Miracle-dz/UniFAR-FTUs huggingface dataset:
Systematic identification of gene family regulators in mouse and human embryonic stem cells

Pluripotent self-renewing embryonic stem cells (ESCs) have been the focus of a growing number of high-throughput experiments, revealing the genome-wide locations of hundreds of transcription factors and histone modifications. While most of these datasets were used in a specific context, all datasets combined offer a comprehensive view of chromatin characteristics and regulatory elements that govern cell states. Here, using hundreds of datasets in ESCs, we generated colocalization maps of chromatin proteins and modifications, and built a discovery pipeline for regulatory proteins of gene families. By comparing genome-wide binding data with over-expression and knockdown analysis of hundreds of genes, we discovered that the pluripotency-related factor NR5A2 separates mitochondrial from cytosolic ribosomal genes, regulating their expression. We further show that genes with a common chromatin profile are enriched for distinct Gene Ontology (GO) categories. Our approach can be generalized to reveal common regulators of any gene group; discover novel gene families, and identify common genomic elements based on shared chromatin features.
Deficiency of tPA Exacerbates White Matter Damage, Neuroinflammation, Glymphatic Dysfunction and Cognitive Dysfunction in Aging Mice

Tissue plasminogen activator (tPA) is a serine protease primarily involved in mediating thrombus breakdown and regulating catabolism of amyloid-beta (Aβ). The aim of this study is to investigate age-dependent decline of endogenous tPA and the effects of tPA decline on glymphatic function and cognitive outcome in mice. Male, young (3m), adult (6m) and middle-aged (12m) C57/BL6 (wild type) and tPA knockout (tPA-/-) mice were subject to a battery of cognitive tests and white matter (WM) integrity, neuroinflammation, and glymphatic function were evaluated. Adult WT mice exhibit significantly decreased brain tPA level compared to young WT mice and middle-aged WT mice have significantly lower brain tPA levels than young and adult WT mice. Middle-aged WT mice exhibit significant neuroinflammation, reduced WM integrity and increased thrombin deposition compared to young and adult mice, and increased blood brain barrier (BBB) permeability and reduced cognitive ability compared to young WT mice. In comparison to adult WT mice, adult tPA-/- mice exhibit significant BBB leakage, decreased dendritic spine density, increased thrombin deposition, neuroinflammation, and impaired functioning of the glymphatic system. Compared to age-matched WT mice, adult and middle-aged tPA-/- mice exhibit significantly increased D-Dimer expression and decreased perivascular Aquaporin-4 expression. Compared to age-matched WT mice, young, adult and middle-aged tPA-/- mice exhibit significant cognitive impairment, axonal damage, and increased deposition of amyloid precursor protein (APP), Aβ, and fibrin. Endogenous tPA may play an important role in contributing to aging induced cognitive decline, axonal/WM damage, BBB disruption and glymphatic dysfunction in the brain.
Soil-transmitted helminth infections, associated factors and nutritional status in an estate community in Sri Lanka

Objectives: To determine the prevalence, intensity, and risk factors associated with soil transmitted helminth (STH) infections and to explore the association between STH infections and nutritional status of an estate community. Methods: A cross-sectional study was conducted in Hanthana Tea Estate (HTE) in Kandy, Sri Lanka, from September 2013 to November 2014. Demographic data were obtained using an interviewer-administrated structured questionnaire. Haemoglobin and serum albumin concentrations were measured in children. Faecal samples were analyzed by direct smears in saline and iodine and Kato-Katz technique using single-stool samples. Anthropometric measurements were obtained to calculate weight-for-age (WAZ), height-for-age (HAZ), and body-mass-index-for-age (BAZ) to evaluate underweight, stunting and wasting, respectively. Results: A total of 233 children (50% female, aged between 1 and 12 years, mean age 6.2±3.4) and 98 parents (93% female, aged between 20 and 52 years, mean age 33±6.2 years) participated in this study. The prevalence of STH infections in children and adults were 27.4% and 14.3% respectively. Ascaris lumbricoides was found in children and adult populations predominantly (26.6% and 14.3% respectively) followed by Trichuris trichiura (0.8% and 1%). Of the infected group, 57.8% of children and 92.8% of adults had a light infection. Moderate infection was found in 40.6% of the children, and 7.2% of the adults. Only one child had a heavy egg count (≥ 50000). The prevalence of STH infections was significantly higher among children than adults (p = 0.014). Not hand washing before a meal (p = 0.002) and after defecation (p Conclusions: Prevalence of STH infections was notably high in both children (27.4%) and their parents (14.3%), indicating a high level of morbidity among the study population. Therefore, a coordinated control and prevention programme considering the diverse socio-demographic characteristics of estate communities is needed to eliminate STH infections in the study population.
Identification of the role of plasma membrane calcium ATPase isoform 4 (PMCA4) in modulating cardiac hypertrophy using a novel small molecule inhibitor

Cardiac hypertrophy and heart failure are affecting almost one million people in the UK alone. The available therapies of cardiac hypertrophy are for symptomatic treatment. Recently attention has been moved towards identification of novel drugs which intervene with signalling pathways involved in hypertrophy. To achieve this goal it was important to understand the role of genes involved in the development of cardiac hypertrophy. One of such genes is plasma membrane calcium ATPase isoform 4 (PMCA4). Although several studies which used genetically modified animal models suggested the involvement of PMCA4 during the development of cardiac hypertrophy, the actual role of PMCA4 is still unclear. In this study, we will clarify the role of PMCA4 during the development of cardiac hypertrophy using a novel PMCA4 specific inhibitor. Until now there is no known PMCA4 specific inhibitor so a library of 1280 medically optimised compounds was screened using a novel in vitro assay which measures the ATPase activity of PMCA4. The compound aurintricarboxylic acid (ATA) was identified, which inhibited PMCA4 ATPase activity with higher affinity (IC50= 100 nM) compared with related ATPases. In isolated neonatal rat cardiomyocytes, ATA showed dose dependent inhibition of phenylephrine-induced hypertrophy. In vivo studies showed that ATA (5mg/kg body weight/day IP) significantly reduced the development of pressure-overload induced hypertrophy in wild type mice following two weeks transverse aortic constriction (TAC). Echocardiography and haemodynamic analyses showed that ATA treatment significantly reduced the abnormal left ventricular remodelling after TAC compared with vehicle treatment. ATA treated TAC mice showed a significant reduction in the enlargement of heart weight/tibia length ratio as well as cardiomyocyte cross sectional surface area compared with vehicle treated TAC mice. A significant reduction in the expression of the hypertrophic markers ANP and BNP and, importantly, in the percentage of fibrosis was observed in ATA treated TAC mice compared with vehicle treated TAC mice. In addition, ATA treatment significantly reversed the already established pressure overload induced hypertrophy following three weeks TAC. ATA treatment to TAC mice led to a significant reduction in the expression of the bona fide calcineurin target MCIP1 and a reduction in NFAT phosphorylation level in vivo and NFAT transcriptional activity in vitro. ATA did not show a direct inhibition to the active form of calcineurin nor to the phosphatase activity of full length calcineurin.In conclusion, we have identified ATA as a novel and specific inhibitor to PMCA4 ATPase activity. Pharmacological inhibition of PMCA4 significantly reduces the hypertrophic response to pressure overload likely through inhibition of calcineurin/NFAT signalling.
Family in Rehabilitation, Empowering Carers for Improved Malnutrition Outcomes: Protocol for the FREER Pilot Study

Background Interventions to improve the nutritional status of older adults and the integration of formal and family care systems are critical research areas to improve the independence and health of aging communities and are particularly relevant in the rehabilitation setting. Objective The primary outcome aimed to determine if the FREER (Family in Rehabilitation: EmpowERing Carers for improved malnutrition outcomes) intervention in malnourished older adults during and postrehabilitation improve nutritional status, physical function, quality of life, service satisfaction, and hospital and aged care admission rates up to 3 months postdischarge, compared with usual care. Secondary outcomes evaluated include family carer burden, carer services satisfaction, and patient and carer experiences. This pilot study will also assess feasibility and intervention fidelity to inform a larger randomized controlled trial. Methods This protocol is for a mixed-methods two-arm historically-controlled prospective pilot study intervention. The historical control group has 30 participants, and the pilot intervention group aims to recruit 30 patient-carer pairs. The FREER intervention delivers nutrition counseling during rehabilitation, 3 months of postdischarge telehealth follow-up, and provides supportive resources using a novel model of patient-centered and carer-centered nutrition care. The primary outcome is nutritional status measured by the Scored Patient-Generated Subjective Global Assessment Score. Qualitative outcomes such as experiences and perceptions of value will be measured using semistructured interviews followed by thematic analysis. The process evaluation addresses intervention fidelity and feasibility. Results Recruitment commenced on July 4, 2018, and is ongoing with eight patient-carer pairs recruited at the time of manuscript submission. Conclusions This research will inform a larger randomized controlled trial, with potential for translation to health service policies and new models of dietetic care to support the optimization of nutritional status across a continuum of nutrition care from rehabilitation to home. Trial Registration Australian New Zealand Clinical Trials Registry Number (ACTRN) 12618000338268; https://www.anzctr. org.au/Trial/Registration/TrialReview.aspx? id=374608&isReview=true (Archived by WebCite at http://www.webcitation.org/74gtZplU2). International Registered Report Identifier (IRRID) DERR1-10.2196/12647
Comparison of Maternal Stress Response to Midazolam/Fentanyl and Propofol During Cesarean Delivery Under Spinal Anesthesia: A Double-Blinded Randomized Controlled Trial

Background: This research evaluated the effects of propofol and midazolam/fentanyl on maternal blood pressure, heart rate, recall, and full satisfaction with spinal anesthesia. A double-blinded randomized controlled trial was designed. Methods: The sample size was calculated as 100 patients (a type I error of 5% and statistical power of 80%) who were scheduled for elective cesarean delivery under spinal anesthesia. These patients were randomized into two equal groups by block randomization used for allocation sequence: midazolam/fentanyl and propofol groups. We measured the maternal heart rate (HR), systolic, and diastolic blood pressure (SBP and DBP) before induction, every three minutes in the operating room, and every five minutes until discharge from the recovery room. Data were analyzed by SPSS 18.0 and P value < 0.05 was considered as the significance level. Results: 100 women (mean age: 29.7 ± 5.1 years and gestational age: 37.2 ± 1.2 weeks) were enrolled. The SBP and HR decreased during the study in both groups, but it was significant only in the midazolam/fentanyl group (SBP: from 120.0 ± 10.3 to 113.9 ± 4.8, P = 0.025; and HR: from 75.0 ± 7.6 to 65.3 ± 5.5, P = 0.046). DBP reduced in both groups, but it was only significant in the propofol group (from 68.5 ± 7.2 to 56.9 ± 2.1, P = 0.039). The maternal recall of the birth time, child weight, and full satisfaction were significantly better in the propofol group than in the midazolam/fentanyl group (P = 0.046, P = 0.009, and P = 0.039, respectively). Conclusions: Propofol and midazolam/fentanyl could be useful in cesarean sections under spinal anesthesia thought propofol may induce more effective sedation with higher satisfaction. Accordingly, the propofol use during caesarian sections under spinal anesthesia is suggested due to its anti-stress effects, good delivery recall, and good sedation satisfaction.
Comparison of ultrasound-guided serratus plane block and thoracic paravertebral block for postoperative analgesia after thoracotomy: a randomized controlled trial

Background Post-thoracotomy pain can be severe and difficult to control. Paravertebral block (PVB) has been proven to be effective in controlling post-thoracotomy pain; however, it has its own set of complications. Ultrasound-guided serratus plane block (SPB) is a newly described field block that may provide thoracic wall analgesia. Objective This prospective randomized controlled study was carried out to compare the analgesic effects of PVB and SPB on post-thoracotomy pain. Patients and methods The study was done on 60 adult patients aged 18–65 years undergoing thoracotomy for pulmonary resection. The patients were randomly allocated to receive either thoracic PVB or SPB guided by ultrasound before induction of general anesthesia. The primary outcome was the visual analogue scale, which was recorded on arrival to the ICU and then at 1, 2, 4, 8, 12, 18, and 24 h postoperatively both at rest and during coughing. The secondary outcomes were time to perform the block, onset of sensory block, number of blocked dermatomes, block success rate, total postoperative morphine consumption, and any complications related to the regional block. Results The time to perform the block was significantly shorter in SPB than in PVB (3.76±1.1 vs. 6.14±1.6 min, P<0.05). The onset of complete sensory block was significantly faster with SPB than with PVB (14.3±2.8 vs. 17.6±3.5 min, P<0.05). The visual analogue scale was also comparable between the two blocks at all measuring times except at 12 and 18 h postoperatively, where it was significantly higher with SPB than with PVB during coughing (P<0.05). The total postoperative morphine consumption was significantly lower in the PVB group than in the SPB group (13.2±2.6 vs. 18.4±1.8 mg, P<0.05). There was no significant difference between the two blocks regarding complications. Conclusion SPB had a shorter time to perform and a faster onset of action than thoracic PVB and provided adequate analgesia in the early postoperative period; however, postoperative morphine consumption was higher in patients who received SPB.
Peningkatan kualitas nutritif putak melalui fermentasi campuran Trichoderma reesei dan Aspergillus niger Sebagai pakan ruminansia

MARITJE A HILAKORE. Improving Putak Nutritive Quality Using Mixed Culture Trichoderma reesei and Aspergillus niger As Ruminant Feed. Under the supervisions of SURYAHADI, KOMANG G WIRYAWAN, and DJUMALI MANGUNWIDJAJA Putak is a local feed in East Timor, East Nusa Tenggara Province. It is obtained from the pit of palm tree which is called gewang tree (Corypha elata robx). Putak contains high carbohydrate and fiber but low in protein. The evaluation of putak potency as a feed source and co-cultured of Trichoderma reesei and Aspergillus niger as an inoculants to improve the nutritive quality of the putak for use in goats diets were carried out in a series of 3 experiments. The first experiment was conducted to determine the inoculum optimum level and incubation time of each microbe on nutrient composition. Aspergillus niger contained 2.4 x 10 7 g -1 cfu with inoculum levels were 0.5, 1.0, 1.5 and 2.0% (w/w), whereas Trichoderma reesei contained 1.98 x 10 5 g -1 cfu and 5.0, 7.5, 10% (w/w) inoculum levels. Incubation time were 2, 3 and 4 days. This study showed that the best content of crude protein and true protein was at three days incubation and the inoculum level was 1.5% (w/w) for A.niger, while, T.reesei at four days and 7.5% (w/w) inoculum. Second experiment conducted to determine delay time to combine both microbes in mixed culture on nutrient composition and rumen fermentability. The best result of this study was when A.niger was inoculated two days after T.reesei, where crude protein and true protein was higher and crude fiber was lower than monoculture. Level of volatile fatty acids (VFA) and ammonia ( N-NH3) were suitable to support microbial production. The last experiment to test goats response to diets containing putak fermentation and fed on rice straw based ration on daily gain, ration and rice straw consumption, N retention and fiber digestibility. The result showed that using 40% putak fermentation in goat diets give the best response to all variables measured.
Prevention of catheter-associated UTI

We surveyed existing guidelines and literature on the prevention of catheter-associated urinary tract infection (CAUTI). Key principles include avoiding unnecessary urinary catheterization, maintaining a closed aseptic drainage system and minimizing duration of catheterization. Institutional guidelines on appropriate indications for catheterization, reminder and stop-order systems, and policies on restricted urinary catheterization and nurse-directed catheter removal are effective and recommended. Urinary catheter care bundles and infection control interventions described in various guidelines are summarized and should be considered. While routine use of anti-infective coated catheters are not recommended, anti-infective-impregnated catheters may reduce risks of CAUTI for short term catheterization, and may be considered if shown to be cost effective. Evidence for the use of routine systemic antibiotic prophylaxis for the prevention of CAUTI is inconsistent and insufficient. Treatment of symptomatic CAUTI should be guided by local uropathogens, susceptibility patterns and urine culture results, and antibiotic should be deescalated to the narrowest spectrum choice where possible. Routine treatment of catheter-associated asymptomatic bacteriuria in not recommended.
The effect of resistance training with and without testosterone injection on plasma levels of nesfatin-1 in adult male rats

Background and Objective : Nesfatin-1 is an effective peptide in the regulation of energy balance. The aim of this research was investigation of the effects of resistance training with and without testosterone injection on plasma levels of nesfatin-1 in adult male rats. Materials and Methods : For this purpose, 40 Wistar rats with a weight range of 205 to 265 g and aged approximately 10 weeks were randomly divided into four groups: control group, testosterone group, resistance training group, and resistance training with testosterone injections group. In testosterone group and resistance training with testosterone injections group, three times per week, 1 mg per kg body weight of testosterone was injected. Resistance training protocol was consisted of 5 sessions per week (for 12 weeks) on a ladder and rats performed 10 repetitions. Results: Findings indicate that levels of nesfatin-1 in resistance training and resistance training with testosterone injection groups were significantly higher compared with control group (P˂0.05) . Also, a significant change in levels of nesfatin-1 in the resistance training group compared with testosterone group (P˂0.05) was observed. In contrast, significant changes of nesfatin-1 in the resistance training with testosterone injections group was not observed compared to testosterone group (P ˃ 0.05). Conclusion: Results of this study support the undeniable benefits of resistance training for the increased nesfatin-1 and exercise can be used to regulate appetite and energy expenditure. Because the present study is the first research about the effects of exercise training with testosterone injections on plasma levels of nesfatin -1, more studies in this field are needed for more accurate conclusions.
ANTIOXIDANT ACTIVITY OF N-SUBSTITUTED İNDOLE 2- AND 3-CARBOXAMIDES

A series of N-substituted indole amide derivatives was tested for in vitro effects on rat liver microsomal NADPH-dependent lipid peroxidation (LP) and superoxide anion (SOD) formation. Vitamin E (a-tocopherol) decreased the LP level by about 63% at 104M concentration. A significant decrease in male liver microsomal LP level was noted for the compounds 1, 8 and 10 at a concentration of 10 4M comparing with a-tocopherol. The inhibition of 0 2( by compounds 8 and 10 were found highly efficient. Both activity results show that these compounds are promising antioxidants.
Rel/NF-?B and I?B factors in oncogenesis

Abstract Rel/NF-κB transcription factors play fundamental roles in the immune system. These structurally-related proteins share common pathways of activation that involve their release from inhibitory IκB factors in response to stimuli. Accumulating evidence also points to a role for Rel and IκB proteins in cellular growth control and oncogenesis. The rearrangement and amplification of genes encoding Rel/ NF-κB and IκB proteins in several human cancers, together with the acute oncogenicity of the retroviral v- rel oncogene in birds and mammals, suggests a correlation between their effects on gene expression and their role in malignancy. This review focuses on the current status of the association of Rel/ NF-κB and IκB proteins with neoplastic cell transformation in vitro and in vivo .
Diagnostic Value of Candida Colonization Index in The Early Diagnosis of Invasive Candidal Infection

Objective: To investigate the diagnostic value of Candida colonization index (CCI) in the early diagnosis of invasive candidal infection in medical mix (medical and surgical intensive care units (ICU). Methods: Mouth, axillae, nasogastric catheter, rectum, and urine culture samples taken from the patients admitted to the reanimation and neurological ICU for 19 months were retrospectively evaluated and CCI were calculated. Results: CCI reached ≥0,5 in the cultures of 29 patients. 29 patients developed candidal infection; 27 (27/29) of them had CCI ≥0,5. 18 patients developed urinary infections, 10 patients developed candidemia, and 1 patient developed wound infection. CCI ≥0,5 was found as the only independent predictor for invasive candidal infection (p<0,001, OR: 701,553, %95 CI; 28,310-17385,22). The positive predictive value, sensitivity, and specifity of CCI for the candidal infection were found to be 93.1% and 96.2%, respectively. Conclusions: We concluded that monitoring for CCI in patients with unknown fever, severe sepsis or septic shock in the medical ICU offers an early diagnosis and intervention to prevent invasive candidal infection. Independently from the other risk factors, CCI may be considered as an effective test for early diagnosis of invasive candidal infection in medical and surgical ICU patients.