Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease-associated mosaic variation in clinical exome sequencing: a two-year pediatric tertiary care experience

Exome sequencing (ES) has become an important tool in pediatric genomic medicine, improving identification of disease-associated variation due to assay breadth. Depth is also afforded by ES, enabling detection of lower-frequency mosaic variation compared to Sanger sequencing in the studied tissue, thus enhancing diagnostic yield. Within a pediatric tertiary-care hospital, we report two years of clinical ES data from probands evaluated for genetic disease to assess diagnostic yield, characteristics of causal variants, and prevalence of mosaicism among disease-causing variants. Exome-derived, phenotype-driven variant data from 357 probands was analyzed concurrent with parental ES data, when available. Blood was the source of nucleic acid. Sequence read alignments were manually reviewed for all assessed variants. Sanger sequencing was used for suspected de novo or mosaic variation. Clinical provider notes were reviewed to determine concordance between laboratory-reported data and the ordering provider's interpretation of variant-associated disease causality. Laboratory-derived diagnostic yield and provider-substantiated diagnoses had 91.4% concordance. The cohort returned 117 provider-substantiated diagnoses among 115 probands for a diagnostic yield of 32.2%. De novo variants represented 64.9% of disease-associated variation within trio analyses. Among the 115 probands, five harbored disease-associated somatic mosaic variation. Two additional probands were observed to inherit a disease-associated variant from an unaffected mosaic parent. Among inheritance patterns, de novo variation was the most frequent disease etiology. Somatic mosaicism is increasingly recognized as a significant contributor to genetic disease, particularly with increased sequence depth attainable from ES. This report highlights the potential and importance of detecting mosaicism in ES.
Characteristics of disease progress in patients with coronavirus disease 2019 in Wuhan, China

Abstract Coronavirus disease 2019 (COVID-19) patients were classified into four clinical stages (uncomplicated illness, mild, severe and critical pneumonia) depending on disease severity. We aim to investigate the corresponding clinical, radiological and laboratory characteristics between different clinical stages. A retrospective, single-centre study of 101 confirmed patients with COVID-19 at Renmin Hospital of Wuhan University from 2 January to 28 January 2020 was enrolled; follow-up endpoint was on 8 February 2020. Clinical data were collected and compared during the course of illness. The median age of the 101 patients was 51.0 years and 33.6% were medical staff. Fever (68%), cough (50%) and fatigue (23%) are the most common symptoms. About 26% patients underwent the mechanical ventilation and 98% patients were treated with antibiotics. Thirty-seven per cent patients were cured and 11 died. On admission, the number of patients with uncomplicated illness, mild, severe and critical pneumonia were 2 [2%], 86 [85%], 11 [11%] and 2 [2%]. Forty-four of the 86 mild pneumonia progressed to severe illness within 4 days, with nine patients worsened due to critical pneumonia within 4 days. Two of the 11 severe patients improved to mild condition while three others deteriorated. Significant differences were observed among groups of different clinical stages in numbers of influenced pulmonary segments (6 vs. 12 vs. 17, P < 0.001). A significantly upward trend was witnessed in ground-glass opacities overlapped with striped shadows (33% vs. 42% vs. 55% vs. 80%, P < 0.001), while pure ground-glass opacities gradually decreased as disease progressed (45% vs. 35% vs. 24% vs. 13%, P < 0.001) within 12 days. Lymphocytes, prealbumin and albumin showed a downtrend as disease progressed from mild to severe or critical condition, an uptrend was found in white blood cells, C-reactive protein, neutrophils and lactate dehydrogenase. The proportions of serum amyloid A > 300 mg/l in mild, severe and critical conditions were 18%, 46% and 71%, respectively.
INFLUÊNCIA DE DIFERENTES COMBINAÇÕES DE LÂMINAS DE Eucalyptus saligna E Pinus taeda EM PAINÉIS LVL

This research aimed to investigate the influence of the positioning of Eucalyptus saligna and Pinus taeda wood veneers on layers of laminated veneer lumber (LVL) panels. The compositions were manufactured in six different combinations of five veneers of 3.2 mm thickness, glued with phenol-formaldehyde, resulting in treatments composed of wood of the same species or with a combination of two wood types. The evaluation of the proposed arrangements was performed under the characterization of physical properties (moisture content and density) and mechanical properties (modulus of elasticity - MOE and modulus of rupture - MOR) verified in flatwise and edgewise static bending tests. The results obtained indicated that, in most situations, the different positions of the veneers with higher density (in the outer, intermediate and inner layers) influenced the mechanical properties of the panels. The influence detected was varied for MOE and MOR, especially when comparing the flatwise and edgewise test values. In certain positions, on the layers of the LVL compositions, the presence of eucalypt veneers resulted in stiffness and strength increases. However, the treatments formed by interposed veneers of eucalypt and pine demonstrated interesting performances for structural use, in either flatwise or edgewise position, once they present values of MOE and MOR that allow to distinguish them as 1st class, according to the North American standard APA/EWS PRL-501 (2001).
New‐onset refractory status epilepticus and febrile infection‐related epilepsy syndrome

New‐onset refractory status epilepticus (NORSE) and febrile infection‐related epilepsy syndrome (FIRES) are relatively rare clinical presentations. They are characterized by de novo onset of refractory status epilepticus (RSE) without clearly identifiable acute or active cause (structural, toxic, or metabolic). We reviewed the literature using PubMed reports published between 2003 and 2019 and summarized the clinical, neurophysiological, imaging, and treatment findings. Focal motor seizures, which tend to evolve into status epilepticus, characterize the typical presentation. Disease course is biphasic: acute phase followed by chronic phase with refractory epilepsy and neurological impairment. Aetiology is unknown, but immune‐inflammatory‐mediated epileptic encephalopathy is suspected. Electroencephalograms show variety in discharges (sporadic or periodic, focal, generalized, or more frequently bilateral), sometimes with a multifocal pattern. About 70% of adult NORSE have abnormal magnetic resonance imaging (MRI); in paediatric series of FIRES, 61.2% of patients have a normal brain MRI at the beginning and only 18.5% during the chronic phase. No specific therapy for FIRES and NORSE currently exists; high doses of barbiturates and ketogenic diet can be used with some effectiveness. Recently, anakinra and tocilizumab, targeting interleukin pathways, have emerged as potential specific therapies. Mortality rate is around 12% in children and even higher in adults (16–27%).
Temporal components of genetic variation in migrating and wintering American wigeon

Data from allele frequencies of wintering American wigeon (Anas americana) from the Southern High Plains (SHP) of Texas were used to monitor changes in genetic characteristics of the wintering population through time, and to estimate the average proportion of total genetic variation partitioned among parent breeding populations. Wigeon were surveyed electrophoretically for genetic variation at 25 biochemical loci. Changes in total gene diversity were observed throughout the study period (5 October 1988 to 15 March 1989) at numerous loci. Significant temporal changes in the genetic composition of the wintering population were detected, and a minimum of 7% of the total genetic variation in these wigeon was thought to be partitioned among the breeding populations represented on the SHP. A new influx of migrating wigeon, weather-related movements of wigeon, or spatial subdivision of breeding populations on the SHP may be responsible for shifts observed in the genetic characteristics of the wintering populatio.
Induced systemic resistance and growth promotion in tomato by an indole-3-acetic acid-producing strain of Paenibacillus polymyxa

Paenibacillus polymyxa strain CF05, a plant-growth-promoting rhizobacterium (PGPR) showed inhibitory effect on Fusarium oxysporum f. sp. lycoersici in vitro, causal agent of Fusarium-wilt of tomato. In the greenhouse experiments, tomatoes inoculated with strain CF05 promoted the significant growth. Meanwhile, strain CF05 suppressed the Fusarium-wilt with 78.24% in control efficiency, which was similar to the carbendazim treatment. The bacterial culture supernatant was found to have the presence of indole-3-acetic acid (IAA), which could be accumulated throughout the growth. Furthermore, strain CF05 could greatly stimulate the activities of phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), peroxidase (POD) and superoxide dismutase (SOD) in either the absence or the presence of fungal pathogen, and the stimulation stayed throughout the entire experimental assessment. Activities of POD and SOD reached the maximum amount at the second day post-inoculation (dpi) after inoculation while activities of PAL and PPO reached the maximum amount at the third dpi and the fourth dpi, respectively. Moreover, strain CF05 could stimulate the H2O2 and phenol contents in the initial phase after pathogen inoculation. These results suggest that the sustained and timely induction of defence enzymes and accumulation of H2O2 and phenolics treated with P. polymyxa might have contributed to restriction of invasion of fungal pathogen in tomato roots. In summary, P. polymyxa strain CF05, which elicited both plant growth promotion and induction of defence response, could be potential agent to improve the yield of tomato and manage Fusarium-wilt disease.
Within-Basin Variation in the Short-Term Effects of a Major Flood on Stream Fishes and Invertebrates

ABSTRACT We measured changes in invertebrate and fish abundance before and after a major flood event in the northeastern US, in three stream reaches that differed with respect to flood intensity. Fish and invertebrate abundance was lower at all three sites following the flood. The smallest change in fish and invertebrate abundance occurred in the site experiencing the lowest-magnitude flood (~ bankfull). The two remaining sites experienced overbank flooding and major changes in species abundances. Changes in abundance were greatest at the site experiencing greater geomorphic change (bedload movement and sedimentation), even though hydrologic intensity (velocity, shear stress, unit stream power) was greater at the other site. Aquatic invertebrate and underyearling fish abundances were substantially reduced at these sites, while overyearling salmonids exhibited normal or greater-than-normal abundance. Among invertebrates, abundances of baetid mayflies, which are multivoltine and disperse rapidly via drift, recovered more rapidly than other mayfly families. Our results reinforce the contention that geologic setting can strongly influence the short-term impact of floods. In addition, we provide direct evidence that particular species and age classes are resistant to even the most extreme floods expected in a given region.
Cytomegalovirus serologic matching in deceased donor kidney allocation optimizes high‐ and low‐risk (D+R− and D−R−) profiles and does not adversely affect transplant rates

Cytomegalovirus (CMV) is a major cause of infection‐related morbidity and mortality in kidney transplantation. The most significant risk for developing CMV infection after transplant depends upon donor (D) and recipient (R) CMV serostatus. In 2012, our Organ Procurement Organization (OPO) began a novel pretransplant CMV prevention strategy via matching deceased kidney donors and recipients by CMV serostatus. Prior to the matching protocol, our distribution of seropositive and seronegative donors and recipients was similar to the United States at large. After the matching protocol, high‐risk D+R− were reduced from 18.5% to 2.9%, whereas low‐risk D−R− were increased from 13.5% to 24%. There was no adverse effect on transplant rates and no differential effect on waiting times for R+ vs R− after the protocol was implemented. This protocol could be implemented on a regional or national level to optimize low and high‐risk CMV seroprofiles and potentially improve CMV‐related outcomes in kidney transplantation.
Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression

Long intergenic non–protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324–miR-769-5p–STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.
Metabolic changes during pregnancy in glucose‐intolerant NZO mice: A polygenic model with prediabetic metabolism

Gestational diabetes mellitus (GDM) is a complex metabolic disease involving genetic and environmental factors. Recent studies have underlined its heterogeneity, so it is reasonable to divide patients into subpopulations depending on whether an insulin secretion or sensitivity defect is predominant. Since testing for GDM is usually performed in the second trimester, misinterpretation of prediabetes as gestational diabetes may occur. As with type 2 diabetes (T2DM), rodent models are needed for both GDM and prediabetes, but few do exist. Here, we compared the metabolic changes in pregnant normal NMRI mice with those in New Zealand obese (NZO) mice. Male animals of this strain are an established model of T2DM, whereas female mice of this strain are protected from hyperglycemia and β‐cell death. We demonstrate that female NZO mice exhibited impaired glucose tolerance, preconceptional hyperinsulinemia, and hyperglucagonemia without any signs of manifest diabetes. The NZO model showed, compared with the NMRI control strain, a reduced proliferative response of the Langerhans islets during pregnancy (3.7 ± 0.4 vs. 7.2 ± 0.8% Ki‐67‐positive nuclei, p = .004). However, oral glucose tolerance tests revealed improved stimulation of insulin secretion in both strains. But this adaption was not sufficient to prevent impaired glucose tolerance in NZO mice compared with the NMRI control (p = .0002). Interestingly, glucose‐stimulated insulin secretion was blunted in isolated primary NZO islets in perifusion experiments. In summary, the NZO mouse reflects important characteristics of human GDM and prediabetes in pregnancy and serves as a model for subpopulations with early alterations in glucose metabolism and primary insulin secretion defect.
Bar Adsorptive Microextraction Coated with Carbon-Based Phase Mixtures for Performance-Enhancement to Monitor Selected Benzotriazoles, Benzothiazoles, and Benzenesulfonamides in Environmental Water Matrices

In the present work we propose, for the first time, bar adsorptive microextraction coated with carbon-based phase mixtures, followed by microliquid desorption and high performance liquid chromatography-diode array detection (BAμE-μLD/HPLC-DAD) analysis, to enhance the performance of the determination of traces of benzotriazoles (BTRs), benzothiazoles (BTs), and benzenesulfonamide derivatives (BSDs) in environmental water matrices. Assessing six carbon-based sorbents (CA1, CN1, B test EUR, SX PLUS, SX 1, and R) with different selectivity properties allowed us to tailor the best phase mixture (R, 12.5%/CN1, 87.5%) that has convenient porosity, texture, and surface chemistry (pHPZC,mix ~6.5) for trace analysis of benzenesulfonamide, 1-hydroxybenzotriazole, 1H-benzotriazole, 5-methyl-1H-benzotriazole, benzothiazole, and 1,3-benzothiazol-2-ol chemicals in aqueous media. Optimized experimental conditions provided average recoveries ranging from 37.9% to 59.2%, appropriate linear dynamic ranges (5.0 to 120.0 µg L−1; r2 ≥ 0.9964), limits of detection between 1.0 and 1.4 μg L−1, and good precisions (relative standard deviation (RSD) ≤ 9.3%). The proposed methodology (BAμE(R, 12.5%/CN1, 87.5%)-μLD/HPLC-DAD) also proved to be a suitable sorption-based static microextraction alternative to monitor traces of BTRs, BTs, and BSDs in rain, waste, tap, and estuarine water samples. From the data obtained, the proposed approach showed that the BAμE technique with the addition of lab-made devices allows users to adapt the technique to use sorbents or mixtures of sorbents with the best selectivity characteristics whenever distinct classes of target analytes occur simultaneously in the same application.
‘Today I feel strong’: African American women overcoming HIV-related stigma

Abstract Objective: African American account for more than 60% of women living with HIV/AIDS in the United States. This population is disproportionately affected in areas of diagnosis, treatment, and morbidity. HIV-related stigma has been found to play a pivotal role in the experiences of African American women living with HIV/AIDS (WLWHA) impacting self-perception, treatment adherence, depression, interpersonal relationships, and overall quality of life. Limited studies have explored the ways in which HIV-related stigma impacts the self-perceptions of African American WLWHA. To explore these experiences, this study examined the ways in which HIV-related stigma impacts the intrapersonal experiences of African American WLWHA. Design: A phenomenological investigation was conducted to explore the experiences of African American WLWHA. Main Outcome Measure: In-depth, semi-structured qualitative interviews. Results: Interpretive phenomenological analysis revealed four emergent themes: (1) increased vulnerability; (2) processing the diagnosis of HIV/AIDS; (3) surviving HIV/AIDS; and (4) quality of life. Conclusion: Findings of this study contribute to existing literature by highlighting the intricacies of the lived experiences of African American WLWHA from initial diagnosis to present day. Exploring the trajectory of the illness among this population allows for a deeper understanding of the ways in which HIV/AIDS impacts the intrapersonal experiences and self-perceptions of WLWHA.
Natural antioxidants in emulsions O/W

Abstract This study compared the capacity of propolis extract (PE) and thyme waste extract (TWE) to prevent the oxidation of oil in water (O/W) emulsion, as well as their impact on emulsion apparent viscosity (AV) in the presence of wheat germ and almond oils as lipid phase. For this, central composite design (CCD) and principal component analysis (PCA) were performed. Oxidation process was monitored by evaluating the formation of primary and secondary lipid oxidation products, at the same time the AV behavior was determined evaluating consistency index and flow behavior index. The results revealed that the increase of PE% and TWE% decreases TBARS (Thiobarbituric Acid Reactive Substances) and hydroperoxides formation. Viscosity increases with the rise of TWE% over (0.04%), whereas lower concentrations of PE% decreases it. Those results have been confirmed in the PCA analysis. TWE showed higher resistance to oxidation, although PE was more effective as antioxidant than TWE.
Patient-reported outcomes predict return to work and health-related quality of life six months after cardiac rehabilitation: Results from a German multi-centre registry (OutCaRe)

Background Multi-component cardiac rehabilitation (CR) is performed to achieve an improved prognosis, superior health-related quality of life (HRQL) and occupational resumption through the management of cardiovascular risk factors, as well as improvement of physical performance and patients’ subjective health. Out of a multitude of variables gathered at CR admission and discharge, we aimed to identify predictors of returning to work (RTW) and HRQL 6 months after CR. Design Prospective observational multi-centre study, enrolment in CR between 05/2017 and 05/2018. Method Besides general data (e.g. age, sex, diagnoses), parameters of risk factor management (e.g. smoking, hypertension), physical performance (e.g. maximum exercise capacity, endurance training load, 6-min walking distance) and patient-reported outcome measures (e.g. depression, anxiety, HRQL, subjective well-being, somatic and mental health, pain, lifestyle change motivation, general self-efficacy, pension desire and self-assessment of the occupational prognosis using several questionnaires) were documented at CR admission and discharge. These variables (at both measurement times and as changes during CR) were analysed using multiple linear regression models regarding their predictive value for RTW status and HRQL (SF-12) six months after CR. Results Out of 1262 patients (54±7 years, 77% men), 864 patients (69%) returned to work. Predictors of failed RTW were primarily the desire to receive pension (OR = 0.33, 95% CI: 0.22–0.50) and negative self-assessed occupational prognosis (OR = 0.34, 95% CI: 0.24–0.48) at CR discharge, acute coronary syndrome (OR = 0.64, 95% CI: 0.47–0.88) and comorbid heart failure (OR = 0.51, 95% CI: 0.30–0.87). High educational level, stress at work and physical and mental HRQL were associated with successful RTW. HRQL was determined predominantly by patient-reported outcome measures (e.g. pension desire, self-assessed health prognosis, anxiety, physical/mental HRQL/health, stress, well-being and self-efficacy) rather than by clinical parameters or physical performance. Conclusion Patient-reported outcome measures predominantly influenced return to work and HRQL in patients with heart disease. Therefore, the multi-component CR approach focussing on psychosocial support is crucial for subjective health prognosis and occupational resumption. Trial registration The study was registered at the German Clinical Trial Registry and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (DRKS00011418; http://www.drks.de/DRKS00011418, http://apps.who.int/trialsearch/Trial2.aspx? TrialID=DRKS00011418).