Miracle-dz/UniFAR-FTUs huggingface dataset:
Trihalomethanes in Drinking Water and the Risk of Death from Kidney Cancer: Does Hardness in Drinking Water Matter?

The objectives of this study were to (1) examine the relationship between total trihalomethanes (TTHM) levels in public water supplies and risk of development of kidney cancer and (2) determine whether hardness levels in drinking water modify the effects of TTHM on risk of kidney cancer induction. A matched case-control study was used to investigate the relationship between the risk of death attributed to kidney cancer and exposure to TTHM in drinking water in 53 municipalities in Taiwan. All kidney cancer deaths in the 53 municipalities from 1998 through 2007 were obtained. Controls were deaths from other causes and were pair-matched to the cancer cases by gender, year of birth, and year of death. Each matched control was selected randomly from the set of possible controls for each cancer case. Data on TTHM levels and levels of hardness in drinking water were also collected. The municipality of residence for cancer cases and controls was presumed to be the source of the subject's TTHM and hardness exposure via drinking water. Relative to individuals whose TTHM exposure level was <4.9 ppb, the adjusted OR (95% CI) for kidney cancer was 0.98 (0.77–1.25) for individuals who resided in municipalities served by drinking water with a TTHM exposure ≥4.9 ppb. However, evidence of an interaction was noted between the use of soft water and drinking water TTHM concentrations. Increased knowledge of the interaction between hardness and TTHM levels in reducing risk of kidney cancer development will aid in public policy decision and establishing standards to prevent disease occurrence.
Anti-immunoglobulin E treatment decreases worm burden and egg production in Schistosoma mansoni-infected normal and interferon gamma knockout mice

The immunoglobulin E (IgE) response is generally considered an essential component of the host defense against parasitic helminths such as Schistosoma mansoni. In contrast, work on antischistosome vaccines suggests that interferon gamma (IFN-gamma) is the critical immune mediator for vaccine-induced immunity to the parasite. In this study, the total IgE response to a primary S. mansoni infection was suppressed by anti-IgE treatment in both normal mice and in mice with defective IFN genes (gene knockout [GKO]). Reduction of the IgE response resulted in decreased worm burden and a decrease in the number of eggs produced per worm in both normal and GKO mice. Whereas anti-IgE treatment also resulted in reduced hepatosplenomegaly, granulomas around existing schistosome eggs showed normal cellularity. Serum interleukin 4 levels fell in response to the reduction in serum IgE as well. The data suggest that IgE plays a detrimental, rather than beneficial, role for the host in schistosomiasis. Furthermore, the absence of IFN-gamma was found to be of little consequence to the host- response to adults or eggs in a primary schistosome infection.
Regulation of IFN Response in Vertebrates IFN-Inducible Protein Reveals Evolving Characterization of Fish IRF3 as an

In mammals, IFN regulatory factor (IRF) 3 is a critical player in modulating transcription of type I IFN and IFN-stimulated genes (ISGs). In this study, we describe the roles of crucian carp ( Carassius auratus L.) IRF3 in activating ﬁsh IFN and ISGs. Fish IRF3 exhibits a large sequence divergence from mammalian orthologs. Whereas mammalian IRF3 is constitutively expressed, ﬁsh IRF3 protein is signiﬁcantly upregulated by IFN, poly-IC, and other stimuli known as IFN inducers in mammals. The IFN-inducible property of ﬁsh IRF3 is consistent with the comparative analysis of 5 9 ﬂanking regulatory region of vertebrate IRF3 genes, which reveals the presence of typical IFN-stimulated response elements in ﬁsh and amphibians, but an absence in tetrapods. Further-more, either IFN or poly-IC induces phosphorylation and cytoplasmic-to-nuclear translocation of IRF3, which seems essential for its function in that phosphomimic active IRF3 exhibits stronger transactivation than wild type IRF3. Finally, overexpression of ﬁsh IRF3 activates production of IFN that in turn triggers ISG transcription through Stat1 pathway, whereas transfection of dominant negative mutant IRF3-DN abrogates poly-IC induction of ISGs, probably owing to blockade of IFN production. Therefore, regulation of IFN response by vertebrate IRF3 is another ancient trait. These data provide evidence of the evolving function of vertebrate IRF3 on regulating IFN response. The Journal of Immunology , 2010, 185: 000–000.
Central Cortico‐Subcortical Involvement: A Distinct Pattern of Brain Damage Caused by Perinatal and Postnatal Asphyxia in Term Infants

Objective The MR findings in a characteristic pattern of hypoxic-ischemic brain damage in term infants are described. Materials and Methods The MR images of seven patients with cerebral palsy and a specific pattern of central cortico-subcortical cerebral damage were studied retrospectively and correlated with clinical findings. Results All seven patients were born at term. Five of the seven patients had a clear history of severe perinatal asphyxia. All children had severe encephalopathic symptomatology, including spastic tetraplegia, extrapyramidal symptoms, and a mental deficit. The MR showed localized atrophy of the cortex and in addition cystic changes, gliosis, and tissue loss of the adjacent white matter. In all patients, the lesions were band shaped in the left-right direction and characteristically located in areas bordering the central sulcus. The segment of the corpus callosum underlying the affected area was always thin. In some patients, lesions were also found bilaterally in the occipital regions, hippocampus, and basal ganglia. The areas involved match the regions that are known to show active myelination on MR in the term neonate. Conclusion Recognition of this specific pattern on MR in children with cerebral palsy enables the classification of such lesions as resulting from peri- or postnatal asphyxia, even if the perinatal history is unknown or equivocal, and makes other etiologies less likely. Index Terms Infants—Central nervous system—Brain—Asphyxia—Brain, ischemia—Magnetic resonance imaging.
Subclinical Hypothyroidism in Childhood Cancer Survivors

Purpose In childhood cancer survivors, the most common late effect is thyroid dysfunction, most notably subclinical hypothyroidism (SCH). Our study evaluated the risk factors for persistent SCH in survivors. Materials and Methods Survivors (n=423) were defined as patients who survived at least 2 years after cancer treatment completion. Thyroid function was assessed at this time and several years thereafter. Two groups of survivors with SCH were compared: those who regained normal thyroid function during the follow-up period (normalized group) and those who did not (persistent group). Results Overall, 104 of the 423 survivors had SCH. SCH was observed in 26% of brain or nasopharyngeal cancer survivors (11 of 43) and 21.6% of leukemia survivors (35 of 162). Sixty-two survivors regained normal thyroid function, 30 remained as persistent SCH, and 12 were lost to follow-up. The follow-up duration was 4.03 (2.15–5.78) years. Brain or nasopharyngeal cancer and Hodgkin disease were more common in the persistent group than in the normalized group (p=0.002). More patients in the persistent group received radiation (p=0.008). Radiation to the head region was higher in this group (2394±2469 cGy) than in the normalized group (894±1591 cGy; p=0.003). On multivariable analysis, lymphoma (p=0.011), brain or nasopharyngeal cancer (p=0.039), and head radiation dose ≥1800 cGy (p=0.039) were significant risk factors for persistent SCH. Conclusion SCH was common in childhood cancer survivors. Brain or nasopharyngeal cancer, lymphoma, and head radiation ≥1800 cGy were significant risk factors for persistent SCH.
Micronisation and hot-air roasting as pre-treatments to control hard-to-cook phenomenon in cowpeas

Storage of legumes at accelerated conditions of hig h temperature and high relative humidity (HTHH) similar to tropical conditions leads to deve lopment of the hard-to-cook (HTC) phenomenon. Cowpeas with the HTC defect are charac terised by long cooking time. The objective of this study was to determine the effect of accelerated storage conditions (40 C and 80% RH for 40 days) that simulate tropical conditio ns on the development of HTC defect development in cowpeas. Three cowpea types were us d (Bechuana white , Agripienk and Mae– e–tsiliwane). The hard-to-cook (HTC) defect developed in cowp eas stored under HTHH conditions but not in those kept under refrigeratio n c nditions (4 C) as indicated by increased cooking time. The accelerated conditions of HTHH s torage used in this study were effective in inducing the hard–to-cook (HTC) defect. The cowpea s differed in their susceptibility to HTC defect, with Bechuana white being the least susceptible to the defect. The in creased cooking time in HTHH stored legumes was associated with dec reased phytate content and decreased water soluble pectin content which was in support o f the phytase-phytate-pectin theory. However, the role of lignification in the developme nt of HTC defect could not be established as both peroxidase activity and lignin content did not increase during HTHH storage. 3.1.
EFSA CONTAM Panel (EFSA Panel on Contaminants in the Food Chain), 2015. Scientific Opinion on acrylamide in food

EFSA was asked to deliver a scientific opinion on acrylamide (AA) in food. AA has widespread uses as an industrial chemical. It is also formed when certain foods are prepared at temperatures above 120 °C and low moisture, especially in foods containing asparagine and reducing sugars. The CONTAM Panel evaluated 43 419 analytical results from food commodities. AA was found at the highest levels in solid coffee substitutes and coffee, and in potato fried products. Mean and 95th percentile dietary AA exposures across surveys and age groups were estimated at 0.4 to 1.9 μg/kg body weight (b.w.) per day and 0.6 to 3.4 μg/kg b.w. per day, respectively. The main contributor to total dietary exposure was generally the category ‘Potato fried products (except potato crisps and snacks)’. Preferences in home-cooking can have a substantial impact on human dietary AA exposure. Upon oral intake, AA is absorbed from the gastrointestinal tract and distributed to all organs. AA is extensively metabolised, mostly by conjugation with glutathione but also by epoxidation to glycidamide (GA). Formation of GA is considered to represent the route underlying the genotoxicity and carcinogenicity of AA. Neurotoxicity, adverse effects on male reproduction, developmental toxicity and carcinogenicity were identified as possible critical endpoints for AA toxicity from experimental animal studies. The data from human studies were inadequate for dose-response assessment. The CONTAM Panel selected BMDL10 values of 0.43 mg/kg b.w. per day for peripheral neuropathy in rats and of 0.17 mg/kg b.w. per day for neoplastic effects in mice. The Panel concluded that the current levels of dietary exposure to AA are not of concern with respect to non-neoplastic effects. However, although the epidemiological associations have not demonstrated AA to be a human carcinogen, the margins of exposure (MOEs) indicate a concern for neoplastic effects based on animal evidence. © European Food Safety Authority, 2015
Prescribing of FDA-approved and compounded hormone therapy differs by specialty

Objective:To determine the prescribing patterns of general practitioners (GPs), obstetrician/gynecologists (OB/GYNs), and wellness physicians (WPs) of menopausal hormone therapy (HT) for both compounded (CHT) and Food and Drug Administration (FDA)-approved products, using a survey of US physicians. Methods:Nine thousand one US physicians were invited to participate in a survey to report on their HT-prescribing patterns. Physicians were eligible if they prescribed HT for at least six patients per month. Results:The survey was completed by 440 eligible physicians (893 responded of 9,001 invited) including 171 GPs, 170 OB/GYNs, and 84 WPs. Physicians prescribed HT for 15% to 30% of their female patients, with WPs numerically most likely to prescribe HT. Menopausal symptoms were the leading reason for HT prescriptions among all specialties. WPs seemed more likely to prescribe HT for general/cardiovascular health (28%), and for shorter durations, than other specialties. WPs prescribed proportionally more compounded (vs FDA-approved) estrogens/progestogens than GPs or OB/GYNs, but OB/GYNs seemed to prescribe more compounded dehydroepiandrosterone and testosterone (prescribed alone) than did others. OB/GYNs seemed least likely to consider CHT being more safe or effective than FDA-approved HT. Symptom relief was the main determinant of efficacy for all specialties; WPs also used blood (61%) or saliva testing (25%) for dose adjustment. Conclusions:Although all physician specialties surveyed prescribed HT, differences in prescribing CHT versus FDA-approved formulations by medical specialty/practice seemed to exist. Of those surveyed, OB/GYNs and GPs prescribed proportionally more FDA-approved HT, whereas WPs, similarly, prescribed more CHT. More discussion is needed concerning physicians’ decisions to prescribe CHT versus FDA-approved formulations.
Integration of stationary and transportable storage systems into multi-stage expansion planning of active distribution grids

The integration of storage systems is a promising option to reduce or defer conventional expansion measures in distribution grids. In this paper an integrated approach for grid expansion planning and deployment of permanent stationary and temporary transportable energy storage is presented. In order to adequately represent storage systems, multiple investment stages and a sophisticated evaluation process are considered. The latter takes time-coupling storage behavior and multifunctional storage operation into account. The proposed approach uses a genetic algorithm with modified operators and linear and non-linear programming models for the fitness evaluation of storage and grid operation. The results of a test case demonstrate the validity of the proposed algorithm.
Risk Factors for Recurrence of Atrial Fibrillation in Horses After Cardioversion to Sinus Rhythm

Background Although atrial fibrillation (AF) can be successfully treated in horses, recurrence occurs frequently. In humans, atrial function after cardioversion can predict recurrence. Objectives To examine the prognostic value of atrial mechanical function at 24 hours after cardioversion and other potential predictor variables for AF recurrence in horses. Animals 117 horses treated for AF at 4 referral centers. Methods Retrospective study. Inclusion criteria were successful cardioversion, echocardiography at 24 hours after cardioversion and ≥4 months follow‐up. To determine factors associated with AF recurrence, a multivariable survival model was built. Results 133 AF episodes in 117 horses were included. AF recurred in 36/100 horses with a first AF episode and in 57/133 AF episodes overall. Factors associated with recurrence in horses with a first episode were previous unsuccessful treatment attempt (hazard ratio HR 2.36, 95% confidence interval CI 1.11–4.99, P = .025) and mild or moderate mitral regurgitation (HR 2.70, 95% CI 1.23–5.91, P = .013). When the last AF episode of all horses was included, previous AF (HR 2.53, 1.33–4.82, P = .005) and active left atrial fractional area change ≤9.6% (HR 3.43, 1.22–9.67, P = .020) were significant predictors. Conclusions and Clinical Importance The only echocardiographic variable of left atrial function with significant prognostic value for recurrence was low active left atrial fractional area change. Further research is necessary to evaluate whether echocardiography at a later timepoint could provide more prognostic information.
Vertebral fractures and other predictors of back pain among older women

We examined the prevalence and predictors of back pain (BKP) among 645 postmenopausal Japanese‐American women in Hawaii with a mean age of 73.9 years (ranging from 55 to 93 years) and serial spine radiographs during the preceding 12 years. The overall prevalence of BKP was 32.9% and appeared to be constant up to age 80, with an increase thereafter. At most ages, pain in the lower back was the most common, upper BKP was less so, and mid‐BKP was the least common. The overall prevalence of BKP among Japanese‐American women in Hawaii was about half of that reported for U.S. Caucasians. Vertebral fractures were divided into three categories based on the length of time since the fracture was identified on radiographs. BKP was only associated with recent vertebral fractures (during the previous 4 years, on average) and increased progressively with the number and severity of fractured vertebrae. A history of a single recent fracture was associated with a 2.8‐fold increase in the odds of BKP; two recent fractures with a 7.8‐fold increase and three recent fractures with a 21.7‐fold increase in the odds of BKP. In addition, self‐reported disk problems, body mass index, and the number of other painful joints also showed independent associations with BKP. Height, spine bone mineral density (BMD), calcaneus BMD, smoking, and number of live births were not significantly associated with BKP. (J Bone Miner Res 1996;11:1026–1032)
Comparison of Atmospheric Travel Distances of Several PAHs Calculated by Two Fate and Transport Models (The Tool and ELPOS) with Experimental Values Derived from a Peat Bog Transect

Multimedia fate and transport models are used to evaluate the long range transport potential (LRTP) of organic pollutants, often by calculating their characteristic travel distance (CTD). We calculated the CTD of several polycyclic aromatic hydrocarbons (PAHs) and metals using two models: the OECD POV& LRTP Screening Tool (The Tool), and ELPOS. The absolute CTDs of PAHs estimated with the two models agree reasonably well for predominantly particle-bound congeners, while discrepancies are observed for more volatile congeners. We test the performance of the models by comparing the relative ranking of CTDs with the one of experimentally determined travel distances (ETDs). ETDs were estimated from historical deposition rates of pollutants to peat bogs in Eastern Canada. CTDs and ETDs of PAHs indicate a low LRTP. To eliminate the high influence on specific model assumptions and to emphasize the difference between the travel distances of single PAHs, ETDs and CTDs were analyzed relative to the travel distances of particle-bound compounds. The ETDs determined for PAHs, Cu, and Zn ranged from 173 to 321 km with relative uncertainties between 26% and 46%. The ETDs of two metals were shorter than those of the PAHs. For particle-bound PAHs the relative ETDs and CTDs were similar, while they differed for Chrysene.
Characterization of a gyrB mutation responsible for low-level nalidixic acid resistance in Neisseria gonorrhoeae

Nalidixic acid-resistant derivatives of Neisseria gonorrhoeae WR302 were identified and categorized into two classes on the basis of their susceptibilities to this antimicrobial agent. The MIC of nalidixic acid for the derivative strain MUG116 was fourfold greater than that for its isogenic parental strain WR302 (2 versus 0.5 micrograms/ml, respectively). MUG324 was significantly more resistant to nalidixic acid (greater than 64 micrograms/ml). The MICs of other antimicrobial agents known to interact with either the gyrA or gyrB gene products were determined. Although the nalidixic acid MIC for MUG116 increased, no significant increases in the MICs of other agents that interact with the gyrA gene product were seen. The MICs of all agents that interact with the gyrA gene product were significantly increased for MUG324. The gene that imparts low-level nalidixic acid resistance was cloned from strain MUG116. The DNA sequence of this gene was determined, and by comparing the deduced amino acid sequence with sequences of proteins in data bases, this protein was found to be approximately 70% homologous with the gyrB gene product of Escherichia coli.
Killer Cell Immunoglobulin-Like Receptor Gene Associations with Autoimmune and Allergic Diseases, Recurrent Spontaneous Abortion, and Neoplasms

Killer cell immunoglobulin-like receptors (KIRs) are a family of cell surface inhibitory or activating receptors expressed on natural killer cells and some subpopulations of T lymphocytes. KIR genes are clustered in the 19q13.4 region and are characterized by both allelic (high numbers of variants) and haplotypic (different numbers of genes for inhibitory and activating receptors on individual chromosomes) polymorphism. This contributes to diverse susceptibility to diseases and other clinical situations. Associations of KIR genes, as well as of genes for their ligands, with selected diseases such as psoriasis vulgaris and atopic dermatitis, rheumatoid arthritis, recurrent spontaneous abortion, and non-small cell lung cancer are discussed in the context of NK and T cell functions.
Identification of an Essential Region for Translocation of Clostridium difficile Toxin B

Clostridium difficile toxin A (TcdA) and toxin B (TcdB) are the major virulence factors involved in C. difficile-associated diarrhea and pseudomembranous colitis. TcdA and TcdB both contain at least four distinct domains: the glucosyltransferase domain, cysteine protease domain, receptor binding domain, and translocation domain. Few studies have investigated the translocation domain and its mechanism of action. Recently, it was demonstrated that a segment of 97 amino acids (AA 1756–1852, designated D97) within the translocation domain of TcdB is essential for the in vitro and in vivo toxicity of TcdB. However, the mechanism by which D97 regulates the action of TcdB in host cells and the important amino acids within this region are unknown. In this study, we discovered that a smaller fragment, amino acids 1756–1780, located in the N-terminus of the D97 fragment, is essential for translocation of the effector glucosyltransferase domain into the host cytosol. A sequence of 25AA within D97 is predicted to form an alpha helical structure and is the critical part of D97. The deletion mutant TcdB∆1756–1780 showed similar glucosyltransferase and cysteine protease activity, cellular binding, and pore formation to wild type TcdB, but it failed to induce the glucosylation of Rho GTPase Rac1 of host cells. Moreover, we found that TcdB∆1756–1780 was rapidly degraded in the endosome of target cells, and therefore its intact glucosyltransferase domain was unable to translocate efficiently into host cytosol. Our finding provides an insight into the molecular mechanisms of action of TcdB in the intoxication of host cells.
Both DNA Polymerases δ and ε Contact Active and Stalled Replication Forks Differently

ABSTRACT Three DNA polymerases, polymerases α, δ, and ε (Pol α, Pol δ, and Pol ε), are responsible for eukaryotic genome duplication. When DNA replication stress is encountered, DNA synthesis stalls until the stress is ameliorated. However, it is not known whether there is a difference in the association of each polymerase with active and stalled replication forks. Here, we show that each DNA polymerase has a distinct pattern of association with active and stalled replication forks. Pol α is enriched at extending Okazaki fragments of active and stalled forks. In contrast, although Pol δ contacts the nascent lagging strands of active and stalled forks, it binds to only the matured (and not elongating) Okazaki fragments of stalled forks. Pol ε has greater contact with the nascent single-stranded DNA (ssDNA) of the leading strand on active forks than on stalled forks. We propose that the configuration of DNA polymerases at stalled forks facilitates the resumption of DNA synthesis after stress removal.