Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal Associations of 12th-Grade Binge Drinking With Risky Driving and High-Risk Drinking

Binge drinking 12th-graders have a greater likelihood of risky driving, extreme binge drinking, and experiencing blackout episodes several years after leaving high school. BrightcoveDefaultPlayer10.1542/6138656116001PEDS-VA_2018-4095 Video Abstract OBJECTIVE: To study the longitudinal associations of 12th-grade binge drinking with driving while impaired (DWI), riding with an impaired driver (RWI), blackouts, extreme binge drinking, and risky driving (self-reported Checkpoints Risky Driving Scale) among emerging adults up to 4 years after leaving high school. METHODS: The data were all 7 waves (W 1 to W 7 of the NEXT Generation Health Study; a US nationally representative study (N = 2785) with a probability cohort of 10th-graders (mean age = 16.2 years; SE = 0.03) starting in the 2009–2010 year. Binary and ordinal logistic regressions were used for the analysis. RESULTS: Binge drinking prevalence in W1 to W3 was 27.2%, 23.8%, and 26.8%, respectively. Twelfth-grade binge drinking was associated with a higher likelihood of DWI, RWI, blackouts, and risky driving in W4 to W7 and extreme binge drinking in W7. Adolescents who binged ≥3 times in high school were more likely to DWI, RWI, blackout (W4 to W7), be involved in extreme binge drinking (W7), and report riskier driving several years after high school. In some waves, parental practices appeared to have enduring effects in protecting against DWI, RWI, and blackouts. CONCLUSIONS: Twelfth-grade binge drinking is a robust predictor of early adulthood DWI, RWI, blackout, extreme binge drinking, and risky driving. Our study suggests that ongoing parental practices could be protective against DWI, RWI, and blackouts once adolescents transition from high school into early adulthood. Prevention programs that incorporate binge drinking–focused screening and bolster parental practices may reduce the likelihood of later major alcohol-related health-risk behaviors and consequences in emerging adults.
Production of Abzymes in Th, CBA, and C57BL/6 Mice before and after MOG Treatment: Comparing Changes in Cell Differentiation and Proliferation

Till yet there is no data concerning mechanisms of autoimmune diseases development. Experimental autoimmune encephalomyelitis (EAE) prone C57BL/6 (T- and B-lymphocyte response), non-autoimmune CBA, and Th mice with T cell response were immunized with myelin oligodendrocyte glycoprotein (MOG35–55) to compare different characteristics of autoimmune reaction development. Bone marrow differentiation profiles of hematopoietic stem cells (HSCs), lymphocyte proliferation in various organs associated with the production of antibodies against DNA, myelin basic protein (MBP), and MOG, as well as abzymes hydrolyzing these antigens, were analyzed before and after immunization. Profiles of HSC differentiation [BFU-E (erythroid burst-forming unit (early erythroid colonies), CFU-E (erythroid burst-forming unit (late erythroid colonies), CFU-GM (granulocytic-macrophagic colony-forming unit), and CFU-GEMM granulocytic-erythroid-megakaryocytic-macrophagic colony-forming unit] and patterns of lymphocyte proliferation in different organs (brain, spleen, thymus, and lymph nodes) were very different for C57BL/6, CBA, and Th mice. We conclude that only C57BL/6 mice were predisposed to spontaneous and MOG-induced acceleration of EAE development. CBA mice are not prone to the development of autoimmune reactions. After immunization, Th mice demonstrate changes in several parameters similar to C57BL/6 and other to CBA mice; Th mice are more prone to developing autoimmune reactions than CBA mice. Our data may be important for understanding the combined presence in mice lymphocytes with T and B cell responses for spontaneous and induced autoimmune diseases.
Pediatric Pulmonology

Department of Anesthesiology, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China Department of Obstetrics, Zhucheng People's Hospital, Zhucheng, Shandong, China Department of Anesthesiology and Pediatric Clinical Pharmacology Laboratory, Shanghai Children's Medical Center Affiliated to School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Midkine level may be used as a noninvasive biomarker in Crohn’s disease

Background/aim Crohn’s disease (CD) is a kind of inflammatory bowel disease. Midkine (MDK) is an endogenous inflammatory marker. We aimed to investigate the relationship between MDK levels and inflammation and hence determine whether MDK can be used as a noninvasive biomarker in active CD. Materials and methods Sixty-five consecutive patients over the age of 18 with CD and 36 healthy controls were included in this study. CD patients’ venous blood samples were taken before treatment. Serum MDK levels were determined in human plasma samples by enzyme-linked immunosorbent assay (ELISA) method. Results The mean age of the study patients was 44.8 ± 12.5 years, 35 patients were female, and 30 were male. Of these 65 patients, 37 had active CD and 28 were in the remission phase. MDK levels were significantly higher in active and remission CD than in healthy controls (P = 0.01, P = 0.038, respectively). Conclusion We report that there is an association between MDK levels and CD activation, and therefore with enhanced inflammation. MDK levels were significantly correlated with inflammatory indices. In line with our findings, we suggest the theory that MDK inhibitors may be useful in treating Crohn’s disease.
Evaluating the Placebo Status of Nebulized Normal Saline in Patients With Acute Viral Bronchiolitis: A Systematic Review and Meta-analysis.

Importance In therapeutic trials for acute viral bronchiolitis, consistent clinical improvement in groups that received nebulized normal saline (NS) as placebo raises the question of whether nebulized NS acts as a treatment rather than a placebo. Objective To measure the short-term association of nebulized NS with physiologic measures of respiratory status in children with bronchiolitis by analyzing the changes in these measures between the use of nebulized NS and the use of other placebos and the changes before and after nebulized NS treatment. Data Sources MEDLINE and Scopus were searched through March 2019, as were bibliographies of included studies and relevant systematic reviews, for randomized clinical trials evaluating nebulized therapies in bronchiolitis. Study Selection Randomized clinical trials comparing children 2 years or younger with bronchiolitis who were treated with nebulized NS were included. Studies enrolling a treatment group receiving an alternative placebo were included for comparison of NS with other placebos. Data Extraction and Synthesis Data abstraction was performed per PRISMA guidelines. Fixed- and random-effects, variance-weighted meta-analytic models were used. Main Outcomes and Measures Pooled estimates of the association with respiratory scores, respiratory rates, and oxygen saturation within 60 minutes of treatment were generated for nebulized NS vs another placebo and for change before and after receiving nebulized NS. Results A total of 29 studies including 1583 patients were included. Standardized mean differences in respiratory scores for nebulized NS vs other placebo (3 studies) favored nebulized NS by -0.9 points (95% CI, -1.2 to -0.6 points) at 60 minutes after treatment (P < .001). There were no differences in respiratory rate or oxygen saturation comparing nebulized NS with other placebo. The standardized mean difference in respiratory score (25 studies) after nebulized NS was -0.7 (95% CI, -0.7 to -0.6; I2 = 62%). The weighted mean difference in respiratory scores using a consistent scale (13 studies) after nebulized NS was -1.6 points (95% CI, -1.9 to -1.3 points; I2 = 72%). The weighted mean difference in respiratory rate (17 studies) after nebulized NS was -5.5 breaths per minute (95% CI, -6.3 to -4.6 breaths per minute; I2 = 24%). The weighted mean difference in oxygen saturation (23 studies) after nebulized NS was -0.4% (95% CI, -0.6% to -0.2%; I2 = 79%). Conclusions and Relevance Nebulized NS may be an active treatment for acute viral bronchiolitis. Further evaluation should occur to establish whether it is a true placebo.
The “athlete’s heart” features in amateur male marathon runners

Background Training on a professional level can lead to cardiac structural adaptations called the “athlete’s heart”. As marathon participation requires intense physical preparation, the question arises whether the features of “athlete’s heart” can also develop in recreational runners. Methods The study included 34 males (mean age 40 ± 8 years) who underwent physical examination, a cardiopulmonary exercise test and echocardiographic examination (ECHO) before a marathon. ECHO results were compared with the sedentary control group, reference values for an adult male population and those for highly-trained athletes. Runners with abnormalities revealed by ECHO were referred for cardiac magnetic resonance imaging (CMR). Results The mean training distance was 56.5 ± 19.7 km/week, peak oxygen uptake was 53.7 ± 6.9 mL/kg/min and the marathon finishing time was 3.7 ± 0.4 h. Compared to sedentary controls, amateur athletes presented larger atria, increased left ventricular (LV) wall thickness, larger LV mass and basal right ventricular (RV) inflow diameter (p < 0.05). When compared with ranges for the general adult population, 56% of participants showed increased left atrial volume, indexed to body surface area (LAVI), 56% right atrial area and interventricular septum thickness, while 47% had enlarged RV proximal outflow tract diameter. In 50% of cases, LAVI exceeded values reported for highly-trained athletes. Due to ECHO abnormalities, CMR was performed in 6 participants, which revealed hypertrophic cardiomyopathy in 1 runner. Conclusions “Athlete’s heart” features occur in amateur marathon runners. In this group, ECHO reference values for highly-trained elite athletes should be considered, rather than those for the general population and even then LAVI can exceed the upper normal value.
Potential Beneficial Effects of Vitamin D in Coronary Artery Disease

Vitamin D plays a pivotal role in bone homeostasis and calcium metabolism. However, recent research has indicated additional beneficial effects of vitamin D on the cardiovascular system. This review aims to elucidate if vitamin D can be used as an add-on treatment in coronary artery disease (CAD). Large-scale epidemiological studies have found a significant inverse association between serum 25(OH)-vitamin D levels and the prevalence of essential hypertension. Likewise, epidemiological data have suggested plasma levels of vitamin D to be inversely correlated to cardiac injury after acute myocardial infarction (MI). Remarkably, in vitro trials have showed that vitamin D can actively suppress the intracellular NF-κB pathway to decrease CAD progression. This is suggested as a mechanistic link to explain how vitamin D may decrease vascular inflammation and atherosclerosis. A review of randomized controlled trials with vitamin D supplementation showed ambiguous results. This may partly be explained by heterogeneous study groups. It is suggested that subgroups of diabetic patients may benefit more from vitamin D supplementation. Moreover, some studies have indicated that calcitriol rather than cholecalciferol exerts more potent beneficial effects on atherosclerosis and CAD. Therefore, further studies are required to clarify these assumptions.
A Kinase and a Glycosylase Catabolize Pseudouridine in the Peroxisome to Prevent Toxic Pseudouridine Monophosphate Accumulation

Pseudouridine, a frequent nucleoside modification in noncoding RNA and mRNA, is degraded in Arabidopsis peroxisomes to prevent the accumulation of the toxic intermediate pseudouridine monophosphate. Pseudouridine (Ψ) is a frequent nucleoside modification that occurs in both noncoding RNAs and mRNAs. In pseudouridine, C5 of uracil is attached to the Rib via an unusual C-glycosidic bond. This RNA modification is introduced on the RNA by site-specific transglycosylation of uridine (U), a process mediated by pseudouridine synthases. RNA is subject to constant turnover, releasing free pseudouridine, but the metabolic fate of pseudouridine in eukaryotes is unclear. Here, we show that in Arabidopsis (Arabidopsis thaliana), pseudouridine is catabolized in the peroxisome by (1) a pseudouridine kinase (PUKI) from the PfkB family that generates 5′-pseudouridine monophosphate (5′-ΨMP) and (2) a ΨMP glycosylase (PUMY) that hydrolyzes ΨMP to uracil and ribose-5-phosphate. Compromising pseudouridine catabolism leads to strong pseudouridine accumulation and increased ΨMP content. ΨMP is toxic, causing delayed germination and growth inhibition, but compromising pseudouridine catabolism does not affect the Ψ/U ratios in RNA. The bipartite peroxisomal PUKI and PUMY are conserved in plants and algae, whereas some fungi and most animals (except mammals) possess a PUMY-PUKI fusion protein, likely in mitochondria. We propose that vacuolar turnover of ribosomal RNA produces most of the pseudouridine pool via 3′-ΨMP, which is imported through the cytosol into the peroxisomes for degradation by PUKI and PUMY, a process involving a toxic 5′-ΨMP intermediate.
Association of Sleep Quality and Macronutrient Distribution: A Systematic Review and Meta-Regression

Sleep is involved in metabolic, emotional and cognitive regulation and is therefore an essential part of our health. Although an association between sleep quality and macronutrient intake has been reported, studies on the effect of macronutrient distribution with sleep quality are limited, and available results are inconsistent. In this study, we aim to assess the association between sleep quality and macronutrient distribution in healthy adults from systematically reviewed cross-sectional studies and randomized controlled trials (RCTs). A total of 19 relevant articles were selected and it was observed that good sleepers (sleep duration ≥ 7 h, global sleep score ≤ 5, sleep latency ≤ 30 min and sleep efficiency >85%) had a higher energy distribution from dietary protein than poor sleepers. On the other hand, good sleepers showed a relatively lower percentage of energy from dietary carbohydrate and fat than poor sleepers. However, meta-regression analysis revealed no dose-dependent association between the macronutrient distributions and sleep duration. These results suggest that consuming a greater proportion of dietary protein may benefit on improving sleep quality in healthy adults. However, findings may be susceptible to reverse causality and additional RCTs are needed.
Lung-on-a-chip: the future of respiratory disease models and pharmacological studies

Abstract Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.
The Adaptive Morphology of Bacillus subtilis Biofilms: A Defense Mechanism against Bacterial Starvation

Biofilms are commonly defined as accumulations of microbes, embedded in a self-secreted, polysaccharide-rich extra-cellular matrix. This study aimed to characterize specific morphological changes that occur in Bacillus subtilis biofilms under nutrient-limiting growth conditions. Under varying levels of nutrient depletion, colony-type biofilms were found to exhibit different rates of spatial expansion and green fluorescent protein production. Specifically, colony-type biofilms grown on media with decreased lysogeny broth content exhibited increased spatial expansion and more stable GFP production over the entire growth period. By modeling the surface morphology of colony-type biofilms using confocal and multiphoton microscopy, we analyzed the appearance of distinctive folds or “wrinkles” that form as a result of lysogeny broth content reduction in the solid agar growth media. When subjected to varying nutritional conditions, the channel-like folds were shown to alter their morphology; growth on nutrient-depleted media was found to trigger the formation of large and straight wrinkles connecting the colony core to its periphery. To test a possible functional role of the formed channels, a fluorescent analogue of glucose was used to demonstrate preferential native uptake of the molecules into the channels’ interiors which supports their possible role in the transport of molecules throughout biofilm structures.
The continuing arc toward phototropic enlightenment

Abstract Phototropism represents a simple physiological mechanism—differential growth across the growing organ of a plant—to respond to gradients of light and maximize photosynthetic light capture (in aerial tissues) and water/nutrient acquisition (in roots). The phototropin blue light receptors, phot1 and phot2, have been identified as the essential sensors for phototropism. Additionally, several downstream signal/response components have been identified, including the phot-interacting proteins NON-PHOTOTROPIC HYPOCOTYL 3 (NPH3) and PHYTOCHROME SUBSTRATE 4 (PKS4). While the structural and photochemical properties of the phots are quite well understood, much less is known about how the phots signal through downstream regulators. Recent advances have, however, provided some intriguing clues. It appears that inactive receptor phot1 is found dispersed in a monomeric form at the plasma membrane in darkness. Upon light absorption dimerizes and clusters in sterol-rich microdomains where it is signal active. Additional studies showed that the phot-regulated phosphorylation status of both NPH3 and PKS4 is linked to phototropic responsiveness. While PKS4 can function as both a positive (in low light) and a negative (in high light) regulator of phototropism, NPH3 appears to function solely as a key positive regulator. Ultimately, it is the subcellular localization of NPH3 that appears crucial, an aspect regulated by its phosphorylation status. While phot1 activation promotes dephosphorylation of NPH3 and its movement from the plasma membrane to cytoplasmic foci, phot2 appears to modulate relocalization back to the plasma membrane. Together these findings are beginning to illuminate the complex biochemical and cellular events, involved in adaptively modifying phototropic responsiveness under a wide varying range of light conditions.
Detection and Quantification of Extracellular Vesicles via FACS: Membrane Labeling Matters!

The field of extracellular vesicle (EV) research is challenged by the lack of standardized protocols to identify and specifically distinguish between exosomes and ectosomes, which are released via exocytosis or plasma membrane shedding, respectively. Using sequential centrifugation, we separated EV subpopulations from supernatants of COLO 357 pancreas carcinoma cells based on size and mass. After 10,000× g centrifugation, we reconstituted high-speed (hs) EVs from the pellet, directly labeled them with the membrane dye carboxyfluorescein diacetate succinimidyl ester (CFSE), and performed flow cytometry based analysis. The aim was to optimize the conditions for EV labeling and detection and hence to obtain a maximum yield of intact hsEVs. We found that, for sufficient labeling of EVs, minimal temperature variations and short incubation times correlated with EV stability. Furthermore, threshold adjustment significantly improved the sensitivity of the flow cytometer for the detection of CFSE labeled hsEVs. When cells were CFSE labeled, we observed a transition of fluorescence onto EVs that were reconstituted from the pellet but not onto those that remained in the supernatant after hs centrifugation, suggesting the indirect labeling of EVs based on the way of biogenesis as a specific method for the distinction of exosomes and ectosomes. Protocol standardization is of major importance for the use of EVs as diagnostic markers in liquid biopsies.
Projective Technique Testing Approach to the Understanding of Psychological Pain in Suicidal and Non-Suicidal Psychiatric Inpatients

Psychological pain is a core clinical factor for understanding suicide, independently from depression. The aim of this study is to assess the role of psychological pain on suicide risk and to evaluate the relationship between psychache and different psychiatric disorders. We conducted the present cross-sectional study on 291 inpatients with a diagnosis of major depressive disorder, bipolar disorder, and schizophrenia. We administered Shneidman’s Psychological Pain Assessment Scale (PPAS) for the assessment of mental pain and the Mini International Neuropsychiatric Interview (MINI) for the assessment of suicide risk. There was a significant association between current psychache and worst-ever psychache and suicide risk in inpatients affected by a depressive disorder, bipolar disorder and schizophrenia. Furthermore, we found a significant difference in current psychache between inpatients with major depressive disorder and inpatients with schizophrenia and in worst-ever psychache between inpatients with bipolar disorder and inpatients with schizophrenia, with lower scores in inpatients with schizophrenia. The assessment of psychache appears to be useful for predicting suicidal risk and should be used routinely for identifying and treating suicide risk in clinical practice.