Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of Nedd4 haploinsufficiency on insulin sensitivity, adiposity and neuronal behaviors

The neural precursor cell expressed developmentally down-regulated gene 4 (NEDD4) is a HECT-type E3 ubiquitin ligase that has received broad attention in recent years. Many of its reported substrates are active players in metabolism, implying a potential role of NEDD4 itself in metabolic regulation. Since homozygous Nedd4 deletion leads to embryonic or perinatal lethality, we investigated the function of NEDD4 in metabolic regulation in vivo, using Nedd4-haploinsufficient mice in a high fat dietinduced obesity (HFDIO) model. Our studies show that Nedd4-haploinsufficient mice fed a normal diet (ND) exhibited decreased body weight in both genders and proportionally reduced tissue mass compared to their age-matched wild-type littermates. The heterozygotic Nedd4-deficient mice displayed moderate insulin resistance and mild hyperinsulinemia. These findings are consistent with others’ studies in which depletion of Nedd4 in mouse embryonic fibroblasts (MEFs) led to a decline in insulin-like growth factor I (IGF-1) and insulin signaling. Surprisingly, Nedd4-haploinsufficient mice were partially protected against highfat diet (HFD) induced obesity. Total weight gain was decreased by 30% in Nedd4haploinsufficient mice on HFD, which was associated with reduced adiposity, improved insulin sensitivity in white adipose tissue (WAT), alleviated hepatic steatosis and attenuated lipid-induced inflammation. NEDD4 reduction did not affect serum glucose or lipid profile. The energy intake and physical activity were almost indistinguishable between the two groups. We present data indicating that these beneficial effects of Nedd4 haploinsufficiency under conditions promoting obesity or type 2 diabetes (T2D) derive from at least two mechanisms: 1) elevated levels of -agonist induced lipolysis through stimulation of -adrenergic signaling as evidenced by enhanced adrenergic receptor 2-AR) cell surface levels; 2) repressed expression of a key adipogenic regulator, peroxisome proliferator-activated receptor gamma (PPAR ) in Nedd4-haploinsufficient mice in the WAT. Downregulation of NEDD4 in 3T3-L1 preadipocytes impaired the adipogenic response, resulting in decreased PPAR expression. Thus, the reduced adiposity in Nedd4-haploinsufficient mice fed a HFD compared to littermate wild-type mice may be explained at least in part by their increased lipolysis and suppressed adipogenesis. Our data also imply that NEDD4 may have differential functions in modulating insulin signaling under physiological and pathological conditions. In this study, we tested the possible impact of NEDD4 reduction on cognitive function and anxiety behaviors. Preliminary results showed that Nedd4-haploinsufficient mice had impaired learning and memory performance but increased anxiety compared to wild-type littermates. NEDD4 may modulate different behavioral functions by targeting specific substrates for protein degradation in a brain-region-specific manner. Precise substrates that cause the alteration in such behaviors are yet to be determined by future studies.
Human cytomegalovirus seropositivity is associated with decreased survival in glioblastoma patients

Abstract Background Human cytomegalovirus (HCMV) is an oncomodulatory human herpesvirus that has been detected in glioblastoma (GBM) and is associated with worse prognosis in patients with the disease. The effects of HCMV systemic infection on survival in GBM patients, however, are largely unknown. We aimed to determine the association between HCMV serostatus at diagnosis and survival via a retrospective cohort study of GBM patients. Methods Plasma from 188 GBM patients treated at the Ben and Catherine Ivy Center (Seattle, WA) was tested for HCMV serostatus via enzyme-linked immunosorbent assays of anti-HCMV immunoglobulin (Ig)G. HCMV IgG serostatus was analyzed with respect to each patient’s progression-free and overall survival (OS) via log-rank and multivariable Cox regression analysis. Results Ninety-seven of 188 (52%) patients were anti-HCMV IgG seropositive. Median OS was decreased in the IgG+ cohort (404 days) compared to IgG− patients (530 days; P = .0271). Among O6-methylguanine-DNA methyltransferase (MGMT) unmethylated patients (n = 96), median OS was significantly decreased in IgG+ patients (336 days) compared to IgG− patients (510 days; P = .0094). MGMT methylation was associated with improved OS in IgG+ patients versus those who were unmethylated (680 vs 336 days; P = .0096), whereas no such association was observed among IgG− patients. Conclusions In this study, HCMV seropositivity was significantly associated with poorer OS in GBM patients. This finding suggests prior infection with HCMV may play an important role in GBM patient outcomes, and anti-HCMV antibodies may, therefore, prove a valuable prognostic tool in the management of GBM patients.
Treatment of Anestrous in Iraqi Buffaloes using Ovsynch alone or in Combination with CIDR

The aim of this study was to test the efficacy of the Ovsynch alone or in combination with CIDR treated buffaloes on conception rate of anestrous Iraqi buffaloes. The present study was conducted on 50 anestrous buffaloes suffering from postpartum ovarian inactivity. Buffaloes were randomly assigned to three treatment groups. Buffaloes in Treatment 1 (n=20) received on day 0 GnRH 250 μg and a 25 mg of PGF2α on day 7, two days later a second injection of GnRH (250 μg). Buffaloes in Treatment 2 (n=20) injected on day 0 of the experiment, GnRH 250 μg and a CIDR was placed in the anterior vagina. On day 7, they were injected with 25 mg of PGF2α and on the following day (day 8) the CIDR were removed. On day 9 a second dose of GnRH (250 μg) was injected. Treatment 3 a control group (n=10) received no treatments. Results showed that in treatment 1, 7 out of 20 buffaloes received treatment exhibited estrus within 74.8 ± 6.3 after second GnRH administration. The estrus induction rate was 35%. Total number of buffaloes became pregnant was 1 (5%). In treatment 2 75% of the buffaloes received treatment exhibited estrus within 77.8 ± 5.6 h after CIDR removal. Total number of buffaloes became pregnant was 7 (31.8%). Lower (P <0.05) Pregnancy rate was achieved in buffaloes treated with Ovsynch than other buffaloes treated with Ovsynch plus CIDR. Higher rates of estrus induction (75%; P<0.05) and conception rate (7 buffaloes out of 20) were found in buffaloes treated with Ovsynch plus CIDR. In conclusion, our results indicate that the addition of Ovsynch to a progesterone-based CIDR protocol substantially improves the estrus induction and pregnancy rates in postpartum anestrous buffaloes.
miR-205-5p downregulation decreases gemcitabine sensitivity of breast cancer cells via ERp29 upregulation

Breast cancer is the most common cancer in women worldwide, and the incidence and mortality rates are increasing every year. Dysregulation of microRNAs (miRNAs or miRs) is an important step in the initiation and development of breast cancer. Previous studies demonstrated that miR-205-5p is closely associated with occurrence and development of breast cancer; however, underlying mechanisms remain unclear. In the present study, reverse transcription-quantitative polymerase chain reaction assays were used to analyze miR-195-5p and endoplasmic reticulum protein 29 (ERp29) levels in breast cancer and matched normal tissues. Western blot analysis was performed to analyze ERp29 and heat shock protein 27 (HSP27) protein expression levels. Cell viability, flow cytometry and luciferase reporter assay were used to examine cell proliferation, apoptosis and direct miRNA-mRNA binding, respectively. The results revealed that miR-205-5p expression in breast cancer tissues and cell lines was decreased compared with normal tissues and a normal cell line. Overexpression of miR-205-5p significantly augmented cytotoxicity effects of gemcitabine treatment in MDA-MB-231 and BT549 cells. It was observed that miR-205-5p negatively regulated ERp29 expression in breast cancer cells. Dual luciferase assays confirmed that ERp29 was a target of miR-205-5p in breast cancer cells. Additionally, following the established gemcitabine-resistant MDA-MB-231 cells (MDA-MB-231/GEM), ERp29 and HSP27 expression was upregulated and miR-205-5p was downregulated compared with parental cells. Overexpression of miR-205-5p reversed gemcitabine resistance in MDA-MB-231/GEM cells. In conclusion, the present study indicated that miR-205-5p may inhibit gemcitabine resistance in breast cancer cells via inhibition of ERp29 expression.
Domestic violence and its association with pre-term or low birthweight delivery in Vietnam

Objective To examine the association between various types of domestic violence (DV) during pregnancy (emotional violence, physical violence, and sexual violence) and pre-term or low birthweight delivery in women living in Ho Chi Minh city, Vietnam. Methods A cross-sectional study was conducted in ten districts of Ho Chi Minh city during the period of January 1, 2015–July 4, 2016, with 1,099 women aged 18–49 years old who had delivered at least one child within the past 2years and were living in Ho Chi Minh city. Results DV prevalence during pregnancy among women aged 18–49 years in Ho Chi Minh city was 23.4%. Emotional violence accounted for 16.8%; physical violence 7.3%, and sexual violence 12.4%. Results of multivariable logistic regression analysis showed that DV during pregnancy was associated with a 1.44-times increased risk of pre-term or/and low birthweight delivery (POR=1.44, 95% CI=1.04–1.99). Conclusion Domestic violence during pregnancy was associated with increased risk of pre-term/low birthweight delivery in Vietnamese women. These findings suggest the need for DV screening during antenatal care. Once DV is detected, the victims should be provided with counseling services and referred to available local support services so that they are provided with timely intervention.
Changing clinical profile of Dengue infection: A newer perspective in the pediatric population

Abstract Background: Traditionally complications of Dengue infection is limited to vascular and haematological system. The present study describes the changing clinico-epidemiological and laboratory profile of children hospitalized with dengue infection. Methods: Prospective observational study of children hospitalized with a diagnosis of dengue illness from October to December, 2010 at a tertiary care centre in Kolkata. Results: Of 50 children admitted with dengue infection, 24 had dengue fever (DF), 18 dengue hemorrhagic fever (DHF) and 8 had dengue shock syndrome (DSS). The mean age of affected children was 6.25 ± 3.34 years, mostly being males from rural areas. The common clinical manifestations were fever, rash, body ache, hemorrhagic manifestations and oedema. While headache and body ache was commoner among DF cases, rash and hemorrhagic manifestations were significantly more among DHF group. Incidence of altered sensorium, neck rigidity, fulminant hepatitis, and splenomegaly were significantly higher among the DHF/DSS group. 12% case fatality rate was found. Conclusion: Clinical manifestations of dengue seem to be changing. Fever, rash and bodyache are not the only clinical presentations. Encephalopathy, encephalitis, 6th cranial nerve palsy, fulminant hepatic failure, acute acalculous cholecystitis, myocarditis, myelitis, splenomegaly are some unusual but novel presentations of dengue in pediatric population that clinician in endemic area should be aware of though they are not mentioned in conventional guidelines Dengue is no longer restricted to urban areas but has propensity to spread to rural areas also.
Urine lipoarabinomannan (LAM) and antimicrobial usage in seriously-ill HIV-infected patients with sputum smear-negative pulmonary tuberculosis.

Background Based on current WHO guidelines, hospitalized tuberculosis (TB) and HIV co-infected patients with CD4 count <100 cells/mm3 who are urine lipoarabinomannan (LAM) positive should be initiated on TB treatment. This recommendation is conditional, and data are limited in sputum smear-negative patients from TB endemic countries where the LAM test is largely inaccessible. Other potential benefits of LAM, including reduction in antibiotic usage have, hitherto, not been explored. Methods We consecutively enrolled newly-admitted seriously-ill HIV-infected patients (n=187) with suspected TB from three hospitals in KwaZulu-Natal, South Africa. All patients were empirically treated for TB as per the WHO 2007 smear-negative TB algorithm (patients untreated for TB were not recruited). Bio-banked urine, donated prior to anti-TB treatment, was tested for TB-infection using a commercially available LAM-ELISA test. TB sputum and blood cultures were performed. Results Data from 156 patients containing CD4 count, urine-LAM, sputum and blood culture results were analysed. Mean age was 37 years, median CD4-count was 75 cells/mm3 [interquartile range (IQR), 34-169 cells/mm3], 54/156 (34.6%) were sputum culture-positive, 12/54 (22.2%) blood-culture positive, and 53/156 (34.0%) LAM-positive. Thus, LAM sensitivity was 55.6% (30/54). The study design did not allow for calculation of specificity. Urine-LAM positivity was associated with low CD4 count (P=0.002). Ninety-point-six percent (48/53) of LAM-positive patients received antibiotics [15/48 (31.3%), 23/48 (47.9%) and 10/48 (20.8%) received one, two or three different antibiotics respectively], while the duration of antibiotic therapy was more than 5 days in 26 of 46 (56.5%) patients. Conclusions Urine LAM testing in sputum smear-negative severely-ill hospitalized patients with TB-HIV co-infection and advanced immunosuppression, offered an immediate rule-in diagnosis in one-third of empirically treated patients. Moreover, LAM, by providing a rapid alternative diagnosis, could potentially reduce antibiotic overusage in such patients thereby reducing health-care costs and facilitating antibiotic stewardship.
Assessment of complications following use of pneumatic tourniquet for elective orthopedic procedures at National Orthopedic Hospital, Enugu

<p class="abstract"><strong>Background:</strong> A pneumatic tourniquet is a constricting or compressing device with an inflatable cuff used to control venous or arterial circulation to an extremity for a period of time. Tourniquet safety is related to the cuff pressure and duration of application. The objective of this study was to determine the common complications that follow the use of pneumatic tourniquet in elective orthopaedic surgical procedures at National Orthopaedic Hospital Enugu. </p><p class="abstract"><strong>Methods:</strong> This was a prospective study over 18 month period (June 2014 – November 2015) at National Orthopaedic Hospital, Enugu. Following ethical approval and written informed consent, patients who met the inclusion criteria were consecutively recruited. The study was conducted using the ‘intelligent pneumatic tourniquet’<strong><em> </em></strong>with single bladder reusable cylindrical cuff. The cuff pressure was determined in each case by addition of 100mmHg to the baseline systolic BP for the upper limbs and 150 mmHg to the baseline systolic BP for the lower limbs. The data collected included patients’ demographics, cuff pressure, cuff location, tourniquet duration and complication encountered among other parameters. </p><p class="abstract"><strong>Results: </strong>A total of 160 procedures in 152 patients were included and analyzed using SPSS version 20.0. The prevalence rate of 1.9% for nerve palsy, 1.3% for tourniquet pain, 1.9% for surgical site infection and 5.6% for pressure sore were found in the study. No other complication was encountered. </p><p class="abstract"><strong>Conclusions:</strong> From the results of this study, it is concluded that the use of pneumatic tourniquet under the prescribed conditions is associated with low prevalence of complications. </p>
Pathomorphological and immunohisto-chemical findings in a case of extragenital canine transmissible venereal tumour.

An extragenital canine transmissible venereal tumour was described pathomorphologically and immunohistochemically in the nasal sinus of a 7-year-old female German Shepherd dog. The tumour removed from the nasal sinus weighed 45 g and was multilobullary, firm in consistency, with grayishwhite colour. Histopathologically, ovoidor round-shaped neoplastic cells with prominent, clear, large, round to ovoid hyperchromatic nuclei were seen. In general the cells were with a less dense distinct cytoplasm, solid or in cords. Immunohistochemically, positive reactions in tumour cells were detected by p53 protein, vimentin and α1 chymotrypsin antibodies.
Breast lesions cytology and correlation with histopathology

Background: Breast carcinoma is the leading cause of death due to cancer in women. It is difficult to determine whether a lump is benign or malignant from clinical assessment. Fine needle aspiration cytology (FNAC) is a convenient and rapid procedure. Present study was carried out to correlate fine needle aspiration cytology and histopathology of breast lesions. Methods: A study consisting of fine needle aspiration cytology (FNAC) 201 of breast lesions and their histopathological correlation was conducted at tertiary care hospital with medical college in over a period of one years. The diagnostic accuracy of this series was assessed and compared with data obtained from the Indian and international literature. Statistical analysis like sensitivity, specificity, positive predictive value, efficiency, and negative predictive value were carried out. Results: The diagnostic accuracy of this series i.e. sensitivity 88.24%, specificity 100%, positive predictive value 100%, efficiency 95.52%, and negative predictive value 93.2% was compared with similar studies in literature. Conclusions: FNAC is an effective modality for the diagnosis of breast lesions. It is a safe, simple, and cost effective outpatient procedure associated with negligible complications. It helps the clinicians for early diagnosis and specific management thus reducing morbidity and mortality.
Clinical Evaluation of Working Distance in Caucasian and Chinese Adults: A Comparison Study in France and Singapore

ARVO 2007 – Fort Lauderdale Working distance was continuously recorded at 10 Hz by means of a Polhemus Fastrack. Previous studies on French adults1,2 have shown that working distances were significantly different with task and presbyopia but not with ametropia. Moreover, working distance was different between writing/reading Chinese characters and Roman letters3. The aim of the present study was to investigate differences in working distance between Caucasian and Chinese young adults and presbyopes wearing progressive addition lenses (PALs).
A study on clinical profile of patients presenting with adverse drug reaction: a hospital based prospective observational study

Background: The aim of the study was to study the clinical profile of patients presenting with adverse drug reaction.Methods: The study was conducted in the Department of Medicine, IGMC Shimla from 01 July 2015 to 30 June 2016. A total of 129 patients were included in this study. A detailed history was taken followed by examination of patients. The routine investigations were done and special investigations as per need. For analysis patients detail, suspected drugs and the adverse drug reactions caused by them were used.Results: Bleeding from various sites was the most common event (39.5%), followed by symptomatic hypoglycemia 22.5% of events and symptomatic hyponatremia in 16.3% events. Amongst various drug classes anticoagulants were the most commonly involved drug class followed by oral hypoglycaemic agents, diuretics and antiplatelets. Type A was predominant ADR constituting (97.7%) of total ADRs and only (2.3%) of ADRs were of type B. After causality assessment, majority 86 (66.6%) were probable related and large number 127 (98.3%) of ADRs were serious which recovered after hospitalization.Conclusions: Our study revealed that ADRs are frequent and are easily recognized in clinical practice and are mostly preventable. Most ADRs are due to the use of drugs with high toxicity for example, warfarin often results in bleeding. It also shows that careful drug monitoring in hospitals may lead to reduction of many such ADRs, suggesting that some type A, ADRs may be due to inadequate monitoring of therapies and doses. This study will aid the development of interventions to reduce the impact of ADRs in hospital in-patients.
Evaluating ibrutinib in the treatment of symptomatic Waldenstrom’s macroglobulinemia

Abstract Waldenstrom’s macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma with indolent course and prolonged disease course. The first-in-class Bruton’s tyrosine kinase inhibitor, ibrutinib, has shown significant activity and a distinct adverse event profile among both newly diagnosed and relapsed/refractory WM patients. Interestingly, clinical responses to ibrutinib have been shown to be dependent on patients’ MYD88 and CXCR4 mutational status. The recent outcomes of the Phase III iNNOVATE trial showed that the combination of ibrutinib with rituximab resulted in a significantly prolonged progression-free survival compared with rituximab monotherapy, which provides a novel therapeutic option in the clinical practice especially for the rituximab-refractory WM patients. However, the need for continuous drug administration along with the unique toxicity manifestations may render the patient management challenging. Furthermore, our understanding of the underlying resistant mechanisms to ibrutinib is currently being evolved.
Quantitative Association Between Serum/Dietary Magnesium and Cardiovascular Disease/Coronary Heart Disease Risk: A Dose-Response Meta-analysis of Prospective Cohort Studies.

BACKGROUND The quantitative association between serum/dietary magnesium and cardiovascular disease (CVD) remains unclear. We conducted a dose-response meta-analysis to evaluate the quantitative association between serum/dietary magnesium and CVD, including coronary heart disease (CHD). METHODS PubMed, China National Knowledge Infrastructure, and Web of Science were searched for publications. STATA 12.0 was used to analyze data. We used the random-effects model to reduce heterogeneity. RESULTS Eighteen prospective cohort studies with 544,581 participants and 22,658 CVD cases were included. The follow-up duration was 1-28 years. The pooled relative risk (RR) of CVD for the relatively normal versus lowest serum and dietary magnesium level was 0.64 {[95% confidence interval (CI): 0.51-0.80] and 0.90 [95% CI: 0.84-0.96]}. The pooled RR of CHD for the relatively normal versus lowest serum and dietary magnesium level was 0.70 (95% CI: 0.57-0.85) and 0.86 (95% CI: 0.77-0.94). We noted a significant association between increasing serum magnesium levels (per 0.1-mg/dL increase) and risk of CVD (RR: 0.93, 95% CI: 0.88-0.97) and CHD (RR: 0.90, 95% CI: 0.84-0.96) and between dietary magnesium levels (per 100-mg/d increase) and risk of CVD (RR: 0.90, 95% CI: 0.83-0.96) and CHD (RR: 0.92, 95% CI: 0.82-0.98). Serum/dietary Mg level comparisons presented a 7%-10% decrease in CVD/CHD risk. The dose-response meta-analyses showed linear relationships between serum magnesium and CVD (Pnonlinearity = 0.833) or CHD (Pnonlinearity = 0.193) and dietary magnesium and CVD (Pnonlinearity = 0.463) or CHD (Pnonlinearity = 0.440). CONCLUSIONS Increasing dietary magnesium or serum magnesium level is linearly and inversely associated with the risk of total CVD and CHD events.