bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine D2 up-regulation in psychosis patients after antipsychotic drug treatment
Authors: Thompson Ilse A. , de Vries Erik F.J. , Sommer Iris E.C. 
Published: February 2020

Purpose of review
Recently, it has been questioned whether the re-emergence of psychotic symptoms following antipsychotic discontinuation or dose reduction is attributable to underlying psychotic vulnerability or to rebound effects of chronic use of antipsychotic medication. It was repeatedly shown that relapse rates are high after discontinuation of maintenance treatment. A potential contributing factor could be the increase in density of postsynaptic dopamine D2 receptors in the striatum and the higher affinity of D2 receptors for dopamine after chronic blockade.

Recent findings
To date, little clinical evidence is available for the mechanisms involved in postsynaptic striatal D2 receptor up-regulation after use of antipsychotic medication, and most knowledge comes from animal studies.

Summary
Further research is needed to investigate whether antipsychotic medication causes neuroadaptations leading to a dopamine supersensitive state in humans, how long such hypersensitive states may last and what differences exist between high and low D2 affinity antipsychotic drugs. Further, information is needed on discontinuation schedules that provide optimal protection for relapse during hypersensitive periods.
The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19
Authors: Sarkar Bishajit , Ullah Md. Asad , Johora Fatema Tuz , Taniya Masuma Afrin , Araf Yusha 
Published: February 2020

AbstractWuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.
The Pathogenicity of SARS-CoV-2 in hACE2 Transgenic Mice
Authors: Bao Linlin , Deng Wei , Huang Baoying , Gao Hong , Liu Jiangning , Ren Lili , Wei Qiang , Yu Pin , Xu Yanfeng , Qi Feifei , Qu Yajin , Li Fengdi , Lv Qi , Wang Wenling , Xue Jing , Gong Shuran , Liu Mingya , Wang Guanpeng , Wang Shunyi , Song Zhiqi , Zhao Linna , Liu Peipei , Zhao Li , Ye Fei , Wang Huijuan , Zhou Weimin , Zhu Na , Zhen Wei , Yu Haisheng , Zhang Xiaojuan , Guo Li , Chen Lan , Wang Conghui , Wang Ying , Wang Xinming , Xiao Yan , Sun Qiangming , Liu Hongqi , Zhu Fanli , Ma Chunxia , Yan Lingmei , Yang Mengli , Han Jun , Xu Wenbo , Tan Wenjie , Peng Xiaozhong , Jin Qi , Wu Guizhen , Qin Chuan 
Published: February 2020

AbstractSevere acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Koch’s postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.
Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage
Authors: Liu Jingyuan , Liu Yao , Xiang Pan , Pu Lin , Xiong Haofeng , Li Chuansheng , Zhang Ming , Tan Jianbo , Xu Yanli , Song Rui , Song Meihua , Wang Lin , Zhang Wei , Han Bing , Yang Li , Wang Xiaojing , Zhou Guiqin , Zhang Ting , Li Ben , Wang Yanbin , Chen Zhihai , Wang Xianbo 
Published: February 2020

AbstractBackgroundSevere ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence.MethodsThe study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve.ResultsThe neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676–0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR < 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process.ConclusionsThe NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.
Isolevuglandins promote autoimmunity and hypertension in systemic lupus erythematosus
Authors: Patrick David M. , de la Visitación Nestor , Ormseth Michelle J. , Stein C. Michael , Davies Sean S. , Yermalitksy Valery N. , Amarnath Venkataraman , Crofford Leslie J. , Williams Jonathan M. , Dikalov Sergey , Dikalova Anna , Xiao Liang , Van Beusecum Justin P. , Ao Mingfang , Fogo Agnes B. , Kirabo Annet , Harrison David G. 
Published: February 2020

ABSTRACTHypertension, vascular inflammation and renal inflammation are characteristic of systemic lupus erythematosus (SLE), a multisystem autoimmune disease that is complex and poorly understood. Oxidation products of arachidonic and other fatty acids, termed isolevuglandins (isoLG) lead to formation of post-translational protein modifications that are immunogenic. We demonstrate isoLG enrichment in dendritic cells (DCs), B cells, and plasma cells from juvenile femaleB6.SLE123mice. In adultB6.SLE123andNZBWF1mice, isoLG adducts are enriched in plasma cells and splenic DCs compared toC57Bl/6andNZWmice respectively. Treatment with the isoLG-scavenger 2-hydroxybenzylamine (2-HOBA) reduced blood pressure, improved renal function, and attenuated renal injury. Moreover, 2-HOBA reduced bone marrow plasma cells, total IgG levels, and anti-dsDNA antibody titers. We also demonstrate that mice with SLE generate specific IgG antibodies against isoLG adducted protein, confirming the immunogenicity of isoLG adducts. Finally, we found that isoLG adducted peptides are markedly enriched in monocytes from patients with SLE which was accompanied by an increase in superoxide production. These findings support a role of isoLG adducts in the genesis and maintenance of systemic autoimmunity and its associated hypertension in SLE. Scavenging of isoLGs promises to be a novel therapy for this disease.
Metabolomic changes associated with frontotemporal lobar degeneration syndromes
Authors: Murley Alexander G. , Jones P Simon , Gilchrist Ian Coyle , Bowns Lucy , Wiggins Julie , Tsvetanov Kamen A. , Rowe James B. 
Published: February 2020

AbstractObjectiveWidespread metabolic changes are seen in neurodegenerative disease and could be used as biomarkers for diagnosis and disease monitoring. They may also reveal disease mechanisms that could be a target for therapy. In this study we looked for blood-based biomarkers in syndromes associated with frontotemporal lobar degeneration.MethodsPlasma metabolomic profiles were measured from 134 patients with frontotemporal lobar degeneration (behavioural variant frontotemporal dementia n=30, non fluent variant primary progressive aphasia n=26, progressive supranuclear palsy n=45, corticobasal syndrome n=33) and 32 healthy controls.ResultsForty-nine of 842 metabolites were significantly altered in frontotemporal lobar degeneration (after false-discovery rate correction for multiple comparisons). These were distributed across a wide range of metabolic pathways including amino acids, energy and carbohydrate, cofactor and vitamin, lipid and nucleotide pathways. The metabolomic profile supported classification between frontotemporal lobar degeneration and controls with high accuracy (88.1-96.6%) while classification accuracy was lower between the frontotemporal lobar degeneration syndromes (72.1-83.3%). One metabolic profile, comprising a range of different pathways, was consistently identified as a feature of each disease versus controls: the degree to which a patient expressed this metabolomic profile was associated with their subsequent survival (hazard ratio 0.74 [0.59-0.93], p = 0.0018).ConclusionsThe metabolic changes in FTLD are promising diagnostic and prognostic biomarkers. Further work is required to replicate these findings, examine longitudinal change, and test their utility in differentiating between FTLD syndromes that are pathologically distinct but phenotypically similar.
Statistical Inference for Coronavirus Infected Patients in Wuhan
Authors: Zhou Yong-Dao , Dong Jianghu James 
Published: February 2020

ImportanceThe new coronavirus outbreak has seriously affected the quality of life in China. Wuhan is the disaster area, where the number of cases has increased rapidly. However, the current measures of infected patients in Wuhan are still underestimated.ObjectiveTo estimate the overall infected patients in Wuhan from several sampled data. The correct estimated infected patients can be helpful for the government to arrange the needed beds in hospital wards to meet the actual needs.DesignWe proposed to use the sampling survey to estimate the overall infected patients in Wuhan. The sampling survey is a kind of non-comprehensive survey. It selected some units from all the survey objects to carry out the survey and made the estimation and inference to all the survey objects. Sampling surveys can obtain information that reflects the overall situation, although it is not a comprehensive survey.SettingWe estimated the overall infection rate in Wenzhou city, which has a better data collection system. Simultaneously, another different samples of Wuhan tourists to Singapore will be used to validate the infection rate in Wenzhou city. Combined these two samples, we give the estimation of the number of infected patients in Wuhan and other prefecture-level cities in Hubei Province.ParticipantsThe number of people who returned from Wuhan to Wenzhou was selected from the daily notification of the pneumonia epidemic caused by a new coronavirus infection in the city.Exposures for observational studiesThe daily rate of the pneumonia epidemic caused by the new coronavirus infection in Wenzhou City. The numerator is the number of people diagnosed and whether each person diagnosed had a history of living in Wuhan. The denominator is the total number of people returning to Wenzhou from Wuhan. Based on this rate, it is reasonable to predict the number of the infected patients.Main Outcome(s) and Measure(s)According to the most conservative estimate from our proposed sampling method, at least total 54,000 infected patients are in Wuhan. Therefore, the current 8,000 beds in hospital wards and the 20,000 beds in square-class hospitals are far away from meeting the actual needs.
Distribution of the 2019-nCoV Epidemic and Correlation with Population Emigration from Wuhan, China
Authors: Chen Zeliang , Zhang Qi , Lu Yi , Guo Zhongmin , Zhang Xi , Zhang Wenjun , Guo Cheng , Liao Conghui , Li Qianlin , Han Xiaohu , Lu Jiahai 
Published: February 2020

AbstractBACKGROUNDSThe ongoing new coronavirus (2019-nCoV) pneumonia outbreak is spreading in China and has not reached its peak. Five millions of people had emigrated from Wuhan before the city lockdown, which potentially represent a source of virus spreaders. Case distribution and its correlation with population emigration from Wuhan in early epidemic are of great importance for early warning and prevention of future outbreak.METHODSThe officially reported cases of 2019-nCoV pneumonia were collected as of January 30, 2020. Time and location information of these cases were extracted analyzed with ArcGIS and WinBUGS. Population migration data of Wuhan City and Hubei province were extracted from Baidu Qianxi and analyzed for their correlation with case number.FINDINGSThe 2019-nCoV pneumonia cases were predominantly distributed in Hubei and other provinces of South China. Hot spot provinces included Sichuan and Yunnan provinces that are adjacent to Hubei. While Wuhan city has the highest number of cases, the time risk is relatively stable. Numbers of cases in some cities are relatively low, but the time risks are continuously rising. The case numbers of different provinces and cities of Hubei province were highly correlated with the emigrated populations from Wuhan. Lockdown of 19 cities of Hubei province, and implementation of nationwide control measures efficiently prevented the exponential growth of case number.INTERPRETATIONPopulation emigrated from Wuhan was the main infection source for other cities and provinces. Some cities with low case number but were in rapid increase. Due to the upcoming Spring Festival return transport wave, understanding of the trends of risks in different regions is of great significance for preparedness for both individuals and institutions.FUNDINGSNational Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, State Key Program of National Natural Science of China.
Cohesin-dependent and independent mechanisms support chromosomal contacts between promoters and enhancers
Authors: Thiecke Michiel J. , Wutz Gordana , Muhar Matthias , Tang Wen , Bevan Stephen , Malysheva Valeriya , Stocsits Roman , Neumann Tobias , Zuber Johannes , Fraser Peter , Schoenfelder Stefan , Peters Jan-Michael , Spivakov Mikhail 
Published: February 2020

AbstractIt is currently assumed that 3D chromosomal organisation plays a central role in transcriptional control. However, recent evidence shows that steady-state transcription of only a minority of genes is affected by depletion of architectural proteins such as cohesin and CTCF. Here, we have used Capture Hi-C to interrogate the dynamics of chromosomal contacts of all human gene promoters upon rapid architectural protein degradation. We show that promoter contacts lost in these conditions tend to be long-range, with at least one interaction partner localising in the vicinity of topologically associated domain (TAD) boundaries. In contrast, many shorter-range chromosomal contacts, particularly those that connect active promoters with each other and with active enhancers remain unaffected by cohesin and CTCF depletion. We demonstrate that the effects of cohesin depletion on nascent transcription can be explained by changes in the connectivity of their enhancers. Jointly, these results provide a mechanistic explanation to the limited, but consistent effects of cohesin and CTCF on steady-state transcription and point towards the existence of alternative enhancer-promoter pairing mechanisms that are independent of these proteins.
Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone
Authors: Wiegering Antonia , Dildrop Renate , Vesque Christine , Schneider-Maunoury Sylvie , Gerhardt Christoph 
Published: February 2020

AbstractA range of severe human diseases called ciliopathies are caused by the dysfunction of primary cilia. Primary cilia are cytoplasmic protrusions consisting of the basal body (BB), the axoneme and the transition zone (TZ). The BB is a modified mother centriole from which the axoneme, the microtubule-based ciliary scaffold, is formed. At the proximal end of the axoneme, the TZ functions as the ciliary gate governing ciliary protein entry and exit. Since ciliopathies often develop due to mutations in genes encoding proteins that localise to the TZ, the understanding of the mechanisms underlying TZ function is of eminent importance. Here, we show that the ciliopathy protein Rpgrip1l governs ciliary gating by ensuring the proper amount of Cep290 at the vertebrate TZ. Further, we identified the flavonoid eupatilin as a potential agent to tackle ciliopathies caused by mutations inRPGRIP1Las it rescues ciliary gating in the absence of Rpgrip1l.
Modeling How Community Assembly Alters the Functioning of Ecosystems
Authors: Koffel Thomas , Kremer Colin T , Bannar-Martin K. , Ernest S.K. Morgan , Eisenhauer Nico , Roscher Christiane , Cabral Juliano Sarmento , Leibold Mathew A. 
Published: February 2020

AbstractAlthough the effects of species richness on ecosystem functioning have been extensively studied, there is increased interest in understanding how community assembly in general might alter the functioning of ecosystems. We focus on two complementary approaches for evaluating how community assembly influences ecosystem function (here, productivity). The first quantifies the relative importance of complementarity and selection by contrasting monocultures with polycultures. The second identifies the effects of species losses and/or gains relative to the baseline polyculture, as well as the indirect effects on other species’ productivity. We evaluate and contrast these two approaches, using simulated communities structured by different, known competition mechanisms, where species compete for different resources and experience varying levels of environmental heterogeneity. We find that the metrics provided by these approaches can jointly discriminate the mechanisms of competition driving productivity. We then apply our methods to data from a long-term biodiversity-ecosystem experiment (the Jena Experiment) and find that the data do not correspond to any of the competition scenarios we modeled. We address two additional possible complications: facilitation by nitrogen fixing plants, and non-equilibrium behavior during community assembly, and find that a combination of resource competition and facilitation by nitrogen fixing plants is the more likely explanation for the results obtained at Jena.
Spatial Distribution of Discarded Vehicle Tires and Their Influence onAedes albopictusandCulex quinquefasciatusPopulations, New Orleans, Louisiana
Authors: Sallam Mohamed F. , Ahmed Tamer , Sylvain-Lear Cynthia , Riegel Claudia , Moise Imelda K. 
Published: February 2020

AbstractDiscarded vehicle tires play an important role in the colonization of container mosquito populations, particularly their geographic expansion. We assessed the spatial distribution of illegally discarded tires and their response to land use-land cover (LULC), and demographic factors using geospatial analysis and generalized regression. Multiple stepwise regressions were used to evaluate the response of the Container Index (CI) of colonizedAedes albopictus(Skuse), andCulex quinquefasciatusSay to macro- and microhabitats variables. The illegally discarded tires were distributed over 11 planning districts with clustering distribution for tires frequency and overdispersed distribution for tires number. Out of 1,137 (∼37.08%) water-holding tires, 598 (∼52.64%) tires at 65 (∼38.46%) sites were positive for colonized mosquito populations. A total of 13 mosquito species were identified, with the highest CI ofAe. albopictus(44.19%) andCx. quinquefasciatus(22.18%).Aedes albopictuscolonized all 65 sample sites andCx. quinquefasciatusfound at 32 sites. The Container Index (CI) of colonized mosquito was clustered in seven planning districts forAe. albopictusand five planning districts forCx. quinquefasciatus. Microhabitat (muddy water) rather than macrohabitats variables predicted both species’ colonization, especiallyAe. albopictus. The contribution of macro- and microhabitat characteristics in predicting colonized mosquito in water-holding tires was discussed.
Classifyber, a robust streamline-based linear classifier for white matter bundle segmentation
Authors: Bertò Giulia , Bullock Daniel , Astolfi Pietro , Hayashi Soichi , Zigiotto Luca , Annicchiarico Luciano , Corsini Francesco , Benedictis Alessandro De , Sarubbo Silvio , Pestilli Franco , Avesani Paolo , Olivetti Emanuele 
Published: February 2020

AbstractVirtual delineation of white matter bundles in the human brain is of paramount importance for multiple applications, such as pre-surgical planning and connectomics. A substantial body of literature is related to methods that automatically segment bundles from diffusion Magnetic Resonance Imaging (dMRI) data indirectly, by exploiting either the idea of connectivity between regions or the geometry of fiber paths obtained with tractography techniques, or, directly, through the information in volumetric data. Despite the remarkable improvement in automatic segmentation methods over the years, their segmentation quality is not yet satisfactory, especially when dealing with datasets with very diverse characteristics, such as different tracking methods, bundle sizes or data quality. In this work, we propose a novel, supervised streamline-based segmentation method, called Classifyber, which combines information from atlases, connectivity patterns, and the geometry of fiber paths into a simple linear model. With a wide range of experiments on multiple datasets that span from research to clinical domains, we show that Classifyber substantially improves the quality of segmentation as compared to other state-of-the-art methods and, more importantly, that it is robust across very diverse settings. We provide an implementation of the proposed method as open source code, as well as web service.