Miracle-dz/UniFAR-FTUs huggingface dataset:
On the adaptive significance of stress-induced immunosuppression

We approach the field of stress immunology from an ecological point of view and ask: why should a heavy physical workload, for example as a result of a high reproductive effort, compromise immune function? We argue that immunosuppression by neuroendocrine mechanisms, such as stress hormones, during heavy physical workload is adaptive, and consider two different ultimate explanations of such immunosuppression. First, several authors have suggested that the immune system is suppressed to reallocate resources to other metabolic demands. In our view, this hypothesis assumes that considerable amounts of energy or nutrients can be saved by suppressing the immune system; however, this assumption requires further investigation. Second, we suggest an alternative explanation based on the idea that the immune system is tightly regulated by neuroendocrine mechanisms to avoid hyperactivation and ensuing autoimmune responses. We hypothesize that the risk of autoimmune responses increases during heavy physical workload and that the immune system is suppressed to counteract this.
Development and Preliminary Validation of the Questionnaire on Pediatric Gastrointestinal Symptoms to Assess Functional Gastrointestinal Disorders in Children and Adolescents

Objective: The aim of this study was to develop a questionnaire assessing symptoms associated with pediatric functional gastrointestinal disorders (FGIDs) and to provide preliminary evidence for its validity and reliability in a tertiary care setting. Methods: The Questionnaire on Pediatric Gastrointestinal Symptoms (QPGS) was designed as both a parent report and child self-report measure based on the pediatric Rome II criteria for FGIDs. It was constructed in English, translated into French, and pilot tested in both languages. Initial validation was performed using the French version. Participants were 315 consecutive new patients aged 4 to 18, and their parents, presenting to a gastroenterology clinic and classified as having a functional problem. Content validity, item discrimination capacity, and reliability (parent-child concordance and temporal stability) were examined. Results: Analyses of parent and child reports indicated that all items were pertinent and variably distributed. Although children were reliable reporters, up to 42% of parents did not know about their children's gastrointestinal functioning. As many as 60% of parents of children 10 to 18 could not respond to questions about defecation and subjective symptoms. Concordance was generally fair to good, with Kappas and intraclass correlations of 0.40 to 0.70 on most items. Test-retest reliability was moderate to good for the majority of items. Conclusion: This study supports the content validity of the QPGS. Form A is a reliable measure for parents of children 4 to 9 years old, but the child self-report Form C appears to be more reliable for 10 to 18 year olds.
Ideal observers and optimal ROC hypersurfaces in N-class classification

The likelihood ratio, or ideal observer, decision rule is known to be optimal for two-class classification tasks in the sense that it maximizes expected utility (or, equivalently, minimizes the Bayes risk). Furthermore, using this decision rule yields a receiver operating characteristic (ROC) curve which is never above the ROC curve produced using any other decision rule, provided the observer's misclassification rate with respect to one of the two classes is chosen as the dependent variable for the curve (i.e., an "inversion" of the more common formulation in which the observer's true-positive fraction is plotted against its false-positive fraction). It is also known that for a decision task requiring classification of observations into N classes, optimal performance in the expected utility sense is obtained using a set of N-1 likelihood ratios as decision variables. In the N-class extension of ROC analysis, the ideal observer performance is describable in terms of an (N/sup 2/-N-1)-parameter hypersurface in an (N/sup 2/-N)-dimensional probability space. We show that the result for two classes holds in this case as well, namely that the ROC hypersurface obtained using the ideal observer decision rule is never above the ROC hypersurface obtained using any other decision rule (where in our formulation performance is given exclusively with respect to between-class error rates rather than within-class sensitivities).
Strategies to improve recruitment to research studies.

BACKGROUND Research studies are essential to improving healthcare. However, many fail to recruit their planned number of participants. There are many interventions that researchers try to improve recruitment. Finding which ones are effective would be of benefit to the research community and society. OBJECTIVES To quantify the effects of strategies to improve participation in research studies. SEARCH STRATEGY We aimed to find all randomized and quasi-randomized controlled trials of strategies to improve recruitment to research studies. We searched nine electronic databases and manually searched the reference lists of relevant trials. We assessed the eligibility of each trial using pre-defined criteria. SELECTION CRITERIA Randomized and quasi-randomized controlled trials of methods to increase recruitment in research studies. This includes non-healthcare studies. Studies that required only questionnaire completion were excluded. DATA COLLECTION AND ANALYSIS We extracted data on the method evaluated, nature of the population, nature of the study to be recruited into, randomisation or quasi-randomisation method, allocation concealment, numbers and proportions in each arm. We used risk ratios and their 95% confidence intervals to describe the effects in individual trials, and assessed heterogeneity of these ratios between trials. MAIN RESULTS We identified 15 eligible trials, including a total of 33,719 participants. All strategies were aimed at participants for healthcare studies. No strategies were identified at the level of researcher collaborators or ethics committees. Because of heterogeneity between trials and within strategies, the results were not synthesised. Trials of monetary incentives, an additional questionnaire at invitation and treatment information on the consent form demonstrated benefit; these specific interventions from individual trials are not easily generalizable. AUTHORS' CONCLUSIONS On this evidence, it is not possible to predict the effect most interventions will have on recruitment. Funders and researchers should ensure that the evaluation of recruitment strategies are incorporated into research studies.
Vaginal estriol–lactobacilli combination and quality of life in endocrine-treated breast cancer

Abstract Objective We investigated the effect of a combination of vaginal ultra-low-dose estriol with lactobacilli on the sexual functioning domain of quality of life during the treatment of breast cancer survivors on an aromatase inhibitor with vaginal atrophy. Subjects and methods This was an open-label, bicentric, exploratory, clinical study in 16 postmenopausal breast cancer survivors on aromatase inhibitors suffering from vaginal atrophy-induced sexual disorders. Atrophy symptoms were assessed by scoring with an 11-point estimation scale (0 = not at all, 10 = worst imaginable feeling). Sexuality parameters of quality of life and medication adherence were recorded in a patient's diary and in the Female Somatic Sexual Experience Instrument (FSSEI) questionnaire. Patients underwent an initial treatment for 4 weeks (one vaginal tablet of Gynoflor® containing 0.03 mg estriol daily), followed by maintenance therapy (three vaginal Gynoflor® tablets weekly) for 8 weeks. Results Vaginal dryness continuously improved from a median score of 8 at entry to a score of 4 at the end of initial therapy, and a median score of 2 at the end of maintenance therapy. Normal sexual activity before breast cancer diagnosis was reported by 14 women (88%). At study entry, only three women (19%) were sexually active. At the end of the Gynoflor® regimen, ten women (63%) reported sexual activity, of which seven (44%) reported sexual intercourse. The FSSEI demonstrated a non-significant trend of improvement of parameters related to sexuality. Conclusions Local vaginal therapy with Gynoflor® in breast cancer survivors on aromatase inhibitors reporting atrophic vaginitis could be considered as a useful treatment for the quality of sexual life.
High-dose proton beam therapy for stage I non-small cell lung cancer: Clinical outcomes and prognostic factors

Abstract Background. Evidence has suggested that radiation therapy with a lower dose per fraction may be a reasonable option for the treatment of centrally located non-small cell lung cancer (NSCLC). The aim of this study was to evaluate the safety and efficacy of two proton beam therapy (PBT) protocols for stage I NSCLC and to determine prognostic factors. Material and methods. This study included patients clinically diagnosed with stage I NSCLC. Based on the location of the tumor, one of the two PBT protocols was administered. Patients with peripherally located tumors were given 66 Gy relative biological dose effectiveness (RBE) over 10 fractions (Protocol A) while patients with centrally located tumors were given 80 Gy (RBE) over 25 fractions (Protocol B). Results. Between January 2009 and May 2012, 56 eligible patients were enrolled (protocol A: 32 patients; protocol B: 24 patients). The three-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 81.3% [95% confidence interval (CI) 75.9–86.7%], 73.4% (95% CI 67.2–79.6%), and 96.0% (95% CI 93.2–98.8%), respectively. There were no significant differences in outcomes between the two protocols. Late grade 2 and 3 pulmonary toxicities were observed in nine patients (13.4%) and one patient (1.5%), respectively; no grade 4 or 5 toxicities were observed. Sex, age, performance status, T-stage, operability, and tumor pathology were not associated with OS and PFS. Only maximum standardized uptake value (SUVmax; < 5 vs. ≥ 5) was identified as a significant prognostic factor for OS and PFS. Conclusion. Both high-dose PBT protocols achieved high LC rates with tolerable toxicities in stage I NSCLC patients, and SUVmax was a significant prognostic factor.
Accuracy of asymmetry indices of ground reaction forces for diagnosis of hind limb lameness in dogs.

OBJECTIVE To determine the accuracy of asymmetry indices of ground reaction forces (GRF) for diagnosis of hind limb lameness in dogs. ANIMALS 36 healthy dogs and 13 dogs with naturally acquired cranial cruciate ligament rupture or hip dysplasia. PROCEDURES Lameness for affected dogs ranged from not detectable to minor and constant. While dogs trotted on an instrumented treadmill, GRF variables were recorded and analyzed with asymmetry indices. Each index was tested for its ability to discriminate between healthy and affected dogs. Combinations of several indices were also assessed. RESULTS Vertical force variables had better accuracy than craniocaudal force variables. Peak vertical force was the most accurate variable. Partial asymmetry during trotting was detected in healthy dogs. A multivariate approach that used peak vertical force and maximal rising slope yielded the optimum combination to distinguish between healthy and affected dogs. In addition, sensitivity of 92% or specificity of 95% may be achieved with 2 cutoff values while simultaneously maintaining specificity or sensitivity, respectively, at > 85%. CONCLUSIONS AND CLINICAL RELEVANCE Asymmetry indices of GRFs were accurate for detection of hind limb lameness in dogs. This is particularly relevant for study designs in which only a single gait evaluation is possible.
The global importance of ticks

Ticks and tick-borne diseases affect animal and human health worldwide and are the cause of significant economic losses. Approximately 10% of the currently known 867 tick species act as vectors of a broad range of pathogens of domestic animals and humans and are also responsible for damage directly due to their feeding behaviour. The most important tick species and the effects they cause are listed. The impact on the global economy is considered to be high and although some estimates are given, there is a lack of reliable data. The impact of ticks and tick-borne diseases on animal production and public health and their control are discussed.
Measurements of CP-Violating Asymmetries in the Decay B{sup 0}{yields}K{sup +}K{sup -}K{sup 0}

We analyze the decay B{sup 0}{yields}K{sup +}K{sup -}K{sup 0} using 383x10{sup 6} BB events collected by the BABAR detector at SLAC to extract CP violation parameter values over the Dalitz plot. Combining all K{sup +}K{sup -}K{sup 0} events, we find A{sub CP}=-0.015{+-}0.077{+-}0.053 and {beta}{sub eff}=0.352{+-}0.076{+-}0.026 rad, corresponding to a CP violation significance of 4.8{sigma}. A second solution near {pi}/2-{beta}{sub eff} is disfavored with a significance of 4.5{sigma}. We also report A{sub CP} and {beta}{sub eff} separately for decays to {phi}(1020)K{sup 0}, f{sub 0}(980)K{sup 0}, and K{sup +}K{sup -}K{sup 0} with m{sub K{sup +}}{sub K{sup -}}>1.1 GeV/c{sup 2}.
Sexual selection resulting from extrapair paternity in collared flycatchers

Extrapair paternity has been suggested to represent a potentially important source of sexual selection on male secondary sexual characters, particularly in birds with predominantly socially monogamous mating systems. However, relatively few studies have demonstrated sexual selection within single species by this mechanism, and there have been few attempts to assess the importance of extrapair paternity in relation to other mechanisms of sexual selection. We report estimates of sexual selection gradients on male secondary sexual plumage characters resulting from extrapair paternity in the collared flycatcher Ficedula albicollis, and compare the importance of this form of sexual selection with that resulting from variation in mate fecundity. Microsatellite genotyping revealed that 15% of nestlings, distributed nonrandomly among 33% of broods (N=79), were the result of extrapair copulations. Multivariate selection analyses revealed significant positive directional sexual selection on two uncorrelated secondary sexual characters in males (forehead and wing patch size) when fledgling number was used as the measure of fitness. When number of offspring recruiting to the breeding population was used as the measure of male fitness, selection on these traits appeared to be directional and stabilizing, respectively. Pairwise comparisons of cuckolded and cuckolding males revealed that males that sired young through extrapair copulations had wider forehead patches, and were paired to females that bred earlier, than the males that they cuckolded. Path analysis was used to partition selection on these traits into pathways via mate fecundity and sperm competition, and suggested that the sperm competition pathway accounted for between 64 and 90% of the total sexual selection via the two paths. The selection revealed in these analyses is relatively weak in comparison with many other measures of selection in natural populations. We offer some explanations for the relatively weak selection detected. Copyright 1999 The Association for the Study of Animal Behaviour.
ProBDNF and its receptors are upregulated in glioma and inhibit the growth of glioma cells in vitro.

BACKGROUND High-grade glioma is incurable, with a short survival time and poor prognosis. The increased expression of p75 neurotrophin receptor (NTR) is a characteristic of high-grade glioma, but the potential significance of increased p75NTR in this tumor is not fully understood. Since p75NTR is the receptor for the precursor of brain-derived neurotrophic factor (proBDNF), it is suggested that proBDNF may have an impact on glioma. METHODS In this study we investigated the expression of proBDNF and its receptors p75NTR and sortilin in 52 cases of human glioma and 13 cases of controls by immunochemistry, quantitative real-time PCR, and Western blot methods. Using C6 glioma cells as a model, we investigated the roles of proBDNF on C6 glioma cell differentiation, growth, apoptosis, and migration in vitro. RESULTS We found that the expression levels of proBDNF, p75NTR, and sortilin were significantly increased in high-grade glioma and were positively correlated with the malignancy of the tumor. We also observed that tumors expressed proBDNF, p75NTR, and sortilin in the same cells with different subcellular distributions, suggesting an autocrine or paracrine loop. The ratio of proBDNF to mature BDNF was decreased in high-grade glioma tissues and was negatively correlated with tumor grade. Using C6 glioma cells as a model, we found that proBDNF increased apoptosis and differentiation and decreased cell growth and migration in vitro via p75NTR. CONCLUSIONS Our data indicate that proBDNF and its receptors are upregulated in high-grade glioma and might play an inhibitory effect on glioma.
Sex Differences in Genetic and Environmental Factors Contributing to Body-Height

Abstract Sex differences in the heritability of self-reported body-height in two Finnish twin cohorts were studied by using sex-limitation models. The first cohort was born in 1938–1949 (N = 4873 twin pairs) and the second in 1975–1979 (N = 2374 twin pairs). Body-height was greater in the younger cohort (difference of 3.1 cm for men and 2.9 cm for women). The heritability estimates were higher among men (h2 = 0.87 in the older cohort and h2 = 0.82 in the younger cohort) than women (h2 = 0.78 and h2 = 0.67, respectively). Sex-specific genetic factors were not statistically significant in either cohort, suggesting that the same genes contribute to variation in body height for both men and women. The stronger contribution of environmental factors to body-height among women questions the hypothesis that women are better buffered against environmental stress, at least for this phenotype.
Role of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A polymorphisms in irinotecan‐induced neutropenia in Asian cancer patients

The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan‐induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90‐min intravenous infusion of 375 mg/m2 once every 3 weeks (n = 45). Genotypic–phenotypic correlates showed a non‐significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN‐38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN‐38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC ≤ 500/µL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3‐fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN‐38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study. (Cancer Sci 2007; 98: 1461–1467)
Stabilization of a metastable state of Torpedo californica acetylcholinesterase by chemical chaperones

Chemical modification of Torpedo californica acetylcholinesterase by the natural thiosulfinate allicin produces an inactive enzyme through reaction with the buried cysteine Cys 231. Optical spectroscopy shows that the modified enzyme is “native‐like,” and inactivation can be reversed by exposure to reduced glutathione. The allicin‐modified enzyme is, however, metastable, and is converted spontaneously and irreversibly, at room temperature, with t1/2 ≃ 100 min, to a stable, partially unfolded state with the physicochemical characteristics of a molten globule. Osmolytes, including trimethylamine‐N‐oxide, glycerol, and sucrose, and the divalent cations, Ca2+, Mg2+, and Mn2+ can prevent this transition of the native‐like state for >24 h at room temperature. Trimethylamine‐N‐oxide and Mg2+ can also stabilize the native enzyme, with only slight inactivation being observed over several hours at 39°C, whereas in their absence it is totally inactivated within 5 min. The stabilizing effects of the osmolytes can be explained by their differential interaction with the native and native‐like states, resulting in a shift of equilibrium toward the native state. The stabilizing effects of the divalent cations can be ascribed to direct stabilization of the native state, as supported by differential scanning calorimetry.
The second ADF/cofilin actin-binding site exists in F-actin, the cofilin-G-actin complex, but not in G-actin.

ADF/cofilins are actin binding proteins that bind actin close to both the N- and C-termini (site 1), and we have found a second cofilin binding site (site 2) centered around helix 112-125 [Renoult, C. , Ternent, D. , Maciver, S.K. , Fattoum, A. , Astier, C. , Benyamin, Y. & Roustan, C. (1999) J. Biol. Chem. 274, 28893-28899]. We proposed a model in which ADF/cofilin intercalated between subdomains 1 and 2 of two longitudinally associated actin monomers within the actin:cofilin cofilament, explaining the change in twist that ADF/cofilins induce in the filament [McGough, A. Pope, B. , Chiu, W. & Weeds, A. (1998) J. Cell Biol. 138, 771-781]. Here, we have determined the fuller extent of the cofilin footprint on site 1 of actin. Site 1 is primarily the G-actin binding site. Experiments with both peptide mimetics and fluorescently labeled cofilin suggest that site 2 only becomes available for cofilin binding within the filament, possibly due to motion between subdomains 1 and 2 within an actin monomer. We have detected motion between subdomains 1 and 2 of G-actin by FRET induced by cofilin, to reveal the second cofilin-binding site. This motion may also explain how cofilins inhibit the nucleotide exchange of actin, and why the actin:cofilin complex is polymerizable without dissociation.