Miracle-dz/UniFAR-FTUs huggingface dataset:
The cost-effectiveness of a bedaquiline-containing short-course regimen for the treatment of multidrug-resistant tuberculosis in South Africa

ABSTRACT Background: Bedaquiline-containing regimens have demonstrated improved outcomes over injectable-containing regimens in the long-term treatment of multidrug-resistant tuberculosis (MDR-TB). Recently, the World Health Organization (WHO) recommended replacing injectables in the standard short-course regimen (SCR) with a bedaquiline-containing regimen. The South African national TB program similarly recommends a bedaquiline-containing regimen. Here, we investigated the cost-effectiveness of a bedaquiline-containing SCR versus an injectable-containing SCR for the treatment of MDR-TB in South Africa. Methods: A Markov model was adapted to simulate the incidence of active patients with MDR-TB. Patients could transition through eight health states: active MDR-TB, culture conversion, cure, follow-up loss, secondary MDR-TB, extensively DR-TB, end-of-life care, and death. A 5% discount was assumed on costs and outcomes. Health outcomes were expressed as disability-adjusted life years (DALYs). Results: Over a 10-year time horizon, a bedaquiline-containing SCR dominated an injectable-containing SCR, with an incremental saving of US $982 per DALY averted. A bedaquiline-containing SCR was associated with lower total costs versus an injectable-containing SCR (US $597 versus $657 million), of which US $3.2 versus $21.9 million was attributed to adverse event management. Conclusions: Replacing an injectable-containing SCR with a bedaquiline-containing SCR is cost-effective, offering a cost-saving alternative with improved patient outcomes for MDR-TB.
Lipid profile changes during the menopausal transition.

OBJECTIVES There is evidence that the menopausal transition in women is accompanied by changes in the metabolic profile. We evaluated the lipid profile during the perimenopause to postmenopause transition and its association with menopausal status. METHODS This is a retrospective observational study of laboratory studies from women presenting to the gynecology unit of Hospital Quirón Salud, Madrid (2007-2018) with irregular menstruation, amenorrhea or menopausal symptoms. Inclusion criteria were one or more blood samples with determinations of fasting glucose and lipids (total cholesterol, low-density lipoprotein cholesterol [LDL-c], high-density lipoprotein cholesterol [HDL-c] and triglycerides [TGs]) from women with a menopause diagnosis recorded in the hospital database. The determinations were classified as perimenopausal or postmenopausal based on the date of last menstruation. RESULTS In total, 13,517 laboratory studies (3,073 perimenopausal and 10,444 postmenopausal) from 275 women were analyzed. Total cholesterol, LDL-c, and TG levels were significantly higher in postmenopausal women than in perimenopausal women, whereas HDL-c levels were significantly lower (P < 0.05 in all cases). Further adjustment by age showed differences only in LDL-c levels. Menopausal status, TG levels, and the number of pregnancies were independently related with total cholesterol and LDL-c levels. HDL-c levels were independently affected by menopausal age, TG levels, and number of pregnancies. Finally, TG concentration was independently affected by total cholesterol, LDL-c, and HDL-c levels. CONCLUSION Our study suggests that significant changes in LDL-c levels occur during the menopausal transition. Total cholesterol and LDL-c changes are independently affected by menopausal status and HDL-c is influenced by menopausal age.
Be Afraid, Be Very Afraid! Motivated Intergroup Emotion Regulation

Group-based emotions can shape group members’ behaviors and intergroup relations. Therefore, we propose that people may try to regulate emotions of outgroup members to attain ingroup goals. We call this phenomenon “motivated intergroup emotion regulation. ” In four studies, conducted in both hypothetical and real-world contexts, we show that deterrence and reconciliation goals influence how fearful or calm people want outgroup members to feel, respectively. We further show that such motivated intergroup emotion regulation can guide behavior toward the outgroup, influencing how outgroup members feel (Studies 1, 2, and 4) and behave (Study 4). We demonstrate how affiliation with the ingroup, which renders ingroup goals more salient, shapes what ingroup members want outgroup members to feel (Studies 3 and 4) and subsequently how outgroup members feel and behave (Study 4). Finally, we discuss how motivated intergroup emotion regulation might contribute to understanding motivation in emotion regulation, group-based emotions, and intergroup relations.
Myocardial fibrosis in athletes—Current perspective

Abstract Several previous studies suggested that prolonged and extensive physical activity might lead to increased prevalence of myocardial fibrosis in athletes. The review summarizes these studies focusing on common patterns of myocardial fibrosis observed in athletes, their potential causes and significance. It also presents recent research on parametric imaging shedding new light on diffuse myocardial fibrosis in athletes. Finally, it reviews how these traditional and novel cardiac magnetic resonance (CMR) techniques can be incorporated in the diagnostic work up to differentiate athlete's heart from cardiomyopathies.
Brain manganese and the balance between essential roles and neurotoxicity

Manganese (Mn) is an essential micronutrient required for the normal development of many organs, including the brain. Although its roles as a cofactor in several enzymes and in maintaining optimal physiology are well-known, the overall biological functions of Mn are rather poorly understood. Alterations in body Mn status are associated with altered neuronal physiology and cognition in humans, and either overexposure or (more rarely) insufficiency can cause neurological dysfunction. The resultant balancing act can be viewed as a hormetic U-shaped relationship for biological Mn status and optimal brain health, with changes in the brain leading to physiological effects throughout the body and vice versa. This review discusses Mn homeostasis, biomarkers, molecular mechanisms of cellular transport, and neuropathological changes associated with disruptions of Mn homeostasis, especially in its excess, and identifies gaps in our understanding of the molecular and biochemical mechanisms underlying Mn homeostasis and neurotoxicity.
Safety and immunogenicity of a novel quadrivalent subunit influenza vaccine in animal models

ABSTRACT Background: Compared with trivalent influenza vaccines, quadrivalent influenza vaccines are expected to provide wider protection against influenza B virus infections. We developed a novel quadrivalent subunit influenza vaccine which was distinct from the influenza vaccines available on the market in production process. In this research, we evaluated the safety and immunogenicity of the quadrivalent subunit influenza vaccine in animal models. Methods: In toxicity assessment, 40 SD rats were randomly assigned to be intramuscularly injected with 1.0 ml of the tested vaccine (33 μg/ml) or 0.9% sodium chloride solution. In irritation assessment, eight rabbits were randomly assigned to receive 0.5 ml of tested vaccine or phosphate buffer solution intramuscularly. Thirty-two guinea pigs were randomly assigned to be intramuscularly injected with high-dose tested vaccine (0.5 ml), low-dose tested vaccine (0.05 ml), ovalbumin, or 0.9% sodium chloride solution, respectively, for sensitization assessment. In immunogenicity assessment, 50 BALB/c mice were equally randomized to receive one dose of tested vaccine, two doses of tested vaccine with an interval of 14 days, 0.5 ml of trivalent subunit influenza vaccine, 0.5 ml of monovalent subunit influenza vaccine, or 0.5 ml of phosphate buffer solution. Orbital blood was collected before and 28 and 42 days after administration of the injections for detecting influenza antibody titers. Results: No abnormal toxicity and irritation in rats and rabbits showed in the gross autopsy and histopathological examinations. The results of sensitization in guinea pigs indicated that no obvious allergic symptoms observed in the high-dose and low-dose vaccine groups within 30 min after twice provocations, and the result of sensitization evaluation was negative. Vaccine induced significant immune responses in mice with 100% seroconversion rates at 28 and 42 days after the first dose. The geometric mean titers (GMTs) of hemagglutination inhibition (HI) antibodies at day 28 in one-dose quadri–vaccine and two-dose quadri–vaccine groups were comparable to those in the tri–vaccine or mono-vaccine groups for shared influenza strains. However, the GMTs of HI antibodies against H1N1 (P = 0.025) and BV (P = 0.049) at day 42 in one-dose quadri–vaccine group were significantly lower than those in the tri–vaccine or mono-vaccine groups. The GMTs of HI antibodies against H1N1, H3N1, BY, and BV at day 28 and day 42 were comparable between one-dose quadri–vaccine and two-dose quadri–vaccine groups. Conclusions: The quadrivalent subunit influenza vaccine was safe and immunogenic in animal models. One dose of the vaccine could elicit a satisfactory antibody response in mice.
Does the Evidence Support the Existence of the Simian Polyomavirus SV40 Vp4 Viroporin?

The simian polyomavirus SV40 was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3. Since a missense mutation of the putative Vp4 start codon (Vp2M228I) was found to give reduced progeny release and delayed lysis, Vp4 was claimed to be a viroporin. However, two independent research groups, including our own, were unable to replicate these findings. In contrast, we found no Vp4 expression in SV40-infected cells and no reduction in progeny release for Vp4-deficient virus, and finally, we found that the single amino acid substitution unavoidably introduced into the overlapping Vp2/Vp3 genes during Vp4 mutagenesis reduced early steps but not virus release. ABSTRACT The simian polyomavirus SV40 was reported to express Vp4, an N-terminally truncated form of the minor capsid proteins Vp2 and Vp3. Since a missense mutation of the putative Vp4 start codon (Vp2M228I) was found to give reduced progeny release and delayed lysis, Vp4 was claimed to be a viroporin. However, two independent research groups, including our own, were unable to replicate these findings. In contrast, we found no Vp4 expression in SV40-infected cells and no reduction in progeny release for Vp4-deficient virus, and finally, we found that the single amino acid substitution unavoidably introduced into the overlapping Vp2/Vp3 genes during Vp4 mutagenesis reduced early steps but not virus release. Remarkably, the existence of the viroporin Vp4 still seems to be widely accepted, which presumably is preventing important research on polyomavirus release. With this perspective, we will review and comment on the most important experiments that led to the disputed announcement of the viroporin Vp4.
Virtual screening web servers: designing chemical probes and drug candidates in the cyberspace

Abstract The interplay between life sciences and advancing technology drives a continuous cycle of chemical data growth; these data are most often stored in open or partially open databases. In parallel, many different types of algorithms are being developed to manipulate these chemical objects and associated bioactivity data. Virtual screening methods are among the most popular computational approaches in pharmaceutical research. Today, user-friendly web-based tools are available to help scientists perform virtual screening experiments. This article provides an overview of internet resources enabling and supporting chemical biology and early drug discovery with a main emphasis on web servers dedicated to virtual ligand screening and small-molecule docking. This survey first introduces some key concepts and then presents recent and easily accessible virtual screening and related target-fishing tools as well as briefly discusses case studies enabled by some of these web services. Notwithstanding further improvements, already available web-based tools not only contribute to the design of bioactive molecules and assist drug repositioning but also help to generate new ideas and explore different hypotheses in a timely fashion while contributing to teaching in the field of drug development.
Platelet Counting: Ugly Traps and Good Advice. Proposals from the French-Speaking Cellular Hematology Group (GFHC)

Despite the ongoing development of automated hematology analyzers to optimize complete blood count results, platelet count still suffers from pre-analytical or analytical pitfalls, including EDTA-induced pseudothrombocytopenia. Although most of these interferences are widely known, laboratory practices remain highly heterogeneous. In order to harmonize and standardize cellular hematology practices, the French-speaking Cellular Hematology Group (GFHC) wants to focus on interferences that could affect the platelet count and to detail the verification steps with minimal recommendations, taking into account the different technologies employed nowadays. The conclusions of the GFHC presented here met with a "strong professional agreement" and are explained with their rationale to define the course of actions, in case thrombocytopenia or thrombocytosis is detected. They are proposed as minimum recommendations to be used by each specialist in laboratory medicine who remains free to use more restrictive guidelines based on the patient’s condition.
HMGA2 mediated epigenetic regulation of Gata6 controls epithelial WNT signaling during lung development

Organ regeneration requires a proper balance between self-renewal and differentiation of tissue specific progenitor cells. Progenitor expansion and differentiation recapitulate many of the mechanisms regulating embryonic development. Here, we uncovered the role of the high mobility group AT-hook protein 2 (HMGA2) as a key regulator of epithelial differentiation during embryonic lung development. Hmga2 loss-of-function increased WNT signaling resulting not only in defective epithelial differentiation but also expansion of progenitors in the developing lung. We found that HMGA2 direct regulation of Gata6 is crucial in fine-tuning WNT signaling in airway epithelium. Furthermore, we combined proteomic, ChIP-seq, and transcriptome data to show that HMGA2-induced transcription requires phosphorylation of the histone variant H2AX at S139 (H2AXS139ph; γ-H2AX) mediated by the protein kinase ataxia telangiectasia mutated (ATM). The interplay between HMGA2, ATM, and H2AX is a novel mechanism of transcription initiation. Our results also link H2AXS139ph to transcription, assigning a new function for this DNA damage marker. Together, our data demonstrate that HMGA2-mediated changes in chromatin structure regulate WNT signaling and control the balance between progenitor expansion and differentiation required for proper lung development. Ref: Singh I, et al., (2015) Cell Research; Jul;25(7):837-50 Singh I, et al., (2014) BMC Biol; Mar 24;12:21 Ozturk N, Singh I, et al., (2014) Front Cell Dev Biol.; Mar 6;2:5
Emerging MRI Techniques to Redefine Treatment Response in Patients With Glioblastoma

Glioblastoma is the most common and most malignant primary brain tumor. Despite aggressive multimodal treatment, its prognosis remains poor. Even with continuous developments in MRI, which has provided us with newer insights into the diagnosis and understanding of tumor biology, response assessment in the posttherapy setting remains challenging. We believe that the integration of additional information from advanced neuroimaging techniques can further improve the diagnostic accuracy of conventional MRI. In this article, we review the utility of advanced neuroimaging techniques such as diffusion‐weighted imaging, diffusion tensor imaging, perfusion‐weighted imaging, proton magnetic resonance spectroscopy, and chemical exchange saturation transfer in characterizing and evaluating treatment response in patients with glioblastoma. We will also discuss the existing challenges and limitations of using these techniques in clinical settings and possible solutions to avoiding pitfalls in study design, data acquisition, and analysis for future studies.
Descripción de un caso de sarcoidosis liquenoide con hallazgos clínicos e histopatológicos característicos

Sarcoidosis is a multisystem inflammatory disease characterized by the formation of noncaseating granulomas in various organs and tissues. The majority of patients with systemic sarcoidosis will present with lung and lymph node involvement. In addition, 20% have skin involvement that may be the only manifestation of the disease or may be an important prognostic marker for involvement of other organs. There are multiple forms of presentation of cutaneous sarcoidosis, which may be a true challenge.We report a patient with a one month history of an eruption of skin colored papules. Some were grouped in a symmetrical distribution on the trunk, inner arms, and lumbar region. Pathologic examination revealed an infiltrate in the papillary dermis showing a band of noncaseating granulomas along with disruption of the basal lamina and lichenoid changes. The clinicopathological correlation confirmed the diagnosis of lichenoid sarcoidosis. We consider our case interesting owing to the clinical presentation and the lichenoid distribution of granulomas.
A Parallel Evolutionary Computing-Embodied Artificial Neural Network Applied to Non-Intrusive Load Monitoring for Demand-Side Management in a Smart Home: Towards Deep Learning

Non-intrusive load monitoring (NILM) is a cost-effective approach that electrical appliances are identified from aggregated whole-field electrical signals, according to their extracted electrical characteristics, with no need to intrusively deploy smart power meters (power plugs) installed for individual monitored electrical appliances in a practical field of interest. This work addresses NILM by a parallel Genetic Algorithm (GA)-embodied Artificial Neural Network (ANN) for Demand-Side Management (DSM) in a smart home. An ANN’s performance in terms of classification accuracy depends on its training algorithm. Additionally, training an ANN/deep NN learning from massive training samples is extremely computationally intensive. Therefore, in this work, a parallel GA has been conducted and used to integrate meta-heuristics (evolutionary computing) with an ANN (neurocomputing) considering its evolution in a parallel execution relating to load disaggregation in a Home Energy Management System (HEMS) deployed in a real residential field. The parallel GA that involves iterations to excessively cost its execution time for evolving an ANN learning model from massive training samples to NILM in the HEMS and works in a divide-and-conquer manner that can exploit massively parallel computing for evolving an ANN and, thus, reduce execution time drastically. This work confirms the feasibility and effectiveness of the parallel GA-embodied ANN applied to NILM in the HEMS for DSM.
Micronutrient Consequences of Long Term Proton Pump Inhibitor Therapy

Proton pump inhibitors (PPIs) are currently the mainstay of treatment for gastro-oesophageal reflux disease, peptic ulcer disease and dyspepsia. In this area, they have enjoyed remarkable success and there are many patients worldwide who use PPIs on a long-term basis. In recent years concerns regarding adverse effects of PPIs have emerged frequently in the medical literature with several small and large scale studies conducted to look into this. The main areas of interest have been increased risk of neuroendocrine tumours, increased risk of dementia, increased risk of infections (enteric, pneumonia, Clostridium difficle ), cardiovascular, renal and lower gastrointestinal side effects and effects on mineral and vitamin metabolism. In this review article, we focus mainly on the metabolic consequences of long term PPI therapy.
A Gene-Set Enrichment and Protein–Protein Interaction Network-Based GWAS with Regulatory SNPs Identifies Candidate Genes and Pathways Associated with Carcass Traits in Hanwoo Cattle

Non-synonymous SNPs and protein coding SNPs within the promoter region of genes (regulatory SNPs) might have a significant effect on carcass traits. Imputed sequence level data of 10,215 Hanwoo bulls, annotated and filtered to include only regulatory SNPs (450,062 SNPs), were used in a genome-wide association study (GWAS) to identify loci associated with backfat thickness (BFT), carcass weight (CWT), eye muscle area (EMA), and marbling score (MS). A total of 15, 176, and 1 SNPs were found to be significantly associated (p < 1.11 × 10−7) with BFT, CWT, and EMA, respectively. The significant loci were BTA4 (CWT), BTA6 (CWT), BTA14 (CWT and EMA), and BTA19 (BFT). BayesR estimated that 1.1%~1.9% of the SNPs contributed to more than 0.01% of the phenotypic variance. So, the GWAS was complemented by a gene-set enrichment (GSEA) and protein–protein interaction network (PPIN) analysis in identifying the pathways affecting carcass traits. At p < 0.005 (~2,261 SNPs), 25 GO and 18 KEGG categories, including calcium signaling, cell proliferation, and folate biosynthesis, were found to be enriched through GSEA. The PPIN analysis showed enrichment for 81 candidate genes involved in various pathways, including the PI3K-AKT, calcium, and FoxO signaling pathways. Our finding provides insight into the effects of regulatory SNPs on carcass traits.
Roles for Event Representations in Sensorimotor Experience, Memory Formation, and Language Processing

The unifying theme for the papers in this volume is that event-predictive representations play an important role in cognitive processes, and they are a particularly fruitful object of study for cognitive scientists. In this paper, we present our own model of event representations that draws together several disparate strands of research into event representations, relating to event perception, event encodings in working memory and their role in prediction, and events as they are reported in language. Our main claim is that the notion of deictic routines originally developed by Ballard et al. (1997) is of great use in explaining how these different types of event representation interface with one another.