nils-herrmann/clean_scirepeval huggingface dataset:
Rationale, design and objectives of ARegPKD, a European ARPKD registry study

Autosomal recessive polycystic kidney disease (ARPKD) is a rare but frequently severe disorder that is typically characterized by cystic kidneys and congenital hepatic fibrosis but displays pronounced phenotypic heterogeneity. ARPKD is among the most important causes for pediatric end stage renal disease and a leading reason for liver-, kidney- or combined liver kidney transplantation in childhood. The underlying pathophysiology, the mechanisms resulting in the observed clinical heterogeneity and the long-term clinical evolution of patients remain poorly understood. Current treatment approaches continue to be largely symptomatic and opinion-based even in most-advanced medical centers. While large clinical trials for the frequent and mostly adult onset autosomal dominant polycystic kidney diseases have recently been conducted, therapeutic initiatives for ARPKD are facing the challenge of small and clinically variable cohorts for which reliable end points are hard to establish.



ARegPKD is an international, mostly European, observational study to deeply phenotype ARPKD patients in a pro- and retrospective fashion. This registry study is conducted with the support of the German Society for Pediatric Nephrology (GPN) and the European Study Consortium for Chronic Kidney Disorders Affecting Pediatric Patients (ESCAPE Network). ARegPKD clinically characterizes long-term ARPKD courses by a web-based approach that uses detailed basic data questionnaires in combination with yearly follow-up visits. Clinical data collection is accompanied by associated biobanking and reference histology, thus setting roots for future translational research.



The novel registry study ARegPKD aims to characterize miscellaneous subcohorts and to compare the applied treatment options in a large cohort of deeply characterized patients. ARegPKD will thus provide evidence base for clinical treatment decisions and contribute to the pathophysiological understanding of this severe inherited disorder.
Community and District Empowerment for Scale-up (CODES): a complex district-level management intervention to improve child survival in Uganda: study protocol for a randomized controlled trial.

Innovative and sustainable strategies to strengthen districts and other sub-national health systems and management are urgently required to reduce child mortality. Although highly effective evidence-based and affordable child survival interventions are well-known, at the district level, lack of data, motivation, analytic and planning capacity often impedes prioritization and management weaknesses impede implementation. The Community and District Empowerment for Scale-up (CODES) project is a complex management intervention designed to test whether districts when empowered with data and management tools can prioritize and implement evidence-based child survival interventions equitably.



The CODES strategy combines management, diagnostic, and evaluation tools to identify and analyze the causes of bottlenecks to implementation, build capacity of district management teams to implement context-specific solutions, and to foster community monitoring and social accountability to increase demand for services. CODES combines UNICEF tools designed to systematize priority setting, allocation of resources and problem solving with Community dialogues based on Citizen Report Cards and U-Reports used to engage and empower communities in monitoring health service provision and to demand for quality services. Implementation and all data collection will be by the districts teams or local Community-based Organizations who will be supported by two local implementing partners. The study will be evaluated as a cluster randomized trial with eight intervention and eight comparison districts over a period of 3 years. Evaluation will focus on differences in uptake of child survival interventions and will follow an intention-to-treat analysis. We will also document and analyze experiences in implementation including changes in management practices.



By increasing the District Health Management Teams' capacity to prioritize and implement context-specific solutions, and empowering communities to become active partners in service delivery, coverage of child survival interventions will increase. Lessons learned on strengthening district-level managerial capacities and mechanisms for community monitoring may have implications, not only in Uganda but also in other similar settings, especially with regard to accelerating effective coverage of key child survival interventions using locally available resources.
Importance of image-guided stereotactic biopsy to confirm diagnosis in an oncological setting

In current practice, the neurosurgical community relies heavily on computed tomography (CT) and magnetic resonance imaging (MRI) for making the diagnosis of brain lesions, especially when surgically inaccessible. However, the specificity of these neuroimaging modalities remains limited, and errors in diagnosis are frequent. In an attempt to ascertain how often the diagnosis based on imaging studies is proved wrong by biopsy, we reviewed the findings from 100 consecutive stereotactic biopsies performed in an oncological setting.  The records of 100 consecutive stereotactic biopsies were postoperatively reviewed. The preoperative clinical and radiologic differential diagnoses were compared with diagnosis made on tissue retrieved by biopsy.  In 19% of patients, the preoperative clinical and radiological diagnoses and postoperative diagnosis were different, and reliance on brain imaging data alone would have led to an incorrect tentative diagnosis and the wrong choice of treatment.  The high rate of discrepancy between clinical and radiological diagnoses on the one hand and biopsy-proven diagnosis on the other hand is a compelling reason to establish tissue diagnosis. Stereotactic biopsies of brain lesions are relatively safe and should be performed in cases where tissue characteristics affect prognosis, where therapy carries an inherent risk, and in those patients under treatment for cancer or immune deficiencies in whom there is an unusually broad differential diagnosis.
Alcohol and breast cancer risk defined by estrogen and progesterone receptor status: a case-control study.

Alcohol consumption increases breast cancer risk. Some studies suggested that this association is stronger or limited to tumors expressing estrogen receptors (ER).



We investigated the role of alcohol according to ER and progesterone receptor (PR) status in a case-control study on breast cancer conducted from 1991 to 1994 in three Italian areas. Cases were 989 women with incident, histologically confirmed breast cancer. Controls were 1,350 women admitted to hospitals in the same catchment areas for acute nonneoplastic diseases. A validated food-frequency questionnaire was used to collect information on dietary habits and lifetime consumption of various alcoholic beverages. Multiple logistic regression models were used to estimate odds ratios and 95% confidence interval (95% CI).



Alcohol drinking was associated with ER+ tumors (odds ratio, 2.16; 95% CI, 1.68-2.76 for an intake of > or =13.8 g/d as compared with nondrinkers). The odds ratio was 1.13 (95% CI, 1.07-1.20) for a 10-g increase in daily intake. For ER- tumors, the relation with alcohol consumption was not significant (odds ratio, 1.36; 95% CI, 0.93-2.01). When breast cancers were further classified according to PR, the findings for ER+PR+ cancers were similar to those for all ER+ ones, with an odds ratio of 2.34 (95% CI, 1.81-3.04) for an intake of > or =13.8 g/d. No significant association emerged for ER-PR- tumors (odds ratio, 1.25; 95% CI, 0.81-1.94).



This study supports the hypothesis that alcohol is more strongly related to ER+ than to ER- breast tumors.
Systemic lupus erythematosus and genetic variation in the interleukin 1 gene cluster: a population based study in the southeastern United States.

Interleukin (IL)1alpha and IL1beta, and their endogenous receptor antagonist (IL1Ra), have been related to the pathology of systemic lupus erythematosus (SLE), but the role of IL1 polymorphisms in the aetiology of SLE is unknown.



To examine polymorphisms at IL1alpha -889(C-->T), IL1alpha +4845(C-->T), IL1beta -511(C-->T), IL1beta +3953(G-->T), and IL1Ra (86 bp VNTR) in a population based study of SLE in North Carolina and South Carolina.



Genotypes from 230 cases who met ACR classification criteria, and from 275 controls matched for age, sex, and state, were analysed separately for African Americans and whites. Odds ratios (ORs) were estimated by logistic regression models for each locus alone and also after adjusting for polymorphisms at adjacent loci.



An increased risk of SLE for the IL1alpha -889C/C genotype compared with carriage of the -889T allele was found in both African Americans (OR = 3.1, p = 0.001) and whites (OR = 2.9, p = 0.005). In African Americans, carriage of the IL1beta -511T allele was associated with a higher risk of SLE than carriage of the -511C/C genotype (OR = 2.4, p = 0.017), independent of variation at IL1alpha -889.



The observed associations support the hypothesis that genetic variation in IL1 is involved in the aetiology of SLE and merit further investigation.
Predictors of symptomatic remission in first-episode psychosis outpatients treated with quetiapine: a naturalistic study.

The aim of this naturalistic study was to assess course and predictors of symptomatic remission in outpatients with first-episode psychosis during quetiapine monotherapy.



In 131 outpatients presenting with first-episode psychosis, socio-demographic and clinical variables including PANSS-8 and CGI-S scores were compared at baseline and follow-up between the subgroups with and without symptomatic remission during 12 weeks of flexible-dose treatment with quetiapine.



Logistic regression revealed a low degree of negative symptoms at baseline, younger age, shorter duration of psychotic episode, early treatment response, and the absence of concomitant diseases as predictors for symptomatic remission whereas general disease severity, PANSS-8 total score, gender, alcohol or substance abuse had no predictive value.



Our study underlines the predictive value of early treatment response and a low degree of negative symptoms in outpatients with first-episode psychosis. It also confirms the usability of the symptomatic remission criterion as a cross-sectional threshold criterion in clinical practice.
Tailored internet-administered treatment of anxiety disorders for primary care patients: study protocol for a randomised controlled trial

Internet-administered cognitive behavioural therapy (ICBT) has been found to be effective for a range of anxiety disorders. However, most studies have focused on one specific primary diagnosis and co-morbidity has not been considered. In primary care settings, patients with anxiety often suffer from more than one psychiatric condition, making it difficult to disseminate ICBT for specific conditions. The aim of this study will be to investigate if ICBT tailored according to symptom profile can be a feasible treatment for primary care patients with anxiety disorders. It is a randomised controlled trial aimed to evaluate the treatment against an active control group.



Participants with anxiety disorders and co-morbid conditions (N = 128), will be recruited from a primary care population. The Clinical Outcome in Routine Evaluation (CORE-OM) will serve as the primary outcome measure. Secondary measures include self-reported depression, anxiety, quality of life and loss of production and the use of health care. All assessments will be collected via the Internet and measure points will be baseline, post treatment and 12 months post treatment.



This trial will add to the body of knowledge on the effectiveness of ICBT for anxiety disorders in primary care. The trial will also add knowledge on the long term effects of ICBT when delivered for regular clinic patients
Effects of peripheral chemoreceptors deactivation on sympathetic activity in heart transplant recipients.

Heart transplantation initially normalizes sympathetic hyperactivity directed at the muscle circulation. However, sympathetic activity increases with time after transplantation and the exact mechanisms responsible for sympathetic control in heart transplant recipients remain unclear. We examined the effects of peripheral chemoreflex deactivation caused by breathing 100% oxygen on muscle sympathetic nerve activity (expressed as number of burst per minute and mean burst amplitude), heart rate, and mean blood pressure in 13 heart transplant recipients, 13 patients with essential hypertension, and 10 controls. Heart transplant recipients disclosed the highest sympathetic activity, whereas it did not differ between controls and patients with essential hypertension (51+/-16 versus 37+/-14 versus 39+/-12 burst/min, respectively; P<0.05). Breathing 100% oxygen, in comparison with 21% oxygen, reduced sympathetic activity (-4+/-4 versus -1+/-2 burst/min, P<0.01; 85+/-9 versus 101+/-8% of amplitude at baseline, P<0.001) and mean blood pressure (-4+/-5 versus +3+/-6 mm Hg; P<0.05) in heart transplant recipients, decreased sympathetic activity (-4+/-4 versus 0+/-3 burst/min, P<0.05; 90+/-16 versus 101+/-9% of amplitude at baseline, P<0.05) in patients with essential hypertension, but did not reduce sympathetic activity (2+/-4 versus 3+/-3 burst/min, P=NS; 95+/-11 versus 95+/-13% of amplitude at baseline, P=NS) in control subjects. The sympathetic response to hyperoxia was more marked in heart transplant recipients than in controls (85+/-9 versus 95+/-11% of baseline amplitude; P<0.05). The decrease in sympathetic activity was most evident in patients with the longest time after heart transplantation (r=-0.75, P<0.01). In conclusion, tonic chemoreflex activation increases resting muscle sympathetic nerve activity and favors blood pressure elevation after heart transplantation.
Evaluation of disposable filtration systems for harvesting high cell density fed batch processes

In the underlying study we evaluated different single-use filtration systems for cell separation and harvest clarification in 1,000 L scale. A screening of different depth filters was carried out with various single-use filters from Pall, Cuno (3M), Millipore and Sartorius Stedim. In total, we included 85 depth filtrations in the screening. Out of that, two single-use filtration systems were chosen and further tested in 200 L scale. Based on these results, a single-use filtration set-up for harvesting production scale fed batch processes was determined.
The effect of adding whole-body vibration to squat training on the functional performance and self-report of disease status in elderly patients with knee osteoarthritis: a randomized, controlled clinical study.

The study objectives were to evaluate the effects of adding whole-body vibration to squat training on functional performance and self-report of disease in elderly individuals with knee osteoarthritis (OA).



This was a prospective, randomized trial in which selected variables were evaluated at three periods: 3 weeks prior to the training, immediately prior, and after the end of the training.



Twenty-three (23) elderly subjects were evaluated using four functional performance tests: Berg Balance Scale (BBS), Timed Get Up and Go Test (TGUG), Chair Stand Test (CST), and 6-Minute Walk Test (6MWT), and a self-report of the status of disease (WOMAC).



The intervention lasted for 12 weeks, 3 times per week. The participants were randomized into two groups: (1) squat training with whole-body vibration, and (2) squat training without vibration.



Although there was no statistical difference in functional performance and self-report of disease status between the groups, performance in all the functional tests and in all the domains of WOMAC improved in the vibration group compared to their initial status. In the exercise group, performance improved only two tests (BBS and 6MWT), and there was a reduction in self-reported pain (WOMAC) compared to their initial status.



Although the addition of whole-body vibration to squat training failed to result in a significant improvement in functional performance and self-reported status of knee osteoarthritis in the elderly, the intragroup results suggest that whole-body vibration may represent a feasible and effective way of improving the functionality and self-perception of disease status in older adults with knee OA.
Sex differences in the administration-time-dependent effects of low-dose aspirin on ambulatory blood pressure in hypertensive subjects.

Previous studies have revealed sex differences in blood pressure (BP) regulation, pathophysiology of hypertension, and treatment responses to medication. On the other hand, low-dose aspirin has been shown to reduce BP when administered at bedtime, as opposed to upon awakening, in hypertensive subjects and pregnant women at risk for preeclampsia. The purpose of this research was to investigate the potential sex differences in the administration-time-dependent influence of aspirin on BP. We studied 130 men and 186 women with untreated mild hypertension, 44.1 +/- 13.2 yrs of age, randomized to receive aspirin (100 mg/day) either on awakening or at bedtime daily for three months. BP was measured for 48 h before and after treatment. With ASA on awakening, ambulatory BP was unchanged in men and slightly but significantly elevated in women (1.7/1.4 mmHg in the 48 h SBP/DBP means, respectively; p < 0.023). BP was significantly reduced after aspirin at bedtime and to a larger extent in women (-8.0/-5.6 mmHg in SBP/DBP) than men (5.5/3.4 mmHg, respectively; p < 0.009 between men and women). Factors influencing a stronger response of BP to aspirin at bedtime included female sex, elevated fasting glucose, and high glomerular filtration rate. This study corroborates the significant administration-time-dependent effect of low-dose aspirin on ambulatory BP in subjects with untreated mild hypertension, while documenting significant sex differences in the BP response to aspirin. Accordingly, results indicate that bedtime is the optimal time for aspirin ingestion in both men and women. This timed administration of low-dose aspirin could provide a cost-effective valuable approach for BP control and potential added cardiovascular protection, especially in hypertensive women.
10 mV – 1V step-up converter for energy harvesting applications

This paper presents an ultra-low-voltage step-up converter for energy harvesting applications, which is able to operate from supply voltages below the thermal voltage kT/q. The operation of the main blocks of the converter, namely an enhanced swing ring oscillator and a Dickson charge pump, both operating at ultra-low voltage, is described. The extremely low voltage operation, made feasible through the arrangement presented, is demonstrated via a prototype built with off-the-shelf devices and zero-VT transistors in a 130 nm CMOS technology. The prototype generates a DC output equal to 1V at current consumptions of 10 nA and 1 μA from input voltages of 10 and 25 mV, respectively.
Provision of bednets and water filters to delay HIV-1 progression: cost-effectiveness analysis of a Kenyan multisite study.

To estimate the effectiveness, costs and cost-effectiveness of providing long-lasting insecticide-treated nets (LLINs) and point-of-use water filters to antiretroviral therapy (ART)-naïve HIV-infected adults and their family members, in the context of a multisite study in Kenya of 589 HIV-positive adults followed on average for 1.7 years.



The effectiveness, costs and cost-effectiveness of the intervention were estimated using an epidemiologic-cost model. Model epidemiologic inputs were derived from the Kenya multisite study data, local epidemiological data and from the published literature. Model cost inputs were derived from published literature specific to Kenya. Uncertainty in the model estimates was assessed through univariate and multivariate sensitivity analyses.



We estimated net cost savings of about US$ 26 000 for the intervention, over 1.7 years. Even when ignoring net cost savings, the intervention was found to be very cost-effective at a cost of US$ 3100 per death averted or US$ 99 per disability-adjusted life year (DALY) averted. The findings were robust to the sensitivity analysis and remained most sensitive to both the duration of ART use and the cost of ART per person-year.



The provision of LLINs and water filters to ART-naïve HIV-infected adults in the Kenyan study resulted in substantial net cost savings, due to the delay in the initiation of ART. The addition of an LLIN and a point-of-use water filter to the existing package of care provided to ART-naïve HIV-infected adults could bring substantial cost savings to resource-constrained health systems in low- and middle-income countries.
Increasing work-place healthiness with the probiotic Lactobacillus reuteri: A randomised, double-blind placebo-controlled study

Short term illnesses, usually caused by respiratory or gastrointestinal diseases are disruptive to productivity and there is relatively little focus on preventative measures. This study examined the effect of the probiotic Lactobacillus reuteri protectis (ATCC55730) on its ability to improve work-place healthiness by reducing short term sick-leave caused by respiratory or gastrointestinal infections.



262 employees at TetraPak in Sweden (day-workers and three-shift-workers) that were healthy at study start were randomised in a double-blind fashion to receive either a daily dose of 108 Colony Forming Units of L. reuteri or placebo for 80 days. The study products were administered with a drinking straw. 181 subjects complied with the study protocol, 94 were randomised to receive L. reuteri and 87 received placebo.



In the placebo group 26.4% reported sick-leave for the defined causes during the study as compared with 10.6% in the L. reuteri group (p < 0.01). The frequency of sick-days was 0.9% in the placebo group and 0.4% in the L. reuteri group (p < 0.01). Among the 53 shift-workers, 33% in the placebo group reported sick during the study period as compared with none in the L. reuteri group(p < 0.005).
A phase II study of oxaliplatin, docetaxel, and GM-CSF in patients with previously treated advanced melanoma

Although much focus has been placed on immunotherapy for melanoma, further development of chemotherapy approaches is needed. Melanoma is responsive to platinum compounds and taxanes, but there is limited experience with combinations of these agents. Oxaliplatin has been reported to have detectable activity in melanoma, and a phase I study has identified a tolerable dose and schedule of oxaliplatin in combination with docetaxel and hematopoietic growth factor support. GM-CSF has a theoretical advantage of immune potentiation. These considerations supported the study of oxaliplatin, docetaxel, and GM-CSF in patients with advanced melanoma. Eligibility included adequate organ function, PS ≤ 2, at most one prior chemotherapy and one prior immunotherapy, no prior treatment with oxaliplatin or taxanes and no chremophor allergy. After premedication, docetaxel was administered day 1 at 75 mg/m2, then oxaliplatin on day 2 at 85 mg/m2. GM-CSF (250 mcg/m2) was administered s.c. days 3–12. Cycles were 21 days in length, and disease reevaluation was performed every two cycles by RECIST criteria. Nineteen patients received at least one cycle, eight with one prior systemic therapy, five with two prior systemic therapies. Five patients did not complete two cycles and were not formally evaluable for response. Five patients had stable disease (SD), including one who failed two prior therapies and went on to receive ten cycles. The remaining nine patients displayed progressive disease (PD) after two cycles. Notable toxicities included seven cases (37%) of grade III/IV neutropenia and two (11%) hypersensitivity reactions. This combination of oxaliplatin, docetaxel, and GM-CSF has limited clinical activity in previously treated patients with advanced melanoma. Exploration in treatment-naïve patients may still be warranted.