bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bridging Heterogeneous Mutation Data to Enhance Disease-Gene Discovery
Authors: Zhou Kaiyin , Wang Yuxing , Cohen Kevin Bretonnel , Kim Jin-Dong , Ma Xiaohang , Shen Zhixue , Meng Xiangyu , Xia Jingbo 
Published: August 2020

Abstract
Background: Bridging heterogeneous mutation data fills in the gap between various data categories and propels discovery of disease-related genes. It is known that genome-wide association study (GWAS) infers significant mutation associations which link genotype and phenotype, and it is under-powered for pinpointing causal genes due to high false positive or negative rate. In the meantime, mutation events widely reported in literature unveil typical functional biological process, including mutation types like gain-of-function and loss-of-function. Methods: To bring together the heterogeneous mutation data, we propose a pipeline, “Gene-Disease Association prediction by Mutation Data Bridging (GDAMDB)”, with a statistic generative model. The model learns the distribution parameters of mutation associations and mutation types, and recovers false negative GWAS mutations which fail to pass significant test but represent supportive evidences of functional biological process in literature. Results: Eventually, GDAMDB is applied in Alzheimer’s disease which is a common inheritable neurodegenerative disorder with unknown pathological mechanism, and it predicted 79 AD-associated genes. Besides 12 of them come from the original GWAS study, 57 of them are supported to be AD-related by other GWAS or literature report. Conclusion: Our model is capable of enhancing the GWAS-based gene association discovery by well combining text mining results. The positive result indicates that bridging the heterogeneous mutation data is contributory for the novel disease-related gene discovery.
Classification of OCT Images for Detecting Diabetic Retinopathy Disease Using Machine Learning
Authors: Aldahami Marwan , Alqasemi Umar 
Published: August 2020

Abstract
Background Optical Coherence Tomography (OCT) imaging aids in retinal abnormality detection by showing the tomographic retinal layers. OCT images are a useful tool for detecting Diabetic Retinopathy (DR) disease because of their capability of capturing micrometer-resolution.Method An automated technique was introduced to differentiate DR images from normal ones. 214 images were subjected to the experiment, of which 160 images were used for classifiers’ training, and 54 images were used for testing. Different features were extracted to feed our classifiers, including statistical features and local binary pattern (LBP) features.Results The experimental results demonstrated that our classifiers were able to discriminate DR retina from the normal retina with ROC Area Under the Curve (AUC) of 100%.Conclusions The retinal OCT images have common texture patterns and using a powerful tool for pattern analysis like LBP features has a significant impact on the achieved results. The result has better performance than previously proposed methods in the literature.
Regional Binding of Tau and Amyloid Pet Tracers in Down Syndrome Autopsy Brain Tissue
Authors: Lemoine Laetitia , Ledreux Aurelie , Mufson Elliott J , Perez Sylvia E , Simic Goran , Doran Eric , Lott Ira , Carroll Steven , Bharani Krishna , Thomas Sarah , Gilmore Anah , Hamlett Eric D , Nordberg Agneta , Granholm Ann-Charlotte 
Published: August 2020

Abstract
INTRODUCTION: Tau pathology is a major age-related event in Down syndrome with Alzheimer’s disease (DS-AD). Although recently, several different Tau PET tracers have been developed as biomarkers for AD, these tracers showed different binding properties in Alzheimer disease and other non-AD tauopathies. They have not been yet investigated in tissue obtained postmortem for DS-AD cases. Here, we evaluated the binding characteristics of two Tau PET tracers (3H-MK6240 and 3H-THK5117) and one amyloid (3H-PiB) ligand in the medial frontal gyrus (MFG) and hippocampus (HIPP) in tissue from adults with DS-AD and DS cases with mild cognitive impairment (MCI) compared to sporadic AD. METHODS: Tau and amyloid autoradiography were performed on paraffin-embedded sections. To confirm respective ligand targets, adjacent sections were immunoreacted for phospho-Tau (AT8) and stained for amyloid staining using Amylo-Glo. RESULTS: The two Tau tracers showed a significant correlation with each other and with AT8, suggesting that both tracers were binding to Tau deposits. 3H-MK6240 Tau binding correlated with AT8 immunostaining but to a lesser degree than the 3H-THK5117 tracer, suggesting differences in binding sites between the two Tau tracers. 3H-THK5117, 3H-MK6240 and 3H-PIB displayed dense laminar binding in the HIPP and MFG in adult DS brains. A regional difference in Tau binding between adult DS and AD was observed suggesting differential regional Tau deposition in adult DS compared to AD, with higher THK binding density in the MFG in adult with DS compared to AD. No significant correlation was found between 3H-PiB and Amylo-Glo staining in adult DS brains suggesting that the amyloid PIB tracer binds to additional sites. CONCLUSIONS: This study provides new insights into the regional binding distribution of a first-generation and a second-generation Tau tracer in limbic and neocortical regions in adults with DS, as well as regional differences in Tau binding in adult with DS vs. those with AD. These findings provide new information about the binding properties of two Tau radiotracers for the detection of Tau pathology in adults with DS in vivo and provide valuable data regarding Tau vs. amyloid binding in adult DS compared to AD.
SARS-CoV-2 infection induces robust germinal center CD4 T follicular helper cell responses in rhesus macaques
Authors: Elizaldi Sonny , Lakshmanappa Yashavanth Shaan , Roh Jamin , Schmidt Brian , Carroll Timothy , Weaver Kourtney , Smith Justin , Deere Jesse , Dutra Joseph , Stone Mars , Franz Sergej , Sammak Rebecca , Olstad Katherine , Reader J. Rachel , Ma Zhong-Min , Nguyen Nancy , Watanabe Jennifer , Usachenko Jodie , Immareddy Ramya , Yee JoAnn , Weiskopf Daniela , Sette Alessandro , Hartigan-O'Connor Dennis , McSorley Stephen , Morrison John , Tran Nam , Simmons Graham , Busch Michael , Kozlowsk Pamela , Rompay Koen van , Miller Christopher , Iyer Smita 
Published: August 2020

Abstract
CD4 T follicular helper (Tfh) cells are important for the generation of durable and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that SARS-CoV-2 infection resulted in transient accumulation of pro-inflammatory monocytes and proliferating Tfh cells with a Th1 profile in peripheral blood. CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes. We observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.
Oxysterols Present in Alzheimer’s Disease Braininduce Synaptoxicity by Activating Astrocytes: A Major Role for Lipocalin-2
Authors: Staurenghi Erica , Cerrato Valentina , Gamba Paola , Testa Gabriella , Giannelli Serena , Leoni Valerio , Caccia Claudio , Buffo Annalisa , Noble Wendy , Perez-Nievas Beatriz Gomez , Leonarduzzi Gabriella 
Published: August 2020

Abstract
Background: Among Alzheimer’s disease (AD) brain hallmarks, the presence of reactive astrocytes was demonstrated to correlate with neuronal loss and cognitive deficits. Evidence indeed supports the role of reactive astrocytes as mediators of changes in neurons, including synapses. However, the complexity and the outcomes of astrocyte reactivity are far from being completely elucidated. Another key role in AD pathogenesis is played by alterations in brain cholesterol metabolism. Oxysterols (cholesterol oxidation products) are crucial for brain cholesterol homeostasis, and we previously demonstrated that changes in the brain levels of various oxysterols correlate with AD progression. Moreover, oxysterols have been shown to contribute to various pathological mechanisms involved in AD pathogenesis.In order to deepen the role of oxysterols in AD, we investigated whether they could contribute to astrocyte reactivity, and consequently impact on neuronal health.Methods: Mouse primary astrocyte cultures were used to test the effect of two oxysterol mixtures, that represent the oxysterol composition respectively of mild or severe AD brains, on astrocyte morphology, markers of reactivity, and secretion profile. Co-culture experiments were performed to investigate the impact of oxysterol-treated astrocytes on neurons. Neuronal cultures were exposed to astrocyte conditioned media (ACM) deprived of lipocalin-2 (Lcn2) to investigate the contribution of this mediator to synaptotoxicity.Results: Results showed that oxysterols induce a clear morphological change in astrocytes, accompanied by the upregulation of some reactive astrocyte markers, including Lcn2. Moreover, ACM analysis revealed a significant increase in the release of Lcn2, cytokines, and chemokines in response to oxysterols. A significant reduction of postsynaptic density protein 95 (PSD95) and a concurrent increase in cleaved caspase-3 protein levels have been demonstrated in neurons co-cultured with oxysterol-treated astrocytes, pointing out that mediators released by astrocytes have an impact on neurons. Among these mediators, Lcn2 has been demonstrated to play a major role on synapses, affecting neurite morphology and decreasing dendritic spine density. Conclusions: These data demonstrated that oxysterols present in the AD brain promote astrocyte reactivity, determining the release of several mediators that affect neuronal health and synapses. Lcn2 has been shown to exert a key role in mediating the synaptotoxic effect of oxysterol-treated astrocytes.
Short-term efficacy of trial medicine treatment may play a predictive value for the choice of therapy methods among brain abscess patients
Authors: Liu Zengjin , Guo Shewei , Sun Hongwei , Liu Xianzhi 
Published: August 2020

Abstract
Background: Traditionally, brain abscess with diameter beyond 2.5cm is considered to be treated with surgical methods, however in some cases medical treatment alone also got good results. Which patients with the abscess diameter beyond 2.5cm could be treated with medicine alone? Objective: 32 brain abscess patients accepted one week of trial medicine therapy and were divided into surgical group and conservative group according the ultimate therapy method. Methods: Some clinical factors including Glasgow Coma Scale (GCS), Karnofsky performance scores (KPS), and mini-mental state examination (MMSE), abscess sizes and edema indexes (EI) were recorded, and these factors were analyzed to observe the differences between the two groups.Results: The surgical group had larger abscess sizes (4.21±0.62cm vs 2.85±0.98cm p<0.001), lower GCS (10.00±1.04 vs 11.44±1.92 p=0.017), lower KPS (40.71±12.69 vs 52.78±20.24 p=0.061), and lower MMSE scores (8.57±1.40 vs 11.67±2.38 p=0.0008) before treatment than the conservative group. After trial therapy, the conservative group got higher extent of MMSE improvement (10.06±2.67 vs 4.86±0.66 p<0.0001) and abscesses sizes decline (0.7±0.40cm vs 0.15 ± 0.18cm p=0.0002) than surgical group, logistic analysis indicated consecutive variation of MMSE and change of abscess sizes during trial treatment might correlated closely to the ultimate treatment methods (p=0.027; p=0.019). Conclusions: These data might provide some clues for the selection of treatment methods for brain abscess patients.
Early Spot Sign is Associated with Functional Outcomes in Primary Intracerebral Hemorrhage Survivors
Authors: Hsiao Ming Yen , Tseng Wen-Che , Wang Yu-Fen , Wang Tyng-Guey 
Published: August 2020

Abstract
Background The computed tomography angiography (CTA) spot sign is a validated predictor of hematoma expansion and 30-day mortality in intracerebral hemorrhage (ICH). However, whether the spot sign predicts worse functional outcomes among ICH survivors remains unclear. This study investigated the frequency of the spot sign and its association with functional outcomes and length of hospital stay among ICH survivors.Methods This was a retrospective analysis of consecutive patients with primary ICH who received CTA within 24 h from presentation to admission to the emergency department of a single medical center between January 2007 and December 2017. Patients who died before discharge and those referred from other hospitals were excluded. CTAs with motion artifacts were excluded from the analysis. The presence of a spot sign was examined by an experienced neuroradiologist. Functional outcomes were determined based on the modified Rankin Scale (mRS) score and Barthel Index (BI). Severe dependency in activities of daily living (ADL) was defined as BI of ≤60 and severe disability as an mRS score of ≥4. Odds ratio (OR) and multiple linear regression were used as measures of association.Results In total, 66 patients met the inclusion criteria, of whom 9 (13.64%) were positive for a spot sign. No significant differences were observed in baseline characteristics between patients with and without a spot sign. Patients with a spot sign tended to be severely dependent in ADL at discharge (66.67% vs 41.07%; OR = 2.87; p = 0.15) and were more likely to require ICH-related surgery (66.67% vs 24.56%; OR = 6.14; p = 0.01). In multiple linear regression, patients with a higher spot sign score had a significantly longer hospital stay (coefficient = 9.57; 95% CI = 2.11–17.03; p = 0.013).Conclusions The presence of a spot sign is a common finding and is associated with longer hospital stay and possibly worse functional outcomes in ICH survivors.
Predictors of neurological deterioration during admission for patients with cerebellar strokes
Authors: Amornpojnimman Thanyalak , Sathirapanya Pornchai , Intusoma Utcharee , Sanghan Nuttha , Kaewborisutsakul Anukoon 
Published: August 2020

Abstract
Background: Despite less common, cerebellar stroke frequently results in unfavorable outcomes, especially after deterioration. Therefore, this study was aimed to identify the significant predictors of neurological deterioration during admission (NDDA) in ischemic and hemorrhagic cerebellar strokes.Materials and methods: We retrospectively reviewed all medical records of the patients diagnosed with ischemic and hemorrhagic cerebellar strokes during 2002-2018 in Songklanagarind hospital. Comparison of patients’ demographic data, initial clinical presentations, neuroradiological results, timing and signs of NDDA, and outcomes between cerebellar strokes were descriptively analyzed. Logistic regression model was applied for determining the significant predictors of NDDA from initial clinical presentations.Results: 74 of 100 patients were eligible. They comprised of 42 (57%) cerebellar ischemia (CI) and 32 (43%) cerebellar hemorrhage (CH). Elevated diastolic blood pressure (DBP) and the neuro-radiological evidences suggesting increased posterior cranial fossa pressure were significantly prevalent in neurological deterioration patients. NDDA was found in 31 patients (42%) without significant difference between CI and CH. 42 (56.8%) patients had poor neurological outcomes. The independent predictors for NDDA were DBP B 120 mmHg (adjusted odds ratio [adj. OR] 15.39, 95% CI 1.58-149.59; p = 0.004), time from onset to arrival (adj. OR 0.98, 95% CI 0.97-1.00; p = 0.044), and hemispheric cerebellar signs (adj. OR 0.22, 95% CI 0.06-0.75; p = 0.012).Conclusions: CH was not an independent predictor of NDDA in overall cerebellar strokes. Only high DBP predicted NDDA, whereas time to arrival and hemispheric signs showed protective impact.
A Simple Scoring Algorithm for Health Literacy in Community-Dwelling Older Adults
Authors: Hou Wen-Hsuan , Chang Yao-Mao , Chen Mu-Jean , Tsai Han-Wei , Su Chien-Tien , Han Der-Sheng , Chan Ding-Cheng , Kuo KEN N. , Li Chung-Yi 
Published: August 2020

Abstract
Background:

Health literacy (HL) is the capacity to access, understand, appraise, and apply health information to make appropriate health decisions. This study aimed to establish a predictive algorithm for identifying community-dwelling older adults at a high risk of low HL.
Methods:

A total of 648 older adults were included and 85% was used to generate the prediction model for scoring algorithm while 15% was used to test the fitness of the model. Pearson’s chi-squared test and multiple logistic regression were used to identify the factors associated with the HL level. An optimal cutoff point was identified based on the maximum sensitivity and specificity.
Results:

350 patients (54.6%) was classified as the low HL level. Twenty-four variables were identified for significantly differentiating between high and low HL. Eight factors including socio-environmental determinant and health outcome related factors significantly predicted low HL. The scoring algorithm yielded an area under the curve of 0.71 and optimal cutoff of 5 represented mediocre sensitivity (62.0%) and good specificity (76.2%).
Conclusion:

This simple scoring algorithm efficiently and effectively identify community-dwelling older adults a low HL.
Fall Awareness Behaviour And Its Associated Factors Among Community Dwelling Older Adults
Authors: WEN GOH JING , Singh Devinder Kaur Ajit , MESBAH NORMALA , HANAFI ANIS AFIFA MOHD , AZWAN ADLYN FARHANA 
Published: August 2020

Abstract
Falls are one of the major causes of mortality and morbidity in older adults. However, despite adoption of prevention strategies, the number of falls in older adults has not declined. The aim of this study was to examine fall awareness behaviour and its associated factors. A total of 140 community dwelling older adults (mean age of 70.69±4.3 years) participated in this study. Physical performance was assessed using timed up and go(TUG), gait speed(GS), chair stand and hand grip tests. Fall Awareness Behaviour (FaB) and Fall Risk Assessment Questionnaires (FRAQ) were administered to assess behaviours and fall prevention knowledge respectively. Stepwise linear regression analysis showed that the practice of fall awareness behaviours (R2=.256) was significantly associated with being male [95% C.I: 2.178 to 7.789, p<.001], having lower BMI [95% C.I: -0.692 to -0.135, p<.05], living with family [95% C.I: 0.022 to 5.953, p<.05] and those having higher functional mobility [95% C.I: -2.008 to -0.164, p<.05]. Fall awareness behaviours should be emphasized among older females, those with lower functional mobility, higher BMI and living alone.
Inhibition of Mitochondrial Fission Reverses the Immunoescape of Solid Tumors via IRE1α-XBP-1s-TPP2 axis
Authors: Li Jinsong , Lei Xinyuan , Ruan Yi , Lin Hsinyu , Chen Weixiong , Xie Shule , Li Qunxing , Wang Jue , Lin Huayue , Zhu Xiaofeng , Yuan Xiaoqing , Ou Zhanpeng , Tian Tian , Lv Xiaobin , Fu Sha , Zhu Xiaorui , Zhou Jian , Pan Guokai , Xia Xin , Tannous Bakhos , Ferrone Soldano , Fan Song 
Published: August 2020

Abstract
Hypoexpression of human major histocompatibility complex (MHC) class I is widely known to be an important strategy of immune evasion in most cases of malignancies that lead to poor prognosis. We demonstrated that mitochondrial dynamics can be exploited as an efficient target in regulating MHC-I expression and cancer immunogenicity. Clinically, MHC-I expression and fragmentation of mitochondria are both closely associated to patient survival but are negatively correlated to one another. Mechanistically, it was observed that endoplasmic reticulum (ER) stress, an integrated signal transduction pathway activated in most rapidly proliferating tumor cells, played a crucial role in connecting mitochondrial fragmentation and cancer cell immunogenicity particularly via the IRE1α-XBP-1 s axis. XBP-1 s, which is activated by imbalanced mitochondrial fission and prolonged oxidative stress, served as a potent transcription factor, promoted the expression of aminopeptidase TPP2 and destructed the applicable antigenic peptide to impede MHC-I complex maturation and the activation of adaptive immune system upon cancer antigen. Our findings highlight the importance of mitochondrial dynamics in determining solid tumor immunogenicity and suggest that mediating mitochondrial fragmentation might provide a novel approach in anti-tumor immunotherapy.
Avoiding the unintended consequences of climate change mitigation for African river basins
Authors: Castelletti Andrea , Giuliani Matteo , Lamontagne Jonathan , Hejazi Mohamad , Reed Patrick 
Published: August 2020

Abstract
Emerging climate change mitigation policies focus on the implementation of global measures relying on carbon prices to attain rapid emissions reductions, with limited consideration for the impacts of global policies at local scales. Here, we use the Zambezi River Basin in Southern Africa to demonstrate how local multisector dynamics across interconnected Water-Energy-Food (WEF) systems are impacted by global climate change mitigation policies. Our analysis provides quantitative evidence of the unintended vulnerabilities that emerge for this basin across a broad array of potential climate and socio-economic futures. Our results indicate that climate change mitigation policies related to land use change emissions can have negative side effects on local water demands, generating increased risks for failures across all the components of the WEF systems in the Zambezi River Basin. Analogous vulnerabilities could impact many river basins in Southern and Western Africa. It is critical to connect global climate change mitigation policies to local regional dynamics to better navigate the full range of possible future scenarios while supporting policy makers in prioritizing sustainable mitigation and adaptation solutions.
Alimentary System is Directly Attacked by SARS-COV-2 and Further Prevent Immune Dysregulation Caused by COVID-19
Authors: Chen Sai , Zhou Jing , UG Xiaoqi Ou , Cheng Wei , Qin Yun , Guo Yingqiang , Jiang Yunhan 
Published: August 2020

Abstract
Background SARS-COV-2 has caused digestive system symptom, whereas the role of which remains equivocal.Methods Patients with COVID-19 were classified into 4 groups according to symptom. The study traced the onset and duration of symptoms, compared laboratory examinations among each group and conducted bioinformatic analysis. Immune indices were further analyzed.Results By March 16, 25 patients with COVID-19 (3 with digestive system symptom, 14 with respiratory system symptom, 4 with combined symptom and 4 asymptomatic) and 13 with suspect COVID-19 were admitted to West China Hospital, Sichuan University. Digestive system symptom group had the highest level of ESR (mm/h, P༜0.0001), serum ferritin (ng/ml, P༜0.0001), hepatic enzymes (P༜0.05), and retentive lymphocyte count/percentage (P༜0.05) and its subsets (P༜0.05). Combined group (respiratory combined with subsequent digestive system symptom) had the highest level of IL-6 (pg/ml, P = 0.0046), CRP (mg/L, P = 0.0004) and moderate lymphocyte depletion while respiratory system symptom group and asymptomatic group suffered the most from lymphocyte depletion (P༜0.05). Bioinformatic analysis indicated co-expression of binding related proteins of SARS-COV-2 (ACE2, TMPRSS2 and Furin) in small intestine. CD147 was extensively expressed in alimentary tract. CTSL, PIKfyve, TPC2 and CTSB could be detected with ≥ moderate expressions in a variety of organs including alimentary system.Conclusions Alimentary system is directly attacked by SARS-COV-2 other than hyperinflammation and immune dysregulation. Involvement of alimentary system might further protect mild and moderate cases from lymphocyte depletion caused by COVID-19.