Miracle-dz/UniFAR-FTUs huggingface dataset:
Upregulation of Human Endogenous Retrovirus-K Is Linked to Immunity and Inflammation in Pulmonary Arterial Hypertension

Background: Immune dysregulation has been linked to occlusive vascular remodeling in pulmonary arterial hypertension (PAH) that is hereditary, idiopathic, or associated with other conditions. Circulating autoantibodies, lung perivascular lymphoid tissue, and elevated cytokines have been related to PAH pathogenesis but without a clear understanding of how these abnormalities are initiated, perpetuated, and connected in the progression of disease. We therefore set out to identify specific target antigens in PAH lung immune complexes as a starting point toward resolving these issues to better inform future application of immunomodulatory therapies. Methods: Lung immune complexes were isolated and PAH target antigens were identified by liquid chromatography tandem mass spectrometry, confirmed by enzyme-linked immunosorbent assay, and localized by confocal microscopy. One PAH antigen linked to immunity and inflammation was pursued and a link to PAH pathophysiology was investigated by next-generation sequencing, functional studies in cultured monocytes and endothelial cells, and hemodynamic and lung studies in a rat. Results: SAM domain and HD domain-containing protein 1 (SAMHD1), an innate immune factor that suppresses HIV replication, was identified and confirmed as highly expressed in immune complexes from 16 hereditary and idiopathic PAH versus 12 control lungs. Elevated SAMHD1 was localized to endothelial cells, perivascular dendritic cells, and macrophages, and SAMHD1 antibodies were prevalent in tertiary lymphoid tissue. An unbiased screen using metagenomic sequencing related SAMHD1 to increased expression of human endogenous retrovirus K (HERV-K) in PAH versus control lungs (n=4). HERV-K envelope and deoxyuridine triphosphate nucleotidohydrolase mRNAs were elevated in PAH versus control lungs (n=10), and proteins were localized to macrophages. HERV-K deoxyuridine triphosphate nucleotidohydrolase induced SAMHD1 and proinflammatory cytokines (eg, interleukin 6, interleukin 1&bgr;, and tumor necrosis factor &agr;) in circulating monocytes, pulmonary arterial endothelial cells, and also activated B cells. Vulnerability of pulmonary arterial endothelial cells (PAEC) to apoptosis was increased by HERV-K deoxyuridine triphosphate nucleotidohydrolase in an interleukin 6-independent manner. Furthermore, 3 weekly injections of HERV-K deoxyuridine triphosphate nucleotidohydrolase induced hemodynamic and vascular changes of pulmonary hypertension in rats (n=8) and elevated interleukin 6. Conclusions: Our study reveals that upregulation of the endogenous retrovirus HERV-K could both initiate and sustain activation of the immune system and cause vascular changes associated with PAH.
The Uncertainty of Science and the Science of Uncertainty

Halfway through Roberto Bolano's chef d'oeuvre 2666 : A Novel (Farrar, Straus and Giroux, 2004), one character declares, “If you know, you know, if you do not know, you learn. ” In that book, 4 academics, a journalist, and several policemen search for the bizarre truth behind a horrific series
[High prevalence of overweight, obesity, insulin resistance and metabolic syndrome in rural children and adolescents].

BACKGROUND Childhood and adolescent obesity is a major public health problem in Chile. AIM To characterize cardiometabolic risk factors in a population of schoolchildren from Carahue, Chile. MATERIAL AND METHODS Cross-sectional assessment of 208 children aged 10.4 ± 1.0 years (106 women). A clinical evaluation was carried out including pubertal development according to Tanner and anthropometric parameters. A fasting blood sample was obtained to measure glucose, insulin and lipid profile. HOMA-IR and Quicki indices were calculated. Insulin resistance (IR) was established according to Burrows criteria and Barja criteria, previously proposed for the Chilean pediatric population. The metabolic syndrome (MetS) was established using the modified Cook criteria. RESULTS Thirty eight percent of children had overweight and 33.1% obesity. MetS was only observed in obese subjects and the frequency in this subgroup was 38%. The prevalence of IR was 51% according to the Burrows criteria and 19% according to Barja criteria. It was more common in participants who were overweight, obese or had abdominal obesity. Children with insulin resistance according to Barja criteria, had worse anthropometric measures than their counterparts without resistance. When Burrows criteria was used, no differences in anthropometric measures were observed between participants with or without resistance. The frequency of MetS was 26 and 18% in children with insulin resistance according to Barja and Burrows criteria, respectively. Insulin levels and insulin sensitivity indexes were positively correlated with anthropometric parameters. CONCLUSIONS There was a high prevalence of overweight, obesity and MetS in these participants. Our results suggest that the IR criteria according to Barja allows to identify cases with higher metabolic risk.
Development of a Novel Tool to Assess Intimate Partner Violence Against Transgender Individuals

Intimate partner violence (IPV) takes on unique dimensions when directed against transgender individuals, with perpetrators leveraging transphobia to assert power and control. Standard IPV measurement tools do not assess this type of IPV. Four questions to assess transgender-related IPV (T-IPV) were developed: (a) being forced to conform to an undesired gender presentation or to stop pursuing gender transition; (b) being pressured to remain in a relationship by being told no one would date a transgender person; (c) being “outed” as a form of blackmail; and (d) having transition-related hormones, prosthetics, or clothing hidden or destroyed. The T-IPV tool was administered to 150 female-to-male transmasculine individuals completing a study of cervical cancer screening in Boston from March 2015-September 2016. Construct validity was assessed by examining correlations between T-IPV and two validated screeners of other forms of IPV (convergent) and employment status and fruit consumption (divergent). The association between T-IPV and negative health outcomes (posttraumatic stress disorder [PTSD], depression, psychological symptoms, binge drinking, number of sexual partners, and sexually transmitted infection [STI] diagnosis) were also calculated. Lifetime T-IPV was reported by 38.9%, and 10.1% reported past-year T-IPV. T-IPV was more prevalent among those who reported lifetime physical (51.7% vs. 31.7%, p = .01) and sexual (58.7% vs. 19.4%, p < .001) IPV than those who did not. Lifetime T-IPV was associated with PTSD (adjusted odds ratio [AOR] = 2.23, 95% confidence interval [CI] = [1.04, 4.80]), depression (AOR = 2.70, 95% CI = [1.22, 5.96]), and psychological distress (AOR = 2.82, 95% CI = [1.10, 7.26]). The T-IPV assessment tool demonstrated adequate reliability and validity and measures a novel type of abuse that is prevalent and associated with significant mental health burden. Future work should further validate the measure and pilot it with male-to-female transfeminine individuals.
Frequent ice cream consumption is associated with reduced striatal response to receipt of an ice cream-based milkshake.

BACKGROUND Weight gain leads to reduced reward-region responsivity to energy-dense food receipt, and consumption of an energy-dense diet compared with an isocaloric, low-energy-density diet leads to reduced dopamine receptors. Furthermore, phasic dopamine signaling to palatable food receipt decreases after repeated intake of that food, which collectively suggests that frequent intake of an energy-dense food may reduce striatal response to receipt of that food. OBJECTIVE We tested the hypothesis that frequent ice cream consumption would be associated with reduced activation in reward-related brain regions (eg, striatum) in response to receipt of an ice cream-based milkshake and examined the influence of adipose tissue and the specificity of this relation. DESIGN Healthy-weight adolescents (n = 151) underwent fMRI during receipt of a milkshake and during receipt of a tasteless solution. Percentage body fat, reported food intake, and food craving and liking were assessed. RESULTS Milkshake receipt robustly activated the striatal regions, yet frequent ice cream consumption was associated with a reduced response to milkshake receipt in these reward-related brain regions. Percentage body fat, total energy intake, percentage of energy from fat and sugar, and intake of other energy-dense foods were not related to the neural response to milkshake receipt. CONCLUSIONS Our results provide novel evidence that frequent consumption of ice cream, independent of body fat, is related to a reduction in reward-region responsivity in humans, paralleling the tolerance observed in drug addiction. Data also imply that intake of a particular energy-dense food results in attenuated reward-region responsivity specifically to that food, which suggests that sensory aspects of eating and reward learning may drive the specificity.
Seeing red: diet and endometriosis risk.

Endometriosis is an estrogen-dependent chronic gynecologic disorder that significantly reduces the quality of life of affected women. Characterized by adhesions of endometrial fragments in extra-uterine sites (predominantly in the peritoneal cavity and ovary but occasionally on the diaphragm, liver, and abdominal wall), the condition occurs in ~10% of the general population and is associated with infertility, pelvic pain, and increased risks for ovarian and other cancers (1,2).
Preschoolers’ secure base script representations predict teachers’ ratings of social competence and externalizing behavior

ABSTRACT Recent meta-analyses have reported significant effects of attachment quality on social competence, mostly using observational assessments of attachment behavior to assess security. We analyze the associations between attachment security – assessed as a secure base script, and social competence with peers – measured by teachers’ ratings on two self-report instruments, in a Portuguese sample of 82 preschool children (34 boys and 48 girls). We also tested the association between children’s secure base script scores and teacher ratings for externalizing and internalizing symptomatology. Results show significant sex differences. Girls had higher scores on secure base script and were rated by teachers as more socially competent, while boys received higher ratings for aggressive/externalizing behaviors. Nonetheless, when the effect of child sex was controlled, attachment representations were positively associated with child social competence and negatively associated with ratings of externalizing behaviors.
Increased risk of pneumonia and bronchiolitis after bacterial colonization of the airways as neonates.

RATIONALE The frequency of pneumonia and bronchiolitis exhibits considerable variation in otherwise healthy children, and suspected risk factors explain only a minor proportion of the variation. We hypothesized that alterations in the airway microbiome in early life may be associated with susceptibility to pneumonia and bronchiolitis in young children. OBJECTIVES To investigate the relation between neonatal airway colonization and pneumonia and bronchiolitis during the first 3 years of life. METHODS Participants comprised children of the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) cohort, a prospective birth cohort study of 411 children born to mothers with asthma. Aspirates from the hypopharynx at age 4 weeks were cultured for Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus. Clinical information on pneumonia and bronchiolitis within the first 3 years of life was prospectively collected by the research physicians at the center. Analyses were adjusted for covariates associated with pneumonia and bronchiolitis and bacterial airway colonization. MEASUREMENTS AND MAIN RESULTS Hypopharyngeal aspirates and full clinical follow-up until 3 years of age were available for 265 children. Of these, 56 (21%) neonates were colonized with S. pneumoniae, H. influenzae, and/or M. catarrhalis at 4 weeks of age. Colonization with at least one of these microorganisms (but not S. aureus) was significantly associated with increased incidence of pneumonia and bronchiolitis (adjusted incidence rate ratio, 1.79 [1.29-2.48]; P < 0.005) independently of concurrent or later asthma. CONCLUSIONS Neonatal airway colonization with S. pneumoniae, H. influenzae, or M. catarrhalis is associated with increased risk of pneumonia and bronchiolitis in early life independently of asthma. This suggests a role of pathogenic bacterial colonization of the airways in neonates for subsequent susceptibly to pneumonia and bronchiolitis.
Effects of varying radiation dosages on MMP1 expression, and MMP1 knockdown on the viability and migration of SW620 cells

Colorectal cancer (CRC), also known as bowel cancer, is one of the leading causes of cancer-associated mortality worldwide at present. The aim of the present study was to detect the effects of matrix metalloproteinase 1 (MMP1) on the viability and migration of a CRC cell line in the presence or absence of variation X-ray radiation doses. The CRC cell line, SW620, was cultured and treated with different X-ray doses (0, 0.1, 0.5, 1, 3 and 6 Gy). MMP1 expression was downregulated via the application of a specific small interfering (si)-RNA. The viability and migration of SW620 cells prior to and following transfection were detected with MTT and Transwell chamber assays, respectively. The application of siRNA transfection to silence MMP1 in SW620 cells resulted in reduced cell viability and migration (P<0.05). Compared with the control, the cell viability and migration of cells were significantly reduced when exposed to 0.5, 1, 3, and 6 Gy X-ray radiation (P<0.05). In SW620 cells treated with different X-ray doses, the mRNA expression levels of MMP1 were significantly reduced (P<0.05). Cells treated with 0.5 Gy X-ray exposure exhibited the lowest mRNA expression levels of MMP1 when compared with other doses of X-ray radiation. The expression of MMP1 was associated with the promotion of the viability and migration of SW620 cells. X-ray radiation with 6 Gy dosages significantly reduced cell viability when compared with the control. Thus, MMP1-targeted therapy combined with radiotherapy could be used for treating CRC.
Robust regression for optimal individualized treatment rules

Because different patients may respond quite differently to the same drug or treatment, there is an increasing interest in discovering individualized treatment rules. In particular, there is an emerging need to find optimal individualized treatment rules, which would lead to the “best” clinical outcome. In this paper, we propose a new class of loss functions and estimators based on robust regression to estimate the optimal individualized treatment rules. Compared to existing estimation methods in the literature, the new estimators are novel and advantageous in the following aspects. First, they are robust against skewed, heterogeneous, heavy‐tailed errors or outliers in data. Second, they are robust against a misspecification of the baseline function. Third, under some general situations, the new estimator coupled with the pinball loss approximately maximizes the outcome's conditional quantile instead of the conditional mean, which leads to a more robust optimal individualized treatment rule than the traditional mean‐based estimators. Consistency and asymptotic normality of the proposed estimators are established. Their empirical performance is demonstrated via extensive simulation studies and an analysis of an AIDS data set.
Extrahepatic Cancer Suppresses Nuclear Receptor–Regulated Drug Metabolism

Purpose: To determine the mechanisms by which tumors situated in extrahepatic sites can cause profound changes in hepatic drug clearance, contributing to altered drug response and chemotherapy resistance. Experimental Design: We studied in wild-type or transgenic CYP3A4 reporter mice implanted with the murine Engelbreth–Holm–Swarm sarcoma changes in nuclear receptor and hepatic transcription factor expression and/or function, particularly related to CYP3A gene regulation. Results: Repression of hepatic CYP3A induction was dramatic and associated with reduced levels of C/EBPβ isoforms, impaired pregnane X receptor, and constitutive androstane receptor function. Unexpectedly, extrahepatic tumors strongly reduced nuclear accumulation of retinoid X receptor alpha (RXRα) in hepatocytes, providing a potential explanation for impaired function of nuclear receptors that rely on RXRα dimerization. Profiling revealed 38 nuclear receptors were expressed in liver with 14 showing between 1.5- and four-fold reduction in expression in livers of tumor-bearing animals, including Car, Trβ, Lxrβ, Pparα, Errα/β, Reverbα/β, and Shp. Altered Pparα and γ induction of target genes provided additional evidence of perturbed hepatic metabolic control elicited by extrahepatic tumors. Conclusions: Extrahepatic malignancy can affect hepatic drug metabolism by nuclear receptor relocalization and decreased receptor expression and function. These findings could aid the design of intervention strategies to normalize drug clearance and metabolic pathways in cancer patients at risk of chemotherapy-induced toxicity or cancer cachexia. Clin Cancer Res; 17(10); 3170–80. ©2011 AACR.
Prediction Models for Early Childhood Obesity: Applicability and Existing Issues

Statistical models have been developed for the prediction or diagnosis of a wide range of outcomes. However, to our knowledge, only 7 published studies have reported models to specifically predict overweight and/or obesity in early childhood. These models were developed using known risk factors and vary greatly in terms of their discrimination and predictive capacities. There are currently no established guidelines on what constitutes an acceptable level of risk (i.e., risk threshold) for childhood obesity prediction models, but these should be set following consideration of the consequences of false-positive and false-negative predictions, as well as any relevant clinical guidelines. To date, no studies have examined the impact of using early childhood obesity prediction models as intervention tools. While these are potentially valuable to inform targeted interventions, the heterogeneity of the existing models and the lack of consensus on adequate thresholds limit their usefulness in practice.
The Impulse Response of Negatively Focused Spherical Ultrasound Detectors and Its Effect on Tomographic Optoacoustic Reconstruction

In optoacoustic tomography, negatively focused detectors have been shown to improve the tangential image resolution without sacrificing sensitivity. Since no exact inversion formulas exist for optoacoustic image reconstruction with negatively focused detectors, image reconstruction in such cases is based on using the virtual-detector approximation, in which it is assumed that the response of the negatively focused detector is identical, up to a constant time delay, to that of a point-like detector positioned in the detector’s center of curvature. In this paper, we analyze the response of negatively focused spherical ultrasound detectors in three dimensions and demonstrate how their properties affect the optoacoustic reconstruction. Our analysis sheds new light on commonly reported experimental reconstruction artifacts in optoacoustic systems that employ negatively focused detectors. Based on our analysis, we introduce a simple correction to the virtual-detector approximation that significantly enhances image contrast and reduces artifacts.
Access to emergency departments for acute events and identification of sickle cell disease in refugees.

Department of Medicine, University of Verona AOUI Verona, Verona, Italy; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Department of Epidemiology & Biostatistics, Imperial College, London, United Kingdom; Centro della Microcitemia, Ospedale Galliera, Genoa, Italy; Pediatric Haematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy; Department of Woman Child and General and Surgery, Università degli Studi della Campania L.Vanvitelli, Napoli, Italy; Medicina Interna, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico, Milano, Italy; Talassemia, Ospedale Garibaldi, Catania, Italy; Clinica Emato-Oncologica Pediatrica, Università di Padova, Padova, Italy; Campus of Hematogy , AOOR Villa Sofia-Cervello, Ematologia Azienza Ospedaliero-Universitaria "Policlinico-Vittorio Emanuele«, Catania, Italy; Ematologia con Talassemia, ARNAS Ospedale Civico Di Cristina, Palermo, Italy; Centro per la Cura delle Talassemie, Ospedale di Ragusa, Ragusa, Italy; USMAF SASN Sicilia, Ministero Della Salute, Catania, Italy; Ematologia con Talassemia, ARNAS Ospedale Civico Di Cristina, Palermo, Italy.
Kinematic and kinetic differences in block and split-stance standing starts during 30 m sprint-running

Abstract This study aimed to understand the kinematic and kinetic differences between two sprint starts: block and split-stance standing. Fourteen sub-elite male sprinters (100 m time: 11.40 ± 0.39 s) performed block and split-stance standing starts sprints over 30 m of in-ground force platforms in a randomised order. Independent t-tests and repeated measures mixed model analysis of variance were used to analyse the between-condition variables across conditions, and over four step phases. Block start sprints resulted in significantly (p < .05) faster 5 m (5.0%, effect size [ES] = 0.89) and 10 m (3.5%, ES = 0.82) times, but no significant differences were found at 20 and 30 m. No significant differences were found in any kinematic measure between starting positions. However, block starts resulted in significantly (p < .001) greater propulsive impulses (6.8%, ES = 1.35) and net anterior-posterior impulses (6.5%, ES = 1.12) during steps 1–4, compared to the standing start. Block starts enable athletes to produce a greater amount of net anterior-posterior impulse during early accelerated sprinting, resulting in faster times up to 10 m. When seeking to improve initial acceleration performance, practitioners may wish to train athletes from a block start to improve horizontal force production.