Miracle-dz/UniFAR-FTUs huggingface dataset:
Surface chemistry-dependent antiviral activity of silver nanoparticles

The toxicity towards viruses of silver nanoparticles (AgNPs) has been reported to be dependent on several factors such as particle concentration, size, and shape. Although these factors may indeed contribute to the toxicity of AgNPs, the results presented in this work demonstrate that surface chemistry and especially surface charge is a crucial factor governing their antiviral activity. Here, this work investigated the influence of capping agents representing various surface charges ranging from negative to positive. These AgNPs were capped with citrate, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) mercaptoacetic acid (MAA) and (branched polyethyleneimine (BPEI). We show that AgNPs exhibited surface charge-dependent toxicity towards MS2 bacteriophages. Among the capping agents under investigation, BPEI capped AgNPs (Ag/BPEI) exhibited the highest reduction of MS2 resulting in ≥6 log10-units reductions, followed by 4–5 log10-units reductions with PVP and PEG capping’s and 3–4 log10-units with MAA and citrate cappings. Bare nanoparticles reported a mere 1–2 log10-units reduction. Electrostatic interaction between the positively charged BPEI-coating and the negatively charged virus surface played a significant role in bringing the MS2 closer to toxic silver ions (Ag+). Further results obtained from TEM showed that Ag/BPEI nanoparticles could directly damage the structure of the MS2 bacteriophages. AgNPs and cationic capping agents’ observed synergy can lead to much lower and much more efficient dosing of AgNPs for antiviral applications.
MicroRNA-142 Critically Regulates Group 2 Innate Lymphoid Cell Homeostasis and Function

Key Points MicroRNA-142 isoforms critically regulate ILC2 homeostasis and effector functions. MicroRNA-142 isoforms regulate the ILC2 lineage cell intrinsically. Socs1 and Gfi1 are miR-142 isoform regulated targets in ILC2s. Visual Abstract Innate lymphoid cells are central to the regulation of immunity at mucosal barrier sites, with group 2 innate lymphoid cells (ILC2s) being particularly important in type 2 immunity. In this study, we demonstrate that microRNA(miR)-142 plays a critical, cell-intrinsic role in the homeostasis and function of ILC2s. Mice deficient for miR-142 expression demonstrate an ILC2 progenitor–biased development in the bone marrow, and along with peripheral ILC2s at mucosal sites, these cells display a greatly altered phenotype based on surface marker expression. ILC2 proliferative and effector functions are severely dysfunctional following Nippostrongylus brasiliensis infection, revealing a critical role for miR-142 isoforms in ILC2-mediated immune responses. Mechanistically, Socs1 and Gfi1 expression are regulated by miR-142 isoforms in ILC2s, impacting ILC2 phenotypes as well as the proliferative and effector capacity of these cells. The identification of these novel pathways opens potential new avenues to modulate ILC2-dependent immune functions.
Protein Phosphatase 2B Dual Function Facilitates Synaptic Integrity and Motor Learning

Protein phosphatase 2B (PP2B) is critical for synaptic plasticity and learning, but the molecular mechanisms involved remain unclear. Here we identified different types of proteins that interact with PP2B, including various structural proteins of the postsynaptic densities (PSDs) of Purkinje cells (PCs) in mice. Deleting PP2B reduced expression of PSD proteins and the relative thickness of PSD at the parallel fiber to PC synapses, whereas reexpression of inactive PP2B partly restored the impaired distribution of nanoclusters of PSD proteins, together indicating a structural role of PP2B. In contrast, lateral mobility of surface glutamate receptors solely depended on PP2B phosphatase activity. Finally, the level of motor learning covaried with both the enzymatic and nonenzymatic functions of PP2B. Thus, PP2B controls synaptic function and learning both through its action as a phosphatase and as a structural protein that facilitates synapse integrity. SIGNIFICANCE STATEMENT Phosphatases are generally considered to serve their critical role in learning and memory through their enzymatic operations. Here, we show that protein phosphatase 2B (PP2B) interacts with structural proteins at the synapses of cerebellar Purkinje cells. Differentially manipulating the enzymatic and structural domains of PP2B leads to different phenotypes in cerebellar learning. We propose that PP2B is crucial for cerebellar learning via two complementary actions, an enzymatic and a structural operation.
Redox imbalance is related to HIV and pregnancy

Redox imbalance may compromise the homeostasis of physiological processes indispensable to gestational development in HIV-infected women. The present study aims to evaluate markers of the redox system in the development of pregnancy of these women. HIV-positive pregnant women, HIV-negative pregnant women and non-pregnant were studied. Redox markers superoxide dismutase (SOD), catalase (CAT), protein carbonylation and malondialdehyde (MDA) were assessed at first or second trimester, third trimester and postpartum from pregnant and from non-pregnant women. According to the longitudinal analysis model, CAT activity was increased in the postpartum in HIV-positive women and before delivery in HIV-negative women. Increased carbonylation was observed in the pre-delivery period of HIV-negative pregnant women and MDA concentrations were higher in HIV-positive pregnant women compared to those non-infected by HIV at all times. According to the factorial model, higher SOD and CAT activities were observed in HIV-positive women in the initial months of pregnancy and in non-pregnant women. Carbonylation at third trimester was more evident in HIV-negative pregnant women. MDA levels were higher in HIV-positive pregnant women. Increased oxidative stress may occur in HIV-infected pregnant women. Nevertheless, the HIV virus is not solely responsible for this process; instead, mechanisms inherent to the pregnancy seem to play a role in this imbalance.
Gastrointestinal parasites of indigenous pigs (Sus domesticus) in south‐central Nepal

Abstract Background Intestinal parasites have a significant impact on productivity of pigs. Additionally, presence of zoonotic parasites in pig faeces used as fertilizer and ingestion of raw or undercooked pork products originated from parasite‐infested pigs pose a risk to human health. Objectives The aim of the study was to estimate the prevalence and diversity of gastrointestinal (GI) parasites in indigenous pigs (Sus domesticus) maintained under traditional rearing system in Nepal. Methods Fresh faecal samples (n = 100) were collected from the pigs of varying age and sex maintained in 18 small‐scale farms in south‐central Nepal. Samples were processed using various standard methods and examined for parasite eggs, cysts or oocysts. Results Prevalence of GI parasites in indigenous pigs was 91%, comprising of 14 different genera of protozoans and helminths. Male pigs generally had a higher (97.5%) prevalence of GI parasites than females (87%). While 90% of the suckling and weaner piglets were positive for the GI parasites, all growers and 85% the adult pigs were infected with the parasites. Entamoeba spp. were the primary protozoans in all age groups. Strongyloides sp. was more prevalent helminths in suckling and weaner piglets, whereas Ascarid spp. were higher in both growers and adults. Triplet infection was higher (33.3%) in suckling and weaner piglets, while quadruplet and pentuplet infections were higher (p < .05) among growers (46.7%) and adults (30%), respectively. Conclusions The indigenous pigs harbour a higher prevalence and greater diversity of GI parasites. GI parasitism varies by sex and age of the pigs.
Effect of dietary crude protein level on growth performance, blood characteristics, and indicators of intestinal health in weanling pigs.

An experiment was conducted to test the hypothesis that reducing crude protein (CP) in starter diets for pigs reduces post-weaning diarrhea and improves intestinal health. One hundred eighty weanling pigs were allotted to 3 diets containing 22, 19, or 16% CP. Fecal scores were visually assessed every other day. Blood samples were collected from 1 pig per pen on d 1, 6, 13, 20, and 27, and 1 pig per pen was euthanized on d 12. Results indicated that reducing dietary CP reduced (P < 0.01) overall average daily gain, gain to feed ratio, final body weight, and fecal scores of pigs. Pigs fed the 16% CP diet had reduced (P < 0.01) serum albumin compared with pigs fed other diets. Blood urea nitrogen, haptoglobin, interleukin-1β, and interleukin-6 concentrations in serum were greatest (P < 0.01) on d 13, whereas tumor necrosis factor-α and interleukin-10 concentrations were greatest (P < 0.01) on d 6. Villus height in the jejunum increased (P < 0.05) and crypt depth in the ileum was reduced (P < 0.01) if the 19% CP diet was fed to pigs compared with the 22% CP diet. A reduction (P < 0.05) in mRNA abundance of interferon-γ, chemokine ligand 10, occludin, trefoil factor-2, trefoil factor-3, and mucin 2 was observed when pigs were fed diets with 16% CP. In conclusion, reducing CP in diets for weanling pigs reduces fecal score and expression of genes associated with inflammation.
Turnover rate of coenzyme A in mouse brain and liver

Coenzyme A (CoA) is a fundamental cofactor involved in a number of important biochemical reactions in the cell. Altered CoA metabolism results in severe conditions such as pantothenate kinase-associated neurodegeneration (PKAN) in which a reduction of the activity of pantothenate kinase isoform 2 (PANK2) present in CoA biosynthesis in the brain consequently lowers the level of CoA in this organ. In order to develop a new drug aimed at restoring the sufficient amount of CoA in the brain of PKAN patients, we looked at its turnover. We report here the results of two experiments that enabled us to measure the half-life of pantothenic acid, free CoA (CoASH) and acetylCoA in the brains and livers of male and female C57BL/6N mice, and total CoA in the brains of male mice. We administered (intrastriatally or orally) a single dose of a [13C3-15N-18O]-labelled coenzyme A precursor (fosmetpantotenate or [13C3-15N]-pantothenic acid) to the mice and measured, by liquid chromatography-mass spectrometry, unlabelled- and labelled-coenzyme A species appearance and disappearance over time. We found that the turnover of all metabolites was faster in the liver than in the brain in both genders with no evident gender difference observed. In the oral study, the CoASH half-life was: 69 ± 5 h (male) and 82 ± 6 h (female) in the liver; 136 ± 14 h (male) and 144 ± 12 h (female) in the brain. AcetylCoA half-life was 74 ± 9 h (male) and 71 ± 7 h (female) in the liver; 117 ± 13 h (male) and 158 ± 23 (female) in the brain. These results were in accordance with the corresponding values obtained after intrastriatal infusion of labelled-fosmetpantotenate (CoASH 124 ± 13 h, acetylCoA 117 ± 11 and total CoA 144 ± 17 in male brain).
Intralymphatic Glutamic Acid Decarboxylase With Vitamin D Supplementation in Recent-Onset Type 1 Diabetes: A Double-Blind, Randomized, Placebo-Controlled Phase IIb Trial

OBJECTIVE To evaluate the efficacy of aluminum-formulated intralymphatic glutamic acid decarboxylase (GAD-alum) therapy combined with vitamin D supplementation in preserving endogenous insulin secretion in all patients with type 1 diabetes (T1D) or in a genetically prespecified subgroup. RESEARCH DESIGN AND METHODS In a multicenter, randomized, placebo-controlled, double-blind trial, 109 patients aged 12–24 years (mean ± SD 16.4 ± 4.1) with a diabetes duration of 7–193 days (88.8 ± 51.4), elevated serum GAD65 autoantibodies, and a fasting serum C-peptide >0.12 nmol/L were recruited. Participants were randomized to receive either three intralymphatic injections (1 month apart) with 4 μg GAD-alum and oral vitamin D (2,000 IE daily for 120 days) or placebo. The primary outcome was the change in stimulated serum C-peptide (mean area under the curve [AUC] after a mixed-meal tolerance test) between baseline and 15 months. RESULTS Primary end point was not met in the full analysis set (treatment effect ratio 1.091 [CI 0.845–1.408]; P = 0.5009). However, GAD-alum–treated patients carrying HLA DR3-DQ2 (n = 29; defined as DRB1*03, DQB1*02:01) showed greater preservation of C-peptide AUC (treatment effect ratio 1.557 [CI 1.126–2.153]; P = 0.0078) after 15 months compared with individuals receiving placebo with the same genotype (n = 17). Several secondary end points showed supporting trends, and a positive effect was seen in partial remission (insulin dose–adjusted HbA1c ≤9; P = 0.0310). Minor transient injection site reactions were reported. CONCLUSION Intralymphatic administration of GAD-alum is a simple, well-tolerated treatment that together with vitamin D supplementation seems to preserve C-peptide in patients with recent-onset T1D carrying HLA DR3-DQ2. This constitutes a disease-modifying treatment for T1D with a precision medicine approach.
Use of Disease-Modifying Therapies in Pediatric Relapsing-Remitting Multiple Sclerosis in the United Kingdom

Objectives To compare the real-world effectiveness of newer disease-modifying therapies (DMTs) vs injectables in children with relapsing-remitting multiple sclerosis (RRMS). Methods In this retrospective, multicenter study, from the UK Childhood Inflammatory Demyelination Network, we identified children with RRMS receiving DMTs from January 2012 to December 2018. Clinical and paraclinical data were retrieved from the medical records. Annualized relapse rates (ARRs) before and on treatment, time to relapse, time to new MRI lesions, and change in Expanded Disability Status Scale (EDSS) score were calculated. Results Of 103 children treated with DMTs, followed up for 3.8 years, relapses on treatment were recorded in 53/89 (59.5%) on injectables vs 8/54 (15%) on newer DMTs. The ARR was reduced from 1.9 to 1.1 on injectables (p < 0.001) vs 1.6 to 0.3 on newer DMTs (p = 0.002). New MRI lesions occurred in 77/89 (86.5%) of patients on injectables vs 26/54 (47%) on newer DMTs (p = 0.0001). Children on newer DMTs showed longer time to relapse, time to switch treatment, and time to new radiologic activity than patients on injectables (log-rank p < 0.01). After adjustment for potential confounders, multivariable analysis showed that injectables were associated with 12-fold increased risk of clinical relapse (adjusted hazard ratio [HR] = 12.12, 95% CI = 1.64–89.87, p = 0.015) and a 2-fold increased risk of new radiologic activity (adjusted HR = 2.78, 95% CI = 1.08–7.13, p = 0.034) compared with newer DMTs. At 2 years from treatment initiation, 38/103 (37%) patients had MRI activity in the absence of clinical relapses. The EDSS score did not change during the follow-up, and only 2 patients had cognitive impairment. Conclusion Newer DMTs were associated with a lower risk of clinical and radiologic relapses in patients compared with injectables. Our study adds weight to the argument for an imminent shift in practice toward the use of newer, more efficacious DMTs in the first instance. Classification of Evidence This study provides Class IV evidence that newer DMTs (oral or infusions) are superior to injectables (interferon beta/glatiramer acetate) in reducing both clinical relapses and radiologic activity in children with RRMS.
Socioeconomic, geographic and health system factors associated with rising C-section rate in Indonesia: a cross-sectional study using the Indonesian demographic and health surveys from 1998 to 2017

Introduction Caesarean section (C-section) has been a public health concern globally. This study investigated the change in C-section rate in 1998–2017 in Indonesia and explored the socioeconomic, geographic and health system factors associated with the use of C-section. Methods We analysed data from demographic health surveys in 2002–2003, 2007, 2012 and 2017 in Indonesia. We included women who reported giving birth within 5 years of each round of the survey (n=56 462) into the analysis. Cross-tabulation was used to examine change of C-section rate by year. We conducted bivariate and multivariate logistic regressions to study the determinants of C-section use. Results In Indonesia, the C-section rate increased from 4.0% in 1998 to 18.5% in 2017. In 2017, the C-section rate in urban areas (22.9%) was almost two times that in rural areas (11.8%). It was almost three times among the richest wealth quintile (36.5%), compared with the poorest wealth quintile (12.9%). Between 2008 and 2017, the difference in the C-section rate by public services enlarged between the poorest and the richest groups. The absolute increase of the C-sections by private services was more than public services over time. In 2013–2017, the C-section rates by public and private services were 22.5% and 23.1%, respectively. After adjusting for all variables, higher education, higher household wealth, primiparity and use of public childbirth services were positively associated with C-section. Conclusions The C-section rate increased steadily in the past two decades in Indonesia. Women’s socioeconomic status and health system factors were associated with the increased use of C-section.
Three‐dimensional visualization of the human membranous labyrinth: The membrana limitans and its role in vestibular form

The inner ear contains the end organs for balance (vestibular labyrinth) and hearing (cochlea). The vestibular labyrinth is comprised of the semicircular canals (detecting angular acceleration) and otolith organs (utricle and saccule, which detect linear acceleration and head tilt relative to gravity). Lying just inferior to the utricle is the membranous membrana limitans (ML). Acting as a keystone to vestibular geometry, the ML provides support for the utricular macula and acts as a structural boundary between the superior (pars superior) and inferior (pars inferior) portions of the vestibular labyrinth. Given its importance in vestibular form, understanding ML morphology is valuable in establishing the spatial organization of other vestibular structures, particularly the utricular macula. Knowledge of the 3D structure and variation of the ML, however, remain elusive. Our study addresses this knowledge gap by visualizing, in 3D, the ML and surrounding structures using micro‐CT data. By doing so, we attempt to clarify: (a) the variation of ML shape; (b) the reliability of ML attachment sites; and (c) the spatial relationship of the ML to the stapes footplate using landmark‐based Generalized Procrustes, Principal Component and covariance analyses. Results indicate a consistent configuration of three distinct bony ML attachments including an anterolateral, medial, and posterior attachment which all covary with bony structure. Our results set the stage for further understanding into vestibular and more specifically, utricular macula spatial configuration within the human head, offering the potential to aid in clinical and evolutionary studies which rely on a 3D understanding of vestibular spatial configuration.
Medical Students’ Perception and Perceived Value of Peer Learning in Undergraduate Clinical Skill Development and Assessment: Mixed Methods Study

Background The effectiveness of peer learning in clinical skill development is well recognized and researched, given the many benefits gained such as enhanced learning, alleviation of the burden on faculty, and early development of teaching skills for future doctors. However, little is known in terms of its effectiveness as an assessment tool and the extent to which peer assessment can be relied upon in the absence of faculty support. Objective This study was conducted to assess medical students’ perception toward peer learning, which is based on self-regulated learning as a tool of assessment, and to compare peer evaluation with faculty evaluation of clinical skill performance. Methods A cohort of 36 third-year medical students were exposed to peer learning (same-level) in clinical skills education for 3 months. A convergent mixed methods approach was adapted to collect data from 3 sources, namely, students’ perception of peer learning, performance scores, and reflective observational analysis. A 5-point Likert-type scale was used to assess students’ (n=28) perception on the value of peer learning. The students were asked to assess their peers by using a preset checklist on clinical skill performance, and scores were compared to faculty assessment scores. Reflective observational data were collected from observing video recordings of some of the peer learning sessions. The findings from all 3 sources were integrated using joint display analysis. Results Out of 28 students, 25 students completed the survey and 20 students perceived peer learning as valuable in clinical skills education. The mean score of peer assessment was higher than that of faculty assessment. There was a significant difference in student performance between supervised teaching and peer learning groups (P=.003). Most students focused on the mastery of skill with little attention to the technique’s quality. Further, students were unable to appreciate the relevance of the potential clinical findings of physical examination. Conclusions Peer learning in clinical skills education, based on self-regulated learning, empowers students to develop a more responsible approach toward their education. However, peer assessment is insufficient to evaluate clinical skill performance in the absence of faculty support. Therefore, we recommend that peer learning activities be preceded by supervised faculty-taught sessions.
Quantification of Regional Cerebral Blood Flow Using Diffusion Imaging With Phase Contrast

The perfusion‐related diffusion coefficient obtained from triexponential diffusion analysis is closely correlated with regional cerebral blood flow (rCBF), as assessed by arterial spin labeling (ASL) methods. However, this provides only a semiquantitative measure of rCBF, thereby making absolute rCBF quantification challenging.
Sensitivity of Process Design to Phase Equilibrium—A New Perturbation Method Based Upon the Margules Equation

It is widely recognized by experts that the computer-based design of chemical processes depends strongly on the correlated thermodynamic and transport properties, and the effect of property uncertainties should be incorporated into the design. The most significant source of property uncertainties on process design is from the correlations of phase equilibrium. Many approaches have been proposed, but uncertainty analysis is not a routine component of today’s industrial practice, mainly because education and awareness is lacking, and the proposed methods are difficult to apply. The purpose of this paper is to report a new approach to uncertainty analysis that is intuitively appealing and easy to apply in process simulation. The proposed approach focuses on activity coefficients and is based upon the simplification that, for the purpose of perturbation, the liquid mixture can be treated as a set of pseudobinaries described by the Margules equation. The resulting perturbation in the activity coefficient of co.