Miracle-dz/UniFAR-FTUs huggingface dataset:
Hospital Outcomes of Infants with Neonatal Opioid Withdrawal Syndrome at a Tertiary Care Hospital with High Rates of Concurrent Nonopioid (Polysubstance) Exposure

Abstract Objective Neonatal opioid withdrawal syndrome (NOWS) describes infants' withdrawal signs and symptoms after birth due to an interruption of prenatal opioid exposure. Many infants with NOWS are also exposed to nonopioids, however. This study was to determine hospital outcomes of infants exposed to opioids alone or coexposed with nonopioid substances (polysubstance). Study Design We reviewed infants of ≥34 weeks of gestation with prenatal opioid exposure from April 2015 to May 2018. We compared the median lengths of stay (LOS) and treatment (LOT) and the percentages of infants requiring pharmacologic and adjunctive treatment in infants exposed to opioids alone or polysubstance. We used Wilcoxon's test for continuous outcomes or Chi-squared test for categorical outcomes to determine statistical significance. We used multivariable regression model to calculate each drug category's estimates of adjusted mean ratios for LOS and LOT plus estimates of adjusted odds ratios for pharmacologic/adjunctive treatments. Results Of the 175 infants, 33 (19%) infants had opioid exposure alone. Opioid exposure included short- and/or long-acting opioids. A total of 142 (81%) had polysubstance exposure with 47% of mothers using nicotine products. We saw similar hospital outcomes between infants exposed to opioids alone or polysubstance; however, a higher percentage of infants with both short- and long-acting opioid exposure required pharmacologic treatment compared with either opioid alone. Focusing on individual drug categories, we detected differential hospital outcomes in which short-acting opioids decreased LOT, whereas long-acting opioids increased LOS, LOT, and need for pharmacologic and adjunctive treatment. Coexposure of opioids with stimulants decreased LOT and reduced need for adjunctive treatment. Coexposures with antidepressants increased LOT, while with antiepilepetics increased LOS. Conclusion Because infants with NOWS often have coexposures to other nonopioid substances, appreciating the associated risks of individual or combination of drugs in modulating hospital outcomes may help counsel families on their infants' expected hospital course. Key Points Hospital outcomes were similar between infants exposed to opioids alone or polysubstance including opioids. Infants with short- and long-acting opioids required pharmacologic treatment more often than either opioid alone. Differential hospital outcomes exist for various co-exposures of opioids with nonopioids.
An assessment of statistical methods for non-independent data in ecological meta-analyses.

In ecological meta-analyses, non-independence among observed effect sizes from the same source paper is common. If not accounted for, non-independence can seriously undermine inferences. We compared the performance of four meta-analysis methods that attempt to address such non-independence and the standard random-effect model that ignores non-independence. We simulated data with various types of within-paper non-independence, and assessed the standard deviation of the estimated mean effect size and type I error rate of each method. Although all four methods performed substantially better than the standard random-effects model that assumes independence, there were differences in performance among the methods. A two-step method that first summarizes the multiple observed effect sizes per paper using a weighted mean and then analyzes the reduced data in a standard random-effects model, and a robust variance estimation method performed consistently well. A hierarchical model with both random paper and study effects gave precise estimates but had a higher type I error rates, possibly reflecting limitations of currently available meta-analysis software. Overall, we advocate the use of the two-step method with a weighted paper mean and the robust variance estimation method as reliable ways to handle within-paper non-independence in ecological meta-analyses.
Response to Almalki et al.: Resuming endoscopy services during the COVID-19 pandemic

We thank Almalki et al.[1] for their insightful comments on the current situation of endoscopy services in the country, and we clearly share their concerns. The repercussions of the pandemic have been echoed not only in the original position statement from the Saudi Gastroenterology Association (SGA)[2] but also by numerous other societies. The pandemic has resulted in significant restrictions to patient care in the form of hospital visits, which adds insult to injury since challenges to access specialized care existed even before the pandemic. [3] The pandemic has also been a source of anxiety for patients and healthcare providers alike as depicted in a series of papers in the Journal in the last few months. [4‐7]
Early cytomegalovirus DNAemia and antiviral dose adjustment in high vs intermediate risk kidney transplant recipients

Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation.
The ESCRT-III complex is required for nuclear pore complex sequestration and regulates gamete replicative lifespan in budding yeast meiosis

ABSTRACT Cellular aging occurs as a cell loses its ability to maintain homeostasis. Aging cells eliminate damaged cellular compartments and other senescence factors via self-renewal. The mechanism that regulates cellular rejuvenation remains to be further elucidated. Using budding yeast gametogenesis as a model, we show here that the endosomal sorting complex required for transport (ESCRT) III regulates nuclear envelope organization. During gametogenesis, the nuclear pore complex (NPC) and other senescence factors are sequestered away from the prospore nuclei. We show that the LEM-domain protein Heh1 (Src1) facilitates the nuclear recruitment of ESCRT-III, which is required for meiotic NPC sequestration and nuclear envelope remodeling. Furthermore, ESCRT-III-mediated nuclear reorganization appears to be critical for gamete rejuvenation, as hindering this process curtails either directly or indirectly the replicative lifespan in gametes. Our findings demonstrate the importance of ESCRT-III in nuclear envelope remodeling and its potential role in eliminating senescence factors during gametogenesis.
The advance in research methods for large-scale protein-protein interactions

In 2000, the first network of large-scale protein-protein interactions was accomplished in yeast. It was a historic moment and became another hot spot of protein research. Subsequently, such proteins interaction maps were also brought to success in the fly, worm and even human during five years. So rapid progress in large-scale protein-protein interactions turned up many new angles of view for investigating the mechanisms of cell functions, actually it also suggested the development and complement of research method itself. In this article we summarized the progress of techniques in large-scale protein-protein interactions and showed their differences. Anyway, the researchers should choose right means to perform their diverse intentions.
Rapamycin and mTORC2 inhibition synergistically reduce contraction‐stimulated muscle protein synthesis

Muscle contractions increase protein synthesis in a mechanistic target of rapamycin (mTOR)‐dependent manner, yet it is unclear which/how mTOR complexes regulate muscle protein synthesis. We investigated the requirement of mTOR Complex 2 (mTORC2) in contraction‐stimulated muscle protein synthesis. mTORC2 inhibition by muscle‐specific Rictor knockout (Rictor mKO) did not prevent contraction‐induced muscle protein synthesis. Rapamycin prevented contraction‐induced muscle protein synthesis in Rictor mKO but not wild‐type mice.
Metabolite profiling reveals the interaction of chitin-glucan with the gut microbiota

ABSTRACT Dietary fibers are considered beneficial nutrients for health. Current data suggest that their interaction with the gut microbiota largely contributes to their physiological effects. In this context, chitin-glucan (CG) improves metabolic disorders associated with obesity in mice, but its effect on gut microbiota has never been evaluated in humans. This study explores the effect of a 3-week intervention with CG supplementation in healthy individuals on gut microbiota composition and bacterial metabolites. CG was given to healthy volunteers (n = 15) for three weeks as a supplement (4.5 g/day). Food diary, visual analog and Bristol stool form scales and a “quality of life” survey were analyzed. Among gut microbiota-derived metabolites, bile acids (BA), long- and short-chain fatty acids (LCFA, SCFA) profiling were assessed in stool samples. The gut microbiota (primary outcome) was analyzed by Illumina sequencing. A 3-week supplementation with CG is well tolerated in healthy humans. CG induces specific changes in the gut microbiota composition, with Eubacterium, Dorea and Roseburia genera showing the strongest regulation. In addition, CG increased bacterial metabolites in feces including butyric, iso-valeric, caproic and vaccenic acids. No major changes were observed for the fecal BA profile following CG intervention. In summary, our work reveals new potential bacterial genera and gut microbiota-derived metabolites characterizing the interaction between an insoluble dietary fiber -CG- and the gut microbiota. Graphical abstract
Predictors of postprandial glycaemia, insulinaemia and insulin resistance in adolescents

Abstract Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F (3,98) = 36·78, P < 0·001, adjusted R 2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F (7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F (2,102) = 14·06, P < 0·001, adjusted R 2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.
Adipocyte ADAM17 plays a limited role in metabolic inflammation

ABSTRACT The role of ADAM17, its substrates, and its natural inhibitor has been well studied in the context of inflammation, including metabolic inflammation, with mixed results. Previous studies examining global Adam17 knockdown models and ADAM17 inhibition using overexpression of endogenous ADAM17 inhibitors have shown improved metabolic health and decreased metabolic inflammation. However, there have been no studies examining the role of adipocyte ADAM17 using in vivo models. In this study, we developed an adipocyte-specific Adam17 knockout model using Adipoq-Cre-expressing mice crossed with Adam17-floxed mice. Using this model, we show that loss of adipocyte ADAM17 plays no evident role in baseline metabolic responses. Surprisingly, in a state of metabolic stress using high-fat diet (HFD), we observed that adipocyte ADAM17 had little effect overall on the metabolic phenotype as well as inflammatory cell populations. Using whole-body metabolic phenotyping, we show that loss of ADAM17 has no effect on energy utilization both at a baseline state as well as following HFD. However, lastly, using high-parameter flow cytometry, we show that loss of adipocyte ADAM17 alters macrophage and eosinophil populations following HFD. Overall, the studies presented here give more insight into the role of ADAM17 in metabolic responses and metabolic inflammation, specifically in adipocytes.
Characterization of Seasonal Pharmacokinetic Variability in Woodchucks

The eastern woodchuck (Marmota monax) is a hibernating species extensively used as an in vivo efficacy model for chronic human hepatitis B virus infection. Under laboratory conditions, woodchucks develop a pseudohibernation condition; thus, the pharmacokinetics (PK) of small-molecule therapeutics may be affected by the seasonal change. The seasonal PK of four probe compounds were characterized over 12 months in seven male and nine female laboratory-maintained woodchucks. These compounds were selected to study changes in oxidative metabolism [antipyrine (AP)], glucuronidation [raltegravir (RTG)], renal clearance [lamivudine (3TC)], and hepatic function [indocyanine green (ICG)]. Seasonal changes in physiologic parameters and PK were determined. Seasonal body weight increases were ≥30%. Seasonal changes in body temperature and heart rate were <10%. The mean AP exposure remained unchanged from April to August 2017, followed by a significant increase (≥1.0-fold) from August to December and subsequent decrease to baseline at the end of study. A similar trend was observed in RTG and 3TC exposures. The ICG exposure remained unchanged. No significant sex difference in PK was observed, although female woodchucks appeared to be less susceptible to seasonal PK and body weight changes. Significant seasonal PK changes for AP, RTG, and 3TC indicate decreases in oxidative metabolism, phase II glucuronidation, and renal clearance during pseudohibernation. The lack of seasonal change in ICG exposure suggests there are no significant changes in hepatic function. This information can be used to optimize the scheduling of woodchuck studies to avoid seasonally driven variation in drug PK. SIGNIFICANCE STATEMENT Woodchuck is a hibernating species and is commonly used as a nonclinical model of hepatitis B infection. Investigation of seasonal PK changes is perhaps of greater interest to pharmaceutical industry scientists, who use the woodchuck model to optimize the scheduling of woodchuck studies to avoid seasonally driven variation in drug PK and/or toxicity. This information is also valuable to drug metabolism and veterinary scientists in understanding woodchuck's seasonal metabolism and behavior under the pseudohibernation condition.
Recent Progress in Graphene/Polymer Nanocomposites

Nanocomposites, multiphase solid materials with at least one nanoscaled component, have been attracting ever‐increasing attention because of their unique properties. Graphene is an ideal filler for high‐performance multifunctional nanocomposites in light of its superior mechanical, electrical, thermal, and optical properties. However, the 2D nature of graphene usually gives rise to highly anisotropic features, which brings new opportunities to tailor nanocomposites by making full use of its excellent in‐plane properties. Here, recent progress on graphene/polymer nanocomposites is summarized with emphasis on strengthening/toughening, electrical conduction, thermal transportation, and photothermal energy conversion. The influence of the graphene configuration, including layer number, defects, and lateral size, on its intrinsic properties and the properties of graphene/polymer nanocomposites is systematically analyzed. Meanwhile, the role of the interfacial interaction between graphene and polymer in affecting the properties of nanocomposites is also explored. The correlation between the graphene distribution in the matrix and the properties of the nanocomposite is discussed in detail. The key challenges and possible solutions are also addressed. This review may provide a constructive guidance for preparing high‐performance graphene/polymer nanocomposite in the future.
Microfluidic Biomaterials

Since their initial description in 2005, biomaterials that are patterned to contain microfluidic networks (“microfluidic biomaterials”) have emerged as promising scaffolds for a variety of tissue engineering and related applications. This class of materials is characterized by the ability to be readily perfused. Transport and exchange of solutes within microfluidic biomaterials is governed by convection within channels and diffusion between channels and the biomaterial bulk. Numerous strategies have been developed for creating microfluidic biomaterials, including micromolding, photopatterning, and 3D printing. In turn, these materials have been used in many applications that benefit from the ability to perfuse a scaffold, including the engineering of blood and lymphatic microvessels, epithelial tubes, and cell‐laden tissues. This article reviews the current state of the field and suggests new areas of exploration for this unique class of materials.
Genome-wide identification of the Sec-dependent secretory protease genes in Erwinia amylovora and analysis of their expression during infection of immature pear fruit

The general secretory (Sec) pathway represents a common mechanism by which bacteria secrete proteins, including virulence factors, into the extracytoplasmic milieu. However, there is little information about this system, as well as its associated secretory proteins, in relation to the fire blight pathogen Erwinia amylovora. In this study, data mining revealed that E. amylovora harbors all of the essential components of the Sec system. Based on this information, we identified putative Sec-dependent secretory proteases in E. amylovora on a genome-wide scale. Using the programs SignalP, LipoP, and Phobius, a total of 15 putative proteases were predicted to contain the N-terminal signal peptides (SPs) that might link them to the Sec-dependent pathway. The activities of the predicted SPs were further validated using an Escherichia coli-based alkaline phosphatase (PhoA) gene fusion system that confirmed their extracytoplasmic property. Transcriptional analyses showed that the expression of 11 of the 15 extracytoplasmic protease genes increased significantly when E. amylovora was used to inoculate immature pears, suggesting their potential roles in plant infection. The results of this study support the suggestion that E. amylovora might employ the Sec system to secrete a suite of proteases to enable successful infection of plants, and shed new light on the interaction of E. amylovora with host plants.
The role of cognitive reserve in the relationship between metabolic syndrome and cognitive functioning

ABSTRACT Metabolic syndrome (MetS) is a cluster of vascular risk factors that can impact cognition. Cognitive reserve (CR), specifically early operators of reserve (e.g., education), have not been explored in the relationship between MetS and cognition. Adults 45–90 years old (n = 149) underwent neuropsychological testing and evaluation for MetS. Exploratory and confirmatory factor analyses defined neuropsychological domains and created a CR score based on early operators of CR. Regression analyses examined the association among MetS, CR, and neuropsychological performance. CFA revealed two neuropsychological factors: Episodic Memory and Executive Functioning. Controlling for age and physical ability, MetS and CR were significant predictors of the Factors. With CR in the model, MetS became a non-significant predictor of Executive Functioning; CR and physical ability were the most significant predictors. CR and MetS significantly predicted Episodic Memory . The results are discussed in the context of neuroprotective factors and cognitive aging.
Does the volume overload exaggerate the severity of mitral regurgitation in patients with decompensated heart failure?

Background/aim Diagnosing and managing functional mitral regurgitation (MR) is often challenging and requires an integrated approach including a comprehensive echocardiographic examination. However, the effects of volume overload on the echocardiographic assessment of MR severity are uncertain. The purpose of this study was to weigh the effects of volume overload in the echocardiographic assessment of MR severity among patients with heart failure (HF). Materials and methods Twenty-nine patients with decompensated HF, who had moderate or severe MR, were included in the present study. The volume status and the N-terminal pro-B-type natriuretic peptide (proBNP) levels were recorded and the echocardiographic parameters were assessed. After the conventional treatment for HF, the proBNP levels and the echocardiographic parameters were assessed again. Results The mean age of the patients was 72 ± 9 years and the average hospitalization time was 10.9 ± 5.9 days. Between the beginning and the end of the treatment, there were significant reductions in the effective regurgitant orifice area (EROA) (0.36 ± 0.09 cm2 to 0.29 ± 0.09 cm2, P < 0.001), vena contracta (VC) (P < 0.001), the regurgitant volume (RV) (P < 0.001), and systolic pulmonary artery pressure (sPAP) (P < 0.001). Conclusion This is the first study to investigate the relationship of changes in severity of MR with volume-load by monitoring the proBNP levels among patients with HF. The present results demonstrated that volume reduction, as evidenced by a decline in the proBNP levels, was accompanied by a marked reduction in the EROA, VC, and the RV among patients with left ventricular dysfunction.
Diagnostic performances of neutrophil to lymphocyte ratio and lymphocyte to monocyte ratio in acute ischemic stroke caused by cervicocranial arterial dissection

Inflammation plays an important role in the initiation and progression of cervicocranial arterial dissection (CCAD). New inflammatory indices derived from full cell blood count may be associated with increased risk of acute ischemic stroke (AIS) caused by CCAD. The goal of this study is to evaluate the diagnostic performances of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ratio (LMR) in CCAD.
Perirenal fat thickness as a predictor of postoperative complications after laparoscopic distal gastrectomy for gastric cancer

Laparoscopic distal gastrectomy is used widely in surgery for gastric cancer. Excess visceral fat can limit the ability to dissect the suprapancreatic region, potentially increasing the risk of local complications, particularly pancreatic fistula. This study evaluated perirenal fat thickness as a surrogate for visceral fat to see whether this was related to complications after laparoscopic distal gastrectomy.