Miracle-dz/UniFAR-FTUs huggingface dataset:
Jointly pooling aggregated effect sizes and their standard errors from studies with continuous clinical outcomes

The DerSimonian–Laird (DL) weighted average method for aggregated data meta‐analysis has been widely used for the estimation of overall effect sizes. It is criticized for its underestimation of the standard error of the overall effect size in the presence of heterogeneous effect sizes. Due to this negative property, many alternative estimation approaches have been proposed in the literature. One of the earliest alternative approaches was developed by Hardy and Thompson (HT), who implemented a profile likelihood instead of the moment‐based approach of DL. Others have further extended this likelihood approach and proposed higher‐order likelihood inferences (e.g., Bartlett‐type corrections). In addition, corrections factors for the estimated DL standard error, like the Hartung–Knapp–Sidik–Jonkman (HKSJ) adjustment, and the restricted maximum likelihood (REML) estimation have been suggested too. Although these improvements address the uncertainty in estimating the between‐study variance better than the DL method, they all assume that the true within‐study standard errors are known and equal to the observed standard errors of the effect sizes. Here, we will treat the observed standard errors as estimators for the within‐study variability and we propose a bivariate likelihood approach that jointly estimates the overall effect size, the between‐study variance, and the potentially heteroskedastic within‐study variances. We study the performance of the proposed method by means of simulation, and compare it to DL (with and without HKSJ), HT, their higher‐order likelihood methods, and REML. Our proposed approach seems to have better or similar coverages compared to the other approaches and it appears to be less biased in the case of heteroskedastic within‐study variances when this heteroskedasticty is correlated with the effect size.
ESPGHAN Position Paper on Management and Follow-up of Children and Adolescents With Celiac Disease

There is a need for consensus on the recommendations for follow-up of children and adolescents with celiac disease. Objectives: To gather the current evidence and to offer recommendations for follow-up and management. Methods: The Special Interest Group on Celiac Diseases of the European Society of Paediatric Gastroenterology Hepatology and Nutrition formulated ten questions considered to be essential for follow-up care. A literature search (January 2010–March 2020) was performed in PubMed or Medline. Relevant publications were identified and potentially eligible studies were assessed. Statements and recommendations were developed and discussed by all coauthors. Recommendations were voted upon: joint agreement was set as at least 85%. Results: Publications (n = 2775) were identified and 164 were included. Using evidence or expert opinion, 37 recommendations were formulated on: The need to perform follow-up, its frequency and what should be assessed, how to assess adherence to the gluten-free diet, when to expect catch-up growth, how to treat anemia, how to approach persistent high serum levels of antibodies against tissue-transglutaminase, the indication to perform biopsies, assessment of quality of life, management of children with unclear diagnosis for which a gluten-challenge is indicated, children with associated type 1 diabetes or IgA deficiency, cases of potential celiac disease, which professionals should perform follow-up, how to improve the communication to patients and their parents/caregivers and transition from pediatric to adult health care. Conclusions: We offer recommendations to improve follow-up of children and adolescents with celiac disease and highlight gaps that should be investigated to further improve management.
Analysis of Pleurotin binding to human thioredoxin reductase using docking and molecular dynamics simulation

Abstract Thioredoxin reductase (TrxR) has been considered a potential target for cancer chemotherapy. It acts by controlling the redox homeostasis of human cells and, therefore, interfering in its function may trigger apoptosis, which is a crucial tumor suppression mechanism. Despite the great effort in the search for TrxR inhibitors, none was approved for human therapy. In the present study a virtual screening for natural organic compounds is discussed for a set of 72 compounds with known IC-50 for TrxR inhibition. The results suggest the Pleurotin, a naphthoquinone obtained from Hohenbuehelia grisea fungus, as a potential TrxR inhibitor, which acts by binding to the active site of the enzyme, between the N- and C-terminal domains. The presence of the ligand blocks the approximation of the C-terminal arm to the N-terminal, which is an essential step of the enzyme function. Besides, the two equivalent binding sites of TrxR were explored, by docking two ligands simultaneously. The results indicate that both sites have an allosteric correlation and, the presence of the ligand in one site may interfere, or even prevent, the binding of the second ligand at the other site. All these findings are quantitatively discussed based on the analysis of long molecular dynamics trajectories, which provides a full description of the ligand-receptor binding modes, average binding energies and conformational changes. Communicated by Ramaswamy H. Sarma
Assessing the ecological validity of soundscape reproduction in different laboratory settings

The ever-growing body of soundscape research includes studies conducted both in everyday life environments and in laboratory settings. Yet, laboratory settings differ from in-situ and therefore may elicit different perceptions. The present study explores the ecological validity of soundscape reproduction in the laboratory using first-order Ambisonics and of different modes of questionnaire administration. Furthermore, it investigates the influence of the contextual factors of time of day, day of the week, and location on site on soundscape evaluations in situ and in the laboratory, based on the Swedish Soundscape Quality Protocol. We first tested measurement invariance between the computer-based and pen-and-paper administration of the soundscape questionnaire. We then investigated the influence of the above-mentioned contextual factors on soundscape evaluations, as well as the effect of stimuli selection in the laboratory. The analyses confirmed the underlying dimensions of proposed soundscape assessment questionnaires, confirmed metric invariance between computer and pen-and-paper, and revealed significant influences of time, day, and location on soundscape scales. This research represents a critical step in rigorously assessing soundscape evaluations in the laboratory and establishes solid evidence for the use of both in situ and laboratory soundscape studies.
Methotrexate for Primary Maintenance Therapy in Mild-to-Moderate Crohn Disease in Children

Objectives: Despite limited data, methotrexate (MTX) is often used as primary maintenance therapy in pediatric Crohn disease (CD). We sought to assess the effectiveness of MTX as “initial” primary maintenance therapy in newly diagnosed mild/moderate pediatric CD and ascertain baseline predictive factors. Methods: Single-center 10-year retrospective review of newly diagnosed CD patients treated with MTX as primary maintenance therapy. We compared baseline characteristics of those patients with sustained response/clinical remission to those patients who escalated to anti-TNF therapy within 1 year. Pediatric Crohn Disease Activity Index (PCDAI) ≤ 10 defined remission. Results: We identified 65 patients (mean age, 11.8 years; 72 % male; mean ± SD PCDAI, 17.8 ± 10.5) who started MTX ≤4 months of diagnosis as their primary maintenance therapy. Initial therapy prior to MTX was corticosteroids (CS) (54/65), defined diet (4/65), and combination CS/diet (6/65). Oral dosing was used in 55%; mean dose was 11.4 mg/m2 orally and 12.5 mg/m2 subcutaneously. At 1 year, 36 of 65 (55%) were on MTX monotherapy, and of those, 32 of 36 were in clinical remission; 81% were in steroid-free remission for the year following induction. For the 36 patients on MTX at 1 year, 14 (39%) had gross mucosal healing (22% of the original cohort). Ten additional patients had mucosal improvement (37% of total healed/improved). Fifteen patients (23%) were early failures, transitioning to anti-TNF ≤4 months. Baseline PCDAI, hemoglobin, ESR, albumin, and route of administration were not predictive of outcome. MTX was well tolerated in our cohort, with only 1 patient stopping due to elevated aminotransferases. No patient required CD surgery in the 1-year follow-up. Conclusions: MTX may have a primary maintenance role in mild/moderate CD.
Impact of biotin supplemented diet on mouse pancreatic islet β-cell mass expansion and glucose induced electrical activity

ABSTRACT Biotin supplemented diet (BSD) is known to enhance β-cell replication and insulin secretion in mice. Here, we first describe BSD impact on the islet β-cell membrane potential (Vm) and glucose-induced electrical activity. BALB/c female mice (n ≥ 20) were fed for nine weeks after weaning with a control diet (CD) or a BSD (100X). In both groups, islet area was compared in pancreatic sections incubated with anti-insulin and anti-glucagon antibodies; Vm was recorded in micro dissected islet β-cells during perfusion with saline solutions containing 2.8, 5.0, 7.5-, or 11.0 mM glucose. BSD increased the islet and β-cell area compared with CD. In islet β-cells of the BSD group, a larger ΔVm/Δ[glucose] was found at sub-stimulatory glucose concentrations and the threshold glucose concentration for generation of action potentials (APs) was increased by 1.23 mM. Moreover, at 11.0 mM glucose, a significant decrease was found in AP amplitude, frequency, ascending and descending slopes as well as in the calculated net charge influx and efflux of islet β-cells from BSD compared to the CD group, without changes in slow Vm oscillation parameters. A pharmacological dose of biotin in mice increases islet insulin cell mass, shifts islet β-cell intracellular electrical activity dose response curve toward higher glucose concentrations, very likely by increasing KATP conductance, and decreases voltage gated Ca2+ and K+ conductance at stimulatory glucose concentrations. Graphical Abstract
Effect of sodium-glucose co-transporter-2 inhibitors on arterial stiffness: A systematic review and meta-analysis of randomized controlled trials

Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.
Variational Quantum Algorithm for Approximating Convex Roofs

Many entanglement measures are first defined for pure states of a bipartite Hilbert space, and then extended to mixed states via the convex roof extension. In this article we alter the convex roof extension of an entanglement measure, to produce a sequence of extensions that we call $f$-$d$ extensions, for $d \in \mathbb{N}$, where $f:[0,1]\to [0, \infty)$ is a fixed continuous function which vanishes only at zero. We prove that for any such function $f$, and any continuous, faithful, non-negative function, (such as an entanglement measure), $\mu$ on the set of pure states of a finite dimensional bipartite Hilbert space, the collection of $f$-$d$ extensions of $\mu$ detects entanglement, i.e. a mixed state $\rho$ on a finite dimensional bipartite Hilbert space is separable, if and only if there exists $d \in \mathbb{N}$ such that the $f$-$d$ extension of $\mu$ applied to $\rho$ is equal to zero. We introduce a quantum variational algorithm which aims to approximate the $f$-$d$ extensions of entanglement measures defined on pure states. However, the algorithm does have its drawbacks. We show that this algorithm exhibits barren plateaus when used to approximate the family of $f$-$d$ extensions of the Tsallis entanglement entropy for a certain function $f$ and unitary ansatz $U(\theta)$ of sufficient depth. In practice, if additional information about the state is known, then one needs to avoid using the suggested ansatz for long depth of circuits.
Modeling of slab-on-grade heat transfer in EnergyPlus simulation program

The heat flow through the floor and the ground of a single-story slab-on-grade building is one of the most influential aspects in its thermal and energy performance. However, there are still many uncertainties and only few studies on the subject. This study compares different modeling alternatives of the parameters related to the heat transfer between the floor and the ground, and their influence in the thermal performance of a naturally ventilated single-story house located in Sao Carlos, Brazil, using the programs EnergyPlus (8.5.0) and Slab (.75). The comparison between the modeling alternatives indicated wide variation in the results. When compared with Slab, the KusudaAchenbach method of the object Ground Domain presented the largest variation, with a difference of 55.2 % in the number of degree-hours of discomfort. It was observed that even the way of using Slab - for example, with or without the convergence procedure - could cause significant differences in the results. The thermal conductivity of the soil was a parameter of great impact, resulting in differences of up to 57.5 % in discomfort. Such results provide indications of the variability and impact of the different modeling options for this type of heat transfer in EnergyPlus.
When Resilience Becomes Risk: A Latent Class Analysis of Psychosocial Resources and Allostatic Load Among African American Men

There is a well-established link between psychosocial risks and psychological health among African American (AA) men. Yet, the psychosocial sources and physical health consequences of resilience (i.e., the ability to maintain good health despite adversity) remain underexplored. Using data from 283 AA men in the Nashville Stress and Health Study, the present study investigated the links between psychosocial resilience and allostatic load (AL), a biological indicator of physiological dysregulation. Latent class analysis (LCA) identified distinct resilience profiles comprising eight psychosocial resources across four categories: coping strategies, sense of control, racial identity, and social support. Analysis of variance (ANOVA) tests determined significant class differences in men’s AL scores. LCA results confirm a four-class model was the best fit: Class 1 (high resources, 32%), Class 2 (high coping but low control, 13%), Class 3 (low resources but high racial identity, 20%), and Class 4 (low resources but high mastery, 34%). Results reveal lower AL (better health) among Classes 1 (m = 0.35) and 4 (m = 0.31) and higher AL (worse health) among Classes 2 (m = 0.44) and 3 (m = 0.44). Findings indicate that the “quality” rather than the “quantity” of psychosocial resources matters for physical health among AA men, as positive health outcomes were observed among both low- and high-resource classes. Results suggest different resource combinations produce distinct patterns of resilience among AA men and underscore the need to further elucidate complex resilience processes among this population.
Synergistic effect of probiotic, chicory root powder and coriander seed powder on growth performance, antioxidant activity and gut health of broiler chickens

Gut health plays an important role on production and performance of broilers. This trial was undertaken with an aim to evaluate the synergistic effect of probiotic, chicory root powder and coriander seed powder on the performance and gut health of broiler chicken. For this purpose, a total of 240 day-old broiler chicks were randomly allotted to six dietary treatments with 8 replicates of 5 birds in each. Treatment groups included T1 as control i.e., basal diet (BD) without any growth promoter and T2—BD + antibiotic (BMD 0.05%). In the remaining experimental diets, T3—probiotic (@ 0.01%) + chicory root powder (@ 1.0%), T4—probiotic (@ 0.01%) + coriander seed powder (@ 1.5%), T5—chicory root powder (@ 1.0%) + coriander seed powder (@ 1.5%) and T6—probiotic (@ 0.01%) + chicory root powder (@ 1.0%) + coriander seed powder (@ 1.5%). The results indicated that supplementation of probiotic + chicory (T3), probiotic + coriander (T4), chicory + coriander (T5) and probiotic + chicory + coriander (T6) in combination resulted in significantly (P<0.05) higher weight gain and better FCR compared to control and antibiotic groups at 42 d of age. Supplementation of different dietary groups did not show any significant (P>0.05) effect on feed intake of broilers. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) increased the glutathione peroxidase (GSHPx), glutathione reductase (GSHRx) and superoxide dismutase (SOD) enzyme activity when compared to control and antibiotic groups at 42 d of age. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) lowered the pH in the gut, increased Lactobacillus counts, and reduced E. coli and Salmonella counts in the ileum compared to control and antibiotic groups. Supplementation of all the test diets (T3 to T6) significantly (P<0.05) increased the villus height (VH), crypt depth (CD), VH:CD ratio and villus width (VW) in the duodenum and only VH and CD in the ileum compared to control and antibiotic groups. Significantly (P<0.05) higher jejunal VH and VW and increased the goblet cell number in duodenum, jejunum and ileum was recorded in all test diets (T3 to T6) compared to control and antibiotic groups. Therefore, combinations of probiotic (0.01%), chicory root powder (1.0%) and coriander seed powder (1.5%) can be used as feed additive for improving performance and gut health of broiler chicken.
k-Median Clustering via Metric Embedding: Towards Better Initialization with Differential Privacy

When designing clustering algorithms, the choice of initial centers is crucial for the quality of the learned clusters. In this paper, we develop a new initialization scheme, called HST initialization, for the $k$-median problem in the general metric space (e.g., discrete space induced by graphs), based on the construction of metric embedding tree structure of the data. From the tree, we propose a novel and efficient search algorithm, for good initial centers that can be used subsequently for the local search algorithm. Our proposed HST initialization can produce initial centers achieving lower errors than those from another popular initialization method, $k$-median++, with comparable efficiency. The HST initialization can also be extended to the setting of differential privacy (DP) to generate private initial centers. We show that the error from applying DP local search followed by our private HST initialization improves previous results on the approximation error, and approaches the lower bound within a small factor. Experiments justify the theory and demonstrate the effectiveness of our proposed method. Our approach can also be extended to the $k$-means problem.
Topsy-Turvy: integrating a global view into sequence-based PPI prediction

Abstract Summary Computational methods to predict protein–protein interaction (PPI) typically segregate into sequence-based ‘bottom-up’ methods that infer properties from the characteristics of the individual protein sequences, or global ‘top-down’ methods that infer properties from the pattern of already known PPIs in the species of interest. However, a way to incorporate top-down insights into sequence-based bottom-up PPI prediction methods has been elusive. We thus introduce Topsy-Turvy, a method that newly synthesizes both views in a sequence-based, multi-scale, deep-learning model for PPI prediction. While Topsy-Turvy makes predictions using only sequence data, during the training phase it takes a transfer-learning approach by incorporating patterns from both global and molecular-level views of protein interaction. In a cross-species context, we show it achieves state-of-the-art performance, offering the ability to perform genome-scale, interpretable PPI prediction for non-model organisms with no existing experimental PPI data. In species with available experimental PPI data, we further present a Topsy-Turvy hybrid (TT-Hybrid) model which integrates Topsy-Turvy with a purely network-based model for link prediction that provides information about species-specific network rewiring. TT-Hybrid makes accurate predictions for both well- and sparsely-characterized proteins, outperforming both its constituent components as well as other state-of-the-art PPI prediction methods. Furthermore, running Topsy-Turvy and TT-Hybrid screens is feasible for whole genomes, and thus these methods scale to settings where other methods (e.g. AlphaFold-Multimer) might be infeasible. The generalizability, accuracy and genome-level scalability of Topsy-Turvy and TT-Hybrid unlocks a more comprehensive map of protein interaction and organization in both model and non-model organisms. Availability and implementation https://topsyturvy.csail. mit.edu. Supplementary information Supplementary data are available at Bioinformatics online.
CS2: A Controllable and Simultaneous Synthesizer of Images and Annotations with Minimal Human Intervention

The destitution of image data and corresponding expert annotations limit the training capacities of AI diagnostic models and potentially inhibit their performance. To address such a problem of data and label scarcity, generative models have been developed to augment the training datasets. Previously proposed generative models usually require manually adjusted annotations (e.g., segmentation masks) or need pre-labeling. However, studies have found that these pre-labeling based methods can induce hallucinating artifacts, which might mislead the downstream clinical tasks, while manual adjustment could be onerous and subjective. To avoid manual adjustment and pre-labeling, we propose a novel controllable and simultaneous synthesizer (dubbed CS$$