Miracle-dz/UniFAR-FTUs huggingface dataset:
Mediation analysis of the alcohol‐postmenopausal breast cancer relationship by sex hormones in the EPIC cohort

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex‐hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol‐consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol‐related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor‐positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1‐standard deviation (1‐SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol‐related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1‐SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol‐BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
Altitude Training and Recombinant Human Erythropoietin: Considerations for Doping Detection

The benefit of training at altitude to enhance exercise performance remains equivocal although the most widely accepted approach is one where the athletes live and perform lower-intensity running at approximately 2300 m with high-intensity training at approximately 1250 m. The idea is that this method maintains maximal augmentations in total hemoglobin mass while reducing the performance impairment of high-intensity sessions performed at moderate altitude and thus preventing any detraining that can occur when athletes live and train at moderate altitude. This training regimen, however, is not universally accepted and some argue that the performance enhancement is due to placebo and training camp effects. Altitude training may affect an athlete’s hematological parameters in ways similar to those observed following blood doping. Current methods of detection appear insufficient to differentiate between altitude training and blood doping making the interpretation of an athlete’s biological passport difficult. Further research is required to determine the optimal method for altitude training and to enhance current detection methods to be able to differentiate better blood doping and altitude exposure.
Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma Is Not Associated with Pathological Misclassification of Tumor Histotype

Purpose: Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes are observed in a subset of patients. The explanation for this is unknown but may be due to misclassification of high-grade serous ovarian cancer (HGSOC) as OCCC or mixed histology. Experimental Design: To discover potential biomarkers of survival benefit following platinum-based chemotherapy, we ascertained a cohort of 68 Japanese and Australian patients in whom progression-free survival (PFS) and overall survival (OS) could be assessed. We performed IHC reclassification of tumors, and targeted sequencing and immunohistochemistry of known driver genes. Exome sequencing was performed in 10 patients who had either unusually long survival (N = 5) or had a very short time to progression (N = 5). Results: The majority of mixed OCCC (N = 6, 85.7%) and a small proportion of pure OCCC (N = 3, 4.9%) were reclassified as likely HGSOC. However, the PFS and OS of patients with misclassified samples were similar to that of patients with pathologically validated OCCC. Absent HNF1B expression was significantly correlated with longer PFS and OS (P = 0.0194 and 0.0395, respectively). Mutations in ARID1A, PIK3CA, PPP2R1A, and TP53 were frequent, but did not explain length of PFS and OS. An exploratory exome analysis of patients with favorable and unfavorable outcomes did not identify novel outcome-associated driver mutations. Conclusions: Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome.
Diagnostic Biomarkers to Diagnose Acute Allograft Rejection After Liver Transplantation: Systematic Review and Meta-Analysis of Diagnostic Accuracy Studies

Objective: A systematic review and meta-analysis of diagnostic biomarkers for noninvasive diagnosis of acute allograft rejection following liver transplantation. Background: Noninvasive blood and urine markers have been widely explored in recent decades for diagnosing acute rejection after liver transplantation. However, none have been translated into routine clinical use so far due to uncertain diagnostic accuracy, and liver biopsy remains the gold standard. Methods: Systematic literature searches of Medline, Cochrane and Embase were conducted up to February 2019 to identify studies evaluating the use of noninvasive markers in diagnosing allograft rejection following liver transplantation. Meta-analysis was performed using a random effects model with DerSimonian–Laird weighting and the hierarchical summary receiver operating curve. Results: Of 560 identified studies, 15 studies (1,445 patients) met the inclusion criteria. The following markers were tested: acid labile nitroso-compounds (NOx), serum amyloid A protein, procalcitonin, peripheral blood eosinophil count, peripheral blood T-cell activation and interleukin 2 (IL-2) receptor, guanylate-binding protein-2 mRNA, graft-derived cell-free DNA, pi-glutathione S-transferase, alpha-glutathione S-transferase and serum HLA class I soluble antigens. Only eosinophil count was tested in multiple studies, and they demonstrated high heterogeneity (I2 = 72% [95% CI: 0.5–0.99]). IL-2 receptor demonstrated the highest sensitivity (89% [95% CI: 0.78–0.96]) and specificity (81% [95% CI: 0.69–0.89]). Conclusion: IL-2 receptor expression demonstrated the highest diagnostic accuracy, while the peripheral eosinophil count was the only marker tested in more than one study. Presently, liver biopsy remains superior to noninvasive diagnostic biomarkers as most studies exhibited inferior designs, hindering possible translation into clinical application.
Worker safety perception analysis of South Korean construction sites

Purpose. The aim of this article was to measure the safety perception level of workers on a South Korean construction site and investigate safety problems using the Nordic occupational safety climate questionnaire (NOSACQ-50). Methods. The survey was carried out via the NOSACQ-50 with 175 workers from five South Korean construction companies to evaluate their perception level. The results were then compared with the NOSACQ-50 criteria. Results. The safety perception of this South Korean construction site is high when compared with the NOSACQ-50 criteria. This high level was especially pronounced for the seventh dimension of the efficacy of the safety system, which showed the highest level among all dimensions. In addition, we suggested improvements and interventions to sustain a safety climate amongst workgroups. Conclusions. This study confirms that the seventh dimension showed the highest safety perception amongst all dimensions in South Korea. In the future, these findings can be utilized to develop an evaluation tool for the safety climate of the construction industry in South Korea.
Revisiting ADHD age-of-onset in adults: to what extent should we rely on the recall of childhood symptoms?

Abstract Background ADHD diagnosis requires the presence of symptoms before the age of twelve. In clinical assessment of adults, the most frequent strategy to check this criterion is investigating self-report recall of symptoms, despite little evidence on the validity of this approach. We aim to evaluate the recall accuracy and factors associated with its reliability in a large population-based sample of adults. Methods Individuals from the 1993 Pelotas Birth Cohort were followed-up from childhood to adulthood. At the age of 22, 3810 individuals were assessed through structured interviews by trained psychologists regarding mental health outcomes, including ADHD diagnosis and ADHD symptoms in childhood. The retrospective recall was compared with available information on ADHD childhood symptoms at the age of eleven. We also assessed factors related to recall accuracy through multiple regression analyses. Results Self-reported recall of childhood symptoms at 22 years of age had an accuracy of only 55.4%, with sensitivity of 32.8% and positive predictive value of 40.7%. Current inattention symptoms were associated with lower risk and social phobia with higher risk for false-positive endorsement, while higher levels of schooling correlated with lower risk and male gender with higher risk for false-negative endorsement. Conclusions Clinicians treating male patients with social phobia and ADHD symptoms should assess even more carefully retrospective recall of ADHD childhood symptoms. Moreover, characteristics associated with recall improvement do not impact accuracy robustly. In this context, the recall of childhood ADHD symptoms seems an unreliable method to characterize the neurodevelopmental trajectory in adults with currently-impairing ADHD symptomatology.
Neonatal Fc receptor expression in macrophages is indispensable for IgG homeostasis

ABSTRACT The maintenance of the homeostasis of immunoglobulin G (IgG) represents a fundamental aspect of humoral immunity that has direct relevance to the successful delivery of antibody-based therapeutics. The ubiquitously expressed neonatal Fc receptor (FcRn) salvages IgG from cellular degradation following pinocytic uptake into cells, conferring prolonged in vivo persistence on IgG. However, the cellular sites of FcRn function are poorly defined. Pinocytic uptake is a prerequisite for FcRn-mediated IgG salvage, prompting us to investigate the consequences of IgG uptake and catabolism by macrophages, which represent both abundant and highly pinocytic cells in the body. Site-specific deletion of FcRn to generate mice harboring FcRn-deficient macrophages results in IgG hypercatabolism and ~threefold reductions in serum IgG levels, whereas these effects were not observed in mice that lack functional FcRn in B cells and dendritic cells. Consistent with the degradative activity of FcRn-deficient macrophages, depletion of these cells in FcRn-deficient mice leads to increased persistence and serum levels of IgG. These studies demonstrate a pivotal role for FcRn-mediated salvage in compensating for the high pinocytic and degradative activities of macrophages to maintain IgG homeostasis.
Early-life socioeconomic circumstances explain health differences in old age, but not their evolution over time

Background Early-life socioeconomic circumstances (SEC) are associated with health in old age. However, epidemiological evidences on the influence of these early-life risk factors on trajectories of healthy ageing are inconsistent, preventing drawing solid conclusion about their potential influence. Here, to fill this knowledge gap, we used a statistical approach adapted to estimating change over time and an outcome-wide epidemiology approach to investigate whether early-life SEC were associated with the level of and rate of decline of physical, cognitive and emotional functioning over time. Methods We used data on more than 23 000 adults in older age from the Survey of Health, Ageing and Retirement in Europe, a 12-year large-scale longitudinal study with repeated measurements of multiple health indicators of the same participants over time (2004 –2015, assessments every 2 years). Confounder-adjusted linear growth curve models were used to examine the associations of early-life SEC with the evolution of muscle strength, lung function, cognitive function, depressive symptoms and well-being over time. Results We consistently found an association between early-life SEC and the mean levels of all health indicators at age 63.5, with a critical role played by the cultural aspect of disadvantage. These associations were only partly explained by adult-life SEC factors. By contrast, evidences supporting an association between early-life SEC and the rate of change in health indicators were weak and inconsistent. Conclusions Early-life SEC are associated with health in old age, but not with trajectories of healthy ageing. Conceptual models in life course research should consider the possibility of a limited influence of early-life SEC on healthy ageing trajectories.
Quantitative Proteomic Analysis of the Response of Probiotic Putative Lactococcus lactis NCDO 2118 Strain to Different Oxygen Availability Under Temperature Variation

Lactococcus lactis is a gram positive facultative anaerobe widely used in the dairy industry and human health. L. lactis subsp. lactis NCDO 2118 is a strain that exhibits anti-inflammatory and immunomodulatory properties. In this study, we applied a label-free shotgun proteomic approach to characterize and quantify the NCDO 2118 proteome in response to variations of temperature and oxygen bioavailability, which constitute the environmental conditions found by this bacterium during its passage through the host gastro-intestinal tract and in other industrial processes. From this proteomic analysis, a total of 1,284 non-redundant proteins of NCDO 2118 were characterized, which correspond to approximately 54% of its predicted proteome. Comparative proteomic analysis identified 149 and 136 proteins in anaerobic (30°C and 37°C) and non-aerated (30°C and 37°C) conditions, respectively. Our label-free proteomic analysis quantified a total of 1,239 proteins amongst which 161 proteins were statistically differentially expressed. Main differences were observed in cellular metabolism, stress response, transcription and proteins associated to cell wall. In addition, we identified six strain-specific proteins of NCDO 2118. Altogether, the results obtained in our study will help to improve the understanding about the factors related to both physiology and adaptive processes of L. lactis NCDO 2118 under changing environmental conditions.
The Irradiation Effect Of Quartz Crystal Resonators By Picosecond Laser

Quartz crystal resonators are important frequency control elements in electronic products with a complicated manufacturing process. During operations of a resonator, the coupling between the main functioning mode and the spurious modes should be avoided, since it will greatly increase the resistance and reduce the quality factor value, making it unable to work steadily and efficiently. In order to limit the spurious modes and reduce the mode couplings, an experimental study was conducted on the processing of quartz crystals by picosecond lasers. And we have investigated the effects of parameters of picosecond laser irradiation on properties of quartz crystal blanks. We irradiated both ends of quartz crystal blanks with a picosecond laser beam, and the laser power was controlled to limit the total input. Then we manufactured quartz crystal resonators with the laser processed blanks and measured their properties. After the quartz crystal blanks are irradiated with different power levels, the performance of the quartz crystal resonator does have some changes. Our goal is to explore the effects of laser irradiation on quartz crystals and optimize quartz crystal resonators with the selection of irradiation areas and power levels. With the noticeable effects from the first batch of test samples, we are studying novel irradiation schemes for more samples and measurements.
Pacific Southwest United States Holocene Droughts and Pluvials Inferred From Sediment δ18O(calcite) and Grain Size Data (Lake Elsinore, California)

Records of past climate can inform us on the natural range and mechanisms of climate change. In the arid Pacific southwest United States (PSW), which includes southern California, there exist a variety of Holocene records that can be used to infer past winter conditions (moisture and/or temperature). Holocene records of summer climate, however, are rare from the PSW. In the future, climate changes due to anthropogenic forcing are expected to increase the severity of drought in the already water stressed PSW. Hot droughts are of considerable concern as summer temperatures rise. As a result, understanding how summer conditions changed in the past is critical to understanding future predictions under varied climate forcings. Here, we present a c. 10.9 kcal BP 18O(calcite) record from Lake Elsinore, California, interpreted to reflect 18O(lake water) values as controlled by over-water evaporation from summer-to-early fall. Our results reveal three millennial scale intervals: 1) the highly evaporative Early Holocene (10.55-6.65 kcal BP), 2) the less evaporative Mid-Holocene (6.65-2.65 kcal BP); and, 3) the evaporative Late Holocene (2.65-0.55 kcal BP). These results are coupled with an inferred winter precipitation runoff (sand content) record from Kirby et al. (2010). Using these data together, we estimate the duration and severity of centennial-scale Holocene droughts and pluvials (e.g., high 18O(calcite) values plus low sand content = drought and vice versa). Furthermore, the coupled 18O(calcite) and sand data provide a generalized Holocene lake level history. The most severe, long-lasting droughts (i.e., maximum summer-to-early fall evaporation and minimum winter precipitation runoff) occur in the Early Holocene. Fewer, less severe, and shorter duration droughts occurred during the Mid-Holocene as pluvials became more common. Droughts return with less severity and duration in the Late Holocene. Notably, the Little Ice Age is characterized as the wettest period during the Late Holocene.
LncRNA MIR4435-2HG predicts poor prognosis in patients with colorectal cancer

Background LncRNA MIR4435-2HG is observed in a variety of cancers, while its role in colorectal cancer is unknown. We aimed to demonstrate the relationship between MIR4435-2HG and colorectal cancer based on The Cancer Genome Atlas (TCGA) database. Materials and Methods Patients with colorectal cancer were collected from TCGA. We compared the expression of MIR4435-2HG in colorectal cancer and normal tissues with Wilcoxon rank sum test, and logistic regression was used to evaluate the relationship between MIR4435-2HG and clinicopathological characters. Moreover, Kaplan–Meier and Cox regression was performed to evaluate the correlation between MIR4435-2HG and survival rate. Gene set enrichment analysis (GSEA) was also conducted to annotate biological function of MIR4435-2HG. Results MIR4435-2HG level was elevated in colorectal cancer tissues. Increased level of MIR4435-2HG was significantly correlated with TNM stage (OR = 1.66 for T1/T2 vs. T3/T4; OR = 1.68 for N0 vs. N1/N2), stage (OR = 1.66 for stage 1/2 vs. stage 3/4), and carcinoembryonic antigen level before treatment (OR = 1.70 for <5 vs. ≥5) (all P-value <0.05). High MIR4435-2HG expression had a poorer progression-free survival (p = 0.048), and overall survival (OS) (P = 0.028), which were validated in the GSE92921 and GSE29621 datasets. MIR4435-2HG expression (P = 0.040, HR = 1.955 (95% CI [1.031–3.710])) was independently correlated with OS. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway, the cell surface interactions at the vascular wall, and integrin cell surface interactions were differentially enriched in MIR4435-2HG high expression phenotype. Conclusions Increased MIR4435-2HG might be a potential biomarker for the diagnosis and prognosis of colorectal cancer. Moreover, MIR4435-2HG might participate in the development of colorectal cancer via the P38/MAPK and VEGF pathway.
Validation of a Device for the Ambulatory Monitoring of Sleep Patterns: A Pilot Study on Parkinson's Disease

The development of wearable devices has increase interest in the use of ambulatory methods to detect sleep disorders more objectively than those permitted by subjective scales evaluating sleep quality, while subjects maintain their usual lifestyle. This study aims to validate an ambulatory circadian monitoring (ACM) device for the detection of sleep and wake states and apply it to the evaluation of sleep quality in patients with Parkinson disease (PD). A polysomnographic validation study was conducted on a group of patients with different sleep disorders in a preliminary phase, followed by a pilot study to apply this methodology to PD patients. The ACM device makes it possible to estimate the main sleep parameters very accurately, as demonstrated by: (a) the lack of significant differences between the mean values detected by PSG and ACM in time in bed (TIB), total sleep time (TST), sleep efficiency (SE), and time awake after sleep onset (WASO); (b) the slope of the correlation lines between the parameters estimated by the two procedures, very close to 1, which demonstrates the linearity of the predictions; (c) the low bias value in the estimates obtained through ACM. Sleep in PD is associated with lower distal skin temperature, efficiency and overall sleep time; greater WASO, activity during sleep and duration of naps and a worse circadian function index. In summary, the ACM device has proven to be clinically useful to evaluate sleep in an objective manner, thanks to the integrated management of different complementary variables, having advantages over conventional actigraphy.