Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Scutellarin in Ameliorating Lung Injury in a Rat Model of Bilateral Hind Limb Ischemia–Reperfusion

The lung is one of the most sensitive organs that are vulnerable to injuries induced by lower limb ischemia–reperfusion. Scutellarin is a flavonoid glycoside extracted from the Chinese herb Erigeron breviscapus. This study aimed to investigate the role of scutellarin in ameliorating lung injury in a rat model of bilateral hind limb ischemia–reperfusion. Twenty‐four adult male albino rats were equally divided into four groups; control, scutellarin, bilateral hind limb ischemia–reperfusion, and bilateral hind limb ischemia–reperfusion followed by scutellarin (at a dose of 20 mg/kg/day for 14 days). Lung specimens were processed for different biochemical and histological techniques. The bilateral hind limb ischemia–reperfusion group showed a significant increase in lung malondialdehyde and myeloperoxidase levels as well as a significant decrease in lung glutathione and superoxide dismutase. Histological examination revealed collapsed alveoli, polymorphic mononuclear cell infiltration, thickened dilated congested blood vessels, and excessive collagen fiber deposition in thickened interalveolar septa. A significant increase in iNOS and Bax immunohistochemical expression was associated with a significant decrease in Bcl2 and COX2 expression. Scutellarin administration following bilateral hind limb ischemia–reperfusion significantly ameliorated all studied parameters. It can be concluded that scutellarin could be beneficial in improving bilateral hind limb ischemia–reperfusion‐induced lung damage most probably through its antioxidant, anti‐inflammatory, and antiapoptotic effects. Anat Rec, 302:2070–2081, 2019. © 2019 American Association for Anatomy
Prevention and management of transcatheter balloon‐expandable aortic valve malposition

Early clinical outcomes in selected high‐risk patients undergoing catheter‐based aortic valve replacement (AVR) compare favorably with conventional surgical AVR. Improved understanding of the mechanisms of success and failure of transcatheter AVR will likely improve outcomes further. To this end, we examined our experience during the developmental phases of transcatheter AVR and describe the causes and management of prosthetic valve malposition.
Diabetic Ketoacidosis Revealing Severe Glucose-6-Phosphate Dehydrogenase Deficiency (G6PD-D) Deficiency with Methemoglobinemia: A Case Report

Patient: Male, 17 Final Diagnosis: Diabetic ketoacidosis revealing severe G6PD deficiency with methemoglobinemia Symptoms: Jaundice Medication: — Clinical Procedure: None Specialty: Hematology Objective: Unusual clinical course Background: Glucose-6-phosphate dehydrogenase deficiency (G6PD-D) is the most common red blood cell enzymopathy disorder. Severe hemolysis due to G6PD-D may rarely manifest as methemoglobinemia. Although acute hemolytic crises are usually induced by the exposure to certain oxidative stresses, diabetic ketoacidosis may also elicit hemolytic reactions in G6PD deficient persons. Case Report: A 17-year-old male with type 1 diabetes mellitus presented with diabetic ketoacidosis and features of hemolytic anemia which turned to be G6PD-D related. Interestingly, the arterial blood gas of the patient showed an elevated methemoglobin level (8.1%). Conclusions: G6PD-D induced hemolysis is conventionally caused by oxidative stress, however, we report here a case of G6PD-D induced methemoglobinemia as a complication of diabetic ketoacidosis that has not been, as far as we know, previously reported.
Contribution of sex‑based immunological differences to the enhanced immune response in female mice following vaccination with hepatitis B vaccine.

Hepatitis B virus (HBV) vaccination is regarded as the most economical and effective method for the prevention and control of HBV infection, a major global health problem. Previous studies have suggested that there may be sex‑specific differences regarding the immune response to the HBV vaccine in humans; however, the mechanisms associated with these sex‑specific differences are yet to be elucidated. In the present study, sex‑based immunological differences in mice following HBV vaccination were investigated to determine the mechanisms underlying sexual dimorphism, with the aim of identifying potential targets for clinical intervention. Balb/c mice (n=6) were vaccinated intramuscularly on 3 different days (days 0, 14 and 28) with the HBV vaccine. Sera were analyzed via ELISA for the presence of HBV surface antigen (HBsAg)‑specific immunoglobulin G (IgG), and of different IgG subtypes, 3 weeks following the third injection. Enzyme‑linked immunosorbent spot assays were conducted to determine interleukin‑4/interferon‑γ secretion. Immunological memory stimulated by the vaccine was detected via flow cytometry analysis and ELISA 1 week following the booster immunization. The seroconversion of the treated female group was higher compared with the male group at one week following the second vaccination. Female mice exhibited significantly increased HBsAg antibody titers compared with males at 1‑5 weeks following the third vaccination. Sera obtained from vaccinated female mice exhibited markedly increased titers of IgG1 and IgG2b compared with those from male mice. Furthermore, female mice exhibited elevated cytotoxic T lymphocyte responses and immune memory. Collectively, the results of the present study indicated that sex‑based immunological differences affected the dynamics and characteristics of the immune response in mice immunized with the HBV vaccine.
Non-invasive treatment with near-infrared light: A novel mechanisms-based strategy that evokes sustained reduction in brain injury after stroke

Ischemic stroke is a debilitating disease that causes significant brain injury. While restoration of blood flow is critical to salvage the ischemic brain, reperfusion can exacerbate damage by inducing generation of reactive oxygen species (ROS). Recent studies by our group found that non-invasive mitochondrial modulation with near-infrared (NIR) light limits ROS generation following global brain ischemia. NIR interacts with cytochrome c oxidase (COX) to transiently reduce COX activity, attenuate mitochondrial membrane potential hyperpolarization, and thus reduce ROS production. We evaluated a specific combination of COX-inhibitory NIR (750 nm and 950 nm) in a rat stroke model with longitudinal analysis of brain injury using magnetic resonance imaging. Treatment with NIR for 2 h resulted in a 21% reduction in brain injury at 24 h of reperfusion measured by diffusion-weighted imaging (DWI) and a 25% reduction in infarct volume measured by T2-weighted imaging (T2WI) at 7 and 14 days of reperfusion, respectively. Additionally, extended treatment reduced brain injury in the acute phase of brain injury, and 7 and 14 days of reperfusion, demonstrating a >50% reduction in infarction. Our data suggest that mitochondrial modulation with NIR attenuates ischemia–reperfusion injury and evokes a sustained reduction in infarct volume following ischemic stroke.
High diagnostic adequacy and accuracy of the new 20G procore needle for EUS-guided tissue acquisition: Results of a large multicentre retrospective study

Background and Objective: EUS-guided fine-needle biopsy has become the standard for tissue sampling. A new 20G ProCore™ (PC) needle has been developed to overcome the limitations of tissue acquisition of the smaller needles (22G, 25G) and the rigidity of the larger one (19G). The aim of this study is to assess the performance of the 20G PC needle. Materials and Methods: Patients who underwent EUS-guided tissue acquisition with the 20G PC needle of pancreatic and extra-pancreatic mass lesions were retrospectively identified at three Italian centers (Bologna, Fermo, and Palermo). Diagnostic adequacy, accuracy, and tissue core acquisition were the outcome measures. All the cases were performed without rapid on-site evaluation. Results: A total of 384 patients with pancreatic (62.2%) and extra-pancreatic lesions were included in the study. For pancreatic lesions, adequacy, accuracy, sensitivity, and specificity were 92.4%, 91.5%, 90.8%, and 100%, respectively, with a number needed to misdiagnose (NNM) of 11.8. The tissue core was obtained in 72% of cases. Transduodenal approach was performed in 150 pancreatic lesions; adequacy, accuracy, and tissue core acquisition were 88.7%, 90%, and 66%, respectively (NNM 10). For extrapancreatic lesions, adequacy, accuracy, sensitivity, specificity, and tissue core sampling were 95.3%, 95.3%, 92.6%, 100%, and 84.5% (NNM 21.3). Conclusions: The 20G PC needle showed high diagnostic adequacy and accuracy, regardless the access route.
Nail fold dermoscopy in collagen vascular disorders: A cross-sectional study

Background: The collagen vascular disorders, particularly systemic sclerosis, dermatomyositis, systemic lupus erythematosus and mixed connective tissue disorder, are often characterized by microangiopathic abnormalities of the nail folds. Nail fold dermoscopy is a well-established technique to assess these vascular changes. Aims: To evaluate finger nail capillary vascular abnormalities by dermoscopy and their correlation with cutaneous and systemic involvement in the patients of collagen vascular disorders. Methods: This was a cross-sectional study involving patients of collagen vascular disorders presenting to Government Medical College, Amritsar over a period of 2 years. Nail fold dermoscopy was done in these patients and correlated with cutaneous and systemic involvement. Statistical analysis was done using SPSS 17.0 version. Results: A total of 30 patients were enrolled in the study. Sixteen (53.3%), 11 (36.7%) and 3 (10%) patients of systemic sclerosis, systemic lupus erythematosus and mixed connective tissue disorder, respectively were included for nail fold dermoscopy. The commonest change recorded in our study was dilated capillaries in 21 (70%) patients, followed by capillary dropouts in 17 (56.7%) patients and avascular areas in 16 (53.3%) patients. Of 17 patients presenting with sclerodactyly, active, early and late patterns were seen in 7 (41.2%), 2 (11.8%) and 7 (41.2%) patients, respectively. Out of 13 patients with respiratory involvement, active, early and late patterns were seen in 1, 1 and 7 (53.8%) patients, respectively (P value = 0.004). Limitations: Owing to lesser number of patients in our study, it is difficult to draw conclusive recommendations, and more studies with a larger sample size are required. Conclusion: Dermoscopy is a valuable tool not only to diagnose collagen vascular disorders but also for prognostication by correlating with systemic involvement.
FMRP - G-quadruplex mRNA - miR-125a interactions: Implications for miR-125a mediated translation regulation of PSD-95 mRNA

Fragile X syndrome, the most common inherited form of intellectual disability, is caused by the CGG trinucleotide expansion in the 5’-untranslated region of the Fmr1 gene on the X chromosome, which silences the expression of the fragile X mental retardation protein (FMRP). FMRP has been shown to bind to a G-rich region within the PSD-95 mRNA, which encodes for the postsynaptic density protein 95, and together with microRNA-125a to mediate the reversible inhibition of the PSD-95 mRNA translation in neurons. The miR-125a binding site within the PSD-95 mRNA 3’-untranslated region (UTR) is embedded in a G-rich region bound by FMRP, which we have previously demonstrated folds into two parallel G-quadruplex structures. The FMRP regulation of PSD-95 mRNA translation is complex, being mediated by its phosphorylation. While the requirement for FMRP in the regulation of PSD-95 mRNA translation is clearly established, the exact mechanism by which this is achieved is not known. In this study, we have shown that both unphosphorylated FMRP and its phosphomimic FMRP S500D bind to the PSD-95 mRNA G-quadruplexes with high affinity, whereas only FMRP S500D binds to miR-125a. These results point towards a mechanism by which, depending on its phosphorylation status, FMRP acts as a switch that potentially controls the stability of the complex formed by the miR-125a-guided RNA induced silencing complex (RISC) and PSD-95 mRNA.
Signal transducer and activator of transcription 5b drives malignant progression in a PDGFB‐dependent proneural glioma model by suppressing apoptosis

Signal transducer and activator of transcription 5b (STAT5b) is likely the relevant STAT5 isoform with respect to the process of malignant progression in gliomas. STAT5b is a latent cytoplasmic protein involved in cell signaling through the modulation of growth factors, apoptosis, and angiogenesis. Previous in vitro studies have shown increased STAT5b expression in glioblastomas relative to low‐grade tumors and normal brain. We recently demonstrated that phosphorylated STAT5b associates with delta epidermal growth factor receptor in the nucleus and subsequently binds the promoters of downstream effector molecules, including aurora kinase A. Analysis of TCGA dataset reveals that STAT5b is predominantly expressed in proneural (PN) gliomas relative to mesenchymal and neural gliomas. Here, we modeled ectopic expression of STAT5b in vivo using a platelet‐derived growth factor subunit B (PDGFB)‐dependent mouse model of PN glioma to determine its effect on tumor formation and progression. We showed that coexpression of STAT5b and PDGFB in mice yielded a significantly higher rate of high‐grade gliomas than PDGFB expression alone. We also observed shorter survival in the combined expression set. High‐grade tumors from the STAT5b + PDGFB expression set were found to have a lower rate of apoptosis than those from PDGFB alone. Furthermore, we showed that increased expression of STAT5b + PDGFB led to increased expression of downstream STAT5b targets, including Bcl‐xL, cyclin D1 and aurora kinase A in high‐grade tumors when compared to tumors derived from PDGFB alone. Our findings show that STAT5b promotes the malignant transformation of gliomas, particularly the PN subtype, and is a potential therapeutic target.
Hepatic vein oxygenation, liver blood flow, and the rate of ethanol metabolism in recently abstinent alcoholic patients

Abstract. To determine whether hepatic hypoxia is associated with hepatocellular necrosis in alcoholics, oxygen tension in the hepatic vein and hepatic blood flow were determined in thirteen patients without overt clinical liver disease. Ethanol metabolic rate was also assayed as an index of liver metabolism. Hepatic blood flow and ethanol metabolic rate were also determined in six normal volunteers. According to liver histology patients were separated into two groups, with and without hepatocellular necrosis. Alcoholics with necrosis showed a higher (P < 0–002) ethanol metabolic rate (405±0–23 mmol/kg/h) than those without necrosis (2–46±0–34). Hepatic blood flow in the total group of alcoholics was not significantly different from controls; in the group with necrosis it was lower (651‐7±44‐6 ml/min/m2) than in the group without necrosis (878‐3±81‐6; P < 0025). Hepatic vein pO2 was lower (P < 001) in patients with hepatocellular necrosis (31‐7±0–68 mmHg) than in patients without necrosis (35‐7±0–99). In the whole group, a significant negative correlation (r= ‐0 76, P < 0–003) was observed between hepatic vein pO2 and ethanol metabolic rate. Acute administration of ethanol (21‐7 mmol/kg) did not alter hepatic blood flow in six normal individuals nor in five alcoholic patients, although an increase in hepatic vein pO2 was observed in the latter. The changes observed in hepatic vein pO2, functional hepatic blood flow, and ethanol metabolic rate which correlate with hepatocellular necrosis, may be of pathogenic importance in alcoholic liver disease.
Prognostic impact of p16 and PD-L1 expression in patients with oropharyngeal squamous cell carcinoma receiving a definitive treatment

Aims Limited information is available regarding the precise differences in the tumour immune microenvironment (TIM) of patients with human papilloma virus (HPV)-associated and non-HPV-associated oropharyngeal squamous cell carcinoma (OPSCC). Here, we retrospectively reviewed 137 patients with OPSCC treated with a definitive treatment to identify molecular relationships in the TIM. Materials and methods We used immunohistochemical analysis to assess p16 status, programmed death ligand 1 (PD-L1) level, and/or CD8+ tumour-infiltrating lymphocyte (TIL) density, followed by prognostic evaluation of these immune-related parameters. Results Multivariate analyses demonstrated that PD-L1 level on immune cells but not on tumour cells or CD8+ TIL density was a significant predictive factor of disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analyses demonstrated that patients positive for p16 and PD-L1 expression on immune cells had favourable DFS and OS, whereas patients negative for p16 and PD-L1 expression on immune cells showed worse DFS and OS. Conclusions We demonstrated that PD-L1 expression on immune cells but not tumour cells might represent a useful prognostic biomarker in patients with OPSCC receiving a definitive treatment. We propose that a co-assessment of p16 and PD-L1 expression on immune cells would have greater prognostic potential compared with evaluation of each factor alone in patients with OPSCC.
Moderate-intensity exercise allows enhanced protection against oxidative stress-induced cardiac dysfunction in spontaneously hypertensive rats

The progression of myocardial injury secondary to hypertension is a complex process related to a series of physiological and molecular factors including oxidative stress. This study aimed to investigate whether moderate-intensity exercise (MIE) could improve cardiac function and oxidative stress in spontaneously hypertensive rats (SHRs). Eight-week-old male SHRs and age-matched male Wistar-Kyoto rats were randomly assigned to exercise training (treadmill running at a speed of 20 m/min for 1 h continuously) or kept sedentary for 16 weeks. Cardiac function was monitored by polygraph; cardiac mitochondrial structure was observed by scanning electron microscope; tissue free radical production was measured using dihydroethidium staining. Expression levels of SIRT3 and SOD2 protein were measured by western blot, and cardiac antioxidants were assessed by assay kits. MIE improved the cardiac function of SHRs by decreasing left ventricular systolic pressure (LVSP), and first derivation of LVP (+LVdP/dtmax and −LVdP/dtmax). In addition, exercise-induced beneficial effects in SHRs were mediated by decreasing damage to myocardial mitochondrial morphology, decreasing production of reactive oxygen species, increasing glutathione level, decreasing oxidized glutathione level, increasing expression of SIRT3/SOD2, and increasing activity of superoxide dismutase. Exercise training in SHRs improved cardiac function by inhibiting hypertension-induced myocardial mitochondrial damage and attenuating oxidative stresses, offering new insights into prevention and treatment of hypertension.
Data-driven Schema Normalization

Ensuring Boyce-Codd Normal Form (BCNF) is the most popular way to remove redundancy and anomalies from datasets. Normalization to BCNF forces functional dependencies (FDs) into keys and foreign keys, which eliminates duplicate values and makes data constraints explicit. Despite being well researched in theory, converting the schema of an existing dataset into BCNF is still a complex, manual task, especially because the number of functional dependencies is huge and deriving keys and foreign keys is NP-hard. In this paper, we present a novel normalization algorithm called Normalize , which uses discovered functional dependencies to normalize relational datasets into BCNF. Nor-malize runs entirely data-driven, which means that redundancy is removed only where it can be observed, and it is (semi-)automatic, which means that a user may or may not interfere with the normalization process. The algorithm introduces an eﬃcient method for calculating the closure over sets of functional dependencies and novel features for choosing appropriate constraints. Our evaluation shows that Normalize can process millions of FDs within a few minutes and that the constraint selection techniques support the construction of meaningful relations during normalization.
Alterations of empathy in mothers with a history of early life maltreatment, depression, and borderline personality disorder and their effects on child psychopathology

Abstract Background Early life maltreatment (ELM), borderline personality disorder (BPD), and major depressive disorder (MDD) have been associated with empathy deficits in different domains. Lack of maternal empathy has also been related to child behavioral problems. As ELM, BPD, and MDD often co-occur, we aimed to identify dissociable effects on empathy due to these three factors. In addition, we aimed to investigate their indirect effects via empathy on child psychopathology. Methods We included 251 mothers with and without MDD (in remission), BPD and ELM and their children, aged 5–12. We used the Interpersonal Reactivity Index as a measure of empathy on four different dimensions (personal distress, empathic concern, perspective taking, and fantasy) and the Child Behavior Checklist as a measure of child psychopathology. Results Having included all three factors (ELM, MDD, BPD) in one analysis, we found elevated personal distress in MDD and BPD, and lower levels of perspective-taking in BPD, but no effects from ELM on any empathy subscales. Furthermore, we found indirect effects from maternal BPD and MDD on child psychopathology, via maternal personal distress. Conclusion The present study demonstrated the dissociable effects of maternal ELM, MDD, and BPD on empathy. Elevated personal distress in mothers with BPD and MDD may lead to higher levels of child psychopathology.
Smartwatch Performance for the Detection and Quantification of Atrial Fibrillation.

Background Atrial fibrillation (AF) burden and duration appear to be related to stroke risk. A wearable consumer electronic device could provide long-term assessment of these measures inexpensively and noninvasively. This study compares the accuracy of an AF-sensing watch (AFSW; Apple Watch with KardiaBand) with simultaneous recordings from an insertable cardiac monitor (ICM; Reveal LINQ). Methods SmartRhythm 2.0, a convolutional neural network, was trained on anonymized data of heart rate, activity level, and ECGs from 7500 AliveCor users. The network was validated on data collected in 24 patients with ICMs and a history of paroxysmal AF who simultaneously wore the AFSW with SmartRhythm 0.1 software. The primary outcome was sensitivity of the AFSW for AF episodes ≥1 hour. Secondary end points included sensitivity of the AFSW for detection of AF by subject and sensitivity for total AF duration across all subjects. Subjects with >50% false-positive AF episodes on ICM were excluded. Results We analyzed 31 348.9 hours (mean (SD), 11.3 (4.4) hours/day) of simultaneous AFSW and ICM recordings in 24 patients. The ICM detected 82 episodes of AF ≥1 hour while the AFSW was worn, with a total duration of 1127.1 hours. Of these, the SmartRhythm 2.0 neural network detected 80 episodes (episode sensitivity, 97.5%) with a total duration of 1101.1 hours (duration sensitivity, 97.7%). Three of the 18 subjects with AF ≥1 hour had AF only when the watch was not being worn (patient sensitivity, 83.3%; or 100% during time worn). Positive predictive value for AF episodes was 39.9%. Conclusions An AFSW is highly sensitive for detection of AF and assessment of AF duration in an ambulatory population when compared with an ICM. Such devices may represent an inexpensive, noninvasive approach to long-term AF surveillance and management.