Miracle-dz/UniFAR-FTUs huggingface dataset:
Hepatitis C virus protein interaction network for HCV clearance and association of DAA to HCC occurrence via data mining approach: A systematic review and critical analysis

HCV has been associated with a pro‐inflammatory state, which predisposes to hepatocellular carcinoma (HCC). However, the different molecular mechanisms underlying the effect of HCV infection on HCC progression remain unclear. Although HCV infection illustrates the potential role of host genetics in the outcome of infectious diseases, there is no clear overview of some single nucleotide polymorphisms (SNPs) influencing spontaneous or treatment‐induced HCV eradication. We studied the possible role of HCV infection in the processes of HCC initiation and performed a systematic analysis using data mining approaches to identify host polymorphisms associated with treatment response and HCC development using topological analysis of protein‐proteins interactions (PPI) networks. On the basis of our analysis performed, we identified key hub proteins related to HCV‐treatment response infection and to HCC development. Host genetic polymorphisms, such as inosine triphosphatase (ITPA), interferon, lambda 3 (IFNL3), Q5 interferon, lambda 4 (IFNL4), toll‐like receptors (TLRs) and interferon‐stimulated gene 15 (ISG‐15), were identified as key genes for treatment prediction and HCC evolution. By comparing unique genes for HCV‐treatment response and genes particular to HCV‐HCC development, we found a common PPI network that may participate in more extensive signalling processes during anti‐HCV treatment, which can play important roles in modulating the immune response to the occurrence of HCC. Data mining is an effective tool for identifying potential regulatory pathways involved in treatment response and HCC development. Our study may contribute to a better understanding of HCV immunopathogenesis and highlights the complex role of host genetics in HCV clearance.
The Epidemiology of Low Back Pain and Injury in Dance: A Systematic Review.

BACKGROUND Dance is a physical pursuit that involves loading the spine through repetitive dynamic movements and lifting tasks. As such, low back pain (LBP) and low back injury (LBI) have been identified as common health problems in contemporary and classical ballet dancers. However, clarity regarding the experience of LBP and LBI in dance is lacking. OBJECTIVES To systematically review and synthesize the epidemiology of LBP and LBI in dance populations. METHODS A comprehensive search of 6 electronic databases, back catalogs of dance science-specific journals, and reference lists of relevant articles and a forward citation search were performed. RESULTS Fifty full-text articles were included in the final systematic review. There was considerable methodological heterogeneity among the included studies. The median (range) point, yearly, and lifetime prevalence of LBP was 27% (17%-39%), 73% (41%-82%), and 50% (17%-88%), respectively. The lower back contributed to 11% (4%-22%) of time loss and 11% (5%-23%) of medical-attention injuries. CONCLUSION Dancers are vulnerable to LBP and LBI. The use of definitions that are sensitive to the complexity of LBP and LBI would facilitate improved understanding of the problem within dance, inform health care strategies, and allow for monitoring LBP-specific intervention outcomes. J Orthop Sports Phys Ther 2019;49(4):239-252. Epub 18 Jan 2019. doi:10.2519/jospt.2019. 8609.
Influence of Piracetam on Gliclazide—Glycated Human Serum Albumin Interaction. A Spectrofluorometric Study

Advanced Glycation End-Products (AGEs) are created in the last step of protein glycation and can be a factor in aging and in the development or worsening of many degenerative diseases (diabetes, chronic kidney disease, atherosclerosis, Alzheimer’s disease, etc.). Albumin is the most susceptible to glycation plasma protein. Modified albumin by AGEs may be more resistant to enzymatic degradation, which further increases the local accumulation of AGEs in tissues. The aim of the present study was to analyze in vitro glycation of serum albumin in the presence of piracetam (PIR) and the gliclazide (GLZ)-glycated albumin interaction. The analysis of PIR as an inhibitor and GLZ interaction with nonglycated human albumin (HSA) and glycated by fructose human albumin (gHSAFRC), in the absence and presence of piracetam (gHSAFRC-PIR), was performed by fluorescence quenching of macromolecules. On the basis of obtained data we concluded that under the influence of glycation, association constant (Ka) of gliclazide to human serum albumin decreases and GLZ binds to HSA with less strength than under physiological conditions. PIR strongly inhibited the formation of AGEs in the system where the efficiency of HSA glycation was the largest. The analysis of piracetam influence on the GLZ-glycated albumin interaction has shown that piracetam increases the binding strength of GLZ to glycated albumin and weakens its therapeutic effect. Based on the obtained data we concluded that monitoring therapy and precautions are required in the treatment when the combinations of gliclazide and piracetam are used at the same time.
WFSBP* and IAWMH** Guidelines for the treatment of alcohol use disorders in pregnant women

Abstract Objectives: These practice guidelines for the treatment of alcohol use disorders during pregnancy were developed by members of the International Task Force of the World Federation of Societies of Biological Psychiatry and the International Association for Women’s Mental Health. Methods: We performed a systematic review of all available publications and extracted data from national and international guidelines. The Task Force evaluated the data with respect to the strength of evidence for the efficacy and safety of each medication. Results and Discussion: There is no safe level of alcohol use during pregnancy. Abstinence is recommended. Ideally, women should stop alcohol use when pregnancy is planned and, in any case, as soon as pregnancy is known. Detecting patterns of alcohol maternal drinking should be systematically conducted at first antenatal visit and throughout pregnancy. Brief interventions are recommended in the case of low or moderate risk of alcohol use. Low doses of benzodiazepines, for the shortest duration, may be used to prevent alcohol withdrawal symptoms when high and chronic alcohol intake is stopped and hospitalisation is recommended. Due to the low level of evidence and/or to low benefit/risk ratio, pharmacological treatment for maintenance of abstinence should not be used during pregnancy. At birth, foetal alcohol spectrum disorders must be searched for, and alcohol metabolites should be measured in meconium of neonates in any doubt of foetal alcohol exposure.
Paving with Precast Concrete Made with Recycled Mixed Ceramic Aggregates: A Viable Technical Option for the Valorization of Construction and Demolition Wastes (CDW)

This research aimed to prove the feasibility of producing two types of precast elements widely used in construction, such as curbstones and paving blocks, using recycled concrete made with a 50% substitution of the natural gravel by recycled mixed aggregates with a significant ceramic content (>30%). In order to prove the quality of such mass concrete recycled precast elements, two different mixes were used: the first one was a conventional concrete mix provided by Prefabricados de Hormigón Pavimentos Páramo S.L. , one of the collaborating companies in this study, and the other was a mixture in which wt 50% of the natural coarse aggregates were substituted for recycled mixed aggregates ceramic (RMAc). This recycled aggregate is a heterogeneous mixture of unbound aggregates, concrete, ceramic, etc., used as a secondary recycled aggregate and commonly produced in a lot of recycling plants in many European countries. This material was supplied by Tecnología y Reciclado S.L. , the other collaborating company. Both mixtures were representative in order to establish the comparative behavior between them, taking into account that smaller percentages of replacement of the natural with recycled aggregates will also produce good results. This percentage of substitution represents a high saving of natural resources (gravel) and maintains a balanced behavior of the recycled concrete, so this new material can be considered to be a viable and reliable option for precast mass concrete paving elements. The characterization of the recycled precast elements, covering mechanical, microstructural, and durability properties, showed mostly similar behavior when compared to the analogous industrially-produced pieces made with conventional concrete.
Anti‐Inflammatory Effects of a Vegan Diet Versus the American Heart Association–Recommended Diet in Coronary Artery Disease Trial

Background Dietary interventions may play a role in secondary cardiovascular prevention. hsCRP (High‐sensitivity C‐reactive protein) is a marker of risk for major adverse cardiovascular outcomes in coronary artery disease. Methods and Results The open‐label, blinded end‐point, EVADE CAD (Effects of a Vegan Versus the American Heart Association‐Recommended Diet in Coronary Artery Disease) trial randomized participants (n=100) with coronary artery disease to 8 weeks of a vegan or American Heart Association–recommended diet with provision of groceries, tools to measure dietary intake, and dietary counseling. The primary end point was high‐sensitivity C‐reactive protein. A linear regression model compared end points after 8 weeks of a vegan versus American Heart Association diet and adjusted for baseline concentration of the end point. Significance levels for the primary and secondary end points were set at 0.05 and 0.0015, respectively. A vegan diet resulted in a significant 32% lower high‐sensitivity C‐reactive protein (β, 0.68, 95% confidence interval [0.49–0.94]; P=0.02) when compared with the American Heart Association diet. Results were consistent after adjustment for age, race, baseline waist circumference, diabetes mellitus, and prior myocardial infarction (adjusted β, 0.67 [0.47–0.94], P=0.02). The degree of reduction in body mass index and waist circumference did not significantly differ between the 2 diet groups (adjusted β, 0.99 [0.97–1.00], P=0.10; and adjusted β, 1.00 [0.98–1.01], P=0.66, respectively). There were also no significant differences in markers of glycemic control between the 2 diet groups. There was a nonsignificant 13% reduction in low‐density lipoprotein cholesterol with the vegan diet when compared with the American Heart Association diet (adjusted β, 0.87 [0.78–0.97], P=0.01). There were no significant differences in other lipid parameters. Conclusions In patients with coronary artery disease on guideline‐directed medical therapy, a vegan diet may be considered to lower high‐sensitivity C‐reactive protein as a risk marker of adverse outcomes. Clinical Trial Registration URL: http://www.clinicaltrials. gov. Unique identifier: NCT02135939.
Anatomic Features of the Tibial Plateau Predict Outcomes of ACL Reconstruction Within 7 Years After Surgery

Background: Multiple anatomic features of the femoral condyles and tibial plateau have been shown to influence knee biomechanics and risk of anterior cruciate ligament (ACL) injury. However, it remains unclear how these anatomic factors affect the midterm outcomes of ACL reconstruction. Hypothesis: Decreased femoral notch width, increased posterior and coronal slopes, and decreased concavity of the tibial plateau are associated with inferior clinical, patient-reported, and osteoarthritis-related outcomes 7 years after ACL reconstruction. Study Design: Cohort study; Level of evidence, 3. Methods: Prospectively collected data from 44 patients who did not have a subsequent graft or contralateral ACL failure within 7 years after unilateral ACL reconstruction were reviewed (mean ± SD age, 23.7 ± 9.2 years; 64% women). Notch width (after notchplasty), posterior slopes of the medial and lateral tibial plateau, maximum depth of the medial tibial plateau, and coronal tibial slope were measured from magnetic resonance images. Anatomic predictors of side-to-side differences in anterior-posterior knee laxity, Knee injury and Osteoarthritis Outcome Score (KOOS), medial joint space width, and side-to-side differences in Osteoarthritis Research Society International (OARSI) x-ray score, measured at 7 years, were identified with linear regression (bivariate) and stepwise regression (multivariate). Results: Increased posterior slope of the lateral tibial plateau was associated with increased side-to-side difference in knee laxity (bivariate model only), increased side-to-side difference in the OARSI score, and decreased KOOS subscores (R2 > .10, P < .05). Increased posterior slope of the medial tibial plateau was associated with a higher side-to-side difference in the OARSI x-ray score (bivariate model only) and lower KOOS subscores (R2 > .11, P < .03). Increased coronal tibial slope was associated with lower KOOS subscores (R2 > .11, P < .03). Decreased medial tibial depth was associated with increased knee laxity as well as decreased KOOS subscores (ie, quality of life and symptoms; R2 > .12, P < .03). Postoperative notch width was not a significant predictor for any surgical outcome. None of the anatomic features were predictive of medial joint space width narrowing. Conclusion: Results partially support the hypothesis and highlight the importance of knee anatomy on several outcomes of ACL reconstruction among patients without subsequent graft or contralateral ACL injures. Increasing slopes in the coronal and sagittal planes with decreasing concavity of the medial tibial plateau lead to less favorable outcomes 7 years after surgery.
Interleukin-4 supplementation improves the pathophysiology of hypertension in response to placental ischemia in RUPP rats.

Preeclampsia (PE) is characterized by chronic inflammation and elevated agonistic autoantibodies to the angiotensin type 1 receptor (AT1-AA), endothelin-1, and uterine artery resistance index (UARI) during pregnancy. Previous studies report an imbalance among immune cells, with T-helper type 2 (Th2) cells being decreased during PE. We hypothesized that interleukin-4 (IL-4) would increase Th2 cells and improve the pathophysiology in response to placental ischemia during pregnancy. IL-4 (600 ng/day) was administered via osmotic minipump on gestational day 14 to normal pregnant (NP) and reduced uterine perfusion pressure (RUPP) rats. Carotid catheters were inserted, and Doppler ultrasound was performed on gestational day 18. Blood pressure (mean arterial pressure), TNF-α, IL-6, AT1-AA, natural killer cells, Th2 cells, and B cells were measured on gestational day 19. Mean arterial pressure was 97 ± 2 mmHg in NP ( n = 9), 101 ± 3 mmHg in IL-4-treated NP ( n = 14), and 137 ± 4 mmHg in RUPP ( n = 8) rats and improved to 108 ± 3 mmHg in IL-4-treated RUPP rats ( n = 17) ( P < 0.05). UARI was 0.5 ± 0.03 in NP and 0.8 in RUPP rats and normalized to 0.5 in IL-4-treated RUPP rats ( P < 0.05). Plasma nitrate-nitrite levels increased in IL-4-treated RUPP rats, while placental preproendothelin-1 expression, plasma TNF-α and IL-6, and AT1-AA decreased in IL-4-treated RUPP rats compared with untreated RUPP rats ( P < 0.05). Circulating B cells and placental cytolytic natural killer cells decreased after IL-4 administration, while Th2 cells increased in IL-4-treated RUPP compared with untreated RUPP rats. This study illustrates that IL-4 decreased inflammation and improved Th2 numbers in RUPP rats and, ultimately, improved hypertension in response to placental ischemia during pregnancy.
Cardiometabolic Effects of Testosterone in Transmen and Estrogen Plus Cyproterone Acetate in Transwomen

CONTEXT The impact of gender-affirming hormone therapy (HT) on cardiometabolic parameters is largely unknown. OBJECTIVE The effects of 1 year of treatment with oral or transdermal administration of estrogen (plus cyproterone) and transdermal or IM application of testosterone on serum lipid levels and blood pressure (BP) were assessed in transgender persons. DESIGN AND METHODS In this prospective, observational substudy of the European Network for the Investigation of Gender Incongruence, measurements were performed before and after 12 months of HT in 242 transwomen and 188 transmen from 2010 to 2017. RESULTS Mean values are reported. In transmen, HT increased diastolic BP (2.5%; 95% CI, 0.6 to 4.4) and levels of total cholesterol (TC; 4.1%; 95% CI, 1.5 to 6.6), low-density lipoprotein-cholesterol (LDL-C; 13.0%; 95% CI, 9.2 to 16.8), and triglycerides (36.9%; 95% CI, 29.8 to 44.1); high-density lipoprotein-cholesterol levels decreased (HDL-C; 10.8%; 95% CI, -14.0 to -7.6). In transwomen, HT slightly decreased BP (systolic BP, -2.6%, 95% CI, -4.2 to -1.0; diastolic BP, -2.2%, 95% CI, -4.0 to -0.4) and decreased levels of TC (-9.7%; 95% CI, -11.3 to -8.1), LDL-C (-6.0%; 95% CI, -8.6 to 3.6), HDL-C (-9.3%; 95% CI, -11.4 to -7.3), and triglycerides (-10.2%; 95% CI, -14.5 to -5.9). CONCLUSION Unfavorable changes in lipid profile were observed in transmen; a favorable effect was noted in transwomen. HT effects on BP were negligible. Long-term studies are warranted to assess whether and to what extent HT in trans individuals results in a differential effect on cardiovascular disease outcomes.
The Role of UV-B light on Small RNA Activity During Grapevine Berry Development

We explored the effects of ultraviolet B radiation (UV-B) on the developmental dynamics of microRNAs and phased small-interfering-RNA (phasi-RNAs)-producing loci by sequencing small RNAs in vegetative and reproductive organs of grapevine (Vitis vinifera L.). In particular, we tested different UV-B conditions in in vitro-grown plantlets (high-fluence exposition) and in berries from field-grown (radiation filtering) and greenhouse-grown (low- and high-fluence expositions) adult plants throughout fruit development and ripening. The functional significance of the observed UV-coordinated miRNA responses was supported by degradome evidences of ARGONAUTE (AGO)-programmed slicing of mRNAs. Co-expression patterns of the up-regulated miRNAs miR156, miR482, miR530, and miR828 with cognate target gene expressions in response to high-fluence UV-B was tested by q-RT-PCR. The observed UV-response relationships were also interrogated against two published UV-stress and developmental transcriptome datasets. Together, the dynamics observed between miRNAs and targets suggest that changes in target abundance are mediated transcriptionally and, in some cases, modulated post-transcriptionally by miRNAs. Despite the major changes in target abundance are being controlled primarily by those developmental effects that are similar between treatments, we show evidence for novel miRNA-regulatory networks in grape. A model is proposed where high-fluence UV-B increases miR168 and miR530 that target ARGONAUTE 1 (AGO1) and a Plus-3 domain mRNA, respectively, while decreasing miR403 that targets AGO2, thereby coordinating post-transcriptional gene silencing activities by different AGOs. Up-regulation of miR3627/4376 could facilitate anthocyanin accumulation by antagonizing a calcium effector, whereas miR395 and miR399, induced by micronutrient deficiencies known to trigger anthocyanin accumulation, respond positively to UV-B radiation. Finally, increases in the abundance of an anthocyanin-regulatory MYB-bHLH-WD40 complex elucidated in Arabidopsis, mediated by UV-B-induced changes in miR156/miR535, could contribute to the observed up-regulation of miR828. In turn, miR828 would regulate the AtMYB113-ortologues MYBA5, A6 and A7 (and thereby anthocyanins) via a widely conserved and previously validated auto-regulatory loop involving miR828 and phasi TAS4abc RNAs.
Alpha Oscillations Modulate Preparatory Activity in Marmoset Area 8Ad

Cognitive control often requires suppression of prepotent stimulus-driven responses in favor of less potent alternatives. Suppression of prepotent saccades has been shown to require proactive inhibition in the frontoparietal saccade network. Electrophysiological evidence in macaque monkeys has revealed neural correlates of such inhibition in this network; however, the interlaminar instantiation of inhibitory processes remains poorly understood because these areas lie deep within sulci in macaques, rendering them inaccessible to laminar recordings. Here, we addressed this gap by exploiting the mostly lissencephalic cortex of the common marmoset (Callithrix jacchus). We inserted linear electrode arrays into areas 8Ad—the putative marmoset frontal eye field—and the lateral intraparietal area of two male marmosets and recorded neural activity during performance of a task comprised of alternating blocks of trials requiring a saccade either toward a large, high-luminance stimulus or the inhibition of this prepotent response in favor of a saccade toward a small, low-luminance stimulus. We observed prominent task-dependent activity in both alpha/gamma bands of the LFP and discharge rates of single neurons in area 8Ad during a prestimulus task epoch in which the animals had been instructed which of these two tasks to perform but before peripheral stimulus onset. These data are consistent with a model in which rhythmic alpha-band activity in deeper layers inhibits spiking in upper layers to support proactive inhibitory saccade control. SIGNIFICANCE STATEMENT Failures to inhibit automatic saccadic responses are a hallmark of many neuropsychiatric disorders, but how this process is implemented across the cortical layers in the frontoparietal saccade network remains unknown because many of the areas are inaccessible to laminar recordings in macaques. Here, we investigated laminar neural activity in marmoset monkeys, which have a smooth cortex. Monkeys were required either to generate or inhibit a prepotent saccade response. In area 8Ad, the putative frontal eye field in marmosets, rhythmic alpha-band activity (9–14 Hz) was higher in deeper layers and spiking activity was lower in upper layers when the animals were instructed to suppress a saccade toward a peripheral stimulus. Reduced alpha power during task preparation may be the underlying common neural basis of a saccade suppression deficit.
Commensal Gut Bacteria Convert the Immunosuppressant Tacrolimus to Less Potent Metabolites

Tacrolimus exhibits low and variable drug exposure after oral dosing, but the contributing factors remain unclear. Based on our recent report showing a positive correlation between fecal abundance of Faecalibacterium prausnitzii and oral tacrolimus dose in kidney transplant patients, we tested whether F. prausnitzii and other gut abundant bacteria are capable of metabolizing tacrolimus. Incubation of F. prausnitzii with tacrolimus led to production of two compounds (the major one named M1), which was not observed upon tacrolimus incubation with hepatic microsomes. Isolation, purification, and structure elucidation using mass spectrometry and nuclear magnetic resonance spectroscopy indicated that M1 is a C-9 keto-reduction product of tacrolimus. Pharmacological activity testing using human peripheral blood mononuclear cells demonstrated that M1 is 15-fold less potent than tacrolimus as an immunosuppressant. Screening of 22 gut bacteria species revealed that most Clostridiales bacteria are extensive tacrolimus metabolizers. Tacrolimus conversion to M1 was verified in fresh stool samples from two healthy adults. M1 was also detected in the stool samples from kidney transplant recipients who had been taking tacrolimus orally. Together, this study presents gut bacteria metabolism as a previously unrecognized elimination route of tacrolimus, potentially contributing to the low and variable tacrolimus exposure after oral dosing.