bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reassessment of persistent symptoms, self-reported COVID-19 infection and SARS-CoV-2 serology in the SAPRIS-SERO cohort: identifying possible sub-syndromes of Long Covid
Authors: Spiers Nicola 
Published: February 2022

AbstractBackgroundLong Covid remains a relatively new phenomenon with emerging understanding. Estimated UK prevalence of Long Covid with three or more symptoms lasting for 12 weeks or more was 2.2% at the end of 2021. The population-based French SAPRIS-SERO cohort has novel information about the pattern of symptoms of Long Covid that has been obscured by controversy around the original paper.MethodsSecondary analysis was used to describe and re-interpret the frequencies of persistent symptoms by IgG seropositivity and self-reported Long Covid in the published report of the SAPRIS-SERO survey. Participants in the cross-sectional analysis were 26 823 individuals from the French population-based CONSTANCES cohort, included between 2012 and 2019, who took part in the nested SAPRIS and SAPRIS-SERO surveys. Between May and November 2020, the Euroimmun enzyme-linked immunosorbent assay was used to detect anti-SARS-CoV-2 antibodies. Surveyed online between December 2020 and January 2021, participants self-reported previous COVID-19 infection and physical symptoms during the previous four weeks that were new since March 2020, and had persisted for at least eight weeks.ResultsThere was similarity of prevalence over the majority of symptoms in those self-reporting COVID-19 infection, regardless of blood test result. Persistent symptoms significantly associated with self-reported COVID-19 infection and common in both groups include respiratory tract symptoms and a group of symptoms that might be related to chronic fatigue, malaise or postural issues. Seropositivity for IgG antibodies did not predict symptoms independently of self-reported Long Covid, except for anosmia.ConclusionsThere may be three common sub-syndromes of Long Covid, one with persistent anosmia, another with other respiratory tract symptoms and a third, currently under researched, with symptoms relatable to chronic fatigue. Antibody tests are insufficient for case detection while Long Covid remains poorly understood.Key MessagesIgG seropositivity is insufficient to identify potential cases of Long CovidPersistent anosmia is very strongly associated with IgG seropositivity and may define a subsyndrome of Long CovidOther potential subsyndromes are those with persistent respiratory symptoms and those with persistent symptoms relatable to fatigue, malaise or postural issuesThe Long Covid research effort should be rebalanced towards understanding the fatigue/tiredness subsyndrome.
Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma
Authors: Storti Paola , Marchica Valentina , Vescovini Rosanna , Franceschi Valentina , Russo Luca , Raimondi Vincenzo , Toscani Denise , Garcia Jessica Burroughs , Costa Federica , Palma Benedetta Dalla , Soressi Naomi , Giaimo Mariateresa , Iannozzi Nicolas Thomas , Notarfranchi Laura , Sammarelli Gabriella , Donofrio Gaetano , Giuliani Nicola 
Published: February 2022

AbstractMultiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies.Firstly, we have shown that MM patients with relapsed-refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing-CD8+ T cells were found in MM patients as compared to MGUS.Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.
Late-Ensemble of Convolutional Neural Networks with Test Time Augmentation for Chest XR COVID-19 Detection
Authors: Qayyum Abdul , Razzak Imran , Mazher Moona , Puig Domenec 
Published: February 2022

AbstractCOVID-19, a severe acute respiratory syndrome aggressively spread among global populations in just a few months. Since then, it has had four dominant variants (Alpha, Beta, Gamma and Delta) that are far more contagious than original. Accurate and timely diagnosis of COVID-19 is critical for analysis of damage to lungs, treatment, as well as quarantine management [7]. CT, MRI or X-rays image analysis using deep learning provide an efficient and accurate diagnosis of COVID-19 that could help to counter its outbreak. With the aim to provide efficient multi-class COVID-19 detection, recently, COVID-19 Detection challenge using X-ray is organized [12]. In this paper, the late-fusion of features is extracted from pre-trained various convolutional neural networks and fine-tuned these models using the challenge dataset. The DensNet201 with Adam optimizer and EffecientNet-B3 are fine-tuned on the challenge dataset and ensembles the features to get the final prediction. Besides, we also considered the test time augmentation technique after the late-ensembling approach to further improve the performance of our proposed solution. Evaluation on Chest XR COVID-19 showed that our model achieved overall accuracy is 95.67%. We made the code is publicly available1. The proposed approach was ranked 6th in Chest XR COVID-19 detection Challenge [1].
Longitudinal analysis of UK Biobank participants suggests age and APOE-dependent alterations of energy metabolism in development of dementia
Authors: Liu Jun , Amin Najaf , Sproviero William , Arnold Matthias , Batra Richa , Bonnechere Bruno , Chiou Yu-Jie , Fernandes Marco , Krumsiek Jan , Newby Danielle , Nho Kwangsik , Kim Jun Pyo , Saykin Andrew J , Shi Liu , Winchester Laura , Yang Yang , Nevado-Holgado Alejo J , Kastenmüller Gabi , Kaddurah-Daouk Rima F , van Duijn Cornelia M 
Published: February 2022

AbstractExperimental models shows that bioenergetic homeostasis changes with increasing age based on apolipoprotein E (APOE) gene. However, such link with dementia remains unclear in population. We used H1-NMR metabolome in blood from 118,021 random-selected participants in UK Biobank (n=118,021 individuals), and identified 56 metabolites associated with the risk of dementia. In the participants without developing dementia during follow-up, 82% (46/56) metabolites are also associated with reaction time, and dementia shares metabolite signatures with total brain volume. We found that incident Alzheimer’s disease (AD) is associated with energy metabolism-related metabolites, i.e, β-hydroxybutyrate, acetone, and valine, whose concentrations in blood are influenced by age and APOE genotype. Valine shows a declined trajectories after a plateau at age around 60 years which is in parallel with body mass index. Moreover, we found associations of AD with valine and β-hydroxybutyrate in brain tissue are different as their associations in the periphery, which implies the key role of transports in regulating the energy metabolism of AD. Our study provides strong evidence in population level that the onset of AD in APOE4 carriers is regulated by the impaired energy balance in the brain.
Structural basis for receptor selectivity and inverse agonism in S1P5 receptors
Authors: Lyapina Elizaveta , Marin Egor , Gusach Anastasiia , Orekhov Philipp , Gerasimov Andrey , Luginina Aleksandra , Vakhrameev Daniil , Ergasheva Margarita , Kovaleva Margarita , Khusainov Georgii , Khorn Polina , Shevtsov Mikhail , Kovalev Kirill , Okhrimenko Ivan , Popov Petr , Hu Hao , Weierstall Uwe , Liu Wei , Cho Yunje , Gushchin Ivan , Rogachev Andrey , Bourenkov Gleb , Park Sehan , Park Gisu , Hyun Hyo Jung , Park Jaehyun , Gordeliy Valentin , Borshchevskiy Valentin , Mishin Alexey , Cherezov Vadim 
Published: February 2022

ABSTRACTThe bioactive lysophospholipid sphingosine-1-phosphate (S1P) acts via five different subtypes of S1P receptors (S1PR) - S1P1-5. S1P5 is predominantly expressed in nervous and immune systems, regulating the egress of natural killer cells from lymph nodes and playing a role in immune and neurodegenerative disorders, as well as carcinogenesis. Several S1PR therapeutic drugs have been developed to treat these diseases; however, they lack receptor subtype selectivity, which leads to side effects. In this article, we describe a 2.2 Å resolution room temperature crystal structure of the human S1P5 receptor in complex with a selective inverse agonist determined by serial femtosecond crystallography (SFX) at the Pohang Accelerator Laboratory X-Ray Free Electron Laser (PAL-XFEL) and analyze its structure-activity relationship data. The structure demonstrates a unique ligand-binding mode, involving an allosteric subpocket, which clarifies the receptor subtype selectivity and provides a template for structure-based drug design. Together with previously published S1PR structures in complex with antagonists and agonists, the new S1P5-inverse agonist structure sheds light on the activation mechanism and reveals structural determinants of the inverse agonism in the S1PR-family.
Thermal regime during parental sexual maturation, but not during offspring rearing, modulates DNA methylation in brook charr (Salvelinus fontinalis)
Authors: Venney Clare J , Wellband Kyle W , Normandeau Eric , Houle Carolyne , Garant Dany , Audet Céline , Bernatchez Louis 
Published: February 2022

AbstractEpigenetic inheritance can result in plastic responses to changing environments being faithfully transmitted to offspring. However, it remains unclear how epigenetic mechanisms such as DNA methylation can contribute to multigenerational acclimation and adaptation to environmental stressors. Brook charr (Salvelinus fontinalis), an economically important salmonid, is highly sensitive to thermal stress, and is of conservation concern in the context of climate change. We studied the effects of temperature during parental sexual maturation and offspring rearing on whole-genome DNA methylation in brook charr juveniles (fry). Parents were split between warm and cold temperatures during sexual maturation, mated in controlled breeding designs, then offspring from each family were split between warm (8°C) and cold (5°C) rearing environments. We found 188 differentially methylated regions (DMRs) due to parental maturation temperature after controlling for family structure. In contrast, offspring rearing temperature had a negligible effect on offspring methylation. Stable intergenerational inheritance of DNA methylation and minimal plasticity in progeny could result in transmission of acclimatory epigenetic states to offspring, priming them for a warming environment. Our findings have implications pertaining to the role of intergenerational epigenetic inheritance in response to ongoing climate change.
Nicotinamide Riboside alleviates exercise intolerance in ANT1-deficient mice
Authors: Schaefer Patrick M. , Huang Jessica , Butic Arrienne , Perry Caroline E. , Yardeni Tal , Tan Wendy , Morrow Ryan , Baur Joseph A. , Wallace Douglas C. 
Published: February 2022

SummaryMitochondrial disorders are often characterized by muscle weakness and fatigue. Null mutations in the heart-muscle adenine nucleotide translocator isoform 1 (ANT1) of both humans and mice cause cardiomyopathy and myopathy associated with exercise intolerance and muscle weakness. We have analyzed the exercise physiology of mice deficient in ANT1, demonstrating a peripheral limitation of skeletal muscle mitochondrial respiration. Upon exercise, lack of Nicotinamide adenine dinucleotide+ (NAD+) results in a substrate limitation and stalling of the TCA cycle and mitochondrial respiration. Treatment of ANT1-deficient mice with nicotinamide riboside increased NAD+ levels in skeletal muscle and improved the exercise capacity and mitochondrial respiration. Thus, increasing NAD+ levels with nicotinamide riboside can alleviate the exercise intolerance associated with ANT1-deficiency, indicating the therapeutic potential of NAD+-stimulating compounds in specific mitochondrial myopathies.
Distinct execution modes of a biochemical necroptosis model explain cell type-specific responses and variability to cell-death cues
Authors: Ildefonso Geena V. , Oliver-Metzig Marie , Hoffmann Alexander , Harris Leonard A. , Lopez Carlos F. 
Published: February 2022

ABSTRACTNecroptosis is a form of regulated cell death that has been associated with degenerative disorders, autoimmune processes, inflammatory diseases, and cancer. To better understand the biochemical mechanisms of necroptosis cell death regulation, we constructed a detailed biochemical model of tumor necrosis factor (TNF)-induced necroptosis based on known molecular interactions. Intracellular protein levels, used as model inputs, were quantified using label-free mass spectrometry, and the model was calibrated using Bayesian parameter inference to experimental protein time course data from a well-established necroptosis-executing cell line. The calibrated model accurately reproduced the dynamics of phosphorylated mixed lineage kinase domain-like protein (pMLKL), an established necroptosis reporter. A dynamical systems analysis identified four distinct modes of necroptosis signal execution, which can be distinguished based on rate constant values and the roles of the deubiquitinating enzymes A20 and CYLD in the regulation of RIP1 ubiquitination. In one case, A20 and CYLD both contribute to RIP1 deubiquitination, in another RIP1 deubiquitination is driven exclusively by CYLD, and in two modes either A20 or CYLD acts as the driver with the other enzyme, counterintuitively, inhibiting necroptosis. We also performed sensitivity analyses of initial protein concentrations and rate constants and identified potential targets for modulating necroptosis sensitivity among the biochemical events involved in RIP1 ubiquitination regulation and the decision between complex II degradation and necrosome formation. We conclude by associating numerous contrasting and, in some cases, counterintuitive experimental results reported in the literature with one or more of the model-predicted modes of necroptosis execution. Overall, we demonstrate that a consensus pathway model of TNF-induced necroptosis can provide insights into unresolved controversies regarding the molecular mechanisms driving necroptosis execution for various cell types and experimental conditions.
Follow-up investigation and detailed mutational characterization of the SARS-CoV-2 Omicron variant lineages (BA.1, BA.2, BA.3 and BA.1.1)
Authors: Abbas Qussai , Kusakin Alexey , Sharrouf Kinda , Jyakhwo Susan , Komissarov Aleksey S 
Published: February 2022

AbstractAided by extensive protein mutations, the SARS-CoV-2 Omicron (B.1.1.529) variant overtook the previously dominant Delta variant and rapidly spread around the world. It was shown to exhibit significant resistance to current vaccines and evasion from neutralizing antibodies. It is therefore critical to investigate the Omicron mutations’ trajectories. In this study, a literature search of published articles and SARS-CoV-2 databases was conducted, We explored the full list of mutations in Omicron BA.1, BA.1.1, BA.2, and BA.3 lineages. We described in detail the prevalence and occurrence of the mutations across variants, and how Omicron differs from them. We used GISAID as our primary data source, which provides open-access to genomics data of the SARS-CoV-2 virus, in addition to epidemiological and geographical data. We examined how these mutations interact with each other, their co-occurrence and clustering. Our study offers for the first time a comprehensive description of all mutations with a focus on non-spike mutations and demonstrated that mutations in regions other than the Spike (S) genes are worth investigating further. Our research established that the Omicron variant has retained some mutations reported in other SARS-CoV-2 variants, yet many of its mutations are extremely rare in other variants and unique to Omicron. Some of these mutations have been linked to the transmissibility and immune escape of the virus, and indicate a significant shift in SARS-CoV-2 evolution. The most likely theories for the evolution of the Omicron variant were also discussed.
Cryo-EM structure of the Rhodobaca bogoriensis RC-LH1-PufX dimeric complex at 2.9 Å
Authors: Semchonok Dmitry A. , Siponen Marina I. , Tüting Christian , Charras Quentin , Kyrilis Fotis L. , Hamdi Farzad , Sadian Yashar , Jungas Colette , Kastritis Panagiotis L. 
Published: February 2022

AbstractThe reaction centre-light harvesting 1 (RC-LH1) complex is essential for converting light into proton motive force in photosynthetic bacteria. RC-LH1 is a monomer in most purple bacteria, but in Rhodobacter species, it is a dimer. Its assembly depends on an accessory polypeptide (PufX) and, ultimately, on photosynthetic growth. To date, knowledge on the RC-LH1-PufX structure, where the dimer has two incomplete ‘C’-shaped antenna rings surrounding an RC, is mainly limited to the model organism Rhodobacter sphaeroides. Here we present a cryo-electron microscopy structure at 2.9 Å from Rhodobaca bogorensis strain LBB1. RCs are surrounded by 30 antennas and incorporate protein Y and PufX. RCs are stably connected by PufX, which self-interacts, electrostatically attracts cytochrome c2 (cyt c2) and forms extensive networks with co-factors. This structure underlines coordinated energy transfer in a combinatorial manner, providing a basis to describe bacterial photosynthesis within a dimeric photosynthetic apparatus.
A structural dynamic explanation for observed escape of SARS-CoV-2 BA.2 variant mutation S371L/F
Authors: Miller Nathaniel L. , Clark Thomas , Raman Rahul , Sasisekharan Ram 
Published: February 2022

SummaryThe SARS-CoV-2 Omicron sub-variants BA.1 and BA.2 have become the dominant variants worldwide due to enhanced transmissibility and immune evasion. In response to the rise of BA.1 and BA.2, two recent studies by Liu et al. and Iketani et al. provide a detailed analysis of loss of therapeutic antibody potency through evaluation of escape by pseudotyped viruses harboring BA.1 and BA.2 receptor binding domain (RBD) point mutations. Surprisingly, Liu et al. and Iketani et al. observed a profoundly broad escape effect for the individual mutations S371L and S371F. This result cannot be explained by known escape mechanisms of the SARS-CoV-2 RBD, and conflicts with existing computational and experimental escape measurements for S371 mutations performed on monomeric RBD. Through an examination of these conflicting datasets and a structural analysis of the antibodies assayed by Liu et al. and Iketani et al., we propose a mechanism to explain S371L/F escape according to a perturbation of spike trimer conformational dynamics that has not yet been described for any SARS-CoV-2 escape mutation. The proposed mechanism is relevant to Omicron and future variant surveillance as well as therapeutic antibody design.
Vision-related convergent gene losses revealSERPINE3’s unknown role in the eye
Authors: Indrischek Henrike , Hammer Juliane , Machate Anja , Hecker Nikolai , Kirilenko Bogdan M. , Roscito Juliana G. , Hans Stefan , Norden Caren , Brand Michael , Hiller Michael 
Published: February 2022

AbstractDespite decades of research, knowledge about the genes that are important for development and function of the mammalian eye and are involved in human eye disorders remains incomplete. During mammalian evolution, mammals that naturally exhibit poor vision or regressive eye phenotypes have independently lost many eye-related genes. This provides an opportunity to predict novel eye-related genes based on specific evolutionary gene loss signatures. Building on these observations, we performed a genome-wide screen across 49 mammals for functionally uncharacterized genes that are preferentially lost in species exhibiting lower visual acuity values. The screen uncovered several genes, includingSERPINE3, a putative serine proteinase inhibitor. A detailed investigation of 381 additional mammals revealed thatSERPINE3is independently lost in 18 lineages that typically do not primarily rely on vision, predicting a vision-related function for this gene. To test this, we show thatSERPINE3has the highest expression in eyes of zebrafish and mouse. In the zebrafish retina,serpine3is expressed in Mueller glia cells, a cell type essential for survival and maintenance of the retina. A CRISPR-mediated knockout ofserpine3in zebrafish resulted in alterations in eye shape and defects in retinal layering. Furthermore, two human polymorphisms that are in linkage withSERPINE3are associated with eye-related traits. Together, these results suggest thatSERPINE3has a role in vertebrate eyes. More generally, by integrating comparative genomics with experiments in model organisms, we show that screens for specific phenotype-associated gene signatures can predict functions of uncharacterized genes.