bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal evolution of immunity distributions in a population with waning and boosting
Authors: Barbarossa M. V. , Polner M. , Röst G. 
Published: January 2018

AbstractWe investigate the temporal evolution of the distribution of immunities in a population, which is determined by various epidemiological, immunological and demographical phenomena: after a disease outbreak, recovered individuals constitute a large immune population, however their immunity is waning in the long term and they may become susceptible again. Meanwhile, their immunity can be boosted by repeated exposure to the pathogen, which is linked to the density of infected individuals present in the population. This prolongs the length of their immunity.We consider a mathematical model formulated as a coupled system of ordinary and partial differential equations, that connects all these processes, and systematically compare a number of boosting assumptions proposed in the literature, showing that different boosting mechanisms lead to very different stationary distributions of the immunity at the endemic steady state. In the situation of periodic disease outbreaks, the waveforms of immunity distributions are studied and visualized. Our results show that there is a possibility to infer the boosting mechanism from the population level immune-dynamics.AMS Classification92D30, 34K60, 34K34, 37M05
Rapid Whole Genome Sequencing Decreases Morbidity and Healthcare Cost of Hospitalized Infants
Authors: Farnaes Lauge , Hildreth Amber , Sweeney Nathaly M. , Clark Michelle M. , Chowdhury Shimul , Nahas Shareef , Cakici Julie A. , Benson Wendy , Kaplan Robert H. , Kronick Richard , Bainbridge Matthew N. , Friedman Jennifer , Gold Jeffrey J. , Ding Yan , Veeraraghavan Narayanan , Dimmock David , kingsmore Stephen F. ,   on behalf of the RCIGM Investigators
Published: January 2018

ABSTRACTBACKGROUNDGenetic disorders are a leading cause of morbidity and mortality in infants. Rapid Whole Genome Sequencing (rWGS) can diagnose genetic disorders in time to change acute medical or surgical management (clinical utility) and improve outcomes in acutely ill infants.METHODSRetrospective cohort study of acutely ill inpatient infants in a regional children’s hospital from July 2016–March 2017. Forty-two families received rWGS for etiologic diagnosis of genetic disorders. Probands received standard genetic testing as clinically indicated. Primary end-points were rate of diagnosis, clinical utility, and healthcare utilization. The latter was modelled in six infants by comparing actual utilization with matched historical controls and/or counterfactual utilization had rWGS been performed at different time points.FINDINGSThe diagnostic sensitivity was 43% (eighteen of 42 infants) for rWGS and 10% (four of 42 infants) for standard of care (P=.0005). The rate of clinical utility for rWGS (31%, thirteen of 42 infants) was significantly greater than for standard of care (2%, one of 42; P=.0015). Eleven (26%) infants with diagnostic rWGS avoided morbidity, one had 43% reduction in likelihood of mortality, and one started palliative care. In six of the eleven infants, the changes in management reduced inpatient cost by $800, 000 to $2,000,000.DISCUSSIONThese findings replicate a prior study of the clinical utility of rWGS in acutely ill inpatient infants, and demonstrate improved outcomes and net healthcare savings. rWGS merits consideration as a first tier test in this setting.
Validation of known risk factors associated with carpal tunnel syndrome: A retrospective nationwide 11-year population-based cohort study in South Korea
Authors: Lee Hong-Jae , Lim Hyun Sun , Kim Hyoung Seop 
Published: January 2018

AbstractKey PointsQuestionWhat is the relationship between the previously known risk factors and occurrence of carpal tunnel syndrome (CTS)?FindingsIn this retrospective population-based cohort study that included 512,942 participants sampled from the Korean National Health Insurance System database, we determined the following known risk factors were related to the occurrence of CTS: the age of 40s, female, being overweight, diabetes, rheumatoid arthritis, gout, and Raynaud’s syndrome. However, ESRD, hypothyroidism and smoking were not correlated with CTS occurrence.ImplicationsWe identified the age of 40s, female, overweight, diabetes, rheumatoid arthritis, gout, and Raynaud’s syndrome as risk factors for the occurrence of CTS.AbstractImportanceThere have been few large-scale studies that have included a risk factor analysis for CTS. No prior study has investigated and validated the relationship between the occurrence of CTS and known risk factors using nationwide health care database.ObjectiveTo confirm the actual risk factors for CTS out of various known risk factorsDesignWe conducted this study using a retrospective cohort model based on the combined two databases of the Korean National Health Insurance System; the national periodic health screening program database from 2002–2003 and health insurance database of reimbursement claims from 2003 through 2013.SettingA population-based retrospective cohort study.ParticipantsFirst, we randomly sampled 514,795 patients who represented 10% of the 5,147,950 people who took part in periodic health screenings in 2002–2003. Existing CTS patients were excluded from this group. Therefore, this study finally included 512,942 participants and followed up their medical records from 2003–2013.Main Outcomes and MeasuresDesired outcomes were the incidence rate of CTS in patients with various risk factors and the hazard ratios of risk factors affecting the disease’s occurrence.ResultsThe incidence of CTS was highest in patients in the age of 40s, in the moderate obesity group, in females, and in patients with diabetes mellitus (DM). The hazard ratio analysis revealed that the following risk factors were strongly related to the occurrence of CTS: age of 40s, female, obesity, DM, rheumatoid arthritis, gout, and Raynaud’s syndrome. However, ESRD, hypothyroidism and smoking were not correlated with CTS occurrence.Conclusions and RelevanceIn our large-scale cohort study, risk factors such as being in one’s 40s, obesity, being female, suffering from DM, and rheumatoid arthritis were reaffirmed as those of CTS occurrence.
10 Year Epidemiologic data of Parkinson’s Disease: A Nationwide Population-based Retrospective Cohort of South Korea
Authors: Kim Hyoung Seop , Kwon Joon-Byum , Lim Hyun-Sun , Cha Jiook , Kim Hye Won 
Published: January 2018

AbstractObjectivesThe aims of this study were to determine the prevalence, incidence, and P/I ratio of Parkinson’s disease (PD) in South Korea and to present basic epidemiological information on PD patients for making effective health policies.MethodsWe used National Health Insurance Service-National Sample Cohort (KNHIS-NSC) data to analyze the prevalence, incidence, and P/I ratio of PD from 2003 to 2013 and then followed up using the NHID in 2008 to obtain the hazard ratio (HR) of death in PD itself and other comorbidities from 2008 to 2013.ResultsThe prevalence and incidence of PD increased rapidly from 72.9 and 32.8 in 2003 to 213.4 and 58.0 in 2013, and the P/I ratio increased from 2.22 in 2003 to 3.62 in 2013. The prevalence, incidence, and P/I ratio of PD were all higher in women than in men. The hazard ratio for death was significantly higher in PD patients (15.36) compared to subjects without the disease. Stroke was the most frequent cause of death in the PD patient population followed by cancer and pneumonia.ConclusionThe prevalence, incidence, and P/I ratio of PD rapidly increased as the years progressed. This indirectly proves that the health insurance system in Korea is efficient and has allowed patients with PD to access medical facilities more easily. However, a newer public healthy strategy should be established for patients with PD because PD itself has a high HR for death, and patients with PD have a high mortality rate when stroke and pneumonia are also involved.DisclosureAll authors have reported no biomedical interests and potential conflicts of interests.
Risk factors associated with Parkinson’s disease: An 11-year population-based South Korean study
Authors: Kim Hyoung Seop , Lee Hong-Jae , Cha Jiook , Kwon Junbeom , Lim Hyunsun 
Published: January 2018

ABSTRACTObjectiveTo validate various known risk factors of Parkinsonism and to establish basic information to formulate public health policy by using a 10-year follow-up cohort model.MethodsThis population based nation-wide study was performed using the National Health Insurance Database of reimbursement claims of the Health Insurance Review and Assessment Service of South Korea data on regular health check-ups in 2003 and 2004, with 10 years’ follow-up.ResultsWe identified 7,746 patients with Parkinsonism. Old age, hypertension, diabetes, depression, anxiety, taking statin medication, high body mass index, non-smoking, non-alcohol drinking, and low socioeconomic status were each associated with an increase in the risk of Parkinsonism (fully adjusted Cox proportional hazards model: hazard ratio (HR) 1.259, 95% confidence interval (CI) 1.194–1.328 for hypertension, HR 1.255, 95% CI 1.186–1.329 for diabetes, HR 1.554, 95% CI 1.664–1.965 for depression, HR 1.808, 95% CI 1.462–1.652 for anxiety, and HR 1.157, 95% CI 1.072–1.250 for taking statin medication).ConclusionsIn our study, old age, depression, anxiety, and a non-smoker status were found to be risk factors of Parkinsonism, in agreement with previous studies. However, sex, hypertension, diabetes, taking statin medication, non-drinking of Alcohol, and lower socioeconomic status have not been described as risk factors in previous studies and need further verification in future studies.
A comprehensive manually-curated Compendium of Bovine Transcription Factors
Authors: de Souza Marcela M , Vaquerizas Juan M , Zerlotini Adhemar , Geistlinger Ludwig , Hernández-Rodríguez Benjamín , Tizioto Polyana C , Taylor Jeremy F , Rocha Marina IP , Diniz Wellison JS , Coutinho Luiz L , Regitano Luciana CA 
Published: January 2018

ABSTRACTTranscription factors (TFs) are pivotal regulatory proteins that control gene expression in a context-dependent and tissue-specific manner. In contrast to human, where comprehensive curated TF collections exist, bovine TFs are only rudimentary recorded and characterized. In this article, we present a manually-curated compendium of 865 sequence-specific DNA-binding bovines TFs, which we analyzed for domain family distribution, evolutionary conservation, and tissue-specific expression. In addition, we provide a list of putative transcription cofactors derived from known interactions with the identified TFs. Since there is a general lack of knowledge concerning the regulation of gene expression in cattle, the curated list of TF should provide a basis for an improved comprehension of regulatory mechanisms that are specific to the species.
A comprehensive model of DNA fragmentation for the preservation of High Molecular Weight DNA
Authors: Klingström Tomas , Bongcam-Rudloff Erik , Pettersson Olga Vinnere 
Published: January 2018

ABSTRACTFor long-read sequencing applications, shearing of DNA is a significant issue as it limits the read-lengths generated by sequencing. During extraction and storage of DNA the DNA polymers are susceptible to physical and chemical shearing. In particular, the mechanisms of physical shearing are poorly understood in most laboratories as they are of little relevance to commonly used short-read sequencing technologies. This study draws upon lessons learned in a diverse set of research fields to create a comprehensive theoretical framework for obtaining high molecular weight DNA (HMW-DNA) to support improved quality management in laboratories and biobanks for long-read sequencing applications.Under common laboratory conditions physical and chemical shearing yields DNA fragments of 5-35 kilobases (kb) in length. This fragment length is sufficient for DNA sequencing using short-read technologies but for Nanopore sequencing, linked reads and single molecular real time sequencing (SMRT) poorly preserved DNA will limit the length of the reads generated.The shearing process can be divided into physical and chemical shearing which generates different patterns of fragmentation. Exposure to physical shearing creates a characteristic fragment length where the main cause of shearing is shear stress induced by turbulence. The characteristic fragment length is several thousand base pairs longer than the reads produced by short-read sequencing as the shear stress imposed on short DNA fragments is insufficient to shear the DNA. This characteristic length can be measured using gel electrophoresis or instruments for DNA fragment analysis,. Chemical shearing generates randomly distributed fragment lengths visible as a smear of DNA below the peak fragment length. By measuring the peak of the DNA fragment length distribution and the proportion of very short DNA fragments, both sources of shearing can be measured using commonly used laboratory techniques, providing a suitable quantification of DNA integrity of DNA for sequencing with long-read technologies.
Signaling pathway screening platforms are an efficient approach to identify therapeutic targets in precision-medicine oriented early phase clinical trials
Authors:   Pedro Torres-Ayuso, Sahoo Sudhakar , Galvin Melanie , Leong Hui Sun , Frese Kristopher K , Hughes Andrew , Marais Richard , Dive Caroline , Krebs Matthew G , Brognard John 
Published: January 2018

AbstractPrecision medicine aims to tailor cancer therapies to target specific tumorpromoting aberrations. For tumors that lack actionable drivers, extensive molecular characterization and pre-clinical drug efficacy studies will be required to match patients with the appropriate targeted therapy. A cell line maintained at low passage and a patient-derived xenograft model (PDX) were generated using a fresh biopsy from a patient with a poorly-differentiated neuroendocrine tumor of unknown primary origin. Next-generation sequencing, high throughput signaling network analysis, and drug efficacy trials were then conducted to identify actionable targets for therapeutic intervention. No actionable mutations were identified after whole exome sequencing of the patient’s DNA; however, whole genome sequencing revealed amplification of the 3q and 5p chromosomal arms, that include the PIK3CA and RICTOR genes, respectively. Consistent with amplification of these genes, pathway analysis revealed activation of the AKT pathway. Based on this analysis, efficacy of PIK3CA and AKT inhibitors were evaluated in the tumor biopsy-derived cell culture and PDX, and response to the AKT inhibitor AZD5363 was observed both in vitro and in vivo indicating the patient would benefit from targeted therapies directed against the serine/threonine kinase AKT. In conclusion, our study demonstrates that high throughput signaling pathway analysis complements next-generation sequencing approaches for detection of actionable alterations and will aid in patient stratification into early-phase clinical trials.
Exploring morphological motifs for a single neuron based on multiple 3D reconstructions
Authors: Yang Jian , He Yishan , Zhou Zhi , Zhong Ning , Peng Hanchuan 
Published: January 2018

AbstractThe morphology of individual neurons is useful to study structures and functions of nervous system. Researchers have invented many semi or fully automatic tracing methods to efficiently generate a reconstruction from a single neuron. Different tracing methods have different design principles, and could produce different reconstructions. However, the “common substructures” of various reconstructions, called morphological motifs, should be highly reliable. In this work, we propose a Vaa3D based framework to explore morphological motifs of 3D reconstructions from a single neuron. The framework contains four steps: (1) resampling and sorting each reconstruction according to a standard reconstruction, such as a gold standard reconstruction, consensus reconstruction or a certain reliable reconstruction; (2) applying local alignment algorithm for each pair of the standard reconstruction and a reconstruction, or each pair of two reconstructions; (3) constructing overlaps based on selected points in local alignment pairs; (4) obtaining morphological motifs by post-processing these overlaps. Under the proposed framework, three methods were implemented and tested on a dataset of 73 fruitfly neurons released by the BigNeuron project (http://bigneuron.org), which contains a gold standard reconstruction, a consensus reconstruction and about 40 automatic reconstructions for each neuron. We quantitatively evaluated these three methods to choose reliable morphological motifs.
Gradual repression of selenoprotein W ensures physiological bone remodelling
Authors: Kim Hyunsoo , Lee Kyunghee , Kim Jin Man , Kim Jae-Ryong , Lee Han-Woong , Chung Youn Wook , Shin Hong-In , Park Eui-Soon , Rho Jaerang , Lee Seoung Hoon , Kim Nacksung , Lee Soo Young , Choi Yongwon , Jeong Daewon 
Published: January 2018

AbstractSelenoproteins containing selenium in the form of selenocysteine are critical for bone remodelling. However, their mechanism of action is not well understood. Here, we report the identification of selenoprotein W (SELENOW) through large-scale mRNA profiling of receptor activator of nuclear factor (NF)-κB ligand (RANKL)-induced osteoclast differentiation, as a protein that is downregulated via RANKL/RANK/tumour necrosis factor receptor-associated factor 6/p38 signalling. RNA sequencing analysis revealed that SELENOW regulates osteoclastogenic genes. SELENOW overexpression enhanced osteoclastogenesis in vitro via nuclear translocation of NF-κB and nuclear factor of activated T-cells cytoplasmic 1, whereas its loss suppressed osteoclast formation. SELENOW-deficient and SELENOW-overexpressing mice exhibited osteopetrosis and osteoporosis, respectively. Ectopic SELENOW expression stimulated cell-cell fusion critical for osteoclast maturation as well as bone resorption. Thus, RANKL-dependent repression of SELENOW maintains proper osteoclast differentiation and blocks osteoporosis caused by overactive osteoclasts. These findings demonstrate a biological link between selenium and bone metabolism.
A genetically encoded biosensor reveals location bias of opioid drug action
Authors: Stoeber Miriam , Jullie Damien , Laeremans Toon , Steyaert Jan , Schiller Peter W. , Manglik Aashish , von Zastrow Mark 
Published: January 2018

SummaryOpioid receptors (ORs) precisely modulate behavior when activated by native peptide ligands but distort behaviors to produce pathology when activated by non-peptide drugs. A fundamental question is how drugs differ from peptides in their actions on target neurons. One way that drugs can differ is by imposing selective effects on the conformational equilibrium of individual ORs. We wondered if drugs can also impose selective effects on the location of OR activation in individual OR-expressing neurons. Here we develop a genetically encoded biosensor that directly localizes ligand-induced activation and deactivation of ORs in living cells, and use it to generate the first real-time map of the spatiotemporal organization of μ‐ and δ-OR activation in neurons. Peptide agonists produce a characteristic activation pattern initiated in the plasma membrane and propagating to endosomes after receptor internalization. Drugs produce a different activation pattern by uniquely driving OR activation in the somatic Golgi apparatus and extending throughout the dendritic arbor in Golgi outposts. These results demonstrate a new approach to probe the cellular basis of neuromodulation and reveal that drugs profoundly distort the spatiotemporal landscape of neuronal OR activation.
Base-pair resolution detection of transcription factor binding site by deep deconvolutional network
Authors: Salekin Sirajul , Zhang Jianqiu (Michelle) , Huang Yufei 
Published: January 2018

AbstractMotivationTranscription factor (TF) binds to the promoter region of a gene to control gene expression. Identifying precise transcription factor binding sites (TFBS) is essential for understanding the detailed mechanisms of TF mediated gene regulation. However, there is a shortage of computational approach that can deliver single base pair (bp) resolution prediction of TFBS.ResultsIn this paper, we propose DeepSNR, a Deep Learning algorithm for predicting transcription factor binding location at Single Nucleotide Resolution de novo from DNA sequence. DeepSNR adopts a novel deconvolutional network (deconvNet) model and is inspired by the similarity to image segmentation by deconvNet. The proposed deconvNet architecture is constructed on top of ‘Deep-Bind’ and we trained the entire model using TF specific data from ChIP-exonuclease (ChIP-exo) experiments. DeepSNR has been shown to outperform motif search based methods for several evaluation metrics. We have also demonstrated the usefulness of DeepSNR in the regulatory analysis of TFBS as well as in improving the TFBS prediction specificity using ChIP-seq data.AvailabilityDeepSNR is available open source in the GitHub repository (https://github.com/sirajulsalekin/DeepSNR)Contactyufei.huang@utsa.edu
Genetic contribution to ‘theory of mind’ in adolescence
Authors: Warrier Varun , Baron-Cohen Simon 
Published: January 2018

AbstractDifficulties in ‘theory of mind’ (the ability to attribute mental states to oneself or others, and to make predictions about another’s behaviour based on these attributions) have been observed in several psychiatric conditions. We investigate the genetic architecture of theory of mind in 4,577 13-year-olds who completed the Emotional Triangles Task (Triangles Task), a first-order test of theory of mind. We observe a small but significant female-advantage on the Triangles Task (Cohen’s d = 0.19, P < 0.01), in keeping with previous work using other tests of theory of mind. Genome-wide association analyses did not identify any significant loci, and SNP heritability was small and non-significant. Polygenic scores for six psychiatric conditions (ADHD, anorexia, autism, bipolar disorder, depression, and schizophrenia), and empathy were not associated with scores on the Triangles Task. However, polygenic scores of cognitive aptitude, and cognitive empathy, a term synonymous with theory of mind and measured using the “Reading the Mind in the Eyes” Test, were significantly associated with scores on the Triangles Task at multiple P-value thresholds, suggesting shared genetics between different measures of theory of mind and cognition.
Heat shock factor 5 is conserved in vertebrates and essential for spermatogenesis in zebrafish
Authors: Saju Jolly M. , Hossain Mohammad Sorowar , Liew Woei Chang , Pradhan Ajay , Thevasagayam Natascha May , Anand Amit , Olsson Per-Erik , Orbán László 
Published: January 2018

AbstractHeat shock factors (Hsfs) are transcription factors that regulate response to heat shock and to variety of other environmental and physiological stimuli. Four HSFs (HSF1-4) known in vertebrates till date, perform a wide variety of functions from mediating heat shock response to development and gametogenesis. Here, we describe a new yet conserved member of HSF family, Hsf5, which likely exclusively functions for spermatogenesis. Thehsf5is predominantly expressed in developing testicular tissues, in comparison to wider expression reported for other HSFs. HSF5 loss causes male sterility due to drastically reduced sperm count, and severe abnormalities in remaining few spermatozoa. While hsf5 mutant female did not show any abnormality. We show that Hsf5 is required for progression through meiotic prophase 1 during spermatogenesis. Thehsf5mutants indeed show misregulation of a substantial number of genes regulating cell cycle, DNA-damage repair, apoptosis and cytoskeleton proteins. We also show that Hsf5 physically binds to majority of these differentially expressed genes, suggesting its direct role in regulating the expression of many genes important for spermatogenesis.