Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term Relapse of Type 2 Diabetes After Roux-en-Y Gastric Bypass: Prediction and Clinical Relevance

OBJECTIVE Roux-en-Y gastric bypass (RYGB) induces type 2 diabetes remission (DR) in 60% of patients at 1 year, yet long-term relapse occurs in half of these patients. Scoring methods to predict DR outcomes 1 year after surgery that include only baseline parameters cannot accurately predict 5-year DR (5y-DR). We aimed to develop a new score to better predict 5y-DR. RESEARCH DESIGN AND METHODS We retrospectively included 175 RYGB patients with type 2 diabetes with 5-year follow-up. Using machine learning algorithms, we developed a scoring method, 5-year Advanced-Diabetes Remission (5y-Ad-DiaRem), predicting longer-term DR postsurgery by integrating medical history, bioclinical data, and antidiabetic treatments. The scoring method was based on odds ratios and variables significantly different between groups. This score was further validated in three independent RYGB cohorts from three European countries. RESULTS Compared with 5y-DR patients, patients who had relapsed after 5 years exhibited more severe type 2 diabetes at baseline, lost significantly less weight during the 1st year after RYGB, and regained more weight afterward. The 5y-Ad-DiaRem includes baseline (diabetes duration, number of antidiabetic treatments, and HbA1c) and 1-year follow-up parameters (glycemia, number of antidiabetic treatments, remission status, 1st-year weight loss). The 5y-Ad-DiaRem was accurate (area under the receiver operating characteristic curve [AUROC], 90%; accuracy, 85%) at predicting 5y-DR, performed better than the Diabetes Remission score (DiaRem) and the Advanced-DiaRem (AUROC, 81% and 84%; accuracy, 79% and 78%, respectively), and correctly reclassified 13 of 39 patients misclassified with the DiaRem. The 5y-Ad-DiaRem robustness was confirmed in the independent cohorts. CONCLUSIONS The 5y-Ad-DiaRem accurately predicts 5y-DR and appears relevant to identify patients at risk for relapse. Using this score could help personalize patient care after the 1st year post-RYGB to maximize weight loss, limit weight regains, and prevent relapse.
Antenatal vitamin D exposure and childhood eczema, food allergy, asthma and allergic rhinitis at 2 and 5 years of age in the atopic disease‐specific Cork BASELINE Birth Cohort Study

Prospective studies of antenatal and infant vitamin D exposure and atopic disease from extensively characterised, disease‐specific, maternal‐infant cohorts with gold standard analysis of vitamin D status and clinically validated atopic outcomes are lacking. This study aimed to investigate associations between intrauterine vitamin D status and atopic outcomes in an extensively characterised, disease‐specific, maternal‐infant cohort.
OFP1 Interaction with ATH1 Regulates Stem Growth, Flowering Time and Flower Basal Boundary Formation in Arabidopsis

Ovate Family Protein1 (OFP1) is a regulator, and it is suspected to be involved in plant growth and development. Meanwhile, Arabidopsis Thaliana Homeobox (ATH1), a BEL1-like homeodomain (HD) transcription factor, is known to be involved in regulating stem growth, flowering time and flower basal boundary development in Arabidopsis. Previous large-scale yeast two-hybrid studies suggest that ATH1 possibly interact with OFP1, but this interaction is yet unverified. In our study, the interaction of OFP1 with ATH1 was verified using a directional yeast two-hybrid system and bimolecular fluorescence complementation (BiFC). Our results also demonstrated that the OFP1-ATH1 interaction is mainly controlled by the HD domain of ATH1. Meanwhile, we found that ATH1 plays the role of transcriptional repressor to regulate plant development and that OFP1 can enhance ATH1 repression function. Regardless of the mechanism, a putative functional role of ATH1-OFP1 may be to regulate the expression of the both the GA20ox1 gene, which is involved in gibberellin (GA) biosynthesis and control of stem elongation, and the Flowering Locus C (FLC) gene, which inhibits transition to flowering. Ultimately, the regulatory functional mechanism of OFP1-ATH1 may be complicated and diverse according to our results, and this work lays groundwork for further understanding of a unique and important protein–protein interaction that influences flowering time, stem development, and flower basal boundary development in plants.
Effects of Interrupting Sedentary Behavior With Short Bouts of Moderate Physical Activity on Glucose Tolerance in Children With Overweight and Obesity: A Randomized Crossover Trial

OBJECTIVE Sedentary children have greater risk of developing abnormalities in glucose homeostasis. We investigated whether interrupting sedentary behavior (sitting) with very short periods of walking would improve glucose metabolism without affecting dietary intake in children with overweight or obesity. We hypothesized that interrupting sitting with short bouts of moderate-intensity walking would decrease insulin area under the curve (AUC) during an oral glucose tolerance test (OGTT) compared with uninterrupted sitting. RESEARCH DESIGN AND METHODS Overweight/obese (BMI ≥85th percentile) children 7–11 years of age underwent two experimental conditions in random order: prolonged sitting (3 h of continuous sitting) and interrupted sitting (3 min of moderate-intensity walking at 80% of ventilatory threshold every 30 min for 3 h). Insulin, C-peptide, and glucose were measured every 30 min for 3 h during an OGTT. Each session was followed by a buffet meal. Primary outcomes were differences in OGTT hormones and substrates and in buffet meal intake by condition. RESULTS Among 35 children with complete data, mixed-model results identified lower insulin and C-peptide in the interrupted condition (P = 0.007 and P = 0.029, respectively); the intervention reduced insulin AUC by 21% (P < 0.001) and C-peptide AUC 18% (P = 0.001) and improved estimated insulin sensitivity (P = 0.013). Neither buffet total energy intake (1,262 ± 480 vs. 1,260 ± 475 kcal; P = 0.89) nor macronutrient composition of the meal (P values >0.38) differed between conditions significantly. CONCLUSIONS Interrupting sitting with brief moderate-intensity walking improved glucose metabolism without significantly increasing energy intake in children with overweight or obesity. Interrupting sedentary behavior may be a promising intervention strategy for reducing metabolic risk in such children.
Predictors of Successful Weaning From Veno-Arterial Extracorporeal Membrane Oxygenation After Coronary Revascularization for Acute Myocardial Infarction Complicated by Cardiac Arrest: A Retrospective Multicenter Study

Aim: While veno-arterial extracorporeal membrane oxygenation (VA-ECMO) has been utilized to resuscitate and stabilize hemodynamics in patients of acute myocardial infarction (AMI) complicated by cardiac arrest (CA), it is essential to predict the possibility of weaning from ECMO to determine further strategies, including use of ventricular assist device. We aimed to determine predictors of successful weaning from VA-ECMO in the early phase of ECMO treatment. Methods: We identified consecutive patients of AMI complicated by CA treated with VA-ECMO and percutaneous coronary intervention (PCI). Clinical data within 48 h after ECMO initiation were assessed and multiple logistic regression analysis was performed to determine independent predictors of weaning outcome. Results: Fifty-five patients were analyzed. While 28 (51%) patients were successfully weaned from VA-ECMO, 27 (49%) failed to wean. Multivariate analysis identified post-PCI thrombolysis in myocardial infarction (TIMI) flow grade (P = 0.046), mean arterial pressure (MAP) at 4 h after ECMO initiation (P = 0.010), and serum lactate at 24 h (P = 0.015) as independent predictors of successful weaning. Left ventricular ejection fraction (LVEF) at 24 and 48 h was significantly greater in the successful weaning group (P = 0.014, P = 0.025, respectively). Conclusions: Successful weaning from VA-ECMO was predicted by post-PCI TIMI flow grade, MAP at 4 h, and serum lactate at 24 h after VA-ECMO initiation in patients of AMI complicated by CA. Furthermore, in patients who failed to wean from ECMO, LVEF did not recover within 48 h. In such patients, adjunctive use of other circulatory mechanical devices must be considered.
Occupational Therapy, Self-Efficacy, Well-Being in Older Adults Living in Residential Care Facilities: A Randomized Clinical Trial

Introduction: Choosing the type of treatment approach is as important as the treatment itself, also giving and important value to internal variables in the individual that can determine the evolution of the intervention. The main aim of this study is to determine whether individual and/or group occupational therapy leads to changes in generalized self-efficacy and psychological well-being, and to identify the type of therapy that has the best effects on older adults. Method: Prospective, randomized, comparing two treatment groups: individual and group therapy during 6 months. A total sample of 70 patients institutionalized in residential care homes for older adults with a mean age of 85 (SD = 4). Assessment was conducted using the General Self-Efficacy Scale and Ryff’s Well-being Scale. For analyze the main dependent variables we used ANOVA for intra-subject and inter-subject factors and Pearson correlation between well-being and self-efficacy by type of treatment. Results: Groups were equivalent at baseline. The results show statistically significant differences between the two types of therapy, showing a positive correlation between well-being and self-efficacy, being greater at a group level than at and individual level. At the group level, practically all of variables measured in the participants were increased as shown in the results tables, including a better adaptation and predisposition to work four participants died while the study was being conducted. Conclusion: The clinical trial shows that older people in residential centers achieve an increase in emotional well-being and self-efficacy when they receive occupational therapy group, rather than individual treatment not being significant changes. Treatment group participants reported a positive experience and clinical benefits from training program. The clinical trial was registered in the U.S. National Institutes of Health (ClinicalTrials.gov) with NCT02906306 identifier.
MP-HULA: Multipath Transport Aware Load Balancing Using Programmable Data Planes

Datacenter networks offer a large degree of multipath in order to provide large bisectional bandwidth. The end-to-end performance is determined by the load-balancing strategy which needs to be designed to effectively manage congestion. Consequently, congestion aware load-balancing strategies such as CONGA or HULA have been designed. Recently, more and more applications that are hosted on cloud servers use multipath transport protocols such as MPTCP. However, in the presence of MPTCP, existing load-balancing schemes including ECMP, HULA or CONGA may lead to suboptimal forwarding decisions where multiple MPTCP subflows of one connection are pinned on the same bottleneck link. In this paper, we present MP-HULA, a transport layer multi-path aware load-balancing scheme using Programmable Data Planes. First, instead of tracking congestion information for the best path towards the destination, each MP-HULA switch tracks congestion information for the best-k paths to a destination through the neighbor switches. Second, we design MP-HULA using Programmable Data Planes, where each leaf switch can identify, using P4, which MPTCP subflow belongs to which connection. MP-HULA then load-balances different MPTCP subflows of a MPTCP connection on different next hops considering congestion state while aggregating bandwidth. Our evaluation shows that MP-HULA with MPTCP outperforms HULA in average flow completion time (2.1x at 50% load, 1.7x at 80% load).
Studies on Aminoglycoside Susceptibility Identify a Novel Function of KsgA To Secure Translational Fidelity during Antibiotic Stress

Antibiotic resistance has become a global crisis. Studies on the mechanism of bacterial tolerance to antibiotics will not only increase our conceptual understanding of bacterial death but also provide potential targets for novel inhibitors. ABSTRACT Antibiotic resistance has become a global crisis. Studies on the mechanism of bacterial tolerance to antibiotics will not only increase our conceptual understanding of bacterial death but also provide potential targets for novel inhibitors. We screened a mutant library containing a full set of in-frame deletion mutants of Escherichia coli K-12 and identified 140 genes that possibly contribute to gentamicin tolerance. The deletion of ksgA increased the inhibition and killing potency against mid-log-phase bacteria by aminoglycosides. Initially identified as a 16S rRNA methyltransferase, KsgA also has additional functions as a ribosomal biogenesis factor and a DNA glycosylase. We found that the methyltransferase activity of KsgA is responsible for the tolerance, as demonstrated by a site-directed mutagenesis analysis. In contrast to the mechanism for cold sensitivity, the decreased tolerance to aminoglycoside is not related to the failure of ribosomal biogenesis. Furthermore, the DNA glycosylase activity of KsgA contributes minimally to kanamycin tolerance. Importantly, we discovered that KsgA secures protein translational fidelity upon kanamycin killing, in contrast to its role during cold stress and kasugamycin treatment. The results suggest that the compromise in protein translational fidelity in the absence of KsgA is the root cause of an increased sensitivity to a bactericidal aminoglycoside. In addition, KsgA in the pathogenic Acinetobacter baumannii contributes not only to the tolerance against aminoglycoside killing but also to virulence in the host, warranting its potential application as a target for inhibitors that potentiate aminoglycoside therapeutic killing as well as disarm bacterial virulence simultaneously.
Directed Evolution of Saccharomyces cerevisiae for Increased Selenium Accumulation

Selenium-enriched yeast (selenium yeast) are one of the most popular sources of selenium supplementation used in the agriculture and human nutritional supplements industries. To enhance the production efficiency of selenium yeast, we sought to develop a method to identify, and ultimately select for, strains of yeast with enhanced selenium accumulation capabilities. Selenite resistance of four genetically diverse strains of Saccharomyces cerevisiae was assayed in various conditions, including varying carbon sources, nitrogen sources, and phosphate amounts, and they were correlated with selenium accumulation in a commercially relevant selenium-containing growth medium. Glycerol- and selenite-containing media was used to select for six yeast isolates with enhanced selenite resistance. One isolate was found to accumulate 10-fold greater selenium (0.13 to 1.4 mg Se g−1 yeast) than its parental strain. Glycerol- and selenium-containing medium can be used to select for strains of yeast with enhanced selenium accumulation capability. The methods identified can lead to isolation of industrial yeast strains with enhanced selenium accumulation capabilities that can result in greater cost efficiency of selenium yeast production. Additionally, the selection method does not involve the construction of transgenic yeast, and thus produces yeasts suitable for use in human food and nutrient supplements.
Circulating Free Methylated Tumor DNA Markers for Sensitive Assessment of Tumor Burden and Early Response Monitoring in Patients Receiving Systemic Chemotherapy for Colorectal Cancer Liver Metastasis

Background: Neoadjuvant chemotherapy (neoCTx) followed by hepatic resection is the treatment of choice for patients with colorectal cancer liver metastasis (CLM). Treatment response is generally assessed using radiologic imaging after several cycles of chemotherapy. However, earlier assessment of response would be desirable since nonresponders could be switched early to an alternative chemotherapy regimen. Recent evidence suggests that circulating free methylated tumor DNA is a highly sensitive biomarker and may more accurately reflect tumor burden and treatment response than conventional markers for CRC. Patients and Methods: Thirty-four patients with CLM who received neoCTx prior to intended hepatic resection were included in this prospective nonrandomized study. Peripheral blood plasma was collected at baseline and before each cycle of neoCTx and was then analyzed for aberrant methylation of 48 CRC-associated genes. Methylation marker levels were correlated with baseline tumor volume and treatment response and compared with the standard tumor markers CEA and CA 19-9. Results: The methylation markers SEPT9, DCC, BOLL, and SFRP2 were present in all patients at baseline and displayed a stronger correlation with tumor volume than CEA and CA 19-9. Serial measurement of these methylation markers allowed for discrimination between operated and nonoperated patients already after 1 cycle of neoCTx with high sensitivity and specificity. The early dynamic changes of SEPT9 and DCC also seemed to correlate with pathohistological response. Conclusion: Our data suggest that serial measurements of CRC-associated methylation markers could be a particularly valuable tool for early response assessment in patients receiving neoCTx for CLM.
Algorithmic regulation and the rule of law

In this brief contribution, I distinguish between code-driven and data-driven regulation as novel instantiations of legal regulation. Before moving deeper into data-driven regulation, I explain the difference between law and regulation, and the relevance of such a difference for the rule of law. I discuss artificial legal intelligence (ALI) as a means to enable quantified legal prediction and argumentation mining which are both based on machine learning. This raises the question of whether the implementation of such technologies should count as law or as regulation, and what this means for their further development. Finally, I propose the concept of ‘agonistic machine learning’ as a means to bring data-driven regulation under the rule of law. This entails obligating developers, lawyers and those subject to the decisions of ALI to re-introduce adversarial interrogation at the level of its computational architecture. This article is part of a discussion meeting issue ‘The growing ubiquity of algorithms in society: implications, impacts and innovations'.
Modeled replacement of traditional soybean and canola oil with high-oleic varieties increases monounsaturated fatty acid and reduces both saturated fatty acid and polyunsaturated fatty acid intake in the US adult population.

BACKGROUND High-oleic (HO) seed oils are being introduced as replacements for trans fatty acid (TFA)-containing fats and oils. Negative health effects associated with TFAs led to their removal from the US Generally Recognized As Safe list. HO oils formulated for use in food production may result in changes in fatty acid intake at population levels. Objectives The purposes of this study were to 1) identify major food sources of soybean oil (SO) and canola oil (CO), 2) estimate effects of replacing SO and CO with HO varieties on fatty acid intake overall and by age and sex strata, and 3) compare predicted intakes with the Dietary Reference Intakes and Adequate Intakes (AIs) for the essential fatty acids (EFAs) α-linolenic acid (ALA) and linoleic acid (LA). Design Food and nutrient intakes from NHANES waves 2007-2008, 2009-2010, 2011-2012, and 2013-2014 in 21,029 individuals aged ≥20 y were used to model dietary changes. We estimated the intake of fatty acid with the replacement of HO-SO and HO-CO for commodity SO and CO at 10%, 25%, and 50% and evaluated the potential for meeting the AI at these levels. RESULTS Each modeling scenario decreased saturated fatty acids (SFAs), although intakes remained greater than recommended for all age and sex groups. Models of all levels increased the intake of total monounsaturated fatty acids (MUFAs), especially oleic acid, and decreased the intake of total polyunsaturated fatty acids (PUFAs), particularly LA and ALA. Replacement of traditional with HO oils at 25-50% places specific adult age and sex groups at risk of not meeting the AI for LA and ALA. Conclusions The replacement of traditional oils with HO varieties will increase MUFA intake and reduce both SFA and PUFA intakes, including EFAs, and may place specific age and sex groups at risk of inadequate LA and ALA intake.
Joint skeleton estimation of multiple directed acyclic graphs for heterogeneous population

The directed acyclic graph (DAG) is a powerful tool to model the interactions of high‐dimensional variables. While estimating edge directions in a DAG often requires interventional data, one can estimate the skeleton of a DAG (i.e., an undirected graph formed by removing the direction of each edge in a DAG) using observational data. In real data analyses, the samples of the high‐dimensional variables may be collected from a mixture of multiple populations. Each population has its own DAG while the DAGs across populations may have significant overlap. In this article, we propose a two‐step approach to jointly estimate the DAG skeletons of multiple populations while the population origin of each sample may or may not be labeled. In particular, our method allows a probabilistic soft label for each sample, which can be easily computed and often leads to more accurate skeleton estimation than hard labels. Compared with separate estimation of skeletons for each population, our method is more accurate and robust to labeling errors. We study the estimation consistency for our method, and demonstrate its performance using simulation studies in different settings. Finally, we apply our method to analyze gene expression data from breast cancer patients of multiple cancer subtypes.
Members of the GalNAc-T family of enzymes utilize distinct Golgi localization mechanisms

Mucin-type O-glycosylation is an evolutionarily conserved and essential post-translational protein modification that is initiated in the Golgi apparatus by a family of enzymes known as the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts). GalNAc-Ts are type II membrane proteins which contain short N-terminal tails located in the cytoplasm, a transmembrane domain that crosses the Golgi membrane, to which is connected a stem region that tethers the C-terminal catalytic and lectin domains that reside in the Golgi lumen. Although mucin-type O-glycans have been shown to play critical roles in numerous biological processes, little is known about how the GalNAc-Ts are targeted to their site of action within the Golgi complex. Here, we investigate the essential protein domains required for Golgi localization of four representative members of the GalNAc-T family of enzymes. We find that GalNAc-T1 and -T2 require their cytoplasmic tail and transmembrane domains for proper Golgi localization, while GalNAc-T10 requires its transmembrane and luminal stem domains. GalNAc-T7 can use either its cytoplasmic tail or its luminal stem, in combination with its transmembrane domain, to localize to the Golgi. We determined that a single glutamic acid in the GalNAc-T10 cytoplasmic tail inhibits its ability to localize to the Golgi via a cytoplasmic tail-dependent mechanism. We therefore demonstrate that despite their similarity, different members of this enzyme family are directed to the Golgi by more than one set of targeting signals.