Miracle-dz/UniFAR-FTUs huggingface dataset:
Filgotinib versus placebo or adalimumab in patients with rheumatoid arthritis and inadequate response to methotrexate: a phase III randomised clinical trial

Objective To evaluate the efficacy and safety of the Janus kinase-1-preferential inhibitor filgotinib versus placebo or tumour necrosis factor-α inhibitor therapy in patients with active rheumatoid arthritis (RA) despite ongoing treatment with methotrexate (MTX). Methods This 52-week, multicentre, double-blind, placebo-controlled and active-controlled phase III trial evaluated once-daily oral filgotinib in patients with RA randomised 3:3:2:3 to filgotinib 200 mg (FIL200) or filgotinib 100 mg (FIL100), subcutaneous adalimumab 40 mg biweekly, or placebo (through week 24), all with stable weekly background MTX. The primary endpoint was the proportion of patients achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 12. Additional efficacy outcomes were assessed sequentially. Safety was assessed from adverse events and laboratory abnormalities. Results The proportion of patients (n=1755 randomised and treated) achieving ACR20 at week 12 was significantly higher for FIL200 (76.6%) and FIL100 (69.8%) versus placebo (49.9%; treatment difference (95% CI), 26.7% (20.6% to 32.8%) and 19.9% (13.6% to 26.2%), respectively; both p<0.001). Filgotinib was superior to placebo in key secondary endpoints assessing RA signs and symptoms, physical function and structural damage. FIL200 was non-inferior to adalimumab in terms of Disease Activity Score in 28 joints with C reactive protein ≤3.2 at week 12 (p<0.001); FIL100 did not achieve non-inferiority. Adverse events and laboratory abnormalities were comparable among active treatment arms. Conclusions Filgotinib improved RA signs and symptoms, improved physical function, inhibited radiographic progression and was well tolerated in patients with RA with inadequate response to MTX. FIL200 was non-inferior to adalimumab. Trial registration number NCT02889796.
Help-Seeking Within the Context of Patriarchy for Domestic Violence in Urban Uganda

This study in urban Kampala contributes to a growing evidence base about the complex contexts within which women make decisions about reporting domestic violence. Based on an intersecting theoretical lens of structural violence, power, and the body, findings suggested that women reported to formal structures primarily for severe physical or economic abuse. Women did not report less severe abuse, and often abandoned reporting even severe abuse, because of the overarching structural patriarchy and violence that exists, as well as women’s habitus that includes the embodiment of social norms that sanction reporting. Yet, while overwhelmingly women are discouraged from reporting domestic abuse, there were important signs of change.
Hemodynamic Assay of Hind Limb in Multiple Animal Models.

INTRODUCTION Measuring hemodynamic characteristics of injured limbs is paramount to early identification of potentially damaging ischemic conditions, but can often prove difficult attributable to a multitude of factors. Here, we present an in vivo optical imaging technique to characterize pulsatile blood flow quality through the distal extremity in multiple animal models that replicate the signs of distal extremity ischemia. The purpose of this study is to examine the feasibility of the optical imaging technique and relevance to hemodynamic complications such as acute compartment syndrome (ACS) and nonobvious hemorrhage. MATERIALS AND METHODS In one pig and six mice, three different methods were used to create ischemic conditions in the lower extremity, producing symptoms similar to what is observed in ACS. In each condition, perfusion to the distal extremity was measured with the hemodynamic detection device (HDD; Odin Technologies), an optical assessment tool for perfusion and blood flow quality. RESULTS We observed a profound decrease in extremity perfusion immediately after onset of ischemia in all three models. In the porcine model, the HDD's measurements demonstrated similar characteristic flow between the various measurement locations. After the tourniquet was applied, the HDD revealed a 95% decrease in normalized perfusion value (npv) while the intracompartmental pressure rose from 5 to 52 mmHg (a 47mmHg increase). After the tourniquet was removed during reperfusion, the normalized blood flow returned to baseline and the intracompartmental pressure dropped from 20 to 6 mmHg in less than 5 minutes. For each mouse, the HDD test leg demonstrated a measurement of 0.97 npv before femoral ligation and 0.05 npv after femoral ligation, an 89% decrease (P < .01) in flow. Pulsed-wave Doppler ultrasound (PWDU) measurements on the test leg had pre-ligation measurement of 0.84 npv and a post-ligation measurement of 0.001 npv, a 99% decrease. These PWDU measurements revealed almost complete stoppage of blood flow during ischemia, followed by a substantial increase after the femoral artery ligation was removed. CONCLUSIONS Here, we show that a novel, optics-based sensing system can be used to diagnose and assess ACS in animal models. This technology is comparable to other standards used to monitor ACS and nonobvious hemorrhage and may also be a plausible alternative to prolonged invasive monitoring of patients with sustained extremity trauma.
Impact of the COVID-19 Outbreak on Trends in Emergency Department Utilization in Children: a Multicenter Retrospective Observational Study in Seoul Metropolitan Area, Korea

Background Understanding the changes in emergency department (ED) visit patterns during the coronavirus disease 2019 (COVID-19) outbreak is important for effectively operating EDs during the pandemic. We aimed to analyze the changes in pediatric ED visits during the COVID-19 pandemic and examine the relationship between the number of ED visits and the stringency of government social distancing measures. Methods This multicenter retrospective study used data of pediatric (age < 18 years) ED visits in Seoul metropolitan area from June 1, 2018, to May 31, 2020. Patient demographics, ED results, and diagnoses were compared during the COVID-19 period and the previous year. To evaluate the effect of the stringency of social distancing measures on the number of ED visits, a Poisson regression model was developed with month, year, and the average monthly Government Response Stringency Index (GRSI) as fixed effects. Results In total, 190,732 patients were included. The number of pediatric ED visits during the COVID-19 period was 58.1% lower than in the previous year. There were disproportionate decreases in the numbers of ED visits for children in early childhood (66.5%), low-acuity children (55.2-63.8%), those who did not use an ambulance (59.0%), and those visiting the ED for noninjury complaints (64.9%). The proportion of admissions increased from 11.9% to 16.6%. For every 10-point increase in the GRSI, there was a 15.1% decrease in monthly ED visits. Conclusion A striking decrease in pediatric ED visits was observed during the COVID-19 outbreak, the scale which was associated with the stringency of government policies. Changes in the number and characteristics of children visiting the ED should be considered to facilitate the effective operation of EDs during the pandemic.
Peer‐reported bullying, rejection and hallucinatory experiences in childhood

Psychotic experiences, such as hallucinations, occur commonly in children and have been related to bullying victimization. However, whether bullying perpetration, peer rejection, or peer acceptance are related to hallucinatory experiences has remained under‐examined. We used a novel peer nomination method to examine whether (i) bullying perpetration and (ii) social positions within peer networks were associated with future hallucinatory experiences.
Synthesis of a novel nanocomposite containing chitosan as a three‐dimensional printed wound dressing technique: Emphasis on gene expression

In this study, a highly porous three‐dimensional (3D)‐printed wound healing core/shell scaffold fabricated using poly‐lactic acid (PLA). The core of scaffold was composed of hyaluronic acid (HA), copper carbon dots (Cu‐CDs), rosmarinic acid, and chitosan hydrogel. Cu‐CDs were synthesized using ammonium hydrogen citrate under hydrothermal conditions. Formulation containing 1 mg ml−1concentration of Cu‐CDs showed an excellent antibacterial activity against gram bacteria. At 0.25 mg ml−1 of Cu‐CDs concentration, scaffold had a good biocompatibility as confirmed by cytotoxicity assay on L929 fibroblast stem cells. in vivo wound healing experiments on groups of rats revealed that after 15 days of treatment, the optimal formulation of composite scaffold significantly improves the wound healing process compared to the PLA scaffold. This finding was confirmed by histological analysis and the relative expression of PDGF, TGF‐β, and MMP‐1 genes. The biocompatible antibacterial CU‐CDS/PLA/HA/chitosan/rosmarinic acid nanocomposite is a promising wound healing scaffold which highly accelerates the process of skin regeneration.
Artificial Intelligence-Aided Colonoscopy for Polyp Detection: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background: This study aimed to compare artificial intelligence (AI)-aided colonoscopy with conventional colonoscopy for polyp detection. Methods: A systematic literature search was performed in PubMed and Ovid for randomized clinical trials (RCTs) comparing AI-aided colonoscopy with conventional colonoscopy for polyp detection. The last search was performed on July 22, 2020. The primary outcome was polyp detection rate (PDR) and adenoma detection rate (ADR). Results: Seven RCTs published between 2019 and 2020 with a total of 5427 individuals were included. When compared with conventional colonoscopy, AI-aided colonoscopy significantly improved PDR (P < .001, odds ratio [OR] = 1.95, 95% confidence interval [CI]: 1.75 to 2.19, I2 = 0%) and ADR (P < .001, OR = 1.72, 95% CI: 1.52 to 1.95, I2 = 33%). Besides, polyps in the AI-aided group were significantly smaller in size than those in conventional group (P = .004, weighted mean difference = -0.48, 95% CI: -0.81 to -0.15, I2 = 0%). In addition, AI-aided group detected significantly less proportion of advanced adenoma (P = .03, OR = 0.70, 95% CI: 0.50 to 0.97, I2 = 46%), pedicle polyps (P < .001, OR = 0.64, 95% CI: 0.49 to 0.83, I2 = 0%), and pedicle adenomas (P < .001, OR = 0.60, 95% CI: 0.44 to 0.80, I2 = 0%). Conclusion: AI-aided colonoscopy could significantly increase the PDR and ADR, especially for those with small size. Besides, the shape and pathology recognition of the AI technique should be further improved in the future.
Low forest productivity associated with increasing drought‐tolerant species is compensated by an increase in drought‐tolerance richness

Many temperate forests are changing in composition due to a combination of changes in land‐use, management and climate‐related disturbances. Previous research has shown that in some regions these changes frequently favour drought‐tolerant tree species. However, the effects of these changes in composition on forest functioning (e.g. productivity) are unclear. We studied 25 years of change in individual tree biomass growth, ingrowth and mortality, and community composition and total plot biomass across 2663 permanent forest plots in Catalonia (NE Spain) comprising 85,220 trees of 59 species. We focused on the relationship between community‐level forest productivity and drought tolerance (DT), which was estimated using hydraulic traits as well as biogeographic indicators. We found that there was a small increase (1.6%–3.2% on average) in community‐mean DT (DTcwm) during the study period, concurrent with a strong increase (12.4%–19.4% on average) in DT richness (DTric; i.e. trait range). Most importantly, we found that the mean DT was negatively related to forest productivity, which was explained because drought‐tolerant tree species have lower tree‐level growth. In contrast, DT richness was strongly and positively related to forest productivity, probably because it allowed for a more stable production along wet and dry periods. These results suggest a negative impact of ongoing climate change on forest productivity mediated by functional composition shifts (i.e. selection of drought‐tolerant species), and a positive effect of increased DT richness as a consequence of land‐use legacies. Such a trend towards functional diversification, although temporary, would increase forests’ capacity to resist drought and place them in a better position to face the expected change in climate.
Women's fasting habits and dietary diversity during Ramadan in rural Bangladesh

Abstract Little is known about fasting practices and dietary changes during Ramadan in low‐ and lower‐middle‐income countries. Although pregnant women are exempt from fasting, they may still fast. This is of interest as dietary habits during pregnancy may affect the development of the unborn child. In a community‐based sample of young women in rural Sylhet division, Bangladesh, we described fasting practices and beliefs (n = 852). We also examined reported food group consumption and minimally adequate dietary diversity for women (MDD‐W) by Ramadan occurrence (n = 1,895) and by fasting adherence (n = 558) using logistic regression with Hindu women as a seasonal control. During Ramadan in 2018, 78% of pregnant Muslim women fasted every day. Over 80% of Muslim women believe that they should fast during pregnancy and over 50% expect positive health effects on the mother and the unborn child. We found strong evidence that Muslim women have more diverse diets during Ramadan, with higher odds of MDD‐W (OR [95% CI]: 5.0 [3.6, 6.9]) and increased consumption of pulses, dairy, fruit, and large fish. Dietary diversity increased to a lesser extent on non‐fasting days during Ramadan. Ramadan appears to improve dietary quality in both fasting and non‐fasting Muslim women in a rural population in Bangladesh. These results help to interpret findings from studies on Ramadan during pregnancy on later‐life outcomes and thus contribute to a better understanding of intrauterine influences of maternal nutrition on healthy child development.
Degradation of insulating materials under electrical stress

An avalanche of physical and physicochemical phenomena, often self-sustained, leads to the end of life of an insulating material. The collapse of the insulating role of a material is mostly due to the electrical field stress. The path leading from the catastrophic situation, the breakdown, back to its origin is followed in the present paper. A defect, pre-existing or created by the in-service stresses, gives rise to an ionization process in a volume bounded by insulating walls. With time the process does not remain identical due to both changes in the material and gas evolution, which makes it difficult to interpret the detected electrical signal. The end of life will occur through microcracks in which new discharges are initiated, activating the propagation of these structural failures. This change of structure of the insulating material when due to the existence of water molecules will lead to the same kind of final degradation. The polymeric insulating materials could contain additives but they lead only to a partial healing. From polymers of low complexity such as the PE used in cables, assuming that there is no pre-existing defect, one endeavors to understand how a microstructure reacts with a local field or accumulated charges. The present paper summarizes the thoughts of the author pertaining to the problems of aging and dielectric breakdown in organic insulating materials, processes often given a concrete form through experiments.
LARP1 and LARP4: up close with PABP for mRNA 3’ poly(A) protection and stabilization

ABSTRACT La-related proteins (LARPs) share a La motif (LaM) followed by an RNA recognition motif (RRM). Together these are termed the La-module that, in the prototypical nuclear La protein and LARP7, mediates binding to the UUU-3ʹOH termination motif of nascent RNA polymerase III transcripts. We briefly review La and LARP7 activities for RNA 3ʹ end binding and protection from exonucleases before moving to the more recently uncovered poly(A)-related activities of LARP1 and LARP4. Two features shared by LARP1 and LARP4 are direct binding to poly(A) and to the cytoplasmic poly(A)-binding protein (PABP, also known as PABPC1). LARP1, LARP4 and other proteins involved in mRNA translation, deadenylation, and decay, contain PAM2 motifs with variable affinities for the MLLE domain of PABP. We discuss a model in which these PABP-interacting activities contribute to poly(A) pruning of active mRNPs. Evidence that the SARS-CoV-2 RNA virus targets PABP, LARP1, LARP 4 and LARP 4B to control mRNP activity is also briefly reviewed. Recent data suggests that LARP4 opposes deadenylation by stabilizing PABP on mRNA poly(A) tails. Other data suggest that LARP1 can protect mRNA from deadenylation. This is dependent on a PAM2 motif with unique characteristics present in its La-module. Thus, while nuclear La and LARP7 stabilize small RNAs with 3ʹ oligo(U) from decay, LARP1 and LARP4 bind and protect mRNA 3ʹ poly(A) tails from deadenylases through close contact with PABP. Abbreviations: 5ʹTOP: 5ʹ terminal oligopyrimidine, LaM: La motif, LARP: La-related protein, LARP1: La-related protein 1, MLLE: mademoiselle, NTR: N-terminal region, PABP: cytoplasmic poly(A)-binding protein (PABPC1), Pol III: RNA polymerase III, PAM2: PABP-interacting motif 2, PB: processing body, RRM: RNA recognition motif, SG: stress granule.
Glial amplification of synaptic signals

Recent studies have repeatedly demonstrated the cross‐talk of heterogeneous signals between neuronal and glial circuits. Here, we investigated the mechanism and the influence of physiological interactions between neurons and glia in the cerebellum. We found that the cerebellar astrocytes, Bergmann glial cells, react to exogenously applied glutamate, glutamate transporter substrate (d‐aspartate) and synaptically released glutamate. In response, the Bergmann glial cells release glutamate through volume‐regulated anion channels. It is generally assumed that all of the postsynaptic current is mediated by presynaptically released glutamate. However, we showed that a part of the postsynaptic current is mediated by glutamate released from Bergmann glial cells. Optogenetic manipulation of Bergmann glial state with archaerhodpsin‐T or channelrhodopsin‐2 reduced or augmented the amount of glial glutamate release, respectively. Our data indicate that glutamate‐induced glutamate release in Bergmann glia serves as an effective amplifier of excitatory information processing in the brain.
Which indoor residual spraying insecticide best complements standard pyrethroid long-lasting insecticidal nets for improved control of pyrethroid resistant malaria vectors?

Background Where resources are available, non-pyrethroid IRS can be deployed to complement standard pyrethroid LLINs with the aim of achieving improved vector control and managing insecticide resistance. The impact of the combination may however depend on the type of IRS insecticide deployed. Studies comparing combinations of pyrethroid LLINs with different types of non-pyrethroid IRS products will be necessary for decision making. Methods The efficacy of combining a standard pyrethroid LLIN (DuraNet®) with IRS insecticides from three chemical classes (bendiocarb, chlorfenapyr and pirimiphos-methyl CS) was evaluated in an experimental hut trial against wild pyrethroid-resistant Anopheles gambiae s.l. in Cové, Benin. The combinations were also compared to each intervention alone. WHO cylinder and CDC bottle bioassays were performed to assess susceptibility of the local An. gambiae s.l. vector population at the Cové hut site to insecticides used in the combinations. Results Susceptibility bioassays revealed that the vector population at Cové, was resistant to pyrethroids (<20% mortality) but susceptible to carbamates, chlorfenapyr and organophosphates (≥98% mortality). Mortality of wild free-flying pyrethroid resistant An. gambiae s.l. entering the hut with the untreated net control (4%) did not differ significantly from DuraNet® alone (8%, p = 0.169). Pirimiphos-methyl CS IRS induced the highest mortality both on its own (85%) and in combination with DuraNet® (81%). Mortality with the DuraNet® + chlorfenapyr IRS combination was significantly higher than each intervention alone (46% vs. 33% and 8%, p<0.05) demonstrating an additive effect. The DuraNet® + bendiocarb IRS combination induced significantly lower mortality compared to the other combinations (32%, p<0.05). Blood-feeding inhibition was very low with the IRS treatments alone (3–5%) but increased significantly when they were combined with DuraNet® (61% - 71%, p<0.05). Blood-feeding rates in the combinations were similar to the net alone. Adding bendiocarb IRS to DuraNet® induced significantly lower levels of mosquito feeding compared to adding chlorfenapyr IRS (28% vs. 37%, p = 0.015). Conclusions Adding non-pyrethroid IRS to standard pyrethroid-only LLINs against a pyrethroid-resistant vector population which is susceptible to the IRS insecticide, can provide higher levels of vector mosquito control compared to the pyrethroid net alone or IRS alone. Adding pirimiphos-methyl CS IRS may provide substantial improvements in vector control while adding chlorfenapyr IRS can demonstrate an additive effect relative to both interventions alone. Adding bendiocarb IRS may show limited enhancements in vector control owing to its short residual effect.
Concerning Synthesis of New Biobased Polycarbonates with Curcumin in Replacement of Bisphenol A and Recycled Diphenyl Carbonate as Example of Circular Economy

Curcumin (CM) is a natural polyphenol well-known for its antioxidant and pharmaceutical properties, that can represent a renewable alternative to bisphenol A (BPA) for the synthesis of bio-based polycarbonates (PC). In the presented strategy, preparation of the CM-based PC was coupled with chemical recycling of the fossil-based BPA polycarbonate (BPA-PC) conducting a two-steps trans-polymerization that replaces BPA monomer with CM or its tetrahydrogenated colorless product (THCM). In the first step of synthetic strategy, depolymerization of commercial BPA-PC was carried out with phenol as nucleophile, according to our previous procedure based on zinc derivatives and ionic liquids as catalysts, thus producing quantitatively diphenyl carbonate (DPC) e BPA. In the second step, DPC underwent a melt transesterification with CM or THCM monomers affording the corresponding bio-based polycarbonates, CM-PC and THCM-PC, respectively. THCM was prepared by reducing natural bis-phenol with cyclohexene as a hydrogen donor and characterized by 1H-NMR and MS techniques. Polymerization reactions were monitored by infrared spectroscopy and average molecular weights and dispersity of the two biobased polymers THCM-PC and CM-PC were determined by means of gel permeation chromatography (GPC). Optical properties of the prepared polymers were also measured.