bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of amyloid and APOE4 on medial temporal lobe subregions in cognitively unimpaired elderly
Authors: de Flores Robin , Demeilliez-Servouin Solène , Kuhn Elizabeth , Chauveau Léa , Landeau Brigitte , Delcroix Nicolas , Gonneaud Julie , Chételat Gaël 
Published: January 2022

AbstractMedial temporal lobe (MTL) sub-structures are differentially affected in early Alzheimer’s disease (AD), with a specific involvement of the entorhinal cortex (ERC), the perirhinal cortex (PRC) and CA1. However, the impact of amyloid (Aβ) pathology and APOE ε4 on MTL subregional atrophy remains relatively unknown. Our aim was to uncover these effects to further our understanding of the mechanisms underlying MTL atrophy in a population at-risk for AD.We used baseline data from 130 unimpaired older adults (mean age: 68.9 ± 3.8 years) from the Age-Well randomized controlled trial for whom high-resolution structural MRI (T2-weighted; 0.4×0.4×2.5mm3), amyloid-PET (Florbetapir) and APOE genotype were available. Participants were dichotomized into amyloid positive (Aβ+, n=27) and negative (Aβ-, n=103), and APOE ε4 carrier (ε4+, n=35) and non-carriers (ε4-, n=95). Hippocampal subfield (CA1, CA2, CA3, dentate gyrus [DG], subiculum [SUB]) and extra-hippocampal region (ERC, Brodmann area [BA] 35 and 36, and parahippocampal cortex [PHC]) volumes were estimated using ASHS and normalized by total intracranial volume. For each subregion, group comparisons were performed (Aβ+ vs Aβ- and ε4+ vs ε4-) using ANCOVAs, including age, sex and education as covariates. Interactions with age (i.e., Aβ status * age and APOE ε4 status * age) were also investigated for each subregion.No significant differences were observed between Aβ+ and Aβ-, nor between ε4+ and ε4-. However, a significant Aβ status * age interaction were observed for CA1 (p<0.05), where volumes were negatively associated with age in the Aβ+ group only. In addition, significant APOE ε4 status * age interactions were found for CA1, SUB, ERC, DG and the whole hippocampus (p<0.05), where volumes were negatively associated with age in the ε4+ group only.Overall, our analyses showed that both Aβ and APOE ε4 status interact with age on CA1, which is known to be specifically atrophied in early AD. In addition, APOE ε4 status mediated the effects of age on other subregions (SUB, ERC, DG), suggesting a more important contribution of APOE ε4 than amyloid to MTL atrophy in cognitively unimpaired population. These results are particularly important to develop MRI-based biomarkers to detect early AD and further our understanding of the mechanisms underlying MTL atrophy.
“I feel like my body is broken”: Exploring the experiences of people living with long COVID
Authors: Wurz Amanda , Culos-Reed S. Nicole , Franklin Kelli , DeMars Jessica , Wrightson James G. , Twomey Rosie 
Published: January 2022

AbstractBackgroundLong COVID, an illness affecting a subset of individuals after COVID-19, is distressing and poorly understood. Exploring the experiences of people with long COVID could help inform current conceptualizations of the illness, guide supportive care strategies, and validate patients’ perspectives on the condition. Thus, the objective of this study was to better understand and explore individuals’ experiences with long COVID and commonly reported symptoms, using qualitative data collected from open-ended survey responses.MethodsData were collected from adults living with long COVID following a confirmed or suspected SARS-CoV-2 infection who participated in a larger observational, online survey. Within the larger survey, participants had the option of answering seven open-ended items. Data from the open-ended items were analyzed following guidelines for reflective thematic analysis.ResultsFrom the 213 who were included in the online survey, 169 participants who primarily self-identified as women (88.2%), aged 40-49 (33.1%), and who had been experiencing long COVID symptoms for ≥ 6 months (58.6%) responded to the open-ended questions. Four overlapping and interconnected themes were identified: (1) My long COVID symptoms are numerous, hard to describe, and debilitating, (2) All aspects of my day-to-day functioning have been impacted, (3) I can no longer be physically active, and (4) I keep asking for help, but no one is listening, and very little is working.ConclusionFindings highlight the complex nature of long COVID and show the ways in which individuals affected by the illness are negatively impacted. Participants recounted struggling and altering their daily activities while managing relapsing-remitting symptoms, an uncertain prognosis, lost pre-COVID identities, and a healthcare system (that does not always offer guidance nor take them seriously). More support and recognition for the condition are needed to help this cohort navigate the process of adapting to long COVID.
Molecular diagnosis of SARS-CoV-2: a validation of saliva samples
Authors: da Silva Natalia Verissimo Rodrigues , Neves Pereira Samyra Stéphane , Kavalco Karine Frehner , Menegídio Fabiano Bezerra , Medeiros-Santana Luanda , Visôtto Liliane Evangelista , Pasa Rubens 
Published: January 2022

ABSTRACTNasopharyngeal swabs are the most used in sample collecting for covid-19 tests in SARS-CoV-2 molecular diagnosis. However, this sampling method presents some disadvantages, since, in addition to being dependent on imported materials, it is invasive, causes discomfort in patients, and, presents the risk of contamination for the medical collection team. This study aimed at validating saliva samples to obtain viral RNA to be used in the molecular diagnostic test for SARS-CoV-2 using the RT-qPCR technique. Results presented 93,44% concordance in in comparison to nasopharyngeal swabs sampling. Therefore, saliva samples used in SARS-CoV-2 RT-qPCR detection tests presented consistent results.
ECS1 and ECS2 regulate polyspermy and suppress the formation of haploid plants by promoting double fertilization
Authors: Mao Yanbo , Nakel Thomas , Serbes Isil Erbasol , Tekleyohans Dawit G. , Joshi Saurabh , Baum Thomas , Groß-Hardt Rita 
Published: January 2022

AbstractIn flowering plants, the number of pollen tubes that provide sperm cells to the female gametes is restricted by a pollen tube block. This safeguard mechanism is only activated after successful fertilization of both female gametes and involves the disintegration of pollen tube attracting synergid cells. Yu and coworkers previously reported that the endopeptidase ECS1 and ECS2, which are secreted by fertilized egg cells, prevent the attraction of supernumerary pollen tubes by cleaving the pollen tube attractant LURE11. Here we report on an earlier defect in ecs1 ecs2 mutants that is manifested by single rather than double fertilization of either egg or central cell. The defect is accompanied by a delay in synergid disintegration providing an alternative explanation for the extra pollen tubes observed in the double mutant. These results are corroborated by our finding that ecs1 ecs2 plants segregate both, haploid as well as polyspermy derived triploid plants.
AbLang: An antibody language model for completing antibody sequences
Authors: Olsen Tobias H. , Moal Iain H. , Deane Charlotte M. 
Published: January 2022

AbstractMotivationGeneral protein language models have been shown to summarise the semantics of protein sequences into representations that are useful for state-of-the-art predictive methods. However, for antibody specific problems, such as restoring residues lost due to sequencing errors, a model trained solely on antibodies may be more powerful. Antibodies are one of the few protein types where the volume of sequence data needed for such language models is available, for example in the Observed Antibody Space (OAS) database.ResultsHere, we introduce AbLang, a language model trained on the antibody sequences in the OAS database. We demonstrate the power of AbLang by using it to restore missing residues in antibody sequence data, a key issue with B-cell receptor repertoire sequencing, over 40% of OAS sequences are missing the first 15 amino acids. AbLang restores the missing residues of antibody sequences better than using IMGT germlines or the general protein language model ESM-1b. Further, AbLang does not require knowledge of the germline of the antibody and is seven times faster than ESM-1b.Availability and ImplementationAbLang is a python package available at https://github.com/oxpig/AbLang.
Uncovering hidden assembly artifacts: when unitigs are not safe and bidirected graphs are not helpful
Authors: Rahman Amatur , Medvedev Paul 
Published: January 2022

AbstractRecent assemblies by the T2T and VGP consortia have achieved significant accuracy but required a tremendous amount of effort and resources. More typical assembly efforts, on the other hand, still suffer both from mis-assemblies (joining sequences that should not be adjacent) and from under-assemblies (not joining sequences that should be adjacent). To better understand the common algorithm-driven causes of these limitations, we investigated the unitig algorithm, which is a core algorithm at the heart of most assemblers. We prove that, contrary to popular belief, even when there are no sequencing errors, unitigs are not always safe (i.e. they are not guaranteed to be substrings of the sequenced genome). We also prove that the unitigs of a bidirected de Bruijn graph are different from those of a doubled de Bruijn graph and, contrary to our expectations, result in under-assembly. Using experimental simulations, we then confirm that these two artifacts exist not only in theory but also in the output of widely used assemblers. In particular, when coverage is low then even error-free data results in unsafe unitigs; also, unitigs may unnecessarily split palindromes in half if special care is not taken. To the best of our knowledge, this paper is the first to theoretically predict the existence of these assembler artifacts and confirm and measure the extent of their occurrence in practice.
Development and validation of Arc nanobodies: new tools for probing Arc dynamics and function
Authors: Ishizuka Yuta , Mergiya Tadiwos F. , Baldinotti Rodolfo , Xu Ju , Hallin Erik I. , Markússon Sigurbjörn , Kursula Petri , Bramham Clive R. 
Published: January 2022

AbstractActivity-regulated cytoskeleton-associated (Arc) protein plays key roles in long-term synaptic plasticity, memory, and cognitive flexibility. However, an integral understanding of Arc mechanisms is lacking. Arc is proposed to function as an interaction hub in neuronal dendrites and the nucleus, yet Arc can also form retrovirus-like capsids with proposed roles in intercellular communication. Here, we sought to develop anti-Arc nanobodies (ArcNbs) as new tools for probing Arc dynamics and function. Six ArcNbs representing different clonal lines were selected from immunized alpaca. Immunoblotting with recombinant ArcNbs fused to a small ALFA-epitope tag demonstrated binding to recombinant Arc as well as endogenous Arc from rat cortical tissue. ALFA-ArcNb also provided efficient immunoprecipitation of stimulus-induced Arc after carbachol-treatment of SH-SY5Y neuroblastoma cells and induction of long-term potentiation in the rat dentate gyrus in vivo. Epitope mapping showed that all Nbs recognize the Arc C-terminal region containing the retroviral Gag capsid homology domain, comprised of tandem N-and C-lobes. ArcNbs E5 and H11 selectively bound the N-lobe, which harbors a peptide ligand binding pocket specific to mammals. Four additional ArcNbs bound the region containing the C-lobe and terminal tail. For use as genetically encoded fluorescent intrabodies, we show that ArcNbs fused to mScarlet-I are uniformly expressed, without aggregation, in the cytoplasm and nucleus of HEK293FT cells. Finally, mScarlet-I-ArcNb H11 expressed as intrabody selectively bound the N-lobe and enabled co-immunoprecipitation of full-length intracellular Arc. ArcNbs are versatile tools for live-cell labeling and purification of Arc and analysis of capsid domain specific functions.
Computational modeling of the evolutionary transition from C3 to C4 photosynthesis
Authors: Dadras Armin , Marashi Sayed-Amir , Kavousi Kaveh , Banaei-Moghaddam Ali-Mohammad 
Published: January 2022

ABSTRACTC4 photosynthesis is an evolutionary adaptation that minimizes the adverse effects of the high photorespiration rate. Although it is widely accepted that the C4 plants are evolved from C3 ancestors, the knowledge about the details of this process is yet to be complete. One application of constraint-based metabolic network modeling is to simulate evolutionary trajectories that an organism endures under a certain selective pressure. However, this approach is barely used to predict the evolution of a complex trait in eukaryotes. Here, we utilized a genetic algorithm combined with a constraint-based metabolic network model of Arabidopsis thaliana to simulate the trajectories of C3 to C4 conversion under high photorespiration rate conditions combined with different environmental conditions. Our modeling predicted that the C3-C4 intermediates and C4 strategies are superior to C3 photosynthesis in these environmental conditions. Besides, resource scarcities drive different evolutionary trajectories toward the emergence of C4 photosynthesis.AUTHOR SUMMARYIt is estimated that high photorespiration reduces C3 crops productivity up to 50% [1]. Carbon concentrating mechanisms have evolved in many plants to overcome adverse effects of high photorespiration rate in especial environments. C4 photosynthesis is one of these adaptations that separate carbon assimilation reactions spatially between mesophyll and bundle sheath cells of the leaves. It is reported that C4 photosynthesis is evolved more than 65 times in 19 different families of angiosperms independently from C3 ancestors. Therefore, it is hypothesized that the potential modules, at the level of metabolism, anatomy, and gene regulation, which are needed to perform C4 photosynthesis are present in C3 plants. Since C4 plants grow better than C3 plants in hot and dry environments, scientists are working on converting C3 crops such as rice to C4 plants. However, several challenges, including a lack of understanding of the evolutionary paths toward manifestation of C4 trait, have hampered the C3-to-C4 engineering ([2]). Here, we used a metabolic network model of Arabidopsis thaliana as a C3 model plant and attempted to understand the possible evolutionary events leading to emerging of C4 photosynthesis in various scenarios and examined the results.
Outbreak.info Research Library: A standardized, searchable platform to discover and explore COVID-19 resources
Authors: Tsueng Ginger , Mullen Julia L. , Alkuzweny Manar , Cano Marco , Rush Benjamin , Haag Emily ,   Outbreak Curators, Lin Jason , Welzel Dylan J. , Zhou Xinghua , Qian Zhongchao , Latif Alaa Abdel , Hufbauer Emory , Zeller Mark , Andersen Kristian G. , Wu Chunlei , Su Andrew I. , Gangavarapu Karthik , Hughes Laura D. 
Published: January 2022

AbstractTo combat the ongoing COVID-19 pandemic, scientists have been conducting research at breakneck speeds, producing over 52,000 peer-reviewed articles within the first year. To address the challenge in tracking the vast amount of new research located in separate repositories, we developedoutbreak.infoResearch Library, a standardized, searchable interface of COVID-19 and SARS-CoV-2 resources. Unifying metadata from sixteen repositories, we assembled a collection of over 350,000 publications, clinical trials, datasets, protocols, and other resources as of October 2022. We used a rigorous schema to enforce consistency across different sources and resource types and linked related resources. Researchers can quickly search the latest research across data repositories, regardless of resource type or repository location, via a search interface, public API, and R package. Finally, we discuss the challenges inherent in combining metadata from scattered and heterogeneous resources and provide recommendations to streamline this process to aid scientific research.
Development and characterization of a human model of arteriovenous malformation (AVM)-on-a-chip
Authors: Soon Kayla , Li Mengyuan , Wu Ruilin , Turner Williamson D. , Wythe Joshua D. , Fish Jason E. , Nunes Sara S 
Published: January 2022

AbstractBrain arteriovenous malformations (AVMs) are a disorder wherein abnormal, enlarged blood vessels connect arteries directly to veins, without an intervening capillary bed. AVMs are one of the leading causes of hemorrhagic stroke in children and young adults. Most human sporadic brain AVMs are associated with genetic activating mutations in the KRAS gene. Our goal was to develop an in vitro model that would allow for simultaneous morphological and functional phenotypic data capture in real time during AVM disease progression. By generating human endothelial cells harboring a clinically relevant mutation found in most human patients (activating mutations within the small GTPase KRAS) and seeding them in a dynamic microfluidic cell culture system that enables vessel formation and perfusion, we demonstrate that vessels formed by KRAS4AG12V mutant endothelial cells (ECs) were significantly wider and more leaky than vascular beds formed by wild-type ECs, recapitulating key structural and functional hallmarks of human AVM pathogenesis. Immunofluorescence staining revealed a breakdown of adherens junctions in mutant KRAS vessels only, leading to increased vascular permeability, a hallmark of hemorrhagic stroke. Finally, pharmacological blockade of MEK kinase activity, but not PI3K inhibition, improved endothelial barrier function (decreased permeability) without affecting vessel diameter. Collectively, our studies describe the creation of human KRAS-dependent AVM-like vessels in vitro in a self-assembling microvessel platform that is amenable to phenotypic observation and drug delivery.
Applying a genetic risk score for prostate cancer to men with lower urinary tract symptoms in primary care to predict prostate cancer diagnosis: a cohort study in the UK Biobank
Authors: Green Harry D , Merriel Samuel WD , Oram Richard A , Ruth Katherine S , Tyrrell Jessica , Jones Samuel E , Thirlwell Chrissie , Gillings Mireille , Weedon Michael N , Bailey Sarah ER 
Published: January 2022

AbstractObjectivesTo assess how accurately a genetic risk score (GRS) can identify incident prostate cancer in men seeing their general practitioner with lower urinary tract symptoms.DesignCohort study.SettingUK Biobank data linked to primary care records.ParticipantsMen registered with the UK Biobank, eligible for the primary care data linkage, with a record showing that they consulted their general practitioner with lower urinary tract symptoms (LUTS) that could indicate possible undiagnosed prostate cancer.Main outcome measuresA diagnosis of prostate cancer within two years of the patient’s first consultation with their general practitioner for LUTS.ResultsA GRS is associated with prostate cancer in men with symptoms (OR=2.54 [2.16 to 2.99] p=5e-29). An integrated risk model including age and GRS applied to symptomatic men predicted prostate cancer with an AUC of 0.768 (0.739 to 0.796). Men aged 40 years and under in the bottom four GRS quintiles, aged 50 years and under in the bottom two GRS quintiles, and aged 50 to 60 years in the bottom GRS quintile had a two-year prostate cancer incidence below 1%, despite the presence of symptoms. The negative predictive value of the combined model exceeded 99%.ConclusionsThis study is the first to apply a genetic risk score in a clinical setting to improve the triage of men with symptoms of prostate cancer. It demonstrates the added benefit of incorporating an estimate of genetic risk of prostate cancer into the clinical assessment of symptomatic men in primary care. Assessment of prostate cancer risk in men with LUTS is currently based on presenting clinical features alone. Men with the lowest genetic risk of developing prostate cancer could safely avoid invasive investigation, with adequate safety netting, whilst those identified with the greatest risk could be fast-tracked for further investigation.
Multi-trait selection to build resilience in conifer forests: a case study on spruce-shoot weevil interactions
Authors: Klápště Jaroslav , Jaquish Barry , Porth Ilga 
Published: January 2022

AbstractTree planting programs now need to consider climate change increasingly, therefore, the resistance to pests plays an essential role in enabling tree adaptation to new ranges through tree population movement. The weevil Pissodes strobi (Peck) is a major pest of spruces and substantially reduces lumber quality. We revisited a large Interior spruce provenance/progeny trial (2,964 genotypes, 42 families) of varying susceptibility, established in British Columbia. We employed multivariate mixed linear models to estimate covariances between, and genetic control of, juvenile height growth and resistance traits. We performed linear regressions and ordinal logistic regressions to test for impact of parental origin on growth and susceptibility to the pest, respectively. A significant environmental component affected the correlations between resistance and height, with outcomes dependent on families. Parents sourced from above 950 m a.s.l. elevation negatively influenced host resistance to attacks, probably due to higher P. engelmannii proportion. For the genetic contribution of parents sourced from above 1,200 m a.s.l., however, we found less attack severity, probably due to a marked mismatch in phenologies. This clearly highlights that hybrid status might be a good predictor for weevil attacks and delineates the boundaries of successful spruce population movement. Families resulting from crossing susceptible with resistant parents generally showed fast-growing trees were the least affected by weevil attacks. Such results indicate that these “hybrids” might be genetically better equipped with an optimized resource allocation between defence and growth and might provide the solution for concurrent improvement in resistance against weevil attacks, whilst maintaining tree productivity.
Global and local redistribution of somatic mutations enable the prediction of functional XPD mutations in bladder cancer
Authors: Barbour Jayne A. , Ou Tong , Fang Hu , Yue Noel C. , Zhu Xiaoqiang , Wong-Brown Michelle W. , Yang Haocheng , Wong Yuen T. , Bowden Nikola A. , Wu Song , Wong Jason W. H. 
Published: January 2022

AbstractXeroderma pigmentosum group D (XPD) is a DNA helicase with critical functions in transcription initiation and nucleotide excision repair. Missense mutations in XPD are putative drivers in around 10% of bladder cancers (BLCA), but the associated mutational process remains poorly understood. Here, we examine the somatic mutational landscape of XPD wild-type (n=343) and mutant (n=39) BLCA whole genomes. The genome-wide distribution of somatic mutations is significantly altered in XPD mutants, affecting both APOBEC and non-APOBEC associated mutational processes. Specifically, XPD mutants are enriched in T[C>T]N mutations (SBS2) with altered correlation with replication timing. At a locoregional genomic level, mutant XPD BLCA had striking T>G mutation hotspots at CTCF-cohesin binding sites (CBS) with evidence linking XPD to genomic uracil repair. Leveraging differential distribution of somatic mutations, we developed a machine-learning model for predicting pathogenic XPD mutations, which we validated in an independent TCGA cohort with 100% accuracy. Our model enabled the discovery of missed XPD mutation calls and uncovered pathogenic non-hotspot XPD mutations in bladder cancer. Our study reveals how XPD mutations redistribute somatic mutations in cancer genomes and provides a genome sequencing approach to differentiate driver and passenger XPD mutations.