nils-herrmann/clean_scirepeval huggingface dataset:
Microglandular adenosis associated with triple-negative breast cancer is a neoplastic lesion of triple-negative phenotype harbouring TP53 somatic mutations.

Microglandular adenosis (MGA) is a rare proliferative lesion of the breast composed of small glands lacking myoepithelial cells and lined by S100-positive, oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative epithelial cells. There is evidence to suggest that MGA may constitute a non-obligate precursor of triple-negative breast cancer (TNBC). We sought to define the genomic landscape of pure MGA and of MGA, atypical MGA (AMGA) and associated TNBCs, and to determine whether synchronous MGA, AMGA, and TNBCs would be clonally related. Two pure MGAs and eight cases of MGA and/or AMGA associated with in situ or invasive TNBC were collected, microdissected, and subjected to massively parallel sequencing targeting all coding regions of 236 genes recurrently mutated in breast cancer or related to DNA repair. Pure MGAs lacked clonal non-synonymous somatic mutations and displayed limited copy number alterations (CNAs); conversely, all MGAs (n = 7) and AMGAs (n = 3) associated with TNBC harboured at least one somatic non-synonymous mutation (range 3-14 and 1-10, respectively). In all cases where TNBCs were analyzed, identical TP53 mutations and similar patterns of gene CNAs were found in the MGA and/or AMGA and in the associated TNBC. In the MGA/AMGA associated with TNBC lacking TP53 mutations, somatic mutations affecting PI3K pathway-related genes (eg PTEN, PIK3CA, and INPP4B) and tyrosine kinase receptor signalling-related genes (eg ERBB3 and FGFR2) were identified. At diagnosis, MGAs associated with TNBC were found to display subclonal populations, and clonal shifts in the progression from MGA to AMGA and/or to TNBC were observed. Our results demonstrate the heterogeneity of MGAs, and that MGAs associated with TNBC, but not necessarily pure MGAs, are genetically advanced, clonal, and neoplastic lesions harbouring recurrent mutations in TP53 and/or other cancer genes, supporting the notion that a subset of MGAs and AMGAs may constitute non-obligate precursors of TNBCs.
The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1)

Lifestyle modification helps in the primary prevention of diabetes in multiethnic American, Finnish and Chinese populations. In a prospective community-based study, we tested whether the progression to diabetes could be influenced by interventions in native Asian Indians with IGT who were younger, leaner and more insulin resistant than the above populations. We randomised 531 (421 men 110 women) subjects with IGT (mean age 45.9±5.7 years, BMI 25.8±3.5 kg/m2) into four groups. Group 1 was the control, Group 2 was given advice on lifestyle modification (LSM), Group 3 was treated with metformin (MET) and Group 4 was given LSM plus MET. The primary outcome measure was type 2 diabetes as diagnosed using World Health Organization criteria. The median follow-up period was 30 months, and the 3-year cumulative incidences of diabetes were 55.0%, 39.3%, 40.5% and 39.5% in Groups 1–4, respectively. The relative risk reduction was 28.5% with LSM (95% CI 20.5–37.3, p=0.018), 26.4% with MET (95% CI 19.1–35.1, p=0.029) and 28.2% with LSM + MET (95% CI 20.3–37.0, p=0.022), as compared with the control group. The number needed to treat to prevent one incident case of diabetes was 6.4 for LSM, 6.9 for MET and 6.5 for LSM + MET. Progression of IGT to diabetes is high in native Asian Indians. Both LSM and MET significantly reduced the incidence of diabetes in Asian Indians with IGT; there was no added benefit from combining them.
Effect of a 12-Month Intensive Lifestyle Intervention on Hepatic Steatosis in Adults With Type 2 Diabetes

Weight loss through lifestyle changes is recommended for nonalcoholic fatty liver disease (NAFLD). However, its efficacy in patients with type 2 diabetes is unproven.



Look AHEAD (Action for Health in Diabetes) is a 16-center clinical trial with 5,145 overweight or obese adults with type 2 diabetes, who were randomly assigned to an intensive lifestyle intervention (ILI) to induce a minimum weight loss of 7% or a control group who received diabetes support and education (DSE). In the Fatty Liver Ancillary Study, 96 participants completed proton magnetic resonance spectroscopy to quantify hepatic steatosis and tests to exclude other causes of liver disease at baseline and 12 months. We defined steatosis >5.5% as NAFLD.



Participants were 49% women and 68% white. The mean age was 61 years, mean BMI was 35 kg/m(2), mean steatosis was 8.0%, and mean aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were 20.5 and 24.2 units/l, respectively. After 12 months, participants assigned to ILI (n = 46) lost more weight (-8.5 vs. -0.05%; P < 0.01) than those assigned to DSE and had a greater decline in steatosis (-50.8 vs. -22.8%; P = 0.04) and in A1C (-0.7 vs. -0.2%; P = 0.04). There were no significant 12-month changes in AST or ALT levels. At 12 months, 26% of DSE participants and 3% (1 of 31) of ILI participants without NAFLD at baseline developed NAFLD (P < 0.05).



A 12-month intensive lifestyle intervention in patients with type 2 diabetes reduces steatosis and incident NAFLD.
Cemented titanium stems show high migration: transprosthetic drainage system has no advantage over third-generation cementation technique

A newly developed cemented titanium stem with excellent laboratory results using a transprosthetic drainage system (TDS) was clinically tried for the first time. Prognostic radiographic methods including migration measurement and clinical investigation were performed for up to 7 years. Twenty-two patients prospectively and consecutively received total hip replacement using a cemented titanium stem and a threaded Zweymüller cup. Ten stems (CPS) were cemented conventionally with a third-generation cementation technique. In 12 stems (TRIOS) a TDS was used to enhance cement mantle quality. Design of cup and stem was similar in all cases. More than 50% of all stems showed considerable subsidence (>1 mm at 2 years and >2.5 mm at 5 years) and progressive radiolucent lines ( >1 mm at 2 years). Two patients of the TRIOS group had to be revised at 7 years postoperatively. No significant differences were found in radiological parameters (migration, stem subsidence, tilting, occurrence of radiolucent lines) and clinical outcome between the two cementation techniques. All parameters indicate an unfavourable long-term survival. Use of a TDS did not show any significant advantages over the conventional cementation technique. It can be concluded that cementing titanium stems of this design cannot be recommended.
Real-time Hair Simulation on Mobile Device

Hair rendering and simulation is a fundamental part in the representation of virtual characters. But intensive calculation for the dynamic on thousands of hair strands makes the task much challengeable, especially on a portable device. The aim of this short paper is to solve the problem of how to perform real-time hair simulation and rendering on mobile device. In this paper, the process of hair simulation and rendering is adapted according to the property of mobile device hardware. To increase the number of hair strands of simulation, we adopted the Dynamic follow-the-leader (DFTL) method and altered it by our new method of interpolation. We also pictured a rendering strategy basing on the survey of the limitation of mobile GPU. Lastly we present an innovational method that carried out order independent transparency at a relatively inexpensive cost.
Multiple variants of the DRD3, but not BDNF gene, influence age-at-onset of schizophrenia

Age-at-onset (AAO) of schizophrenia appears to be influenced by various factors including gender and genetics. Males appear to be affected earlier than females and variants of brain-derived neurotrophic factor (BDNF) and of dopamine receptor D3 (DRD3) genes, which are thought to be functionally related, may affect AAO of schizophrenia. However, no study has evaluated multiple single-nucleotide polymorphisms (SNPs) covering these two genes and their effect on AAO of schizophrenia. We report here analyses of 10 and 5 polymorphisms spanning DRD3 and BDNF genes, respectively. Two hundred thirty-eight Caucasian patients (163 men, 75 women) who were diagnosed with schizophrenia before age 40 were included. They were recruited from three clinical sites in North America: the Centre for Addiction and Mental Health in Toronto (Drs GR and JLK, n = 112); Case Western Reserve University in Cleveland, Ohio (Dr HYM, n = 72); Hillside Hospital in Glen Oaks, New York (Dr JAL, n = 54). All four clinicians are highly experienced in schizophrenia assessment. Subjects were recruited based on their diagnoses of schizophrenia according to DSM-III-R or DSM-IV and the availability of AAO data. The AAO was defined as the age when the subject first met DSM criteria for schizophrenia. All SNPs were genotyped using standard ABI TaqMan assay protocols. Genotypes were assigned manually post-amplification on the ABI 7500 Sequence Detection System. No significant differences in genotype and sex distributions between the samples from the three different clinical sites were noted using w tests with SPSS software, allowing the samples to be pooled. Hardy–Weinberg equilibrium was respected for the SNPs reported here. The influence of AAO of schizophrenia was studied by two complementary analyses: analysis of variance was performed for mean AAOs, and survival analysis (Cox proportional hazards model) was used to estimate the effect of gender and genotype on AAO of schizophrenia using SPSS (version 14.0.2). Results for the Cox model were corrected for multiple testing using SNP Spectral Decomposition and SNPSpD software, which take into account the linkage
A detailed report of the resource use and costs associated with implementation of a short stay programme for breast cancer surgery

Despite the increased attention for assessing the effectiveness of implementation strategies, most implementation studies provide little or no information on its associated costs. The focus of the current study was to provide a detailed report of the resource use and costs associated with implementation of a short stay programme for breast cancer surgery in four Dutch hospitals.



The analysis was performed alongside a multi-centre implementation study. The process of identification, measurement and valuation of the implementation activities was based on recommendations for the design, analysis and reporting of health technology assessments. A scoring form was developed to prospectively determine the implementation activities at professional and implementation expert level. A time horizon of 5 years was used to calculate the implementation costs per patient.



Identified activities were consisted of development and execution of the implementation strategy during the implementation project. Total implementation costs over the four hospitals were €83.293. Mean implementation costs, calculated for 660 patients treated over a period of 5 years, were €25 per patient. Subgroup analyses showed that the implementation costs ranged from €3.942 to €32.000 on hospital level. From a local hospital perspective, overall implementation costs were €21 per patient, after exclusion of the costs made by the expert centre.



We provided a detailed case description of how implementation costs can be determined. Notable differences in implementation costs between hospitals were observed.
Correction: A Rule-Based Prognostic Model for Type 1 Diabetes by Identifying and Synthesizing Baseline Profile Patterns

The DPT-1 Study Group is not included in the author byline. They should be listed as the seventh author. The full membership of the study group can be found in Appendix S2 below. There are errors in the Funding section. The correct funding information is as follows: This work has been supported by the University of South Florida and funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shiver National Institute of Child Health and Human Development (NICHD, the National Center for Research Resources (NCRR), the National Center on Minority Health and Health Disparities (NCMHD), the Office of Research on Women’s Health (ORWH), the Juvenile Diabetes Research Foundation (JDRF); and the American Diabetes Association (ADA). The NIH grant numbers which supported this research are: DK060782, DK060916, DK060987, DK061010, DK061029, DK061030, DK061034, DK061035, DK061036, DK061037, DK061038, DK061040, DK061041, DK061042, DK061058, DK061055. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Validation of the health ABC heart failure model for incident heart failure risk prediction: the Cardiovascular Health Study.

The recently developed and internally validated Health ABC HF model uses 9 routinely available clinical variables to determine incident heart failure risk. In this study, we sought to externally validate the Health ABC HF model.



Observed 5-year incidence of heart failure, defined as first hospitalization for new-onset heart failure, was compared with 5-year risk estimates derived from the Health ABC HF model among participants without heart failure at baseline in the Cardiovascular Health Study. During follow-up, 400 of 5335 (7.5%) participants developed heart failure over 5 years versus 364 (6.8%) predicted by the Health ABC HF model (predicted-to-observed ratio, 0.90). Observed versus predicted 5-year heart failure probabilities were 3.2% versus 2.8%, 9.0% versus 7.0%, 15.9% versus 13.7%, and 24.6% versus 30.8% for the <5%, 5% to 10%, 10% to 20%, and >20% 5-year risk categories, respectively. The Hosmer-Lemeshow chi(2) was 14.72 (degrees of freedom, 10; P=0.14), and the C index was 0.74 (95% CI, 0.72 to 0.76). Calibration and discrimination demonstrated adequate performance across sex and race overall; however, risk was underestimated in white men, especially in the 5% to 10% risk category. Model performance was optimal when participants with normal left ventricular function at baseline were assessed separately. Performance was consistent across age groups. Analyses with death as a competing risk yielded similar results.



The Health ABC HF model adequately predicted 5-year heart failure risk in a large community-based study, providing support for the external validity of the model. This tool may be used to identify individuals to whom to target heart failure prevention efforts.
Enhanced Apoptosis of Monocytes from Complication-Free Juvenile-Onset Diabetes Mellitus Type 1 May Be Ameliorated by TNF-α Inhibitors

Diabetes mellitus type 1 is associated with an enhanced apoptosis of different cells and tissues, accelerating occurrence of diabetic microvascular complications. The aim of our study was to determine spontaneous apoptotic potential of the monocyte subsets in juvenile-onset complication-free diabetes mellitus type 1 and to compare them with the corresponding values of the healthy. Moreover, we wanted to assess effects of TNF-R1 blocking agents and those of general TNF-α blocker (Infliximab) on spontaneous apoptosis of monocytes. Sixty randomly selected DM1 patients (14.5 ± 3.2 years) and 30 healthy (13.5 ± 2.8 years) volunteers were enrolled in the study. Our results indicate that three monocyte subsets are distinguishable in the groups of young diabetic patients and the healthy, similarly to in the blood of adults. DM1 patients were characterized by higher values of apoptotic monocytes than the healthy. The manipulation with drugs inhibiting TNF-R1 expression diminished the pool of CD16(+) apoptotic monocytes. Infliximab reduced the apoptotic CD16(-) cells. In conclusion, diabetes mellitus type 1 is associated with greater apoptosis of three monocyte subsets which may contribute to the development of microvascular complications. TNF-α modifiers appear to ameliorate monocyte apoptosis. They may be useful for controlling excessive monocyte apoptosis in diabetic patients.
Randomized phase II study of lonaprisan as second-line therapy for progesterone receptor-positive breast cancer

W. Jonat1*, T. Bachelot2, T. Ruhstaller3, I. Kuss4, U. Reimann4 & J. F. R. Robertson5 Department of Gynaecology and Obstetrics, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany; Department of Medical Oncology and Lyon Cancer Research Centre, Centre Léon Bérard, Lyon, France; Breast Centre St. Gallen, Kantonsspital St. Gallen, St. Gallen, Switzerland; Bayer Pharma AG, Berlin, Germany; Academic Division of Breast Surgery, University of Nottingham, Royal Derby Hospital, Derby, UK
Correlates of cigarette smoking during pregnancy and its genetic and environmental overlap with nicotine dependence.

Cigarette smoking during pregnancy (CSDP) is associated with a number of negative outcomes in the offspring. Therefore, clarifying the correlates of CSDP and the extent to which CSDP is associated with nicotine dependence is an important step toward reducing its rate in the general population. Using data from 1,134 adult Australian female monozygotic and dizygotic twin pairs, we explored the associations between CSDP and sociodemographic and psychiatric correlates and between CSDP and patterns of cigarette smoking. Further, we examined the role of heritable and environmental influences on CSDP and investigated whether these latent risk factors are shared with a predisposition to nicotine dependence. Women smoking during an entire pregnancy reported heavier dependence and more unsuccessful quit attempts, compared with the community sample of mothers and with women who smoked during only part of a pregnancy. Educational attainment, weekly church attendance, spousal current smoking, and nicotine dependence also were associated with CSDP. Heritable influences explained 34% of the variation in CSDP, with the remainder related to nonshared environmental factors. A large proportion of the genetic influences on CSDP were shared with DSM-III-R nicotine dependence, with little overlap across the nonshared environmental influences. A lifetime history of difficulty with smoking cessation, in conjunction with social background and psychiatric comorbidity, especially during pregnancy, needs to be considered by treatment providers when counseling expectant mothers about the potential risks of CSDP.
Hepatitis B virus surface proteins accelerate cholestatic injury and tumor progression in Abcb4-knockout mice

Understanding of the pathophysiology of cholestasis associated carcinogenesis could challenge the development of new personalized therapeutic approaches and thus improve prognosis. Simultaneous damage might aggravate hepatic injury, induce chronic liver disease and even promote carcinogenesis. We aimed to study the effect of Hepatitis B virus surface protein (HBsAg) on cholestatic liver disease and associated carcinogenesis in a mouse model combining both impairments. Hybrids of Abcb4-/- and HBsAg transgenic mice were bred on fibrosis susceptible background BALB/c. Liver injury, serum bile acid concentration, hepatic fibrosis, and carcinogenesis were enhanced by the combination of simultaneous damage in line with activation of c-Jun N-terminal kinase (JNK), proto-oncogene c-Jun, and Signal transducer and activator of transcription 3 (STAT3). Activation of Protein Kinase RNA-like Endoplasmic Reticulum Kinase (PERK) and Eukaryotic translation initiation factor 2A (eIF2α) indicated unfolded protein response (UPR) in HBsAg-expressing mice and even in Abcb4-/- without HBsAg-expression.



Cholestasis-induced STAT3- and JNK-pathways may predispose HBsAg-associated tumorigenesis. Since STAT3- and JNK-activation are well characterized critical regulators for tumor promotion, the potentiation of their activation in hybrids suggests an additive mechanism enhancing tumor incidence.
Reservoir Computing: Quo Vadis?

Reservoir Computing (RC) is an umbrella term for adaptive computational paradigms that rely on an excitable dynamical system, also called the "reservoir." The paradigms have been shown to be particularly promising for temporal signal processing. RC was also explored as a potential candidate for emerging nanoscale architectures. In this article we reflect on the current state of RC and muse about its future. In particular, we propose a set of open problems that we think need to be addressed in order to make RC more mainstream.
Neuropsychiatric symptoms in patients with dementia in primary care: a study protocol

Neuropsychiatric symptoms (NPS) frequently occur in patients with dementia. To date, prospective studies on the course of NPS have been conducted in patients with dementia in clinical centers or psychiatric services. The primary goal of this study is to investigate the course of NPS in patients with dementia and caregiver distress in primary care. We also aim to detect determinants of both the course of NPS in patients with dementia and informal caregiver distress in primary care.



This is a prospective observational study on the course of NPS in patients with dementia in primary care. Thirty-seven general practitioners (GPs) in 18 general practices were selected based on their interest in participating in this study. We will retrieve electronic medical files of patients with dementia from these general practices. Patients and caregivers will be followed for 18 months during the period January 2012 to December 2013. Patient characteristics will be collected at baseline. Time to death or institutionalization will be measured. Co-morbidity will be assessed using the Charlson index. Psychotropic drug use and primary and secondary outcome measures will be measured at 3 assessments, baseline, 9 and 18 months. The primary outcome measures are the Neuropsychiatric Inventory score for patients with dementia and the Sense of Competence score for informal caregivers. In addition to descriptive analyses frequency parameters will be computed. Univariate analysis will be performed to identify determinants of the course of NPS and informal caregiver distress. All determinants will then be tested in a multivariate regression analysis to determine their unique contribution to the course of NPS and caregiver distress.



The results of this study will provide data on the course of NPS, which is clinically important for prognosis. The data will help GPs and other professionals in planning follow-up visits and in the timing for offering psycho-education, psychosocial interventions and the provision of care. In addition, these data will enlarge health professionals' awareness of NPS in their patients with dementia.