Miracle-dz/UniFAR-FTUs huggingface dataset:
Test–Retest Reliability of Concussion Baseline Assessments in United States Service Academy Cadets: A Report from the National Collegiate Athletic Association (NCAA)–Department of Defense (DoD) CARE Consortium

Abstract Objective: In response to advancing clinical practice guidelines regarding concussion management, service members, like athletes, complete a baseline assessment prior to participating in high-risk activities. While several studies have established test stability in athletes, no investigation to date has examined the stability of baseline assessment scores in military cadets. The objective of this study was to assess the test–retest reliability of a baseline concussion test battery in cadets at U.S. Service Academies. Methods: All cadets participating in the Concussion Assessment, Research, and Education (CARE) Consortium investigation completed a standard baseline battery that included memory, balance, symptom, and neurocognitive assessments. Annual baseline testing was completed during the first 3 years of the study. A two-way mixed-model analysis of variance (intraclass correlation coefficent (ICC)3,1) and Kappa statistics were used to assess the stability of the metrics at 1-year and 2-year time intervals. Results: ICC values for the 1-year test interval ranged from 0.28 to 0.67 and from 0.15 to 0.57 for the 2-year interval. Kappa values ranged from 0.16 to 0.21 for the 1-year interval and from 0.29 to 0.31 for the 2-year test interval. Across all measures, the observed effects were small, ranging from 0.01 to 0.44. Conclusions: This investigation noted less than optimal reliability for the most common concussion baseline assessments. While none of the assessments met or exceeded the accepted clinical threshold, the effect sizes were relatively small suggesting an overlap in performance from year-to-year. As such, baseline assessments beyond the initial evaluation in cadets are not essential but could aid concussion diagnosis.
Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model

Protective neutralizing antibodies Antibodies produced by survivors of coronavirus disease 2019 (COVID-19) may be leveraged to develop therapies. A first step is identifying neutralizing antibodies, which confer strong protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rogers et al. used a high-throughput pipeline to isolate and characterize monoclonal antibodies from convalescent donors. Antibodies were selected for binding to the viral spike protein, which facilitates entry into host cells by binding to the angiotensin-converting enzyme 2 (ACE2) receptor. Most isolated antibodies bound to regions of the spike outside of the receptor binding domain (RBD); however, a larger proportion of the RBD-binding antibodies were neutralizing, with the most potent binding at a site that overlaps the ACE2 binding site. Two of the neutralizing antibodies were tested in Syrian hamsters and provided protection against SARS-CoV-2 infection. Science, this issue p. 956 Passive transfer of a neutralizing antibody provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on the receptor binding domain (RBD) and to distinct non-RBD epitopes on the spike (S) protein. As indicated by maintained weight and low lung viral titers in treated animals, the passive transfer of a nAb provides protection against disease in high-dose SARS-CoV-2 challenge in Syrian hamsters. The study suggests a role for nAbs in prophylaxis, and potentially therapy, of COVID-19. The nAbs also define protective epitopes to guide vaccine design.
Deep learning‐based classification and mutation prediction from histopathological images of hepatocellular carcinoma

1 Department of Liver Surgery & Liver Transplantation, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, China 2 School of Computer Science, Northwestern Polytechnical University, Xi’an, China 3 Key Laboratory of Big Data Storage and Management, Northwestern Polytechnical University, Ministry of Industry and Information Technology, Xi’an, China 4 Department of Radiology, West China Hospital, Sichuan University, Chengdu, China 5 Laboratory of Pathology, Department of Pathology, West China Hospital, Sichuan University, Chengdu, China 6 School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, China 7 Shenzhen Luohu People’s Hospital, The Third Affiliated Hospital of Shenzhen University, Shenzhen, China
Can Treatment With Citicoline Eyedrops Reduce Progression in Glaucoma? The Results of a Randomized Placebo-controlled Clinical Trial

Precis: Citicoline eyedrops in patients with progressing glaucoma. Purpose: This study aimed to test whether the additional therapy with citicoline eyedrops to intraocular pressure (IOP)-lowering treatment could slow glaucoma progression in patients with worsening of damage and IOP 18 mm Hg or less. Design: This was a randomized, double-masked, placebo-controlled, multicenter 3-year study. Outcomes: The outcomes studied were difference in the visual field (mean deviation, MD, of 24-2; MD of 10-2) rates of progression and difference in retinal nerve fiber layer (RNFL) thickness change between the 2 study groups at 3 years. Methods: Patients with mild to moderate open-angle glaucoma (OAG) showing damage progression of at least −0.5 dB/y in the 2 years before enrollment despite IOP ≤18 mm Hg were randomized to receive citicoline eyedrops or placebo 3 times daily for 3 years. Patients were followed every 3 months and underwent a visual field examination with 24-2 and 10-2 strategies and RNFL assessment. Analysis of variance and linear models were used to test the differences between groups. Results: Eighty patients were randomized in the trial. The mean 3-year rates of progression were −1.03 (2.14) dB in the citicoline group and −1.92 (2.23) dB in the placebo group (P=0.07) for 24-2 MD and −0.41 (3.45) dB in the citicoline group and −2.22 (3.63) dB in the placebo group (P=0.02) for 10-2 MD. On average, patients receiving citicoline eyedrops lost 1.86 μm of RNFL in 3 years, versus 2.99 μm in the placebo group (P=0.02). Conclusions: Additional treatment with citicoline eyedrops to IOP-lowering treatment might reduce disease progression in patients with progressing glaucoma despite IOP ≤18 mm Hg.
Effects of art therapy in cancer care: A systematic review and meta-analysis.

OBJECTIVE To evaluate the effect of art therapy on cancer patients' quality of life and physical and psychological symptoms. METHODS The databases PubMed, Embase, Web of Science, The Cochrane Library, Clinical Trial.gov, the China National Knowledge Infrastructure (CNKI), Wanfang and the Chinese Biomedical Literature Database (CBM) were searched from their inception up to 20 August 2019. Trials examining the effects of art therapy on physical and psychological symptoms and quality of life versus a control group were included. The methodological quality of the included randomised controlled trials was assessed using the risk of bias tool of Cochrane Handbook. Meanwhile, the Newcastle-Ottawa Quality Assessment Scale (NOS) was used to evaluate the methodological quality of the non-randomised studies. RESULTS Twelve studies involving 587 cancer patients were included. The results revealed that art therapy significantly reduced anxiety symptoms (standard mean difference [SMD] = -0.46, 95% confidence interval [CI] [-0.90, 0.02], p = .04), depression symptoms (SMD = -0.47, 95% CI [-0.72, 0.21], p < .01), and fatigue (SMD = -0.38, 95% CI [-0.68, -0.09], p = .01) in cancer patients. Art therapy also significantly improved the quality of life of cancer patients (SMD = 0.43, 95% CI [0.18, 0.68], p < .01). CONCLUSIONS Art therapy had a positive effect on quality of life and symptoms in cancer patients and can be used as a complementary treatment for cancer patients.
The role of vitamin D in inflammatory bowel disease: a guide for clinical practice

ABSTRACT Introduction Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract that carries significant morbidity and mortality. Given the need to identify modifiable risk factors to prevent IBD development and to mitigate disease severity, vitamin D has become a major candidate of interest. Areas covered In this review, we discuss the regulatory role played by vitamin D in intestinal immune homeostasis, updates in the recent literature exploring its role in de novo IBD pathogenesis and established IBD activity. We also discuss societal recommendations on its therapeutic role in maintaining bone health and future directions for studying its role in regulating disease activity. Expert opinion In contrast to findings from earlier studies suggesting a causal role in IBD, recent findings indicate that vitamin D deficiency may be a sequela rather than a cause of IBD. Additionally, clinical trials exploring vitamin D therapy in reducing disease activity remain inconclusive thus far, with the current evidence best supporting a therapeutic role of vitamin D in bone health. Future studies are needed to clarify the role of vitamin D in IBD development and disease activity and to determine its therapeutic potential for IBD disease activity.
Cardiovascular disease and the impact of COVID‐19

Cardiovascular disease and the impact of COVID-19Running Head: COVID-19 and cardiovascularAnusha Yoganathan1, Menahel Sajjad1, Amer Harky1,2University of Liverpool, Liverpool, UKDepartment of Cardiothoracic Surgery, Liverpool Heart and Chest, Liverpool, UK
Plasma cell targeting to prevent antibody‐mediated rejection

Plasma cells (PCs) are the major source of pathogenic allo‐ and autoantibodies and have historically demonstrated resistance to therapeutic targeting. However, significant recent clinical progress has been made with the use of second‐generation proteasome inhibitors (PIs). PIs provide efficient elimination of plasmablast‐mediated humoral responses; however, long‐lived bone marrow (BM) resident PCs (LLPCs) demonstrate therapeutic resistance, particularly to first‐generation PIs. In addition, durability of antibody (Ab) reduction still requires improvement. More recent clinical trials have focused on conditions mediated by LLPCs and have included mechanistic studies of LLPCs from PI‐treated patients. A recent clinical trial of carfilzomib (a second‐generation irreversible PI) demonstrated improved efficacy in eliminating BM PCs and reducing anti‐HLA Abs in chronically HLA‐sensitized patients; however, Ab rebound was observed over several weeks to months following PI therapy. Importantly, recent murine studies have provided substantial insights into PC biology, thereby further enhancing our understanding of PC populations. It is now clear that BMPC populations, where LLPCs are thought to primarily reside, are heterogeneous and have distinct gene expression, metabolic, and survival signatures that enable identification and characterization of PC subsets. This review highlights recent advances in PC biology and clinical trials in transplant populations.
The crosstalk between antiretrovirals pharmacology and HIV drug resistance

ABSTRACT Introduction The clinical development of antiretroviral drugs has been followed by a rapid and concomitant development of HIV drug resistance. The development and spread of HIV drug resistance is due on the one hand to the within-host intrinsic HIV evolutionary rate and on the other to the wide use of low genetic barrier antiretrovirals. Areas covered We searched PubMed and Embase on 31 January 2020, for studies reporting antiretroviral resistance and pharmacology. In this review, we assessed the molecular target and mechanism of drug resistance development of the different antiretroviral classes focusing on the currently approved antiretroviral drugs. Then, we assessed the main pharmacokinetic/pharmacodynamic of the antiretrovirals. Finally, we retraced the history of antiretroviral treatment and its interconnection with antiretroviral worldwide resistance development both in , and middle-income countries in the perspective of 90–90-90 World Health Organization target. Expert opinion Drug resistance development is an invariably evolutionary driven phenomenon, which challenge the 90–90-90 target. In high-income countries, the antiretroviral drug resistance seems to be stable since the last decade. On the contrary, multi-intervention strategies comprehensive of broad availability of high genetic barrier regimens should be implemented in resource-limited setting to curb the rise of drug resistance.
Return to work following diagnosis of low-grade glioma

Objective Return-to-work (RTW) following diagnosis of infiltrative low-grade gliomas is unknown. Methods Swedish patients with histopathologic verified WHO grade II diffuse glioma diagnosed between 2005 and 2015 were included. Data were acquired from several Swedish registries. A total of 381 patients aged 18–60 were eligible. A matched control population (n = 1,900) was acquired. Individual data on sick leave, compensations, comorbidity, and treatments assigned were assessed. Predictors were explored using multivariable logistic regression. Results One year before surgery/index date, 88% of cases were working, compared to 91% of controls. The proportion of controls working remained constant, while patients had a rapid increase in sick leave approximately 6 months prior to surgery. After 1 and 2 years, respectively, 52% and 63% of the patients were working. Predictors for no RTW after 1 year were previous sick leave (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.88–0.96, p < 0.001), older age (OR 0.96, 95% CI 0.94–0.99, p = 0.005), and lower functional level (OR 0.64 95% CI, 0.45–0.91 p = 0.01). Patients receiving adjuvant treatment were less likely to RTW within the first year. At 2 years, biopsy (as opposed to resection), female sex, and comorbidity were also unfavorable, while age and adjuvant treatment were no longer significant. Conclusions Approximately half of patients RTW within the first year. Lower functional status, previous sick leave, older age, and adjuvant treatment were risk factors for no RTW at 1 year after surgery. Female sex, comorbidity, and biopsy only were also unfavorable for RTW at 2 years.
MicroRNA‐10a promotes epithelial‐to‐mesenchymal transition and stemness maintenance of pancreatic cancer stem cells via upregulating the Hippo signaling pathway through WWC2 inhibition

MicroRNAs (miRNAs)‐mediated cancer stem cells (CSCs) have drawn wide attention. This study aimed to probe the role of miR‐10a in epithelial–mesenchymal transition (EMT) and stemness maintenance of pancreatic CSCs (PCSCs). Differentially expressed miRs and genes in pancreatic cancer (PC) were predicted via an online database, and the miR‐10a and WW and C2 domain containing 2 (WWC2) expression were identified via a comparative study in PC and pancreatitis tissues. PCNCs were isolated and identified, and then the functional roles of miR‐10a and WWC2 in proliferation, invasion, migration, self‐renewal, colony formation abilities, EMT, and stemness maintenance of PCNCs were determined. The effects of miR‐10a on tumor growth in vivo were studied by performing a xenograft tumor in nude mice. Consequently, miR‐10a was highly expressed while WWC2 was lowly expressed in PC tissues. miR‐10a could target WWC2 expression. miR‐10a inhibition reduced EMT and stemness maintenance of PCSCs via enhancing WWC2 expression. The in vitro results were reproduced in in vivo studies. miR‐10a promoted EMT and stemness maintenance of PCSCs via activating the Hippo signaling pathway. Our study provided evidence that miR‐10a inhibition reduced EMT and stemness maintenance of PCSCs via upregulating WWC2 expression and inhibiting the Hippo signaling pathway.
Impact of lockdown measures during COVID-19 on air quality– A case study of India

ABSTRACT A novel infectious coronavirus disease (COVID-19) identified in late 2019 has now been labelled as a global pandemic by World Health Organization (WHO). The COVID-19 outbreak has shown some positive impacts on the natural environment. In present work, India is taken as a case study to evaluate the effect of lockdown on air quality of three Indian cities. The variation in concentration of key air pollutants including , , , and during two phases, pre-lockdown and post-lockdown phases, was analysed. The concentration of , , and reduced by 55%, 49%, 60% and 19%, and 44%, 37%, 78% and 39% for Delhi and Mumbai, respectively, during post-lockdown phase. Overall, the findings in present study may provide confidence to the stakeholders involved in air quality policy development that a significant improvement in air quality can be achieved in future if better pollution control plans are strictly executed.
Combined microneedling with topical application of platelet-rich plasma versus microneedling alone in the treatment of stria distensae: clinicopathological analysis

Abstract Background Striae distensae (SD) are common skin conditions. Objectives This study was done to test the hypothesis that ‘the use of microneedling (MN) before platelet-rich plasma (PRP) application will allow for deeper penetration and therefore, augment its efficacy in the treatment of SD. ’ Patients and methods Forty patients with SD were divided into (i) Group I, the patients were treated with MN only, and (ii) Group II, the patients were treated with combined MN-PRP. The clinical improvement was evaluated by two dermatologists. Skin biopsies were obtained before and after therapy to examine immunohistological changes. Results As compared to the use of MN alone, therapy with combined MN-PRP was associated with: (i) a marked to the excellent improvement of the skin lesions of SD, (ii) a more significant deposition of collagen and elastic fibers, (iii) increased proliferative activity in the epidermis, and (iv) a decreased caspase-3 protein expression values in the epidermis. Conclusions This study proved that the combined MN-PRP is more effective than MN alone for the treatment of the lesions of SD. The underlying molecular mechanisms are open for future studies.
Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications

The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.
Variants in CHRNB2 and CHRNA4 Identified in Patients with Insular Epilepsy

Abstract: Purpose: Our purpose was to determine the role of CHRNA4 and CHRNB2 in insular epilepsy. Method: We identified two patients with drug-resistant predominantly sleep-related hypermotor seizures, one harboring a heterozygous missense variant (c.77C>T; p. Thr26Met) in the CHRNB2 gene and the other a heterozygous missense variant (c.1079G>A; p. Arg360Gln) in the CHRNA4 gene. The patients underwent electrophysiological and neuroimaging studies, and we performed functional characterization of the p. Thr26Met (c.77C>T) in the CHRNB2 gene. Results: We localized the epileptic foci to the left insula in the first case (now seizure-free following epilepsy surgery) and to both insulae in the second case. Based on tools predicting the possible impact of amino acid substitutions on the structure and function of proteins (sorting intolerant from tolerant and PolyPhen-2), variants identified in this report could be deleterious. Functional expression in human cell lines of α4β2 (wild-type), α4β2-Thr26Met (homozygote), and α4β2/β2-Thr26Met (heterozygote) nicotinic acetylcholine receptors revealed that the mutant subunit led to significantly higher whole-cell nicotinic currents. This feature was observed in both homo- and heterozygous conditions and was not accompanied by major alterations of the current reversal potential or the shape of the concentration-response relation. Conclusions: This study suggests that variants in CHRNB2 and CHRNA4, initially linked to autosomal dominant nocturnal frontal lobe epilepsy, are also found in patients with predominantly sleep-related insular epilepsy. Although the reported variants should be considered of unknown clinical significance for the moment, identification of additional similar cases and further functional studies could eventually strengthen this association.
RIPK3 blockade attenuates kidney fibrosis in a folic acid model of renal injury

Renal fibrosis is common to all forms of progressive kidney disease. However, current therapies to limit renal fibrosis are largely ineffective. Phosphorylation of receptor‐interacting serine/threonine‐protein kinase (RIPK) 3 has been recently suggested to be a key regulator of the pyrin domain containing 3 (NLRP3) inflammasome, which provides new insights into mechanisms of chronic kidney disease (CKD). However, the specific effect of RIPK3 on renal cortical fibrosis has not been fully understood. To study the function of RIPK3, both genetic ablation and pharmacological inhibition of RIPK3 (dabrafenib) were used in the study. Our studies identify that RIPK3 promotes renal fibrosis via the activation of the NLRP3 inflammasome in a mouse model of folic acid‐induced nephropathy. Both interventional strategies decreased the renal fibrotic response, and beneficial effects converged on the NLRP3 inflammasome. This study demonstrates a role for RIPK3 as the mediator of renal fibrosis via the upregulation of inflammasome activation. Dabrafenib, as an inhibitor of RIPK3, may be an effective treatment to limit the progression of the tubulointerstitial fibrosis.