Miracle-dz/UniFAR-FTUs huggingface dataset:
The Microtubule-Associated Innate Immune Sensor GEF-H1 Does Not Influence Mouse Norovirus Replication in Murine Macrophages

Norovirus is an acute infection of the gastrointestinal tract causing rapid induction of vomiting and diarrhoea. The infection is sensed and controlled by the innate immune system, particularly by the RNA helicase MDA-5 and type I and III interferons (IFNs). We have observed that intracellular replication of murine norovirus (MNV) occurs in membranous clusters proximal to the microtubule organising centre, a localisation dependent on intact microtubules. Recently, it was shown that the host protein guanine nucleotide exchange factor-H1 (GEF-H1) is a microtubule-associated innate immune sensor that activates interferon Regulatory Factor 3 to induce the production of type I IFNs. Thus, we interrogated the potential role of GEF-H1 in controlling MNV infections. We observed that GEF-H1 was recruited to the MNV replication complex; however RNAi-mediated suppression of GEF-H1 did not outwardly affect replication. We furthered our studies to investigate the impact of GEF-H1 on MNV innate detection and observed that GEF-H1 did not contribute to type I IFN induction during MNV infection or influenza virus infection but did result in a small reduction of interferon–β (IFNβ) during West Nile virus infection. Intriguingly, we discovered an interaction of GEF-H1 with the viral MNV non-structural protein 3 (NS3), an interaction that altered the location of GEF-H1 within the cell and prevented the formation of GEF-H1-induced microtubule fibres. Thus, our results indicate that GEF-H1 does not contribute significantly to the innate immune sensing of MNV, although its function may be modulated via interaction with the viral NS3 protein.
Resting heart rate and cardiovascular outcomes in diabetic and non-diabetic individuals at high cardiovascular risk analysis from the ONTARGET/TRANSCEND trials.

Aims Resting heart rate (RHR) has been shown to be associated with cardiovascular outcomes in various conditions. It is unknown whether different levels of RHR and different associations with cardiovascular outcomes occur in patients with or without diabetes, because the impact of autonomic neuropathy on vascular vulnerability might be stronger in diabetes. Methods and results We examined 30 937 patients aged 55 years or older with a history of or at high risk for cardiovascular disease and after myocardial infarction, stroke, or with proven peripheral vascular disease from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination followed for a median of 56 months. We analysed the association of mean achieved RHR on-treatment with the primary composite outcome of cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, the components of the composite primary outcome, and all-cause death as continuous and categorical variables. Data were analysed by Cox regression analysis, ANOVA, and χ2 test. These trials were registered with ClinicalTrials.gov. number NCT00153101. Patients were recruited from 733 centres in 40 countries between 1 December 2001 and 31 July 2008 (ONTARGET) and 1 November 2001 until 30 May 2004 (TRANSCEND). In total, 19 450 patients without diabetes and 11 487 patients with diabetes were stratified by mean RHR. Patients with diabetes compared to no diabetes had higher RHRs (71.8 ± 9.0 vs. 67.9 ± 8.8, P < 0.0001). In the categories of <60 bpm, 60 ≤ 65 bpm, 65 ≤ 70 bpm, 70 ≤ 75 bpm, 75 ≤ 80 bpm and ≥80 bpm, non-diabetic patients had an increased hazard of the primary outcome with mean RHR of 75 ≤ 80 bpm (adjusted hazard ratio [HR] 1.17 (1.01-1.36)) compared to RHR 60 ≤ 65 bpm. For patients with in-trial RHR ≥80 bpm the hazard ratios were highest (diabetes: 1.96 (1.64-2.34), no diabetes: 1.73 (1.49-2.00), For cardiovascular death hazards were also clearly increased at RHR ≥80 bpm (diabetes [1.99, (1.53-2.58)], no diabetes [1.73 (1.38-2.16)]. Similar results were obtained for hospitalization for heart failure and all-cause death while the effect of RHR on myocardial infarction and stroke was less pronounced. Results were robust after adjusting for various risk indicators including beta-blocker use and atrial fibrillation. No significant association to harm was observed at lower RHR. Conclusion Mean RHR above 75-80 b.p.m. was associated with increased risk for cardiovascular outcomes except for stroke. Since in diabetes, high RHR is associated with higher absolute event numbers and patients have higher RHRs, this association might be of particular clinical importance in diabetes. These data suggest that RHR lowering in patients with RHRs above 75-80 b.p.m. needs to be studied in prospective trials to determine if it will reduce outcomes in diabetic and non-diabetic patients at high cardiovascular risk. Clinical Trial registration http://clinicaltrials.gov. Unique identifier: NCT00153101.
Successful entecavir plus prednisolone treatment for hepatitis B virus-associated membranoproliferative glomerulonephritis

Rationale: Adult-onset hepatitis B virus-associated membranoproliferative glomerulonephritis (HBV-MPGN) is generally refractory, and an effective treatment for this condition has not been established. The indications for steroids in HBV-MPGN are an important clinical concern. Patient concerns: A 28-year-old woman with a chronic hepatitis B virus infection developed nephrotic syndrome in her second month of pregnancy, with urinary protein levels of 3 to 10 g/d that continued into her postpartum period. She was a carrier of HBV with HBeAg seroconversion. As her renal impairment could have been a result of pregnancy, we observed her for 10 months postpartum without any intervention. However, spontaneous remission after childbirth was not achieved and urine protein levels were sustained at 1 to 3 g/d. About 10 months after delivery, elevated serum liver enzyme levels were observed. Diagnosis: Biopsies showed MPGN, with deposition of hepatitis B antigen in the glomeruli, and chronic B-type hepatitis with a severity grade of A1F0. She was diagnosed with HBV-MPGN. Interventions: The patient was started on entecavir 0.5 mg/d in March 2008. Within 1 month, serum HBV DNA became undetectable; within 3 months, her alanine aminotransferase levels normalized. However, urinary protein excretion did not decrease to <2 g/d. On a second renal biopsy, performed 7 months after entecavir treatment, proliferative lesions of the glomeruli were observed; therefore, prednisolone was started at an initial dose of 30 mg/d. Outcomes: Her proteinuria improved immediately and prednisolone was tapered over 10 months. A third renal biopsy showed a remarkable resolution of HBV-MPGN, with a significant decrease in mesangial proliferation and immune complex deposition. HBV reactivation was not observed during the prednisolone treatment. Lessons: Additional prednisolone therapy in combination with antiviral therapy should be considered for refractory HBV-MPGN, with sufficient care taken regarding HBV reactivation.
Excitation of murine cardiac myocytes by nanosecond pulsed electric field

Opening of voltage‐gated sodium channels takes tens to hundreds of microseconds, and mechanisms of their opening by nanosecond pulsed electric field (nsPEF) stimuli remain elusive. This study was aimed at uncovering the mechanisms of how nsPEF elicits action potentials (APs) in cardiomyocytes.
Tuneable thermal expansion of poly (3,4-ethylenedioxythiophene) polystyrene sulfonate

Linear coefficient of thermal expansion is calculated for a mixture of poly(3,4-ethylenedioxythiophene) and polystyrene sulfonate (PEDOT:PSS) using density functional theory and the Debye–Grüneisen model. The linear coefficient of thermal expansion is a key factor in thermal management (thermal conductivity, thermal stress and thermal fatigue) of microelectronic and energy devices, being common applications of the conjugated polymeric PEDOT:PSS system. The obtained value of 53 × 10−6 K−1 at room temperature can be rationalised based on the electronic structure analysis. The PEDOT and PSS units are bonded by a dipole–dipole interaction between S in PEDOT and H in PSS. A C–C bond in a benzene ring (PSS) or thiophene (PEDOT) is up to 13 times stronger than the S–H bond. By adjusting the population of the S–H bonds by deprotonating PSS, the linear coefficient of thermal expansion can be enhanced by 57%. This allows for tuning the thermal properties of PEDOT:PSS in cutting-edge devices.
Efficacy and safety of artificial urinary sphincter (AUS): Results of a large multi‐institutional cohort of patients with mid‐term follow‐up

To assess efficacy and safety as well as predictive factors of dry rate and freedom from surgical revision in patients underwent AUS placement. The artificial urinary sphincter (AUS) is still considered the standard for the treatment of moderate to severe post‐prostatectomy stress urinary incontinence (SUI). However, data reporting efficacy and safety from large series are lacking.
Curcumin intervention for cognitive function in different types of people: A systematic review and meta‐analysis

Curcumin is a polyphenolic natural compound with diverse and attractive biological activities, which may prevent or ameliorate pathological processes underlying age‐related cognitive decline, dementia, or mood disorders. However, clinical trials and animal studies have yielded conflicting conclusions regarding its effectiveness for cognition in different individuals. The aim of this review is to meta‐analytically assess the effectiveness of curcumin for cognitive function in different types of people. A preliminary search on PubMed, Embase, Web of Science, ClinicalTrials.gov, Cochrane Library, Chinese National Knowledge Infrastructure, and Wanfang Data and China Biology Medicine disc was performed to identify randomized controlled trials investigating the effect of curcumin on cognition. Six clinical trials with a total of 289 subjects met inclusion criteria for this review. We used a random‐effects model to calculate the pooled standardized difference of means (SMD). For older adults who received curcumin, scores on measures of cognitive function (SMD = 0.33, 95% confidence interval [CI] [0.05, 0.62]; p = 0.02), occurrence of adverse events (odds ratio [OR] = 5.59, 95% CI [0.96, 36.80]; p = 0.05), and measures of depression (SMD = −0.29, 95% CI [0.64, 0.05]; p = 0.09) indicated significant memory improvement. In patients with Alzheimer's disease (AD), scores in measures of cognition status (SMD = −0.90, 95% CI [1.48, −0.32]; p = 0.002) indicated that there was a trend for treated subjects to do worse than placebo‐treated subjects on the Mini‐Mental State Examination. The occurrence of adverse events (OR = 0.87, 95% CI [0.10, 7.51]; p = 0.90) was similar to those who received placebo. Due to insufficient data, it was impossible to provide a narrative account of only the outcomes for schizophrenia. Curcumin appears to be more effective in improving cognitive function in the elderly than in improving symptoms of AD and schizophrenia. Curcumin is also safe and tolerated among these individuals. Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Further high‐quality trials with larger sample sizes or bioavailability‐improved curcumin formulations may be considered for reliable assessment.
MiR-24 promotes migration and invasion of non-small cell lung cancer by targeting ZNF367.

PURPOSE Non-small lung cancer (NSCLC) is one of most common cancers worldwide. microRNAs (miRNAs) play an important role in animal biological processes, such as cell growth, differentiation and apoptosis. The aim of this study was to investigate whether MiR-24 can regulate cell proliferation of NSCLC by targeting ZNF367. METHODS Real time quantitative PCR (qRT-PCR) was used to detect the expression levels of MiR-24 and ZNF367. Western blot assay was employed to analyze the protein levels. Luciferase reporter assay was used to test the target gene of MiR-24. MTT assay was used to detect cell proliferation. RESULTS MiR-24 was significantly up-regulated in NSCLC tissues compared with their corresponding nontumorous tissues (p<0.05). Over-expression of MiR-24 could significantly promoted cell migration and invasion (p<0.05). ZNF367 was a downstream target of MiR-24 and down-regulated by MiR-24. Knockdown of ZNF367 remarkably promoted NSCLC cell proliferation (p<0.05). CONCLUSIONS The novel identified MiR-24/ZNF367 axis offers new insights into tumorigenesis of NSCLC and a new biomarker for NSCLC treatment.
Serum levels of total antioxidant status, nitric oxide and nitric oxide synthase in minor recurrent aphthous stomatitis patients

Background: Recurrent aphthous stomatitis (RAS) is one of the most common inflammatory ulcerative conditions of oral cavity with uncertain etiology. Several studies have reported that oxidative stress may be associated with RAS. The aim of this study was to compare the serum levels of total antioxidant status (TAS), nitric oxide (NO) and nitric oxide synthase (NOS) in minor RAS (MiRAS) patients with healthy individuals and determine the possible association of MiRAS with the 3 physiological parameters mentioned above. Methods: Ninety patients with idiopathic MiRAS and 90 race-, age- and sex-matched healthy individuals were included in this study. All these subjects were allocated to 3 groups: MiRAS patients in the active stage (Group A); the same MiRAS patients in Group A in the inactive stage (Group B); healthy individuals without MiRAS (Group C). Serum levels of TAS, NO and NOS were determined by the spectrophotometric method. Independent sample t test and paired t test were performed for statistical evaluation. Results: Serum TAS level of Group A was significantly decreased than that of Group C, whereas the serum level of NO was significantly higher in Group A as compared to Group C (P < .05). The serum levels of TAS and NO in Group B were no significant differences when compared with those in Group A or Group C. No significant differences in NOS activities were also found between the 3 groups (P > .05). Conclusions: MiRAS is associated with decreased TAS and increased NO levels, but NOS may not play an important role in the aetiopathogenesis.
Survivorship Science at the NIH: Lessons Learned From Grants Funded in Fiscal Year 2016

Federal investment in survivorship science has grown markedly since the National Cancer Institute's creation of the Office of Cancer Survivorship in 1996. To describe the nature of this research, provide a benchmark, and map new directions for the future, a portfolio analysis of National Institutes of Health-wide survivorship grants was undertaken for fiscal year 2016. Applying survivorship-relevant terms, a search was conducted using the National Institutes of Health Information for Management, Planning, Analysis and Coordination grants database. Grants identified were reviewed for inclusion and categorized by grant mechanism used, funding agency, and principal investigator characteristics. Trained pairs of coders classified each grant by focus and design (observational vs interventional), population studied, and outcomes examined. A total of 215 survivorship grants were identified; 7 were excluded for lack of fit and 2 for nonresearch focus. Forty-one (19.7%) representing training grants (n = 38) or conference grants (n = 3) were not coded. Of the remaining 165 grants, most (88.5%) were funded by the National Cancer Institute; used the large, investigator-initiated (R01) mechanism (66.7%); focused on adult survivors alone (84.2%), often breast cancer survivors (47.3%); were observational in nature (57.3%); and addressed a broad array of topics, including psychosocial and physiologic outcomes, health behaviors, patterns of care, and economic/employment outcomes. Grants were led by investigators from diverse backgrounds, 28.4% of whom were early in their career. Present funding patterns, many stable since 2006, point to the need to expand research to include different cancer sites, greater ethnoculturally diverse samples, and older (>65 years) as well as longer-term (>5 years) survivors and address effects of newer therapies.
Niche adaptation limits bacteriophage predation of Vibrio cholerae in a nutrient-poor aquatic environment

Significance Virulent phages can reduce populations of bacteria and help shape bacterial evolution. Here, we used three virulent phages to understand their equilibrium with V. cholerae in nutrient-limiting aquatic microcosms. It has been proposed that phages quench cholera outbreaks, but no direct evidence of phage predation in aquatic environments had been established. Here, we show that different phages possess varied abilities to infect in certain niches or stages of the host bacterial life cycle. Unveiling the phage/bacterial interactions in their natural setting is important to the understanding of cholera outbreaks and could be ultimately used to help develop a method for outbreak prediction and/or control. Vibrio cholerae, the causative agent of cholera, has reservoirs in fresh and brackish water where it interacts with virulent bacteriophages. Phages are the most abundant biological entity on earth and coevolve with bacteria. It was reported that concentrations of phage and V. cholerae inversely correlate in aquatic reservoirs and in the human small intestine, and therefore that phages may quench cholera outbreaks. Although there is strong evidence for phage predation in cholera patients, evidence is lacking for phage predation of V. cholerae in aquatic environments. Here, we used three virulent phages, ICP1, ICP2, and ICP3, commonly shed by cholera patients in Bangladesh, as models to understand the predation dynamics in microcosms simulating aquatic environments. None of the phages were capable of predation in fresh water, and only ICP1 was able to prey on V. cholerae in estuarine water due to a requirement for salt. We conclude that ICP2 and ICP3 are better adapted for predation in a nutrient rich environment. Our results point to the evolution of niche-specific predation by V. cholerae-specific virulent phages, which complicates their use in predicting or monitoring cholera outbreaks as well as their potential use in reducing aquatic reservoirs of V. cholerae in endemic areas.
Association of Geriatric Nutritional Risk Index with Mortality in Hemodialysis Patients: A Meta-Analysis of Cohort Studies

Background/Aims: Geriatric nutritional risk index (GNRI) was developed as a “nutrition-related” risk index and was reported in different populations as associated with the risk of all-cause and cardiovascular morbidity and mortality. Therefore, GNRI can be used to classify patients according to a risk of complications in relation to conditions associated with protein-energy wasting (PEW). However, not all reports pointed to the prognostic ability of the GNRI. The purpose of this study was to assess the associations of GNRI with mortality in chronic hemodialysis patients. Methods: We electronically searched original articles published in peer-reviewed journals from their inception to September 2018 in The PubMed, Embase, and the Cochrane Library databases. The primary outcome was all-cause and cardiovascular mortality. We pooled unadjusted and adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) using Review Manager 5.3 software. Results: A total of 10,739 patients from 19 cohort studies published from 2010 to 2018 were included. A significant negative association was found between the GNRI and all-cause mortality in patients with chronic hemodialysis (OR, 0.90; 95% CI, 0.84-0.97, p=0.004) (per unit increase) and (OR, 2.15; 95% CI, 1.88-2.46, p＜0.00001) (low vs. high GNRI). Moreover, there was also a significant negative association between the GNRI (per unit increase) and cardiovascular events (OR, 0.98; 95% CI, 0.97-1.00, p=0.01), as well as cardiovascular mortality (OR, 0.89; 95% CI, 0.80-0.99, p=0.03). Conclusion: Our findings supported the hypothesis that the low GNRI is associated with an increased risk of all-cause and cardiovascular mortality in chronic hemodialysis patients. Based on our literature review, GNRI has been found to be an effective tool for identifying patients with nutrition-related risk of all-cause and cardiovascular disease.
A systematic review of sex differences in concussion outcome: What do we know?

Abstract Objective: The purpose of this review was to examine sex differences in concussion, or mild traumatic brain injury (mTBI) outcome, updating previous critical reviews of the literature. Method: Within adult human studies, we reviewed a wide range of concussion outcome variables: prevalence of concussion, injury characteristics, postconcussion symptom trajectories and psychiatric distress, neuropsychological performance, and neuroimaging findings. Sports-related concussion, civilian, and military samples were included in the review. Results: Given the robust concussion literature, there is a relative paucity of research addressing sex differences following concussion. The majority of available studies focused on sports-related concussion, with fewer studies targeting other civilian causes of concussion or military-related concussion in females. Prevalence of concussion was generally reported to be higher in females than males. Although symptom reporting largely showed a pattern for females to report greater overall symptoms than males, examining individual symptoms or symptom clusters resulted in mixed findings between the sexes. Neuropsychological studies generally showed females performing more poorly than males on measures of visual memory following concussion, though this finding was not consistently reported. Conclusion: Research examining sex differences in humans following concussion, in general, is in its infancy, and exploration of sex differences in studies outside of the sports concussion domain is particularly nascent. Given the increased prevalence of concussion and potential higher symptom reporting among women, ongoing research is necessary to better understand the role of biological sex on outcome following concussion. Understanding sex differences has important implications for assessment, management, and treatment of concussion.
Enfermedad de Chagas sistémico en fase aguda por transmisión oral: diagnóstico integral de un caso autopsiado.

RESUMEN Se presenta el primer caso autopsiado en Venezuela con enfermedad de Chagas por transmision oral. Se trata de una joven de 24 anos de edad con 8 semanas de embarazo quien contrajo la enfermedad conjuntamente con 71 ninos y 14 adultos, la mayoria integrantes de la comunidad escolar “Romulo Monasterios” en la localidad de Chichiriviche de la Costa en el estado Vargas, donde ocurrio el segundo brote agudo de enfermedad de Chagas por transmision oral registrado en Venezuela. El diagnostico epidemiologico, clinico, serologico y parasitologico en sangre y liquido pleural extraidos en vida, fueron confirmados con los hallazgos histopatologicos y moleculares (PCR) de los tejidos. Se plantean las caracteristicas peculiares del caso asi como algunos aspectos de la transmision oral, ampliamente estudiados en nuestro pais en animales de experimentacion.
Measuring familism in dementia family caregivers: the revised familism scale

Abstract Objectives: Familism is a cultural value that has been shown to be important for understanding the dementia caregiving process. The aim of this study is to analyze the psychometric properties of the Revised Familism Scale (RFS). Method: Face-to-face assessments were done with 199 dementia family caregivers. Exploratory factor analysis, discriminant validity, and reliability analyses of the RFS were carried out. Results: The results suggest that the RFS has good psychometric properties and is composed of three factors: “Familial interconnectedness”, “Familial obligations”, and “Extended family support”. Conclusion: The RFS seems to be a reliable measure of familism, a multidimensional construct measuring a relevant cultural value for dementia family caregivers.