Miracle-dz/UniFAR-FTUs huggingface dataset:
Title : Variation in the circle of Willis in a Sri Lankan Population

Background: The variations of the circle of Willis (CW) are clinically important as patients with efficient effective collateral circulations have a lower risk of transient ischemic attack and stroke than those with ineffective collaterals. The aim of the present cadaveric study was to investigate the anatomical variations of the CW and to compare the frequency of occurrence of the different variations with previous autopsy studies as variations in the anatomy of the CW as a whole have not been studied in the Indian subcontinent. Methods: The external diameter of all the arteries forming the CW in 225 normal Sri Lankan adult cadaver brains was measured using a calibrated grid to determine the occurrence of prevalence in the variation in CW. Pearson Brown ranked correlation (ρ) Chisquared tests and a correspondence analysis were performed to study the anatomical variations in the CW across the 6 studies of diverse ethnic populations. Results: We report 15 types of variations of CW out of 28 22 types previously described and one additional type: hypoplastic precommunicating part of the anterior cerebral arteries (A1) and contralateral posterior communicating arteries (PcoA) 5(2.2%). A global chisquared test was used to compare across all 6 studies and pairwise chisquared tests were used to test for differences between each pair of studies; all comparisons were statistically significant (p=0.0000) indicating differences among the studies. A subsequent correspondence analysis revealed a marked difference between the
Comprehensive Analysis of Circulating microRNA Specific to the Liver, Heart, and Skeletal Muscle of Cynomolgus Monkeys

Circulating microRNAs (miRNAs) could represent sensitive and specific biomarkers for tissue injury. However, their utility as biomarkers in nonclinical toxicological studies using nonhuman primates is limited by a lack of information on their organ specificity and circulating levels under resting condition of the animals. Herein, liver, heart, and skeletal muscle-specific expression patterns of miRNAs were determined in 27 tissues/organs from male and female monkeys (n =2/sex) by next-generation sequencing (NGS) analysis. This analysis revealed organ-specific miRNAs in the liver (miR-122), heart (miR-208a and miR-499a), and skeletal muscle (miR-206). Next, plasma was collected from conscious-naive male and female cynomolgus monkeys (n = 25/sex) to better understand the expressions of organ-specific circulating miRNAs. The absolute values of circulating miRNAs were quantified using a Taqman microRNA assay. MiR-1, miR-133a, and miR-208b showed preferential expression in the heart and skeletal muscles, whereas miR-192 was abundant in the liver, stomach, small intestine, and kidney. These miRNAs had identical sequences to their human counterparts. Six organ-specific miRNAs (miR-1, miR-122, miR-133a, miR-192, miR-206, and miR-499a) could be evaluated quantitatively by quantitative real-time reverse transcription polymerase chain reaction with or without preamplification. No significant sex differences were noted for these circulating miRNAs. For their circulation levels, miR-133a showed more than 900-fold interindividual variation, whereas miR-122 showed only a 20-fold variation. In conclusion, we profiled circulating organ-specific miRNAs for the liver, heart, and skeletal muscle of cynomolgus monkeys.
Overexpression of LncRNA HOTAIR is Associated with Poor Prognosis in Thyroid Carcinoma: A Study Based on TCGA and GEO Data

Abstract The role of long non-coding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) in thyroid carcinoma (TC) remains unclear. The current study was aimed to assess the clinical value of HOTAIR expression levels in TC based on publically available data and to evaluate its potential signaling pathways. The expression data of HOTAIR and clinical information concerning TC were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), respectively. Furthermore, 3 online biological databases, Starbase, Cbioportal, and Multi Experiment Matrix, were used to identify HOTAIR-related genes in TC. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Panther pathway analyses were then undertaken to study the most enriched signaling pathways in TC (EASE score<0.1, Bonferroni<0.05). The TCGA results demonstrated that the expression level of HOTAIR in TC tissues was significantly increased compared with non-cancerous tissues (p<0.001). HOTAIR over-expression was significantly associated with poor survival in TC patients (p=0.03). Meta-analyses of GEO datasets revealed a trend consistent with the above results on HOTAIR expression levels in TC (SMD=0.23; 95%CI, 0.00–0.45; p=0.047). Finally, the results of functional analysis for HOTAIR-related genes indicated that HOTAIR might participate in tumorigenesis via the Wnt signaling pathway. In conclusion, our study demonstrates that HOTAIR may be involved in thyroid carcinogenesis, and the over-expression of HOTAIR could act as a biomarker associated with a poor outcome in TC patients. Moreover, the Wnt signaling pathway may be the key pathway regulated by HOTAIR in TC.
Comparing the Vancouver Scar Scale With the Cutometer in the Assessment of Donor Site Wounds Treated With Various Dressings in a Randomized Trial

Cutaneous scarring observed in wounds is, to a significant degree, dependent upon the time it takes for the wounds to heal. Various topical dressings are proposed to influence healing time in donor sites. In this prospective randomized study, we examined the effect of Vaseline gauze (VD; Branolind, Paul Hartmann AG, Germany), Biobrane® (BD; Bertek Pharmaceuticals, Inc., Morgantown, WV), an occlusive film dressing Barrier Flex (OD; Moelnlycke Health Care GmbH, Germany), and an equine collagen foil, Tissu Foil E® (CD; Baxter, Heidelberg, Germany), on re-epithelialization and scarring in standardized donor site wounds. At 6 months after surgery, donor site scars and normal uninjured mirror sided skin were evaluated in 33 patients using both the Vancouver Scar Scale (VSS) and the cutometer SEM 575 (Courage and Khazaka). The median healing time for OD was 14 days, BD 16 days, CD 19 days, and VD 19 days. The single parameter pliability of the VSS was not significantly different from uninjured skin when all donor site scars were pooled. No difference was found between the four groups. Viscoelastic analysis of all pooled patient data showed a significant difference for Uf (total deformation), Ua (total recovery), Ur (immediate retraction), Ue (immediate distension), Ur/Ue, and Ur/Uf, indicating that donor sites significantly differed from normal uninjured skin. No significant correlation between objective viscoelastic measurements and the subjective pliability assessment of the VSS was found. Viscoelastic differences were greatest in the VD and BD groups. Viscolelastic differences did not significantly correlate with healing time. Various wound dressings had minimal yet significant influence on healing time and scarring. In contrast to the VSS, viscoelastic measurements of skin pliability can objectify scarring when few differences are anticipated.
Vitamin B-12 and homocysteine status in a folate-replete population : results from the Canadian Health Measures Survey 1 – 3

Background: Vitamin B-12 is an important cofactor required for nucleotide and amino acid metabolism. Vitamin B-12 deficiency causes anemia and neurologic abnormalities—a cause for concern for the elderly, who are at increased risk of vitamin B-12 malabsorption. Vitamin B-12 deficiency is also associated with an increased risk of neural tube defects and hyperhomocysteinemia. The metabolism of vitamin B-12 and folate is interdependent, which makes it of public health interest to monitor biomarkers of vitamin B-12, folate, and homocysteine in a folic acid–fortified
Uromodulin p.Cys147Trp mutation drives kidney disease by activating ER stress and apoptosis

Uromodulin-associated kidney disease (UAKD) is caused by mutations in the uromodulin (UMOD) gene that result in a misfolded form of UMOD protein, which is normally secreted by nephrons. In UAKD patients, mutant UMOD is poorly secreted and accumulates in the ER of distal kidney epithelium, but its role in disease progression is largely unknown. Here, we modeled UMOD accumulation in mice by expressing the murine equivalent of the human UMOD p.Cys148Trp point mutation (UmodC147W/+ mice). Like affected humans, these UmodC147W/+ mice developed spontaneous and progressive kidney disease with organ failure over 24 weeks. Analysis of diseased kidneys and purified UMOD-producing cells revealed early activation of the PKR-like ER kinase/activating transcription factor 4 (PERK/ATF4) ER stress pathway, innate immune mediators, and increased apoptotic signaling, including caspase-3 activation. Unexpectedly, we also detected autophagy deficiency. Human cells expressing UMOD p.Cys147Trp recapitulated the findings in UmodC147W/+ mice, and autophagy activation with mTOR inhibitors stimulated the intracellular removal of aggregated mutant UMOD. Human cells producing mutant UMOD were susceptible to TNF-&agr;– and TRAIL-mediated apoptosis due to increased expression of the ER stress mediator tribbles-3. Blocking TNF-&agr; in vivo with the soluble recombinant fusion protein TNFR:Fc slowed disease progression in UmodC147W/+ mice by reducing active caspase-3, thereby preventing tubule cell death and loss of epithelial function. These findings reveal a targetable mechanism for disease processes involved in UAKD.
The Effect of Vitamin D Supplementation on Bone Metabolic Markers in Chronic Kidney Disease

Use of active forms of vitamin D is advocated in patients with chronic kidney disease (CKD) for treatment of mineral bone disease because of the presumption that native forms of vitamin D would not undergo significant activation to calcitriol, the most active biological form of vitamin D. We present secondary analysis looking at bone turnover in subjects who completed the randomized, double blind, placebo‐controlled trial investigating the effect of cholecalciferol supplementation on vascular function in nondiabetic CKD stage G3G4 and vitamin D ≤20 ng/mL (Clinical Trials Registry of India: CTRI/2013/05/003648). Patients were randomized (1:1) to receive either two directly observed oral doses of 300,000 IU of cholecalciferol or matching placebo at baseline and 8 weeks. Of the 120 subjects enrolled, 58 in the cholecalciferol group and 59 in the placebo group completed the study. At 16 weeks, the serum 25(OH)D and 1,25(OH)2D levels increased in the cholecalciferol group but not in the placebo group (between‐group difference in mean change: 23.40 ng/mL; 95% CI, 19.76 to 27.06; p < 0.001, and 14.98 pg/mL; 95% CI, 4.48 to 27.18; p = 0.007, respectively). Intact parathyroid hormone (iPTH) decreased in the cholecalciferol group (between‐group difference in mean change –100.73 pg/mL (95% CI, –150.50 to –50.95; p < 0.001). Serum total and bone‐specific alkaline phosphatase (SAP, BAP) and serum C‐terminal cross‐linked collagen type I telopeptides (CTX‐1) were significantly reduced in cholecalciferol group (between group difference for change in mean: –20.25 U/L; 95% CI, –35.14 to –5.38 U/L; p = 0.008 for SAP; –12.54 U/L; 95% CI, –22.09 to –2.98 U/L; p = 0.013 for BAP; and –0.21 ng/mL; 95% CI, –0.38 to –0.05 ng/mL; p = 0.05 for CTX‐1). Correlation analysis showed significant correlation of Δ25(OH)D with ΔiPTH (r = –0.409, p < 0.0001), Δ1,25(OH)2D (r = 0.305, p = 0.001), ΔSAP (r = –0.301, p = 0.002), ΔBAP (r = –0.264, p = 0.004), and ΔCTX‐1 (r = –0.210, p = 0.0230). Cholecalciferol supplementation corrects vitamin D deficiency and is effective in lowering serum intact parathyroid hormone and bone turnover markers in early stages of CKD. © 2017 American Society for Bone and Mineral Research.
TRIM37, a novel E3 ligase for PEX5-mediated peroxisomal matrix protein import

Most proteins destined for the peroxisomal matrix depend on the peroxisomal targeting signals (PTSs), which require the PTS receptor PEX5, whose deficiency causes fatal human peroxisomal biogenesis disorders (PBDs). TRIM37 gene mutations cause muscle–liver–brain–eye (mulibrey) nanism. We found that TRIM37 localizes in peroxisomal membranes and ubiquitylates PEX5 at K464 by interacting with its C-terminal 51 amino acids (CT51), which is required for PTS protein import. PEX5 mutations (K464A or &Dgr;CT51), or TRIM37 depletion or mutation, reduce PEX5 abundance by promoting its proteasomal degradation, thereby impairing its functions in cargo binding and PTS protein import in human cells. TRIM37 or PEX5 depletion induces apoptosis and enhances sensitivity to oxidative stress, underscoring the cellular requirement for functional peroxisomes. Therefore, TRIM37-mediated ubiquitylation stabilizes PEX5 and promotes peroxisomal matrix protein import, suggesting that mulibrey nanism is a new PBD.
Renal biochemical and histopathological alterations of diabetic rats under treatment with hydro alcoholic Morus nigra extrac

Introduction: Morus nigra fruit is known to have antioxidant effects and used to control the blood sugar level in traditional medicine. Objectives: This study was conducted to investigate the biochemical and histopathological changes in the serum and kidneys of diabetic rats treated with hydroalcoholic M. nigra extract. Materials and Methods: In this study, 60 male Wistar rats were divided into five groups of 12 each. After induction of diabetes with alloxan, the diabetic rats were treated with hydroalcoholic extract of M. nigra at different concentrations. Then, the animals were anesthetized and the serum levels of glucose, creatinine, and urea as well as kidney tissue catalase level measured. The kidney tissue was also histopathologically examined. Results: Milder glomerular damage was seen in the group treated with 800 mg/kg of the M. nigra extract compared with diabetic and positive controls, and no difference in the expansion of mesenchymal tissue into renal glomerular vessels observed between the group treated with 800 mg/kg of M. nigra extract and diabetic and positive controls. Furthermore, creatinine levels were significantly higher and urea levels significantly lower in the group treated with 800 mg/kg of M. nigra extract than healthy and positive control groups (P<0.05). Conclusion: Administration of M. nigra extract at 800 mg/kg can prevent kidney tissue damage in diabetic rats and this fruit seems to be beneficial to patients with diabetes.
A Successful Pharmacist-Based Quality Initiative to Reduce Inappropriate Stress Ulcer Prophylaxis Use in an Academic Medical Intensive Care Unit

Stress ulcer prophylaxis (SUP) is often inappropriately utilized, particularly in critically ill patients. The objective of this study is to find an effective way of reducing inappropriate SUP use in an academic medical intensive care unit (ICU). Medical ICU patients receiving SUP were identified over a 1-month period, and their charts were reviewed to determine whether American Society of Health-System Pharmacists guidelines were followed. Inappropriate usage was calculated as inappropriate patient-days and converted to incidence per 100 patient-days. Two interventions were implemented: (1) Pharmacists reviewed indications for SUP on each patient during daily team rounds and daily medication reconciliation and (2) residents rotating on ICU services were educated on a bimonthly basis. Postintervention data were obtained in a similar fashion. Prior to intervention, the incidence of inappropriate SUP usage was calculated to be 26.75 per 100 patient-days (n = 1099 total patient-days). Total cost attributable to the inappropriate use was $2433. Post intervention, we were able to decrease the inappropriate incidence of SUP usage to 7.14 per 100 patient-days (n = 1149 total patient-days). In addition, total cost of inappropriate use was reduced to $239.80. Our study highlights an effective multidisciplinary approach to reduce the inappropriate use of SUP in an academic medical ICU. We were able to reduce the incidence of inappropriate use of SUP by 73.31% (P < .001). Furthermore, we were able to decrease the costs by approximately $2200/month.
Reliability of wireless monitoring using a wearable patch sensor in high-risk surgical patients at a step-down unit in the Netherlands: a clinical validation study

Background and objectives Intermittent vital signs measurements are the current standard on hospital wards, typically recorded once every 8 hours. Early signs of deterioration may therefore be missed. Recent innovations have resulted in ‘wearable’ sensors, which may capture patient deterioration at an earlier stage. The objective of this study was to determine whether a wireless ‘patch’ sensor is able to reliably measure respiratory and heart rate continuously in high-risk surgical patients. The secondary objective was to explore the potential of the wireless sensor to serve as a safety monitor. Design In an observational methods comparisons study, patients were measured with both the wireless sensor and bedside routine standard for at least 24 hours. Setting University teaching hospital, single centre. Participants Twenty-five postoperative surgical patients admitted to a step-down unit. Outcome measures Primary outcome measures were limits of agreement and bias of heart rate and respiratory rate. Secondary outcome measures were sensor reliability, defined as time until first occurrence of data loss. Results 1568 hours of vital signs data were analysed. Bias and 95% limits of agreement for heart rate were −1.1 (−8.8 to 6.5) beats per minute. For respiration rate, bias was −2.3 breaths per minute with wide limits of agreement (−15.8 to 11.2 breaths per minute). Median filtering over a 15 min period improved limits of agreement of both respiration and heart rate. 63% of the measurements were performed without data loss greater than 2 min. Overall data loss was limited (6% of time). Conclusions The wireless sensor is capable of accurately measuring heart rate, but accuracy for respiratory rate was outside acceptable limits. Remote monitoring has the potential to contribute to early recognition of physiological decline in high-risk patients. Future studies should focus on the ability to detect patient deterioration on low care environments and at home after discharge.
Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development

Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome‐wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing‐1–like (DOT1L). We have been studying thyroid hormone (T3)‐dependent amphibian metamorphosis in two highly related species, the pseudo‐tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study. We previously showed that H3K79 methylation levels are induced at T3 target genes during natural and T3‐induced metamorphosis and that Dot1L is itself a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in turn functions as a T3 receptor (TR) coactivator to promote vertebrate development. We show here that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3. Furthermore, making use of the ability to carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we demonstrate that endogenous Dot1L is critical for T3‐induced activation of endogenous TR target genes while transgenic Dot1L enhances endogenous TR function in premetamorphic tadpoles in the presence of T3. Our studies thus for the first time provide complementary gain‐ and loss‐of functional evidence in vivo for a cofactor, Dot1L, in gene activation by TR during vertebrate development. —Wen, L. , Fu, L. , Shi, Y. ‐B. Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development. FASEB J. 31, 4821–4831 (2017). www.fasebj. org
An exploratory study of the experience of fibromyalgia diagnosis in South Africa

Within the conceptual framework of ‘medically-ill-defined’ conditions, this article focuses on the experiences of ‘diagnosis’ through a narrative analysis of fibromyalgia (a chronic musculoskeletal pain disorder) in South Africa. In-depth interviews were used to collect narratives from 15 participants. The findings show how the contested and confusing experience of fibromyalgia diagnosis can be understood, by viewing the interactions that patients have with their practitioners, families, peers and colleagues. The currency of fibromyalgia as a diagnosis and the inequalities present in the South African health care system characterise the experiences of symptom recognition, diagnosis and treatment. The analysis reveals how those living with fibromyalgia search for diagnosis, and struggle to maintain legitimacy for their experience in the complex constellation of porous symptoms that appear infrequently. The findings of this study confirm the existing evidence that shows fibromyalgia to be a challenging illness experience, which is attributed to the lack of clarity and legitimacy, and high contestation that surrounds the condition. Additionally, this study presents the ways that limited access to diagnosis and treatment for fibromyalgia in the South African context shapes this specific illness experience, and the value of using narrative approaches to gain insight into how people live with hidden and poorly understood conditions in this environment.
Peak effects in stable linear difference equations

ABSTRACT We consider asymptotically stable scalar difference equations with unit-norm initial conditions. First, it is shown that the solution may happen to deviate far away from the equilibrium point at finite time instants prior to converging to zero. Second, for a number of root distributions and initial conditions, exact values of deviations or lower bounds are provided. Several specific difference equations known from the literature are also analysed and estimates of deviations are proposed. Third, we consider difference equations with non-random noise (ie bounded-noise autoregression) and provide upper bounds on the solutions. Possible generalizations, eg to the vector case are discussed and directions for future research are outlined.
IRRITABLE MOOD IN ADULT MAJOR DEPRESSIVE DISORDER: RESULTS FROM THE WORLD MENTAL HEALTH SURVEYS

Although irritability is a core symptom of DSM‐IV major depressive disorder (MDD) for youth but not adults, clinical studies find comparable rates of irritability between nonbipolar depressed adults and youth. Including irritability as a core symptom of adult MDD would allow detection of depression‐equivalent syndromes with primary irritability hypothesized to be more common among males than females. We carried out a preliminary examination of this issue using cross‐national community‐based survey data from 21 countries in the World Mental Health (WMH) Surveys (n = 110,729).