Miracle-dz/UniFAR-FTUs huggingface dataset:
Contradictions between DAPT and PRECISE-DAPT scores with the severity of coronary lesion in acute coronary syndrome

Abstract This study aimed to identify the correlation of contradiction between DAPT score and PRECISE-DAPT score with the severity of coronary lesion in acute coronary syndromes (ACS). In total, 458 patients with ACS after a percutaneous coronary intervention (PCI) who had tolerated 1-year uneventful dual antiplatelet therapy (DAPT) were enrolled and divided into groups based on the Gensini score, number of stenosed vessels, and left main (LM) disease. Both DAPT score and PRECISE-DAPT score were calculated and the proportion of patients receiving conflicting recommendations from each score was compared among the groups. DAPT score as well as the proportion of patients with DAPT score ≥2 were associated with the Gensini score and the number of stenosed vessels. Similarly, PRECISE-DAPT score as well as the proportion of patients with PRECISE-DAPT score ≥25 were associated with the Gensini score and the number of stenosed vessels. The proportion of patients with DAPT score ≥2 along with PRECISE-DAPT score ≥25 were associated with Gensini score, but they had no significant association with the number of stenosed vessels (P = .006 and P = .075, respectively). None of those aforementioned items were associated with LM disease. The inconsistencies of DAPT scores and PRECISE-DAPT scores are frequent and associated with the severity of coronary disease, represented by the Gensini score. Appropriate clinical decisions should be individualized.
Optimized mouse model of embolic MCAO: From cerebral blood flow to neurological outcomes

The embolic middle cerebral artery occlusion (eMCAO) model mimics ischemic stroke due to large vessel occlusion in humans and is amenable to thrombolytic therapy with rtPA. However, two major obstacles, the difficulty of the eMCAO surgery and unpredictable occurrence of clot autolysis, had impeded its application in mice. In this study, we modified catheters to produce suitable fibrin-rich embolus and optimized the eMCAO model using cerebral blood flow (CBF) monitored by both laser Doppler flowmetry (LDF) and 2D laser speckle contrast imaging (LSCI) to confirm occlusion of MCA. The results showed that longer embolus resulted in higher mortality. There was a compensatory increase in MCA territory perfusion after eMCAO associated with decreased infarct volume; however, this was only partly dependent on recanalization as clot autolysis was only observed in ∼30% of mice. Cortical CBF monitoring with LSCI showed that the size of peri-core area at 3 h displayed the best correlation with infarct volume that is attributed to compensatory collateral blood flow. The peri-core area best predicted functional outcome after eMCAO. In summary, we developed a reliable eMCAO mouse model that better mimics embolic ischemic stroke in humans, which will increase the potential for successful translation of stroke neuroprotective therapies.
Human Bone Marrow Adipose Tissue is a Metabolically Active and Insulin-Sensitive Distinct Fat Depot

Abstract Context Bone marrow (BM) in adult long bones is rich in adipose tissue, but the functions of BM adipocytes are largely unknown. We set out to elucidate the metabolic and molecular characteristics of BM adipose tissue (BMAT) in humans. Objective Our aim was to determine if BMAT is an insulin-sensitive tissue, and whether the insulin sensitivity is altered in obesity or type 2 diabetes (T2DM). Design This was a cross-sectional and longitudinal study. Setting The study was conducted in a clinical research center. Patients or Other Participants Bone marrow adipose tissue glucose uptake (GU) was assessed in 23 morbidly obese subjects (9 with T2DM) and 9 healthy controls with normal body weight. In addition, GU was assessed in another 11 controls during cold exposure. Bone marrow adipose tissue samples for molecular analyses were collected from non-DM patients undergoing knee arthroplasty. Intervention(s) Obese subjects were assessed before and 6 months after bariatric surgery and controls at 1 time point. Main Outcome Measure We used positron emission tomography imaging with 2-[18F]fluoro-2-deoxy-D-glucose tracer to characterize GU in femoral and vertebral BMAT. Bone marrow adipose tissue molecular profile was assessed using quantitative RT-PCR. Results Insulin enhances GU in human BMAT. Femoral BMAT insulin sensitivity was impaired in obese patients with T2DM compared to controls, but it improved after bariatric surgery. Furthermore, gene expression analysis revealed that BMAT was distinct from brown and white adipose tissue. Conclusions Bone marrow adipose tissue is a metabolically active, insulin-sensitive and molecularly distinct fat depot that may play a role in whole body energy metabolism.
The pathological role of ferroptosis in ischemia/reperfusion-related injury

Ischemia/reperfusion (I/R) is a pathological process that occurs in numerous organs throughout the human body, and it is frequently associated with severe cellular damage and death. Recently it has emerged that ferroptosis, a new form of regulated cell death that is caused by iron-dependent lipid peroxidation, plays a significantly detrimental role in many I/R models. In this review, we aim to revise the pathological process of I/R and then explore the molecular pathogenesis of ferroptosis. Furthermore, we aim to evaluate the role that ferroptosis plays in I/R, providing evidence to support the targeting of ferroptosis in the I/R pathway may present as a therapeutic intervention to alleviate ischemia/reperfusion injury (IRI) associated cell damage and death.
Prediction of the SARS-CoV-2 (2019-nCoV) 3C-like Protease (3CLpro) Structure: Virtual Screening Reveals Velpatasvir, Ledipasvir, and Other Drug Repurposing Candidates

We prepared the three-dimensional model of the 2019-nCoV 3C-like protease (3CLpro) using the crystal structure of the highly-similar (96% identity) ortholog from the SARS-CoV. All residues involved in the catalysis, substrate binding and dimerisation are 100% conserved. Comparison of the polyprotein PP1AB sequences showed 86% identity. The 3C-like cleavage sites on the coronaviral polyproteins are highly conserved. Based on the near-identical substrate specificities and high sequence identities, we are in the opinion that some of the previous progress of specific inhibitors development for the SARS-CoV enzyme can be conferred on its 2019-nCoV counterpart. With the 3CLpro molecular model, we performed virtual screening for purchasable drugs and proposed 16 candidates for consideration. Among these, the antivirals ledipasvir or velpatasvir are particularly attractive as therapeutics to combat the 2019-nCoV with minimal side effects, commonly fatigue and headache. The drugs Epclusa (velpatasvir / sofosbuvir) and Harvoni (ledipasvir / sofosbuvir) could be very effective owing to their dual inhibitory actions on two viral enzymes.
Regularizing Hyperspectral and Multispectral Image Fusion by CNN Denoiser

Hyperspectral image (HSI) and multispectral image (MSI) fusion, which fuses a low-spatial-resolution HSI (LR-HSI) with a higher resolution multispectral image (MSI), has become a common scheme to obtain high-resolution HSI (HR-HSI). This article presents a novel HSI and MSI fusion method (called as CNN-Fus), which is based on the subspace representation and convolutional neural network (CNN) denoiser, i.e., a well-trained CNN for gray image denoising. Our method only needs to train the CNN on the more accessible gray images and can be directly used for any HSI and MSI data sets without retraining. First, to exploit the high correlations among the spectral bands, we approximate the desired HR-HSI with the low-dimensional subspace multiplied by the coefficients, which can not only speed up the algorithm but also lead to more accurate recovery. Since the spectral information mainly exists in the LR-HSI, we learn the subspace from it via singular value decomposition. Due to the powerful learning performance and high speed of CNN, we use the well-trained CNN for gray image denoising to regularize the estimation of coefficients. Specifically, we plug the CNN denoiser into the alternating direction method of multipliers (ADMM) algorithm to estimate the coefficients. Experiments demonstrate that our method has superior performance over the state-of-the-art fusion methods.
Targeted next generation sequencing revealed a novel deletion-frameshift mutation of KCNH2 gene in a Chinese Han family with long QT syndrome

Abstract Introduction: Long QT syndrome (LQTS) is electrocardiographically characterized by a prolonged QT interval and manifests predisposition to life-threatening arrhythmia which often leads to sudden cardiac death. Type 2 LQTS (LQT2) is the second most common subtype of LQTS and caused by mutations in KCNH2 gene. Up to date, >900 mutations have been reported to be related to LQT2. However, mutational screening of the KCNH2 gene is still far from completeness. Identification of KCNH2 mutations is particularly important in diagnosis of LQT2 and will gain more insights into the molecular basis for the pathogenesis of LQT2. Patient concerns: A Chinese Han family with LQTS phenotypes was examined. Diagnosis: A novel deletion-frameshift mutation, c. 381_408delCAATTTCGAGGTGGTGATGGAGAAGGAC, in exon 3 of KCNH2 gene was identified in a Chinese family with LQTS. On the basis of this finding and clinical manifestations, the final diagnosis of LQT2 was made. Interventions: Next-generation sequencing (NGS) of DNA samples was performed to detect the mutation in the LQTS-related genes on the proband and her mother, which was confirmed by Sanger sequencing. The proband was then implanted with an implantable cardioverter defibrillator and prescribed metoprolol 47.5 mg per day. Outcomes: This novel heterozygous mutation results in a frameshift mutation after the 128th residue (Asparagine), which replaced the original 1031 amino acids with 27 novel amino acids (p.N128fsX156). Conclusion: This novel mutation presumably resulted in a frameshift mutation, p.N128fsX156. Our data expanded the mutation spectrum of KCNH2 gene and facilitated clinic diagnosis and genetic counseling for this family with LQTS.
A Comparison of the Psycholinguistic Styles of Schizophrenia-Related Stigma and Depression-Related Stigma on Social Media: Content Analysis

Background Stigma related to schizophrenia is considered to be the primary focus of antistigma campaigns. Accurate and efficient detection of stigma toward schizophrenia in mass media is essential for the development of targeted antistigma interventions at the population level. Objective The purpose of this study was to examine the psycholinguistic characteristics of schizophrenia-related stigma on social media (ie, Sina Weibo, a Chinese microblogging website), and then to explore whether schizophrenia-related stigma can be distinguished from stigma toward other mental illnesses (ie, depression-related stigma) in terms of psycholinguistic style. Methods A total of 19,224 schizophrenia- and 15,879 depression-related Weibo posts were collected and analyzed. First, a human-based content analysis was performed on collected posts to determine whether they reflected stigma or not. Second, by using Linguistic Inquiry and Word Count software (Simplified Chinese version), a number of psycholinguistic features were automatically extracted from each post. Third, based on selected key features, four groups of classification models were established for different purposes: (a) differentiating schizophrenia-related stigma from nonstigma, (b) differentiating a certain subcategory of schizophrenia-related stigma from other subcategories, (c) differentiating schizophrenia-related stigma from depression-related stigma, and (d) differentiating a certain subcategory of schizophrenia-related stigma from the corresponding subcategory of depression-related stigma. Results In total, 26.22% of schizophrenia-related posts were labeled as stigmatizing posts. The proportion of posts indicating depression-related stigma was significantly lower than that indicating schizophrenia-related stigma (χ21=2484.64, P<.001). The classification performance of the models in the four groups ranged from . 71 to . 92 (F measure). Conclusions The findings of this study have implications for the detection and reduction of stigma toward schizophrenia on social media.
ERK3/MAPK6 controls IL-8 production and chemotaxis

ERK3 is a ubiquitously expressed member of the atypical mitogen activated protein kinases (MAPKs) and the physiological significance of its short half-life remains unclear. By employing gastrointestinal 3D organoids, we detect that ERK3 protein levels steadily decrease during epithelial differentiation. ERK3 is not required for 3D growth of human gastric epithelium. However, ERK3 is stabilized and activated in tumorigenic cells, but deteriorates over time in primary cells in response to lipopolysaccharide (LPS). ERK3 is necessary for production of several cellular factors including interleukin-8 (IL-8), in both, normal and tumorigenic cells. Particularly, ERK3 is critical for AP-1 signaling through its interaction and regulation of c-Jun protein. The secretome of ERK3-deficient cells is defective in chemotaxis of neutrophils and monocytes both in vitro and in vivo. Further, knockdown of ERK3 reduces metastatic potential of invasive breast cancer cells. We unveil an ERK3-mediated regulation of IL-8 and epithelial secretome for chemotaxis.
Atlas Sampling for Prone Breast Automatic Segmentation of Organs at Risk: The Importance of Patients’ Body Mass Index and Breast Cup Size for an Optimized Contouring of the Heart and the Coronary Vessels

Objective: Delineation of organs at risk is a time-consuming task. This study evaluates the benefits of using single-subject atlas-based automatic segmentation of organs at risk in patients with breast cancer treated in prone position, with 2 different criteria for choosing the atlas subject. Together with laterality (left/right), the criteria used were either (1) breast volume or (2) body mass index and breast cup size. Methods: An atlas supporting different selection criteria for automatic segmentation was generated from contours drawn by a senior radiation oncologist (RO_A). Atlas organs at risk included heart, left anterior descending artery, and right coronary artery. Manual contours drawn by RO_A and automatic segmentation contours of organs at risk and breast clinical target volume were created for 27 nonatlas patients. A second radiation oncologist (RO_B) manually contoured (M_B) the breast clinical target volume and the heart. Contouring times were recorded and the reliability of the automatic segmentation was assessed in the context of 3-D planning. Results: Accounting for body mass index and breast cup size improved automatic segmentation results compared to breast volume-based sampling, especially for the heart (mean similarity indexes >0.9 for automatic segmentation organs at risk and clinical target volume after RO_A editing). Mean similarity indexes for the left anterior descending artery and the right coronary artery edited by RO_A expanded by 1 cm were ≥0.8. Using automatic segmentation reduced contouring time by 40%. For each parameter analyzed (eg, D2%), the difference in dose, averaged over all patients, between automatic segmentation structures edited by RO_A and the same structure manually drawn by RO_A was <1.5% of the prescribed dose. The mean heart dose was reliable for the unedited heart segmentation, and for right-sided treatments, automatic segmentation was adequate for treatment planning with 3-D conformal tangential fields. Conclusions: Automatic segmentation for prone breast radiotherapy stratified by body mass index and breast cup size improved segmentation accuracy for the heart and coronary vessels compared to breast volume sampling. A significant reduction in contouring time can be achieved by using automatic segmentation.
Impact of antithrombotic agents on radiological lesion progression in acute traumatic brain injury: A CENTER-TBI propensity-matched cohort analysis.

An increasing number of elderly patients are being affected by TBI and a significant proportion are on pre-hospital antithrombotic therapy for cardio- or cerebrovascular indications. We have quantified the impact of antiplatelet/anticoagulant (APAC) agents on radiological lesion progression in acute TBI, using a novel, semi-automated approach to volumetric lesion measurement, and explored the impact of use on clinical outcomes in the CENTER-TBI study. We used a 1:1 propensity-matched cohort design, matching controls to APAC users based on demographics, baseline clinical status, pre-injury comorbidities and injury severity. Subjects were selected from a pool of patients enrolled in CENTER-TBI with computed tomography (CT) scan at admission and repeated within 7d of injury. We calculated absolute changes in volume of intraparenchymal, extra-axial, intraventricular and total intracranial hemorrhage between scans, and compared volume of hemorrhagic progression, proportion of patients with significant degree of progression (>25% of initial volume), proportion with new intracranial hemorrhage on follow-up CT as well as clinical course and outcomes. A total of 316 patients were included (158 APAC users; 158 controls). The mean volume of progression was significantly higher in the APAC group for extra-axial (3.1 vs 1.3 mL, p=0.01), but not intraparenchymal (3.8 vs 4.6 mL, p=0.65), intraventricular (0.2 vs 0.0 mL, p=0.79) or total intracranial hemorrhage (7.0 vs 6.0 mL, p=0.08). More patients had significant hemorrhage growth (54.1 vs 37.0%, p=0.003) and delayed intracranial hemorrhage (4 of 18 vs none; p=0.04) in the APAC group compared to controls, but this was not associated with differences in length of stay, rates of neurosurgical intervention, mortality or GOSE at 6 months. Preinjury use of antithrombotic agents was associated with greater expansion of extra-axial lesions, higher rates of significant hemorrhagic progression and higher risk of delayed traumatic intracranial hemorrhage, but this was not associated with worse clinical course or functional outcomes.
EAN/ERS/ESO/ESRS statement on the impact of sleep disorders on risk and outcome of stroke

Sleep disorders are highly prevalent in the general population and may be linked in a bidirectional fashion to stroke, which is one of the leading causes of morbidity and mortality. Four major scientific societies established a task force of experts in neurology, stroke, respiratory medicine, sleep medicine and methodology, to critically evaluate the evidence regarding potential links and the impact of therapy. 13 research questions were evaluated in a systematic literature search using a stepwise hierarchical approach: first, systematic reviews and meta-analyses; second, primary studies post-dating the systematic reviews/meta-analyses. A total of 445 studies were evaluated and 88 included. Statements were generated regarding current evidence and clinical practice. Severe obstructive sleep apnoea (OSA) doubles the risk for incident stroke, especially in young to middle-aged patients. Continuous positive airway pressure (CPAP) may reduce stroke risk, especially in treatment-compliant patients. The prevalence of OSA is high in stroke patients and can be assessed by polygraphy. Severe OSA is a risk factor for recurrence of stroke and may be associated with stroke mortality, while CPAP may improve stroke outcome. It is not clear if insomnia increases stroke risk, while pharmacotherapy of insomnia may increase it. Periodic limb movements in sleep (PLMS), but not restless limb syndrome (RLS), may be associated with an increased risk of stroke. Preliminary data suggest a high frequency of post-stroke insomnia and RLS and their association with a less favourable stroke outcome, while treatment data are scarce. Overall, the evidence base is best for OSA relationship with stroke and supports active diagnosis and therapy. Research gaps remain especially regarding insomnia and RLS/PLMS relationships with stroke. Evidence suggests a bidirectional relationship between sleep and stroke. However, the pathophysiological base of the associations and the possibilities of improving prevention and outcome through sleep-related interventions require further evaluation. http://bit.ly/36De7Cy
Shape selection and mis-assembly in viral capsid formation by elastic frustration

The successful assembly of a closed protein shell (or capsid) is a key step in the replication of viruses and in the production of artificial viral cages for bio/nanotechnological applications. During self-assembly, the favorable binding energy competes with the energetic cost of the growing edge and the elastic stresses generated due to the curvature of the capsid. As a result, incomplete structures such as open caps, cylindrical or ribbon-shaped shells may emerge, preventing the successful replication of viruses. Using elasticity theory and coarse-grained simulations, we analyze the conditions required for these processes to occur and their significance for empty virus self-assembly. We find that the outcome of the assembly can be recast into a universal phase diagram showing that viruses with high mechanical resistance cannot be self-assembled directly as spherical structures. The results of our study justify the need of a maturation step and suggest promising routes to hinder viral infections by inducing mis-assembly.
A comparison of tiotropium/olodaterol vs tiotropium alone in terms of treatment effect for chronic obstructive pulmonary disease

Abstract Background: Combinations of long-acting bronchodilators with different mechanisms of action are recommended to improve prognosis and reduce risk of adverse events of chronic obstructive pulmonary disease (COPD). It is unclear whether the new combination therapy with long-acting muscarinic antagonist (LAMA) tiotropium (TIO) and long acting beta-agonists (LABA) olodaterol (OLO) was superior to tiotropium alone. Methods: We measured the efficacy of the TIO/OLO combination vsTIO alone for COPD patients based on electronic databases up to February 2019. After rigorous quality review, data was extracted from eligible trials. All the main outcomes were pooled analysis using RevMan software. Results: A total of 6 randomized controlled trials (RCTs) were identified. The pooled results of our meta-analysis demonstrated that FEV1 [MD = 0.03, 95% CI (−0.01,0.07), P = . 18], FVC [MD = -0.03, 95%CI (−0.06,0.00), P = . 09] and FEV1%pred [MD = 0.35, 95%CI (−0.30, 0.99), P = . 29] all showed no significant difference between the 2 groups. The overall incidence of adverse effects (AEs) [OR = 1.01,95%CI (0.93,1.09), P = . 87] and serious AEs [OR = 1.04,95% CI (0.82, 1.32), P = . 72] in the combination group was similar to that of the TIO alone group, without statistical significance. Conclusion: These studies reported that the TIO/OLO combination did not show superior effects than tiotropium alone for COPD. Additionally, both therapies were well tolerated.