bluuebunny/crossref_metadata_2025_split huggingface dataset:
The reconstitution of body mass index in HIV positive subjects under antiretroviral treatment in Kinshasa
Authors: Tshima Guyguy Kabundi , Mulumba Paul Madishala 
Published: January 2019

AbstractObjectiveWe aimed to evaluate BMI changes in HIV adults’ subjects in the first year of ART in malaria endemic areas.MethodsWe used linear regression analysis showing that the change in weight at 12 months (y) in a malaria-endemic area is related to malaria infection at admission and its different episodes as illustrated by equation: y = a + bxi + ε, where x is malaria on admission, i refers to episodes of clinical malaria infection during the year, b is the slope, a is a constant and ε are confounding factors such as tuberculosis or poor eating habits.ResultsWe found a positive value for b (b = 0.697), and this shows that weight loss at 12 months is correlated with the diagnosis of severe malaria at admission. In other words, severe malaria eliminates the weight gained under ART.ConclusionsMalaria is the leading cause of weight loss under ART.Important recommendation for future:This study suggests nutritional education based on local foods containing antioxidants to fight the oxidative stress generated by HIV and stimulated byPlasmodium falciparumduring febrile episodes. Oxidative stress is blocked by NADPHase which is a metalloenzyme based on selenium.Thus, to prevent a weight loss or the occurrence of the protein-energy malnutrition among people living with HIV, it is necessary to use the nutritional education.RésuméObjectifNous voulions évaluer les modifications de l’IMC chez les patients VIH adultes au cours de la première année du traitement antirétroviral dans une zone d’endémie palustreMatériel et MéthodesNous avons utilisé une analyse de régression linéaire montrant que la variation de poids à 12 mois (y) dans une zone d’endémie palustre est liée à l’infection palustre à l’admission et à ses différents épisodes, comme l’illustre l’équation suivante: y = a + bxi + ε, où x est le paludisme à l’admission, i les épisodes de paludisme clinique survenus au cours de l’année, b est la pente, a est une constante et ε sont des facteurs de confusion tels que la tuberculose ou de mauvaises habitudes alimentaires..RésultatsNous avons trouvé une valeur positive pour b (b = 0,697), ce qui montre que la perte de poids à 12 mois est en corrélation avec le diagnostic de paludisme grave à l’admission. En d’autres termes, le paludisme grave élimine le poids gagné sous traitement antirétroviral.ConclusionsLe paludisme est la principale cause de perte de poids sous ARV.Recommandation importante pour l’avenir : Cette étude suggère une éducation nutritionnelle basée sur des aliments locaux contenant des anti-oxydants pour lutter contre le stress oxydatif généré par le VIH et stimulé par lePlasmodium falciparumlors des poussées fébriles. Le stress oxydatif est bloqué par la NADPHase qui est une métalloenzyme à base de sélénium. Ainsi, il est nécessaire d’utiliser l’éducation nutritionnelle pour prévenir la perte du poids sous ARV.
Effects of body mass index on relationship status, social contact, and socioeconomic position: Mendelian Randomization study in UK Biobank
Authors: Howe Laura D , Kanayalal Roshni , Beaumont Robin N , Davies Alisha R , Frayling Timothy M , Harrison Sean , Jones Samuel E , Sassi Franco , Wood Andrew R , Tyrrell Jessica 
Published: January 2019

AbstractObjectiveTo assess whether body mass index (BMI) has a causal effect on social and socioeconomic factors, including whether both high and low BMI can be detrimental.DesignMendelian Randomization, using genetic variants for BMI to obtain unconfounded estimates, and non-linear Mendelian Randomization.SettingUK Biobank.Participants378,244 men and women of European ancestry, mean age 57 (SD 8 years).Main outcome measuresTownsend deprivation index, income, age completed full time education, degree level education, job class, employment status, cohabiting relationship status, participation in leisure and social activities, visits from friends and family, and having someone to confide in.ResultsHigher BMI was causally associated with higher deprivation, lower income, fewer years of education, lower odds of degree-level education and skilled employment. For example, a 1 SD higher genetically-determined BMI (4.8kg/m2 in UK Biobank) was associated with £1,660 less income per annum [95%CI: £950, £2,380]. Non-linear Mendelian Randomization provided evidence that both low BMI (bottom decile, <22kg/m2) and high BMI (top seven deciles, >24.6kg/m2) can increase deprivation and reduce income. In men only, higher BMI was related to lower participation in leisure and social activities. There was no evidence of causal effects of BMI on visits from friends and family or in having someone to confide in. Non-linear Mendelian Randomization analysis showed that low BMI (bottom three deciles, <23.5kg/m2) reduces the odds of cohabiting with a partner or spouse for men, whereas high BMI (top two deciles, >30.7kg/m2) reduces the odds of cohabitation with a partner or spouse for women.ConclusionsBMI affects social and socioeconomic outcomes, with both high and low BMI being detrimental for some measures of SEP. This suggests that in addition to health benefits, maintaining healthy ranges of BMI across the population could have benefits both for individuals and society.
Reproducibility of functional brain alterations in major depressive disorder: evidence from a multisite resting-state functional MRI study with 1,434 individuals
Authors: Xia Mingrui , Si Tianmei , Sun Xiaoyi , Ma Qing , Liu Bangshan , Wang Li , Meng Jie , Chang Miao , Huang Xiaoqi , Chen Ziqi , Tang Yanqing , Xu Ke , Gong Qiyong , Wang Fei , Qiu Jiang , Xie Peng , Li Lingjiang , He Yong ,   DIDA-Major Depressive Disorder Working Group
Published: January 2019

AbstractResting-state functional MRI (R-fMRI) studies have demonstrated widespread alterations in brain function in patients with major depressive disorder (MDD). However, a clear and consistent conclusion regarding a repeatable pattern of MDD-relevant alterations is still limited due to the scarcity of large-sample, multisite datasets. Here, we address this issue by including a large R-fMRI dataset with 1,434 participants (709 patients with MDD and 725 healthy controls) from five centers in China. Individual functional activity maps that represent very local to long-range connections are computed using the amplitude of low-frequency fluctuations, regional homogeneity and distance-related functional connectivity strength. The reproducibility analyses involve different statistical strategies, global signal regression, across-center consistency, clinical variables, and sample size. We observed significant hypoactivity in the orbitofrontal, sensorimotor, and visual cortices and hyperactivity in the frontoparietal cortices in MDD patients compared to the controls. These alterations are not affected by different statistical analysis strategies, global signal regression and medication status and are generally reproducible across centers. However, these between-group differences are partially influenced by the episode status and the age of disease onset in patients, and the brain-clinical variable relationship exhibits poor cross-center reproducibility. Bootstrap analyses reveal that at least 400 subjects in each group are required to replicate significant alterations (an extent threshold of P<.05 and a height threshold of P<.001) at 50% reproducibility. Together, these results highlight reproducible patterns of functional alterations in MDD and relevant influencing factors, which provides crucial guidance for future neuroimaging studies of this disorder.
Ontological Dimensions of Cognitive-Neural Mappings
Authors: Bolt Taylor , Nomi Jason S. , Arens Rachel , Vij Shruti G. , Riedel Michael , Salo Taylor , Laird Angela R. , Eickhoff Simon B. , Uddin Lucina Q. 
Published: January 2019

AbstractThe growing literature reporting results of cognitive-neural mappings has increased calls for an adequate organizing ontology, or taxonomy, of these mappings. This enterprise is non-trivial, as relevant dimensions that might contribute to such an ontology are not yet agreed upon. We propose that any candidate dimensions should be evaluated on their ability to explain observed differences in functional neuroimaging activation patterns. In this study, we use a large sample of task-based functional magnetic resonance imaging (task-fMRI) results and a data-driven strategy to identify these dimensions. First, using a data-driven dimension reduction approach and multivariate distance matrix regression (MDMR), we quantify the variance among activation maps that is explained by existing ontological dimensions. We find that ‘task paradigm’ categories explain the most variance among task-activation maps than other dimensions, including latent cognitive categories. Surprisingly, ‘study ID’, or the study from which each activation map was reported, explained close to 50% of the variance in activation patterns. Using a clustering approach that allows for overlapping clusters, we derived data-driven latent activation states, associated with re-occurring configurations of the canonical fronto-parietal/salience, sensory-motor, and default mode network activation patterns. Importantly, with only four data-driven latent dimensions, one can explain greater variance among activation maps than all conventional ontological dimensions combined. These latent dimensions may inform a data-driven cognitive ontology, and suggest that current descriptions of cognitive processes and the tasks used to elicit them do not accurately reflect activation patterns commonly observed in the human brain.
Combinatorial Treatment Increases IKAP Levels in Human Cells Generated from Familial Dysautonomia Patients
Authors: Yannai Sivan , Zonszain Jonathan , Donyo Maya , Ast Gil 
Published: January 2019

AbstractFamilial Dysautonomia (FD) is an autosomal recessive congenital neuropathy that results from a point mutation at the 5’ splice site of intron 20 in the IKBKAP gene. This mutation decreases production of the IKAP protein, and treatments that increase the level of the full-length IKBKAP transcript are likely to be of therapeutic value. We previously found that phosphatidylserine (PS), an FDA-approved food supplement, elevates IKAP levels in cells generated from FD patients. Here we demonstrate that combined treatment of cells generated from FD patients with PS and kinetin or PS and the histone deacetylase inhibitor trichostatin A (TSA) resulted in an additive elevation of IKAP compared to each drug alone. This indicates that the compounds influence different pathways. We also found that pridopidine enhances production of IKAP in cells generated from FD patients. Pridopidine has an additive effect on IKAP levels when used in combination with kinetin or TSA, but not with PS; suggesting that PS and pridopidine influence IKBKAP levels through the same mechanism. Indeed, we demonstrate that the effect of PS and pridopidine is through sigma-1 receptor-mediated activation of the BDNF signaling pathway. A combination treatment with any of these drugs with different mechanisms has potential to benefit FD patients.
Survival Analysis and Prognostic Factors of Time to First Domestic Violence after Marriage among Married Women in Africa
Authors: Fagbamigbe A. F. , Akintayo A. O. , Oshodi O. , Makinde F. T. , Babalola M. , Damilola E. A. , Enabor O. C. 
Published: January 2019

ABSTRACTBackgroundDomestic violence remains a public health challenge worldwide. Studies in the sub-Saharan Africa have shown high level of violence against women, especially from intimate partners. What is not known is how soon domestic violence happens after marriage among ever-married women. This study assessed the timing of first domestic violence among ever-married women and identified its determinants in Nigeria, Kenya, and Mozambique.Data and MethodData of 56440 ever-married women of reproductive age pooled from DHS conducted in Nigeria (2013), Kenya (2014) and Mozambique (2011) was used. The timing of first domestic violence was estimated as the period between marriage and the first experience of domestic violence. Ever-married women without violence experience were censored on the date of the survey. Survival analysis techniques were used to assess the timing and the factors influencing the timing p=0.05.ResultThe prevalence of domestic violence in Nigeria, Kenya and Mozambique was 12.1%, 7.5%, and 15.4% respectively. The median time to first domestic violence across the three countries was 3 years. We found a higher prevalence of violence among formerly married women than currently married women. Women who married before age 20 years have a significantly higher risk of experiencing violence (Nigeria: aHR= 2.36 (95% CI (1.97- 2.83), Kenya: aHR= 1.89 (95% CI (1.31- 2.73) and Mozambique: aHR=1.60 (95% CI (1.24 −2.12)) than older women. Women in poorer wealth quintile were at higher risk of violence across the three countries. Other factors associated with the timing of first domestic violence are respondents’, location of residence and educational attainment.ConclusionDomestic violence has remained high in Mozambique, Nigeria and Kenya. There was a significant relationship between timing of first domestic violence and whether or not a woman remains in a marriage. Education and delayed marriage could help reduce violence in marriage.
China’s Development Assistance for Health on Key Tropical Diseases: A SWOT Analysis
Authors: Li Hong-Mei , Ding Wei , Huang Lu-Lu , Ma Xue-Jiao , Qian Ying-Jun , Wang Duo-Quan , Xiao Ning , Guan Ya-Yi , Zhou Xiao-Nong 
Published: January 2019

AbstractBackgroundWHO focused and gave priority on ten serious tropical diseases, while China has made remarkable achievements on tropical diseases control. In addition, China has a history of more than 60 years in the health assistance, however, its assistance for tropical diseases started late.MethodsA qualitative questionnaire was distributed to inquiry the opinions of professionals on China’s health assistance on tropical diseases and published articles were searched to collect those data. SWOT analysis, as a tool of qualitative analysis, was used to classify and evaluate the current strengths, the weakness, the opportunities, and the threats of health assistance on tropical diseases in China.ResultsBased on SWOT analysis, the internal factors and external environments are obtained. The strengths are focused on China’s achievements on tropical diseases control, surveillance response system of tropical diseases, and human resources of public health; the weakness laid on sustainability of aid projects and funding, applicability of Chinese experience, and lack of composite talents; the opportunities are mainly in the global need of tropical diseases control, China’s health cooperation in Belt & Road and Africa, and the actively participating of international organizations in health assistance; as well as the threats are reflected in the complex international situation, domestic needs of tropical diseases control, and the significant gaps between China and developed countries.ConclusionThe internal strengths and weaknesses of development assistance for health on tropical diseases are clearly presented in the SWOT framework, as well as the external opportunities and threats and corresponding coping strategies. In the era of global health, China should strengthen and improve the health assistance for tropical diseases.Author summaryTropical diseases are serious infections in tropical and sub-tropical regions, with billions of persons infected and millions of deaths every year, especially in Africa. WHO also called for global efforts to control and eliminate tropical diseases. In the era of global health, development assistance on tropical diseases is important to demonstrate the soft power of national diplomacy, and China has started its health assistance in 1963. In this paper, a qualitative questionnaire and published articles were combined to collect data, and then SWOT analysis was used to analyze the internal factors and external environment, that is the current strengths, the weakness, the opportunities, and the threats of the China’s Health Assistance on key tropical diseases. Based on those results, we put forward the countermeasures and suggestions for the future cooperation of tropical diseases. At the end of this paper, we call on Chinese professionals should make use of their own advantages and actively improve the global tropical diseases control.
Accuracy of gene expression prediction from genotype data with PrediXcan varies across diverse populations
Authors: Mikhaylova Anna , Thornton Timothy 
Published: January 2019

AbstractPredicting gene expression with genetic data has garnered significant attention in recent years. PrediXcan is one of the most widely used gene-based association methods for testing imputed gene expression values with a phenotype due to the invaluable insight the method has shown into the relationship between complex traits and the component of gene expression that can be attributed to genetic variation. The prediction models for PrediXcan, however, were obtained using supervised machine learning methods and training data from the Depression and Gene Network (DGN) and the Genotype-Tissue Expression (GTEx) data, where the majority of subjects are of European descent. Many genetic studies, however, include samples from multi-ethnic populations, and in this paper we assess the accuracy of gene expression predictions with PrediXcan in diverse populations. Using transcriptomic data from the GEUVADIS (Genetic European Variation in Health and Disease) RNA sequencing project and whole genome sequencing data from the 1000 Genomes project, we evaluate and compare the predictive performance of PrediXcan in an African population (Yoruban) and four European populations. Prediction results are obtained using a range of models from PrediXcan weight databases, and Pearson’s correlation coefficient is used to measure prediction accuracy. We demonstrate that the predictive performance of PrediXcan varies across populations (F-test p-value < 0.001), where prediction accuracy is the worst in the Yoruban sample compared to European samples. Moreover, the performance of PrediXcan varies not only among distant populations, but also among closely related populations as well. We also find that the qualitative performance of PrediXcan for the populations considered is consistent across all weight databases used.
Mix-and-inject XFEL crystallography reveals gated conformational dynamics during enzyme catalysis
Authors: Dasgupta Medhanjali , Budday Dominik , de Oliveira Saulo H.P. , Madzelan Peter , Marchany-Rivera Darya , Seravalli Javier , Hayes Brandon , Sierra Raymond G. , Boutet Sebastian , Hunter Mark , Alonso-Mori Roberto , Batyuk Alexander , Wierman Jennifer , Lyubimov Artem , Brewster Aaron S. , Sauter Nicholas K. , Applegate Gregory A. , Tiwari Virendra K. , Berkowitz David B. , Thompson Michael C. , Cohen Aina , Fraser James S. , Wall Michael E. , van den Bedem Henry , Wilson Mark A. 
Published: January 2019

Summary ParagraphProtein dynamics play an important role in enzyme catalysis1-4. Many enzymes form covalent catalytic intermediates that can alter enzyme structure and conformational dynamics5,6. How these changes in enzyme structure and dynamics facilitate passage along the reaction coordinate is a fundamental unanswered question in structural enzymology. Here, we use Mix-and-Inject Serial Femtosecond X-ray Crystallography (MISC) at an X-ray Free Electron Laser (XFEL)7-10, ambient temperature X-ray crystallography, computer simulations, and enzyme kinetics to characterize how covalent modification of the active site cysteine residue in isocyanide hydratase (ICH) alters the enzyme’s conformational ensemble throughout the catalytic cycle. With MISC, we directly observe formation of a thioimidate covalent intermediate during ICH catalysis. The intermediate exhibits changes in the active site electrostatic environment, disrupting a hydrogen bond and triggering a cascade of conformational changes in ICH. X-ray-induced formation of a cysteine-sulfenic acid at the catalytic nucleophile (Cys101-SOH) with conventional crystallography at ambient temperature induces similar conformational shifts, demonstrating that these enzyme motions result from cysteine modification. Computer simulations show how cysteine modification-gated structural changes allosterically propagate through the ICH dimer. Mutations at Gly150 that modulate helical mobility reduce ICH catalytic turnover and alter its pre-steady state kinetic behavior, establishing that helical mobility is important for ICH catalytic efficiency. Taken together, our results demonstrate the potential of mix-and-inject XFEL crystallography to capture otherwise elusive mechanistic details of enzyme catalysis and dynamics from microcrystalline samples7,11. This approach can connect conformational dynamics to function for the large class of systems that rely on covalently modified cysteine residues for catalysis or regulation, resolving long-standing questions about enzyme mechanism and functionally relevant non-equilibrium enzyme motions.
Investigating causal pathways between liability to ADHD and substance use, and liability to substance use and ADHD risk, using Mendelian randomization
Authors: Treur Jorien L , Demontis Ditte , Smith George Davey , Sallis Hannah ,   ADHD working group of the Psychiatric Genomics Consortium, Richardson Tom G , Wiers Reinout W , Børglum Anders D , Verweij Karin JH , Munafò Marcus R 
Published: January 2019

ABSTRACTBackgroundAttention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance (ab)use, but the nature of this association is not fully understood. In view of preventive efforts, a vital question is whether there are causal effects, from ADHD to substance use and/or from substance use to ADHD.MethodsWe applied bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies (GWASs) on ADHD, smoking (initiation, cigarettes/day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks/week and alcohol use disorder), cannabis use (initiation and cannabis use disorder (CUD)) and coffee consumption (cups/day). Genetic variants robustly associated with the ‘exposure’ were selected as instruments and then identified in the ‘outcome’ GWAS. Effect estimates from individual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses were applied (weighted median, weighted mode, MR-Egger, generalized summary-data-based MR, and Steiger filtering).ResultsWe found strong evidence that liability to ADHD increases likelihood of smoking initiation and also cigarettes per day among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation and CUD. In the other direction, there was evidence that liability to smoking initiation and CUD increase ADHD risk. There was no clear evidence of causal effects between liability to ADHD and alcohol or caffeine consumption.ConclusionsWe find evidence for causal effects of liability to ADHD on smoking and cannabis use, and of liability to smoking and cannabis use on ADHD risk, indicating bidirectional pathways. Further work is needed to explore causal mechanisms.