nils-herrmann/clean_scirepeval huggingface dataset:
Deoxyribonucleic acid methylation and gene expression of PPARGC1A in human muscle is influenced by high-fat overfeeding in a birth-weight-dependent manner.

Low birth weight (LBW) and unhealthy diets are risk factors of metabolic disease including type 2 diabetes (T2D). Genetic, nongenetic, and epigenetic data propose a role of the key metabolic regulator peroxisome proliferator-activated receptor gamma, coactivator 1alpha (PPARGC1A) in the development of T2D.



Our objective was to investigate gene expression and DNA methylation of PPARGC1A and coregulated oxidative phosphorylation (OXPHOS) genes in LBW and normal birth weight (NBW) subjects during control and high-fat diets.  SUBJECTS, AND MAIN OUTCOME  Twenty young healthy men with LBW and 26 matched NBW controls were studied after 5 d high-fat overfeeding (+50% calories) and after a control diet in a randomized manner. Hyperinsulinemic-euglycemic clamps were performed and skeletal muscle biopsies excised. DNA methylation and gene expression were measured using bisulfite sequencing and quantitative real-time PCR, respectively.



When challenged with high-fat overfeeding, LBW subjects developed peripheral insulin resistance and reduced PPARGC1A and OXPHOS (P < 0.05) gene expression. PPARGC1A methylation was significantly higher in LBW subjects (P = 0.0002) during the control diet. However, PPARGC1A methylation increased in only NBW subjects after overfeeding in a reversible manner. DNA methylation of PPARGC1A did not correlate with mRNA expression.



LBW subjects developed peripheral insulin resistance and decreased gene expression of PPARGC1A and OXPHOS genes when challenged with fat overfeeding. The extent to which our finding of a constitutively increased DNA methylation in the PPARGC1A promoter in LBW subjects may contribute needs to be determined. We provide the first experimental support in humans that DNA methylation induced by overfeeding is reversible.
Violent and nonviolent suicide in veterans with substance-use disorders.

Substance-use disorders (SUDs) increase the risk of suicide. Examining risk factors for violent or nonviolent suicide in those with SUDs could improve suicide-prevention efforts in these individuals. We examined the demographic and clinical predictors of violent and nonviolent suicide among patients with SUDs.



This study examined Veterans Affairs (VA) patients with SUDs who were alive at the beginning of Fiscal Year (FY) 2002 and died by suicide during FYs 2002 through 2006 (n = 854) and a random sample of 4,228 SUD patients who did not die by suicide during this period. Data were obtained from VA medical records and the National Death Index. Patients were considered to have an SUD if they received two or more diagnoses of the same SUD from FY 1997 to FY 2001.



Of those who died by suicide, 70% (n = 600) used violent means. Diagnoses of depressive, other anxiety, bipolar and posttraumatic stress disorders, schizophrenia, and personality disorders were associated with increased risk of both violent and nonviolent suicide; however, these associations were stronger for nonviolent than violent suicide deaths. Risk of nonviolent suicide was greater among patients with opioid-use disorders or a clinical diagnosis of abuse or dependence (according to the International Classification of Diseases, Tenth Revision) on multiple substances.



Most VA patients with SUDs who died from suicide used violent means. No specific SUD was associated with increased risk of violent suicide, but several SUD diagnoses were associated with increased risk of nonviolent suicide. Concurrent psychopathology increased risk for both suicide types; however, the relationship was strongest for nonviolent suicide.
Dichotic Listening Tests of Functional Brain Asymmetry Predict Response to Fluoxetine in Depressed Women and Men

Patients having a depressive disorder vary widely in their therapeutic responsiveness to a selective serotonin reuptake inhibitor (SSRI), but there are no clinical predictors of treatment outcome. Studies using dichotic listening, electrophysiologic and neuroimaging measures suggest that pretreatment differences among depressed patients in functional brain asymmetry are related to responsiveness to antidepressants. Two new studies replicate differences in dichotic listening asymmetry between fluoxetine responders and nonresponders, and demonstrate the importance of gender in this context. Right-handed outpatients who met DSM-IV criteria for major depression, dysthymia, or depression not otherwise specified were tested on dichotic fused-words and complex tones tests before completing 12 weeks of fluoxetine treatment. Perceptual asymmetry (PA) scores were compared for 75 patients (38 women) who responded to treatment and 39 patients (14 women) who were nonresponders. Normative data were also obtained for 101 healthy adults (61 women). Patients who responded to fluoxetine differed from nonresponders and healthy adults in favoring left- over right-hemisphere processing of dichotic stimuli, and this difference was dependent on gender and test. Heightened left-hemisphere advantage for dichotic words in responders was present among women but not men, whereas reduced right-hemisphere advantage for dichotic tones in responders was present among men but not women. Pretreatment PA was also predictive of change in depression severity following treatment. Responder vs nonresponder differences for verbal dichotic listening in women and nonverbal dichotic listening in men are discussed in terms of differences in cognitive function, hemispheric organization, and neurotransmitter function.
Different functional loops between cerebral cortex and the subthalmic area in Parkinson's disease.

We investigate the extent to which functional circuits coupling cortical and subthalamic activity are multiple and segregated by frequency in untreated Parkinson's disease (PD). To this end, we recorded EEG and local field potentials (LFPs) from macroelectrodes inserted into the subthalamic nucleus area (SA) in nine awake patients following functional neurosurgery for PD. Patients were studied after overnight withdrawal of medication. Coherence between EEG and SA LFPs was apparent in the theta (3-7 Hz), alpha (8-13 Hz), lower beta (14-20 Hz) and upper beta (21-32 Hz) bands, although activity in the alpha and upper beta bands dominated. Theta coherence predominantly involved mesial and lateral areas, alpha and lower beta coherence the mesial and ipsilateral motor areas, and upper beta coherence the midline cortex. SA LFPs led EEG in the theta band. In contrast, EEG led the depth LFP in the lower and upper beta bands. SA LFP activity in the alpha band could either lead or lag EEG. Thus there are several functional sub-loops between the subthalamic area and cerebral cortical motor regions, distinguished by their frequency, cortical topography and temporal relationships. Tuning to distinct frequencies may provide a means of marking and segregating related processing, over and above any anatomical segregation of processing streams.
Sexual behaviour of heterosexual individuals with HIV infection naive for antiretroviral therapy in Italy.

Specific information about determinants of sexual behaviour of HIV infected heterosexuals, like injecting drug use (IDU), are essential to design interventions aimed at promoting safer sex practices.



We analysed data on sexual behaviour collected, between March 1997 and March 1999, through a self administered questionnaire among 1050 IDUs and 642 non-IDU heterosexuals enrolled in a prospective multicentre cohort study on the natural history of HIV infection.



Among non-IDU heterosexuals, more women (48.5%) than men (25.1%) (p<0.001) reported that they were infected by HIV positive regular partners whose HIV status they were not aware of. Among the 1119 heterosexual males, one fifth reported having had more than 25 sexual partners during their lifetime. Condom use in the last sexual intercourse was more common among heterosexual IDUs (64.9%) than among non-IDU heterosexual males (58.3%) (p=0.05). Heterosexual IDU males were more likely (66.7%) than non-IDU heterosexuals (50.6%) to have an HIV negative partner (p<0.001). Of the 573 heterosexual females studied, 10.2% reported having had more than 25 lifetime sex partners. This proportion was higher among heterosexual IDUs (18.8%) than among non-IDU heterosexuals (4.3%) (p<0.001). Nearly 50% of the women in both groups reported having used a condom in the last intercourse. Almost 57% of heterosexual IDUs had a current HIV negative partner, compared with 34.9% non-IDU heterosexuals (p<0.001). In both sexes, the findings from univariate analysis were confirmed by multiple logistic regression analysis.



This study identified some important differences, in both males and females, in sexual lifestyles according to injecting drug use (for example, in terms of HIV negative partners). This observation indicates the need to tailor HIV prevention messages according to history of injecting drug use.
HIV-specific IL-10-positive CD8+ T cells suppress cytolysis and IL-2 production by CD8+ T cells.

IL-10 producing T cells inhibit Ag-specific CD8+ T cell responses and may play a role in the immune dysregulation observed in HIV infection. We have previously observed the presence of HIV-specific IL-10-positive CD8+ T cells in advanced HIV disease. In this study, we examined the suppressive function of the Gag-specific IL-10-positive CD8+ T cells. Removal of these IL-10-positive CD8+ T cells resulted in increased cytolysis and IL-2, but not IFN-gamma, production by both HIV- and human CMV-specific CD8+ T cells. In addition, these IL-10-positive CD8+ T cells mediated suppression through direct cell-cell contact, and had a distinct immunophenotypic profile compared with other regulatory T cells. We describe a new suppressor CD8+ T cell population in advanced HIV infection that may contribute to the immune dysfunction observed in HIV infection.
Association of polymorphisms in myeloperoxidase and catalase genes with precancerous changes in the gastric mucosa of patients at inner-city hospitals in New York.

Gastric carcinogenesis is a multistep process progressing from chronic gastritis, through glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia. We have previously demonstrated that minority patients at New York City hospitals are infected with a relatively virulent strain of H. pylori (Hp) and that Hp infection is associated with an increased incidence of precancerous changes in the gastric mucosa. Nevertheless, precancerous changes are not observed in every Hp-infected individual, suggesting that environmental and genetic factors may also play a role in the formation and appearance of precancerous lesions. In the present study, the association between polymorphisms in the promoter regions of human myeloperoxidase (MPO -463G--> A) and catalase (CAT -262C-->T) genes and the appearance of precancerous changes in the gastric mucosa of our patient population were examined. Patients enrolled in this study were undergoing endoscopy for gastrointestinal complaints. Samples were collected from 126 patients at Kings County Hospital in Brooklyn and St. John's Episcopal Hospital in Queens. One antral biopsy was taken for genotyping, while additional biopsies were taken from the antrum and fundic region for histological analysis and were scored with respect to acute and chronic inflammation, GA, IM and Hp infestation according to the Sydney classification. MPO and CAT genotypes were determined by PCR and RFLP. CAT genotypes did not influence the incidence or severity of precancerous lesions in the fundic or antral regions of the stomach, whereas the MPO -463A allele was associated with an increase in intensity of gastric atrophy in the fundic mucosa. In Hp-infected individuals, the MPO -463G/G genotype was associated with an increase in the incidence of IM in the antrum, whereas the A allele was associated with an increase in IM in the fundic region. These paradoxical findings suggest that different MPO genotypes are associated with the appearance of IM in distinct anatomical regions of the stomach. However, since the majority of gastric cancer (GC) cases in our patient population occurred in the antrum, the MPO -463G/G genotype, which is associated with increased MPO expression and antral IM, may be considered a risk factor for GC.
Feasibility and accuracy evaluation of three human papillomavirus assays for FTA card-based sampling: a pilot study in cervical cancer screening

Liquid-state specimen carriers are inadequate for sample transportation in large-scale screening projects in low-resource settings, which necessitates the exploration of novel non-hazardous solid-state alternatives. Studies investigating the feasibility and accuracy of a solid-state human papillomavirus (HPV) sampling medium in combination with different down-stream HPV DNA assays for cervical cancer screening are needed. We collected two cervical specimens from 396 women, aged 25–65 years, who were enrolled in a cervical cancer screening trial. One sample was stored using DCM preservative solution and the other was applied to a Whatman Indicating FTA Elute® card (FTA card). All specimens were processed using three HPV testing methods, including Hybrid capture 2 (HC2), careHPV™, and Cobas®4800 tests. All the women underwent a rigorous colposcopic evaluation that included using a microbiopsy protocol. Compared to the liquid-based carrier, the FTA card demonstrated comparable sensitivity for detecting high grade Cervical Intraepithelial Neoplasia (CIN) using HC2 (91.7 %), careHPV™ (83.3 %), and Cobas®4800 (91.7 %) tests. Moreover, the FTA card showed a higher specificity compared to a liquid-based carrier for HC2 (79.5 % vs. 71.6 %, P = 0.015), comparable specificity for careHPV™ (78.1 % vs. 73.0 %, P > 0.05), but lower specificity for the Cobas®4800 test (62.4 % vs. 69.9 %, P = 0.032). Generally, the FTA card-based sampling medium’s accuracy was comparable with that of liquid-based medium for the three HPV testing assays. FTA cards are a promising sample carrier for cervical cancer screening. With further optimization, it can be utilized for HPV testing in areas of varying economic development.
Efficacy of Fish Oil on Serum of TNFα, IL-1β, and IL-6 Oxidative Stress Markers in Multiple Sclerosis Treated with Interferon Beta-1b

Multiple sclerosis (MS) is a chronic inflammatory disease, which leads to focal plaques of demyelination and tissue injury in the central nervous system. Oxidative stress is also thought to promote tissue damage in multiple sclerosis. Current research findings suggest that omega-3 polyunsaturated fatty acids (PUFAs) such as eicosapenta-enoic acid (EPA) and docosahexaenoic acid (DHA) contained in fish oil may have anti-inflammatory, antioxidant, and neuroprotective effects. The aim of the present work was to evaluate the efficacy of fish oil supplementation on serum proinflammatory cytokine levels, oxidative stress markers, and disease progression in MS. 50 patients with relapsing-remitting MS were enrolled. The experimental group received orally 4 g/day of fish oil for 12 months. The primary outcome was serum TNF α levels; secondary outcomes were IL-1 β 1b, IL-6, nitric oxide catabolites, lipoperoxides, progression on the expanded disability status scale (EDSS), and annualized relapses rate (ARR). Fish oil treatment decreased the serum levels of TNF α , IL-1 β , IL-6, and nitric oxide metabolites compared with placebo group (P ≤ 0.001). There was no significant difference in serum lipoperoxide levels during the study. No differences in EDSS and ARR were found.



Fish oil supplementation is highly effective in reducing the levels of cytokines and nitric oxide catabolites in patients with relapsing-remitting MS.
Validation of an activity-based data form developed to reflect interventions used by pediatric physical therapists.

The purpose of this study was to validate the Pediatric Physical Therapy Intervention Activities (PPTIA) data form when used by pediatric physical therapists to describe interventions used in the treatment of children with developmental disabilities. The form is based on use of the clinical practice improvement approach.



A panel of 9 experts was assembled to establish face validity for the PPTIA by assessing clarity, accuracy, and relevance. Then, a content validity questionnaire was mailed to a sample of 41 pediatric physical therapists from around the United States to complete after using the PPTIA in clinical practice.



Seven experts completed and returned the face validity survey and 27 therapists completed the content validity questionnaire. Two revisions to the PPTIA were made based on participant feedback.



The overall opinion of the experts and clinicians was that the PPTIA was a valid form for documenting intervention with children.
Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study.

Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting.



Postmenopausal women (N = 14) with resectable, HR+, human epidermal growth factor receptor 2-negative (HER2-) early BC were randomized 1:1:1 to receive 2.5 mg/day letrozole alone (Arm 1), or with 400 or 600 mg/day ribociclib (Arm 2 or 3). Circulating tumor DNA and tumor biopsies were collected at baseline and, following 14 days of treatment, prior to or during surgery. The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1. Additional assessments included safety, pharmacokinetics, and genetic profiling.



Mean decreases in the Ki67-positive cell fraction from baseline were: Arm 1 69% (range 38-100%; n = 2), Arm 2 96% (range 78-100%; n = 6), Arm 3 92% (range 75-100%; n = 3). Decreased phosphorylated Rb levels and CDK4, CDK6, CCND2, CCND3, and CCNE1 gene expression were observed following ribociclib treatment. Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data. The ribociclib plus letrozole combination was well tolerated, with no Grade 3/4 adverse events over the treatment.



The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+, HER2- BC (NCT01919229).
Lower serum potassium associated with increased mortality in dialysis patients: A nationwide prospective observational cohort study in Korea

Abnormal serum potassium concentration has been suggested as a risk factor for mortality in patients undergoing dialysis patients. We investigated the impact of serum potassium levels on survival according to dialysis modality.



A nationwide, prospective, observational cohort study for end stage renal disease patients has been ongoing in Korea since August 2008. Our analysis included patients whose records contained data regarding serum potassium levels. The relationship between serum potassium and mortality was analyzed using competing risk regression.



A total of 3,230 patients undergoing hemodialysis (HD, 64.3%) or peritoneal dialysis (PD, 35.7%) were included. The serum potassium level was significantly lower (P < 0.001) in PD (median, 4.5 mmol/L; interquartile range, 4.0-4.9 mmol/L) than in HD patients (median, 4.9 mmol/L; interquartile range, 4.5-5.4 mmol/L). During 4.4 ± 1.7 years of follow-up, 751 patients (23.3%) died, mainly from cardiovascular events (n = 179) and infection (n = 120). In overall, lower serum potassium level less than 4.5 mmol/L was an independent risk factor for mortality after adjusting for age, comorbidities, and nutritional status (sub-distribution hazard ratio, 1.30; 95% confidence interval 1.10-1.53; P = 0.002). HD patients showed a U-shaped survival pattern, suggesting that both lower and higher potassium levels were deleterious, although insignificant. However, in PD patients, only lower serum potassium level (<4.5 mmol/L) was an independent predictor of mortality (sub-distribution hazard ratio, 1.35; 95% confidence interval 1.00-1.80; P = 0.048).



Lower serum potassium levels (<4.5 mmol/L) occur more commonly in PD than in HD patients. It represents an independent predictor of survival in overall dialysis, especially in PD patients. Therefore, management of dialysis patients should focus especially on reducing the risk of hypokalemia, not only that of hyperkalemia.
Non-invasive assessment of distribution volume ratios and binding potential: tissue heterogeneity and interindividually averaged time-activity curves

Due to the stochastic nature of radioactive decay, any measurement of radioactivity concentration requires spatial averaging. In pharmacokinetic analysis of time-activity curves (TAC), such averaging over heterogeneous tissues may introduce a systematic error (heterogeneity error) but may also improve the accuracy and precision of parameter estimation. In addition to spatial averaging (inevitable due to limited scanner resolution and intended in ROI analysis), interindividual averaging may theoretically be beneficial, too. The aim of this study was to investigate the effect of such averaging on the binding potential (BP) calculated with Logan’s non-invasive graphical analysis and the “simplified reference tissue method” (SRTM) proposed by Lammertsma and Hume, on the basis of simulated and measured positron emission tomography data {[11C]d-threo-methylphenidate (dMP) and [11C]raclopride (RAC) PET}. dMP was not quantified with SRTM since the low k 2 (washout rate constant from the first tissue compartment) introduced a high noise sensitivity. Even for considerably different shapes of TAC (dMP PET in parkinsonian patients and healthy controls, [11C]raclopride in patients with and without haloperidol medication) and a high variance in the rate constants (e.g. simulated standard deviation of K 1=25%), the BP obtained from average TAC was close to the mean BP (error <5%). However, unfavourably distributed parameters, especially a correlated large variance in two or more parameters, may lead to larger errors. In Monte Carlo simulations, interindividual averaging before quantification reduced the variance from the SRTM (beyond a critical signal to noise ratio) and the bias in Logan’s method. Interindividual averaging may further increase accuracy when there is an error term in the reference tissue assumption E=DV 2−DV′ (DV 2 = distribution volume of the first tissue compartment, DV′ = distribution volume of the reference tissue). This can be explained by the fact that the distribution volume ratio (DVR=DV/DV′) obtained from averaged TAC is an approximation for ΣDV/ΣDV′ rather than for ΣDVR/n. We conclude that Logan’s non-invasive method and SRTM are suitable for heterogeneous tissues and that discussion of group differences in PET studies generally should include qualitative and quantitative assessment of interindividually averaged TAC.