Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction models for dementia and neuropathology in the oldest old Hall , Anette 2019-01-22

Background: We developed multifactorial models for predicting incident dementia and brain pathology in the oldest old using the Vantaa 85+ cohort. Methods: We included participants without dementia at baseline and at least 2 years of follow-up (N = 245) for dementia prediction or with autopsy data (N = 163) for pathology. A supervised machine learning method was used for model development, considering sociodemographic, cognitive, clinical, vascular, and lifestyle factors, as well as APOE genotype. Neuropathological assessments included β-amyloid, neurofibrillary tangles and neuritic plaques, cerebral amyloid angiopathy (CAA), macroand microscopic infarcts, α-synuclein pathology, hippocampal sclerosis, and TDP-43. Results: Prediction model performance was evaluated using AUC for 10 × 10-fold cross-validation. Overall AUCs were 0.73 for dementia, 0.64–0.68 for Alzheimer’s disease (AD)or amyloid-related pathologies, 0.72 for macroinfarcts, and 0.61 for microinfarcts. Predictors for dementia were different from those in previous reports of younger populations; for example, age, sex, and vascular and lifestyle factors were not predictive. Predictors for dementia versus pathology were also different, because cognition and education predicted dementia but not ADor amyloid-related pathologies. APOE genotype was most consistently present across all models. APOE alleles had a different impact: ε4 did not predict dementia, but it did predict all ADor amyloid-related pathologies; ε2 predicted dementia, but it was protective against amyloid and neuropathological AD; and ε3ε3 was protective against dementia, neurofibrillary tangles, and CAA. Very few other factors were predictive of pathology. Conclusions: Differences between predictors for dementia in younger old versus oldest old populations, as well as for dementia versus pathology, should be considered more carefully in future studies.
What Determines Protection of Property Rights? An Analysis of Direct and Indirect Effects

Using cross-country data, the authors evaluate historical determinants of protection of property rights. They examine four historical theories that focus on conceptually distinct causal variables believed to shape institutions: legal origin, endowments, ethnic diversity, and religion. There is only one realization of the data with relatively few observations, which have by now been well explored in the literature. Given the correlations between the explanatory variables, it is difficult to fashion empirical tests which are consistent in their treatment of the competing theories and to know which regressions to take seriously, giving rise to competing interpretations in the literature. The authors use Directed Acyclic Graph (DAG) methodology to identify which historical factors are direct determinants of property rights protection and which are not, and subject the outcomes to a battery of robustness tests. The empirical results support ethnic fractionalization as a robust determinant of property rights protection. Despite the attention it has received in the literature, the impact of legal origin on protection of property rights appears fragile and dependent on the inclusion of transition economies in the sample.
Musculoskeletal Consequences in Cyber-Addicted Students - Is It Really A Matter of Health? A ROC Curve Analysis for Prioritizing Risk Factors

Background: The high prevalence and also multiple consequences of addiction to various online content, including online games and social networks, have become a major challenge. The ability to predict musculoskeletal disorders from this addiction can help reveal in students' health status in the near future. The aim of this study was to determine the prevalence of this addiction and the ability to predict neck pain from this matter in students. Study Design: A cross sectional study. Methods: This study was carried out among 665 students. Data collection was performed through three questionnaires on problematic use of online games, social networking addiction, and Nordic musculoskeletal disorders. Data were compared with Chi-square and independent T-test, and the logistic regression model was then presented at a significant level of 0.05. Finally, the area under the receiver operating characteristic (ROC) curve and Discriminant analysis were conducted to clarify associations. Results: The prevalence of Internet-related content addiction was 32.8%. The results showed that addiction to social networks and online games can increase the risk of neck disorder. Also 0.58 area under ROC curve depicted the ability to predict neck pain from this addiction. Conclusions: In students with internet - related content addiction, neck disorder can be predicted. Given the high prevalence of internet addiction in students, it is essential to take immediate and appropriate interventions to avoid the associated adverse effects such as neck problems.
Puzzles and Surprises in Employment and Productivity in U.S. Manufacturing After the Great Recession

Though U.S. manufacturing output recovered more slowly from the Great Recession than historical experience would have predicted, manufacturing employment, which peaked in 1979, grew between 2010 and 2017. This was the second-longest period of manufacturing employment growth in the entire postwar period. Linking these developments was an historically unprecedented, protracted absolute decline in labour productivity. This article provides an overview of these puzzling aggregate developments and of the diverse industrylevel changes they summarize. The roles of foreign competition, mis-measurement of real output, and the computer industry are explored, and the value of looking within multi-industry aggregates like manufacturing is illustrated.
Land market distortions: Theory and evidence from Guatemala

Farm size and land allocation are important factors in explaining lagging agricultural productivity in developing countries. This paper formally examines the effect of land market distortions on the allocation of land across farmers and overall agricultural productivity. We first develop a theoretical framework to model the optimal size distribution of farms and assess to what extent market distortions can explain non-optimal land allocation and output inefficiency. We then calibrate the model to the case of Guatemala and evaluate potential drivers of the distortions across locations. We find that aggregate agricultural productivity across regions is over the range of 54-95% of the efficient output for different major crops considered. We evaluate alternative factors correlated with these distortions and provide some policy recommendations to improve efficiency. Acknowledgement : We thank the Instituto Nacional de Estadistica (INE) and the Secretaria de Seguridad Alimentaria y Nutricional (SESAN) of Guatemala for their help in accessing and collecting part of the data used in the analysis. Francisco Ceballos provided excellent research assistance. All errors are our own.
Human Nutrition and Metabolism Distribution of Protein Turnover Changes with Age in Humans as Assessed by Whole-Body Magnetic Resonance Image Analysis to Quantify Tissue Volumes 1

We tested the hypothesis that nonmuscle lean tissue mass and its rate of protein catabolism remain constant with aging despite changes in the proportional contribution of these tissues to whole-body protein metabolism. Whole-body protein kinetics, using the 60-h oral [ N]glycine method, and muscle and nonmuscle protein catabolism, based on protein kinetic data, urinary N-methylhistine excretion and lean tissue volumes defined by whole-body magnetic resonance imaging, from eight healthy elderly subjects (5 females and 3 males, mean age 71.5 y) were compared with those of seven young persons (3 females and 4 males, mean age 28 y). There were no significant age or gender effects on rates of protein kinetics per L total lean tissue. There was a lower (P , 0.004) rate of muscle protein catabolism in the elderly (1.8 6 0.2 vs. 2.6 6 0.1 g z L z d) and a trend (P 5 0.08) for lower muscle volume (19.7 6 1.5 vs. 25.0 6 2.4 L). This contrasted with intraabdominal lean tissue, where the rate of protein catabolism (13.8 6 0.6 vs. 13.2 6 0.9 g z L z d) and volume (7.5 6 0.3 vs 8.0 6 0.5 L) did not differ between age groups. Thus, the decrease in the contribution by muscle to whole-body protein metabolism with age is associated with an increase from 62 to 74% (P , 0.001) in the contribution by nonmuscle lean tissues. These findings have potential implications for the nutrition of both normal and sick elderly persons. J. Nutr. 130:
Expression and clinical significance of 5-HT and 5-HT3R in the intestinal mucosa of patient with diarrhea-type irritable bowel syndrome

Expression levels and clinical significance of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with diarrhea-type irritable bowel syndrome (D-IBS) were investigated. A retrospective analysis was performed on 46 tissue specimens (observation group) of the intestinal mucosa of patients with D-IBS, who were diagnosed in the Tongde Hospital of Zhejiang Province and received colonoscopy from March 2016 to December 2017, and 18 tissue specimens (control group) of the intestinal mucosa of healthy subjects who received physical examinations. The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients in the observation and control group were detected by ELISA, and the relationship between 5-HT, 5-HT3R and the clinicopathological parameters of patients with D-IBS was analyzed. Pearson's correlation analysis was used to analyze the correlation of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with D-IBS. The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients in the observation group were significantly higher than those of the patients in the control group (344.86±67.52 ng/ml and 13.04±8.34 pg/ml) (P<0.001). There was a positive correlation between the expression level of 5-HT and the expression level of 5-HT3R in the intestinal mucosa tissue of patients with D-IBS (r=0.725, P<0.001). The expression levels of 5-HT and 5-HT3R in the intestinal mucosa tissue of patients with D-IBS were both significantly higher than those of the healthy subjects. The expression levels of 5-HT and 5-HT3R in patients with D-IBS were correlated with age, sex and the history of gastrointestinal infection. 5-HT and 5-HT3R may be involved in the pathogenesis of D-IBS, and potentially used for clinical treatment.
Identification of neoantigen-specific T cells and their targets: implications for immunotherapy of head and neck squamous cell carcinoma

ABSTRACT To develop a practically applicable method for T-cell receptor (TCR)-engineered T cell immunotherapy targeting neoantigens, we have been attempting to identify neoantigen-specific T cell receptors (TCRs) and establish TCR-engineered T cells in a 3–4-month period. In this study, we report the characterization of T cell repertoires in tumor microenvironment (TME) and identification of neoantigen-specific TCRs after stimulation of patient-derived T cells. We screened 15 potential neoantigen peptides and successfully identified two CD8+HLA-dextramer+ T cells, which recognized MAGOHBG17A and ZCCHC14P368L. All three dominant TCR clonotypes from MAGOHBG17A-HLA dextramer-sorted CD8+ T cells were also found in T cells in TME, while none of dominant TCR clonotypes from ZCCHC14P368L-HLA dextramer-sorted CD8+ T cells was found in the corresponding TME. The most dominant TCRA/TCRB pairs for these two neoantigens were cloned into HLA-matched healthy donors’ T lymphocytes to generate TCR-engineered T cells. The functional assay showed MAGOHBG17A TCR-engineered T cells could be significantly activated in a mutation-specific, HLA-restricted and peptide-dose-dependent manner while ZCCHC14P368L TCR-engineered T cells could not. Our data showed neoantigen-reactive T cell clonotypes that were identified in the patient’s peripheral blood could be present in the corresponding TME and might be good TCRs targeting neoantigens.
Nicotine oxidation by genetic variants of CYP2B6 and in human brain microsomes

Common variation in the CYP2B6 gene, encoding the cytochrome P450 2B6 enzyme, is associated with substrate‐specific altered clearance of multiple drugs. CYP2B6 is a minor contributor to hepatic nicotine metabolism, but the enzyme has been proposed as relevant to nicotine‐related behaviors because of reported CYP2B6 mRNA expression in human brain tissue. Therefore, we hypothesized that CYP2B6 variants would be associated with altered nicotine oxidation, and that nicotine metabolism by CYP2B6 would be detected in human brain microsomes. We generated recombinant enzymes in insect cells corresponding to nine common CYP2B6 haplotypes and demonstrate genetically determined differences in nicotine oxidation to nicotine iminium ion and nornicotine for both (S) and (R)‐nicotine. Notably, the CYP2B6.6 and CYP2B6.9 variants demonstrated lower intrinsic clearance relative to the reference enzyme, CYP2B6.1. In the presence of human brain microsomes, along with nicotine‐N‐oxidation, we also detect nicotine oxidation to nicotine iminium ion. However, unlike N‐oxidation, this activity is NADPH independent, does not follow Michaelis‐Menten kinetics, and is not inhibited by NADP or carbon monoxide. Furthermore, metabolism of common CYP2B6 probe substrates, methadone and ketamine, is not detected in the presence of brain microsomes. We conclude that CYP2B6 metabolizes nicotine stereoselectively and common CYP2B6 variants differ in nicotine metabolism activity, but did not find evidence of CYP2B6 activity in human brain.
Attitudes and Preferences Regarding the Use of Rapid Self-Testing for Sexually Transmitted Infections and HIV in San Diego Area Men Who Have Sex With Men

Abstract Background Sexually transmitted infections (STIs) increase the risk of HIV transmission and are present at high rates among men who have sex with men (MSM). Adherence to HIV/STI testing guidelines is low in the United States. Testing programs that utilize rapid self-administered HIV/STI tests improve testing rates, though multiple factors influence their uptake. Methods MSM were recruited at an HIV/STI testing and treatment program in 2014 and provided consent, demographics, risk behaviors, HIV/STI test preferences, and perceived testing barriers via an online questionnaire. Comparisons of testing preferences and barriers were made based on age, risk group, and HIV serostatus using the Fisher exact test. Results HIV testing preferences included rapid oral test (71.1%), home test location (78.5%), electronic delivery of HIV-negative test results (76.4%), and direct provider notification for HIV-positive test results (70%), with respondents age >45 years being significantly more likely to prefer home testing (P = .033). STI testing preferences included self-collection of specimens (73.2%), home test location (61%), electronic delivery of negative STI test results (76.4%), and direct provider notification for positive STI test results (56.6%) with no significant differences between age, HIV serostatus, or risk groups. The most frequently reported HIV and STI testing barrier was lack of known prior HIV/STI exposure (57.3% for HIV, 62.9% for STI) with respondents age <45 years more frequently citing inconvenience as a barrier to testing (HIV: 50.9% vs 17.4%, P = .010; STI: 58.3% vs 31.8%, P = .070). Conclusions Although additional research is needed, increasing resources directed specifically toward home testing has the potential to translate into improved uptake of rapid HIV/STI testing. Efforts to improve convenience in testing programs must be balanced with the need for continued educational outreach.
Sevoflurane exerts protective effects on liver ischemia/reperfusion injury by regulating NFKB3 expression via miR-9-5p

Hepatic ischemia/reperfusion (IR) injury is a critical contraindication of hepatobiliary surgery and results in severe liver damage. It is imperative to identify underlying pathophysiological mechanisms. In the current study, a rat model of liver IR was established to explore the mechanisms of sevoflurane during surgical intervention on IR. The detection of cytokines was performed using ELISA and reverse transcription-quantitative polymerase chain reaction and western blot assays were used to detect mRNA and protein expression levels, respectively. The target protein of microRNA (miR)-9-5p was identified by in vitro luciferase reporter assay. Cell apoptosis was detected by Annexin-V/propidium iodide and TUNEL staining assays. The results demonstrated that sevoflurane exerted protective effect against liver IR. Sevoflurane administration ameliorated a cytokine storm by decreasing serum levels of interleukin (IL)-1 and −6 and tumor necrosis factor (TNF)-α, and improved liver function was determined. IR-induced damage was mediated by an increase in transcription factor p65 expression and activation of the nuclear factor (NF)-κB signaling pathway, which were suppressed by sevoflurane treatment. In situ analysis predicted that NFKB3, encoding for p65, may be targeted by miR-9-5p and the hypothesis was verified by in vitro reporter assays using wild type and mutant sequences of the NFKB3 3′-untranslated region. Furthermore, pretreatment of hepatic tissue with a miR-9-5p mimic inhibited IR-associated injury as suggested by the decrease in the Suzuki score and decreased serum levels of TNF-α, IL-1 and IL-6. The results indicated that sevoflurane protected the liver from IR injury by increasing miR-9-5p expression and miR-9-5p may be a potential treatment target in IR.
Bone loss and biomechanical reduction of appendicular and axial bones under ketogenic diet in rats

A ketogenic diet (KD) is composed of low-carbohydrate, high-fat and adequate levels of protein. It has been used for decades as a method to treat pediatric refractory epilepsy. However, recently, its side effects on the bones have received increasing attention. In order to comprehensively evaluate the effect of KD on the microstructures and mechanical properties of the skeleton, 14 male Sprague-Dawley rats were equally divided into two groups and fed with a KD (ratio of fat to carbohydrate and protein, 3:1) or a standard diet for 12 weeks. Body weight, as well as blood ketone and glucose levels, were monitored during the experiment. Bone morphometric analyses via micro-computerized tomography were performed on cortical and trabecular bone at the middle L4 vertebral body, the proximal humerus and tibia. The compressive stiffness and strength of scanned skeletal areas were calculated using micro-finite element analysis. The KD led to higher ketone levels and lower glucose levels, with reduced body weight and total bone mineral density (TBMD). After 12 weeks, the diet reduced the bone volume fraction, the trabecular number of cancellous bone, cortical thickness, total cross-sectional area inside the periosteal envelope and the bone area of cortical bone in the tibia and humerus, while increasing trabecular separation. However, KD may not affect the L4 vertebral body. The serum calcium or phosphate concentrations in the blood remained unchanged. In addition, bone stiffness and strength were clearly decreased by the KD, and significantly correlated with the BMD and bone area at all scanned sites. In conclusion, KD led to significant bone loss and reduced biomechanical function in appendicular bones, with a lesser impact on axial bones.
Prevalence of sexual harassment of nurses and nursing students in China: a meta-analysis of observational studies

Sexual harassment experienced by nurses and nursing students is common and significantly associated with negative consequences. This study is a meta-analysis of the pooled prevalence of sexual harassment of nurses and nursing students in China. Electronic databases (PubMed, EMBASE, PsycINFO, Web of Science and Ovid, China National Knowledge Internet, WanFang, SinoMed and Chinese VIP Information) were independently and systematically searched by two reviewers from their commencement date to 12 March 2018. Forty-one studies that reported the prevalence of sexual harassment were analyzed using the random-effects model. The pooled prevalence of sexual harassment was 7.5% (95% CI: 5.5%-10.1%), with 7.5% (5.5%-10.2%) in nurses and 7.2% (3.0%-16.2%) in nursing students. Subgroup analyses showed that the year of survey and sample size were significantly associated with the prevalence of sexual harassment, but not the seniority of nursing staff, department, hospital, economic region, timeframe, age, working experience or subtypes of harassment. In China, sexual harassment was found to be common in nurses and nursing students. Considering the significant negative impact of sexual harassment, effective preventive and workplace measures should be developed.
Lamin A buffers CK2 kinase activity to modulate aging in a progeria mouse model.

The causative progeria lamin A mutation inhibits CK2 enzyme activity to accelerate aging in laboratory mice. Defective nuclear lamina protein lamin A is associated with premature aging. Casein kinase 2 (CK2) binds the nuclear lamina, and inhibiting CK2 activity induces cellular senescence in cancer cells. Thus, it is feasible that lamin A and CK2 may cooperate in the aging process. Nuclear CK2 localization relies on lamin A and the lamin A carboxyl terminus physically interacts with the CK2α catalytic core and inhibits its kinase activity. Loss of lamin A in Lmna-knockout mouse embryonic fibroblasts (MEFs) confers increased CK2 activity. Conversely, prelamin A that accumulates in Zmpste24-deficent MEFs exhibits a high CK2α binding affinity and concomitantly reduces CK2 kinase activity. Permidine treatment activates CK2 by releasing the interaction between lamin A and CK2, promoting DNA damage repair and ameliorating progeroid features. These data reveal a previously unidentified function for nuclear lamin A and highlight an essential role for CK2 in regulating senescence and aging.