Miracle-dz/UniFAR-FTUs huggingface dataset:
Acetic acid is an oxidative stressor in gastric cancer cells

Acetic acid can cause cellular injury. We previously reported that acetic acid induces cancer cell-selective death in rat gastric cells. However, the mechanism is unclear. Generally, cancer cells are more sensitive to reactive oxygen species than normal cells. Accordingly, in this study, we investigated the involvement of oxidative stress in cancer cell-selective death by acetic acid using normal gastric mucosal cells and cancerous gastric mucosal cells. The cancer cell-selective death was induced at the concentration of 2–5 µM acetic acid. Cancerous gastric mucosal cells had increased expression of monocarboxylic transporter 1 and high uptake of acetic acid, compared to normal gastric mucosal cells. The exposure of cancerous gastric mucosal cells to acetic acid enhanced production of reactive oxygen species and expression of monocarboxylic transporter 1, and induced apoptosis. In contrast, acetic acid showed minor effects in normal gastric mucosal cells. These results indicate that acetic acid induced cancer cell-selective death in gastric cells through a mechanism involving oxidative stress.
Moment transparency

We introduce moment transparency, a new solution to real-time order-independent transparency. It expands upon existing approximate transmittance function techniques by using moments to capture and reconstruct the transmittance function. Because the moment-based transmittance function can be processed analytically using standard hardware blend operations, it is efficient and overcomes limitations of previous techniques.
Circulating Follicular Helper and Follicular Regulatory T Cells Are Severely Compromised in Human CD40 Deficiency: A Case Report

Mutations in genes that control class switch recombination and somatic hypermutation during the germinal center (GC) response can cause diverse immune dysfunctions. In particular, mutations in CD40LG, CD40, AICDA, or UNG cause hyper-IgM (HIGM) syndrome, a heterogeneous group of primary immunodeficiencies. Follicular helper (Tfh) and follicular regulatory (Tfr) T cells play a key role in the formation and regulation of GCs, but their role in HIGM pathogenesis is still limited. Here, we found that compared to CD40 ligand (CD40L)- and activation-induced cytidine deaminase (AICDA)-deficient patients, circulating Tfh and Tfr cells were severely compromised in terms of frequency and activation phenotype in a child with CD40 deficiency. These findings offer useful insight for human Tfh biology, with potential implications for understanding the molecular basis of HIGM syndrome caused by mutations in CD40.
Missing Value Imputation Based on Deep Generative Models

Missing values widely exist in many real-world datasets, which hinders the performing of advanced data analytics. Properly filling these missing values is crucial but challenging, especially when the missing rate is high. Many approaches have been proposed for missing value imputation (MVI), but they are mostly heuristics-based, lacking a principled foundation and do not perform satisfactorily in practice. In this paper, we propose a probabilistic framework based on deep generative models for MVI. Under this framework, imputing the missing entries amounts to seeking a fixed-point solution between two conditional distributions defined on the missing entries and latent variables respectively. These distributions are parameterized by deep neural networks (DNNs) which possess high approximation power and can capture the nonlinear relationships between missing entries and the observed values. The learning of weight parameters of DNNs is performed by maximizing an approximation of the log-likelihood of observed values. We conducted extensive evaluation on 13 datasets and compared with 11 baselines methods, where our methods largely outperforms the baselines.
A qualitative study of clinical champions in context: Clinical champions across three levels of acute care

Objectives: To compare activities and field descriptions of clinical champions across three levels of stroke centers. Methods: A cross-sectional qualitative study using quota sampling was conducted. The setting for this study was 38 acute stroke centers based in US Veterans Affairs Medical Centers with 8 designated as Primary, 24 as Limited Hours, and 6 as Stroke Support Centers. Key informants involved in stroke care were interviewed using a semi-structured approach. A cross-case synthesis approach was used to conduct a qualitative analysis of clinical champions’ behaviors and characteristics. Clinical champion behaviors were described and categorized across three dimensions: enthusiasm, persistence, and involving the right people. Results: Clinical champions at Primary Stroke Centers represented diverse medical disciplines and departments (education, quality management); directed implementation of acute stroke care processes; coordinated processes across service lines; and benefited from supportive contexts for implementation. Clinical champions at Limited Hours Stroke Centers varied in steering implementation efforts, building collaboration across disciplines, and engaging in other clinical champion activities. Clinical champions at Stroke Support Centers were implementing limited changes to stroke care and exhibited few behaviors fitting the three clinical champion dimensions. Other clinical champion behaviors included educating colleagues, problem-solving, implementing new care pathways, monitoring progress, and standardizing processes. Conclusion: These data demonstrate clinical champion behaviors for implementing changes to complex care processes such as acute stroke care. Changes to complex care processes involved coordination among clinicians from multiple services lines, persistence facing obstacles to change, and enthusiasm for targeted practice changes.
The Sensory Quality and Volatile Profile of Dark Chocolate Enriched with Encapsulated Probiotic Lactobacillus plantarum Bacteria

Cocoa and dark chocolate have a wide variety of powerful antioxidants and other nutrients that can positively affect human health. Probiotic dark chocolate has the potential to be a new product in the growing number of functional foods. In this study, encapsulated potential probiotic Lactobacillus plantarum 564 and commercial probiotic Lactobacillus plantarum 299v were added in the production of dark chocolate. The results show very good survival of probiotic bacteria after production and during storage, reaching 108cfu/g in the first 60 days and over 106cfu/g up to 180 days. No statistically significant difference (p > 0.05) in chemical composition and no major differences in the volatile profiles between control and experimental chocolate samples were observed, indicating no impact of probiotic bacteria on compositional and sensory characteristics of dark chocolate. The sensory evaluation of control and both probiotic dark chocolate samples showed excellent sensory quality after 60 and 180 days of storage, demonstrating that probiotics did not affect aroma, texture and appearance of chocolate. Due to a high viability of bacterial cells and acceptable sensory properties, it can be concluded that encapsulated probiotics Lb. plantarum 564 and Lb. plantarum 299v could be successfully used in the production of probiotic dark chocolate.
Health Risk Associated with Exposure to PM10 and Benzene in Three Italian Towns

Air pollution in urban areas is a major concern as it negatively affects the health of a large number of people. The purpose of this study was to assess the inhalation health risk for exposure to PM10 and benzene of the populations living in three Italian cities. Data regarding PM10 and benzene daily measured by “traffic” stations and “background” stations in Torino, Perugia, and Lecce during 2014 and 2015 were compared to the limits indicated in the Directive 2008/50/EC. In addition, an inhalation risk analysis for exposure to benzene was performed for adults and children by applying the standard United States Environmental Protection Agency’s (USEPA) methodology. The levels of PM10 detected in Torino exceeded the legal limits in both years with an increased mean concentration >10 µg/m3 comparing with background station. Benzene concentrations never exceeded the legislative target value. The increased cancer risk (ICR) for children exposed to benzene was greater than 1 × 10−6 only in the city of Torino, while for adults, the ICR was higher than 1 × 10−6 in all the cities. The results suggest the need for emission reduction policies to preserve human health from continuous and long exposure to air pollutants. A revision of legal limits would also be recommended.
Interrater Reliability of the Structured Clinical Interview for the DSM–5 Alternative Model of Personality Disorders Module i: Level of Personality Functioning Scale

Abstract The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM–5) presents an alternative model for personality disorders in which severity of personality pathology is evaluated by the Level of Personality Functioning Scale (LPFS). The Structured Interview for the DSM–5 Alternative Model for Personality Disorders, Module I (SCID–5–AMPD I) is a new tool for LPFS assessment, but its interrater reliability (IRR) has not yet been tested. Here we examined the reliability of the Norwegian translation of the SCID–5–AMPD I, applying two different designs: IRR assessment based on ratings of 17 video-recorded SCID–5–AMPD I interviews by five raters; and test–retest IRR based on interviews of 33 patients administered by two different raters within a short interval. For the video-based investigation, intraclass correlation coefficient (ICC) values ranged from . 77 to . 94 for subdomains, . 89 to . 95 for domains, and . 96 for total LPFS. For the test–retest investigation, ICC ranged from . 24 to . 72 for subdomains, . 59 to . 90 for domains, and . 75 for total LPFS. The test–retest study revealed questionable reliability estimates for some subdomains. However, overall the level of personality functioning was measured with a sufficient degree of IRR when assessed by the SCID–5–AMPD I.
Synthesis, Molecular Docking and Anticancer Activity of Diflunisal Derivatives as Cyclooxygenase Enzyme Inhibitors

Cyclooxygenase enzymes play a vital role in inflammatory pathways in the human body. Apart from their relation with inflammation, the additional involvement of COX-2 enzyme with cancer activity was recently discovered. In some cancer types the level of COX-2 enzyme is increased indicating that this enzyme could be a suitable target for cancer therapy. Based on these findings, we have synthesized some new diflunisal thiosemicarbazides and 1,2,4-triazoles and tested them against androgen-independent prostate adenocarcinoma (PC-3), colon carcinoma (HCT-116), human breast cancer (T47D), breast carcinoma (MCF7) and human embryonic kidney (HEK-293) cell lines. Specifically, the diflunisal and thiosemicarbazide functionality are combined during the synthesis of original compounds anticipating a potency enhancement. Compounds 6, 10, 15 and 16 did not show cytotoxic effects for the HEK293 cell line. Among them, compounds 15 and 16 demonstrated anticancer activity for the breast cancer cell line T47D, whereas compounds 6 and 10 which are thiosemicarbazide derivatives displayed anti-tumourigenic activity against the PC-3 cell line, consistent with the literature. However, no activity was observed for the HCT-116 cancer cell line with the tested thiosemicarbazide derivatives. Only compound 16 displayed activity against the HCT-116 cell line. Therefore, it was speculated that the diflunisal and thiosemicarbazide functionalities potentiate anticancer activity on prostate cancer and the thiosemicarbazide functionality decreases the anticancer activity of diflunisal on colon cancer cell lines. In order to gain insight into the anticancer activity and COX-2 inhibition, molecular docking studies were carried out for COX-1 and COX-2 enzymes utilizing the newly synthesized compounds 15, and 16. Both 15 and 16 showed high selectivity and affinity toward COX-2 isozyme over COX-1, which is in agreement with the experimental results.
Circulating eosinophil levels do not predict severe exacerbations in COPD: a retrospective study

Whether the level of circulating eosinophils in chronic obstructive pulmonary disease (COPD) patients can predict the risk of exacerbations of COPD (ECOPD) or response to treatment is debated. Here, we evaluate the prevalence of elevated eosinophils in COPD patients and its relationship with severe ECOPD requiring hospitalisation. We retrospectively reviewed the charts of COPD patients hospitalised in our centre between January 1, 2005 and November 30, 2015 because of ECOPD or other reasons (controls). In a second analysis, the ECOPD patients were divided into two subgroups based on having ECOPD in the next year after the index event or not. Circulating eosinophils, both during clinical stability and hospitalisation, as well as clinical and functional data and the relation to recurrent exacerbations were analysed. We studied 992 COPD patients (318 ECOPD patients and 674 controls). Among ECOPD patients, 121 had one or more ECOPD during the year after the index event. The prevalence of eosinophils ≥2% was 72% in ECOPD patients and 71% in controls (p=0.93). Among ECOPD patients, eosinophil levels ≥2%, ≥4% or ≥300 cells·μL−1, either when clinically stable or during hospitalisation, did not show a significant association with the rate of recurrent severe exacerbations. The severity of airflow limitation was associated with recurrent exacerbations, but inhaled corticosteroid treatment was not. The majority of COPD patients have circulating eosinophils >2% and a significant association with the risk of severe ECOPD or response to inhaled corticosteroids was not demonstrated. Eosinophil levels are not associated with increased risk of future severe COPD exacerbation and treatment with ICSs does not show a significant association with risk reduction of severe exacerbation in patients with low or high circulating eosinophils http://ow.ly/Cc8W30kuPWr
Stable isotope signatures of meteoric water in the Cuvelai-Etosha Basin, Namibia: Seasonal characteristics, trends and relations to southern African patterns

ABSTRACT The study area is the Namibian part of the Cuvelai-Etosha Basin (CEB), located in central northern Namibia. The CEB is home to 40 % of Namibia’s population, and most of the people live in rural areas. These people depend on both surface and groundwater resources which are limited in this dryland (mean annual rainfall ranging from 250 to 550 mm/a). The isotopic signatures of δ18O and δ2H from water samples (n = 61) collected over a course of 9 years from various research projects and existing (but mainly unpublished) data of meteoric water of the CEB (10 sites) were evaluated and local meteoric water lines (LMWLs) developed. Further, the data is discussed in the context of seasonal characteristics and trends and compared to available data from the Global Network of Isotopes in Precipitation (GNIP) for the southern African region. Our results extend the portfolio of previously published LMWLs for southern Africa and provide a more precise baseline for any isotope-based study in that region. The slope of the LMWL from the GNIP stations correlates with latitude. This correlation cannot be found within the CEB. The dominant control on the isotopic signature of the CEB of precipitation is seasonal.
Unexpected prion phenotypes in experimentally transfused animals: predictive models for humans?

ABSTRACT The recently reevaluated high prevalence of healthy carriers (1/2,000 in UK) of variant Creutzfeldt-Jakob Disease (v-CJD), whose blood might be infectious, suggests that the evolution of this prion disease might not be under full control as expected. After experimental transfusion of macaques and conventional mice with blood derived from v-CJD exposed (human and animal) individuals, we confirmed in these both models the transmissibility of v-CJD, but we also observed unexpected neurological syndromes transmissible by transfusion: despite their prion etiology confirmed through transmission experiments, these original cases would escape classical prion diagnosis, notably in the absence of detectable abnormal PrP with current techniques. It is noteworthy that macaques developed an original, yet undescribed myelopathic syndrome associating demyelination and pseudo-necrotic lesions of spinal cord, brainstem and optical tract without affecting encephalon, which is rather evocative of spinal cord disease than prion disease in human medicine. These observations strongly suggest that the spectrum of human prion diseases may extend the current field restricted to the phenotypes associated to protease-resistant PrP, and may notably include spinal cord diseases.
Endoscopic management and follow-up of patients with a submucosal esophageal adenocarcinoma

Introduction The risk of lymph node metastases (LNM) in submucosal esophageal adenocarcinoma (EAC) patients is subject to debate. These patients might be treated endoscopically if the risk of LNM appears to be low. Objective The objective of this article is to evaluate the outcome of patients who underwent an endoscopic resection (ER) and subsequent endoscopic follow-up for a submucosal EAC. Methods All patients who underwent ER for submucosal EAC between January 2012 and August 2016 and were subsequently managed with endoscopic follow-up were retrospectively identified. Primary outcome was the number of patients diagnosed with LNM; secondary outcomes included intraluminal recurrences. Results Thirty-five patients (median age 68 years) were included: 17 low-risk (submucosal invasion <500 microns, G1–G2, no lymphovascular invasion (LVI)), and 18 high-risk (submucosal invasion >500 microns, and/or G3–G4, and/or LVI, and/or a tumor-positive deep resection margin (R1)) EACs. After a median follow-up of 23 (IQR 15–43) months, in which patients underwent a median of six (IQR 4–8) endoscopies and a median of four (IQR 2–8) endoscopic ultrasound procedures, none of the included patients were diagnosed with LNM. Five (14%) patients developed a local intraluminal recurrence a median of 18 (IQR 11–21) months after baseline ER that were treated endoscopically. Conclusions In 35 patients with a submucosal EAC, no LNM were found during a median follow-up of 23 months. Endoscopic therapy may be an alternative for surgery in selected patients with a submucosal EAC.
Prognostic role of chromogranin A in castration-resistant prostate cancer: a meta-analysis

We aimed to investigate the prognostic value of chromogranin A (CgA) in castration-resistant prostate cancer (CRPC). We conducted a systematic literature search of PubMed, Web of Science, and EMBASE for citations published prior to September 2017 that described CgA and CRPC and performed a standard meta-analysis on survival outcomes. Our meta-analysis included eight eligible studies with 686 patients. The results were as follows: progression-free survival (PFS) was associated with CgA level (hazard ratio [HR] = 2.47, 95% confidence interval [CI]: 1.47–4.14, P = 0.0006); PFS was relative to CgA change (HR = 9.22, 95% CI: 3.03–28.05, P < 0.0001); and overall survival (OS) was relative to CgA level (HR = 1.47, 95% CI: 1.15–1.87, P = 0.002). When we divided the patients into two groups according to therapy status, the result for OS relative to CgA level was an HR of 1.26 (95% CI: 1.09–1.45, P = 0.001) in the first-line hormonal therapy group, and an HR of 2.33 (95% CI: 1.40–3.89, P = 0.001) in the second-line hormonal therapy or chemotherapy group. This meta-analysis indicated that a high CgA level had a negative influence on OS and PFS in CRPC patients. In addition, CRPC patients with a rising CgA had a shorter PFS. Further studies are needed to verify the prognostic value of CgA in CRPC.
Retention of Knowledge Levels of Health Care Providers in Cancer Screening Through Telementoring

Purpose Every year > 450,000 individuals are diagnosed with cancer and approximately 350,000 die of it in India. The Ministry of Health and Family Welfare has released an Operational Framework for the Management of Common Cancers that highlights population-based cancer screening programs in primary health care facilities by health care providers (HCPs) and capacity building of HCPs. The purpose of this study is to present a low-cost training model that is highly suitable for resource-deficient settings, such as those found in India, through Extension for Community Health Outcome (ECHO), a knowledge-sharing tool, to enable high-quality training of HCPs. Materials and Methods An in-person, 3-day training program was conducted for 27 HCPs in the tribal primary health care center of Gumballi in Karnataka, India, to teach the basics of cancer screening in oral, breast, and cervical cancer. The training of HCPs was done using the ECHO platform while they implemented the cancer screening, thus enabling them to build the much needed knowledge and skill set to conduct cancer screening in their respective communities. Results The knowledge level of the HCPs was tracked before the intervention, immediately after the 3-day training program, and 6 months after the ECHO intervention, which clearly showed progressive acquisition and retention of knowledge. A marked improvement in knowledge level score from an average of 6.3 to 13.7 on a 15-point scale was noticed after the initial in-person training. The average knowledge further increased to a score of 14.4 after 6 months as a result of training using the ECHO platform. Conclusion ECHO is an affordable and effective model to train HCPs in cancer screening in a resource-constrained setting.
Uncertainty Quantification for Online Learning and Stochastic Approximation via Hierarchical Incremental Gradient Descent

Stochastic gradient descent (SGD) is an immensely popular approach for online learning in settings where data arrives in a stream or data sizes are very large. However, despite an ever- increasing volume of work on SGD, much less is known about the statistical inferential properties of SGD-based predictions. Taking a fully inferential viewpoint, this paper introduces a novel procedure termed HiGrad to conduct statistical inference for online learning, without incurring additional computational cost compared with SGD. The HiGrad procedure begins by performing SGD updates for a while and then splits the single thread into several threads, and this procedure hierarchically operates in this fashion along each thread. With predictions provided by multiple threads in place, a t-based confidence interval is constructed by decorrelating predictions using covariance structures given by a Donsker-style extension of the Ruppert--Polyak averaging scheme, which is a technical contribution of independent interest. Under certain regularity conditions, the HiGrad confidence interval is shown to attain asymptotically exact coverage probability. Finally, the performance of HiGrad is evaluated through extensive simulation studies and a real data example. An R package higrad has been developed to implement the method.