Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and Efficacy of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Renal Impairment

Direct oral anticoagulants (DOACs) are gaining popularity for patients with nonvalvular atrial fibrillation (AF) for stroke prevention. Less bleeding risk with comparable stroke prevention compared to warfarin was shown. DOACs have predictable anticoagulant effects, infrequent monitoring requirements and less drug-food interactions compared to warfarin. However, safety and efficacy data of DOACs in patients with chronic kidney disease (CKD) are limited. This is a retrospective study to evaluate thromboembolic and bleeding events in patients with AF (with/without CKD) in October 2010 and July 2017. A total of 495 patients were included and only 150 patients had CKD. Our study found that patients with renal impairment on a DOAC do not have a higher incidence of bleeding events. It showed significant increase in thromboembolic events in CKD patients with dabigatran compared to CKD patients with apixaban with odds ratio of 6.58 (95%CI 1.35–32.02, p = 0.02).
Recent Advances of Fluid Manipulation Technologies in Microfluidic Paper-Based Analytical Devices (μPADs) toward Multi-Step Assays

Microfluidic paper-based analytical devices (μPADs) have been suggested as alternatives for developing countries with suboptimal medical conditions because of their low diagnostic cost, high portability, and disposable characteristics. Recently, paper-based diagnostic devices enabling multi-step assays have been drawing attention, as they allow complicated tests, such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR), which were previously only conducted in the laboratory, to be performed on-site. In addition, user convenience and price of paper-based diagnostic devices are other competitive points over other point-of-care testing (POCT) devices, which are more critical in developing countries. Fluid manipulation technologies in paper play a key role in realizing multi-step assays via μPADs, and the expansion of biochemical applications will provide developing countries with more medical benefits. Therefore, we herein aimed to investigate recent fluid manipulation technologies utilized in paper-based devices and to introduce various approaches adopting several principles to control fluids on papers. Fluid manipulation technologies are classified into passive and active methods. While passive valves are structurally simple and easy to fabricate, they are difficult to control in terms of flow at a specific spatiotemporal condition. On the contrary, active valves are more complicated and mostly require external systems, but they provide much freedom of fluid manipulation and programmable operation. Both technologies have been revolutionized in the way to compensate for their limitations, and their advances will lead to improved performance of μPADs, increasing the level of healthcare around the world.
Resting State Functional Connectivity Signature Differentiates Cognitively Normal from Individuals Who Convert to Symptomatic Alzheimer's Disease.

BACKGROUND Changes in resting state functional connectivity (rs-fc) occur in Alzheimer's disease (AD), but few longitudinal rs-fc studies have been performed. Most studies focus on single networks and not a global measure of rs-fc. Although the amyloid tau neurodegeneration (AT(N)) framework is increasingly utilized by the AD community, few studies investigated when global rs-fc signature changes occur within this model. OBJECTIVE 1) Identify a global rs-fc signature that differentiates cognitively normal (CN) individuals from symptomatic AD. 2) Assess when longitudinal changes in rs-fc occur relative to conversion to symptomatic AD. 3) Compare rs-fc with amyloid, tau, and neurodegeneration biomarkers. METHODS A global rs-fc signature composed of intra-network connections was longitudinally evaluated in a cohort of cognitively normal participants at baseline (n = 335). Biomarkers, including cerebrospinal fluid (Aβ42 and tau), structural magnetic resonance imaging, and positron emission tomography were obtained. RESULTS Global rs-fc signature distinguished CN individuals from individuals who developed symptomatic AD. Changes occurred nearly four years before conversion to symptomatic AD. The global rs-fc signature most strongly correlated with markers of neurodegeneration. CONCLUSION The global rs-fc signature changes near symptomatic onset and is likely a neurodegenerative biomarker. Rs-fc changes could serve as a biomarker for evaluating potential therapies for symptomatic conversion to AD.
The mitochondrial protein PGAM5 suppresses energy consumption in brown adipocytes by repressing expression of uncoupling protein 1

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.
Bacterial blood stream infections and antibiogram among febrile patients at Bahir Dar Regional Health Research Laboratory Center, Ethiopia

Bacterial blood stream infections (BSIs) are a common cause of morbidity and mortality. Prevailing data on bacterial species causing BSI and their antibiogram are essential for proper management of patients. A retrospective study was conducted on blood culture results that had been processed from March 2013 to January 2015 at Bahir Dar Regional Health Research Laboratory Center. In January 2015, data on age, sex of patients and bacterial isolates with antibiogram were extracted from registration log book. Blood stream causing bacteria were identified according to standard operational procedure for blood culture. Antimicrobial susceptibility tests were performed according to Kirby-Bauer disc diffusion methods. A total of 561 blood specimens were requested for blood culture. Of these, 220 (39.2%, 95% CI: 35.3-43.4%) blood cultures had aerobic bacterial growth. Gram negative bacterial isolates constituted 115 (52.3%) of the isolated bacteria. Staphylococcus aureus 50 (22.7%), coagulase negative staphylococci 35(15.9%), Klebsiella pneumoniae 35 (15.9%), Escherichia coli 19 (8.6%), Pseudomonas aeruginosa 15 (6.8%) and Acinetobacter species 13(5.9%) were the most dominant isolates. Overall, drug resistance for gram positive bacteria were 7 to 61% and for gram negatives 6.9 to 82.6%. Among the gram positive bacteria, high resistance levels were observed against penicillin (61%) and oxacillin (52.9%). The gram negative bacterial isolates showed 66 to 82.6% resistance to ampicillin, ceftriaxone and trimethoprim-sulfamethoxazole. The present study revealed that bacterial blood stream infections linked with high levels of drug resistance would pose a challenge in treatment of patients with BSIs. Hence, blood culture with antibiotic susceptibility tests could play key role for appropriate treatment of patients with bacterial blood stream infection. Key words : Blood culture, Bloodstream infection, antibiogram, Ethiopia
Interactions in stanene centred van der Waals trilayers structures of boron-nitride and graphene: effect of mirror symmetry on electronic interactions

Dispersion-corrected density functional theory was used to investigate structures consisting of a stanene layer sandwiched between atomically-thin boron nitride and graphene. The parameters controlling the mirror symmetry, lattice rotation and stacking sequences were varied systematically to generate fifteen candidate trilayers. Two types of structural buckling occur in the heterostructures depending on whether the lattice vectors are co-aligned or non-collinear. The configurations with the honeycomb lattices rotated by π/6 with respect to the stanene generally have lower binding energy. In the majority of the trilayers, the electronic structures deviate strongly from the band structures of the isolated components. The boron nitride/stanene/boron nitride structure is identified as a special case where stanene has an electronic structure that is not perturbed by interlayer interactions and resembles the ideal monolayer form. For the other candidate structures, however, interlayer interactions drive significant modifications in the electronic structure thus indicating emergent features that go beyond the pure van der Waals description.
Thrombospondin-1 mediates muscle damage in brachio-cervical inflammatory myopathy and systemic sclerosis

Objective To describe the clinical, serologic and histologic features of a cohort of patients with brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc) and unravel disease-specific pathophysiologic mechanisms occurring in these patients. Methods We reviewed clinical, immunologic, muscle MRI, nailfold videocapillaroscopy, muscle biopsy, and response to treatment data from 8 patients with BCIM-SSc. We compared cytokine profiles between patients with BCIM-SSc and SSc without muscle involvement and controls. We analyzed the effect of the deregulated cytokines in vitro (fibroblasts, endothelial cells, and muscle cells) and in vivo. Results All patients with BCIM-SSc presented with muscle weakness involving cervical and proximal muscles of the upper limbs plus Raynaud syndrome, telangiectasia and/or sclerodactilia, hypotonia of the esophagus, and interstitial lung disease. Immunosuppressive treatment stopped the progression of the disease. Muscle biopsy showed pathologic changes including the presence of necrotic fibers, fibrosis, and reduced capillary number and size. Cytokines involved in inflammation, angiogenesis, and fibrosis were deregulated. Thrombospondin-1 (TSP-1), which participates in all these 3 processes, was upregulated in patients with BCIM-SSc. In vitro, TSP-1 and serum of patients with BCIM-SSc promoted proliferation and upregulation of collagen, fibronectin, and transforming growth factor beta in fibroblasts. TSP-1 disrupted vascular network, decreased muscle differentiation, and promoted hypotrophic myotubes. In vivo, TSP-1 increased fibrotic tissue and profibrotic macrophage infiltration in the muscle. Conclusions Patients with SSc may present with a clinically and pathologically distinct myopathy. A prompt and correct diagnosis has important implications for treatment. Finally, TSP-1 may participate in the pathologic changes observed in muscle.
Prenatal, Early-life and Childhood Exposure to Air Pollution and Lung Function: The ALSPAC Cohort.

RATIONALE Exposure to air pollution during intrauterine development and through childhood may have lasting effects on respiratory health. OBJECTIVES To investigate lung function at ages 8 and 15 years in relation to air pollution exposures during pregnancy, infancy and childhood in a UK population-based birth cohort. METHODS Individual exposures to source-specific particulate matter with diameter ≤10µm (PM10) during each trimester, 0-6 months, 7-12 months (1990-1993) and up to age 15 years (1991-2008) were examined in relation to %predicted Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) at ages 8(N=5,276) and 15(N=3,446) years, usinglinear regression models adjusted for potential confounders. A profile regression model was used to identify sensitive time periods. MEASUREMENTS AND MAIN RESULTS We did not find clear evidence for a sensitive exposure period for PM10 from road-traffic: at age 8 years, 1µg/m3 higher exposure during the first trimester was associated with lower %predicted of FEV1(-0.826, 95%CI:-1.357 to -0.296) and FVC(-0.817, 95%CI:-1.357 to -0.276), but similar associations were seen for exposures for other trimesters, 0-6 months, 7-12 months, and 0-7 years. Associations were stronger among boys, children whose mother had a lower education level or smoked during pregnancy. For PM10 from all sources, the third trimester was associated with lower %predicted of FVC (-1.312, 95%CI: -2.100 to -0.525). At age 15 years, no adverse associations were seen with lung function. CONCLUSIONS Exposure to road-traffic PM10 during pregnancy may result in small but significant reductions in lung function at age 8 years.
Walk-In Triage Systems in University Counseling Centers

ABSTRACT To meet the complex mental health needs of students, some university counseling centers (UCCs) have implemented walk-in triage intake systems, which have not yet been empirically investigated. This study compared client and clinician differences (N = 5564) between a traditional scheduled intake system (Year 1) and a walk-in triage system (Year 2) at a large, southeastern UCC. Results showed a significant increase in clients’ attendance rates and clinicians’ caseloads, a significant decrease in no-show rates, and no change in students’ symptom severity at intake between Years 1 and 2. Clinicians’ number of scheduled appointments were unchanged, indicating that clinicians were already at maximum capacity for appointments in Year 1. Results are discussed in terms of the benefits and challenges that walk-in triage systems present to students, universities, and UCCs.
Worldwide prevalence of oral lichen planus: a systematic review and meta-analysis.

OBJECTIVES To assess the global oral lichen planus prevalence. MATERIAL AND METHODS We searched PubMed, Embase, Web of Science, and Scopus for studies published before Sep-2019. We evaluated the quality of studies and carried out several meta-analyses. RESULTS The global pooled prevalence was 1.01%, with a marked geographical difference (p<0.001). The highest prevalence was reported from Europe (1.43%) and the lowest in India (0.49%), where tobacco-associated keratosis appears to mask oral lichen planus resulting in attenuation of its prevalence. From the age of 40y, the prevalence increases significantly and progressively (OR=3.43,95%CI=2.48-4.73,p<0.001). Studies that define diagnostic criteria report a higher prevalence (1.31% vs. 0.70%,p=0.03), although the application of the WHO criteria (year) does not increase the ability to diagnose the disease compared with other criteria(p=0.11). The studies performed by oral medicine/oral pathology specialists report significantly higher prevalence (1.80%) than dentists (0.61%) and dermatologists (0.33%)(p<0.001). CONCLUSIONS We propose that reliable diagnostic criteria should be defined, which should include a set of essential criteria including the presence of white reticular lesions in any location of the oral mucosa. The impact of histopathological confirmation with defined diagnostic criteria must be researched in the future, although its main use should be to determine the presence or absence of epithelial dysplasia. The necessity to improve the knowledge of oral lichen planus among dentists and dermatologists through continuing education is apparent in the results of this meta-analysis.
Infants Diagnosed with Spinal Muscular Atrophy and 4 SMN2 Copies through Newborn Screening – Opportunity or Burden?1

Although the value of newborn screening (NBS) for early detection and treatment opportunity in SMA patients is generally accepted, there is still an ongoing discussion about the best strategy in children with 4 and more copies of the SMN2 gene. This gene is known to be the most important but not the only disease modifier. In our SMA-NBS pilot project in Germany comprising 278,970 infants screened between January 2018 and November 2019 were 38 positive cases with a homozygous SMN1 deletion. 40% of them had 4 or more SMN2 copies. The incidence for homozygous SMN1 deletion was 1 : 7350, which is within the known range of SMA incidence in Germany. Of the 15 SMA children with 4 SMN2 copies, one child developed physical signs of SMA by the age of 8 months. Reanalysis of the SMN2 copy number by a different test method revealed 3 copies. Two children had affected siblings with SMA Type III, who were diagnosed only after detection of the index patient in the NBS. One had a positive family history with an affected aunt (onset of disease at the age of 3 years). Three families were lost to medical follow up; two because of socioeconomic reasons and one to avoid the psychological stress associated with the appointments. Decisions on how to handle patients with 4 SMN2 copies are discussed in the light of the experience gathered from our NBS pilot SMA program.
STDD: Short-Term Depression Detection with Passive Sensing

It has recently been reported that identifying the depression severity of a person requires involvement of mental health professionals who use traditional methods like interviews and self-reports, which results in spending time and money. In this work we made solid contributions on short-term depression detection using every-day mobile devices. To improve the accuracy of depression detection, we extracted five factors influencing depression (symptom clusters) from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), namely, physical activity, mood, social activity, sleep, and food intake and extracted features related to each symptom cluster from mobile devices’ sensors. We conducted an experiment, where we recruited 20 participants from four different depression groups based on PHQ-9 (the Patient Health Questionnaire-9, the 9-item depression module from the full PHQ), which are normal, mildly depressed, moderately depressed, and severely depressed and built a machine learning model for automatic classification of depression category in a short period of time. To achieve the aim of short-term depression classification, we developed Short-Term Depression Detector (STDD), a framework that consisted of a smartphone and a wearable device that constantly reported the metrics (sensor data and self-reports) to perform depression group classification. The result of this pilot study revealed high correlations between participants` Ecological Momentary Assessment (EMA) self-reports and passive sensing (sensor data) in physical activity, mood, and sleep levels; STDD demonstrated the feasibility of group classification with an accuracy of 96.00% (standard deviation (SD) = 2.76).
Contribution of NPY Y5 Receptors to the Reversible Structural Remodeling of Basolateral Amygdala Dendrites in Male Rats Associated with NPY-Mediated Stress Resilience

Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. Endogenous neuropeptide Y (NPY) and corticotrophin-releasing factor (CRF) modulate the responses of the basolateral amygdala (BLA) to stress and are associated with the development of stress resilience and vulnerability, respectively. We characterized persistent effects of repeated NPY and CRF treatment on the structure and function of BLA principal neurons in a novel organotypic slice culture (OTC) model of male rat BLA, and examined the contributions of specific NPY receptor subtypes to these neural and behavioral effects. In BLA principal neurons within the OTCs, repeated NPY treatment caused persistent attenuation of excitatory input and induced dendritic hypotrophy via Y5 receptor activation; conversely, CRF increased excitatory input and induced hypertrophy of BLA principal neurons. Repeated treatment of OTCs with NPY followed by an identical treatment with CRF, or vice versa, inhibited or reversed all structural changes in OTCs. These structural responses to NPY or CRF required calcineurin or CaMKII, respectively. Finally, repeated intra-BLA injections of NPY or a Y5 receptor agonist increased social interaction, a validated behavior for anxiety, and recapitulated structural changes in BLA neurons seen in OTCs, while a Y5 receptor antagonist prevented NPY's effects both on behavior and on structure. These results implicate the Y5 receptor in the long-term, anxiolytic-like effects of NPY in the BLA, consistent with an intrinsic role in stress buffering, and highlight a remarkable mechanism by which BLA neurons may adapt to different levels of stress. Moreover, BLA OTCs offer a robust model to study mechanisms associated with resilience and vulnerability to stress in BLA. SIGNIFICANCE STATEMENT Within the basolateral amygdala (BLA), neuropeptide Y (NPY) is associated with buffering the neural stress response induced by corticotropin releasing factor, and promoting stress resilience. We used a novel organotypic slice culture model of BLA, complemented with in vivo studies, to examine the cellular mechanisms associated with the actions of NPY. In organotypic slice cultures, repeated NPY treatment reduces the complexity of the dendritic extent of anxiogenic BLA principal neurons, making them less excitable. NPY, via activation of Y5 receptors, additionally inhibits and reverses the increases in dendritic extent and excitability induced by the stress hormone, corticotropin releasing factor. This NPY-mediated neuroplasticity indicates that resilience or vulnerability to stress may thus involve neuropeptide-mediated dendritic remodeling in BLA principal neurons.
APP Maturation and Intracellular Localization Are Controlled by a Specific Inhibitor of 37/67 kDa Laminin-1 Receptor in Neuronal Cells

Amyloid precursor protein (APP) is processed along both the nonamyloidogenic pathway preventing amyloid beta peptide (Aβ) production and the amyloidogenic pathway, generating Aβ, whose accumulation characterizes Alzheimer’s disease. Items of evidence report that the intracellular trafficking plays a key role in the generation of Aβ and that the 37/67 kDa LR (laminin receptor), acting as a receptor for Aβ, may mediate Aβ-pathogenicity. Moreover, findings indicating interaction between the receptor and the key enzymes involved in the amyloidogenic pathway suggest a strong link between 37/67 kDa LR and APP processing. We show herein that the specific 37/67 kDa LR inhibitor, NSC48478, is able to reversibly affect the maturation of APP in a pH-dependent manner, resulting in the partial accumulation of the immature APP isoforms (unglycosylated/acetylated forms) in the endoplasmic reticulum (ER) and in transferrin-positive recycling endosomes, indicating alteration of the APP intracellular trafficking. These effects reveal NSC48478 inhibitor as a novel small molecule to be tested in disease conditions, mediated by the 37/67 kDa LR and accompanied by inactivation of ERK1/2 (extracellular signal-regulated kinases) signalling and activation of Akt (serine/threonine protein kinase) with consequent inhibition of GSK3β.