bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comorbid neuropathological diagnoses in early vs late-onset Alzheimer’s disease
Authors: Spina Salvatore , Joie Renaud La , Petersen Cathrine , Nolan Amber L. , Cuevas Deion , Cosme Celica , Hepker Mackenzie , Hwang Ji-Hye , Miller Zachary A. , Huang Eric J. , Karydas Anna M. , Grant Harli , Boxer Adam L. , Gorno-Tempini Maria Luisa , Rosen Howard J. , Kramer Joel H. , Miller Bruce L. , Seeley William W. , Rabinovici Gil D. , Grinberg Lea T. 
Published: October 2020

AbstractCopathologies play an important role in the expression of the AD clinical phenotype and may influence treatment efficacy. Early-onset AD (EOAD), defined as manifesting before age 65, has been viewed as a relatively pure form of AD with a more homogenous neuropathological substrate. We sought to compare the frequency of common neuropathological diagnoses in a consecutive autopsy series of 96 patients with EOAD (median age of onset = 55 years, 44 females) and 48 with late-onset AD (LOAD) (median age of onset = 73 years, 14 females). The UCSF Neurodegenerative Disease Brain Bank database was reviewed to identify patients with a primary pathological diagnosis of AD. Prevalence and stage of Lewy body disease (LBD), limbic age-related TDP-43 encephalopathy (LATE), argyrophilic grain disease (AGD), hippocampal sclerosis (HS), cerebral amyloid angiopathy (CAA), vascular brain injury (VBI) and aging-related tau astrogliopathy (ARTAG) were compared between the two cohorts. We found at least one non-AD pathological diagnosis in 98% of patients with EOAD (versus 100% of LOAD), and the number of comorbid diagnoses per patient was lower in EOAD than in LOAD (median=2 versus 3, Mann-Whitney Z=3.00, p=0.002). LBD and CAA were common in both EOAD and LOAD (CAA: 86% versus 79%, Fisher exact p=0.33; LBD: 49% versus 42%, p=0.48, respectively), although amygdala-predominant LBD was more commonly found in EOAD than LOAD (22% versus 6%, p=0.02). In contrast, LATE (35% versus 8%, p<0.001), HS (15% versus 3%, p=0.02), AGD (58% versus 41%, p=0.052), and VBI (65% versus 39%, p=0.004) were more common in LOAD than EOAD, respectively. The number of copathologies predicted worse cognitive performance at the time of death on MMSE (1.4 points/pathology (95%CI [−2.5, −0.2]) and Clinical Dementia Rating – Sum of Boxes (1.15 point/pathology, 95%CI [0.45, 1.84]), across the EOAD and the LOAD cohorts. Prevalence of at least one ApoE e4 allele was similar across the two cohorts (52%) and was associated with a greater number of copathologies (+0.42, 95%CI [0.01, 0.82], p=0.04), independent of age of symptom onset. Our findings suggest that non-AD pathological diagnoses play an important role in the clinical phenotype of EOAD with potentially significant implications for clinical practice and clinical trials design.
Population attributable fraction for continuously distributed exposures
Authors: Ferguson John , Maturo Fabrizio , Yusuf Salim , O’Donnell Martin 
Published: October 2020

AbstractWhen estimating population attributable fractions (PAF), it is common to partition a naturally continuous exposure into a categorical risk factor. While prior risk factor categorization can help estimation and interpretation, it can result in underestimation of the disease burden attributable to the exposure as well as biased comparisons across different exposures and risk factors. Here, we propose sensible PAF estimands for continuous exposures under a potential outcomes framework. In contrast to previous approaches, we incorporate estimation of the minimum risk exposure value (MREV) into our procedures. While for exposures such as tobacco usage, a sensible value of the MREV is known, often it is unknown and needs to be estimated. Second, in the setting that the MREV value is an extreme-value of the exposure lying in the distributional tail, we argue that the natural estimator of PAF may be both statistically biased and highly volatile; instead, we consider a family of modified PAFs which include the natural estimate of PAF as a limit. A graphical comparison of this set of modified PAF for differing risk factors may be a better way to rank risk factors as intervention targets, compared to the standard PAF calculation. Finally, we analyse the bias that may ensue from prior risk factor categorization, examining whether categorization is ever a good idea, and suggest interpretations of categorized-estimands within a causal inference setting.
COVID-19 neutralizing antibodies predict disease severity and survival
Authors: Garcia-Beltran Wilfredo F. , Lam Evan C. , Astudillo Michael G. , Yang Diane , Miller Tyler E. , Feldman Jared , Hauser Blake M. , Caradonna Timothy M. , Clayton Kiera L. , Nitido Adam D. , Murali Mandakolathur R. , Alter Galit , Charles Richelle C. , Dighe Anand , Branda John A. , Lennerz Jochen K. , Lingwood Daniel , Schmidt Aaron G. , Iafrate A. John , Balazs Alejandro B. 
Published: October 2020

SUMMARYCOVID-19 exhibits variable symptom severity ranging from asymptomatic to life-threatening, yet the relationship between severity and the humoral immune response is poorly understood. We examined antibody responses in 113 COVID-19 patients and found that severe cases resulting in intubation or death exhibited increased inflammatory markers, lymphopenia, and high anti-RBD antibody levels. While anti-RBD IgG levels generally correlated with neutralization titer, quantitation of neutralization potency revealed that high potency was a predictor of survival. In addition to neutralization of wild-type SARS-CoV-2, patient sera were also able to neutralize the recently emerged SARS-CoV-2 mutant D614G, suggesting protection from reinfection by this strain. However, SARS-CoV-2 sera was unable to cross-neutralize a highly-homologous pre-emergent bat coronavirus, WIV1-CoV, that has not yet crossed the species barrier. These results highlight the importance of neutralizing humoral immunity on disease progression and the need to develop broadly protective interventions to prevent future coronavirus pandemics.
Genome-Wide Polygenic Risk Score Identifies Individuals at Elevated Parkinson’s Disease Risk
Authors: Han Yingnan , Teeple Erin , Shankara Srinivas , Sadeghi Mahdiar , Zhu Cheng , Liu Dongyu ,   FinnGen, Wang Clarence , Frau Francesca , Klinger Katherine W. , Madden Stephen L. , Rajpal Deepak , Sardi S. Pablo , Kumar Dinesh 
Published: October 2020

SUMMARYParkinson’s Disease (PD) is the second most common and fastest-growing neurological disorder. Polygenic Risk Scores (PRS) using hundreds to thousands of PD-associated variants support polygenic heritability. Here, for the first time, we apply a genome-wide polygenic risk score approach using 6.2 million variants to compute a PD genome-wide polygenic risk score (PD-GPRS) via the LDPred algorithm. PD-GPRS validation and testing used Accelerating Medicines Partnership – Parkinson’s Disease (AMP-PD) and FinnGen Consortia genomic data from 1,654 PD Cases and 79,123 Controls. PD odds for the top 8%, 2.5%, and 1% of PD-GPRS were three-, four-, and seven times greater compared with lower percentiles, respectively (p<1e-10). PD age of onset and MDS-UPDRS motor scores also differed by PD-GPRS decile. Enrichment for phagosome related, dopamine signaling, immune related, and neuronal signaling pathways was found for genes nearest high PD-GPRS variants identified by MAF analysis. PD-GPRS offers a promising screening tool to identify high-risk individuals for preventive lifestyle or new drug therapy trials.In BriefIn Han and Teeple et al., Parkinson’s Disease inherited risk is quantified by a genome-wide polygenic risk score (PD-GPRS) approach using 6.2 million variants and data from 80,777 individuals. For the top 2.5% and 1% of PD-GPRS, individuals had five- and seven-fold greater odds of PD, respectively. PD-GPRS was found to be associated with overall PD risk, earlier age of onset, and MDS-UPDRS motor scores. Genes nearest to variants observed at higher frequencies among high-GPRS individuals are enriched for PD-implicated pathways.HIGHLIGHTS-Parkinson’s Disease genome-wide polygenic risk score (PD-GPRS) calculated from 6.2 million variants identifies individuals with inherited clinically significant increased neurodegeneration risk.-Top percentile PD-GPRS individuals were found to have up to seven-fold greater odds of PD and earlier age at PD diagnosis.-PD-GPRS scores correlated with all-subjects cohort mean MDS-UPDRS motor scores.-Pathway analysis of genes adjacent to frequently occurring variants in the high PD-GPRS population identified polygenic risk contributions for variations in PD-implicated pathways including dopamine signaling, immune responses, and autophagy pathways.
A Study on the Effects of Containment Policies and Vaccination on the Spread of SARS-CoV-2
Authors: Bokharaie Vahid S. 
Published: October 2020

AbstractThis paper presents a method to predict the spread of the SARS-CoV-2 in a population with a known age-structure, and then, to quantify the effects of various containment policies, including those policies that affect each age-group differently. The model itself is a compartmental model in which each compartment is divided into a number of age-groups. The parameters of the model are estimated using an optimisation scheme and some known results from the theory of monotone systems such that the model output agrees with some collected data on the spread of SARS-CoV-2.To highlight the strengths of this framework, a few case studies are presented in which different populations are subjected to different containment strategies. They include cases in which the containment policies switch between scenarios with different levels of severity. Then a case study on herd immunity due to vaccination is presented. And then it is shown how we can use this framework to optimally distribute a limited number of vaccine units in a given population to maximise their impact and reduce the total number of infectious individuals.MSC subclass92C60, 92C50
Tobacco control policies and smoking cessation treatment utilization: a moderated mediation analysis
Authors: Thrul Johannes , Riehm Kira E. , Cohen Joanna E. , Alexander G. Caleb , Vernick Jon S. , Mojtabai Ramin 
Published: October 2020

AbstractBackgroundTobacco policies, including clean indoor air laws and cigarette taxes, increase smoking cessation in part by stimulating the use of cessation treatments. We explored whether the mediating effect of such treatments varies across socio-demographic groups.MethodsWe used data from 62,165 U.S. adult participants in the 2003 and 2010/11 Current Population Survey-Tobacco Use Supplement (CPS-TUS) who reported smoking cigarettes during the past year. Building on prior structural equation models used to quantify the degree to which smoking cessation treatments (prescription medications, nicotine replacement therapy, counselling/support groups, quitlines, and internet resources) mediated the association between clean indoor air laws, cigarette excise taxes, and recent smoking cessation, we added selected moderators to each model to investigate whether mediation effects varied by sex, race/ethnicity, education, income, and health insurance status.ResultsFor clean indoor air laws, the mediating effect of prescription medication and nicotine replacement therapies varied significantly between racial/ethnic, age, and education groups in 2003. However, none of these moderation effects remained significant in 2010/11. For cigarette excise taxes in 2010/2011, the mediating effect of counseling was stronger in older adults; whereas, the mediating effect of prescription medications tended to be stronger in younger adults. No other moderator reached statistical significance. Smoking cessation treatments did not mediate the effect of taxes on smoking cessation in 2003 and were not included in these analyses.ConclusionsSociodemographic differences in how smoking cessation treatment use mediates between clean indoor air laws and smoking cessation have decreased from 2003 to 2010/11. In most cases, policies appear to stimulate smoking cessation treatment use similarly across varied sociodemographic groups.
Biomimetic Virus-like Particles as SARS-CoV-2 Positive Controls for RT-PCR Diagnostics
Authors: Chan Soo Khim , Du Pinyi , Ignacio Karole , Metha Sanjay , Newton Isabel G. , Steinmetz Nicole F. 
Published: October 2020

ABSTRACTCoronavirus disease 2019 (COVID-19) is a highly transmissible disease that has affected more than 90% of the countries worldwide. At least 17 million individuals have been infected, and some countries are still battling first or second waves of the pandemic. Nucleic acid tests, especially reverse-transcription polymerase chain reaction (RT-PCR), have become the workhorse for early detection of COVID-19 infection. Positive controls for the molecular assays have been developed to validate each test and to provide high accuracy. However, most available positive controls require cold-chain distribution and cannot serve as full-process control. To overcome these shortcomings, we report the production of biomimetic virus-like particles (VLPs) as SARS-CoV-2 positive controls. A SARS-CoV-2 detection module for RT-PCR was encapsidated into VLPs from a bacteriophage and a plant virus. The chimeric VLPs were obtained either by in vivo reconstitution and co-expression of the target detection module and coat proteins or by in vitro assembly of purified detection module RNA sequences and coat proteins. These VLP-based positive controls mimic SARS-CoV-2 packaged RNA while being non-infectious. Most importantly, we demonstrated that the positive controls are scalable, stable, and can serve broadly as controls, from RNA extraction to PCR in clinical settings.Table of contents graphic
Development and pre-clinical characterization of two therapeutic equine formulations towards SARS-CoV-2 proteins for the potential treatment of COVID-19
Authors: León Guillermo , Herrera María , Vargas Mariángela , Arguedas Mauricio , Sánchez Andrés , Segura Álvaro , Gómez Aarón , Solano Gabriela , Corrales-Aguilar Eugenia , Risner Kenneth , Narayanan Aarthi , Bailey Charles , Villalta Mauren , Hernández Andrés , Sánchez Adriana , Cordero Daniel , Solano Daniela , Durán Gina , Segura Eduardo , Cerdas Maykel , Umaña Deibid , Moscoso Edwin , Estrada Ricardo , Gutiérrez Jairo , Méndez Marcos , Castillo Ana Cecilia , Sánchez Laura , Gutiérrez José María , Díaz Cecilia , Alape Alberto 
Published: October 2020

AbstractIn the current global emergency due to SARS-CoV-2 outbreak, passive immunotherapy emerges as a promising treatment for COVID-19. Among animal-derived products, equine formulations are still the cornerstone therapy for treating envenomations due to animal bites and stings. Therefore, drawing upon decades of experience in manufacturing snake antivenom, we developed and preclinically evaluated two anti-SARS-CoV-2 polyclonal equine formulations as potential alternative therapy for COVID-19. We immunized two groups of horses with either S1 (anti-S1) or a mixture of S1, N, and SEM mosaic (anti-Mix) viral recombinant proteins. Horses reached a maximum anti-viral antibody level at 7 weeks following priming, and showed no major adverse acute or chronic clinical alterations. Two whole-IgG formulations were prepared via hyperimmune plasma precipitation with caprylic acid and then formulated for parenteral use. Both preparations had similar physicochemical and microbiological quality and showed ELISA immunoreactivity towards S1 protein and the receptor binding domain (RBD). The anti-Mix formulation also presented immunoreactivity against N protein. Due to high anti-S1 and anti-RBD antibody content, final products exhibited highin vitroneutralizing capacity of SARS-CoV-2 infection, 80 times higher than a pool of human convalescent plasma. Pre-clinical quality profiles were similar among both products, but clinical efficacy and safety must be tested in clinical trials. The technological strategy we describe here can be adapted by other producers, particularly in low- and middle-income countries.
METAMVGL: a multi-view graph-based metagenomic contig binning algorithm by integrating assembly and paired-end graphs
Authors: Zhang Zhenmiao , Zhang Lu 
Published: October 2020

AbstractMotivationDue to the complexity of metagenomic community,de novoassembly on next generation sequencing data is commonly unable to produce microbial complete genomes. Metagenomic binning is a crucial task that could group the fragmented contigs into clusters based on their nucleotide compositions and read depths. These features work well on the long contigs, but are not stable for the short ones. Assembly and paired-end graphs can provide the connectedness between contigs, where the linked contigs have high chance to be derived from the same clusters.ResultsWe developed METAMVGL, a multi-view graph-based metagenomic contig binning algorithm by integrating both assembly and paired-end graphs. It could strikingly rescue the short contigs and correct the binning errors from dead ends subgraphs. METAMVGL could learn the graphs’ weights automatically and predict the contig labels in a uniform multi-view label propagation framework. In the experiments, we observed METAMVGL significantly increased the high-confident edges in the combined graph and linked dead ends to the main graph. It also outperformed with many state-of-the-art binning methods, MaxBin2, MetaBAT2, MyCC, CONCOCT, SolidBin and Graphbin on the metagenomic sequencing from simulation, two mock communities and realSharondata.Availability and implementationThe software is available athttps://github.com/ZhangZhenmiao/METAMVGL.
The central THαβ immunity associated cytokine: IL-10 has a strong anti-tumor ability toward established cancer models in vivo and toward cancer cells in vitro
Authors: Hu Wan-Chung 
Published: October 2020

AbstractCancer immunotherapy is a promising new approach for cancer treatment. We propose to use a new host immunological pathway: THαβ immunity for cancer treatment. THαβ immunity is a natural host immunity which can be used IFN-α/β and its major effectors are IL-10 and IL-15. Thus, we here used these cytokines for treatment both in a mice breast cancer 4T1 model and in a neuroblastoma NXS2 model. 4T1 cells and NXS2 cells were inoculated subcutaneously to wild type BALB/c female mice and AJ mice, respectively. Both Cytokines and an antibody treatment with variable dosages were given. Our results show that IL-10 and IL-15 treatments have significant effects on not only tumor volume shrinkage and but also on mice survival. However, IFN-γ even worsens the tumor volume and mice survival. Antibodies plus IL-10 is no better than IL-10 alone for cancer immunotherapy. This can be due to GD2 antigen expression on immune cells. Moreover, an anti-GD2 antibody could harm immune cells themselves. We found that IL-10 has direct toxicity on tumor cells in vitro. Our results conclude that using THαβ immunity is a good strategy for cancer immunotherapy.
WHIRLY1 of barley and maize share a PRAPP motif conferring nucleoid compaction
Authors: Oetke Svenja , Scheidig Axel J. , Krupinska Karin 
Published: October 2020

ABSTRACTWHIRLY1 in barley was shown to be a major architect of plastid nucleoids. Its accumulation in cells ofE. colicoincided with an induction of nucleoid compaction and growth retardation. While WHIRLY1 of maize had similar effects onE. colicells, WHIRLY1 proteins of Arabidopsis and potato a well as WHIRLY2 proteins had no impact on nucleoid compaction inE. coli. By mutagenesis ofHvWHIRLY1the PRAPP motif at the N-terminus preceding the highly conserved WHIRLY domain was identified to be responsible for the nucleoid compacting activity of HvWHIRLY1 in bacteria. This motif is found in WHIRLY1 proteins of most members of the Poaceae family, but neither in the WHIRLY2 proteins of the family nor in any WHIRLY protein of eudicot species such asArabidopsis thaliana. This finding indicates that a subset of the monocot WHIRLY1 proteins has acquired a specific function as nucleoid compacters by sequence variation in the N-terminal part preceding the conserved WHIRLY domain and that in different groups of higher plants the compaction of nucleoids is mediated by other proteins.
Effect of high proportion concentrate dietary on Yak jejunal structure, physiological function and protein composition during cold season
Authors: Jia Jianlei , Liang Chunnian , Wu Xiaoyun , Xiong Lin , Bao Pengjia , Chen Qian , Yan Ping 
Published: October 2020

AbstractThe current study aimed to investigate the damage of long-term high concentrate diet feeding pattern on Yak jejunal structure, physiological function and protein composition during cold season. Twelve Datong male Yak (Bos grunniens) with the same age from cold season were randomly selected and slaughtered to determine Yak jejunal digestive enzyme activity, morphology and protein composition on different feeding patterns in Tibetan Plateau. The results showed that Yak jejunum digestive enzyme activity and morphology of grazing reared group were better than those in the intensively reared group. A total of 96 differentially expressed proteins were identified by label-free Mass Spectrometry (MS), which could be concluded to two predominant themes: protein structure and inflammatory response. Nine differentially expressed proteins were correlated in Yak jejunum damage in different feeding patterns. According to our study, feeding patterns resulted in the differences in Yak jejunum physiological function, morphology and protein composition. Our results confirmed that feeding of long-term high concentrate diet could damage the jejunum epithelial morphology and function.
Genome-wide characterization and expression profiling of B3 superfamily during flower induction stage in pineapple (Ananas comosusL.)
Authors: Ruan Cheng Cheng , Chen Zhe , Hu Fu Chu , Wang Xiang He , Guo Li Jun , Fan Hong Yan , Luo Zhi Wen , Zhang Zhi Li 
Published: October 2020

AbstractThe B3 superfamily is a plant-specific family, which involves in growth and development process. By now, the identification of B3 superfamily in pineapple (Ananas comosus) has not reported. In this study, 57B3genes were identified and further phylogenetically classified into five subfamilies, all genes contained B3 domain. Chromosomal localization analysis revealed that 54 of 57AcB3genes were located on 21 chromosomes.Collinearity analysis indicated that the segmental duplication was the main event in the evolution of B3 gene superfamily and most of them were under purifying selection. Moreover, there were 7 and 39 pairs of orthologous B3s were identified between pineapple andArabidopsisor rice, respectively, which indicated the closer genetic relationship between pineapple and rice. Most genes hadcis-element of abscisic acid, ethylene, MeJA, light, and abiotic stress. qRT-PCR showed that the expression level of mostAcB3genes were up-regulated within 1 d after ethephon treatment and expressed high level in flower bud differentiation period in stem apex. This study provide a comprehensive understanding ofAcB3sand a basis for future molecular studies of ethephon induced pineapple flowering.