, food insecurity, and adverse health in older adults. Policies to improve employment quality and expand social insurance programs among this group are needed to reduce growing inequities in well-being later in life.
On-line Handwritten Japanese Text Recognition by Improving Segmentation Quality

This paper describes a method of on-line handwritten Japanese text recognition by improving segmentation quality. The method produces hypothetical segmentation points according to features such as distance and overlap between adjacent strokes. Moreover, it extracts multidimensional features from these hypothetical segmentation points and applies an SVM to the extracted features to produces segmentation point probabilities. It constructs a candidate lattice traversing the hypothetical segmentation points, and evaluates the likelihood of the text candidate paths in the candidate lattice composed of character pattern size, character pattern inner gap, character recognition, single-character pattern position, paircharacter patterns position, character segmentation point probability and linguistic context. The likelihood of the text candidate paths are weighted using the number of hypothetical segmentation units with the weighting parameters trained by a genetic algorithm. An experiment on the database HANDS-Kondate_t_bf-2001-11 shows that this method improves segmentation rate and character recognition rate remarkably.
Regulatory T cells in erythema nodosum leprosum maintain anti-inflammatory function

Background The numbers of circulating regulatory T cells (Tregs) are increased in lepromatous leprosy (LL) but reduced in erythema nodosum leprosum (ENL), the inflammatory complication of LL. It is unclear whether the suppressive function of Tregs is intact in both these conditions. Methods A longitudinal study recruited participants at ALERT Hospital, Ethiopia. Peripheral blood samples were obtained before and after 24 weeks of prednisolone treatment for ENL and multidrug therapy (MDT) for participants with LL. We evaluated the suppressive function of Tregs in the peripheral blood mononuclear cells (PBMCs) of participants with LL and ENL by analysis of TNFα, IFNγ and IL-10 responses to Mycobacterium leprae (M. leprae) stimulation before and after depletion of CD25+ cells. Results 30 LL participants with ENL and 30 LL participants without ENL were recruited. The depletion of CD25+ cells from PBMCs was associated with enhanced TNFα and IFNγ responses to M. leprae stimulation before and after 24 weeks treatment of LL with MDT and of ENL with prednisolone. The addition of autologous CD25+ cells to CD25+ depleted PBMCs abolished these responses. In both non-reactional LL and ENL groups mitogen (PHA)-induced TNFα and IFNγ responses were not affected by depletion of CD25+ cells either before or after treatment. Depleting CD25+ cells did not affect the IL-10 response to M. leprae before and after 24 weeks of MDT in participants with LL. However, depletion of CD25+ cells was associated with an enhanced IL-10 response on stimulation with M. leprae in untreated participants with ENL and reduced IL-10 responses in treated individuals with ENL. The enhanced IL-10 in untreated ENL and the reduced IL-10 response in prednisolone treated individuals with ENL was abolished by addition of autologous CD25+ cells. Conclusion The findings support the hypothesis that the impaired cell-mediated immune response in individuals with LL is M. leprae antigen specific and the unresponsiveness can be reversed by depleting CD25+ cells. Our results suggest that the suppressive function of Tregs in ENL is intact despite ENL being associated with reduced numbers of Tregs. The lack of difference in IL-10 response in control PBMCs and CD25+ depleted PBMCs in individuals with LL and the increased IL-10 response following the depletion of CD25+ cells in individuals with untreated ENL suggest that the mechanism of immune regulation by Tregs in leprosy appears independent of IL-10 or that other cells may be responsible for IL-10 production in leprosy. The present findings highlight mechanisms of T cell regulation in LL and ENL and provide insights into the control of peripheral immune tolerance, identifying Tregs as a potential therapeutic target.
Fangchinoline abrogates growth and survival of hepatocellular carcinoma by negative regulation of c‐met/HGF and its associated downstream signaling pathways

Among all cancers, hepatocellular carcinoma (HCC) remains a lethal disease with limited treatment options. In this study, we have analyzed the possible inhibitory effects of Fangchinoline (FCN) on c‐Met, a protein known to regulate the rapid phosphorylation of downstream signals, as well as mediate aberrant growth, metastasis, survival, and motility in cancer. FCN inhibited the activation of c‐Met and its downstream signals PI3K, AKT, mTOR, MEK, and ERK under in vitro settings. Moreover, c‐Met gene silencing lead to suppression of PI3K/AKT/mTOR and MEK/ERK signaling pathways, and induced apoptotic cell death upon exposure to FCN. In addition, FCN markedly inhibited the expression of the various oncogenic proteins such as Bcl‐2/xl, survivin, IAP‐1/2, cyclin D1, and COX‐2. In vivo studies in HepG2 cells xenograft mouse model showed that FCN could significantly attenuate the tumor volume and weight, without affecting significant loss in the body weight. Similar to in vitro studies, expression level of c‐Met and PI3K/AKT/mTOR, MEK/ERK signals was also suppressed by FCN in the tissues obtained from mice. Therefore, the novel findings of this study suggest that FCN can potentially function as a potent anticancer agent against HCC.
Sex/Gender Differences in Verbal Fluency and Verbal-Episodic Memory: A Meta-Analysis

Women are thought to fare better in verbal abilities, especially in verbal-fluency and verbal-memory tasks. However, the last meta-analysis on sex/gender differences in verbal fluency dates from 1988. Although verbal memory has only recently been investigated meta-analytically, a comprehensive meta-analysis is lacking that focuses on verbal memory as it is typically assessed, for example, in neuropsychological settings. On the basis of 496 effect sizes and 355,173 participants, in the current meta-analysis, we found that women/girls outperformed men/boys in phonemic fluency (ds = 0.12–0.13) but not in semantic fluency (ds = 0.01–0.02), for which the sex/gender difference appeared to be category-dependent. Women/girls also outperformed men/boys in recall (d = 0.28) and recognition (ds = 0.12–0.17). Although effect sizes are small, the female advantage was relatively stable over the past 50 years and across lifetime. Published articles reported stronger female advantages than unpublished studies, and first authors reported better performance for members of their own sex/gender. We conclude that a small female advantage in phonemic fluency, recall, and recognition exists and is partly subject to publication bias. Considerable variance suggests further contributing factors, such as participants’ language and country/region.
A diatom record of late Holocene climate variation in the northern A diatom record of late Holocene climate variation in the northern range of Yellowstone National Park, USA range of Yellowstone National Park, USA

The changes in diatom species composition in a sediment core from Crevice Lake, Yellowstone National Park, spanning the past 2550 yr, were used to reconstruct long-term limnological and ecological conditions that may be related to late Holocene climate variability. Planktic forms dominate the fossil diatom assemblages throughout this record, but changes in species dominance indicate varying nutrient levels over time, particularly phosphorus. The changes in the nutrient concentrations in the lake were probably driven by changes in temperature and wind strength that affected the duration of water-column mixing and thus the extent of nutrient recycling from deep waters. Prior to 2100 cal before present (BP), Stephanodiscus minutulus and Synedra tenera dominated, suggesting long cool springs with extensive regeneration of phosphorus from the hypolimnion that resulted from isothermal mixing. From 2100 to 800 cal BP, these species were replaced by Cyclotella michiganiana and Cyclotella bodanica . These species are characteristic of lower nutrient concentrations and are interpreted here to reflect warm summers with long periods of thermal stratification. From 800 to 50 cal BP, S. minutulus dominated the diatom assemblage, suggesting a return to lengthy mixing during spring. The most dramatic late Holocene changes in the fossil diatom assemblages occurred during the transition from the Medieval Period to the Little Ice Age, approximately 800 cal BP.