Miracle-dz/UniFAR-FTUs huggingface dataset:
Protection From Colorectal Cancer After Colonoscopy

BACKGROUND Colonoscopy with detection and removal of adenomas is considered a powerful tool to reduce colorectal cancer (CRC) incidence. However, the degree of protection achievable in a population setting with high-quality colonoscopy resources remains to be quantified. OBJECTIVE To assess the association between previous colonoscopy and risk for CRC. DESIGN Population-based case-control study. SETTING Rhine-Neckar region of Germany. PATIENTS A total of 1688 case patients with colorectal cancer and 1932 control participants aged 50 years or older. MEASUREMENTS A detailed lifetime history of CRC risk factors and preventive factors, including history and results of previous colonoscopies, and of medical data obtained by self-reports and medical records. Odds ratios of CRC associated with colonoscopy in the preceding 10 years were estimated, after adjustment for sex, age, education level, participation in a general health screening examination, family history of CRC, smoking status, body mass index, and use of nonsteroidal anti-inflammatory drugs or hormone replacement therapy. RESULTS Overall, colonoscopy in the preceding 10 years was associated with 77% lower risk for CRC. Adjusted odds ratios for any CRC, right-sided CRC, and left-sided CRC were 0.23 (95% CI, 0.19 to 0.27), 0.44 (CI, 0.35 to 0.55), and 0.16 (CI, 0.12 to 0.20), respectively. Strong risk reduction was observed for all cancer stages and all ages, except for right-sided cancer in persons aged 50 to 59 years. Risk reduction increased over the years in both the right and the left colon. LIMITATION The study was observational, with potential for residual confounding and selection bias. CONCLUSION Colonoscopy with polypectomy can be associated with strongly reduced risk for CRC in the population setting. Aside from strong risk reduction with respect to left-sided CRC, risk reduction of more than 50% was also seen for right-sided colon cancer. PRIMARY FUNDING SOURCE German Research Council and German Federal Ministry of Education and Research.
Comparison of incidence rates of cerebrovascular accidents and transient ischaemic attacks in observational cohort studies of patients prescribed risperidone, quetiapine or olanzapine in general practice in England including patients with dementia

Following changes in the safety information on the use of risperidone and olanzapine in elderly patients with dementia, data from prescription-event monitoring (PEM) studies of risperidone, quetiapine and olanzapine were examined. The aim was to compare incidence rates for events reported as cerebrovascular accident (CVA) and transient ischaemic attack (TIA) during the first 180 days of treatment in patients prescribed atypical antipsychotics for dementia or other indications, because of the possible association between dementia and stroke in users of atypical antipsychotics. A retrospective analysis of data from the three observational studies was conducted using Poisson regression modelling and survival analysis. Within the risperidone, quetiapine and olanzapine cohorts, 23 (0.30%), 6 (0.35%) and 10 (0.11%) patients respectively, were reported to have had a CVA/TIA event. Age, sex and indication (dementia or other) were identified as important confounding variables; age being the most important. The crude rate ratios (RRs) for CVA/TIA for risperidone or quetiapine vs. olanzapine indicated an approximate threefold relative difference in rate during the first six months but after adjustment for age, sex and indication, the RRs were non-significant (1.2 (95% CI 0.5,3.0) and 2.1 (95% CI 0.6,7.7), respectively). For risperidone vs. quetiapine, crude and adjusted RRs were not significantly different. Of the three drugs, the time to event was shortest for risperidone and also shortest for risperidone or quetiapine users where the indication was dementia. The age and sex adjusted RR of CVA/TIA in patients prescribed risperidone for dementia vs. other indications was 6.7 (95% CI 2.4,18.9). The adjusted RRs for quetiapine, according to indication, could not be calculated due to missing information on age and sex. There were no cases of CVA/TIA with dementia for olanzapine, thus the RRs and time to event curves according to indication could not be examined. This study revealed no significant difference in the adjusted RR of CVA/TIA events in the first 180 days of treatment in patients prescribed risperidone or quetiapine when compared with olanzapine. However, dementia appears to be an important risk factor. These results should be considered alongside other pharmacoepidemiological studies on this topic.
An immunohistochemical study of c‐erbb‐2 protein in gastric carcinomas and lymph‐node metastases: Is the c‐erbB‐2 protein really a prognostic indicator?

An immunohistochemical study of the c‐erbB‐2 protein was conducted on formalin‐fixed paraffin‐embedded tissue sections from 136 primary gastric carcinomas and 50 metastatic lymph node tumors obtained at gastrectomy. Expression of the protein was detected in 35 of 136 primary gastric carcinomas (25.7%) and 22 of 50 metastatic lymph nodes (44%). The staining pattern of tumor cells was classified as membranous or cytoplasmic. An immunohistochemical study using serially diluted antibody demonstrated that 82.6% of positive cases in metastatic lymph nodes showed c‐erbB‐2 immunoreactivity stronger than that in the primary tumors. Membranous staining was stronger than cytoplasmic staining. c‐erbB‐2 protein of the cytoplasmic as well as membranous types was confirmed to be a 185‐kDa whole molecule by immunoblotting. Correlation between the expression of c‐erbB‐2 protein and clinical and histological parameters was investigated. No significant correlation between 5‐year survival rate of patients and expression of c‐erbB‐2 protein was found. In the poorly differentiated carcinoma group possessing c‐erbB‐2 protein, overall survival was significantly shorter than in cases without protein expression ( p < 0.01). We conclude that c‐erbB‐2 protein is not a useful prognostic indicator in gastric carcinomas.
Natural Evolution of Perthes Disease: A Study of 610 Children Under 12 Years of Age at Disease Onset

Records and 2,634 pairs of radiographs (anteroposterior and lateral) of 610 patients with Perthes disease were reviewed. The evolution of the disease was divided into seven stages (stages Ia, Ib, IIa, IIb, IIIa, IIIb, and IV) based on plain radiographic appearances. Intraobserver and interobserver reproducibility of this new classification system was assessed. The duration of each stage of the disease was noted. The stages at which epiphyseal extrusion and widening of the metaphysis occurred and the stages at which metaphyseal and acetabular changes appeared were identified. The shape and the size of the femoral head, the extent of trochanteric overgrowth, and the radius of the acetabulum were assessed in hips that had healed. The new classification system of the evolution of Perthes disease was reproducible and helped to identify when crucial events occur during the course of the disease. The median duration of each stage varied between 95 and 335 days. Epiphyseal extrusion and metaphyseal widening was modest in stages Ia, Ib, and IIa but increased dramatically after stage IIb. More than 20% extrusion occurred in 70% of the hips by stage IIIa. Metaphyseal changes were most frequently encountered in stage IIb, while acetabular changes were most prevalent in stage IIIa. At healing, only 24% of untreated patients had spherical femoral heads, while 52% had irregular femoral heads. The timing of epiphyseal extrusion, metaphyseal widening, and the appearance of adverse metaphyseal and acetabular changes suggest that femoral head deformation occurs by stage IIIa in untreated hips. Hence, if containment were to succeed, it should be achieved before this stage.
Evaluation of breakdown characteristics of CO2 gas for non-standard lightning impulse waveforms - breakdown characteristics under single-frequency oscillation waveforms of 5.3 MHz to 20.0 MHz

SF6 gas, an insulation medium used for gas insulated switchgear (GIS), has a high global warming potential, hence the search for an effective alternative means from the environmental perspective. The authors are focusing on CO2 gas, which has a lower global warming potential (GWP), as one of its potential alternatives. In order to use this CO2 gas for actual GIS, the insulation characteristics for actual overvoltage waveforms generated in the field (called non-standard lightning impulse waveforms) must be obtained. For this purpose, the preceding study experimentally obtained and evaluated the insulation characteristics for relatively low frequency oscillation waveforms in disconnector switching surges generated in the actual field. In this paper, the insulation characteristics of the CO2 gas gap for higher frequency oscillation waveforms were experimentally obtained while changing the frequency and damping rate. Consequently, in the high frequency area, if the frequency was raised or the damping rate increased, the dielectric breakdown voltage tended to increase, consistently remaining higher than that for standard lightning impulse waveforms at a level of 1.08 to 1.36 times. Accordingly, it was found that the insulation specification could be rationalized by approximately 10% by converting non-standard lightning impulse waveforms to equivalent standard lightning impulse waveforms. In addition, the influence of gas pressure and gap length was examined and it emerged that the results obtained under basic experimental conditions were likely to be applicable to the conditions close to actual GIS conditions.
Incidence of childhood accidents determined in a study based on home surveys

Summary A retrospective survey of accidents during a 12-month period was carried out at Vila Lobato in the town of Ribeirão Preto, Brazil using home surveys involving 25% of residences in this area. Variables relating to the accidents and data concerning the children involved were analyzed, i.e. sex, age, type of accident, place of occurrence, time of day, time of year, which part of the body was involved and the person accompanying the victim of the accident. There were 260 accidents during the year, mainly involving the 1–5-year (41.1%) and 5–10-year (33.1%) age ranges. The most frequent accidents were falls (46.9%), contusions (26.5%) and cuts (11.9%). Most accidents occurred at home (65.7%), followed by in the street (25.4%) and at school (6.1%). More accidents occurred in the late afternoon (49.6%) and during the summer months and school holidays (38.1%) than at other times. The lower limbs were the sites most often involved (36.9%), followed by the upper limbs (32.3%) and the head (25.4%). Most children (75.7%) were accompanied when they suffered an accident. Slightly more boys (55.4%) than girls (44.6%) had accidents. Statistical analysis of the results by the χ2 test showed significant differences for all variables studied with respect to the occurrence of accidents (p > 0.05), except gender. The authors discuss the need to expand the debate on accidents and for the application of knowledge to prevent them occurring.
SIMPLE CONDITIONS FOR GROWTH OF UNICELLULAR BLUE‐GREEN ALGAE ON PLATES 1, 2

The efficiencies of plating of 2 cultures of unicellular blue‐green algae, 1 coccoid and 1 rod‐shaped, were studied systematically. Reproducible colony growth and accurate viable counts are dependent on the use of a low agar concentration, and on the sterilization of the agar separately from the mineral components of the medium.
Myocardial Ischemic Preconditioning Preserves Postischemic Function of the 26S Proteasome Through Diminished Oxidative Damage to 19S Regulatory Particle Subunits

Rationale: The ubiquitin proteasome system (UPS) becomes dysfunctional as a result of ischemia/reperfusion (I/R), which may lead to dysregulation of signaling pathways. Ischemic preconditioning (IPC) may prevent dysregulation by preventing UPS dysfunction through inhibition of oxidative damage. Objective: Examine the hypothesis that early IPC preserves postischemic UPS function thus facilitating prosurvival signaling events. Methods and Results: I/R decreased proteasome chymotryptic activity by 50% in isolated rat heart and an in vivo murine left anterior descending coronary artery occlusion model. Following IPC, proteasome activity was decreased 25% (P<0.05) in isolated heart and not different from baseline in the murine model. Enriched 26S proteasome was prepared and analyzed for protein carbonyl content. Increased (P<0.05) carbonylation in a 53-kDa band following I/R was diminished by IPC. Immunoprecipitation studies indicated that the 53-kDa carbonylation signal was of proteasomal origin. Two-dimensional gel electrophoresis resolved the 53-kDa band into spots analyzed by liquid chromatography/tandem mass spectrometry containing Rpt3/Rpt5 both of which could be immunoprecipitated conjugated to dinitrophenylhydrazine (DNPH). Higher amounts of DNPH-tagged Rpt5 were immunoprecipitated from the I/R samples and less from the IPC samples. I/R increased Bax levels by 63% (P<0.05) which was decreased by IPC. Lactacystin (lac) pretreatment of preconditioned hearts increased Bax by 140% (P<0.05) and also increased ubiquitinated proteins. Pretreatment of hearts with a proteasome inhibitor reversed the effects of IPC on postischemic Rpt5 carbonylation, cardiac function, morphology and morphometry, and ubiquitinated and signaling proteins. Conclusions: These studies suggest that IPC protects function of the UPS by diminishing oxidative damage to 19S regulatory particle subunits allowing this complex to facilitate degradation of proapoptotic proteins.
The Shape of the Plasma Glucose Curve During an Oral Glucose Tolerance Test as an Indicator of Beta Cell Function and Insulin Sensitivity in End-Pubertal Obese Girls

Abstract It is hypothesized that the shape of the glucose curve during an oral glucose tolerance test is an early indicator of the risk for developing type 2 diabetes mellitus. In this study, we aimed to examine the shape of plasma glucose response curves and study their relationship with insulin sensitivity, insulin secretion and components of the metabolic syndrome in end-pubertal obese girls. Eighty-one end-pubertal obese girls [median (range) age: 14.4 (11.2–18.0) years; BMI: 34.6 (25.4–50.8) kg/m²] who underwent a 2-h oral glucose tolerance test were classified according to the shape of the glucose curve. Four shape types of the plasma glucose response curve were observed: 28 (34.6%) monophasic, 30 (37.0%) biphasic, 14 (17.3%) triphasic, and 9 (11.1%) unclassified. Patients with a monophasic shape had a higher area under the curve for glucose (p=0.008), a lower early-phase insulin secretion (p=0.005), and a poorer beta cell function relative to insulin sensitivity as reflected by the oral disposition index (p=0.022) compared to the bi- and triphasic shape types. In addition, the triglyceride level and TG/HDL-C ratio was higher in patients with a monophasic shape compared to those with a biphasic shape (p=0.040 and p=0.048, respectively). In conclusion, end-pubertal obese girls with a monophasic plasma glucose curve are at increased risk for insulin resistance, which can contribute to the development of type 2 diabetes mellitus and cardiovascular diseases.
Hypoglycemia, S‐ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes

Johannesen J, Svensson J, Bergholdt R, Eising S, Gramstrup H, Frandsen E, Dick‐Nielsen J, Hansen L, Pociot F, Mortensen HB, The Danish Society for Diabetes in Childhood and Adolescence. Hypoglycemia, S‐ACE and ACE genotypes in a Danish nationwide population of children and adolescents with type 1 diabetes.
The lectin complement pathway serine proteases (MASPs) represent a possible crossroad between the coagulation and complement systems in thromboinflammation

Essentials The lectin pathway's MASP‐1/2 activates coagulation factors but the trigger of the activation is unknown. MASP‐1/2 activation was assessed by quantifying complexes between MASPs and antithrombin/C1‐inhibitor. Activated platelets and fibrin were demonstrated to activate MASP‐1 and MASP‐2 both in vitro and in vivo. These findings may represent a crossroad between the complement and the coagulation systems.
Period analysis of variable stars by robust smoothing

Summary. The objective is to estimate the period and the light curve (or periodic function) of a variable star. Previously, several methods have been proposed to estimate the period of a variable star, but they are inaccurate especially when a data set contains outliers. We use a smoothing spline regression to estimate the light curve given a period and then find the period which minimizes the generalized cross‐validation (GCV). The GCV method works well, matching an intensive visual examination of a few hundred stars, but the GCV score is still sensitive to outliers. Handling outliers in an automatic way is important when this method is applied in a ‘data mining’ context to a vary large star survey. Therefore, we suggest a robust method which minimizes a robust cross‐validation criterion induced by a robust smoothing spline regression. Once the period has been determined, a nonparametric method is used to estimate the light curve. A real example and a simulation study suggest that the robust cross‐validation and GCV methods are superior to existing methods.
Phenotypic heterogeneity promotes adaptive evolution

Genetically identical cells frequently display substantial heterogeneity in gene expression, cellular morphology and physiology. It has been suggested that by rapidly generating a subpopulation with novel phenotypic traits, phenotypic heterogeneity (or plasticity) accelerates the rate of adaptive evolution in populations facing extreme environmental challenges. This issue is important as cell-to-cell phenotypic heterogeneity may initiate key steps in microbial evolution of drug resistance and cancer progression. Here, we study how stochastic transitions between cellular states influence evolutionary adaptation to a stressful environment in yeast Saccharomyces cerevisiae. We developed inducible synthetic gene circuits that generate varying degrees of expression stochasticity of an antifungal resistance gene. We initiated laboratory evolutionary experiments with genotypes carrying different versions of the genetic circuit by exposing the corresponding populations to gradually increasing antifungal stress. Phenotypic heterogeneity altered the evolutionary dynamics by transforming the adaptive landscape that relates genotype to fitness. Specifically, it enhanced the adaptive value of beneficial mutations through synergism between cell-to-cell variability and genetic variation. Our work demonstrates that phenotypic heterogeneity is an evolving trait when populations face a chronic selection pressure. It shapes evolutionary trajectories at the genomic level and facilitates evolutionary rescue from a deteriorating environmental stress.
RNA Sequences and Structures Required for the Recruitment and Activity of the Dengue Virus Polymerase*

Dengue virus RNA-dependent RNA polymerase specifically binds to the viral genome by interacting with a promoter element known as stem-loop A (SLA). Although a great deal has been learned in recent years about the function of this promoter in dengue virus-infected cells, the molecular details that explain how the SLA interacts with the polymerase to promote viral RNA synthesis remain poorly understood. Using RNA binding and polymerase activity assays, we defined two elements of the SLA that are involved in polymerase interaction and RNA synthesis. Mutations at the top of the SLA resulted in RNAs that retained the ability to bind the polymerase but impaired promoter-dependent RNA synthesis. These results indicate that protein binding to the SLA is not sufficient to induce polymerase activity and that specific nucleotides of the SLA are necessary to render an active polymerase-promoter complex for RNA synthesis. We also report that protein binding to the viral RNA induces conformational changes downstream of the promoter element. Furthermore, we found that structured RNA elements at the 3′ end of the template repress dengue virus polymerase activity in the context of a fully active SLA promoter. Using assays to evaluate initiation of RNA synthesis at the viral 3′-UTR, we found that the RNA-RNA interaction mediated by 5′-3′-hybridization was able to release the silencing effect of the 3′-stem-loop structure. We propose that the long range RNA-RNA interactions in the viral genome play multiple roles during RNA synthesis. Together, we provide new molecular details about the promoter-dependent dengue virus RNA polymerase activity.
Association Between Intestinal Vitamin D Receptor, Calcium Absorption, and Serum 1,25 Dihydroxyvitamin D in Normal Young and Elderly Women

The exact mechanism for the decrease in intestinal calcium absorption with age is not yet understood. A decrease with age in serum 1,25‐dihydroxyvitamin D (1,25(OH)2D) or a decrease in the intestinal vitamin D receptor (VDR) protein concentration are possible causes. The objective of this study was to examine the effect of age on these factors. Fifty‐nine young women age 25–35 years were compared with 41 elderly women age 65–83 years who underwent measurements of VDR, calcium absorption using a 20 mg and 100 mg calcium carrier, and calciotropic hormones. Calcium absorption by both tests was lower in the elderly women compared with the young women (p < 0.05). Serum 1,25(OH)2D and duodenal VDR protein concentration were not significantly different between the two age groups. Serum 1,25(OH)2D correlated with the 20 mg calcium absorption test in both young (r = 0.35, p < 0.007) and elderly women (r = 0.58, p < 0.0001) and with the 100 mg calcium absorption in the elderly (r = 0.32; p < 0.05). VDR did not correlate with calcium absorption in young women or elderly women, nor did VDR correlate with serum 1,25(OH)2D and serum 25‐hydroxyvitamin D. In summary, the decrease in calcium absorption cannot be explained by a decrease in intestinal VDR. The correlation between serum 1,25(OH)2D and both calcium absorption tests only accounts for 12–30% of the variance in the age‐related change in the calcium absorption tests. Other factors, not yet understood, are responsible for the decline in calcium absorption with age.