Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulation of the mitochondrial Ca2+ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells

Mitochondrial calcium (mCa2+) uptake occurs via the Mitochondrial Ca2+ Uniporter (MCU) complex and plays a critical role in mitochondrial dynamics, mitophagy, and apoptosis. MCU complex activity is in part modulated by the expression of its regulatory subunits. Cardiovascular disease models demonstrated altered gene/protein expression of one or multiple subunits in different cells, including vascular endothelial cells (ECs). MCU complex activity was found necessary for stable flow (s‐flow)‐induced mitophagy and promotion of an atheroprotective EC phenotype. Disturbed flow (d‐flow) is known to lead to an atheroprone phenotype. Despite the role of MCU in flow‐regulated EC function, flow‐induced alterations in MCU complex subunit expression are currently unknown. We exposed cultured human ECs to atheroprotective (steady shear stress, SS) or atheroprone flow (oscillatory shear stress, OS) and measured mRNA and protein levels of the MCU complex members. SS and OS differentially modulated subunit expression at gene/protein levels. Protein expression changes of the core MCU, mCa2+ uptake 1 (MICU1) and MCU regulator 1 (MCUR1) subunits in SS‐ and OS‐exposed, compared to static, ECs suggested an enhanced mCa2+ influx under each flow and a potential contribution to EC dysfunction under OS. In silico analysis of a single‐cell RNA‐sequencing dataset was employed to extract transcript values of MCU subunits in mouse carotid ECs from regions exposed to s‐flow or d‐flow. Mcu and Mcur1 genes showed significant differences in expression after prolonged exposure to each flow. The differential expression of MCU complex subunits indicated a tight regulation of the complex activity under physiological and pathological hemodynamic conditions.
Emergence of [GAR+] cells in yeast from sake brewing affects the fermentation properties

In the traditional (kimoto) method of sake (Japanese rice wine) brewing, Saccharomyces cerevisiae yeast cells are exposed to lactate, which is produced by lactic acid bacteria in the seed mash. Lactate promotes the appearance of glucose‐repression‐resistant [GAR+] cells. Herein, we compared the resistance to glucose repression among kimoto, industrial, and laboratory yeast strains. We observed that the frequencies of the spontaneous emergence of [GAR+] cells among the kimoto strains were higher than those among the industrial and laboratory strains. The fermentation ability of a kimoto yeast (strain U44) was lower than that of an industrial strain (K701), as [GAR+] cells generally showed slower ethanol production. The addition of lactate decreased the fermentation abilities of the K701 strain by increasing the number of [GAR+] cells, but it did not affect those of the U44 strain. These results suggest that lactate controlled fermentation by promoting the appearance of [GAR+] cells in the industrial sake strains but not in the kimoto strains.
Optimizing Status Epilepticus Management in the Emergency Department

Status epilepticus (SE) is a frequent medical emergency that requires expedited treatment to avoid the ensuing high incidence of morbidity and mortality associated with prolonged seizures. Protracted seizure duration itself has the potential to result in maladaptive neuronal responses that can not only further increase seizure duration and worsen clinical outcomes but also lead to reduced responsiveness to pharmacotherapy. Benzodiazepines are consistently recommended as first-line treatment due to their rapid onset and efficacy in terminating seizures, followed by the emergent administration of an antiepileptic drug (AED). Various benzodiazepine and AED options are recommended and can be utilized in this setting, all with their own unique advantages and challenges. With time at a premium, agents should be selected that can be rapidly administered and have an advantageous pharmacokinetic profile in order to limit seizure duration and optimize outcomes. The intent of this review is to provide an outline of the importance of time-to-treatment implementation in this setting, assess the landscape of options that may provide timing advantages, and examine potential strategies for deploying expeditious therapy.
Subdiffusion of beams through interplanetary and interstellar media

The angular distribution of beams being propagated through a medium with random inhomogeneities is analysed. The peculiarity of this medium is that beams are trapped at random locations and random times because of wave localisation in the inhomogeneities. The mean-square deviation of the beam from its initial direction is calculated. The application of this method to the diagnostics of interplanetary and interstellar turbulent media is discussed.
Parents' and children’s intolerance of uncertainty and their reactions to COVID-19: A story of remarkable similarity

The COVID-19 viral outbreak is a one in 100 year public health crisis. In addition to the stunning morbidity and mortality rates related to infection, multiple psychiatric sequelae erupted. Unfortunately, children and adolescents are neither immune to infection nor to the emotional consequences associated with the pandemic. Not surprisingly, the field’s understanding of the psychological consequences of the viral outbreak are nascent. Consequently, this study examines the relationship between parents’ and children’s intolerance of uncertainty (IU) and their reactions to COVID-19. Seventy-three parents and 62 children participated in the on-line survey utilizing innovative measures of IU and COVID-19- related thoughts/behaviors. The results revealed remarkable similarities in parents’ and children’s responses. Parents’ and children’s reports of the impact of COVID on their lives were highly correlated (r = .53, df = 60, p < .001). Parents’ perceptions of children’s COVID-19 thoughts and behaviors were strongly aligned with the youths’ self-report of their COVID reactions (r = .69, df = 60, p < .001) as well as the appraisal of the virus’ impact on their lives (r = .-.42, df = 60, p < .001). Finally, children’s reports of their COVID-19 related thoughts and behaviors were significantly linked to their IU (r = .60, df = 60, p < .001). Methodological limitations notwithstanding, the study’s findings provide compelling implications for the conceptualization, assessment, and treatment of emotional distress in the peri- and post-pandemic periods.
Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke The ARAIS Randomized Clinical Trial

IMPORTANCE Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. OBJECTIVE To assess the efficacy of argatroban plus alteplase for AIS. DESIGN, SETTING, AND PARTICIPANTS This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021
Different congenital hydrocephalus–associated mutations in Trim71 impair stem cell differentiation via distinct gain-of-function mechanisms

Congenital hydrocephalus (CH) is a common neurological disorder affecting many newborns. Imbalanced neurogenesis is a major cause of CH. Multiple CH-associated mutations are within the RNA-binding domain of Trim71, a conserved, stem cell–specific RNA-binding protein. How these mutations alter stem cell fate is unclear. Here, we show that the CH-associated mutations R595H and R783H in Trim71 accelerate differentiation and enhance neural lineage commitment in mouse embryonic stem cells (mESCs), and reduce binding to mRNAs targeted by wild-type Trim71, consistent with previous reports. Unexpectedly, however, each mutant binds an ectopic and distinct repertoire of target mRNAs. R595H-Trim71, but not R783H-Trim71 nor wild-type Trim71, binds the mRNA encoding β-catenin and represses its translation. Increasing β-catenin by overexpression or treatment with a Wnt agonist specifically restores differentiation of R595H-Trim71 mESCs. These results suggest that Trim71 mutations give rise to unique gain-of-function pathological mechanisms in CH. Further, our studies suggest that disruption of the Wnt/β-catenin signaling pathway can be used to stratify disease etiology and develop precision medicine approaches for CH.
Hsa‐miR‐409‐3p regulates endothelial progenitor senescence via PP2A‐P38 and is a potential ageing marker in humans

We explored the roles of hsa‐microRNA (miR)‐409‐3p in senescence and signalling mechanism of human endothelial progenitor cells (EPCs). Hsa‐miR‐409‐3p was found upregulated in senescent EPCs. Overexpression of miRNA mimics in young EPCs inhibited angiogenesis. In senescent EPCs, compared to young EPCs, protein phosphatase 2A (PP2A) was downregulated, with activation of p38/JNK by phosphorylation. Young EPCs treated with siPP2A caused inhibited angiogenesis with activation of p38/JNK, similar to findings in senescent EPCs. Time series analysis showed, in young EPCs treated with hsa‐miR‐409‐3p mimics, PP2A was steadily downregulated for 72 h, while p38/JNK was activated with a peak at 48 hours. The inhibited angiogenesis of young EPCs after miRNA‐409‐3p mimics treatment was reversed by the p38 inhibitor. The effect of hsa‐miR‐409‐3p on PP2A signalling was attenuated by exogenous VEGF. Analysis of human peripheral blood mononuclear cells (PBMCs) obtained from healthy people revealed hsa‐miR‐409‐3p expression was higher in those older than 65 years, compared to those younger than 30 years, regardless of gender. In summary, hsa‐miR‐409‐3p was upregulated in senescent EPCs and acted as a negative modulator of angiogenesis via targeting protein phosphatase 2 catalytic subunit alpha (PPP2CA) gene and regulating PP2A/p38 signalling. Data from human PBMCs suggested hsa‐miR‐409‐3p a potential biomarker for human ageing.
An OCT-based air suction-indentation probe for tissue elasticity measurement

In this study, we developed a miniaturized optical coherence tomography (OCT) probe with a diameter of 4 mm. It was integrated with an air-jet indentation and air suction to induce deformation of tissue. The deforming process of tissue under suction or indentation was continuously monitored by OCT, and deformation of tissue was then derived from the transient OCT signals. Studies on phantoms with different stiffness were conducted. Results showed that the stiffness obtained by the OCT-based suction and indention well correlated with the stiffness detected using conventional mechanical testing. The probe was small enough for endoscopic use. In addition to the elasticity, the viscoelasticity of tissues can also be detected using creep indentation and suction test.
Serum folate mediates the associations of MTHFR rs1801133 polymorphism with blood glucose levels and gestational diabetes mellitus in Chinese Han pregnant women

Abstract This study aimed to explore the mediation effects of one-carbon metabolism (OCM) related nutrients on the association between MTHFR rs1801133 polymorphism and gestational diabetes mellitus (GDM). Folate, vitamin B12 and homocysteine (Hcy) were measured in the serum of 1254 pregnant women. Linear and logistic regressions were used to estimate the associations of OCM nutrients and MTHFR rs1801133 polymorphism with blood glucose levels and GDM risk. Mediation analysis was applied to test the mediation effects of folate, vitamin B12 and Hcy on the association of MTHFR rs1801133 polymorphism with blood glucose concentrations and GDM. Pregnant women with MTHFR rs1801133 CC genotype had higher serum folate (10·75 v. 8·90 and 9·40 ng/ml) and lower serum Hcy (4·84 v. 4·93 and 5·20 μmol/l) than those with CT and TT genotypes. Folate concentrations were positively associated with fasting plasma glucose (FPG), 1-h plasma glucose (1-h PG), 2-h plasma glucose (2-h PG) and GDM risk. Vitamin B12 levels were negatively correlated with FPG and GDM. Although no direct association was found between MTHFR rs1801133 genotypes and GDM, there were significant indirect effects of MTHFR rs1801133 CC genotype on FPG (β: 0·005; 95 % CI: 0·001, 0·013), 1-h PG (β: 0·006; 95 % CI: 0·001, 0·014), 2-h PG (β: 0·007; 95 % CI: 0·001, 0·015) and GDM (β: 0·006; 95 % CI: 0·001, 0·014) via folate. In conclusion, serum folate mediates the effect of MTHFR rs1801133 on blood glucose levels and GDM. Our findings potentially provide a feasible GDM prevention strategy via individualised folate supplementation according to the MTHFR genotypes.
Association of intraabdominal fat with the risk of incident chronic kidney disease according to body mass index among Korean adults

Background The association between abdominal visceral adipose tissue and the risk of incident chronic kidney disease according to body mass index in the Asian population, remains unclear. We evaluated the impact of abdominal adiposity stratified by body mass index on the risk of incident chronic kidney disease. Methods A cohort study included 11,050 adult participants who underwent health check-ups and re-evaluated the follow-up medical examination at a single university-affiliated healthcare center. Cross-sectional abdominal adipose tissue areas were measured using computed tomography. The primary outcome was progression to chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73m2). The highest quartile of visceral adipose tissue was used for the cut-off of central obesity. Results During the mean of 5.6 follow-up years, 104 incident chronic kidney disease cases were identified. The risk for chronic kidney disease incidence was significantly increased in the 3rd and 4th quartile ranges of visceral adipose tissue [hazard ratio (95% confidence interval)]: 4.59 (1.48–14.30) and 7.50 (2.33–24.20), respectively. In the analysis stratified by body mass index, the chronic kidney disease incidence risk was increased in the highest quartile range of visceral adipose tissue in the normal weight group: 7.06 (1.35–37.04). However, there was no significant relationship between visceral adipose tissue and chronic kidney disease in the obese group. Compared to the subjects with normal weight and absent central obesity, the hazard ratio for chronic kidney disease incidence was 2.32 (1.26–4.27) among subjects with normal weight and central obesity and 1.81 (1.03–3.15) among subjects with obesity and central obesity. Conclusion Visceral adipose tissue was a significant risk factor for subsequent chronic kidney disease progression, and the association was identified only in the normal weight group. Normal-weight central obesity was associated with excess risk of chronic kidney disease, similar to the risk in the group with obesity and central obesity.
Genetic architecture of hippocampus subfields volumes in Alzheimer’s disease

Abstract Background The hippocampus is a heterogeneous structure, comprising histologically and functionally distinguishable hippocampal subfields. The volume reductions in hippocampal subfields have been demonstrated to be linked with Alzheimer's disease (AD). The aim of our study is to investigate the hippocampal subfields' genetic architecture based on the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set. Methods After preprocessing the downloaded genetic variants and imaging data from the ADNI database, a co‐sparse reduced rank regression model was applied to analyze the genetic architecture of hippocampal subfields volumes. Homology modeling, docking, molecular dynamics simulations, and Co‐IP experiments for protein–protein interactions were used to verify the function of target protein on hippocampal subfields successively. After that, the association analysis between the candidated genes on the hippocampal subfields volume and clinical scales were performed. Results The results of the association analysis revealed five unique genetic variants (e.g., ubiquitin‐specific protease 10 [USP10]) changed in nine hippocampal subfields (e.g., the granule cell and molecular layer of the dentate gyrus [GC‐ML‐DG]). Among five genetic variants, USP10 had the strongest interaction effect with BACE1, which affected hippocampal subfields verified by MD and Co‐IP experiments. The results of association analysis between the candidated genes on the hippocampal subfields volume and clinical scales showed that candidated genes influenced the volume and function of hippocampal subfields. Conclusions Current evidence suggests that hippocampal subfields have partly distinct genetic architecture and may improve the sensitivity of the detection of AD.
Engineering Pt/Co/AlO x heterostructures to enhance the Dzyaloshinskii–Moriya interaction

The study of interfacial Dzyaloshinskii–Moriya interaction (DMI) in perpendicularly magnetized structurally asymmetric heavy metal/ferromagnet multilayer systems is of high importance due to the formation of chiral magnetic textures in the presence of DMI. Here, we report the impact of cobalt oxidation at the Co/AlO x interface in Pt/Co/AlO x trilayer structures on the DMI by varying the post-growth annealing time, Al thickness and substrate. To quantify DMI we employed magneto-optical imaging of the asymmetric domain wall expansion, hysteresis loop shift, and spin-wave spectroscopy techniques. We further correlated the Co oxidation with low-temperature Hall effect measurements and x-ray photoelectron spectroscopy. Our results emphasize the importance of full characterization of the magnetic films that could be used for magnetic random access memory technologies when subjected to the semiconductor temperature processing conditions, as the magnetic interactions are critical for device performance and can be highly sensitive to oxidation and other effects.
Diagnostic spectrum of hypereosinophilia based on bone marrow pathology: 10 years' experience at a tertiary care hospital

Hypereosinophilia (HE) is defined as peripheral blood (PB) eosinophil count exceeding 1.5 × 109/L. As the causes of HE can be diverse, the work‐up of patients was complicated. In this study, we aimed to categorize the underlying diseases associated with HE and demonstrate minimum diagnostic approach.
Measuring social isolation in older adults: A rapid review informing evidence-based research and practice

ABSTRACT Objectives Older adults account for 18.5% of the Canadian population and are at risk of experiencing social isolation, compared to other age groups. Researchers define social isolation as a lack of social contact and relationships, but many social isolation measures do not reflect this definition. The aim of our study is to review the existing measures of social isolation with older adults to recommend evidence-based measures to researchers and practitioners. Methods We conducted a rapid review on PsycInfo and PsycTests. We included articles that were written in English or French, were peer-reviewed, used an older adult sample, included a self-report social isolation measure, and reported psychometric information. Results Following exclusion of ineligible articles, 12 measures were available for analysis. We further categorized the measures into: five most recommended measures, five measures that require further research, and two measures not recommended for use with older adults. Conclusions We observed a range of measures with varying suitability to be used with older adults; some were empirically driven but did not have strong psychometric properties, or vice-versa. Clinical Implications It is imperative that interventions aimed to address social isolation in older adults use evidence-based measures to assess progress and report treatment effectiveness.
P/Key: PUF based second factor authentication

One-time password (OTP) mechanisms are widely used to strengthen authentication processes. In time-based one-time password (TOTP) mechanisms, the client and server store common secrets. However, once the server is compromised, the client’s secrets are easy to obtain. To solve this issue, hash-chain-based second-factor authentication protocols have been proposed. However, these protocols suffer from latency in the generation of OTPs on the client side because of the hash-chain traversal. Secondly, they can generate only a limited number of OTPs as it depends on the length of the hash-chain. In this paper, we propose a second-factor authentication protocol that utilizes Physically Unclonable Functions (PUFs) to overcome these problems. In the proposed protocol, PUFs are used to store the secrets of the clients securely on the server. In case of server compromise, the attacker cannot obtain the seeds of clients’ secrets and can not generate valid OTPs to impersonate the clients. In the case of physical attacks, including side-channel attacks on the server side, our protocol has a mechanism that prevents attackers from learning the secrets of a client interacting with the server. Furthermore, our protocol does not incur any client-side delay in OTP generation.
Dissecting the genetic basis of heterosis in elite super-hybrid rice

Abstract Y900 is one of the top hybrid rice (Oryza sativa) varieties, with its yield exceeding 15 t·hm−2. To dissect the mechanism of heterosis, we sequenced the male parent line R900 and female parent line Y58S using long-read and Hi-C technology. High-quality reference genomes of 396.41 Mb and 398.24 Mb were obtained for R900 and Y58S, respectively. Genome-wide variations between the parents were systematically identified, including 1,367,758 single-nucleotide polymorphisms, 299,149 insertions/deletions, and 4,757 structural variations. The level of variation between Y58S and R900 was the lowest among the comparisons of Y58S with other rice genomes. More than 75% of genes exhibited variation between the two parents. Compared with other two-line hybrids sharing the same female parent, the portion of Geng/japonica (GJ)-type genetic components from different male parents increased with yield increasing in their corresponding hybrids. Transcriptome analysis revealed that the partial dominance effect was the main genetic effect that constituted the heterosis of Y900. In the hybrid, both alleles from the two parents were expressed, and their expression patterns were dynamically regulated in different tissues. The cis-regulation was dominant for young panicle tissues, while trans-regulation was more common in leaf tissues. Overdominance was surprisingly prevalent in stems and more likely regulated by the trans-regulation mechanism. Additionally, R900 contained many excellent GJ haplotypes, such as NARROW LEAF1, Oryza sativa SQUAMOSA PROMOTER BINDING PROTEIN-LIKE13, and Grain number, plant height, and heading date8, making it a good complement to Y58S. The fine-tuned mechanism of heterosis involves genome-wide variation, GJ introgression, key functional genes, and dynamic gene/allele expression and regulation pattern changes in different tissues and growth stages.