Miracle-dz/UniFAR-FTUs huggingface dataset:
Select targeting of intracellular Toll-interleukin-1 receptor resistance domains for protection against influenza-induced disease

TLRs are a family of PRRs that respond to PAMPs or host-derived Danger-Associated Molecular Patterns (DAMPs) to initiate host inflammation and immune responses. TLR dimerization and recruitment of adapter molecules is critical for intracellular signaling and is mediated through intracellular Toll-Interleukin 1 Receptor Resistance (TIR) domain interactions. Human TIR domains, including reported structures of TIR1, TIR2, TIR6, TIR10, TIRAP, and MyD88, contain Cysteine (Cys) interactions or modifications that are disproportionally at, or near, reported biological TIR interfaces, or in close proximity to functionally important regions. Therefore, we hypothesized that intracellular TIR Cys regulation may have greater functional importance than previously appreciated. Expression of mutant TLR4-C747S or treatment of TLR4 reporter cells with a small molecule, Cys-binding inhibitor of TLR4, TAK-242, abrogated LPS signaling in vitro. Using TAK-242, mice were protected from lethal influenza challenge as previously reported for extracellular TLR4 antagonists. Molecular modeling and sequence analysis of the region surrounding TLR4-Cys747 indicate conservation of a WxxxE motif identified among bacterial and NAD+-consuming TIRs, as well as within the TIRs domains of surface TLRs 1, 2, 4, 6, and 10. Together, these data support the hypothesis that critical Cys within the TIR domain are essential for TLR4 functionality.
Targeting the TLR signalosome with TIR domain-derived cell-permeable decoy peptides: the current state and perspectives

The ability to engineer pharmaceuticals that target the signal-dependent interactions of signaling proteins should revolutionize drug development. One approach to the rational design of protein interaction inhibitors uses decoy peptides, i.e. segments of protein primary sequence, which are derived from interfaces that mediate functional protein interactions. Decoy peptides often retain the ability of the full-length prototype to bind the docking site of the folded protein and thereby block the signal transduction. This review summarizes advances made in the last decade in the development of cell-permeable decoy peptide (CPDP) inhibitors to target the Toll/IL-1R resistance (TIR) domain-mediated protein interactions in TLR signaling, in connection with the recent progress in understanding of the TLR signalosome assembly mechanisms. We present a large collection of currently available, TIR-targeting CPDPs and propose their classification based on the types of TIR–TIR interactions they target. The binding behavior of different CPDP-TIR pairs, studied in cell-based assays and in binary in vitro systems using recombinant TIR domains, is also reviewed. The available affinity data provide benchmarks for rapid preliminary evaluation of future inhibitors. We review literature that evaluates the in vivo potency of select CPDPs and attempt to outline the areas of forthcoming progress, towards the development of CPDP-based TLR inhibitors of pharmaceutical grade.
Spectral quality of monochromatic LED light affects photosynthetic acclimation to high-intensity sunlight of Chrysanthemum and Spathiphyllum.

Vertical farming using LED lights offers potential for the early production phase (few weeks) of young ornamental plants. However, once transferred to the greenhouse, the photosynthetic acclimation of these young plants might depend on this initial light regime. In order to obtain insight about this acclimatization, Chrysanthemum (sun species) and Spathiphyllum (shade species) were pre-conditioned in growth chambers for four weeks under four light qualities: blue (B), red (R), red/blue (RB, 60% R) and white (W) at 100 μmol m-2 s-1 . Monochromatic light (R and B) limited leaf development of both species, which resulted in a lower leaf mass per area when compared to multispectral light (RB for Chrysanthemum, RB and W for Spathiphyllum). R-developed leaves had a lower photosynthetic efficiency in both species. After the light quality pretreatment, plants were transferred to the greenhouse with high-intensity natural light conditions. On the first day of transfer, R and B pre-conditioned leaves of both species had an inhibited photosynthesis. After one week in natural light condition, rapid light curve parameters of Chrysanthemum leaves that developed under B acclimated to sunlight had a similar level than RB-developed leaves unlike R-leaves. Spathiphyllum leaves showed a decrease in maximum electron transport rate (ETRmax ) and this was most pronounced for the R pretreatment. After one month, R pre-conditioned Chrysanthemum had the lowest dry mass, while no effects on the dry weight of Spathiphyllum with respect to the pretreatments were observed. Light quality during pre-conditioning affected the leaf ability to acclimate to natural high light-intensities in greenhouse environment. This article is protected by copyright. All rights reserved.
Prevalence and causes of childhood blindness in India: A systematic review

Childhood blindness is one of the priority targets of Vision 2020—Right To Sight due to its impact on the psychological and social growth of the child. An extensive search was performed to locate research papers on childhood blindness prevalence and its causes in the community based and blind schools, respectively, conducted from 1990 onward up to the present. Cross references were also manually searched along with expert consultation to enlarge the reference data. A total of five community-based studies on the prevalence including two refractive error studies conducted all over India in children less than 16 years were found. The causes of childhood blindness from the available blind school studies revealed that causes of childhood blindness have mainly shifted from corneal causes to whole globe abnormalities. This article highlights that though with the availability of proper healthcare facilities, the trend is changing for the causes but still a lot of effort in the form of timely neonatal eye care facilities, pediatric surgical services and proper refraction strategies is required.
Impact of Diabetes and Low Body Mass Index on Tuberculosis Treatment Outcomes.

BACKGROUND Diabetes was identified as a tuberculosis (TB) risk factor mostly in retrospective studies with limited assessment of metabolic variables. The prospective Effects of Diabetes on Tuberculosis Severity study compared adults with pulmonary TB in Chennai, India, who were classified as having diabetes or normal glucose tolerance at enrollment. METHODS Baseline TB severity, sputum conversion, and treatment outcomes (cure, failure, death, or lost) were compared between groups with respect to glycemic status and body mass index (BMI). RESULTS The cohort of 389 participants included 256 with diabetes and 133 with normal glucose tolerance. Low BMI (<18.5 kg/m2) was present in 99 (74.4%) of non-diabetic participants and 85 (33.2%) of those with diabetes. Among participants with normal or high BMI, rates of cure, treatment failure, or death did not vary by glycemic status. Participants with low BMI had the highest radiographic severity of disease, the longest time to sputum culture conversion, and the highest rates of treatment failure and death. Among participants with low BMI, poorly controlled diabetes (HbA1c ≥8.0%) was unexpectedly associated with better TB treatment outcomes. High visceral adiposity index was associated with adverse outcomes and despite overall correlation with HbA1c, was elevated in some low BMI individuals with normal glucose tolerance. CONCLUSIONS In this South Indian cohort, low BMI was significantly associated with increased risk for adverse TB treatment outcomes while comorbid poorly controlled diabetes lessened that risk. High visceral adiposity index with or without dysglycemia might reflect a novel TB susceptibility mechanism linked to adipose tissue dysfunction.
Genome-Wide Natural Selection Signatures Are Linked to Genetic Risk of Modern Phenotypes in the Japanese Population

Abstract Elucidation of natural selection signatures and relationships with phenotype spectra is important to understand adaptive evolution of modern humans. Here, we conducted a genome-wide scan of selection signatures of the Japanese population by estimating locus-specific time to the most recent common ancestor using the ascertained sequentially Markovian coalescent (ASMC), from the biobank-based large-scale genome-wide association study data of 170,882 subjects. We identified 29 genetic loci with selection signatures satisfying the genome-wide significance. The signatures were most evident at the alcohol dehydrogenase (ADH) gene cluster locus at 4q23 (PASMC = 2.2 × 10−36), followed by relatively strong selection at the FAM96A (15q22), MYOF (10q23), 13q21, GRIA2 (4q32), and ASAP2 (2p25) loci (PASMC < 1.0 × 10−10). The additional analysis interrogating extended haplotypes (integrated haplotype score) showed robust concordance of the detected signatures, contributing to fine-mapping of the genes, and provided allelic directional insights into selection pressure (e.g., positive selection for ADH1B-Arg48His and HLA-DPB1*04:01). The phenome-wide selection enrichment analysis with the trait-associated variants identified a variety of the modern human phenotypes involved in the adaptation of Japanese. We observed population-specific evidence of enrichment with the alcohol-related phenotypes, anthropometric and biochemical clinical measurements, and immune-related diseases, differently from the findings in Europeans using the UK Biobank resource. Our study demonstrated population-specific features of the selection signatures in Japanese, highlighting a value of the natural selection study using the nation-wide biobank-scale genome and phenotype data.
Effects of freshwater crayfish on influenza A virus persistence in water

Several investigations have recently assessed the ability of some aquatic invertebrates to act as tools for avian influenza A virus (IAV) surveillance as well as their potential role(s) in IAV ecology. Because of this, as well as the high IAV seroprevalence rates noted in select mesocarnivores that commonly inhabit aquatic and semi‐aquatic habitats, we evaluated the effects that freshwater crayfish have on IAV in water at three dose levels and monitored for the presence of IAV in crayfish tissues (gill and green gland) and haemolymph at multiple time points. At relatively high, medium and low (approximately 104, 103 and 102 EID50/ml, respectively) doses, mesocosms containing crayfish (Orconectes sp.) had less detectable IAV RNA present when final water samples were assayed (9 days post‐contact [DPC]). In general, containers without crayfish present had nearly three‐fold greater quantities of viral RNA at 9 DPC. A varying number of RNA positive samples were detected for the three crayfish sample types collected. Gill tissue produced the largest number of positive non‐water samples (n = 26), with the highest quantities detected from crayfish sampled on 1 and 4 DPC (103.5 EID50 equivalent/ml). On a few occasions, gill (n = 8) and haemolymph samples (n = 1) produced higher quantities of viral RNA than their respective water samples or water samples collected 1–2 DPC earlier, but these differences were typically minor. Based upon water samples, statistical models indicated that the interaction of dose and crayfish exposure days explained most of the variation in these data. Future efforts should address if crayfish exposed to IAV‐laden water have the capacity to successfully transmit IAVs to mammals and birds which frequently prey upon them.
Zinc Supplementation and Fortification in Mexican Children

Background: Zinc is an essential micronutrient for human health. Approximately 1.4% of deaths worldwide are related to zinc deficiency. In Mexico, 33% of children younger than 5 years are zinc deficient. Objective: To give an overview of zinc supplementation and fortification in children younger than 5 years through the analysis of current regulations in Mexico, the availability of these products, and the opinion of Mexican experts in this field. Methods: We gave an overview of zinc supplementation and fortification strategies in the Mexican pediatric population by conducting a literature review of Mexican studies and national standards concerning zinc supplementation and fortification. Semistructured interviews were conducted with personnel from the main producers of zinc supplements and fortified products and from social assistance programs in Mexico. Results: Zinc supplementation in Mexico has been associated with reduction in the duration and incidence of diarrhea. Through interviews with experts, we identified several barriers in achieving adequate zinc consumption such as problems in social assistance programs that distribute zinc-fortified foods, lack of specific dietary recommendations regarding the intake of zinc, lack of regulation of nonpatented zinc supplements, and inconsistencies in public health actions due to political and administrative changes. Conclusion: Despite current regulation and efforts made by social assistance programs, zinc deficiency continues to be a prevalent public health issue. Mexico requires an in-depth analysis of existing barriers and alternatives in order to reduce zinc deficiency.
Radiation Emergency Readiness Among US Medical Toxicologists: A Survey

ABSTRACT Introduction: Large scale radiologic and nuclear disasters are rare; however, recent events such as the Fukushima Daiichi nuclear reactor emergency in Japan and current global political tensions have highlighted the need for health-care providers with expertise in managing radiation injuries. Medical Toxicologists have the ability to collaborate with other specialists in filling this critical role. Methods: We conducted a cross-sectional survey to assess the attitudes, experiences, and knowledge of medical toxicologists through the assistance of the American College of Medical Toxicology. Results: The survey was completed by 114 medical toxicologists during the enrollment period. Medical toxicologists who had a willingness to participate in radiologic or nuclear emergencies or who had taken care of patients contaminated with radioactive material were more likely to perform well on the knowledge assessment. Conclusion: We identified that there is a group of medical toxicologists who have the willingness, experience, and knowledge to help manage patients in the event of a radiologic or nuclear emergency.
MicroRNA‐4731‐5p delivered by AD‐mesenchymal stem cells induces cell cycle arrest and apoptosis in glioblastoma

Glioblastoma multiforme (GBM) exhibits the most malignant brain tumor with very poor prognosis. MicroRNAs (miRNAs) are regulatory factors that can downregulate the expression of multiple genes. Several miRNAs acting as tumor‐suppressor genes have been identified so far. The delivery of miRNA by mesenchymal stem cell (MSC) due to their ability to specifically target tumors is a new, hopeful therapeutic approach for glioblastoma. The objective of our study is the investigation of the effect of lentivirus‐mediated microRNA‐4731 (miR‐4731) genetic manipulated adipose‐derived (AD)‐MSC on GBM. The downregulation of miR‐4731 in human GBM tumor was detected using the GEO dataset. To evaluate the function of miR‐4731, we overexpressed miR‐4731 using lentiviral vectors in U‐87 and U‐251 GBM cell lines. The effects of miR‐4731 on cell proliferation and cell cycle of glioma cells were analyzed by wound test and flow‐cytometry assay. miR‐4731 inhibited the proliferation of GBM cancer cells. Coculturing was used to study the antiproliferative effect of miR‐4731‐AD‐MSCs on GBM cell lines. Direct and indirect coculture of GBM cell lines with miR‐4731‐AD‐MSCs induced cell cycle arrest and apoptosis. Our findings suggest that AD‐MSCs expressing miR‐4731 have favorable antitumor characteristics and should be further explored in future glioma therapy.
Human Mutation

Department of Endocrine and Metabolic Diseases and Lab of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, Milan, Italy Lab of Medical Cytogenetics and Molecular Genetics, Istituto Auxologico Italiano, IRCCS, Milan, Italy Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy Laboratory of Molecular and Cell Biology, Istituto Dermopatico dell'Immacolata (IDI) IRCCS, Rome, Italy Dipartimento Medico‐Geriatico, Endocrinologia, Azienda ospedaliero‐ Universitaria Careggi, Firenze, Italy Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
“I’m a Little More Trusting”: Components of Trustworthiness in the Decision to Participate in Genomics Research for African Americans

Aims: This study sought to explore the decision to participate in genomics research for African American individuals. Our overall goal was to explore (1) the attributes that significantly contribute to willingness to participate in genomics research; (2) how these attributes are interpreted (what is their meaning? ); (3) how trustworthiness is estimated in the decision to participate in research (i.e., what are the symbolic representations or heuristics of trustworthiness in decision-making? ); and (4) how participants see factors to counterweigh each other. Methods: We sought a methodology that would afford exploration of the compensatory nature of decision-making where some choice attributes may be weighed differently than others as well as the use of heuristics (shortcuts to estimate key concepts in the mentally taxing task of decision-making) for concepts such as trustworthiness. We used a qualitative story deck to create hypothetical research scenarios with variable attributes (i.e., researcher race/ethnicity; institutional affiliation; research goal; and biospecimen requested) to determine how individuals find and interpret information to make decisions about research participation. These semi-structured interviews (n = 82) were conducted in African American barbershops in Baltimore City and Prince George’s County, Maryland. Results: Quantitative and qualitative analysis was completed. Findings include that, even in the absence of interpersonal connection, trustworthiness can be communicated through multiple factors, such as (1) shared values with researchers and (2) familiarity. Conversely, (1) ambiguity, especially regarding the use of biospecimens, (2) negative reputations, and (3) perceptions of “hidden agendas” were associated with a lower willingness to participate. However, the alignment of participant and research goals was weighed more heavily in decisions than other factors. Conclusion: This study finds that negatively assessed characteristics in research design do not result in automatic rejections of participation. Negative assessments can be mitigated by emphasizing the multiple factors that communicate trustworthiness in the consent process, which may improve rates of research participation.
Effect of swimming program on glycemic control in male adolescents with Type 1 diabetes mellitus.

BACKGROUND Regular physical activity and exercise is the third management for the child with diabetes mellitus after diet regime and insulin therapy. The aim of the study is to evaluate the effect of swimming on glycemic control for a male adolescent with type 1 diabetes mellitus. OBJECTIVE The study evaluates the effect of swimming on glycemic control for a male adolescent with type 1 diabetes mellitus. METHODS The quasi-experimental design was conducted on 40 male adolescents with typ1 diabetes, then divided into two groups; study and control groups. 20 adolescents participated in the swimming program (study group) and other 20 did not expose to exercise program (control group) for 10 weeks. a venous blood sample was received to evaluate glycemic control (HbA1c %), in pre and post 10 weeks to compare HbA1c % for both groups. RESULTS Mean age 13.45 ±1.46 years (study group), while for control group age 13.55 ± 1.5 years, and mean and standard deviation for Hba1c % was 9.61 ± 1.15 %, 9.65 ± 2.23 % in the study and control group respectively. The study showed that there was a high significant difference between pre and post-test HbA1c in the study group (p-value < 0.00) also the same result was observed in the control group but negatively (p-value < 0.00) it means the Hb1c % was raised. CONCLUSIONS The study concluded that regular physical activity (swimming) had a positive effect on lowering Glycosylated hemoglobin (HbA1c).
Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial

Abstract Maintenance of the serum 25-hydroxyvitamin D (25-OH-D) concentration at recommended levels is essential due to its role in the regulation of anabolic hormones and athletic performance. However, the results of the clinical experiments in athletes are controversial. The present study aimed to investigate the effect of vitamin D3 supplement on serum levels of anabolic hormones, cortisol, anaerobic and aerobic performance in active males. In this double-blind, randomized controlled trial, 46 active males randomly assigned to vitamin D3 supplement (VDS; 2000 IU/day) or placebo for 12 weeks. The Wingate test, VO2max, and serum levels of 25-OH-D, Parathyroid hormone (PTH), total testosterone, growth hormone (GH), Insulin-like growth factor-1 (IGF-1), and cortisol were assessed. Subjects in the VDS group had a higher serum level of 25-OH-D (p = 0.004), VO2max (p = 0.016), and average power (p = 0.044) compared to the placebo at the end of the study. Also, lower levels of PTH (p = 0.004) and fatigue index (p < 0.001) were observed in VDS group at the end of the study. The serum cortisol levels were reduced significantly only in subjects with vitamin D deficiency in VDS group (p = 0.042). There was a significant reduction in serum testosterone levels in VDS group (p = 0.013). No change was indicated in serum levels of GH and IGF-1 in VDS group compared to the placebo (p > 0.05). The present study showed an improvement in aerobic capacity, anaerobic performance, and vitamin D status following vitamin D3 supplementation. However, more studies are required for the effect of vitamin D3 on serum concentration of anabolic hormones.