bluuebunny/crossref_metadata_2025_split huggingface dataset:
Causal relevance of obesity on the leading causes of death in women and men: A Mendelian randomization study
Authors: Censin Jenny C , Bovijn Jonas , Ferreira Teresa , Pulit Sara L , Mägi Reedik , Mahajan Anubha , Holmes Michael V , Lindgren Cecilia M 
Published: January 2019

AbstractBackgroundObesity traits are causally implicated with risk of cardiometabolic diseases. It remains unclear whether there are similar causal effects of obesity traits on other non-communicable diseases. Also, it is largely unexplored whether there are any sex-specific differences in the causal effects of obesity traits on cardiometabolic diseases and other leading causes of death. We therefore tested associations of sex-specific genetic risk scores (GRSs) for body mass index (BMI), waist-hip-ratio (WHR), and WHR adjusted for BMI (WHRadjBMI) with leading causes of mortality, using a Mendelian randomization (MR) framework.Methods and FindingsWe constructed sex-specific GRSs for BMI, WHR, and WHRadjBMI, including 565, 324, and 338 genetic variants, respectively. These GRSs were then used as instrumental variables to assess associations between the obesity traits and leading causes of mortality using an MR design in up to 422,414 participants from the UK Biobank. We also investigated associations with potential mediators and risk factors, including smoking, glycemic and blood pressure traits. Sex-differences were subsequently assessed by Cochran’s Q-test (Phet).Up to 227,717 women and 194,697 men with mean (standard deviation) age 56.6 (7.9) and 57.0 (8.1) years, body mass index 27.0 (5.1) and 27.9 (4.2) kg/m2and waist-hip-ratio 0.82 (0.07) and 0.94 (0.07), respectively, were included. Mendelian randomization analysis showed that obesity causes coronary artery disease, stroke (particularly ischemic), chronic obstructive pulmonary disease, lung cancer, type 2 and 1 diabetes mellitus, non-alcoholic fatty liver disease, chronic liver disease, and acute and chronic renal failure. A 1 standard deviation higher body mass index led to higher risk of type 2 diabetes in women (OR 3.81; 95% CI 3.42-4.25, P=8.9×10−130) than in men (OR 2.78; 95% CI 2.57-3.02, P=1.0×10−133, Phet=5.1×10−6). Waist-hip-ratio led to a higher risk of chronic obstructive pulmonary disease (Phet=5.5×10−6) and higher risk of chronic renal failure (Phet=1.3×10−4) in men than women.A limitation of MR studies is potential bias if the genetic variants are directly associated with confounders (pleiotropy), but sensitivity analyses such as MR-Egger supported the main findings. Our study was also limited to people of European descent and results may differ in people of other ancestries.ConclusionsObesity traits have an etiological role in the majority of the leading global causes of death. Sex differences exist in the effects of obesity traits on risk of type 2 diabetes, chronic obstructive pulmonary disease, and renal failure, which may have implications on public health.
The pattern of Comorbidities and Associated Risk Factors among Colorectal Cancer Patients in Spain: CoMCoR study
Authors: Luque-Fernandez Miguel Angel , Redondo-Sánchez Daniel , Rodríguez-Barranco Miguel , Carmona-García Ma Carmen , Marcos-Gragera Rafael , Sánchez María José 
Published: January 2019

AbstractColorectal cancer is the second most frequently diagnosed cancer in Spain. Cancer treatment and outcomes can be influenced by tumor characteristics, patient general health status and comorbidities. Numerous studies have analyzed the influence of comorbidity on cancer outcomes, but limited information is available regarding the frequency and distribution of comorbidities in colorectal cancer patients, particularly elderly ones, in the Spanish population. We developed a population-based high-resolution cohort study of all incident colorectal cancer cases diagnosed in Spain in 2011 to describe the frequency and distribution of comorbidities, as well as tumor and healthcare factors. We then characterized risk factors associated with the most prevalent comorbidities, as well as dementia and multimorbidity, and developed an interactive web application to visualize our findings. The most common comorbidities were diabetes (23.6%), chronic obstructive pulmonary disease (17.2%), and congestive heart failure (14.5%). Dementia was the most common comorbidity among patients aged ≥75 years. Patients with dementia had a 30% higher prevalence of being diagnosed at stage IV and the highest prevalence of emergency hospital admission after colorectal cancer diagnosis (33%). Colorectal cancer patients with dementia were nearly three times more likely to not be offered surgical treatment. Age ≥75 years, obesity, male sex, being a current smoker, having surgery more than 60 days after cancer diagnosis, and not being offered surgical treatment were associated with a higher risk of multimorbidity. Patients with multimorbidity aged ≥75 years showed a higher prevalence of hospital emergency admission followed by surgery the same day of the admission (37%). We found a consistent pattern in the distribution and frequency of comorbidities and multimorbidity among colorectal cancer patients. The high frequency of stage IV diagnosis among patients with dementia and the high proportion of older patients not being offered surgical treatment are significant findings that require policy actions.
Digital phenotyping by consumer wearables identifies sleep-associated markers of cardiovascular disease risk and biological aging
Authors: Teo Jing Xian , Davila Sonia , Yang Chengxi , Pua Chee Jian , Yap Jonathan , Tan Swee Yaw , Sahlén Anders , Chin Calvin Woon-Loong , Teh Bin Tean , Rozen Steven G , Cook Stuart Alexander , Yeo Khung Keong , Tan Patrick , Lim Weng Khong 
Published: January 2019

AbstractDespite growing adoption of consumer wearables, the potential for sleep metrics from these devices to contribute to sleep-related biomedical research remains largely uncharacterized. Here we analyze sleep tracking data, along with questionnaire responses and multi-modal phenotypic data, generated from 482 normal volunteers. First, we provide a detailed comparison of wearable-derived and self-reported sleep metrics, particularly total sleep time (TST) and sleep efficiency (SE). We then identified demographic, socioeconomic and lifestyle factors associated with wearable-derived sleep duration. We also analyzed our multi-modal phenotypic data and showed that wearable-derived TST and SE are associated with various cardiovascular disease risk markers, whereas self-reported measures were not. Using whole-genome sequencing data, we estimated leukocyte telomere length and showed that volunteers with insufficient sleep also exhibit premature telomere attrition. Our study highlights the potential for sleep metrics generated by consumer wearables to provide novel insights into data generated from population cohort studies.
The native European Aedes geniculatus mosquito species can transmit Chikungunya virus
Authors: Prudhomme Jorian , Fontaine Albin , Lacour Guillaume , Gantier Jean-Charles , Diancourt Laure , Velo Enkelejda , Bino Silva , Reiter Paul , Mercier Aurélien 
Published: January 2019

AbstractEurope is the world’s leading tourism destination and is receiving every year travelers from areas with active arbovirus transmission. There is thus a threat of mosquito-borne virus emergence in Europe due to the presence of the invasive mosquito vector Aedes albopictus. Little attention has been paid about the possible role of indigenous mosquito species as vectors of emerging arboviruses. Here, we assessed the vector competence dynamic of Ae. geniculatus, a European anthropophilic mosquito species, for chikungunya virus (CHIKV) in comparison with Ae. albopictus.We revealed that Ae. geniculatus was highly susceptible to CHIKV infection and could transmit the virus. By specifically exploring the vector competence dynamic in both mosquito species, we revealed that the cumulative distribution of CHIKV incubation period in Ae. geniculatus was delayed by several days as compared to Ae. albopictus.Our results strengthen the importance of considering indigenous species as potential vectors for emerging arboviruses. They also revealed the importance of considering variation in arbovirus dissemination or transmission dynamics in mosquitoes when performing vector competence assays. We will discuss the implications of our results on a CHIKV outbreak dynamic in a theoretical framework.Sentence summaryThe European mosquito Aedes geniculatus is highly susceptible to CHIKV infection but disseminate and transmit the virus several days later than Ae. albopictus.
Genome-wide Association Study of Alcohol Consumption and Use Disorder in Multiple Populations (N = 274,424)
Authors: Kranzler Henry R. , Zhou Hang , Kember Rachel L. , Smith Rachel Vickers , Justice Amy C. , Damrauer Scott , Tsao Philip S. , Klarin Derek , Rader Daniel J. ,   Regeneron Genetics Center Research Team, Cheng Zhongshan , Tate Janet P. , Becker William C. , Concato John , Xu Ke , Polimanti Renato , Zhao Hongyu , Gelernter Joel ,   on behalf of the VA Million Veteran Program
Published: January 2019

SummaryAlthough alcohol consumption level and alcohol use disorder (AUD) diagnosis are both moderately heritable, their genetic risks and overlap are not well understood. We conducted genome-wide association studies of these traits using longitudinal Alcohol Use Disorder Identification Test-Consumption (AUDIT-C) scores (reflecting alcohol consumption) and AUD diagnoses from electronic health records (EHRs) in a single, large multi-ancestry Million Veteran Program sample. Meta-analysis across population groups (N = 274,424) identified 18 genome-wide significant loci, 5 of which were associated with both traits and 13 with either AUDIT-C (N = 8) or AUD (N = 5). A significant genetic correlation between the traits reflects this overlap. However, downstream analyses revealed biologically meaningful points of divergence. Cell-type group partitioning heritability enrichment analyses indicated that central nervous system was the most significant cell type for AUDIT-C and the only significant cell type for AUD. Polygenic risk scores (PRS) for both traits were associated with alcohol-related disorders in two independent samples. Genetic correlations for 188 non-alcohol-related traits were significantly different for the two traits, as were the phenotypes associated with the traits’ polygenic risk scores. We conclude that EHR-derived, longitudinal, repeated measures of alcohol consumption level and AUD diagnosis can facilitate genetic discovery and help to elucidate the relationship between drinking level and AUD risk. Finally, although heavy drinking is a key risk factor for AUD, it is not a sufficient cause of the disorder.
An inhomogeneous Poisson model of the spatial intensity of opioid overdoses, as represented by EMS naloxone use
Authors: Ryan Christopher W. 
Published: January 2019

1AbstractFrom 1999 to 2017, the age-adjusted annual death rate in the United States from opioid overdose has increased several-fold, to about 18.3 per 100,000 population. The federal government has declared opioid overdose a public health emergency. Spatially-aware analyses and surveillance may contribute to control of this growing problem.As naloxone has only one clinical use—the treatment of opioid overdose—its administration by emergency medical services (EMS) personnel can serve as a surveillance indicator for opioid overdose. I previously demonstrated spatial clustering of naloxone-involved EMS calls, over and above that to be expected fromEMS calls in general. To better understand the nature of that clustering, I modelled the spatial distribution of naloxone-involved EMS calls in a three-county region in south-central New York State as an inhomogeneous Poisson process, using as predictors several census-tract-level sociodemographic variables and the point locations of convenience stores (minimarts). In Monte Carlo simulations, I examined how well the model explained the observed clustering.Although it assumes no interaction between event locations, the inhomogeneous Poisson model was nevertheless able to explain much of the observed spatial clustering. The spatial intensity of EMS calls for opioid overdose, in events per square kilometer, was signficantly higher in census tracts with lower rates of owner-occupancy of housing. Neither the proportion of households in poverty nor the proportion of residents in the 20–44 age band were signficant predictors. Spatial intensity of overdose events decreased by about 10% for each kilometer of distance from the nearest minimart, but this was of borderline signfificance at conventional levels. These findings cast some doubt on the utility of real-time surveillance for apparent spatial clusters of opioid overdose and instead favor a longer-term, systemic strategy comprising efforts to improve neighborhood conditions.
Genomic, Ancestral and Networking Analyses of a High-Altitude Native American Ecuadorian Patient with Congenital Insensitivity to Pain with Anhidrosis
Authors: López-Cortés Andrés , Zambrano Ana Karina , Guevara-Ramírez Patricia , Echeverría Byron Albuja , Guerrero Santiago , Cabascango Eliana , Pérez-Villa Andy , Armendáriz-Castillo Isaac , García-Cárdenas Jennyfer , Yumiceba Verónica , Pérez-M Gabriela , Leone Paola E. , Paz-y-Miño César 
Published: January 2019

ABSTRACTCongenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder characterized by insensitivity to pain, inability to sweat and intellectual disability. CIPA is caused by mutations in the neurotrophic tyrosine kinase receptor type 1 gene (NTRK1) that encodes the high-affinity receptor of nerve growth factor (NGF). Patients with CIPA lack the primary afferents and sympathetic postganglionic neurons leading to lack of pain sensation and the presence of anhidrosis, respectively. Herein, we conducted a genomic analysis of 4,811 genes and 18,933 variants, including 54 mutations of NTRK1 in a high-altitude indigenous Ecuadorian patient with CIPA. As results, the patient presented 87.8% of Native American ancestry, 6.6% of African ancestry and 5.6% of European ancestry. The mutational analysis of the kinase domain of NTRK1 showed two pathogenic mutations, rs80356677 (Asp674Tyr) and rs763758904 (Arg602*). The genomic analysis showed 68 pathogenic and/or likely pathogenic variants in 45 genes, and two variants of uncertain significance in CACNA2D1 (rs370103843) and TRPC4 (rs80164537) genes involved in the pain matrix. The GO enrichment analysis showed 28 genes with relevant mutations involved in several biological processes, cellular components and molecular functions. In addition, the protein-protein interaction (PPi) networking analysis showed that NTRK1, SPTBN2 and GRM6 interact with several proteins of the pain matrix. In conclusion, this is the first time that a study associates genomic, ancestral and networking data in a high-altitude Native American Ecuadorian patient with consanguinity background in order to better understand CIPA pathogenesis.
Elevation of FAM129A in neutrophils exposed to serum of patients with severe sepsis: in silico investigations during a hands on training workshop and follow on validation of protein expression in neutrophils
Authors: Roelands Jessica , Chiche Laurent , Marches Radu , Toufiq Mohammed , Kabeer Basirudeen Ahamed , Alfaki Mohamed Alkhair Ibrahim , Saadaoui Marwa , Lakshmanan Arun Prasath , Bangarusamy Dhinoth Kumar , Murugesan Selvasankar , Bedognetti Davide , Hendrickx Wouter , Khodor Souhaila Al , Terranegra Annalisa , Banchereau Jacques , Garand Mathieu , Chaussabel Damien , Rinchai Darawan 
Published: January 2019

ABSTRACTSteps involved in reductionist investigation approaches can be imitated using public transcriptome datasets as source of training material. In the present report trainees explored an apparent gap in biological knowledge for FAM129A (family with sequence similarity 129 member A). Elevated abundance of FAM129A transcripts were observed in a transcriptome dataset where neutrophils were exposed in vitro to plasma of patients with sepsis. However, no literature linking FAM129A and either neutrophils, sepsis or inflammation could be identified. Additional datasets were selected to independently validate this initial observation and further explore differential expression of FAM129A in the context of sepsis studies. Follow on investigations carried out at the bench confirmed restriction of the expression of FAM129A protein at the surface of circulating blood neutrophils and monocytes. A potential role for FAM129A in neutrophil survival was inferred from profiling of literature associated with FAM129A, which remains to be investigated in further follow on investigations.
Effects of transcranial alternating-current stimulation to secondary motor areas on cortical oscillations in stroke patients
Authors: Krawinkel Lutz A. , Bönstrup Marlene , Feldheim Jan F. , Schulz Robert , Backhaus Winifried , Schneider Till R. , Misselhorn Jonas , Cheng Bastian , Gerloff Christian 
Published: January 2019

AbstractBackgroundThere is growing evidence that secondary motor areas are relevant for recovery after motor stroke. Communication among brain areas occurs via synchronization of oscillatory activity which can potentially be modulated via transcranial alternating-current stimulation (tACS).HypothesisWe hypothesized that tACS to secondary motor areas of the stroke-lesioned hemisphere leads to modulation of task-related connectivity among primary and secondary motor areas, reflected in metrics of EEG coupling in the frequency domain.MethodsWe applied focal tACS at 1mA peak-to-peak intensity to ipsilesional ventral premotor cortex (PMv) and supplementary motor area (SMA) in chronic stroke patients while they moved their impaired hand. To probe effects of stimulation on cortical oscillations, several task-related EEG-based connectivity metrics (coherence, imaginary coherence, phase-locking value, mutual information) were assessed before and after each stimulation.ResultsOverall, we found significant but weak modulations of the motor network by tACS. Stimulation of PMv reduced task-related coupling between (i) both primary motor cortices (M1) (coherence, −0.0514±0.0665 (mean±SD, active stimulation) vs. 0.0085±0.0888 (sham), p=0.0029) and (ii) between ipsilesional M1 and contralesional PMv (coherence, - 0.0386±0.0703 vs. 0.0226±0.0694, p=0.0283; phase-locking value, −0.0363±0.0581 vs. 0.0036±0.0497, p=0.0097) compared with sham stimulation.ConclusionsIn this exploratory analysis, tACS to the ipsilesional PMv induced a weak decrease of task-related connectivity between ipsilesional M1 and contralesional M1 and PMv. As an excess of interhemispheric coupling is under discussion as maladaptive phenomenon of motor reorganization after stroke (e.g., bimodal balance-recovery model), tACS-induced reduction of coupling might be an interesting approach to assist re-normalization of the post-stroke motor network.
Disentangling strictly self-serving mutations from win-win mutations in a mutualistic microbial community
Authors: Hart Samuel F. M. , Pineda Jose Mario Bello , Chen Chi-Chun , Green Robin , Shou Wenying 
Published: January 2019

AbstractMutualisms can be promoted by win-win mutations which directly benefit self (self-serving) and partner (partner-serving). Intuitively, partner-serving phenotype could be quantified as the benefit supply rate to partner by an individual. Here, we demonstrate the inadequacy of this thinking, and propose an alternative measure. Specifically, we evolved well-mixed mutualistic communities where two engineered yeast strains exchanged essential metabolites lysine and hypoxanthine. Among cells that consumed lysine and released hypoxanthine, a chromosome duplication mutation seemed win-win: it improved cell’s affinity for lysine, and increased hypoxanthine release rate per cell. However, increased release rate was due to increased cell size accompanied by increased lysine consumption per birth. Consequently this mutation is solely self-serving, since a fixed amount of intake lysine leads to an identical total hypoxanthine release rate - either by more numerous lower-releasing ancestors or fewer higher-releasing mutants. By extension, individuals with reduced benefit production rates may not be cheaters.
Graphene oxide affects soil bacterial and fungal diversity even at parts-per-trillion concentrations
Authors: Forstner Christian , Orton Thomas G. , Skarshewski Adam , Wang Peng , Kopittke Peter M. , Dennis Paul G. 
Published: January 2019

AbstractGraphene oxide (GO) is an oxidized form of graphene that is relatively cheap and easy to produce. This has heralded its widespread use in a range of industries, with its likelihood of release into the environment increasing accordingly. In pure culture, GO has been shown to influence bacteria and fungi, but its effects on environmental microbial communities remain poorly characterized, despite the important ecosystem services that these organisms underpin. Here, we characterized the effects of GO and graphite, over time and at three concentrations (1 ng, 1 µg and 1 mg kg dry soil-1), on soil bacterial and fungal diversity using 16S rRNA and ITS2 gene amplicon sequencing. Graphite was included as a reference material as it is widely distributed in the environment. Neither GO or graphite had significant effects on the alpha diversity of microbial communities. The composition of bacterial and fungal communities, however, was significantly influenced by GO and graphite. These effects were equally apparent between doses and varied over time. Predicted KEGG pathways and fungal guild structures were not significantly influenced by the treatments. Our study demonstrates that GO can influence soil microbial diversity, even at parts-per-trillion concentration, which is equivalent to the rates of release predicted for similar nanomaterials such as carbon nanotubes.ImportanceGraphene oxide is a nanomaterial with broad and expanding industrial applications. Some evidence indicates that it can influence the growth of microorganisms, many of which support important ecosystem services, such as the provision of food and clean water. The amount of graphene oxide currently entering soils is not known but is likely to be similar to other nanomaterials, such as carbon nanotubes (i.e. parts-per-trillion to parts-per-billion per year). In this study, we demonstrate that graphene oxide added to soil at these concentrations (or higher) can alter the composition of bacterial and fungal communities. Nonetheless, we found that these changes were of similar magnitude to those associated with the addition of graphite, which is common and occurs naturally in soils. Further research is recommended to determine whether the changes in microbial community composition that we have shown can be induced by graphene oxide, have deleterious consequences for soil health.