Miracle-dz/UniFAR-FTUs huggingface dataset:
Multifaceted roles of pericytes in central nervous system homeostasis and disease

Pericytes, the mural cells surrounding microcirculation, are gaining increasing attention for their roles in health and disease of the central nervous system (CNS). As an essential part of the neurovascular unit (NVU), pericytes are actively engaged in interactions with neighboring cells and work in synergy with them to maintain homeostasis of the CNS, such as maintaining the blood–brain barrier (BBB), regulating cerebral blood flow (CBF) and the glymphatic system as well as mediating immune responses. However, the dysfunction of pericytes may contribute to the progression of various pathologies. In this review, we discuss: (1) origin of pericytes and different pericyte markers; (2) interactions of pericytes with endothelial cells (ECs), astrocytes, microglia, oligodendrocytes, and neurons; (3) physiological roles of pericytes in the CNS; (4) effects of pericytes in different CNS diseases; (5) relationship of pericytes with extracellular vesicles (EVs) and microRNAs (miRs); (6) recent advances in pericytes studies and future perspective.
Notch3 in Development, Health and Disease

Notch3 is one of four mammalian Notch proteins, which act as signalling receptors to control cell fate in many developmental and adult tissue contexts. Notch signalling continues to be important in the adult organism for tissue maintenance and renewal and mis-regulation of Notch is involved in many diseases. Genetic studies have shown that Notch3 gene knockouts are viable and have limited developmental defects, focussed mostly on defects in the arterial smooth muscle cell lineage. Additional studies have revealed overlapping roles for Notch3 with other Notch proteins, which widen the range of developmental functions. In the adult, Notch3, in collaboration with other Notch proteins, is involved in stem cell regulation in different tissues in stem cell regulation in different tissues, and it also controls the plasticity of the vascular smooth muscle phenotype involved in arterial vessel remodelling. Overexpression, gene amplification and mis-activation of Notch3 are associated with different cancers, in particular triple negative breast cancer and ovarian cancer. Mutations of Notch3 are associated with a dominantly inherited disease CADASIL (cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy), and there is further evidence linking Notch3 misregulation to hypertensive disease. Here we discuss the distinctive roles of Notch3 in development, health and disease, different views as to the underlying mechanisms of its activation and misregulation in different contexts and potential for therapeutic intervention.
Photoplethysmographic Time-Domain Heart Rate Measurement Algorithm for Resource-Constrained Wearable Devices and its Implementation

This paper presents an algorithm for the measurement of the human heart rate, using photoplethysmography (PPG), i.e., the detection of the light at the skin surface. The signal from the PPG sensor is processed in time-domain; the peaks in the preprocessed and conditioned PPG waveform are detected by using a peak detection algorithm to find the heart rate in real time. Apart from the PPG sensor, the accelerometer is also used to detect body movement and to indicate the moments in time, for which the PPG waveform can be unreliable. This paper describes in detail the signal conditioning path and the modified algorithm, and it also gives an example of implementation in a resource-constrained wrist-wearable device. The algorithm was evaluated by using the publicly available PPG-DaLia dataset containing samples collected during real-life activities with a PPG sensor and accelerometer and with an ECG signal as ground truth. The quality of the results is comparable to the other algorithms from the literature, while the required hardware resources are lower, which can be significant for wearable applications.
Biomarker potential of brain‐secreted extracellular vesicles in blood in Alzheimer's disease

Brain cells secrete extracellular microvesicles (EVs) that cross the blood‐brain barrier. Involved in cell‐to‐cell communication, EVs contain surface markers and a biologically active cargo of molecules specific to their tissue (and cell) of origin, reflecting the tissue or cell's physiological state. Isolation of brain‐secreted EVs (BEVs) from blood provides a minimally invasive way to sample components of brain tissue in Alzheimer's disease (AD), and is considered a form of “liquid biopsy. ”
Antibiotic prophylaxis for transrectal ultrasound-guided prostate needle biopsy: Compared efficacy of ciprofloxacin vs. the ciprofloxacin/fosfomycin tromethamine combination.

INTRODUCTION Some authors advocate an increase in post-prostate needle biopsy (PNB) infections associated with emergent quinolone resistance in E. coli, urging re-evaluation of antibioprophylaxis. In this study, we compared rates of post-PNB urosepsis associated with two oral regimens of antibioprophylaxis: ciprofloxacin (CIP) vs. ciprofloxacin and fosfomycin tromethamine combination (CIP/FOS). METHODS This retrospective pre-post intervention study included all patients who underwent PNB in two Canadian hospitals from January 2012 to December 2015. The primary outcome was urosepsis within one month of PNB. Urosepsis rates were analyzed according to antibioprophylaxis using log-binomial regression, considering the propensity scores weights of collected risk factor data. RESULTS We reviewed 2287 PNB patients. A total of 1090 received CIP and 1197 received CIP/FOS. Urosepsis incidence with CIP was 1.1% (12/1090) and fell to 0.2% (2/1197) with CIP/FOS. Our analysis indicates that CIP/FOS significantly decreased the risk of urosepsis compared to CIP alone (adjusted relative risk [aRR] 0.16; p=0.021). The isolated pathogen was E. coli in 12/14 cases, including seven bacteremias. Among E. coli cases, seven strains were CIP-resistant. Eleven of 12 E. coli, including all CIP-resistant strains, were isolated in patients on CIP alone. One case of B. fragilis bacteremia occurred in the CIP/FOS group. No cases of C. difficile infection were identified in the three months post-PNB. CONCLUSIONS The adoption of CIP/FOS antibiotic prophylaxis significantly lowered the rate of post-PNB urosepsis. Conveniently, this regimen is oral, single-dose, and low-cost.
Experiences of accessing and using breast cancer services in Vietnam: a descriptive qualitative study

Objectives To understand, describe and analyse the experiences of women with breast cancer in Vietnam when accessing and using breast cancer services. Design Descriptive qualitative study. Women were interviewed about their experiences from the first time they became aware of symptoms or changes to their body through treatment and post-treatment. This study is the first descriptive study on breast cancer in Vietnam from the perspective of women with a breast cancer diagnosis. Participants Women (n=13) who had completed or were still receiving treatment for breast cancer, purposively recruited from the north and south of Vietnam. Results An analysis of the experiences of women with breast cancer in Vietnam revealed a lack of awareness and knowledge about breast cancer and symptoms. Family and social support were described as key factors influencing whether a woman accesses and uses breast cancer services. Cost of treatment and out-of-pocket expenditures limited access to services and resulted in significant financial challenges for women and their families. Conclusions Vietnam has made huge strides in improving cancer care, and is tackling a complex and expanding public health challenge, however, there are a number of areas requiring strengthening and future research. While Vietnam has successfully expanded social health insurance coverage, changes that increase the percentage of costs covered for specific treatments, such as chemotherapy or radiotherapy, could benefit women and their families.
Quality by Design: Development of the Quality Target Product Profile (QTPP) for Semisolid Topical Products

In recent years, the “quality by design” (QbD) approach has been used for developing pharmaceutical formulations. This is particularly important for complex dosage forms such as topical semisolid products. The first step for developing a product using this efficient approach is defining the quality target product profile (QTPP), a list of quality attributes (QAs) that are required to be present in the final product. These quality attributes are affected by the ingredients used as well as manufacturing procedure parameters. Hence, critical material attributes (CMAs) and critical process parameters (CPPs) need to be specified. Possible failure modes of a topical semisolid product can be determined based on the physiochemical properties of ingredients and manufacturing procedures. In this review, we have defined and specified QTPP, QAs, CMAs and CPPs that are required for developing a topical semisolid product based on the QbD approach.
Forefront: MiR-34a-Knockout Mice with Wild Type Hematopoietic Cells, Retain Persistent Fibrosis Following Lung Injury

MicroRNAs (miRs) are known to limit gene expression at the post-transcriptional level and have important roles in the pathogenesis of various conditions, including acute lung injury (ALI) and fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). In this study, we found increased levels of miR-34 at times of fibrosis resolution following injury, in myofibroblasts from Bleomycin-treated mouse lungs, which correlates with susceptibility to cell death induced by immune cells. On the contrary, a substantial downregulation of miR-34 was detected at stages of evolution, when fibroblasts resist cell death. Concomitantly, we found an inverse correlation between miR-34 levels with that of the survival molecule FLICE-like inhibitory protein (FLIP) in lung myofibroblasts from humans with IPF and the experimental model. Forced upregulation of miR-34 with miR-34 mimic in human IPF fibrotic-lung myofibroblasts led to decreased cell survival through downregulation of FLIP. Using chimeric miR-34 knock-out (KO)-C57BL/6 mice with miR34KO myofibroblasts but wild-type (WT) hematopoietic cells, we found, in contrast to WT mice, increased and persistent FLIP levels with a more severe fibrosis and with no signs of resolution as detected in pathology and collagen accumulation. Moreover, a mimic of miR-34a decreased FLIP expression and susceptibility to cell death was regained in miR-34KO fibroblasts. Through this study, we show for the first time an inverse correlation between miR-34a and FLIP expression in myofibroblasts, which affects survival, and accumulation in lung fibrosis. Reprogramming fibrotic-lung myofibroblasts to regain susceptibility to cell-death by specifically increasing their miR34a and downregulating FLIP, may be a useful strategy, enabling tissue regeneration following lung injury.
Expression and prognosis analysis of TET family in acute myeloid leukemia

TET family members (TETs) encode proteins that represent crucial factors in the active DNA demethylation pathway. Evidence has proved that TET2 mutation is associated with leukemogenesis, drug response, and prognosis in acute myeloid leukemia (AML). However, few studies revealed the TETs expression and its clinical significance in AML. We conducted a detailed expression and prognosis analysis of TETs expression in human AML cell lines and patients by using public databases. We observed that TETs expression especially TET2 and TET3 was closely associated with AML among various human cancers. TET1 expression was significantly reduced in AML patients, whereas TET2 and TET3 expression was significantly increased. Kaplan-Meier analysis showed that only TET3 expression was associated with overall survival (OS) and disease-free survival (DFS) among both total AML as well as non-M3 AML, and was confirmed by another independent cohort. Moreover, Cox regression analysis revealed that TET3 expression may act as an independent prognostic factor for OS and DFS in total AML. Interestingly, patients that received hematopoietic stem cell transplantation (HSCT) did not show significantly longer OS and DFS than those who did not receive HSCT in TET3 high-expressed groups; whereas, in TET3 low-expressed groups, patients that accepted HSCT showed significantly longer OS and DFS than those who did not accept HSCT. By bioinformatics analysis, TET3 expression was found positively correlated with tumor suppressor gene including CDKN2B, ZIC2, miR-196a, and negatively correlated with oncogenes such as PAX2 and IL2RA. Our study demonstrated that TETs showed significant expression differences in AML, and TET3 expression acted as a potential prognostic biomarker in AML, which may guide treatment choice between chemotherapy and HSCT.
Identification of the Antidepressant Vilazodone as an Inhibitor of Inositol Polyphosphate Multikinase by Structure-Based Drug Repositioning

Inositol polyphosphate multikinase (IPMK) is required for the biosynthesis of inositol phosphates (IPs) through the phosphorylation of multiple IP metabolites such as IP3 and IP4. The biological significance of IPMK’s catalytic actions to regulate cellular signaling events such as growth and metabolism has been studied extensively. However, pharmacological reagents that inhibit IPMK have not yet been identified. We employed a structure-based virtual screening of publicly available U.S. Food and Drug Administration-approved drugs and chemicals that identified the antidepressant, vilazodone, as an IPMK inhibitor. Docking simulations and pharmacophore analyses showed that vilazodone has a higher affinity for the ATP-binding catalytic region of IPMK than ATP and we validated that vilazodone inhibits IPMK’s IP kinase activities in vitro. The incubation of vilazodone with NIH3T3-L1 fibroblasts reduced cellular levels of IP5 and other highly phosphorylated IPs without influencing IP4 levels. We further found decreased Akt phosphorylation in vilazodone-treated HCT116 cancer cells. These data clearly indicate selective cellular actions of vilazodone against IPMK-dependent catalytic steps in IP metabolism and Akt activation. Collectively, our data demonstrate vilazodone as a method to inhibit cellular IPMK, providing a valuable pharmacological agent to study and target the biological and pathological processes governed by IPMK.
Evaluating the Effect of Cardiac Rehabilitation Care Plan on Quality of Life of Patients Undergoing Coronary Artery Bypass Graft Surgery

Introduction : Cardiovascular surgeries are among the conventional surgeries aimed at increasing the survival rate and improving the quality of life of patients. This study aimed to evaluate the effect of cardiac rehabilitation on quality of life of patients undergoing Coronary artery bypass graft (CABG) surgery. Methods : This was a semi-experimental study performed on 160 patients undergoing CABG surgery. The rehabilitation program was carried out for 13 weeks (three sessions per week) in 40 sessions, six weeks after the CABG surgery. The MacNew standard questionnaire and the general health questionnaire (S-f 36) were completed before the beginning of rehabilitation sessions as well as after completion of these sessions by patients. Results : According to the results, the quality of life of patients significantly increased in the physical and emotional areas after the rehabilitation program. The results also indicated that there was a significant difference between various levels of research in the physical functioning variables, dysfunction due to physical health, dysfunction due to emotional health, energy/fatigue of individuals, emotional well-being, social functioning, pain, and general health. Conclusions : The present results indicated the improved quality of life of patients in all the areas after cardiac rehabilitation intervention, compared to before that. Therefore, paying more attention to cardiac rehabilitation is necessary due to its positive effects on increasing the quality of life of patients.
N‐acetylcysteine reduces cocaine‐seeking behavior and anterior cingulate glutamate/glutamine levels among cocaine‐dependent individuals

N‐acetylcysteine (NAC) is a cystine prodrug shown to reduce cocaine‐ and cue‐primed reinstatement of cocaine‐seeking behavior in preclinical studies. In this inpatient study, the effects of NAC maintenance versus placebo on cocaine‐seeking behavior were examined during cocaine‐primed and unprimed self‐administration sessions among non‐treatment‐seeking, cocaine‐dependent individuals. Twelve participants completed this double‐blind, placebo‐controlled, within‐subject crossover study. Each participant was maintained for 1 week (Sat–Fri) on NAC (1200‐mg TID; 3600 mg/day total) and 1 week on placebo (0‐mg TID); medication order was randomized. A subset of participants underwent proton magnetic resonance spectroscopy scans (n = 8) on the third day of medication (Mon) to assess neurochemistry in the rostral anterior cingulate (rACC; voxel = 4.5 cm3). In four randomized sessions (Tue–Fri) each week, each participant could earn unit amounts of cocaine (10 mg, fixed) versus money ($0.50 vs. $1.50) on a choice, progressive ratio schedule after insufflating active versus placebo cocaine‐priming doses (110 mg vs. 4 mg). Relative to the placebo priming dose, the active cocaine priming dose (110 mg) increased cocaine‐seeking behavior (p = .003). NAC reduced cocaine‐primed cocaine‐seeking behavior compared with placebo levels (p = .044) but did not alter placebo‐primed cocaine‐seeking behavior. The larger money alternative ($1.50) suppressed cocaine‐seeking behavior relative to the smaller money alternative ($0.50; p = .011). Compared with placebo levels, NAC significantly decreased rACC glutamate + glutamine levels (p = .035) and numerically decreased rACC glutamate levels (p = .085). These preliminary findings indicate that NAC suppresses cocaine‐seeking behavior in some, but not all, experimental scenarios. Further, our findings suggest NAC may exert its therapeutic effects by modulating excitatory tone in the rACC.
WHO approach to track HIV drug resistance emergence and transmission in countries scaling up HIV treatment

Treatment access programmes are currently expanding in resource-limited settings. The potential barriers to long-term success (such as intermittent drug supply, drug stock-outs, poor patient monitoring, incorrect prescribing practices and low adherence) as well as the need to begin programmes quickly to treat millions of individuals, have raised fears that the aggressive plan to roll out antiretroviral therapy (ART), particularly in Africa, may generate an epidemic of drug-resistant strains of HIV.
Clinical Study of Pancytopenia

Introduction: Pancytopenia is a common and alarming condition encountered by clinicians. We had studied the clinical presentation, laboratory investigations and various etiologies of Pancytopenia. Material and Methods: Study was carried out in a tertiary care centre in western India. A total of 102 patients fulfilling the criteria of pancytopenia were enrolled and studied. Results and conclusion: Megaloblastic anemia was commonest cause of pancytopenia. Easy fatigability and pallor were commonest symptoms and signs respectively. Maximum bleeding manifestations were seen in aplastic anemia and Myelodysplastic syndrome.
Apoptosis and Heart Failure: A Critical Review of the Literature Vascular Cell Apoptosis in Remodeling, Restenosis, and Plaque Rupture Endothelial Cell Apoptosis in Angiogenesis and Vessel Regression Apoptosis During Cardiovascular Development Myocyte Apoptosis in Ischemic Heart Disease

Morphogenesis and developmental remodeling of cardiovascular tissues involve coordinated regulation of cell proliferation and apoptosis. In the heart, clear evidence points toward focal apoptosis as a contributor to development of the embryonic outflow tract, cardiac valves, conducting system, and the developing coronary vasculature. Apoptosis in the heart is likely regulated by survival and death signals that are also present in many other tissues. Cell type–specific regulation may be superimposed on general cell death/survival machinery through tissue-specific transcriptional pathways. In the vasculature, apoptosis almost certainly contributes to developmental vessel regression, and it is of proven importance in remodeling of arterial structure in response to local changes in hemodynamics. Physical forces, growth factors, and extracellular matrix drive vascular cell survival pathways, and considerable evidence points to local nitric oxide production as an important but complex regulator of vascular cell death. In both the heart and vasculature, progress has been impeded by inadequate information concerning the incidence of apoptosis, its relative importance compared with the diverse cell behaviors that remodel developing tissues, and by our primitive knowledge concerning regulation of cell death in these tissues. However, tools are now available to better understand apoptosis in normal and abnormal development of cardiovascular structures, and a framework has been established that should lead to considerable progress in the coming years. (Circ Res. 2000;87:856-864.)
MIMIC III Database: A Descriptive Epidemiology of Severe Cholangitis Patient Cohort

Objective: Electronic medical records include detailed information on clinical care. Besides its clinical utility, they afford researchers to evaluate impact of diagnostic and therapeutic decisions on patient outcomes. However, these dataset are not shared mainly for confidential reasons and remain consequently underused. MIMIC-III (‘Medical Information Mart for Intensive Care’) is a large, single-center database comprising information relating to patients admitted to critical care units at a large tertiary care hospital has been made publicly available. The objective of this study is to investigate and introduce the database content though the descriptive epidemiology of a severe cholangitis patient cohort. Method: We conducted a retrospective study of patients with severe cholangitis admitted to the intensive care unit of the Beth Israel Deaconess Medical Center using the MIMIC-III v1.4 (‘Medical Information Mart for Intensive Care’). We investigated type of data