Miracle-dz/UniFAR-FTUs huggingface dataset:
Mild prolonged chronic hyponatremia and risk of hip fracture in the elderly.

BACKGROUND Hip fractures are among the most serious bone fractures in the elderly, producing significant morbidity and mortality. Several observational studies have found that mild hyponatremia can adversely affect bone, with fractures occurring as a potential complication. We examined if there is an independent association between prolonged chronic hyponatremia (>90 days duration) and risk of hip fracture in the elderly. METHODS We performed a retrospective cohort study in adults >60 years of age from a prepaid health maintenance organization who had two or more measurements of plasma sodium between 2005 and 2012. The incidence of hip fractures was assessed in a very restrictive population: subjects with prolonged chronic hyponatremia, defined as plasma sodium values <135 mmol/L, lasting >90 days. Multivariable Cox regression was performed to determine the hazard ratio (HR) for hip fracture risk associated with prolonged chronic hyponatremia after adjustment for the propensity to have hyponatremia, fracture risk factors and relevant baseline characteristics. RESULTS Among 31 527 eligible patients, only 228 (0.9%) had prolonged chronic hyponatremia. Mean plasma sodium was 132 ± 5 mmol/L in hyponatremic patients and 139 ± 3 mmol/L in normonatremic patients (P < 0.001). The absolute risk for hip fracture was 7/282 in patients with prolonged chronic hyponatremia and 411/313 299 in normonatremic patients. Hyponatremic patients had a substantially elevated rate of hip fracture [adjusted HR 4.52 (95% CI 2.14-9.6)], which was even higher in those with moderate hyponatremia (<130 mmol/L) [adjusted HR 7.61 (95% CI 2.8-20.5)]. CONCLUSION Mild prolonged chronic hyponatremia is independently associated with hip fracture risk in the elderly population, although the absolute risk is low. However, proof that correcting hyponatremia will result in a reduction of hip fractures is lacking.
Problem Gambling Symptomatology and Alcohol Misuse Among Adolescents: A Parallel-Process Latent Growth Curve Model

The objective of the current study was to examine the possible temporal associations between alcohol misuse and problem gambling symptomatology from adolescence through to young adulthood. Parallel-process latent growth curve modeling was used to examine the trajectories of alcohol misuse and symptoms of problem gambling over time. Data were from a sample of adolescents recruited for the Leisure, Lifestyle, and Lifecycle Project in Alberta, Canada (n = 436), which included 4 assessments over 5 years. There was an average decline in problem gambling symptoms followed by an accelerating upward trend as the sample reached the legal age to gamble. There was significant variation in the rate of change in problem gambling symptoms over time; not all respondents followed the same trajectory. There was an average increase in alcohol misuse over time, with significant variability in baseline levels of use and the rate of change over time. The unconditional parallel process model indicated that higher baseline levels of alcohol misuse were associated with higher baseline levels of problem gambling symptoms. In addition, higher baseline levels of alcohol misuse were associated with steeper declines in problem gambling symptoms over time. However, these between-process correlations did not retain significance when covariates were added to the model, indicating that one behavior was not a risk factor for the other. The lack of mutual influence in the problem gambling symptomatology and alcohol misuse processes suggest that there are common risk factors underlying these two behaviors, supporting the notion of a syndrome model of addiction.
Long-Term Influence of CYP 3 A 5 , CYP 3 A 4 , ABCB 1 , and NR 1 I 2 Polymorphisms on Tacrolimus Concentration in Chinese Renal Transplant Recipients

Background: The highly pharmacokinetic variability of tacrolimus makes it difficult to adjust the dose. In the current study, we investigated the influence of gene polymorphisms and other clinical factors on long-term tacrolimus dosing in Chinese renal transplant recipients. Methods: A total of 276 renal transplant recipients were enrolled. The tacrolimus trough concentration and other clinical variables were recorded for 5 years following transplantation. Eight single nucleotide polymorphisms in four genes (CYP3A5, CYP3A4, ABCB1, and NR1I2) were genotyped using polymerase chain reaction–restriction fragment length polymorphism analysis and sequencing. The dose-adjusted tacrolimus trough concentrations were calculated and compared among patients according to allelic status. Results: The alleles CYP3A5*3 and CYP3A4*18B were significantly associated with dose-adjusted tacrolimus blood trough concentrations and had a strong time–genotype interaction with tacrolimus pharmacokinetics. NR1I2 g.7635A>G had a significant interaction with time, but the dose-adjusted tacrolimus concentration did not significantly differ over 5 years posttransplantation, except for the GG genotype of NR1I2 g.7635A>G. Sex differences had an important influence on tacrolimus concentration during the later posttransplantation period. Conclusions: The interindividual variability of tacrolimus concentration appears to be due in part to the effects of these identified genetic variants and clinical characteristics. Thus, genotyping of the CYP3A4 and CYP3A5 genes should be considered with respect to determining tacrolimus dose regimens during the posttransplantation period.
Microsatellite instability is a biomarker for immune checkpoint inhibitors in endometrial cancer

In recent years, it has become evident that tumor cells have immune escape mechanisms, and immune checkpoint inhibitor therapy (anti-PD-1/PD-L1 antibody) has shown benefit in various cancers. In endometrial tumors with microsatellite-instability (MSI), somatic mutations have the potential to encode ‘’non-self’’ immunogenic antigens, and lymphocytes have been shown to infiltrate the tumor. Therefore, immune checkpoint inhibitor therapy might be effective in endometrial cancers with MSI. Expression of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, and MSH6), the presence of tumor-infiltrating lymphocytes (CD8+), and PD-1/PD-L1 expression were assessed by immunohistochemistry in 149 patients with endometrial cancer. We examined whether tumors with MSI had an enhanced immune microenvironment and whether MSI could be a predictor of the therapeutic effect of PD-1/PD-L1 immunotherapy in endometrial cancer. Loss of MMR protein expression was identified in 42 (28.2%) of 149 patients (MSI group) with endometrial cancer. There was no significant relationship between MSI status and age (p = 0.193), histological grade (p = 0.097), FIGO stage (p = 0.508), pelvic lymph node metastasis (p = 0.139), or depth of myometrial invasion (p = 0.494). However, the presence of tumor-infiltrating lymphocytes (CD8+) and PD-L1/PD-1 expression were significantly higher in the MSI group compared to the microsatellite-stable group (p = 0.002, p = 0.001, and p = 0.008, respectively). These results suggest that immune checkpoint inhibitors (anti-PD-1/PD-L1 antibody) could be effective in endometrial cancers with MSI. The presence of MSI may be a biomarker for good response to PD-1/PD-L1 immunotherapy in endometrial cancer.
( 1-7 ) EFFECT OF DIFFERENT LEVELS OF LEMON GRASS OIL ( LGO ) AS ANATURAL GROWTH PROMOTER ON THE PERFORMANCE , CARCASS YIELDS AND SERUM CHEMISTRY OF BROILER CHICKS By

A.M.Mukhtar 1,K.A. Mohamed1.Amal ,O.A 2; ,Ahlam, A.H. 3 1-College of Agriculture Studies, Department of Animal ProductionSudan University of Science and Technology Khartoum North ,Shambat ,P.O. Box:407 2-Faculty of Agriculture, Bakht Al-Roda University 3-Food Research Centre Shambat, Khartoum, Sudan. Corresponding author: Mukhtar Ahmed Mukhtar Email: mukhtarahmed 18201169@ yahoo.com Tel.0111330435
Advances in targeted therapy for acute myeloid leukaemia

In the past few years, research in the underlying pathogenic mechanisms of acute myeloid leukaemia (AML) has led to remarkable advances in our understanding of the disease. Cytogenetic and molecular aberrations are the most important factors in determining response to chemotherapy as well as long‐term outcome, but beyond prognostication are potential therapeutic targets. Our increased understanding of the pathogenesis of AML, facilitated by next‐generation sequencing, has spurred the development of new compounds in the treatment of AML, particularly the creation of small molecules that target the disease on a molecular level. Various new agents, such as tyrosine kinase inhibitors, immune checkpoint inhibitors, monoclonal or bispecific T‐cell engager antibodies, metabolic and pro‐apoptotic agents are currently investigated within clinical trials. The highest response rates are often achieved when new molecularly targeted therapies are combined with standard chemotherapy. Presented here is an overview of novel therapies currently being evaluated in AML.
Duhamel and Transanal Endorectal Pull-throughs for Hirschsprung' Disease: A Systematic Review and Meta-analysis

Abstract Aim The Duhamel pull-through and transanal endorectal pull-through (TEPT) are commonly used for the treatment of Hirschsprung's disease (HD). To date, there has been no meta-analysis evaluating postoperative outcomes following Duhamel pull-through and TEPT. The purpose of this meta-analysis was to compare patient outcome after Duhamel pull-through and TEPT for HD. Materials and Methods Original articles published between 1998 and 2016 were identified using the MEDLINE database. Studies comparing Duhamel pull-through and TEPT were included. Outcomes evaluated included incidence of postoperative constipation, incontinence/soiling, enterocolitis, anastomotic stricture, and leak. We analyzed dichotomous variables by estimating odds ratios (OR) with 95% confidence intervals (CI) and continuous variables using the weighted mean difference with 95% CI. The meta-analysis was done using RevMan 5.3. Result There were no randomized controlled trials. Seven observational clinical studies were included, comprising 260 cases of Duhamel pull-through and 170 cases of TEPT. Anastomotic stricture (OR = 0.10; 95%CI 0.02–0.48; p = 0.004) was lower following Duhamel pull-through than TEPT. There were no significant differences in the incidence of postoperative incontinence/soiling and anastomotic leak. After TEPT, postoperative constipation seems to be lower and enterocolitis higher compared with those after Duhamel pull-through; however, these differences are not significant when the follow-up period is equal between groups. Conclusion The Duhamel pull-through seems to be associated with lower incidence of anastomotic stricture compared with TEPT. The effects of the two analyzed operative techniques on constipation and enterocolitis remain unclear. The quality of evidence supporting the above findings is suboptimal, indicating the need for prospective studies.
ERK/MAPK Signaling Is Required for Pathway-Specific Striatal Motor Functions

The ERK/MAPK intracellular signaling pathway is hypothesized to be a key regulator of striatal activity via modulation of synaptic plasticity and gene transcription. However, prior investigations into striatal ERK/MAPK functions have yielded conflicting results. Further, these studies have not delineated the cell-type-specific roles of ERK/MAPK signaling due to the reliance on globally administered pharmacological ERK/MAPK inhibitors and the use of genetic models that only partially reduce total ERK/MAPK activity. Here, we generated mouse models in which ERK/MAPK signaling was completely abolished in each of the two distinct classes of medium spiny neurons (MSNs). ERK/MAPK deletion in D1R-MSNs (direct pathway) resulted in decreased locomotor behavior, reduced weight gain, and early postnatal lethality. In contrast, loss of ERK/MAPK signaling in D2R-MSNs (indirect pathway) resulted in a profound hyperlocomotor phenotype. ERK/MAPK-deficient D2R-MSNs exhibited a significant reduction in dendritic spine density, markedly suppressed electrical excitability, and suppression of activity-associated gene expression even after pharmacological stimulation. Our results demonstrate the importance of ERK/MAPK signaling in governing the motor functions of the striatal direct and indirect pathways. Our data further show a critical role for ERK in maintaining the excitability and plasticity of D2R-MSNs. SIGNIFICANCE STATEMENT Alterations in ERK/MAPK activity are associated with drug abuse, as well as neuropsychiatric and movement disorders. However, genetic evidence defining the functions of ERK/MAPK signaling in striatum-related neurophysiology and behavior is lacking. We show that loss of ERK/MAPK signaling leads to pathway-specific alterations in motor function, reduced neuronal excitability, and the inability of medium spiny neurons to regulate activity-induced gene expression. Our results underscore the potential importance of the ERK/MAPK pathway in human movement disorders.
Effect of Hormonal Contraception on the Function of Plasmacytoid Dendritic Cells and Distribution of Immune Cell Populations in the Female Reproductive Tract

Objective:Epidemiological evidence suggests an association between the use of hormonal contraception and an increased risk of acquiring sexually transmitted diseases including HIV-1. We sought to elucidate the biological mechanisms underlying the effect of hormonal contraception on the immune system. Design:Cross-sectional study. Methods:To delineate the biological mechanisms underlying the effect of hormonal contraceptives on the immune system, we analyzed the functional capacity of circulating plasmacytoid dendritic cells (pDCs), the distribution of vaginal immune cell populations, and the systemic and genital levels of immune mediators in women using depot medroxyprogesterone acetate (DMPA), NuvaRing, or combined oral contraceptives (COC). Results:The use of DMPA or NuvaRing was associated with reduced capacity of circulating pDCs to produce interferon (IFN)-&agr; and tumor necrosis (TNF-&agr;) in response to TLR-9 stimulation. Systemic levels of IFN-&agr; and cervicovaginal fluid levels of IFN-&agr;, CXCL10, monocyte chemotactic protein-1, and granulocyte-colony stimulating factor were significantly lower in DMPA users compared to control volunteers not using hormonal contraception. The density of CD207+ Langerhans cells in the vaginal epithelium was reduced in NuvaRing and combined oral contraceptive users but not in DMPA users. Conclusions:The presented evidence suggests that the use of some types of hormonal contraception is associated with reduced functional capacity of circulating pDCs and altered immune environment in the female reproductive tract.
Urinary Cytomegalovirus Shedding in the United States: The National Health and Nutrition Examination Surveys, 1999–2004

Background There are no data on the prevalence of cytomegalovirus (CMV) shedding from a representative sample of the US population. This information is critical for understanding and preventing CMV. Methods We tested urine specimens from CMV immunoglobulin (Ig) G-positive participants aged 6-49 years in 3 racial/ethnic groups from the National Health and Nutrition Examination Surveys 1999-2004 for the presence of CMV DNA using real-time polymerase chain reaction assay. We examined the association of sociodemographic characteristics with shedding prevalence and viral loads. Results Among 6828 CMV IgG-positive participants tested, 537 had CMV DNA detected in urine-a shedding prevalence of 9.70%. Among persons aged 6-49 years, shedding prevalence was 3.83%. The prevalence of urinary shedding was inversely associated with increasing age (26.60%, 6.50%, and 3.45% in CMV IgG-positive participants aged 6-11, 12-19, and 20-49 years, respectively; P < .001 for trend test and pairwise comparisons). Urinary viral load also decreased significantly with age (mean, 2.97, 2.69, and 2.43 log10 copies/mL in those age groups, respectively; P < .001 for trend test and pairwise comparisons). Conclusions Urinary CMV shedding and viral loads decreased dramatically with age, likely reflecting higher rates of primary CMV infection and longer duration of shedding in younger individuals. The findings demonstrate that children aged 6-11 years continue to shed CMV at higher rates and viral loads than adolescents and adults and thus may still be an important source for CMV transmission.
Crystal structure of the electron transfer complex rubredoxin–rubredoxin reductase of Pseudomonas aeruginosa

Crude oil spills represent a major ecological threat because of the chemical inertness of the constituent n-alkanes. The Gram-negative bacterium Pseudomonas aeruginosa is one of the few bacterial species able to metabolize such compounds. Three chromosomal genes, rubB, rubA1, and rubA2 coding for an NAD(P)H:rubredoxin reductase (RdxR) and two rubredoxins (Rdxs) are indispensable for this ability. They constitute an electron transport (ET) pathway that shuttles reducing equivalents from carbon metabolism to the membrane-bound alkane hydroxylases AlkB1 and AlkB2. The RdxR–Rdx system also is crucial as part of the oxidative stress response in archaea or anaerobic bacteria. The redox couple has been analyzed in detail as a model system for ET processes. We have solved the structure of RdxR of P. aeruginosa both alone and in complex with Rdx, without the need for cross-linking, and both structures were refined at 2.40- and 2.45-Å resolution, respectively. RdxR consists of two cofactor-binding domains and a C-terminal domain essential for the specific recognition of Rdx. Only a small number of direct interactions govern mutual recognition of RdxR and Rdx, corroborating the transient nature of the complex. The shortest distance between the redox centers is observed to be 6.2 Å.
Radial Distance Estimation with Tapered Whisker Sensors

Rats use their whiskers as tactile sensors to sense their environment. Active whisking, moving whiskers back and forth continuously, is one of prominent features observed in rodents. They can discriminate different textures or extract features of a nearby object such as size, shape and distance through active whisking. There have been studies to localize objects with artificial whiskers inspired by rat whiskers. The linear whisker model based on beam theory has been used to estimate the radial distance, that is, the distance between the base of the whisker and a target object. In this paper, we investigate deflection angle measurements instead of forces or moments, based on a linear tapered whisker model to see the role of tapered whiskers found in real animals. We analyze how accurately this model estimates the radial distance, and quantify the estimation errors and noise sensitivity. We also compare the linear model simulation and nonlinear numerical solutions. It is shown that the radial distance can be estimated using deflection angles at two different positions on the tapered whisker. We argue that the tapered whisker has an advantage of estimating the radial distance better, as compared to an untapered whisker, and active sensing allows that estimation without the whisker’s material property and thickness or the moment at base. In addition, we investigate the potential of passive sensing for tactile localization.
Immunohistochemical and electron microscopic morphometric image analysis of hepatocellular carcinoma in association of HCV infection

ABSTRACT Early detection of hepatocellular carcinoma (HCC) is crucial for successful therapy. The present work examined the value of ultrastructural morphometric image analysis of hepatocyte nuclei in patients with chronic hepatitis C virus (HCV) versus HCC cases with chronic HCV and the corresponding surgical tumor-free safe margins (TFMs), to highlight any early predictive signs of neoplastic cellular transformation. This work also performed an immunohistochemical assessment of cytokeratin 19 (CK19) and Ki-67-positive cells to visualize any associated proliferative activity in the examined groups. The results showed significant decrease in the hepatocyte nuclear surface areas in the HCC and TFMs versus those in the HCV cases. The hepatocyte nucleolar surface area was significantly increased in the HCC cases versus that in the HCV cases. This increase was associated with a significant increase in Ki-67-positive cells in the HCC cases compared to those in the other groups. Conversely, the mean number of CK 19-positive cells was significantly reduced in the HCC cases compared to the cell numbers in TFMs and HCV cases with severe hepatic fibrosis. Liver progenitor cells (LPCs) were discerned in the reactive ductules and canaliculo-ductular junctions that characterized TFMs. LPCs were sporadically distributed in the liver lobules and reactive bile ductules in the HCC samples. In conclusion, CK 19 represents an important marker for distinguishing between dysplastic and malignant liver nodules. Electron microscopic morphometric image analysis may be considered as adjunct factor for assessing hepatocyte malignant transformation. Wider scale studies are needed to authenticate these results.
Knowledge of and Attitudes to Influenza Vaccination among Community Pharmacists in Catalonia (Spain). 2013–2014 Season: A Cross Sectional Study

Annual recommendations on influenza seasonal vaccination include community pharmacists, who have low vaccination coverage. The aim of this study was to investigate the relationship between influenza vaccination in community pharmacists and their knowledge of and attitudes to vaccination. An online cross-sectional survey of community pharmacists in Catalonia, Spain, was conducted between September and November 2014. Sociodemographic, professional and clinical variables, the history of influenza vaccination and knowledge of and attitudes to influenza and seasonal influenza vaccination were collected. The survey response rate was 7.33% (506 out of 6906); responses from 463 community pharmacists were included in the final analyses. Analyses were performed using multivariable logistic regression models and stepwise backward selection method for variable selection. The influenza vaccination coverage in season 2013–2014 was 25.1%. There was an association between vaccination and correct knowledge of the virus responsible for epidemics (adjusted Odds Ratio (aOR) = 1.74; 95% CI 1.03–2.95), recommending vaccination in the postpartum (aOR = 3.63; 95% CI 2.01–6.55) and concern about infecting their clients (aOR = 5.27; 95% CI 1.88–14.76). In conclusion, community pharmacists have a very low influenza vaccination coverage, are not very willing to recommend vaccination to all their customers but they are concerned about infecting their clients.
Developing Graphical Model Editors for Meta-Modelling Tools - Requirements, Conceptualisation, and Implementation

Meta-modelling tools have been proposed to facilitate the development and adoption of domain-specific modelling languages (DSMLs). These languages specify a set of domain-specific concepts and assign diagrammatic representations to them. A considerable amount of work has been done to develop metamodelling tools ensuring syntactical correctness of models created with DSMLs. However, little has been published about the challenges of developing a graphical model editor for meta-modelling tools. Specifying how conceptual elements of a DSML are to be represented graphically is often cumbersome. Moreover, tools are sometimes too inflexible to handle advanced features beyond displaying static icons. Furthermore, graphical representations must be kept consistent in case of reuse in multiple, potentially integrated DSMLs. This paper’s aim is to carve out a set of requirements for graphical model editors as used in meta-modelling tools. We present a conceptual model considering these requirements. Furthermore, we discuss an exemplary software implementation of a model editor.