Miracle-dz/UniFAR-FTUs huggingface dataset:
Alcohol Consumption and Breast Cancer Risk Among Postmenopausal Women Following the Cessation of Hormone Therapy Use: The California Teachers Study Epidemiology,Biomarkers&Prevention

Background: Alcohol consumption increases breast cancer risk, but its effect may be modiﬁed by hormone therapy(HT)use,suchthatexposuretobothmaybesynergistic.BecausemanywomenstoppedtakingHTafter mid-2002, it is important to quantify risks associated with alcohol consumption in the context of HT cessation, as these risks may be more relevant to cancer prevention efforts today. Methods: Among 40,680 eligible postmenopausal California Teachers Study cohort participants, 660 were diagnosed with invasive breast cancer before 2010. Multivariate Cox proportional hazards regression models were used to estimate relative risks (RR) and 95% conﬁdence intervals (CI). Results: Increased breast cancer risk associated with alcohol consumption was observed among postmen-opausalwomenwhowere currentHTusers[RR,1.60;95%conﬁdenceinterval (CI),1.13–2.26andRR, 2.11;95% CI, 1.41–3.15 for < 20 and (cid:1) 20 g/d of alcohol], with risks being similar by HT preparation. Alcohol did not increase risk among women who had stopped using HT within 3 years or 3 to 4 years before completing the follow-up questionnaire or in the more distant past. Results were similar for estrogen receptor positive (ER þ ) and ER þ PR þ progesterone receptors positive (PR þ ) tumors; while power was limited, no increase in risk was observed for ER (cid:3) tumors. Conclusions: Following the cessation of HT use, alcohol consumption is not signiﬁcantly associated with breast cancer risk, although a nonsigniﬁcant increased risk was observed among women who never used HT. Impact: Our ﬁndings conﬁrm that concurrent exposure to HT and alcohol has a substantial adverse impact onbreastcancer risk.However, afterHT cessation, this riskisreduced. Cancer Epidemiol Biomarkers Prev;21(11); 1–8. (cid:2) 2012 AACR.
OP-NDTJ170319 1..7

Background. Among aging hemodialysis patients, loss of physical function has become a major issue. We developed and validated a model of predicting loss of physical function among elderly hemodialysis patients. Methods. We conducted a cohort study involving maintenance hemodialysis patients 65 years of age from the Dialysis Outcomes and Practice Pattern Study in Japan. The derivation cohort included 593 early phase (1996–2004) patients and the temporal validation cohort included 447 late-phase (2005–12) patients. The main outcome was the incidence of loss of physical function, defined as the 12-item Short Form Health Survey physical function score decreasing to 0 within a year. Using backward stepwise logistic regression by Akaike’s Information Criteria, six predictors (age, gender, dementia, mental health, moderate activity and ascending stairs) were selected for the final model. Points were assigned based on the regression coefficients and the total score was calculated by summing the points for each predictor. Results. In total, 65 (11.0%) and 53 (11.9%) hemodialysis patients lost their physical function within 1 year in the derivation and validation cohorts, respectively. This model has good predictive performance quantified by both discrimination and calibration. The proportion of the loss of physical function increased sequentially through low-, middle-, and high-score categories based on the model (2.5%, 11.7% and 22.3% in the validation cohort, respectively). The loss of physical function was strongly associated with 1-year mortality [adjusted odds ratio 2.48 (95% confidence interval 1.26–4.91)]. Conclusions. We developed and validated a risk prediction model with good predictive performance for loss of physical function in elderly hemodialysis patients. Our simple prediction model may help physicians and patients make more informed decisions for healthy longevity.
where Induced Bone Tissue Temperature in Drilling Procedures: A Comparative Laboratory Study with and without

 Abstract — In orthopedic surgery there are various situations in which the surgeon needs to implement methods of cutting and drilling the bone. With this type of procedure the generated friction leads to a localized increase in temperature, which may lead to the bone necrosis. Recognizing the importance of studying this phenomenon, an experimental evaluation of the temperatures developed during the procedure of drilling bone has been done. Additionally the influence of the use of the procedure with / without additional lubrication during drilling of bone has also been done. The obtained results are presented and discussed and suggests an advantage in using additional lubrication as a way to minimize the appearance of bone tissue necrosis during bone drilling
DMSO_A_333373 4361..4369

1School of Nursing, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Medicine, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 3Department of Endocrinology and Metabolism, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China; 4Department of Neurosurgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China; 5Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China
ZONAL DIVERSITY AND COMMUNITY STRUCTURE OF INVERTEBRATE MACROFAUNA IN ROCKY INTERTIDAL AREA OF MANORA, KARACHI, PAKISTAN

: Rocky shores are important ecosystems that supports the wide variety of plants and animals and are characterized by the zonation of species. This three months study was conducted in order to recognize the community structure and zonal distribution of macro fauna at the Manora rocky shore. The sampling was done monthly for three months in the year 2014 at three tidal zones, i.e. High tide zone, Mid tide zone and Low tide zone and a zonal comparison of fauna was performed to identify the distribution pattern of species during pre-monsoon season. A total 1318 individuals belonged to 68 species were identified and counted. The phylum Mollusca was the most diverse phylum which represented by 43 species, followed by Arthropods (16 species), Echinoderms (4 species), Annelids (2 species), Cnidarians (2 species) and Porifera (1 species). The highest faunal diversity (H’= 1.429) was observed at the low tide zone, but the diversity of molluscs was high (H’=1. 329) at the mid tide zone.
Predicting Threats on Electric Health Record Systems

Security is a key concern in the development of electronic health record (EHR) systems. This paper considers Neutralization Theory and the Fear Appeals Model in proposing a conceptual model for use in predicting breach behaviors within EHR systems. The goal of the model is to determine which factors influence security breach intent on the part of the offender. Specifically, perceived penalty, perceived evasiveness, awareness of opportunity, enforcement, and user participation are proposed to act as antecedents to security breach intent, a surrogate for actual breach behavior.
Single-Residue Changes in the C-Terminal Disulﬁde-Bonded Loop of the Pseudomonas aeruginosa Type IV Pilin Inﬂuence Pilus Assembly and Twitching Motility (cid:1)

PilA, the major pilin subunit of Pseudomonas aeruginosa type IV pili (T4P), is a principal structural component. PilA has a conserved C-terminal disulﬁde-bonded loop (DSL) that has been implicated as the pilus adhesinotope. Structural studies have suggested that DSL is involved in intersubunit interactions within the pilus ﬁber. PilA mutants with single-residue substitutions, insertions, or deletions in the DSL were tested for pilin stability, pilus assembly, and T4P function. Mutation of either Cys residue of the DSL resulted in pilins that were unable to assemble into ﬁbers. Ala replacements of the intervening residues had a range of effects on assembly or function, as measured by changes in surface pilus expression and twitching motility. Modiﬁcation of the C-terminal P-X-X-C type II beta-turn motif, which is one of the few highly conserved features in pilins across various species, caused profound defects in assembly and twitching motility. Expression of pilins with suspected assembly defects in a pilA pilT double mutant unable to retract T4P allowed us to verify which subunits were physically unable to assemble. Use of two different PilA antibodies showed that the DSL may be an immunodominant epitope in intact pili compared with pilin monomers. Sequence diversity of the type IVa pilins likely reﬂects an evolutionary compromise between B tag. cleaved dialyzed and sub-
The Photogrammetric Survey of the Phoenician and Punic Necropolis of Nora and Three-Dimensional Rendering Tools for Sharing Data

The hypogea of the Punic necropolis of Nora represented a testing ground for the use of photogrammetry as an archaeological survey tool in a highly critical context, both from the point of view of the survey itself and from the point of view of the understanding and dissemination of the underground evidence. The study describes the acquisition techniques and the tools used to share the 3D models, both among the research team and with external users, with a specific focus on web-based tools (Potree).
Promoting eHealth Literacy in Older Adults: Key Informant Perspectives

Health literacy has the potential to improve an individual’s capacity to access, understand, evaluate, and communicate basic health information and services in order to make appropriate health decisions. We developed a research agenda to help older adults become aware of health literacy and its function in promoting their nutritional health and well-being. A key activity is the development, implementation, and evaluation of an eHealth literacy tool, eSEARCH, targeted at older adults to help improve their eHealth literacy skills. Before consultations were held with this subpopulation to assess their eHealth literacy needs and abilities, key informant interviews were conducted with eight experts in the field of health literacy, the older adult population, and/or online communications. Some experts were identified from the relevant literature; others were identified by informants who had already been interviewed. Informants were asked nine questions about the perceived importance of health literacy in Canada.
Folding stability of amyloid- (cid:1) 40 monomer is an important determinant of the nucleation kinetics in ﬁbrillization

Amyloid formation is initiated by protein misfolding, followed by self-association to ultimately form amyloid ﬁbrils. The discovery of toxic preﬁbrillar oligomers in many amyloidosis underscores the importance of understanding the folding mechanism prior to such aggregation. Here, we investigated the folding properties of the natively unfolded amyloid- (cid:1) (A (cid:1) ) peptide and the familial variants (A21G, E22Q, E22G, E22K, and D23N) in Alzheimer’s disease (AD). In combinations of native electrophoresis, analytical ultracentrifugation, ﬂuorescence emission, and far-UV circular dichroism, we showed that all A (cid:1) 40 variants are predominantly monomeric with similar residual secondary structures, but distinct hydrophobic-exposed protein surfaces. Guanidine hydrochloride (GdnHCl) denaturation in the absence and presence of triﬂuoro-ethanol (TFE) showed that A (cid:1) variants adopt an apparent 2-state equilibrium model with different stabilities, in which wild type is less stable than A21G but more stable than D23N and E22 mutants. By correlating the folding stability with the nucleation phase in ﬁbrillization, we found the more stable the variant, the slower the nucleation, except for D23N. Besides, the unfolding of A (cid:1) conformation leads to reduced formation of mature ﬁbrils, but an increase in nonﬁbrillar, amorphous type of aggregates. Overall, we demonstrated that folding stability of A (cid:1) is an important determinant of the nucleation kinetics. —Ni, C. -L. , Shi, H. -P., Yu, H. -M. , Chang, Y. -C. , and Chen, Y. -R. Folding stability of amyloid- (cid:1) 40 monomer is an important determinant of the nucleation kinetics in ﬁbrillization. FASEB J. 25, 1390–1401 (2011). www.fasebj. org
Transmission of uncertainty shocks

The Working Paper Series of the Czech National Bank (CNB) is intended to disseminate the results of the CNB’s research projects as well as the other research activities of both the staff of the CNB and collaborating outside contributors, including invited speakers. The Series aims to present original research contributions relevant to central banks. It is refereed internationally. The referee process is managed by the CNB Research Division. The working papers are circulated to stimulate discussion. The views expressed are those of the authors and do not necessarily reflect the official views of the CNB.  Abstract Numerous recent studies, starting with Bloom (2009), highlight the impact of varying uncertainty levels on economic activity. These studies mostly focus on individual countries, and cross-country evidence is scarce. In this paper, we use a set of (panel) BVAR models to study the effect of uncertainty shocks on economic developments in EU Member States. We explicitly distinguish between domestic, common and global uncertainty shocks and employ new proxies of uncertainty. The domestic uncertainty indicators are derived from the Business and Consumer Surveys administered by the European Commission. The common EU-wide uncertainty is subsequently derived by means of a factor model. Finally, the global uncertainty indicator – inspired by Jurado et al. (2015) – is extracted as a common factor from a broad set of forecast indicators that are not driven by the business cycle. The results suggest that real output in EU countries drops after spikes in uncertainty, mainly as a result of lower investment. Unlike for the U.S., there is little evidence of activity overshooting following this initial fall. The responses to uncertainty shocks vary across Member States. These differences can be attributed not mainly to different shock sizes, but rather to cross-country structural characteristics. Member States with more flexible labour markets and product markets seem to weather uncertainty shocks better. Likewise, a higher manufacturing share and higher economic diversification help dampen the impact of uncertainty shocks. The role of economic openness is more
May 09, 2020 Aspergillus nidulans Synthesize Insect Juvenile Hormones upon Expression of a Heterologous Regulatory Protein and in Response to Grazing by

Secondary metabolites are known to serve a wide range of specialized functions including communication, developmental control and defense. Genome sequencing of several fungal model species revealed that the majority of predicted secondary metabolite related genes are silent in laboratory strains, indicating that fungal secondary metabolites remain an underexplored resource of bioactive molecules. In this study, we combine heterologous expression of regulatory proteins in Aspergillus nidulans with systematic variation of growth conditions and observe induced synthesis of insect juvenile hormone-III and methyl farnesoate. Both compounds are sesquiterpenes belonging to the juvenile hormone class. Juvenile hormones regulate developmental and metabolic processes in insects and crustaceans, but have not previously been reported as fungal metabolites. We found that feeding by Drosophila melanogaster larvae induced synthesis of juvenile hormone in A. nidulans indicating a possible role of juvenile hormone biosynthesis in affecting fungal-insect antagonisms.
Special Section on Epigenetic Regulation of Drug Metabolizing Enzymes and Transporters Epigenetic Regulation Is a Crucial Factor in the Repression of UGT1A1 Expression in the Human Kidney

Human uridine 5 9 -diphospho-glucuronosyltransferase (UGT) 1A1 catalyzes the metabolism of numerous clinically and pharma-cologically important compounds, such as bilirubin and SN-38. UGT1A1 is predominantly expressed in the liver and intestine but not in the kidney. The purpose of this study was to uncover the mechanism of the tissue-specific expression of UGT1A1, focusing on its epigenetic regulation. Bisulfite sequence analysis revealed that the CpG-rich region near the UGT1A1 promoter ( 2 85 to +40) was hypermethylated (83%) in the kidney, whereas it was hypomethylated (37%) in the liver. A chromatin immunoprecipitation assay demonstrated that histone H3 near the promoter was hypoacetylated in the kidney but hyperacetylated in the liver; this hyperacetylation was accompanied by the recruitment of hepatocyte nuclear factor (HNF) 1 a to the promoter. The UGT1A1 promoter in human kidney-derived HK-2 cells that do not express UGT1A1 was fully methylated, but this promoter was relatively unmethylated in human liver-derived HuH-7 cells that express UGT1A1. Treatment with 5-aza-2 9 -deoxycytidine (5-aza-dC), an inhibitor of DNA methylation, resulted in an increase of UGT1A1 mRNA expression in both cell types, but the increase was much larger in HK-2 cells than in HuH-7 cells. The transfection of an HNF1 a expression plasmid into the HK-2 cells resulted in an increase of UGT1A1 mRNA only in the presence of 5-aza-dC. In summary, we found that DNA hypermethylation, along with histone hypoacetylation, interferes with the binding of HNF1 a , resulting in the defective expression of UGT1A1 in the human kidney. Thus, epigenetic regulation is a crucial determinant of tissue-specific expression of UGT1A1.
Effects of Dosage, PhÃ©nobarbital,and 2-Diethylaminoethyl-2,2-diphen\ balenate on the Binding of Cyclophosphamide and/or Its Metabolites to the DNA, R N A, and Protein of the Embryo and Liver in Pregnant Mice1

SUMMARY The effect of dosage and pretreatment with phÃ©nobarbital or 2-diethylaminoethyl-2,2-diphenylvalerate on the binding of labeled cyclophosphamide and/or its metabolites to macromolecular constituents of the embryo and maternal liver in pregnant mice was studied under conditions nearly identical to those of previous studies of cyclophosphamide teratogenicity. Cyclophosphamide and/or its metabolites were firmly bound, presumably covalently, to the DNA, RNA, and protein of the embryo and liver in pregnant mice. The proportion of drug bound to the DNA, RNA, and protein fractions was roughly related to the proportion of the three cellular constituents in embryonic and adult tissue, thus suggesting an indiscriminate attack by the drug and/or its metabolites on cellular constituents. The extent of binding to embryo and liver DNA was increased about 4-fold following a doubling of the dose, from 10 to 20 mg/kg, in nonpretreated pregnant mice, whereas the binding to RNA (except for liver) and protein was doubled. Pretreatment of pregnant mice with phÃ©nobarbital decreased the binding to embryo DNA and to liver RNA and increased the binding to liver protein produced by cyclophos phamide, 20 mg/kg, but no effect was observed on the binding to RNA or protein of the embryo or to liver DNA. Pretreatment with 2-diethylaminoethyl-2,2-diphenylvalerate decreased the binding to DNA and protein of liver produced by cyclophosphamide, 20 mg/kg, but no effect was observed on the binding to macromolecules of the embryo. The extent of binding to RNA or protein of the embryo showed no correlation with cyclophosphamide teratogenic responses, whereas the binding to DNA of the embryo showed a positive correlation with overall frequencies of malformations pro duced by cyclophosphamide. These findings are consistent with the hypothesis that cyclophosphamide and/or its metabo lites exert their teratogenic effects via the alkylation of embryo DNA.
NephrologyDialysis Transplantation Proteinuria and blood pressure as causal components of progression to end-stage renal failure

Aims. To identify the prognostic factors possibly related to end-stage renal failure development. Subjects and methods. The prognostic factors affecting chronic renal failure progression were analysed in 456 patients who had participated in a formal, multicentre, prospective randomized trial aimed at verifying the role of protein restriction in slowing down or halting the progression of chronic renal failure. The 24-month follow-up foreseen by the protocol was completed by 311 patients and 69 reached an end-point. An inductive analysis on patient survival was made by using the Cox proportional hazard regression model, using a stepwise procedure in order to select only those factors which are significantly associated with survival. For each individual risk factor, a univariate descriptive analysis of survival was performed using the Kaplan-Meier technique. Results. Underlying nephropathy, baseline plasma creatinine, proteinuria, and plasma calcium were all shown to be related to end-stage renal failure on-set. Hypertensive patients (mean blood pressure > 107 mmHg) had a worst cumulative renal survival but the degree of proteinuria was even more important as a prognostic factor of renal death than hypertension. The cumulative renal survival of patients whose proteinuria decreased during the trial follow-up was better than those of patients without changes. However, the interaction between baseline lying mean blood pressure and proteinuria was not significant. Conclusions. Only primary renal disease and proteinuria were related to renal survival, being baseline plasma creatinine confounding factor. By blocking the possible causal role of proteinuria and hypertension, end-stage renal failure could be prevented in a significant percentage of patients.
MYELOID NEOPLASIA COP1 targets C/EBP a for degradation and induces acute myeloid leukemia via Trib1

The ubiquitin ligase constitutively photomorphogenic 1 (COP1) is involved in many bio-logicalresponsesinmammaliancells,butitsroleintumorigenesisremainsunclear.Herewe show that COP1 is a ubiquitin ligase for the tumor suppressor CCAAT/enhancer-binding protein (C/EBP a ) and promotes its degradation in vivo, thereby blocking myeloid differentiation of hematopoietic cells for tumorigenesis. In this process, mammalian homolog of Tribbles, Trib1, which contains a COP1-binding motif, is essential for down-regulation of C/EBP a expression. Murine bone marrow transplantation experiments showed that coex-pressionofCOP1acceleratesdevelopment ofacutemyeloid leukemiainduced byTrib1, whichpathologicallyresemblesthatofp42C/EBP a -deficientmice.Interestingly,coexpression of ligase activity-deficient COP1 mutant abrogated Trib1-induced leukemogenesis. These results indicate that COP1 and Trib1 act as an oncoprotein complex functioning upstream of C/EBP a , and itsligase activityis crucial for leukemogenesis. ( Blood . 2013;122(10):1750-1760)
​ 20 Functional signatures in non-small-cell lung cancer: a systematic review and meta-analysis of sex-based differences in

Spanish National Bioinformatics Institute, ELIXIR-Spain (INB, ELIXIR-ES). * Correspondence: fgarcia@cipf.es Abstract: ​ While studies have established the existence of ​differences in the epidemiological and clinical patterns of lung adenocarcinoma between male and female patients, we know relatively little regarding the molecular mechanisms underlying such sex-based differences. In this study, we explore said differences through a meta-analysis of transcriptomic data. We performed a meta-analysis of the functional profiling of nine public datasets that included 1,366 samples from Gene Expression Omnibus and The Cancer Genome Atlas databases. Meta-analysis results show an enrichment of Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways related to the immune response, nucleic acid metabolism, and purinergic signaling. We discovered the overrepresentation of terms associated with the immune response, particularly with acute inflammatory response, and purinergic signaling in female lung adenocarcinoma patients, which could influence reported clinical differences. Further evaluations of the identified differential biological processes and pathways could lead to the discovery of new biomarkers and therapeutic targets. Our findings also emphasize the relevance of sex-specific analyses in the Notch signaling pathway discovered in