bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling reaction-diffusion-like dynamics in urban congestion propagation: Insights from a large-scale road network
Authors: Bellocchi Leonardo , Geroliminis Nikolas 
Published: March 2020

AbstractWe study the dynamical process of congestion formation for large-scale urban networks by exploring a unique dataset of taxi movements in a megacity. We develop a dynamic model based on a reaction and a diffusion term that properly reproduces the cascade phenomena of traffic. The interaction of these two terms brings the values of the speeds on road network in self-organized patterns and it reveals an elegant physical law that reproduces the dynamics of congestion with very few parameters. The results presented show a promising match with an available real data set of link speeds estimated from more than 40 millions of GPS coordinates per day of about 20,000 taxis in Shenzhen, China.
Magnetic Resonance Spectroscopy as a Non-invasive Method to Quantify Muscle Carnosine in Humans: a Comprehensive Validity Assessment
Authors: da Eira Silva Vinicius , Painelli Vitor de Salles , Shinjo Samuel Katsuyuki , Ribeiro Pereira Wagner , Cilli Eduardo Maffud , Sale Craig , Gualano Bruno , Otaduy Maria Concepción , Artioli Guilherme Giannini 
Published: March 2020

AbstractCarnosine is a dipeptide abundantly found in human skeletal muscle, cardiac muscle and neuronal cells having numerous properties that confers performance enhancing effects, as well as a wide-range of potential therapeutic applications. A reliable and valid method for tissue carnosine quantification is crucial for advancing the knowledge on biological processes involved with carnosine metabolism. In this regard, proton magnetic resonance spectroscopy (1H-MRS) has been used as a non-invasive alternative to quantify carnosine in human skeletal muscle. However, carnosine quantification by 1H-MRS has some potential limitations that warrant a thorough experimental examination of its validity. The present investigation examined the reliability, accuracy and sensitivity for the determination of muscle carnosine in humans using in vitro and in vivo experiments and comparing it to reference method for carnosine quantification (high-performance liquid chromatography – HPLC). We used in vitro 1H-MRS to verify signal linearity and possible noise sources. Carnosine was determined in the m. gastrocnemius by 1H-MRS and HPLC to compare signal quality and convergent validity. 1H-MRS showed adequate discriminant validity, but limited reliability and poor agreement with a reference method. Low signal amplitude, low signal-to-noise ratio, and voxel repositioning are major sources of error.
Extensive splicing changes in an ALS/FTD transgenic mouse model overexpressing cytoplasmic fused in sarcoma
Authors: Ito Daisuke , Taguchi Ryota , Deguchi Maki , Ogasawara Hideaki , Inoue Eiji 
Published: March 2020

AbstractMutations in RNA-binding proteins (RBPs) such as TAR DNA-binding protein 43 (TDP-43) and fused in sarcoma (FUS) are associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Recent evidence suggests that RNA dysregulation mediated by aberrant RBPs may play a critical role in neurodegeneration, but the underlying molecular mechanisms are largely unknown. In this study, we performed whole transcriptome profiling of various brain tissues of a transgenic (Tg) mouse model of ALS/FTD overexpressing the exogenous nuclear localization signal deletion mutant of human FUS (ΔNLS-FUS) to investigate changes associated with the early stages of ALS/FTD. Although there were not many differences in expression profiles between wild-type and Tg mice, we found that Sema3g was significantly upregulated in the frontal cortex and hippocampus of Tg mice. Interestingly, analysis of alternative splicing events identified widespread exons that were differentially regulated in Tg mice in a tissue-specific manner. Our study thus identified aberrant splicing regulation mediated by mutant FUS during the early stages of ALS/FTD. Targeting this aberrant splicing regulation represents a potential therapeutic strategy for ALS/FTD.
Temporal association between zolpidem medication and the risk of suicide: A 12-year population-based, retrospective cohort study
Authors: Cho Chul-Hyun , Jee Hee-Jung , Nam Yoon-Ju , An Hyonggin , Kim Leen , Lee Heon-Jeong 
Published: March 2020

AbstractThere have been concerns about abuse and unnecessary chronic administration of zolpidem, and zolpidem’s relation to suicide risk. To investigate the temporal association of zolpidem with the risk of suicide, we conducted a 12-year, population-based, retrospective cohort study on the National Health Insurance Service–National Sample Cohort (NHIS-NSC), South Korea. Data were collected from 2002 to 2013 from the NHIS-NSC, and data cleaning was performed for 1,125,691 subjects. Cox proportional hazards regression analysis was used to investigate the correlation over time between zolpidem medication and suicide. Over intervals commencing after 80 months of observation, the adjusted hazard ratio of suicides associated with the use of the zolpidem was 2.01 (95% CI: 1.58–2.56; p < 0.001). The mean cumulative number of days of zolpidem prescription was significantly longer in the suicide group than in the non-suicide group after log-transformation (p = 0.005). Cases of chronic use of zolpidem (over six months or one year) were significantly more common in the suicide group compared to the non-suicide group (p = 0.002 and 0.005, respectively). Subjects who received zolpidem medication had a significantly higher risk of suicide after at least 80 months of observation, suggesting a long-term increased suicide risk associated with insomnia exposed to zolpidem medication.
Killer cell immunoglobulin-like receptors (KIR) and human leukocyte antigen-C (HLA-C) allorecognition patterns in women with endometriosis
Authors: Chou Ya-Ching , Chen Chi-Huang , Chen Ming-Jer , Chang Ching-Wen , Chen Pi-Hua , Yu Mu-Hsien , Chen Yi-Jen , Tsai Eing-Mei , Yang Peng-Sheng , Lin Shyr-Yeu , Tzeng Chii-Ruey 
Published: March 2020

AbstractEndometriosis shares similarities with several autoimmune diseases. The human leukocyte antigen (HLA)-C genotype is associated with several human autoimmune diseases. HLA-C is a ligand of killer cell immunoglobulin receptors (KIRs) and is an essential regulator of natural killer cell activity, which is associated with endometriosis progression. Polymorphisms in HLA-C and KIR affect the activity of NK cells and susceptibility to several diseases. Therefore, we attempted to investigate an association between HLA-C genotype and KIR polymorphism and the occurrence of endometriosis. We tested the association of certain KIR and HLA-C combinations and the development of endometriosis by characterizing both KIR and HLA-C genes in 147 women with endometriosis and 117 controls. The HLA-C genotypes and KIR polymorphisms were analyzed via DNA-based method for higher-resolution genotyping. We found that the occurrence of HLA-C*03:03*01 was increased in endometriosis than in control groups. Analysis of various KIR haplotypes revealed differences between the endometriosis and control cohorts. The number of KIR centromeric A/A haplotypes was increased in the endometriosis group than controls. Moreover, the endometriosis cohort was characterized by reduced number of KIR2DS2-positive individuals in the Han Chinese population. Our current findings suggest that the KIR and HLA-C genotypes are associated with the pathogenesis of endometriosis.
New Therapeutic Candidates for the Treatment of Malassezia pachydermatis -Associated Infections
Authors: Sastoque Angie , Triana Sergio , Ehemann Kevin , Suarez Lina , Restrepo Silvia , Wösten Han , de Cock Hans , Fernández-Niño Miguel , González Barrios Andrés Fernando , Celis Ramírez Adriana Marcela 
Published: March 2020

AbstractThe opportunistic pathogenMalassezia pachydermatiscauses bloodstream infections in preterm infants or individuals with immunodeficiency disorders and has been associated with a broad spectrum of diseases in animals such as seborrheic dermatitis, external otitis and fungemia. The current approaches to treat these infections are failing as a consequence of their adverse effects, changes in susceptibility and antifungal resistance. Thus, the identification of novel therapeutic targets againstM. pachydermatisinfections are highly relevant. Here, Gene Essentiality Analysis and Flux Variability Analysis was applied to a previously reportedM. pachydermatismetabolic network to identify enzymes that, when absent, negatively affect biomass production. Three novel therapeutic targets (i.e., homoserine dehydrogenase (MpHSD), homocitrate synthase(MpHCS)and saccharopine dehydrogenase (MpSDH)) were identified that are absent in humans. Notably, L-lysine was shown to be an inhibitor of the enzymatic activity of MpHCS and MpSDH at concentrations of 1 mM and 75 mM, respectively, while L-threonine (1 mM) inhibited MpHSD. Interestingly, L- lysine was also shown to inhibitM. pachydermatisgrowth duringin vitroassays with reference strains and canine isolates, while it had a negligible cytotoxic activity on HEKa cells. Together, our findings form the bases for the development of novel treatments againstM. pachydermatisinfections.
Mortality and causes of death in a population with blindness in Korea: A longitudinal follow-up study using a national sample cohort
Authors: Choi Hyo Geun , Lee Min Joung , Lee Sang-Mok 
Published: March 2020

AbstractThe influence of visual impairment and blindness on the risk of mortality has been reported in diverse cohort studies. However, the results reported have varied from nonsignificant to significant associations. In the present study, we evaluated the influence of blindness on the risk of mortality from 2002 to 2013 using a longitudinal database with a national sample cohort provided by the Korean National Health Insurance Service. Of a total of 1,125,691 subjects, 1,279 subjects who were registered as blind were enrolled, and 5,116 control participants were matched at a 1:4 ratio for age, sex, income, region of residence, and medical histories of hypertension, diabetes mellitus and dyslipidemia. The life/death information contained in this dataset was used for the analysis; this information was originally recorded by the medical doctors on the death certificates of the participants. The percentage of total deaths during the mean follow-up period of 111.0 ± 41.6 months was 28.1% in the blindness group and 19.7% in the matched control group. The risk of mortality was significantly higher in the blindness group than in the control group according to the Cox proportional hazards model with additional adjustments for ischemic heart disease, stroke, and depression (adjusted hazard ratio [HR] of mortality = 1.54, 95% confidence interval [CI] = 1.37–1.74, P < 0.001). In the subgroup analyses, the adjusted HRs for mortality were significantly higher in the blindness group than in the control group regardless of age (young defined as <60 years old vs old defined as ≥60 years old) and sex. The percentage of death due to metabolic diseases and genitourinary diseases was higher in the blindness group than in the matched control group.
Translation of mouse model to human gives insights into periodontitis etiology
Authors: Nashef Aysar , Matthias Munz , Weiss Ervin , Loos Bruno G. , Jepsen Søren , van der Velde Nathalie , Uitterlinden André G. , Wellmann Jürgen , Berger Klaus , Hoffmann Per , Laudes Matthias , Lieb Wolfgang , Franke Andre , Dommisch Henrik , Schäfer Arne , Houri-Haddad Yael , Iraqi Fuad A. 
Published: March 2020

AbstractTo suggest candidate genes involved in periodontitis, we combined gene expression data of periodontal biopsies from Collaborative Cross (CC) mouse lines, with previous reported quantitative trait loci (QTL) in mouse and with human genome-wide association studies (GWAS) associated with periodontitis. Periodontal samples from two susceptible, two resistant and two lines that showed bone formation after periodontal infection were collected during infection and naïve status. Differential expressed genes (DEGs) were analyzed in a case-control and case-only design. After infection, eleven protein-coding genes were significantly stronger expressed in resistant CC lines compared to susceptible ones. Of these, the most upregulated genes were MMP20 (P = 0.001), RSPO4 (P = 0.032), CALB1 (P = 1.06×10−4), and AMTN (P = 0.05). In addition, human orthologous of candidate genes were tested for their association in a case-controls samples of aggressive (AgP) and chronic (CP) periodontitis (5,095 cases, 9,908 controls). In this analysis, variants at two loci, TTLL11/PTGS1 (rs9695213, P = 5.77×10−5) and RNASE2 (rs2771342, P = 2.84×10−5) suggested association with both AgP and CP. In the association analysis with AgP only, the most significant associations were located at the HLA loci HLA-DQH1 (rs9271850, P = 2.52×10−14) and HLA-DPA1 (rs17214512, P = 5.14×10−5). This study demonstrates the utility of the CC RIL populations as a suitable model to investigate the mechanism of periodontal disease.
Using the maximum clustering heterogeneous set-proportion to select the maximum window size for the spatial scan statistic
Authors: Wang Wei , Zhang Tao , Yin Fei , Xiao Xiong , Chen Shiqi , Zhang Xingyu , Li Xiaosong , Ma Yue 
Published: March 2020

AbstractThe spatial scan statistic has been widely used to detect spatial clusters that are of common interest in many health-related problems. However, in most situations, different scan parameters, especially the maximum window size (MWS), result in obtaining different detected clusters. Although performance measures can select an optimal scan parameter, most of them depend on historical prior or true cluster information, which is usually unavailable in practical datasets. Currently, the Gini coefficient and the maximum clustering set-proportion statistic (MCS-P) are used to select appropriate parameters without any prior information. However, the Gini coefficient may be unstable and select inappropriate parameters, especially in complex practical datasets, while the MCS-P may have unsatisfactory performance in spatial datasets with heterogeneous clusters. Based on the MCS-P, we proposed a new indicator, the maximum clustering heterogeneous set-proportion (MCHS-P). A simulation study of selecting the optimal MWS confirmed that in spatial datasets with heterogeneous clusters, the MWSs selected using the MCHS-P have much better performance than those selected using the MCS-P; moreover, higher heterogeneity led to a larger advantage of the MCHS-P, with up to 538% and 69.5% improvement in the Youden's index and misclassification in specific scenarios, respectively. Meanwhile, the MCHS-P maintains similar performance to that of the MCS-P in spatial datasets with homogeneous clusters. Furthermore, the MCHS-P has significant improvements over the Gini coefficient and the default 50% MWS, especially in datasets with clusters that are not far from each other. Two practical studies showed similar results to those obtained in the simulation study. In the case where there is no prior information about the true clusters or the heterogeneity between the clusters, the MCHS-P is recommended to select the MWS in order to accurately identify spatial clusters.
Involvement of estrogen in phosphorus-induced nephrocalcinosis through fibroblast growth factor 23
Authors: Takasugi Satoshi , Shioyama Miho , Kitade Masami , Nagata Masashi , Yamaji Taketo 
Published: March 2020

AbstractExcessive phosphorus intake adversely affects bone and mineral metabolism. Estrogen is one of the factors affecting fibroblast growth factor 23 (FGF23), a phosphorus-regulating hormone. However, the interaction between excess phosphorus and estrogen status has not been fully elucidated. This study investigated the involvement of estrogen in the effects of high phosphorus intake on bone metabolism and ectopic calcification in ovariectomized (OVX) rats. The interaction between high phosphorus diet and OVX was not observed in bone mineral density and aortic calcium. In contrast, high phosphorus intake markedly increased renal calcium concentration in sham rats, whereas the effect was attenuated in OVX rats, which was reversed by a selective estrogen-receptor modulator treatment. A strong positive correlation between renal calcium and serum FGF23 was observed. In addition, fibroblast growth factor receptor 1 (FGFR1: a predominant receptor of FGF23) inhibitor treatment partially decreased renal calcium concentrations in rats with high phosphorus intake. In conclusion, the effect of high phosphorus intake on bone metabolism and aortic calcification did not depend on the estrogen status; in contrast, high phosphorus intake synergistically induced nephrocalcinosis in the presence of estrogenic action on the bone. Furthermore, FGF23 was involved in the nephrocalcinosis induced by high phosphorus intake partially through FGFR1 signaling.
Risk Factors for Progression of Barrett’s Esophagus to High Grade Dysplasia and Esophageal Adenocarcinoma
Authors: Thiruvengadam Swetha Kambhampati , Tieu Alan H. , Luber Brandon , Wang Hao , Meltzer Stephen J. 
Published: March 2020

AbstractBarrett’s esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC). Methods of identifying BE patients at high risk for progression to high-grade dysplasia (HGD) or EAC are needed to improve outcomes and identify who will benefit most from intensive surveillance or ablative therapy. Clinical predictors of BE progression to HGD or EAC are poorly understood, with multiple contradictory studies. We performed a retrospective study which included 460 patients at Johns Hopkins Hospital who underwent at least 2 upper endoscopies 6 months apart showing biopsy-documented BE between 1992 and 2013. Patients with EAC or HGD at the initial endoscopy were excluded. Demographic, clinicopathological, and endoscopic data were collected. Univariate and multivariate Cox proportional hazards analyses with time to progression to HGD and EAC were performed. Among 460 patients included in the study, 132 BE patients developed HGD and 62 developed EAC. Significant EAC risk factors included age, abdominal obesity, caffeine intake, and the presence of HGD. Risk factors for HGD or EAC included age, caffeine intake, and low-grade dysplasia while colonic adenomas trended towards significance. Notably, a history of statin or SSRI usage reduced the risk of EAC or HGD by 49% or 61%, respectively. Our study validated several known and identified several novel risk factors, including a history of colonic adenomas or caffeine usage. Low-grade dysplasia was a risk factor for progression but various endoscopic characteristics were not, suggesting that screening strategies should focus on histology instead. We identified SSRIs as a new potentially chemoprotective medication.
Genome-wide association identifies seven loci for pelvic organ prolapse in Iceland and the UK Biobank
Authors: Olafsdottir Thorhildur , Thorleifsson Gudmar , Sulem Patrick , Stefansson Olafur A. , Medek Helga , Olafsson Karl , Ingthorsson Orri , Gudmundsson Valur , Jonsdottir Ingileif , Halldorsson Gisli H. , Kristjansson Ragnar P. , Frigge Michael L. , Stefansdottir Lilja , Sigurdsson Jon K. , Oddsson Asmundur , Sigurdsson Asgeir , Eggertsson Hannes P. , Melsted Pall , Halldorsson Bjarni V. , Lund Sigrun H. , Styrkarsdottir Unnur , Steinthorsdottir Valgerdur , Gudmundsson Julius , Holm Hilma , Tragante Vinicius , Asselbergs Folkert W. , Thorsteinsdottir Unnur , Gudbjartsson Daniel F. , Jonsdottir Kristin , Rafnar Thorunn , Stefansson Kari 
Published: March 2020

AbstractPelvic organ prolapse (POP) is a downward descent of one or more of the pelvic organs, resulting in a protrusion of the vaginal wall and/or uterus. We performed a genome-wide association study of POP using data from Iceland and the UK Biobank, a total of 15,010 cases with hospital-based diagnosis code and 340,734 female controls, and found eight sequence variants at seven loci associating with POP (P < 5 × 10−8); seven common (minor allele frequency >5%) and one with minor allele frequency of 4.87%. Some of the variants associating with POP also associated with traits of similar pathophysiology. Of these, rs3820282, which may alter the estrogen-based regulation of WNT4, also associates with leiomyoma of uterus, gestational duration and endometriosis. Rs3791675 at EFEMP1, a gene involved in connective tissue homeostasis, also associates with hernias and carpal tunnel syndrome. Our results highlight the role of connective tissue metabolism and estrogen exposure in the etiology of POP.
Aging and Sex Effects on Mastication Performance in Healthy, Nondysphagic, Community-Dwelling Adults
Authors: Milford Erin M. , Wang Bin , Smith Kimberly , Choi Dahye , Martin-Harris Bonnie , Garand Kendrea L. (Focht) 
Published: March 2020

Purpose
This study investigated the impact of age and sex on mastication performance in healthy, nondysphagic, community-dwelling adults as observed during videofluoroscopy.

Method
Videofluoroscopic swallowing study imaging and mastication performance metrics (cycles, duration) were used to evaluate 185 healthy individuals (102 women, 83 men) aged 21–89 years.

Results
A significant effect of age on mastication cycles was not observed; however, a significant but weak effect of age on mastication duration was found. Female participants were observed to have significantly more mastication cycles and longer mastication durations compared to male participants. Three behavioral patterns of mastication performance emerged.

Conclusions
The results of this study contribute to normative data of mastication performance. An individual's sex was found to have a significant effect on mastication performance, although, in contrast to previous studies, age was not observed to significantly alter mastication performance. Differences in study methodologies likely explain the latter finding.
Heritability of Specific Language Impairment and Nonspecific Language Impairment at Ages 4 and 6 Years Across Phenotypes of Speech, Language, and Nonverbal Cognition
Authors: Rice Mabel L. , Taylor Catherine L. , Zubrick Stephen R. , Hoffman Lesa , Earnest Kathleen K. 
Published: March 2020

Purpose
Early language and speech acquisition can be delayed in twin children, a twinning effect that diminishes between 4 and 6 years of age in a population-based sample. The purposes of this study were to examine how twinning effects influence the identification of children with language impairments at 4 and 6 years of age, comparing children with specific language impairment (SLI) and nonspecific language impairment (NLI); the likelihood that affectedness will be shared within monozygotic versus dizygotic twin pairs; and estimated levels of heritability for SLI and NLI. Twinning effects are predicted to result in elevated rates of language impairments in twins.

Method
The population-based twin sample included 1,354 children from 677 twin pairs, 214 monozygotic and 463 dizygotic, enrolled in a longitudinal study. Nine phenotypes from the same comprehensive direct behavioral assessment protocol were investigated at 4 and 6 years of age. Twinning effects were estimated for each phenotype at each age using structural equation models estimated via diagonally weighted least squares. Heritabilities were calculated for SLI and NLI.

Results

As predicted, the twinning effect increased the percentage of affected children in both groups across multiple language phenotypes, an effect that diminished with age yet was still not aligned to singleton age peers. Substantial heritability estimates replicated across language phenotypes and increased with age, even with the most lenient definition of affectedness, at −1
SD
. Patterns of outcomes differed between SLI and NLI groups.

Conclusions
Nonverbal IQ is not on the same causal pathway as language impairments. Twinning effects on language acquisition affect classification of 4- and 6-year-old children as SLI and NLI, and heritability is most consistent in the SLI group. Clinical practice requires monitoring language acquisition of twins to avoid misdiagnosis when young or a missed diagnosis of language impairments at school entry.