Miracle-dz/UniFAR-FTUs huggingface dataset:
The pathogenic p.Gln319Ter variant is not causing congenital adrenal hyperplasia when inherited in one of the duplicated CYP21A2 genes

Objective The study aimed to identify the pathogenic status of p.Gln319Ter (NM_000500.7: c.955C>T) variant when inherited in a single CYP21A2 gene (bimodular RCCX haplotype) and to discriminate between a non-causing congenital adrenal hyperplasia (CAH) allele when inherited in a duplicated and functional CYP21A2 gene context (trimodular RCCX haplotype). Methods 38 females and 8 males with hyperandrogenemia, previously screened by sequencing and identified as carriers for the pathogenic p.Gln319Ter, were herein tested by multiplex ligation-dependent probe amplification (MLPA) and a real-time PCR Copy number Variation (CNV) assay. Results Both MLPA and real-time PCR CNV analyses confirmed a bimodular and pathogenic RCCX haplotype with a single CYP21A2 in 19/46 (41.30%) p.Gln319Ter carriers and who in parallel all shared elevated 17-OHP levels. The remaining 27 individuals that also carried the p.Gln319Ter exhibited low 17-OHP levels as a result of their carriership of a duplicated CYP21A2 with a trimodular RCCX haplotype. Interestingly, all of these individuals also carried in linkage disequilibrium with p.Gln319Ter two single nucleotide polymorphisms, the c.293-79G>A (rs114414746) in intron 2 and the c. *12C>T (rs150697472) in the 3’-UTR. Therefore, these variants can be used to distinguish between pathogenic and non-pathogenic genomic contexts of the c.955T (p.Gln319) in the genetic diagnosis of congenital adrenal hyperplasia (CAH). Conclusion The employed methodologies identified a considerable number of individuals with non-pathogenic p.Gln319Ter from the individuals that typically carry the pathogenic p.Gln319Ter in a single CYP21A2. Therefore, it is extremely important the detection of such haplotypes for the prenatal diagnosis, treatment and genetic counseling in patients with CAH.
Plasma tRF-16-79MP9PD and tRF-28-OB1690PQR304 as potential biomarkers for 4- to 7-year-old children with obstructive sleep apnea-hypopnea syndrome

Background We investigated the expression and the potential value of plasma transfer RNA-derived fragments (tRFs) of children with obstructive sleep apnea–hypopnea syndrome (OSAHS) as screening biomarkers. Methods At first, we randomly selected five plasma samples from the case group and the control group for high-throughput RNA sequencing. Secondly, we screened two tRFs with different expression between the two groups, amplified it by quantitative reverse transcription-PCR (qRT-PCR) on all samples. Then we analyzed the diagnostic value of the tRFs and their correlation with the clinical data. Results A total of 50 OSAHS children and 38 healthy controls were included. Our results demonstrated that the plasma levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 were significantly down-regulated in OSAHS children. Receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) of tRF-16-79MP9PD and tRF-28-OB1690PQR304 was 0.7945 and 0.8276. In addition, the AUC of the combination reached 0.8303 with 73.46% and 76.42% sensitivity and specificity. Correlation analysis showed that the degree of tonsil enlargement, hemoglobin (Hb) and triglyceride (TG). were related to the expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304. Multivariable linear regression analysis showed that degree of tonsil enlargement, Hb and TG related to tRF-16-79MP9PD while degree of tonsil enlargement and Hb related to tRF-28-OB1690PQR304. Conclusions The expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 in the plasma of OSAHS children decreased significantly which were closely related to the degree of tonsil enlargement, Hb and TG, may become novel biomarkers for the diagnosis of pediatric OSAHS.
Effects of organic fertilizers on yield, soil physico-chemical property, soil microbial community diversity and structure of Brassica rapa var. Chinensis

The amount of chemical fertilizer for vegetables is on the high level in China. The use of organic fertilizers to meet the nutrient requirement of crops will be an inevitable practice in sustainable agriculture. In this study, we compared the effects of pig manure fertilizer, rabbit manure fertilizer and chemical fertilizer on yield, quality of Brassica rapa var. Chinensis, soil physico-chemical properties and microbial community by using two consecutive seasons of three fertilizers in a pot experiment. The results were as follows: (1) In the first season, the fresh yield of Brassica rapa var. Chinensis applying chemical fertilizer was significantly (p ≤ 5%) higher than those of applying the pig manure and rabbit manure fertilizer, and the results were the opposite in the second season. The total soluble sugar concentration of fresh Brassica rapa var. Chinensis applying rabbit manure fertilizer was significantly (p ≤ 5%) higher than those of applying pig manure fertilizer and chemical fertilizer in the first season, and the NO3-N content of fresh Brassica rapa var. Chinensis on the contrary. (2) The organic fertilizer increased the concentration of total nitrogen, total phosphorus and organic carbon in soil in both two seasons. Rabbit manure fertilizer increased the soil pH and EC and significantly (p ≤ 5%) reduced the soil NO3-N content. (3) The pig manure and rabbit manure fertilizer significantly (p ≤ 5%) increased the diversity and abundance of soil bacterial of Brassica rapa var. Chinensis, but had no significant effect on soil fungi. Pearson correlation analysis showed that soil TN, TP, organic carbon content and EC were significantly correlated with soil bacterial α - diversity. There were significant differences (p ≤ 5%) in the bacterial community structures between three treatments in two seasons, and significant differences (p ≤ 5%) in the fungal community structures between fertilizer treatments while not between two seasons. Pig manure and rabbit manure fertilizer decreased the relative abundance of soil Acidobacteria and Crenarchaeota, rabbit manure fertilizer significantly increased the abundance of Actinobacteria in the second season. Distance-based redundancy analysis (dbRDA) showed that soil EC, TN, and organic carbon content were key physico-chemical factors in determining bacterial community structure in Brassica rapa var. Chinensis soil, and soil NO3-N, EC, SOC concentration and soil pH in the fungal community structure.
Genome wide association studies and candidate gene mining for understanding the genetic basis of straw silica content in a set of Oryza nivara (Sharma et Shastry) accessions

Rice is a high-silica (SiO2·nH2O) accumulator. Silicon (Si) is designated as a beneficial element associated with multiple positive effects on crops. However, the presence of high silica content is detrimental to rice straw management, hampering its use as animal feed and as raw material in multiple industries. Rice straw management is a serious concern in north-western India, and it is eventually burned in situ by farmers, contributing to air pollution. A practical solution could lie in reducing the silica content in rice while also attaining sound plant growth. A set of 258 Oryza nivara accessions along with 25 cultivated varieties of Oryza sativa was used to assess the variation in straw silica content using the molybdenum blue colorimetry method. A large continuous variation was observed for straw silica content in O. nivara accessions, ranging from 5.08% to 16%, while it varied from 6.18% to 15.81% in the cultivated varieties. The O. nivara accessions containing 43%–54% lower straw silica content than the currently prominent cultivated varieties in the region were identified. A set of 22,528 high-quality single nucleotide polymorphisms (SNPs) among 258 O. nivara accessions was used for estimating population structure and genome-wide association studies (GWAS). A weak population structure with 59% admixtures was identified among O. nivara accessions. Further, multi-locus GWAS revealed the presence of 14 marker-trait associations (MTAs) for straw silica content, with six of them co-localizing with previously reported quantitative trait loci (QTL). Twelve out of 14 MTAs showed statistically significant allelic differences. Thorough candidate gene analyses revealed the presence of promising candidate genes, including those encoding the ATP-binding cassette (ABC) transporter, Casparian thickening, multi-drug and toxin extrusion (MATE) protein, F-box, and MYB-transcription factors. Besides, ortho-QTLs among rice and maize genomes were identified, which could open ways for further genetic analysis of this trait. The findings of the study could aid in further understanding and characterizing genes for Si transport and regulation in the plant body. The donors carrying the alleles for lower straw silica content can be used in further marker-assisted breeding programs to develop rice varieties with lower silica content and higher yield potential.
Remyelination in multiple sclerosis from the miRNA perspective

Remyelination relies on the repair of damaged myelin sheaths, involving microglia cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes. This process drives the pathophysiology of autoimmune chronic disease of the central nervous system (CNS), multiple sclerosis (MS), leading to nerve cell damage and progressive neurodegeneration. Stimulating the reconstruction of damaged myelin sheaths is one of the goals in terms of delaying the progression of MS symptoms and preventing neuronal damage. Short, noncoding RNA molecules, microRNAs (miRNAs), responsible for regulating gene expression, are believed to play a crucial role in the remyelination process. For example, studies showed that miR-223 promotes efficient activation and phagocytosis of myelin debris by microglia, which is necessary for the initiation of remyelination. Meanwhile, miR-124 promotes the return of activated microglia to the quiescent state, while miR-204 and miR-219 promote the differentiation of mature oligodendrocytes. Furthermore, miR-138, miR-145, and miR-338 have been shown to be involved in the synthesis and assembly of myelin proteins. Various delivery systems, including extracellular vesicles, hold promise as an efficient and non-invasive way for providing miRNAs to stimulate remyelination. This article summarizes the biology of remyelination as well as current challenges and strategies for miRNA molecules in potential diagnostic and therapeutic applications.
Biogeochemical structure of the Laptev Sea in 2015-2020 associated with the River Lena plume

The discharge of rivers and the subsequent dispersion of their plumes play a pivotal role in the biogeochemical cycling of the Arctic Ocean. Based on the data collected during annual transects conducted in the autumn period (September-October) from 2015-2020, this study explores the effect of River Lena plume dispersion on the seasonal and interannual changes in the hydrophysical and biogeochemical structure of the southeastern Laptev Sea. The temperature-salinity relationship (T-S), Redfield ratio and multiparameter cluster analysis were used to investigate variations in the water mass structure along the transect. The results revealed that the plume’s interannual and seasonal spreading patterns play a crucial role in regulating the local physical, biogeochemical, and biological processes in the southern Laptev Sea. During September-October, the hydrochemical water mass structure along the transects shifted from highly stratified to unstratified as the plume’s mixing intensity increased. Anomalous hydrochemical distributions were observed due to coastal upwelling, which was primarily characterized by high total alkalinity and nitrate levels, and low organic phosphorus, nitrite, and ammonia levels in the seawater. Wind and cold weather conditions drive deep vertical mixing of seawater, causing the resuspension of bottom sediment and the subsequent enrichment of bottom water by nutrients. Multi-parameter cluster analysis is used to describe the details of water mass structures in the highly dynamic southern Laptev Sea, with water mass structures typically undergoing significant changes within two weeks between September and October. The migration and transformation of water masses throughout the seasons are influenced by the volume of river discharge, fall-winter cooling, and atmospheric circulation patterns. Furthermore, the general atmospheric circulation is confirmed to be the primary cause of the interannual variation in the spread of the Lena River plume over the southeast Laptev Sea.
Fine particulate matter air pollution and the mortality of children under five: a multilevel analysis of the Ethiopian Demographic and Health Survey of 2016

Background Every year, polluted air is costing the globe 543,000 deaths of children under five. The particulate matter below 2.5 μm diameter (PM2.5) is a part of air pollution that has adverse effects on children’s health. In Ethiopia, the effect of ambient PM2.5 is least explored. This study aimed to assess the association between PM2.5 and under-five mortality in Ethiopia. Methods The study used the data from the Ethiopian Demographic Health Surveys conducted in 2016, collected between January 18 and June 27. All children under five who had data on child mortality and location coordinates were included in the study. Exposure to ambient PM2.5 concentration was a satellite-based estimate by the Atmospheric Composition Analysis Group at Washington and Dalhousie University, in the United States and Canada, respectively. Annual mean pollution levels and mortality datasets were matched by children’s geographical location and dates of birth, death, and interview. The relationship between ambient PM2.5 and under-five mortality was determined by a multilevel multivariable logistic regression on R software. The statistical analyses were two-sided at a 95% confidence interval. Results The study addressed 10,452 children with the proportion of under-five mortality being 5.4% (95% CI 5.0–6.8%). The estimated lifetime annual mean exposure of ambient total PM2.5 was 20.1 ± 3.3 μgm−3. A 10-unit increase in the lifetime annual mean ambient total PM2.5 was associated with 2.29 [95% CI 1.44, 3.65] times more odds of under-five mortality after adjusting for other variables. Conclusion Children under five are exposed to higher levels of ambient PM2.5 concentration, exceeding the limit set by the World Health Organization. Ambient PM2.5 is significantly associated with under-five mortality, adjusting for other variables. Strong measures need to be taken to reduce air pollution.
Alterations of biaxial viscoelastic properties of the right ventricle in pulmonary hypertension development in rest and acute stress conditions

Introduction: The right ventricle (RV) mechanical property is an important determinant of its function. However, compared to its elasticity, RV viscoelasticity is much less studied, and it remains unclear how pulmonary hypertension (PH) alters RV viscoelasticity. Our goal was to characterize the changes in RV free wall (RVFW) anisotropic viscoelastic properties with PH development and at varied heart rates. Methods: PH was induced in rats by monocrotaline treatment, and the RV function was quantified by echocardiography. After euthanasia, equibiaxial stress relaxation tests were performed on RVFWs from healthy and PH rats at various strain-rates and strain levels, which recapitulate physiological deformations at varied heart rates (at rest and under acute stress) and diastole phases (at early and late filling), respectively. Results and Discussion: We observed that PH increased RVFW viscoelasticity in both longitudinal (outflow tract) and circumferential directions. The tissue anisotropy was pronounced for the diseased RVs, not healthy RVs. We also examined the relative change of viscosity to elasticity by the damping capacity (ratio of dissipated energy to total energy), and we found that PH decreased RVFW damping capacity in both directions. The RV viscoelasticity was also differently altered from resting to acute stress conditions between the groups—the damping capacity was decreased only in the circumferential direction for healthy RVs, but it was reduced in both directions for diseased RVs. Lastly, we found some correlations between the damping capacity and RV function indices and there was no correlation between elasticity or viscosity and RV function. Thus, the RV damping capacity may be a better indicator of RV function than elasticity or viscosity alone. These novel findings on RV dynamic mechanical properties offer deeper insights into the role of RV biomechanics in the adaptation of RV to chronic pressure overload and acute stress.
Osteopontin depletion in macrophages perturbs proteostasis via regulating UCHL1-UPS axis and mitochondria-mediated apoptosis

Introduction Osteopontin (OPN; also known as SPP1), an immunomodulatory cytokine highly expressed in bone marrow-derived macrophages (BMMΦ), is known to regulate diverse cellular and molecular immune responses. We previously revealed that glatiramer acetate (GA) stimulation of BMMΦ upregulates OPN expression, promoting an anti-inflammatory, pro-healing phenotype, whereas OPN inhibition triggers a pro-inflammatory phenotype. However, the precise role of OPN in macrophage activation state is unknown. Methods Here, we applied global proteome profiling via mass spectrometry (MS) analysis to gain a mechanistic understanding of OPN suppression versus induction in primary macrophage cultures. We analyzed protein networks and immune-related functional pathways in BMMΦ either with OPN knockout (OPN KO ) or GA-mediated OPN induction compared with wild type (WT) macrophages. The most significant differentially expressed proteins (DEPs) were validated using immunocytochemistry, western blot, and immunoprecipitation assays. Results and discussion We identified 631 DEPs in OPN KO or GA-stimulated macrophages as compared to WT macrophages. The two topmost downregulated DEPs in OPN KO macrophages were ubiquitin C-terminal hydrolase L1 (UCHL1), a crucial component of the ubiquitin-proteasome system (UPS), and the anti-inflammatory Heme oxygenase 1 (HMOX-1), whereas GA stimulation upregulated their expression. We found that UCHL1, previously described as a neuron-specific protein, is expressed by BMMΦ and its regulation in macrophages was OPN-dependent. Moreover, UCHL1 interacted with OPN in a protein complex. The effects of GA activation on inducing UCHL1 and anti-inflammatory macrophage profiles were mediated by OPN. Functional pathway analyses revealed two inversely regulated pathways in OPN-deficient macrophages: activated oxidative stress and lysosome-mitochondria-mediated apoptosis (e.g., ROS, Lamp1-2, ATP-synthase subunits, cathepsins, and cytochrome C and B subunits) and inhibited translation and proteolytic pathways (e.g., 60S and 40S ribosomal subunits and UPS proteins). In agreement with the proteome-bioinformatics data, western blot and immunocytochemical analyses revealed that OPN deficiency perturbs protein homeostasis in macrophages—inhibiting translation and protein turnover and inducing apoptosis—whereas OPN induction by GA restores cellular proteostasis. Taken together, OPN is essential for macrophage homeostatic balance via the regulation of protein synthesis, UCHL1-UPS axis, and mitochondria-mediated apoptotic processes, indicating its potential application in immune-based therapies.
Sedimentary deformation relating to episodic seepage in the last 1.2 million years: a multi-scale seismic study from the Vestnesa Ridge, eastern Fram Strait

Seafloor hydrocarbon seepage is a natural fluid release process that occurs worldwide on continental shelves, slopes, and in deep oceanic basins. The Vestnesa sedimentary ridge in the eastern Fram Strait hosts a deep-water gas hydrate system that became charged with hydrocarbons ∼2.7 Ma and has experienced episodic seepage along the entire ridge until a few thousand years ago, when seepage activity apparently ceased in the west but persisted in the east. Although it has been documented that faults and fractures play a key role in feeding the seeps with thermogenic gases, the mechanisms controlling seepage periodicity remain poorly understood. Here we integrate high-resolution P-cable 3D seismic and Chirp data to investigate the spatial and temporal evolution of high-resolution fractures and fluid flow features in the west of the Vestnesa Ridge. We characterize sediment deformation using a fracture density seismic attribute workflow revealing two highly deformed stratigraphic intervals and associated small-scale pockmarks (<20 m diameter). Chronostratigraphic constraints from the region show that these two highly deformed intervals are influenced by at least three major climatic and oceanic events during the last 1.2 million years: the Mid-Pleistocene Transition (∼1.25–0.7 Ma), the penultimate deglaciation (∼130 ka) and the last deglaciation (Heinrich Stadial 1: ∼16 ka). These periods of deformation appear associated with seismic anomalies potentially correlated with buried methane-derived authigenic carbonate and have been sensitive to shifts in the boundary of the free gas-gas hydrate interface. Our results show shifts (up to ∼30 m) in the depth of the base of the gas hydrate stability zone (GHSZ) associated with major changes in ocean bottom water temperatures. This ocean-driven effect on the base of the GHSZ since the Last Glacial Maximum coincides with the already highly deformed Mid-Pleistocene Transition sedimentary interval and likely enhanced deformation and gas leakage along the ridge. Our results have implications for understanding how glacial cycles impact fracture formation and associated seepage activity.
Clinical characteristics and outcomes in febrile infants aged 29–90 days with urinary tract infections and cerebrospinal fluid pleocytosis

Introduction Fever without a focus is a common reason for medical evaluations, hospitalizations, and the antimicrobial treatment of infants younger than 90 days. The presence of cerebrospinal fluid (CSF) pleocytosis could be challenge for clinicians who treat febrile young infants with urinary tract infection (UTI). We evaluated the factors associated with sterile CSF pleocytosis and the clinical outcomes of the patients. Methods A retrospective review of patients aged 29–90 days with febrile UTIs who underwent a non-traumatic lumbar puncture (LP) at Pusan National University Hospital from January 2010 to December 2020 was conducted. CSF pleocytosis was defined as white blood cell (WBC) counts ≥9/mm3. Results A total of 156 patients with UTI were eligible for this study. Four (2.6%) had concomitant bacteremia. However, no patients had culture-proven bacterial meningitis. In correlation analysis, although weak strength, CSF WBC counts were positively correlated with C-reactive protein (CRP) level (Spearman r = 0.234; P = 0.003). Thirty-three patients had CSF pleocytosis [21.2%; 95% confidential interval (CI), 15.5–28.2]. The time from fever onset to the hospital visit, peripheral blood platelet counts, and CRP level at admission were statistically significant in patients with sterile CSF pleocytosis compared to those without CSF pleocytosis. In the multiple logistic regression, only CRP was independently associated with sterile CSF pleocytosis (cutoff, 3.425 mg/dl; adjusted odds ratio, 2.77; 95% CI, 1.19–6.88). The proportion of fever defervescence by hospital day 2 was 87.9% in patients with CSF pleocytosis and 89.4% in those without CSF pleocytosis (P = 0.759). There was no statistical difference in the fever defervescence curves between the two patient groups (P = 0.567). No patients had neurological manifestations or complications. Conclusions Coexisting sterile CSF pleocytosis among febrile infants with UTIs suggest a systemic inflammatory response. However, the clinical outcomes between the two groups were similar. A selective LP should be considered in young infants with evidence of UTI, and inappropriate antibiotic therapy for sterile CSF pleocytosis should be avoided.