Miracle-dz/UniFAR-FTUs huggingface dataset:
αIIbβ3 variants in ten families with autosomal dominant macrothrombocytopenia: Expanding the mutational and clinical spectrum

Background Rare pathogenic variants in either the ITGA2B or ITGB3 genes have been linked to autosomal dominant macrothrombocytopenia associated with abnormal platelet production and function, deserving the designation of Glanzmann Thrombasthenia-Like Syndrome (GTLS) or ITGA2B/ITGB3-related thrombocytopenia. Objectives To describe a series of patients with familial macrothrombocytopenia and decreased expression of αIIbβ3 integrin due to defects in the ITGA2B or ITGB3 genes. Methods We reviewed the clinical and laboratory records of 10 Portuguese families with GTLS (33 patients and 11 unaffected relatives), including the functional and genetic defects. Results Patients had absent to moderate bleeding, macrothrombocytopenia, low αIIbβ3 expression, impaired platelet aggregation/ATP release to physiological agonists and low expression of activation-induced binding sites on αIIbβ3 (PAC-1) and receptor-induced binding sites on its ligand (bound fibrinogen), upon stimulation with TRAP-6 and ADP. Evidence for constitutive αIIbβ3 activation, occurred in 2 out of 9 patients from 8 families studied, but also in 2 out of 12 healthy controls. We identified 7 missense variants: 3 in ITGA2B (5 families), and 4 in ITGB3 (5 families). Three variants (αIIb: p.Arg1026Trp and p.Arg1026Gln and β3: p.Asp749His) were previously reported. The remaining (αIIb: p.Gly1007Val and β3: p.Thr746Pro, p.His748Pro and p.Arg760Cys) are new, expanding the αIIbβ3 defects associated with GTLS. The integration of the clinical and laboratory data allowed the identification of two GTLS subgroups, with distinct disease severity. Conclusions Previously reported ITGA2B and ITGB3 variants related to thrombocytopenia were clustered in a confined region of the membrane-proximal cytoplasmic domains, the inner membrane clasp. For the first time, variants are reported at the outer membrane clasp, at the transmembrane domain of αIIb, and at the membrane distal cytoplasmic domains of β3. This is the largest single-center series of inherited macrothrombocytopenia associated with αIIbβ3 variants published to date.
American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 2

To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID‐19), the acute, infectious phase of SARS–CoV‐2 infection.
The Association Between Suicide-Related Media Coverage and Suicide: A Cross-Sectional Observational Study

Abstract Objective To examine the association between the publication and content of suicide-related media reports and actual suicide in Noord Brabant, a province of the Netherlands. Method Between April 2017 and March 2018, a retrospective cross-sectional observational study was conducted on suicide-related media reports and incident data regarding suicides. Linear regression, Mann-Whitney U and negative binomial regression analyses were conducted. Results In Noord-Brabant, a total of 352 people died from suicide during the observation period and 440 reports were identified by using the search terms “suicide”, “self-killing”, and “self-murder”. No associations between media reports and actual suicides were found for any of the analyses performed. Conclusions No indications were found for an association between media coverage of suicide and increases or decreases in actual suicides in Noord-Brabant. The descriptive statistics of this study reveal that the regional and national Dutch media are doing well with respect to not including elements in their reports that could encourage copycat behavior, such as simplifying, romanticizing or dramatizing. They could improve on including protective content, for example, providing supportive background information. A recommendation for further research is to evaluate causal relationships between media and actual suicide. A stepped wedge trial might be needed, as this provides an ethical research design to investigate this issue in a controlled setting. Also, in such a study, other variables influencing the decision to attempt suicide should be taken into account as much as possible.
MicroRNA-1 regulates the growth and chemosensitivity of breast cancer cells by targeting MEK/ERK pathway.

PURPOSE The microRNAs (miRs) control a vast number of biological and cellular processes. miR-1 has been implicated in the development and progression in different types of cancers. Nonetheless, the function and therapeutic implications of miR-1 have not been studied in breast cancer. This study was undertaken to study the role of miR-1 in human breast cancer cells. METHODS MBA-MD-231 breast cancer line and the normal MB-157 cell line were mainly used in this research. Expression analysis was performed by qRT-PCR. Cell viability was determined by MTT assay and apoptosis was detected by acridine orange (AO)/ethidium bromide (EB) and DAPI staining. Transwell assay was used for cell migration and invasion and western blot analysis was used to determine the protein expression. RESULTS miR-1 was significantly but aberrantly suppressed in breast cancer cells relative to the MB-157 normal cells. Overexpression of miR-1 in MBA-MD-231 suppressed their proliferation dose-dependently. The inhibition of MBA-MD-231 cell proliferation was found to be due to induction of apoptosis. The apoptotic cell percentage was 37.1% in miR-1 mimics transfected in comparison to 3.7% in miR-negative control (NC) transfected cells. Additionally, miR-1 also suppressed the chemosensitivity of the MBA-MD-1 breast cancer cells to cisplatin. Transwell assay showed that miR-1 overexpression suppressed the migration and invasion of the MBA-MD-231 cells. The results clearly showed that overexpression of miR-1 suppressed the phosphorylation of MEK and ERK. CONCLUSION miR-1 acts as a tumor suppressor and may exhibit therapeutic implications in the treatment of breast cancer.
Cold Water Swimming—Benefits and Risks: A Narrative Review

Cold water swimming (winter or ice swimming) has a long tradition in northern countries. Until a few years ago, ice swimming was practiced by very few extreme athletes. For some years now, ice swimming has been held as competitions in ice-cold water (colder than 5 °C). The aim of this overview is to present the current status of benefits and risks for swimming in cold water. When cold water swimming is practiced by experienced people with good health in a regular, graded and adjusted mode, it appears to bring health benefits. However, there is a risk of death in unfamiliar people, either due to the initial neurogenic cold shock response or due to a progressive decrease in swimming efficiency or hypothermia.
Comparison of the laparoscopic versus open surgery in patients aged over 75 years old with colorectal cancer. Short- and Mid-term outcomes.

PURPOSE The benefit of minimally invasive surgery in colorectal cancer patients has been established, however it is not clear whether these advantages apply to older patients as well. The aim of this study was to review short- and mid-term outcomes in elderly patients, over the age of 75 years, with colorectal cancer. METHODS This was a retrospective study of selected patients over the age of 75 who underwent laparoscopic and open surgery for colorectal cancer between February 2013 and January 2018 in a tertiary referral center. All patients were categorized in two groups: Group 1 included patients who had open procedure (OP) and Group 2 those who underwent laparoscopic procedure (LP). Demographic, clinical, short- and midterm postoperative data were collected and analyzed between the two study groups. RESULTS A total of 78 patients were included in our cohort; 39 (50%) were operated with LP. The LP was equally safe in comparison with the OP, considering the similar postoperative complications [9 patients (34.6%) in LP and 5 patients (18.5%) in OP (p=0.224)], including anastomotic leakage in 2 patients (7.7%) in LP and 1 patient (3.7%) in OP group (p=0.61). The median postoperative hospital stay favored the laparoscopic approach (6 days in LP group and 8 days in OP group; p=0.001). The number of harvested lymph nodes were without statistically significant differences [LP group retrieved 20.0 nodes in comparison with 20.5 nodes in OP group (p= 0.816)]. The overall survival analysis showed no difference between the two approaches in 12 and 24 postoperative months (p=0.098 and 0.387, respectively).
Occupational Noise: Auditory and Non-Auditory Consequences

Occupational noise exposure accounts for approximately 16% of all disabling hearing losses, but the true value and societal costs may be grossly underestimated because current regulations only identify hearing impairments in the workplace if exposures result in audiometric threshold shifts within a limited frequency region. Research over the past several decades indicates that occupational noise exposures can cause other serious auditory deficits such as tinnitus, hyperacusis, extended high-frequency hearing loss, and poor speech perception in noise. Beyond the audiogram, there is growing awareness that hearing loss is a significant risk factor for other debilitating and potentially life-threatening disorders such as cardiovascular disease and dementia. This review discusses some of the shortcomings and limitations of current noise regulations in the United States and Europe.
Living in the dark: Bat caves as hotspots of fungal diversity

Bat caves are very special roosts that harbour thousands of bats of one or more species. Such sites may hold an incredible “dark fungal diversity” which is still underestimated. We explored the culturable fungal richness in the air, on bats, and in the guano in a bat cave in Brazil’s Caatinga dry forest. Fungal abundance was 683 colony-forming units (CFU) in the guano, 673 CFU in the air, and 105 CFU on the bats. Based on morphological and phylogenetic analysis of ITS, LSU, and TUB2 sequences, fungal isolates of 59 taxa belonging to 37 genera in the phyla Ascomycota (28 genera, including Aspergillus, Penicillium, Cladosporium, and Talaromyces), Basidiomycota (eight genera, including Rhodotorula and Schizophyllum), and Mucoromycota (only Rhizopus) were identified. The fungal richness in the air was 23 taxa (especially Aspergillus taxa), mainly found at 15 m and 45 m from the cave entrance; on the bodies of bats it was 36 taxa (mainly Aspergillus taxa), especially on their wing membranes (21 taxa, nine of which were exclusively found in this microhabitat); and in guano 10 fungal taxa (especially Aspergillus and Penicillium) were found. The fungal richness associated with guano (fresh and non-fresh) was similar from bats with different eating habits (insectivorous, frugivorous, and haematophagous). Sampling effort was not sufficient to reveal the total fungal taxa richness estimated. Eight (21.6%) of the 37 genera and 17 (53.1%) of the 32 identified fungal species are reported for the first time in caves. Our results highlight bat caves in Brazil as hotspots of fungal diversity, emphasizing the need to protect such special roosts.
Enteric Glia at the Crossroads between Intestinal Immune System and Epithelial Barrier: Implications for Parkinson Disease

Over recent years, several investigations have suggested that Parkinson’s disease (PD) can be regarded as the consequence of a bowel disorder. Indeed, gastrointestinal symptoms can occur at all stages of this neurodegenerative disease and in up to a third of cases, their onset can precede the involvement of the central nervous system. Recent data suggest that enteric glial cells (EGCs) may play a major role in PD-related gastrointestinal disturbances, as well as in the development and progression of the central disease. In addition to their trophic and structural functions, EGCs are crucial for the homeostatic control of a wide range of gastrointestinal activities. The main purpose of this review was to provide a detailed overview of the role of EGCs in intestinal PD-associated alterations, with particular regard for their participation in digestive and central inflammation as well as the dynamic interactions between glial cells and intestinal epithelial barrier. Accumulating evidence suggests that several pathological intestinal conditions, associated with an impairment of barrier permeability, may trigger dysfunctions of EGCs and their shift towards a proinflammatory phenotype. The reactive gliosis is likely responsible for PD-related neuroinflammation and the associated pathological changes in the ENS. Thus, ameliorating the efficiency of mucosal barrier, as well as avoiding IEB disruption and the related reactive gliosis, might theoretically prevent the onset of PD or, at least, counteract its progression.
Deletion in the S1 Region of Porcine Epidemic Diarrhea Virus Reduces the Virulence and Influences the Virus-Neutralizing Activity of the Antibody Induced

Porcine epidemic diarrhea virus (PEDV) causes severe diarrhea and a high rate of mortality in suckling pigs. The epidemic of PEDV that occurred after 2013 was caused by non-insertion and deletion of S gene (S-INDEL) PEDV strains. During this epidemic, a variant of the non-S-INDEL PEDV strain with a large deletion of 205 amino acids on the spike gene (5-17-V) was also found to co-exist with a non-S-INDEL PEDV without deletion (5-17-O). Herein, we describe the differences in the complete genome, distribution, virulence, and antigenicity between strain 5-17-O and variant strain 5-17-V. The deletion of 205 amino acids was primarily located in the S1O domain and was associated with milder clinical signs and lower mortality in suckling pigs than those of the 5-17-O strain. The 5-17-V strain-induced antibody did not completely cross-neutralize the 5-17-O strain. In conclusion, the deletion in the S1 region reduces the virulence of PEDV and influences the virus-neutralizing activities of the antibody it induces.
Potential herbal constituents for psoriasis treatment as protective and effective therapy

Psoriasis is a multifactorial and chronic skin disorder. It is a recurrent disease that requires incessant therapy. Psoriasis treatment includes topical and systemic routes using synthetic drugs that lead to severe unwanted adverse effects. Herbal therapy is widely used for thousands of years in countries like China and India. The use of herbal therapy in the developed region enhanced to a great extent and showed better efficacy towards psoriasis alone or as adjuvant to synthetic therapy. Herbal medicines have gained great attention in the treatment of psoriasis due to their lesser side effects compared to synthetic drugs. In this review, the various plant sources which have been found effective in psoriasis and can be used to develop novel therapeutics have been discussed. The mechanisms by which the phytoconstituents elicit anti‐psoriatic activity and various research studies that have proven the effectiveness of these natural products have also been compiled in this review.
Chemical Ablation of Genicular Nerve with Phenol for Pain Relief in Patients with Knee Osteoarthritis: A Prospective Study

Radiofrequency ablation of the genicular nerve is performed for knee osteoarthritis (KOA) when conservative treatment is not effective. Chemical ablation may be an alternative, but its effectiveness and safety have not been examined. The objective of this prospective open‐label cohort study is to evaluate the effectiveness and safety of ultrasound‐guided chemical neurolysis for genicular nerves with phenol to treat patients with chronic pain from KOA.
Perceived psychological stress and associated factors in the early stages of the coronavirus disease 2019 (COVID-19) epidemic: Evidence from the general Chinese population

Introduction Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by novel coronavirus 2019. Many individuals suffered psychological symptoms in the early stage when the epidemic was uncertain. We explored the perceived psychological stress and associated factors in the early stage of COVID-19 epidemic. Method The Perceived Stress Scale, Simplified Coping Style Questionnaire, Social Support Rating Scale and a general information questionnaire were integrated in an on-line survey conducted from February 1, 2020 until February 4, 2020. Multiple linear regression analysis was performed to explore whether coping style, social support or other factors contributed to psychological stress. Results A total of 1638 participants were included, of whom 44.3% showed moderate psychological stress. Individuals who were younger, female, unmarried, spent more time on the disease, felt more concern about it, reported lower social support (Subjective Social support; Objective social support; Utilization social support), or showed a negative coping style were more likely to suffer higher psychological stress in the early stages of the COVID-19 epidemic. Conclusion Psychological interventions may be targeted to individuals with the risk characteristics identified in this study. It may be helpful to promote social support and positive coping style in the early stage of infectious disease epidemics. This initial evidence from the general Chinese population may be relevant to interventions in other countries for dealing with the COVID-19 and other epidemics.
CORR Insights®: What General and Pain-associated Psychological Distress Phenotypes Exist Among Patients with Hip and Knee Osteoarthritis?

Phenotype is the observable traits that arise from a genetic code modified by environmental influences. Diseases such as palmar fibromatosis make us aware that one can have genes for Dupuytren disease and have observable pathologic findings that vary from none to severe. There is similar variation in the degree of illness for a given degree of verifiable objective pathophysiology and impairment (disease). The word “phenotype” is increasingly used in this context. In the case of illness phenotypes, the genes are measures of both pathophysiology and mental and social health factors. The observable traits are symptom intensity and magnitude of activity intolerance. The hope is that identifying the illness phenotype will point us to the best opportunities for helping people get and stay healthy. Reading through the various techniques used to date, I notice that some groups identify illness phenotypes by analyzing mental health on its continuum (for example, in a cluster analysis) [2] and others by categorizing mental health (for example, in a latent class analysis) [4]. I prefer to analyze mental health on its continuum. Any amount of despair or cognitive bias can represent a health opportunity. Categorization of mental health reinforces arbitrary and unhelpful categories that can contribute to social stigma (setting aside or marginalizing a person as less than a full member of society). Given that I believe the stigma associated with mental health may be the single largest barrier to the adoption of well-supported evidencebased treatment strategies, efforts to reduce stigma are a priority. The evidence regarding illness phenotypes in osteoarthritis provides unequivocal support to the idea that musculoskeletal health strategies should addressmental and social health [2, 4, 5]. In this month’sClinical Orthopaedics and Related Research, Lentz et al. [5] found that nearly three-fourths of patients in their hip and knee arthritis program had illness phenotypes that indicate important mental and social health opportunities.My interpretation of these data is not “some people have mental health opportunities. ” For me, this is evidence that everyone can feel better if they attend to mental and social health. Illness phenotypes can be valuable if they direct us to specific foci of treatment such as cognitive bias or symptoms of distress.
Ultra-high temperature steam gasification of biomass and solid wastes.

Experimental results are presented on the gasification of several waste products using high-temperature steam as the gasification media. Four cellulose-rich surrogate waste products (paper, cardboard, and wood pellets) were gasified with high-temperature steam at different temperatures in the range of 700 to 1,100°C. Gasification is an efficient method for clean conversion of waste to hydrogen-rich syngas having moderate heating value, and producing negligible soot and tars during its conversion. Although gasification is a relatively old technique, it has not been examined at ultrahigh gasification temperatures. Paper, cardboard, and other cellulose-rich waste products represent a majority share of municipal solid waste. Basic chemistry of gasification and main reactions propelling the process are presented here. The experimental facility used provided pure steam or steam–oxygen mixtures from the combustion of hydrogen and oxygen at very high temperatures. The role of the chemical composition of the feeds.
Identification of Novel Genomic Associations and Gene Candidates for Grain Starch Content in Sorghum

Starch accumulated in the endosperm of cereal grains as reserve energy for germination serves as a staple in human and animal nutrition. Unraveling genetic control for starch metabolism is important for breeding grains with high starch content. In this study, we used a sorghum association panel with 389 individuals and 141,557 single nucleotide polymorphisms (SNPs) to fit linear mixed models (LMM) for identifying genomic regions and potential candidate genes associated with starch content. Three associated genomic regions, one in chromosome (chr) 1 and two novel associations in chr-8, were identified using combination of LMM and Bayesian sparse LMM. All significant SNPs were located within protein coding genes, with SNPs ∼ 52 Mb of chr-8 encoding a Casperian strip membrane protein (CASP)-like protein (Sobic.008G111500) and a heat shock protein (HSP) 90 (Sobic.008G111600) that were highly expressed in reproductive tissues including within the embryo and endosperm. The HSP90 is a potential hub gene with gene network of 75 high-confidence first interactors that is enriched for five biochemical pathways including protein processing. The first interactors of HSP90 also showed high transcript abundance in reproductive tissues. The candidates of this study are likely involved in intricate metabolic pathways and represent candidate gene targets for source-sink activities and drought and heat stress tolerance during grain filling.
Chemical Diversity of Soft Coral Steroids and Their Pharmacological Activities

The review is devoted to the chemical diversity of steroids produced by soft corals and their determined and potential activities. There are about 200 steroids that belong to different types of steroids such as secosteroids, spirosteroids, epoxy- and peroxy-steroids, steroid glycosides, halogenated steroids, polyoxygenated steroids and steroids containing sulfur or nitrogen heteroatoms. Of greatest interest is the pharmacological activity of these steroids. More than 40 steroids exhibit antitumor and related activity with a confidence level of over 90 percent. A group of 32 steroids shows anti-hypercholesterolemic activity with over 90 percent confidence. Ten steroids exhibit anti-inflammatory activity and 20 steroids can be classified as respiratory analeptic drugs. Several steroids exhibit rather rare and very specific activities. Steroids exhibit anti-osteoporotic properties and can be used to treat osteoporosis, as well as have strong anti-eczemic and anti-psoriatic properties and antispasmodic properties. Thus, this review is probably the first and exclusive to present the known as well as the potential pharmacological activities of 200 marine steroids.