nils-herrmann/clean_scirepeval huggingface dataset:
An ER-associated miRNA signature predicts prognosis in ER-positive breast cancer

Breast cancer patients with positive estrogen receptor (ER) have a better prognosis. However, no prognostic miRNA signature was reported in the ER-positive breast cancer. The aim of the study was to identify and assess the prognostic significance of a miRNA signature in ER-positive breast cancer.



Two cohorts from The Cancer Genome Atlas (TCGA) dataset were used as training (n =596) and testing set (n =319). Differential expression profiling was identified in the training set. And the prognostic value of the miRNA signature was then assessed in the two cohorts.



A total of 14 miRNAs were observed to be associated with the status of ER by significance analysis of microarrays (SAM) in the training set. Patients were characterized as high score or low score group according to the calculated risk scores from each miRNA. And patients in high score group had worse overall survival compared with those in low score group both in the training and testing set.



Our study revealed a miRNA signature including 14 miRNAs associated with ER status which could act as a prognostic marker in ER-positive breast cancer.
A brief goal-setting and planning intervention to improve well-being for people with psychiatric disorders.

The aim of the current study was to develop the evidence for a brief intervention that targets goal-setting and planning skills (GAP) to improve well-being. Having goals for the future and being able to make progress towards them are key components of many theoretical approaches to well-being [9] and GAP has shown promising results with non-clinical populations  , as well as for people with depression  and forensic inpatients  . We investigated whether GAP could be effectively implemented for people with psychiatric disorders accessing specialist mental health services. As a secondary aim, the study design allowed for some exploration of the feasibility of mental health professionals incorporating a brief intervention focused on well-being into their routine practice. A total of 82 service users were recruited through a large mental health trust in the Greater London area. Participants were eligible for the study if they were: (1) aged 18 or over, (2) in contact (or eligible for contact) with specialist mental health services provided by the trust and (3) willing to take part in a group. Insufficient understanding of verbal and written English was used as an exclusion criterion due to the nature of the intervention. A cross-over design was used, with participants initially randomly allocated to either the intervention or a waiting-list control group. Participants allocated to the waiting-list condition were offered the intervention after they had completed their measures as controls and follow-up measures were taken from all participants 1 month after completing the intervention (see fig. 1 ). Recent policy developments in the UK [1, 2] and internationally  have highlighted the need for mental health professionals to adjust their working practices and place more emphasis on promoting well-being. However, it has also been recognised that workforce skills in this area may be lacking and that more emphasis should be placed on developing the evidence base to help mental health professionals promote well-being and support recovery [4] . The benefits of incorporating approaches from positive psychology into existing understandings of mental health problems have been discussed [4, 5] and there have been a few recent studies that have taken preliminary steps to establish the efficacy of interventions focused on well-being with particular clinical groups [6–8] . However, the research literature in this area is still very limited.  March 29, 2013 Accepted after revision: October 9, 2013  2014
Transient Peripheral Immune Activation follows Elective Sigmoidoscopy or Circumcision in a Cohort Study of MSM at Risk of HIV Infection

Rectal and genital sampling in HIV prevention trials permits assessments at the site of HIV entry. Yet the safety and acceptability of circumcision and sigmoidoscopy (and associated abstinence recommendations) are unknown in uncircumcised men who have sex with men (MSM) at high risk of HIV infection.



Twenty-nine HIV-seronegative high-risk Peruvian MSM agreed to elective sigmoidoscopy biopsy collections (weeks 2 and 27) and circumcision (week 4) in a 28-week cohort study designed to mimic an HIV vaccine study mucosal collection protocol. We monitored adherence to abstinence recommendations, procedure-related complications, HIV infections, peripheral immune activation, and retention.



Twenty-three (79.3%) underwent a first sigmoidoscopy, 21 (72.4%) were circumcised, and 16 (55.2%) completed a second sigmoidoscopy during the study period. All who underwent procedures completed the associated follow-up safety visits. Those completing the procedures reported they were well tolerated, and complication rates were similar to those reported in the literature. Immune activation was detected during the healing period (1 week post-sigmoidoscopy, 6 weeks post-circumcision), including increases in CCR5+CD4+T cells and α4β7+CD4+T cells. Most participants adhered to post-circumcision abstinence recommendations whereas reduced adherence occurred post-sigmoidoscopy.



Rectosigmoid mucosal and genital tissue collections were safe in high-risk MSM. Although the clinical implications of the post-procedure increase in peripheral immune activation markers are unknown, they reinforce the need to provide ongoing risk reduction counseling and support for post-procedure abstinence recommendations. Future HIV vaccine studies should also consider the effects of mucosal and tissue collections on peripheral blood endpoints in trial design and analysis.
Safety of Daily Co-Trimoxazole in Pregnancy in an Area of Changing Malaria Epidemiology: A Phase 3b Randomized Controlled Clinical Trial

Antibiotic therapy during pregnancy may be beneficial and impacts positively on the reduction of adverse pregnancy outcomes. No studies have been done so far on the effects of daily Co-trimoxazole (CTX) prophylaxis on birth outcomes. A phase 3b randomized trial was conducted to establish that daily CTX in pregnancy is not inferior to SP intermittent preventive treatment (IPT) in reducing placental malaria; preventing peripheral parasitaemia; preventing perinatal mortality and also improving birth weight. To establish its safety on the offspring by measuring the gestational age and birth weight at delivery, and compare the safety and efficacy profile of CTX to that of SP.



Pregnant women (HIV infected and uninfected) attending antenatal clinic were randomized to receive either daily CTX or sulfadoxine-pyrimethamine as per routine IPT. Safety was assessed using standard and pregnancy specific measurements. Women were followed up monthly until delivery and then with their offspring up to six weeks after delivery.



Data from 346 pregnant women (CTX = 190; SP = 156) and 311 newborns (CTX = 166 and SP = 145) showed that preterm deliveries (CTX 3.6%; SP 3.0%); still births (CTX 3.0%; SP 2.1%), neonatal deaths (CTX 0%; SP 1.4%), and spontaneous abortions (CTX 0.6%; SP 0%) were similar between study arms. The low birth weight rates were 9% for CTX and 13% for SP. There were no birth defects reported. Both drug exposure groups had full term deliveries with similar birth weights (mean of 3.1 Kg). The incidence and severity of AEs in the two groups were comparable.



Exposure to daily CTX in pregnancy may not be associated with particular safety risks in terms of birth outcomes such as preterm deliveries, still births, neonatal deaths and spontaneous abortions compared to SP. However, more data are required on CTX use in pregnant women both among HIV infected and un-infected individuals.
Evaluation of a training and communication-network nephrology program for community pharmacists

To assess the feasibility and impact of implementing ProFiL program to optimize community-pharmacist management of drug-related problems among chronic kidney disease patients followed in a predialysis clinic. The program comprises a training workshop, communication-network program and consultation service.  Forty-two community pharmacies, 101 pharmacists, and 90 chronic kidney disease patients attending a predialysis clinic in Laval (Canada). Patients were followed-up for 6 months.  In a six-month, pilot, open, cluster-randomized controlled trial, community pharmacies were assigned to ProFiL or the usual care. Chronic kidney disease patients of these pharmacies attending a predialysis clinic were recruited. ProFiL pharmacists attended a workshop, received patient information (diagnoses, medications, and laboratory-test results) and had access to a consultation service. Their knowledge and satisfaction were measured before and after the workshop. The mean numbers of pharmacists’ written recommendations to physicians (pharmaceutical opinions) and refusals to dispense a medication were computed.  Of the ProFiL pharmacists, 84% attended the workshop; their knowledge increased from 52% to 88% (95% CI: 29–40%). Most ProFiL pharmacists rated workshop (95%), communication program (82%) and consultation service (59%) as “excellent” or “very good”; 82% said the program improved the quality of their follow-up. The consultation service received 21 requests. ProFiL and usual care pharmacists issued a mean of 0.50 and 0.02 opinion/patient, respectively, (95% CI of the adjusted difference: 0.28–1.01 opinion/patient).  The results of this pilot study suggest that ProFiL can be implemented and may help community pharmacists intervene more frequently to manage drug-related problems. However, a larger-scale study with longer follow-up is necessary to evaluate the impact of the program on management of drug-related problems and its clinical relevance.
Genome-Wide Study of Gene Variants Associated with Differential Cardiovascular Event Reduction by Pravastatin Therapy

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin. In a combined case-only analysis, 79 single nucleotide polymorphisms (SNPs) were associated with differential CHD event reduction by pravastatin according to genotype (P<0.0001), and these SNPs were analyzed in a second stage that included cases as well as non-cases from CARE and WOSCOPS and patients from the PROspective Study of Pravastatin in the Elderly at Risk/PHArmacogenomic study of Statins in the Elderly at risk for cardiovascular disease (PROSPER/PHASE), a randomized placebo controlled study of pravastatin in the elderly. We found that one of these SNPs (rs13279522) was associated with differential CHD event reduction by pravastatin therapy in all 3 studies: P = 0.002 in CARE, P = 0.01 in WOSCOPS, P = 0.002 in PROSPER/PHASE. In a combined analysis of CARE, WOSCOPS, and PROSPER/PHASE, the hazard ratio for CHD when comparing pravastatin with placebo decreased by a factor of 0.63 (95% CI: 0.52 to 0.75) for each extra copy of the minor allele (P = 4.8 × 10(-7)). This SNP is located in DnaJ homolog subfamily C member 5B (DNAJC5B) and merits investigation in additional randomized studies of pravastatin and other statins.
Statin's cost-effectiveness: a Canadian analysis of commonly prescribed generic and brand name statins.

Generic statins may be considered as a compelling treatment option for managing dyslipidemia, due to their reduced cost, compared to their brand name equivalent. However, further assessment is needed to determine whether using a particular generic statin is more cost-effective relative to other brand-name statins.



The purpose of this study is to compare the cost-effectiveness of the most commonly prescribed statins in Canada with respect to 1) lowering low-density lipoprotein cholesterol level (LDL-C) and 2) achieving National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) LDL-C goal.



The study was conducted from the perspective of Canadian payers over a 1-year time horizon. Clinical data were obtained from the STELLAR trial (n=2268) in which patients received fixed doses of rosuvastatin, atorvastatin, simvastatin and pravastatin. Brand and generic drug costs were based on wholesale acquisition costs. Relative cost-effectiveness was assessed using the net monetary benefit approach (NMB), which allows probabilistic cost-effectiveness comparison of the various treatment options over a wide range of willingness-to-pay (WTP) values for a unit of clinical effect.



Rosuvastatin 10mg was the most cost-effective statin over the largest range of WTP values. Pravastatin 10mg was cost-effective when the clinical outcomes had little or no monetary value. Rosuvastatin 20 mg was more cost-effective at the highest end of the WTP spectrum.



The result of this analysis provides evidence that prescribing generic statins in Canada does not necessarily translate into the most cost-effective option for treating dyslipidemia; especially as the monetary value of 1% decrease in LDL-C or patients achieving NCEP ATP III target increases.
The Effect of Exogenous Glucose-Dependent Insulinotropic Polypeptide in Combination With Glucagon-Like Peptide-1 on Glycemia in the Critically Ill

Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have additive insulinotropic effects when coadministered in health. We aimed to determine whether GIP confers additional glucose lowering to that of GLP-1 in the critically ill.



Twenty mechanically ventilated critically ill patients without known diabetes were studied in a prospective, randomized, double-blind, crossover fashion on 2 consecutive days. Between T0 and T420 minutes, GLP-1 (1.2 pmol/kg·min(-1)) was infused intravenously with either GIP (2 pmol/kg·min(-1)) or 0.9% saline. Between T60 and T420 minutes, nutrient liquid was infused into the small intestine at 1.5 kcal/min.



Adding GIP did not alter blood glucose or insulin responses to small intestinal nutrient. GIP increased glucagon concentrations slightly before nutrient delivery (P=0.03), but not thereafter.



The addition of GIP to GLP-1 does not result in additional glucose-lowering or insulinotropic effects in critically ill patients with acute-onset hyperglycemia.
Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial

In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence.



Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services.



The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2).



A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.
PRRC2A and BCL2L11 gene variants influence risk of non-Hodgkin lymphoma: results from the InterLymph consortium.

Many common genetic variants have been associated with non-Hodgkin lymphoma (NHL), but individual study results are often conflicting. To confirm the role of putative risk alleles in B-cell NHL etiology, we performed a validation genotyping study of 67 candidate single nucleotide polymorphisms within InterLymph, a large international consortium of NHL case-control studies. A meta-analysis was performed on data from 5633 B-cell NHL cases and 7034 controls from 8 InterLymph studies. rs3789068 in the proapoptotic BCL2L11 gene was associated with an increased risk for B-cell NHL (odds ratio = 1.21, P random = 2.21 × 10(-11)), with similar risk estimates for common B-cell subtypes. PRRC2A rs3132453 in the HLA complex class III region conferred a reduced risk of B-cell NHL (odds ratio = 0.68, P random = 1.07 × 10(-9)) and was likewise evident for common B-cell subtypes. These results are consistent with the known biology of NHL and provide insights into shared pathogenic components, including apoptosis and immune regulation, for the major B-cell lymphoma subtypes.
Comparison of the antianginal efficacy of acebutolol and propranolol. A multicenter, randomized, double-blind placebo-controlled study.

The effects of oral acebutolol, a cardioselective f-adrenergic blocking agent with partial agonist activity were compared with those of oral propranolol, a noncardioselective agent devoid of partial agonist activity, on the exercise tolerance and anginal pattern in 46 male patients with chronic stable angina pectoris. A 28-week, multicenter, placebo-controlled, randomized, double-blind, crossover study design was used. Each double-blind treatment phase was followed by a 2-week gradual drug-withdrawal phase and a placebo-controlled drug-free week. Angina frequency, nitroglycerin consumption and symptom-limited exercise tests were assessed throughout the study. Acebutolol and propranolol produced comparable levels of blockade at 1650 ± 375 mg/day and 219 ± 50 mg/day (mean ± SD), respectively, as confirmed by a significant reduction in resting and peak exercise heart rates and rate-pressure products. Compared with placebo (acebutolol vs propranolol, NS), acebutolol produced
Phase II Trial Assessing the Ability of Neoadjuvant Chemotherapy With or Without Second-Look Surgery to Eliminate Measurable Disease for Nongerminomatous Germ Cell Tumors: A Children's Oncology Group Study.

This phase II trial evaluated the effect of neoadjuvant chemotherapy with or without second-look surgery before craniospinal irradiation on response rates and survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors.



Induction chemotherapy consisted of six cycles of carboplatin/etoposide alternating with ifosfamide/etoposide. Patients demonstrating less than complete response after induction chemotherapy were encouraged to undergo second-look surgery. Patients who did not achieve complete response or partial response after chemotherapy with or without second-look surgery proceeded to high-dose chemotherapy with thiotepa and etoposide and autologous peripheral blood stem-cell rescue before craniospinal irradiation.



The study included 102 patients treated between January 2004 and July 2008. Median age was 12 years, and 76% were male; 53.9% had pineal region masses, and 23.5% had suprasellar lesions. Sixty-nine percent of patients achieved complete response or partial response with neoadjuvant chemotherapy. At 5 years, event-free survival was 84% ± 4% (SE) and overall survival was 93% ± 3%. During the median follow-up of 5.1 years, 16 patients recurred or progressed, with seven deaths after relapse. No deaths were attributed to therapy-related toxicity. Relapse occurred at the site of primary disease in 10 patients, at a distant site in three patients, or both in one patient. In two patients, progression was detected by marker increase alone. Increased serum α-fetoprotein was a negative prognostic variable. Histologic subtype and increase of beta-human chorionic gonadotropin were not significantly correlated with worse outcomes.



Neoadjuvant chemotherapy with or without second-look surgery achieved high response rates contributing to excellent survival outcomes in children with newly diagnosed non-germinomatous germ cell tumors. This regimen should be included as a backbone for further studies.
Family cancer caregiving and negative outcomes: the direct and mediational effects of psychosocial resources.

This study tested the hypothesis that various components of the stress process model were related to negative outcomes (depression, guilt, negative health) in cancer caregivers. This study also tested the hypothesis that psychosocial resources (mastery, socioemotional support) mediated the relationship between the various domains of the stress process model and negative outcomes. A total of 238 cancer caregivers were recruited from radiation medicine clinics at the University of Maryland Greenebaum Cancer Center (n = 186) and the University of Minnesota Cancer Center (n = 52). A comprehensive interview battery was administered. A multivariate regression found that primary subjective stressors were the strongest predictors of depression and negative health impact. A path analysis indicated that mastery mediated the relationship between role captivity and negative health impact. These results emphasize the importance of multidimensional assessment in cancer caregiving. The findings also suggest refinements to the stress process model when examining family cancer care.
Peripheral Neuropathy Due to Biweekly Paclitaxel, Epirubicin and Cisplatin in Patients with Advanced Ovarian Cancer

We assessed the peripheral neuropathic changes induced by biweekly combination chemotherapy including paclitaxel 100–165 mg/m2 (in a 3-h infusion), epirubicin 75 mg/m2 and cisplatin 50 mg/m2 (TEC) in patients with advanced ovarian cancer. Neurologic evaluation, including a standardized questionnaire, bed-side neurological examination, and quantitative determination of vibratory perception thresholds (VPT) and grip strength took place before therapy, after 3 and 6 cycles, and thereafter whenever possible. During chemotherapy all patients received granulocyte colony-stimulating factor from days 2 to 12. Pretreated patients received amifostine two times, before epirubicin and before cisplatin administration. Neuropathic symptoms developed in 11/13 non-pretreated patients and in 7/9 chemotherapy-pretreated patients. Neuropathic signs developed in all patients. Neuropathic symptoms and signs were predominantly sensory in character. VPT changes developed primarily in the feet. According to National Cancer Institute of Canada Common Toxicity Criteria, grade 3 peripheral neuropathy after 6 cycles developed in 1/6 and 2/4 non-pretreated patients who received TEC containing paclitaxel 150 and 165 mg/m2, respectively. We conclude that peripheral neuropathy is dose-limiting in chemonaïve patients treated with biweekly TEC combination chemotherapy, at paclitaxel dose level 165 mg/m2 in a 3-h intravenous administration.