Miracle-dz/UniFAR-FTUs huggingface dataset:
Meta-Analysis and Systematic Review of Coagulation Disbalances in COVID-19: 41 Studies and 17,601 Patients

Introduction Coagulation parameters are important determinants for COVID-19 infection. We conducted meta-analysis to assess the association between early hemostatic parameters and infection severity. Methods Electronic search was made for papers that addressed clinical characteristics of COVID-19 patients and disease severity. Results were filtered using exclusion and inclusion criteria and then pooled into a meta-analysis to estimate the standardized mean difference (SMD) with 95% confidence interval (CI) for D-dimers, fibrinogen, prothrombin time, platelet count (PLT), activated partial thromboplastin time. To explore the heterogeneity and robustness of our fundings, sensitivity and subgroup analyses were conducted. Publication bias was assessed with contour-enhanced funnel plots and Egger's test by linear regression. Coagulation parameters data from retrospective cohort study of 451 patients with COVID-19 at National Research Center for Cardiac Surgery were included in meta-analysis of published studies. Results Overall, 41 original studies (17,601 patients) on SARS-CoV-2 were included. For the two groups of patients, stratified by severity, we identified that D-dimers, fibrinogen, activated partial thromboplastin time, and prothrombin time were significantly higher in the severe group [SMD 0.6985 with 95%CI (0.5155; 0.8815); SMD 0.661 with 95%CI (0.3387; 0.9833); SMD 0.2683 with 95%CI (0.1357; 0.4009); SMD 0.284 with 95%CI (0.1472; 0.4208)]. In contrast, PLT was significantly lower in patients with more severe cases of COVID-19 [SMD −0.1684 with 95%CI (−0.2826; −0.0542)]. Neither the analysis by the leave-one-out method nor the influence diagnostic have identified studies that solely cause significant change in the effect size estimates. Subgroup analysis showed no significant difference between articles originated from different countries but revealed that severity assessment criteria might have influence over estimated effect sizes for platelets and D-dimers. Contour-enhanced funnel plots and the Egger's test for D-dimers and fibrinogen revealed significant asymmetry that might be a sign of publication bias. Conclusions The hemostatic laboratory parameters, with exception of platelets, are significantly elevated in patients with severe COVID-19. The two variables with strongest association to disease severity were D-dimers and fibrinogen levels. Future research should aim outside conventional coagulation tests and include analysis of clotting formation and platelet/platelet progenitors characteristics.
Dynamic Changes of Ocular Surface in First-Time Contact Lens Wearers and the Effective Factors of Contact Lens Discomfort

Purpose The purpose of the study is to investigate the dynamic changes in ocular surface indicators in first-time contact lens (CL) wearers and identify the most influential factors in CL discomfort (CLD). Methods A total of 26 healthy non-CL wearers (26 eyes) were recruited and fitted monthly with disposable hydrogel CLs. Each participant underwent a full ocular surface evaluation, which include Efron grading, tear film breakup time, Schirmer's I test, corneal dendritic cell (DCs) imaging by in vivo confocal microscopy (IVCM), and conjunctival microvasculature evaluation by functional slit-lamp biomicroscopy. CLD was assessed using the Ocular Surface Disease Index questionnaire at baseline, 1 week, 1, 3, and 6 months after wearing it and another 6 months after discontinuing it. Results Clinical signs and CLD were significantly increased in the first week (p < 0.05). The microvascular response and DC activation peaked at the 1-month interval (p < 0.05). During CL wear, CLD is positively correlated with corneal staining (B = 0.238, p = 0.002), papillary conjunctivitis (B = 0.245, p < 0.001), and microvascular blood flow velocity (B = 0.353, p < 0.001). After discontinuation, only DC activation remained elevated at 6 months, whereas the other signs recovered. Conclusions The first week of CL wear was the main period for the appearance of ocular surface clinical signs, and the first month was the main period for the activation of subclinical inflammation. Corneal staining and conjunctival microvascular response are the main factors affecting CLD. Even if the clinical signs recover after discontinuing wear, subclinical inflammation may persist.
Strategies of the Party Selectorate: The Two-Level Game in District Selections in Germany’s Mixed Member Electoral System

The article investigates how the opportunity structure and contextual factors influence the selectorates’ strategies in the process of candidate selection. The article argues that these strategies are an under-researched but important explanatory and dynamic link between the parties’ goals and context factors of candidate selection on the one side and the adopted selection criteria and the outcome of candidate selection on the other side. Based on a mixed-methods design, the study scrutinizes the selectorates’ strategies at district selections in Germany’s mixed-member electoral system. The analysis reveals that the local selectorates adopt the traditional inward oriented selection criteria to find the best candidate for the local party branch if the district seat is safe for the party. If, however, the seat is not safe, the selectorates prioritize the electoral goal over the local party organizational goal and strategically adapt the selection criteria to the opportunity structure. By considering both local inter-party competition and regional intra-party competition, they either take up a local voters’ perspective or anticipate the selection criteria of the state party lists in order to increase the chances for a seat in parliament. Thus, due to the mixed-member electoral system, the prevalence of dual candidacies, and decentralized candidate selection methods, intra-party selection in German districts is a two-level game.
Crisis Ahead? Why Human-Robot Interaction User Studies May Have Replicability Problems and Directions for Improvement

There is a confidence crisis in many scientific disciplines, in particular disciplines researching human behavior, as many effects of original experiments have not been replicated successfully in large-scale replication studies. While human-robot interaction (HRI) is an interdisciplinary research field, the study of human behavior, cognition and emotion in HRI plays also a vital part. Are HRI user studies facing the same problems as other fields and if so, what can be done to overcome them? In this article, we first give a short overview of the replicability crisis in behavioral sciences and its causes. In a second step, we estimate the replicability of HRI user studies mainly 1) by structural comparison of HRI research processes and practices with those of other disciplines with replicability issues, 2) by systematically reviewing meta-analyses of HRI user studies to identify parameters that are known to affect replicability, and 3) by summarizing first replication studies in HRI as direct evidence. Our findings suggest that HRI user studies often exhibit the same problems that caused the replicability crisis in many behavioral sciences, such as small sample sizes, lack of theory, or missing information in reported data. In order to improve the stability of future HRI research, we propose some statistical, methodological and social reforms. This article aims to provide a basis for further discussion and a potential outline for improvements in the field.
Targeting the Retinoid X Receptor Pathway Prevents and Ameliorates Murine Chronic Graft-Versus-Host Disease

Most allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients receive peripheral blood stem cell grafts resulting in a 30%–70% incidence of chronic graft-versus-host disease (cGVHD), a major cause of mortality and morbidity in long-term survivors. While systemic steroids remain the standard of care for first-line therapy, patients may require long-term administration, and those with steroid-resistant or refractory cGVHD have a worse prognosis. Although durable and deep responses with second-line therapies can be achieved in some patients, there remains an urgent need for new therapies. In this study, we evaluated the efficacy of IRX4204, a novel agonist that activates RXRs and is in clinical trials for cancer treatment to prevent and treat cGVHD in two complementary murine models. In a major histocompatibility complex mismatched, non-sclerodermatous multiorgan system model with bronchiolitis obliterans, IRX4204 prevented and reversed cGVHD including associated pulmonary dysfunction with restoration of germinal center T-follicular helper: T-follicular regulatory cell balance. In a minor histocompatibility antigen disparate sclerodermatous model, IRX4204 treatment significantly prevented and ameliorated skin cGVHD by reducing Th1 and Th17 differentiation due to anti-inflammatory properties. Together, these results indicate that IRX4204 is a promising therapeutic option to treat cGVHD with bronchiolitis obliterans or sclerodermatous manifestations.
The Relationship Between Atrial Cardiopathy Biomarkers and Prognosis of Patients With Embolic Stroke of Undetermined Source

Objective To compare the proportion of atrial cardiopathy in patients with embolic stroke of undetermined source (ESUS) and other non-cardiac strokes, and to evaluate the prognostic value of atrial cardiopathy biomarkers in patients with ESUS. Methods This retrospective study enrolled patients with ischemic stroke from January 2018 to April 2020 in a single stroke center, and compared the proportion of atrial cardiopathy in (1) ESUS group, (2) large artery atherosclerosis (LAA) group, and (3) small-vessel occlusion (SVO) group. Then, it compared the baseline characteristics between ESUS patients with atrial cardiopathy and cardioembolism (CE) group. In addition, the relationship was compared between the biomarkers of atrial cardiopathy and prognosis in patients with ESUS. Results In total, 316 patients with ischemic stroke were included that included 105 (33.23%) ESUS, 84 (26.58%) LAA, 73 (23.10%) SVO, and 54 (17.09%) CE. Among these patients, patients with ESUS were younger, and had lower triglyceride, lower low-density lipoprotein than non-ESUS group. The proportion of atrial cardiopathy in ESUS group was higher than LAA group or SVO group (42.86 vs. 17.86 vs. 8.22%, p < 0.001). Compared with non-atrial cardiopathy group, patients with atrial cardiopathy were older, had lower EF value, larger left ventricular diameter, and longer PR interval. Among 105 patients with ESUS, 11 (10.78%) cases died, 32 (31.37%) cases had poor functional outcome (mRS >2). In the multivariable model, the risk factor associated with the death risk of patients with ESUS was N-terminal pro-B-type natriuretic peptide (NT-proBNP) >250 pg/ml [p = 0.025, hazard ratio (HR) = 4.626, 95% CI: 1.212–17.652] after a 1-year follow-up. Conclusions Atrial cardiopathy is more common in patients with ESUS, and the characteristics of ESUS patients with atrial cardiopathy are similar to those in patients with CE. NT-proBNP >250 pg/ml is related to the risk of death in patients with ESUS.
A Multi-Omics Pan-Cancer Analysis of 4EBP1 in Cancer Prognosis and Cancer-Associated Fibroblasts Infiltration

Background: Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (4EBP1) involved in inhibition of protein translation and synthesis. However, the phosphoprotein of 4EBP1 (p-4EBP1) promotes the translation and synthesis of several proteins, including multiple classic oncogenic proteins. The prognostic significance of 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 in Pan-cancer are still unclear. Methods: In this study, we provided a multi-Omics investigation for the prognostic value of 4EBP1 mRNA, 4EBP1 protein, and different 4EBP1 phosphoproteins in a Pan-cancer manner based on the TCGA projects. We explored the correlation between 4EBP1 expression and the cancer-associated fibroblast (CAFs) infiltration, respectively using the EPIC, MCPCOUNTER, and TIDE algorithms. The functional states of 4EBP1 were explored using single-cell sequencing analysis in Pan-Cancer. Immunohistochemistry staining was used to detect and verify the expression of 4EBP1 in several cancers. Results: 4EBP1 mRNA was aberrantly overexpressed in most cancers, and was associated with the poor prognosis in ten cancers. Notably, increased 4EBP1 mRNA expression significantly correlated with tumor staging and worse prognosis in BRCA, KIRC, and KIRP, while having the opposite effect in STAD. 4EBP1 expression was associated with the CAFs infiltration level in ten cancer types. Interestingly, the correlation between 4EBP1 and CAFs infiltration had pronounced heterogeneity in digestive system tumors and urinary system tumors. In BLCA, KIRC, and ACC as well as BRCA, 4EBP1 was significantly positively correlated with CAFs infiltration and was associated with a poor prognosis. In STAD and COAD, 4EBP1 is negatively correlated with CAFs infiltration and was associated with a better prognosis. Lastly, the expression and prognostic significance of 4EBP1 protein and different p-4EBP1 varied enormously among cancers. Conclusion: Our multi-omics study indicates that 4EBP1-driven CAFs infiltration is associated with cancer prognosis and 4EBP1 mRNA, 4EBP1 protein, and p-4EBP1 proteins may serve as potential prognostic biomarkers and therapeutic targets in diverse cancer.
Long-Term Wi-Fi Exposure From Pre-Pubertal to Adult Age on the Spermatogonia Proliferation and Protective Effects of Edible Bird’s Nest Supplementation

Children are vulnerable to the radiofrequency radiation (RFR) emitted by Wi-Fi devices. Nevertheless, the severity of the Wi-Fi effect on their reproductive development has been sparsely available. Therefore, this study was conducted to evaluate the Wi-Fi exposure on spermatogonia proliferation in the testis. This study also incorporated an approach to attenuate the effect of Wi-Fi by giving concurrent edible bird’s nest (EBN) supplementation. It was predicted that Wi-Fi exposure reduces spermatogonia proliferation while EBN supplementation protects against it. A total of 30 (N = 30) 3-week-old Sprague Dawley weanlings were divided equally into five groups; Control, Control EBN, Wi-Fi, Sham Wi-Fi, and Wi-Fi + EBN. 2.45 GHz Wi-Fi exposure and 250 mg/kg EBN supplementation were conducted for 14 weeks. Findings showed that the Wi-Fi group had decreased in spermatogonia mitosis status. However, the mRNA and protein expression of c-Kit-SCF showed no significant decrease. Instead, the reproductive hormone showed a reduction in FSH and LH serum levels. Of these, LH serum level was decreased significantly in the Wi-Fi group. Otherwise, supplementing the Wi-Fi + EBN group with 250 mg/kg EBN resulted in a significant increase in spermatogonia mitotic status. Even though EBN supplementation improved c-Kit-SCF mRNA and protein expression, the effects were insignificant. The improvement of spermatogonia mitosis appeared to be associated with a significant increase in blood FSH levels following EBN supplementation. In conclusion, the long-term Wi-Fi exposure from pre-pubertal to adult age reduces spermatogonia proliferation in the testis. On the other hand, EBN supplementation protects spermatogonia proliferation against Wi-Fi exposure.
Do All Roads Lead to Rome? Genes Causing Dravet Syndrome and Dravet Syndrome-Like Phenotypes

Background Dravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A, which encodes the voltage-gated sodium channel NaV1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner. Objective The purpose of this study was to identify genes other than SCN1A that may also cause DS or DS-like phenotypes. Methods A comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized. Results A PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on PCDH19, three on SCN2A, two on SCN8A, five on SCN1B, two on GABRA1, three on GABRB3, three on GABRG2, and three on STXBP1 were included. Only one study was recorded for CHD2, CPLX1, HCN1 and KCNA2, respectively. It is worth noting that a few articles reported on more than one epilepsy gene. Conclusion DS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.
The Influence of Performance-Contingent Rewards on Proactive and Responsive Creativity: Dual-Path Mediating Effects of Work Motivation

Creativity has become prevalent in the routine work of knowledge employees in contemporary enterprises. From the perspective of ambidexterity, drawing upon expectancy theory and self-determination theory (SDT), the present study highlights the driver behind proactive and responsive creativity. Using two-stage longitudinal data collected from 373 knowledge employee-supervisor dyads in information and manufacturing companies in China, the results show that: (1) performance-contingent rewards have an inverted U-shaped influence on proactive creativity and a U-shaped influence on responsive creativity; (2) performance-contingent rewards have an inverted U-shaped influence on autonomous and controlled motivation; (3) autonomous motivation has a positive influence on proactive creativity, but controlled motivation has a negative influence on responsive creativity; (4) autonomous and controlled motivation play a partly mediating mechanism in the non-linear effects of performance-contingent rewards on proactive and responsive creativity, respectively. Managers should enhance the ambidextrous ability to deal with proactive and responsive creativity and establish an applied and dynamic policy of performance-contingent rewards intensity to drive ambidextrous creativity.
Therapeutic Effects of Topical Application of Lycium barbarum Polysaccharide in a Murine Model of Dry Eye

Purpose To evaluate the safety and efficacy of Lycium barbarum polysaccharide (LBP) eye drops in a murine model of dry eye disease (DED). Methods Six- to eight-week-old female C57BL/6 mice were subjected to a combination of desiccating stress (DS) and topical benzalkonium chloride (BAC) to induce DED. Five microliters of LBP eye drops (0.625, 2.5, or 12.5 mg/ml) or PBS was applied topically 3 times per day for 10 days to subsequently test their efficacy. Tear secretion, tear breakup time (TBUT), corneal irregularity, and corneal fluorescein staining scores were measured on days 3 and 10 after treatment. The expression of tumor necrosis factor-alpha (TNF-α) in the cornea was assessed by quantitative (q) RT–PCR on days 10. The ocular irritation of LBP eye drops of corresponding concentrations was evaluated on 10- to 12-week-old female Sprague–Dawley rats. Results Compared with PBS-treated groups, mice treated with 0.625, 2.5, and 12.5 mg/ml LBP showed a significant improvement in the clinical signs of DED in a dose-dependent manner, including corneal epithelial integrity, corneal regularity, and tear production, as well as significant inhibition of inflammatory cell infiltration and TNF-α expression levels in the cornea. All corresponding concentrations of LBP eye drops revealed no obvious ocular irritation. Conclusion Topical application of LBP could ameliorate dry eye in a murine model of DED without obvious ocular irritation.
Erythema and Induration of Bacillus Calmette-Guérin Scar Associated With Multisystem Inflammatory Syndrome in Children in Japan: A Case Report

Multisystem Inflammatory Syndrome in Children (MIS-C) is a rare febrile disorder with multisystem organ involvement temporally associated with coronavirus 2019 infection (COVID-19) and frequently exhibits features mimicking Kawasaki disease (KD), another febrile disorder in children. The pathogenesis and the full clinical spectrum of MIS-C is poorly understood: It is still unclear whether MIS-C and KD are different syndromes or represent a common spectrum. The erythema and induration of Bacillus Calmette-Guérin (BCG) scar is one of the characteristic findings of KD, and is useful for the diagnosis in countries where BCG vaccination is mandated in infancy. Furthermore, such findings in BCG scar were also reported after SARS-CoV-2 vaccination, which may be related to molecular mimicry. However, there are no reports of changes at the BCG scar in MIS-C cases. Here, we report a case of MIS-C in a 3-year-old Hispanic boy in Japan, with erythema and induration at the BCG scar. The patient received BCG vaccination at 16 months of age in Japan. Four weeks before the onset, he had positive polymerase chain reaction (PCR) results for SARS-CoV-2 following household outbreak, although he was asymptomatic. He presented with fever and gastrointestinal symptoms, followed by the appearance of all six principal findings of complete KD. He exhibited congestive heart failure, following intravenous immunoglobulin (IVIG) therapy. He was diagnosed with MIS-C based on characteristic mucocutaneous and gastrointestinal symptoms, decreased cardiac function, and coagulopathy, in addition to laboratory data consistent with MIS-C. The BCG finding was present from the early stage of the disease. The patient was refractory to two doses of IVIGs, and the third IVIG plus prednisolone resulted in defervescence and improvement in heart failure. No coronary involvement was observed. This is the first case of erythema and induration at the BCG scar associated with MIS-C accompanied by KD features, which may give clinical and mechanistic insights in the understanding of the disease. Since the full spectrum of MIS-C is still evolving and both of them are syndromes with overlapped clinical features, further studies are warranted for deep phenotyping of MIS-C with KD features relative to KD in countries with mandatory BCG programs in infancy.