Takshan/R1 huggingface dataset:
Suicide rates in China, 2004-2014: comparing data from two sample-based mortality surveillance systems.

BACKGROUND: The decreasing suicide rate in China has been regarded as a major contributor to the decline of global suicide rate in the past decade. However, previous estimations on China's suicide rates might not be accurate, since often they were based on the data from the Ministry of Health's Vital Registration ("MOH-VR") System, which is biased towards the better-off population. This study aims to compare suicide data extracted from the MOH-VR System with a more representative mortality surveillance system, namely the Center for Disease Control and Prevention's Disease Surveillance Points ("CDC-DSP") System, and update China's national and subnational suicide rates in the period of 2004-2014. METHODS: The CDC-DSP data are obtained from the National Cause-of-Death Surveillance Dataset (2004-2014) and the MOH-VR data are from the Chinese Health Statistics Yearbooks (2005-2012) and the China Health and Family Planning Statistics Yearbooks (2013-2015). First, a negative binomial regression model was used to test the associations between the source of data (CDC-DSP/MOH-VR) and suicide rates in 2004-2014. Joinpoint regression analyses and Kitagawa's decomposition method are then applied to analyze the trends of the crude suicide rates. RESULTS: Both systems indicated China's suicide rates decreased over the study period. However, before the two systems merged in 2013, the CDC-DSP System reported significantly higher national suicide rates (IRR = 1.18, 95% Confidence Interval [CI]: 1.13-1.24) and rural suicide rates (IRR = 1.29, 95% CI: 1.21-1.38) than the MOH-VR System. The CDC-DSP System also showed significant reversing points in 2011 (95% CI: 2006-2012) and 2006 (95% CI: 2006-2008) on the rural and urban suicide trends. Moreover, the suicide rates in the east and central urban regions were reversed in 2011 and 2008. CONCLUSIONS: The biased MOH-VR System underestimated China's national and rural suicide rates. Although not widely appreciated in the field of suicide research, the CDC-DSP System provides more accurate estimations on China's suicide rates and is recommended for future studies to monitor the reversing trends of suicide rates in China's more developed areas.
Cerebral processing of umami: A pilot study on the effects of familiarity.

AIM: The identification of umami taste among people is extremely variable. Based on functional magnetic resonance imaging (fMRI) the aim of this study was to investigate changes of brain activation in participants before and after they were familiarized with this peculiar taste. MATERIAL AND METHOD: A total of 10 healthy, right-handed subjects (7 women, mean age 25 years) participated in this study. A computer-controlled gustometer was used to deliver the umami stimuli at supra-threshold concentrations. After the first session of fMRI experiments, participants went through two weeks of controlled exposure to umami taste, before the second session of fMRI experimentation. RESULTS: Results from psychophysical assessment showed that umami became more familiar (p < 0.001) among the participants after the gustatory exposure. No significant differences for pleasantness and intensity were observed before and after umami training. FMRI data showed that a broader central-nervous network was activated before "umami training" as compared to imaging after "umami training". Significant activation was found in the primary and high level sensory specific gustatory area (insula and anterior cingulate cortex) before training, whereas, significant activation was observed in memory retrieval areas (parahippocampal gyrus) after training. CONCLUSION: The main finding of the present study suggests that repeated exposure to umami taste over a relatively short period of time does not produce an increased response at the level of taste primary and secondary areas, but that increased familiarity with umami leads to an increased activation of the parahippocampal gyrus.
Food cravings in food addiction: exploring a potential cut-off value of the Food Cravings Questionnaire-Trait-reduced.

PURPOSE: The Food Cravings Questionnaires are among the most often used measures for assessing the frequency and intensity of food craving experiences. However, there is a lack of studies that have examined specific cut-off scores that may indicate pathologically elevated levels of food cravings. METHODS: Receiver-Operating-Characteristic analysis was used to determine sensitivity and specificity of scores on the Food Cravings Questionnaire-Trait-reduced (FCQ-T-r) for discriminating between individuals with (n = 43) and without (n = 389) "food addiction" as assessed with the Yale Food Addiction Scale 2.0. RESULTS: A cut-off score of 50 on the FCQ-T-r discriminated between individuals with and without "food addiction" with high sensitivity (85%) and specificity (93%). CONCLUSIONS: FCQ-T-r scores of 50 and higher may indicate clinically relevant levels of trait food craving. LEVEL OF EVIDENCE: Level V, descriptive study.
Smoking, Stress Eating, and Body Weight: The Moderating Role of Perceived Stress.

BACKGROUND: Some individuals respond to stress with increased food intake while others reduce their food intake. Smokers often report using smoking to cope with stress and have a lower body weight than nonsmokers on average. Thus, smokers may tend to eat less when stressed, which may partly explain their lower body weight as compared to nonsmokers. In turn, nonsmokers may tend to eat more when stressed, which may partly explain their higher body weight as compared to smokers. OBJECTIVE: To examine the interplay between smoking and stress-related eating. METHODS: N = 314 (78% female, 14% smokers) participants reported whether they were current smokers, their body height and weight and completed the Salzburg Stress Eating Scale and the Perceived Stress Scale. RESULTS: Smokers did not differ from nonsmokers in body mass index (BMI), stress eating and perceived stress. When perceived stress was high, however, nonsmokers reported eating more and smokers reported eating less than usual. Moreover, in individuals with high perceived stress, being a smoker was indirectly related to lower BMI through eating less when stressed and being a nonsmoker was indirectly related to higher BMI through eating more when stressed. CONCLUSION: Smokers most likely use smoking instead of eating to cope with stress and, therefore, food intake and body weight decrease in stressed smokers. After smoking cessation, these individuals may be more susceptible to weight gain when-similar to nonsmokers-eating instead of smoking is used to cope with stress.
Identification of protein lysine methylation readers with a yeast three-hybrid approach.

BACKGROUND: Protein posttranslational modifications (PTMs) occur broadly in the human proteome, and their biological outcome is often mediated indirectly by reader proteins that specifically bind to modified proteins and trigger downstream effects. Particularly, many lysine methylation sites among histone and nonhistone proteins have been characterized; however, the list of readers associated with them is incomplete. RESULTS: This study introduces a modified yeast three-hybrid system (Y3H) to screen for methyllysine readers. A lysine methyltransferase is expressed together with its target protein or protein domain functioning as bait, and a human cDNA library serves as prey. Proof of principle was established using H3K9me3 as a bait and known H3K9me3 readers like the chromodomains of CBX1 or MPP8 as prey. We next conducted an unbiased screen using a library composed of human-specific open reading frames. It led to the identification of already known lysine methylation-dependent readers and of novel methyllysine reader candidates, which were further confirmed by co-localization with H3K9me3 in human cell nuclei. CONCLUSIONS: Our approach introduces a cost-effective method for screening reading domains binding to histone and nonhistone proteins which is not limited by expression levels of the candidate reading proteins. Identification of already known and novel H3K9me3 readers proofs the power of the Y3H assay which will allow for proteome-wide screens of PTM readers.
The MLL recombinome of acute leukemias in 2017.

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients. Leukemia advance online publication, 8 August 2017; doi:10.1038/leu.2017.213.
Recycling of phenolic compounds in Borneo's tropical peat swamp forests.

BACKGROUND: Tropical peat swamp forests (TPSF) are globally significant carbon stores, sequestering carbon mainly as phenolic polymers and phenolic compounds (particularly as lignin and its derivatives) in peat layers, in plants, and in the acidic blackwaters. Previous studies show that TPSF plants have particularly high levels of phenolic compounds which inhibit the decomposition of organic matter and thus promote peat accumulation. The studies of phenolic compounds are thus crucial to further understand how TPSF function with respect to carbon sequestration. Here we present a study of cycling of phenolic compounds in five forests in Borneo differing in flooding and acidity, leaching of phenolic compounds from senescent Macaranga pruinosa leaves, and absorption of phenolics by M. pruinosa seedlings. RESULTS: The results of the study show that total phenolic content (TPC) in soil and leaves of three species of Macaranga were highest in TPSF followed by freshwater swamp forest and flooded limestone forest, then dry land sites. Highest TPC values were associated with acidity (in TPSF) and waterlogging (in flooded forests). Moreover, phenolic compounds are rapidly leached from fallen senescent leaves, and could be reabsorbed by tree roots and converted into more complex phenolics within the leaves. CONCLUSIONS: Extreme conditions-waterlogging and acidity-may facilitate uptake and synthesis of protective phenolic compounds which are essential for impeded decomposition of organic matter in TPSF. Conversely, the ongoing drainage and degradation of TPSF, particularly for conversion to oil palm plantations, reverses the conditions necessary for peat accretion and carbon sequestration.
Molecular epidemiology of tuberculosis in Tasmania and genomic characterisation of its first known multi-drug resistant case.

BACKGROUND: The origin and spread of tuberculosis (TB) in Tasmania and the types of strains of Mycobacterium tuberculosis complex (MTBC) present in the population are largely unknown. OBJECTIVE: The aim of this study was to perform the first genomic analysis of MTBC isolates from Tasmania to better understand the epidemiology of TB in the state. METHODS: Whole-genome sequencing was performed on cultured isolates of MTBC collected from 2014-2016. Single-locus variant analysis was applied to determine the phylogeny of the isolates and the presence of drug-resistance mutations. The genomic data were then cross-referenced against public health surveillance records on each of the cases. RESULTS: We determined that 83.3% of TB cases in Tasmania from 2014-2016 occurred in non-Australian born individuals. Two possible TB clusters were identified based on single locus variant analysis, one from November-December 2014 (n = 2), with the second from May-August 2015 (n = 4). We report here the first known isolate of multi-drug resistant (MDR) M. tuberculosis in Tasmania from 2016 for which we established its drug resistance mutations and potential overseas origin. In addition, we characterised a case of M. bovis TB in a Tasmanian-born person who presented in 2014, approximately 40 years after the last confirmed case in the state's bovids. CONCLUSIONS: TB in Tasmania is predominantly of overseas origin with genotypically-unique drug-susceptible isolates of M. tuberculosis. However, the state also exhibits features of TB that are observed in other jurisdictions, namely, the clustering of cases, and drug resistance. Early detection of TB and contact tracing, particularly of overseas-born cases, coordinated with rapid laboratory drug-susceptibility testing and molecular typing, will be essential for Tasmania to reach the World Health Organisation's TB eradication goals for low-incidence settings.
Catalogue of antibiotic resistome and host-tracking in drinking water deciphered by a large scale survey.

BACKGROUND: Excesses of antibiotic resistance genes (ARGs), which are regarded as emerging environmental pollutants, have been observed in various environments. The incidence of ARGs in drinking water causes potential risks to human health and receives more attention from the public. However, ARGs harbored in drinking water remain largely unexplored. In this study, we aimed at establishing an antibiotic resistome catalogue in drinking water samples from a wide range of regions and to explore the potential hosts of ARGs. RESULTS: A catalogue of antibiotic resistome in drinking water was established, and the host-tracking of ARGs was conducted through a large-scale survey using metagenomic approach. The drinking water samples were collected at the point of use in 25 cities in mainland China, Hong Kong, Macau, Taiwan, South Africa, Singapore and the USA. In total, 181 ARG subtypes belonging to 16 ARG types were detected with an abundance range of 2.8 × 10-2 to 4.2 × 10-1 copies of ARG per cell. The highest abundance was found in northern China (Henan Province). Bacitracin, multidrug, aminoglycoside, sulfonamide, and beta-lactam resistance genes were dominant in drinking water. Of the drinking water samples tested, 84% had a higher ARG abundance than typical environmental ecosystems of sediment and soil. Metagenomic assembly-based host-tracking analysis identified Acidovorax, Acinetobacter, Aeromonas, Methylobacterium, Methyloversatilis, Mycobacterium, Polaromonas, and Pseudomonas as the hosts of ARGs. Moreover, potential horizontal transfer of ARGs in drinking water systems was proposed by network and Procrustes analyses. CONCLUSIONS: The antibiotic resistome catalogue compiled using a large-scale survey provides a useful reference for future studies on the global surveillance and risk management of ARGs in drinking water. .
Clinical code set engineering for reusing EHR data for research: A review.

INTRODUCTION: The construction of reliable, reusable clinical code sets is essential when re-using Electronic Health Record (EHR) data for research. Yet code set definitions are rarely transparent and their sharing is almost non-existent. There is a lack of methodological standards for the management (construction, sharing, revision and reuse) of clinical code sets which needs to be addressed to ensure the reliability and credibility of studies which use code sets. OBJECTIVE: To review methodological literature on the management of sets of clinical codes used in research on clinical databases and to provide a list of best practice recommendations for future studies and software tools. METHODS: We performed an exhaustive search for methodological papers about clinical code set engineering for re-using EHR data in research. This was supplemented with papers identified by snowball sampling. In addition, a list of e-phenotyping systems was constructed by merging references from several systematic reviews on this topic, and the processes adopted by those systems for code set management was reviewed. RESULTS: Thirty methodological papers were reviewed. Common approaches included: creating an initial list of synonyms for the condition of interest (n=20); making use of the hierarchical nature of coding terminologies during searching (n=23); reviewing sets with clinician input (n=20); and reusing and updating an existing code set (n=20). Several open source software tools (n=3) were discovered. DISCUSSION: There is a need for software tools that enable users to easily and quickly create, revise, extend, review and share code sets and we provide a list of recommendations for their design and implementation. CONCLUSION: Research re-using EHR data could be improved through the further development, more widespread use and routine reporting of the methods by which clinical codes were selected.
The Prevalence of Integrons as the Carrier of Antibiotic Resistance Genes in Natural and Man-Made Environments.

Class 1 integrase intI1 has been considered as a good proxy for anthropogenic pollution because of being linked to genes conferring resistance to antibiotics. The gene cassettes of class 1 integrons could carry diverse antibiotic resistance genes (ARGs) and conduct horizontal gene transfer among microorganisms. The present study applied high-throughput sequencing technique combined with an intI1 database and genome assembly to quantify the abundance of intI1 in 64 environmental samples from 8 ecosystems, and to investigate the diverse arrangements of ARG-carrying gene cassettes (ACGCs) carried by class 1 integrons. The abundance of detected intI1 ranged from 3.83 × 10(-4) to 4.26 × 10° intI1/cell. High correlation (Pearson's r = 0.852) between intI1 and ARG abundance indicated that intI1 could be considered as an important indicator of ARGs in environments. Aminoglycoside resistance genes were most frequently observed on gene cassettes, carried by 57% assembled ACGCs, followed by trimethoprim and beta-lactam resistance genes. This study established the pipeline for broad monitoring of intI1 in various environmental samples and scanning the ARGs carried by integrons. These findings supplemented our knowledge on the distribution of class 1 integrons and ARGs carried on mobile genetic elements, benefiting future studies on horizontal gene transfer of ARGs.
A novel integrated care concept (NICC) versus standard care in the treatment of chronic cardiovascular diseases: protocol for the randomized controlled trial CardioCare MV.

BACKGROUND: Cardiovascular diseases are the major cause of death globally and represent a major economic burden on health care systems. Positive effects of disease management programs have been shown for patients with heart failure (HF). Remote monitoring and telemonitoring with active intervention are beneficial in atrial fibrillation (AF) and therapy-resistant hypertension (TRH), respectively. For these patients, we have developed a novel integrated care concept (NICC) which combines telemedicine with intensive support by a care center, including a call center, an integrated care network including inpatient and outpatient care providers and guideline therapy for patients. METHODS: The aim of the study is to demonstrate the superiority of NICC over guideline therapy alone. The trial is designed as open-label, bi-center, parallel-group design with two groups and a blinded observer. Patients will be included if they are either inpatients or if they are referred to the outpatient clinic of the hospitals by their treating physician. Randomization will be done individually with stratification by cardiovascular disease (AF, HF, TRH), center and admission type. Primary endpoints are based on the 1-year observation period after randomization. The first primary endpoint is the composite endpoint consisting of mortality, stroke and myocardial infarction. The number of hospitalizations form the second primary endpoint. The third primary endpoint is identical to the first primary endpoint plus cardiac decompensation. Adjustments for multiple testing are done using a fall-back strategy. Secondary endpoints include patient adherence, health care costs, quality of life, and safety. A sample size of 2930 gives 80% power at the two-sided 2.5% test level for the first primary endpoint. The power for the second primary endpoint is 99.8% at this sample size, and it is 80% with 1086 patients. DISCUSSION: This study will inform care providers whether quality of care can be improved by an integrated care concept providing telemedicine through a round-the-clock call center approach. We expect that cost of the NICC will be lower than standard care because of reduced hospitalizations. If the study has a positive result, NICC is planned to be immediately rolled out in the federal state of Mecklenburg-West Pomerania and other federal states in Germany. The trial will also guide additional research to disentangle the effects of this complex intervention. TRIAL REGISTRATION: DRKS, ID: DRKS00013124 . Registered on 5 October 2017; ClinicalTrials.gov , ID: NCT03317951. Registered on 17 October 2017.
A cohort of 17 patients with kyphoscoliotic Ehlers-Danlos syndrome caused by biallelic mutations in FKBP14: expansion of the clinical and mutational spectrum and description of the natural history.

PurposeIn 2012 we reported in six individuals a clinical condition almost indistinguishable from PLOD1-kyphoscoliotic Ehlers-Danlos syndrome (PLOD1-kEDS), caused by biallelic mutations in FKBP14, and characterized by progressive kyphoscoliosis, myopathy, and hearing loss in addition to connective tissue abnormalities such as joint hypermobility and hyperelastic skin. FKBP14 is an ER-resident protein belonging to the family of FK506-binding peptidyl-prolyl cis-trans isomerases (PPIases); it catalyzes the folding of type III collagen and interacts with type III, type VI, and type X collagens. Only nine affected individuals have been reported to date. MethodsWe report on a cohort of 17 individuals with FKBP14-kEDS and the follow-up of three previously reported patients, and provide an extensive overview of the disorder and its natural history based on clinical, biochemical, and molecular genetics data. ResultsBased on the frequency of the clinical features of 23 patients from the present and previous cohorts, we define major and minor features of FKBP14-kEDS. We show that myopathy is confirmed by histology and muscle imaging only in some patients, and that hearing impairment is predominantly sensorineural and may not be present in all individuals. ConclusionOur data further support the extensive clinical overlap with PLOD1-kEDS and show that vascular complications are rare manifestations of FKBP14-kEDS.GENETICS in MEDICINE advance online publication, 15 June 2017; doi:10.1038/gim.2017.70.