bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 Antibody response to the Sputnik Vaccine in previous infected Patients and non-infected one
Authors: Abdulsammad Mohamed , Ebrahim Fawzi , Tabal Salah , Bashir Sedigh , Aburgiga Ashraf , Milad Mohamed , Bareem Mohamed 
Published: December 2022

AbstractAt the begging of 2020 saw the development and trials of vaccines against Covid-19 at an unprecedented pace. The first half of 2021 has seen vaccine rollout in many countries, on the other hand, Immunity to covid-19 has exhibited to minimize the risk of having a severe infection and initiate an excellent degree against the disease. This study focuses on the comparison of Anti-Spike IgG antibodies among vaccinated people with or without previous exposure to the coronavirus. To determine whether a single dose of sputnik V can produce significant antibody titer amongst previously infected cases and design vaccine dosage regimens accordingly. This study was performed at Libyan biotechnology research Centre from August 2021 to December 2021. Blood samples were collected from 1811 adult males and females vaccinated with and without a history of exposure to covid-19. Previously infected individuals’ record was noted separately. Samples were immediately analyzed by Beckman Unicel Dxl 600, Access immunoassay system. Data were analyzed using GraphPad Prism 9 Software. A P-value >0.5 was not significant. The Majority of candidates 60% of the total samples were males and on analysis, it was found that 72% of patients were seropositive, on the other hand, individuals who vaccinated and have naïve antibodies from the previous infection showed slightly higher immunological response rather than vaccinated patients without previous infection and this finding can help the policymakers to design a single-dose vaccine regimen for the former category.
Whole-genome sequencing identifies variants inANK1,LRRN1,HAS1,and other genes and regulatory regions for stroke in type 1 diabetes
Authors: Antikainen Anni A. , Haukka Jani K. , Kumar Anmol , Syreeni Anna , Hägg-Holmberg Stefanie , Ylinen Anni , Kilpeläinen Elina , Kytölä Anastasia , Palotie Aarno , Putaala Jukka , Thorn Lena M. , Harjutsalo Valma , Groop Per-Henrik , Sandholm Niina 
Published: December 2022

AbstractAimsIndividuals with type 1 diabetes (T1D) carry a markedly increased risk of stroke, with distinct clinical and neuroimaging characteristics as compared to those without diabetes. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we aimed to find rare and low-frequency genomic variants associated with stroke in T1D. The lead findings were followed up in various datasets to replicate the findings and to assess their specificity to diabetes.Methods and ResultsWe studied stroke genetics in 1,051 individuals with T1D using WGS or WES. We analysed the genome with single-variant analyses, gene aggregate analyses, and aggregate analyses on genomic windows, enhancers and promoters. Furthermore, we attempted replication in T1D using a genome-wide association study (N=3,945) and direct genotyping (N=3,600), and in the general population from the FinnGen project and UK Biobank summary statistics. We identified a rare missense mutation onSREBF1associated with hemorrhagic stroke (rs114001633, p.Pro227Leu,p-value=8.96×10-9), which further replicated in T1D. Using gene aggregate analysis with protein altering or protein truncating variants, we identified exome-wide significant genes:ANK1andLRRN1displayed replication evidence in T1D, whileLRRN1,HAS1andUACAreplicated in the general population (UK Biobank). Furthermore, we performed sliding-window analyses and identified 14 genome-wide significant windows for stroke on 4q33-34.1, of which two replicated in T1D, and a suggestive genomic window onLINC01500, which replicated in T1D. Finally, with the regulatory region aggregate analyses, we identified a stroke-associatedTRPM2-ASpromoter (p-value=5.78×10-6), which we validated with an in vitro cell-based assay.TRPM2has been previously linked to ischemic stroke.ConclusionsHere, we report the first genome-wide analysis on stroke in individuals with diabetes. We identified multiple stroke risk loci with evidence of replication: 4q33-34.1,SREBF1, andANK1for stroke in T1D; andHAS1,UACA,LRRN1,LINC01500, andTRPM2-ASpromoter for stroke potentially generalizable to the non-diabetic population.
Severe acute infection and chronic pulmonary disease are risk factors for developing post-COVID-19 conditions
Authors: Ghosh Pritha , Niesen Michiel J.M. , Pawlowski Colin , Bandi Hari , Yoo Unice , Lenehan Patrick J. , Kumar M. Praveen , Nadig Mihika , Ross Jason , Ardhanari Sankar , O’Horo John C. , Venkatakrishnan AJ , Rosen Clifford J. , Telenti Amalio , Hurt Ryan T. , Soundararajan Venky 
Published: December 2022

AbstractPost-COVID-19 conditions, also known as “long COVID”, has significantly impacted the lives of many individuals, but the risk factors for this condition are poorly understood. In this study, we performed a retrospective EHR analysis of 89,843 individuals at a multi-state health system in the United States with PCR-confirmed COVID-19, including 1,086 patients diagnosed with long COVID and 1,086 matched controls not diagnosed with long COVID. For these two cohorts, we evaluated a wide range of clinical covariates, including laboratory tests, medication orders, phenotypes recorded in the clinical notes, and outcomes. We found that chronic pulmonary disease (CPD) was significantly more common as a pre-existing condition for the long COVID cohort than the control cohort (odds ratio: 1.9, 95% CI: [1.5, 2.6]). Additionally, long-COVID patients were more likely to have a history of migraine (odds ratio: 2.2, 95% CI: [1.6, 3.1]) and fibromyalgia (odds ratio: 2.3, 95% CI: [1.3, 3.8]). During the acute infection phase, the following lab measurements were abnormal in the long COVID cohort: high triglycerides (meanlongCOVID: 278.5 mg/dL vs. meancontrol: 141.4 mg/dL), low HDL cholesterol levels (meanlongCOVID: 38.4 mg/dL vs. meancontrol: 52.5 mg/dL), and high neutrophil-lymphocyte ratio (meanlongCOVID: 10.7 vs. meancontrol: 7.2). The hospitalization rate during the acute infection phase was also higher in the long COVID cohort compared to the control cohort (ratelongCOVID: 5% vs. ratecontrol: 1%). Overall, this study suggests that the severity of acute infection and a history of CPD, migraine, CFS, or fibromyalgia may be risk factors for long COVID symptoms. Our findings motivate clinical studies to evaluate whether suppressing acute disease severity proactively, especially in patients at high risk, can reduce incidence of long COVID.
Trends in patients’ willingness for cancer care and the number of registered cancer cases in Ehime Prefecture during the COVID-19 pandemic
Authors: Teramoto Norihiro , Yamashita Natsumi , Ohira Yutsuko 
Published: December 2022

AbstractBackgroundThe COVID-19 pandemic has reduced diagnosed cancer cases worldwide. This study aimed to elucidate the recovery of cancer care from the COVID-19 pandemic in Ehime Prefecture, Japan.MethodsThis study collected data from the hospital-based cancer registry (HBCR) as well as the number of outpatients, medical information provision fee payments (MIP2), and second opinion patients (SOP) from the Council of Ehime Cancer Care Hospitals (ECCH). Then cancer care and patient requests for hospital transfers before and during the COVID-19 pandemic were analyzed.ResultThe HBCR from the ECCH comprises >80% of cancer cases in Ehime Prefecture. In 2020, the numbers of all registered cases, first-line treatment cases, and cases detected by cancer screening in the HBCR decreased from those in 2018–2019. In 2021, they increased to almost the same levels as those in 2020. In contrast, the number of registered patients that changed hospitals (hospital-change cases) after first-line treatments, patients who lived outside the metropolitan area of Ehime but registered in metropolitan hospitals, MIP2, and SOP remained low in 2021 after decreasing in 2020. Furthermore, using the Wilcoxon rank sum test, the monthly numbers of hospital-change cases, MIP2, and SOP were significantly smaller in 2021 than in 2018–2019.ConclusionThe assessed indicators suggest that the willingness of cancer patients to improve and/or advance cancer care had not returned to pre-pandemic levels by 2021. Hence, psychological measures in society and support for patient caregivers are necessary to prevent self-restraint in patients receiving cancer care.Mini-abstractThe number of registered cases in hospital-based cancer registries returned to pre-COVID-19 levels by 2021, cancer patients’ willingness to further their care did not return to pre-pandemic levels.
G2019S selective LRRK2 kinase inhibitor abrogates mitochondrial DNA damage
Authors: Pena Nicholas , Gonzalez-Hunt Claudia P. , Qi Rui , Barlow Carrolee , Shanks Natalie F. , Carlisle Holly J. , Sanders Laurie H. 
Published: December 2022

ABSTRACTPathogenic mutations inLRRK2cause Parkinson’s disease (PD). The G2019S variant is the most common, which results in abnormally high kinase activity. Compounds that target LRRK2 kinase activity are currently being developed and tested in clinical trials. We recently found that G2019S LRRK2 causes mitochondrial DNA (mtDNA) damage and treatment with multiple classes of LRRK2 kinase inhibitors at concentrations associated with dephosphorylation of LRRK2 reversed mtDNA damage to healthy control levels. Because maintaining the normal function of LRRK2 in heterozygous G2019SLRRK2carriers while specifically targeting the G2019S LRRK2 activity could have an advantageous safety profile, we explored the efficacy of a G2019S mutant selective LRRK2 inhibitor to reverse mtDNA damage in G2019S LRRK2 models and patient cells relative to non-selective LRRK2 inhibitors. Potency of LRRK2 kinase inhibition by EB-42168, a G2019S mutant LRRK2 kinase inhibitor, and MLi-2, a nonselective inhibitor, was determined by measuring phosphorylation of LRRK2 at Ser935 and/or Ser1292 using quantitative western immunoblot analysis. The Mito DNADXassay, a novel system that allows for the accurate real-time quantification of mtDNA damage in a 96-well platform, was performed in parallel. We confirmed that EB-42168 selectively inhibits LRRK2 phosphorylation on G2019S LRRK2 relative to wild-type LRRK2. On the other hand, MLi-2 was equipotent for wild-type and G2019S LRRK2. Acute treatment with EB-42168 inhibited LRRK2 phosphorylation and also restored mtDNA damage to healthy control levels. Precision medicine is a common approach in modern day cancer research that is not yet routinely applied to neurodegenerative diseases. Abrogation of mtDNA damage with mutant selective tool inhibitor EB-42168 demonstrates the promise of a precision medicine approach for LRRK2 G2019S PD. Levels of mtDNA damage may serve as a potential pharmacodynamic biomarker of altered kinase activity that could be useful for small molecule development and clinical trials.
Moving and static faces, bodies, objects and scenes are differentially represented across the three visual pathways
Authors: Küçük Emel , Foxwell Matthew , Kaiser Daniel , Pitcher David 
Published: December 2022

AbstractModels of human cortex propose the existence of neuroanatomical pathways specialised for different behavioural functions. These pathways include a ventral pathway for object recognition, a dorsal pathway for performing visually guided physical actions and a recently proposed third pathway for social perception. In the current study we tested the hypothesis that different categories of moving stimuli are differentially processed across the dorsal and third pathways according to their behavioural implications. Human participants (N=30) were scanned with functional magnetic resonance imaging (fMRI) while viewing moving and static stimuli from five categories (faces, bodies, scenes, objects, and scrambled objects). Whole brain group analyses showed that moving bodies and moving objects increased neural responses in bilateral V5/MT+ and intraparietal sulcus (IPS), parts of the dorsal pathway. In addition, moving faces and moving bodies increased neural responses in bilateral V5/MT+ and the right posterior superior temporal sulcus (rpSTS), parts of the third pathway. This pattern of results was also supported by a separate region of interest (ROI) analysis showing that moving stimuli produced more robust neural responses for all visual object categories, particularly in lateral and dorsal brain areas. Our results suggest that dynamic naturalistic stimuli from different categories are routed along specific visual pathways that process their unique behavioural implications.
Perturbation of the mitochondrial import machinery by aggregation prone Tau affects organelle morphology and reduces neuronal complexity
Authors: Needs Hope I , Wilkinson Kevin A , Henley Jeremy M , Collinson Ian 
Published: December 2022

AbstractProtein import into mitochondria is an intricate and highly conserved process essential for organellar biogenesis, and maintenance of its structure and function. Defects in the import apparatus impact the assembly of the respiratory chain and ATP synthase complexes required for oxidative phosphorylation, compromising the supply of ATP to the cytosol. The consequences of reduced bioenergetic function are particularly severe for cells with high energetic demands, such as neurons. However, relatively little is known about how defective import contributes to neurodegeneration, or how aggregation prone toxic proteins, characteristic of neurodegenerative disease, impact mitochondrial import efficiency. Here, we used HeLa cells to investigate how expressing Tau, or a disease-causing variant, affects mitochondrial import activity, morphology, and function. We found that a variant associated with frontotemporal dementia (TauP301L), but not the native version, colocalises with mitochondria, associating with TOM40–the protein-channel component of the outer membrane import complex. Interestingly, TauP301Lproduction had no discernible effect on overall mitochondrial import function, despite associating with TOM40 and altering mitochondrial morphology. This raised suspicions of a rescue mechanism manifested by the appearance of microtubule and actin containing tunnelling nanotubes (TNTs), used to recruit healthy mitochondria from neighbouring cells and/ or dispose of mitochondria containing aggregated Tau. Furthermore, in primary neuronal cultures TauP301Linduces morphological changes that resemble a neurodegeneration-like phenotype–also mirrored in cells where the import sites are blocked artificially. These results reveal an intriguing link between the production of aggregation prone protein variants, such as TauP301Land others, with the mitochondrial protein import machinery relevant to neurodegenerative disease.
Visual input dynamically changes responses to spatiotemporal tactile input patterns in S1 neurons
Authors: Kristensen Sofie Skårup , Jörntell Henrik 
Published: December 2022

AbstractTo understand how sensory events are represented in and perceived by the brain, one must understand how varying internal brain states affect neuronal decoding of sensory input. Recent studies indicate global state changes in the brain impact the representation of haptic events in neurons of the primary somatosensory cortex (S1). It could be argued that the manipulations used so far to alter the cortical circuitry behavior were artificial and not reflective of normal information processing in the neocortex. In the present study we therefore wanted to explore if natural visual stimulation also could impact the interpretation of given tactile input patterns. We recorded the unitary extracellular responses to a set of spatiotemporal tactile input patterns presented either alone or together with simultaneously multicolor flashing lights from a large number of neurons in parallel in the rat primary somatosensory cortex (S1). We found that the visual input, mildly but consistently altered the temporal spike outputs to tactile input patterns in S1 neurons. We argue that the visual input change the global cortical state to an extent that it affects the cortical representation of haptic events even within the S1 and that this is an indication that the cortical network in its information processing may be far more reliant on globally distributed network dynamics than traditionally thought.
Identifying content-invariant neural signatures of perceptual vividness
Authors: Barnett Benjy , Andersen Lau M. , Fleming Stephen M. , Dijkstra Nadine 
Published: December 2022

AbstractSome conscious experiences are more vivid than others. Although perceptual vividness is a key component of human consciousness, how variation in this magnitude property is registered by the human brain is unknown. A striking feature of magnitudes in other psychological domains, such as number or reward, is the existence of neural magnitude codes that are independent from sensory contents. To test whether perceptual vividness similarly covaries with neural codes that are invariant to sensory content, we reanalysed existing MEG and fMRI data from two distinct studies, quantifying perceptual vividness via subjective ratings of awareness and visibility. Using representational similarity and decoding analyses, we find evidence for the existence of content-invariant neural codes for perceptual vividness distributed across visual, parietal, and frontal cortices. Our findings are consistent with a hypothesis that the subjective vividness of conscious experience is supported by neural signatures similar to magnitude codes in other cognitive domains.Significance StatementThe vividness of conscious experience varies across different stimuli and contexts. Despite being a fundamental feature of conscious awareness, exactly how perceptual vividness is encoded in the human brain remains unclear. Neural codes underpinning magnitude in reward and numerosity domains have been shown to be unchanging as stimulus identity varies. Here, we test whether components of neural activity covarying with the magnitude of perceptual vividness are similarly independent of perceptual content in analyses of MEG and fMRI data. We find dynamic, content-invariant neural signatures of vividness in visual, parietal, and frontal cortices. Our findings introduce the surprising notion that neural signatures of conscious experience might follow similar coding principles to those found for magnitude properties of entirely different cognitive domains.
Toward a Cell Culture Model of Portal Axis Lipid Handling
Authors: Cook Joshua R. , Green Peter H.R. , Haeusler Rebecca A. 
Published: December 2022

AbstractThe health risks posed by excessive visceral white adipose tissue (WAT) may arise from exposure to deleterious intestinal factors in transit through the portal system. These may include an altered bile acid (BA) pool – particularly with respect to 12α-hydroxylated BA (12-HBA), which we have previously demonstrated are closely associated with insulin resistance. However, given the complexity of the enterohepatic milieu, we have worked to develop a co-culture system that allows for controlled study of the interactions between human induced pluripotent stem cell (hiPSC) derived adipocytes and primary human intestinal organoids (hIO). We present preliminary data on the characterization of both cellular compartments and their interactions, particularly in the context of BA treatment. We have recapitulated the basic functionality of each tissue type and have found reciprocal, potentially important changes in gene expression in each. However, we also have encountered numerous technical challenges in the development of this co-culture system and provide methodological observations to assist others seeking to work with a co-culture system of this type.
Down-regulation ofDrosophilaGlutactin, a cholinesterase-like adhesion molecule of the basement membrane, impairs development, compromises adult function and shortens lifespan
Authors: Alvarez-Ortiz Pedro , Guillemette Shawna , Humphrey Rachel , Ballif Bryan A. , Vigoreaux Jim O. 
Published: December 2022

AbstractBasement membranes (BM) play fundamental roles in morphogenesis and tissue maintenance in multicellular organisms. Glutactin is a BM protein that belongs to the Cholinesterase-Like Adhesion Molecules (CLAMs) protein family. InDrosophilaembryos, Glutactin has been shown to outline internal organs and to play a role in synapse formation. Here, we report that Glutactin is broadly expressed in BM surrounding most vital tissues of the larva and the adult, and within the larval muscle sarcomere. Ubiquitous RNAi driven down-regulation of Glutactin expression (Tub>Glt-RNAi) resulted in pronounced impairments in larval and adult locomotor behavior, reduced oviposition, and shortened lifespan. Muscle-specific down-regulation of Glutactin resulted in reduced larval crawling speed indicating a secondary function for Glutactin independent of BM expression.Tub>Glt-RNAipupa showed abdominal scars, suggestive of defects in histoblast nest expansion and replacement of larval epidermal cells, and a high mortality rate at eclosion. Surviving adults showed a range of morphological and physiological defects including excess melanization and pigmentation, incomplete rotation and duplication of the genitalia, and abnormal heart morphology and contraction. Insofar excess melanization is symptomatic of internal tissue damage, we propose that Glutactin is essential for the mechanical stabilization of the BM and for its ability to withstand internal stresses.
Latent neural population dynamics underlying normal breathing, opioid induced respiratory depression, and gasping
Authors: Bush Nicholas E , Ramirez Jan-Marino 
Published: December 2022

AbstractBreathing is vital and must be concurrently robust and flexible. This rhythmic behavior is generated and maintained within a rostro-caudally aligned set of medullary nuclei called the Ventral Respiratory Column (VRC). The rhythmic properties of individual VRC nuclei are well known, yet technical challenges have limited the interrogation of the entire VRC population simultaneously. Here, we characterize over 13,000 VRC units using high-density electrophysiology, opto-tagging, and histological reconstruction. Population dynamics analysis reveals interactions between inspiratory and expiratory dynamical states give rise to a low-dimensional, elliptical neural manifold. The structure of this manifold is robust and maintained even during opioid-induced respiratory depression (OIRD). However, during severe hypoxia-induced gasping, the low-dimensional dynamics of the VRC reconfigure from rotational to all-or-none, ballistic efforts.
Quantifying negative selection in human 3’ UTRs uncovers constrained targets of RNA-binding proteins
Authors: Findlay Scott D. , Romo Lindsay , Burge Christopher B. 
Published: December 2022

ABSTRACTMany non-coding variants associated with phenotypes occur in 3’ untranslated regions (3’ UTRs) and may affect interactions with RNA-binding proteins (RBPs) to regulate post-transcriptional gene expression. However, identifying functional 3’ UTR variants has proven difficult. We used allele frequencies from the Genome Aggregation Database (gnomAD) to identify classes of 3’ UTR variants under strong negative selection in humans. We developed intergenic mutability-adjusted proportion singleton (iMAPS), a generalized measure related to MAPS, to quantify negative selection in non-coding regions. This approach, in conjunction within vitroandin vivobinding data, identifies precise RBP binding sites, miRNA target sites, and polyadenylation signals (PASs) under strong selection. For each class of sites, we identified thousands of gnomAD variants under selection comparable to missense coding variants, and found that sites in core 3’ UTR regions upstream of the most-used PAS are under strongest selection. Together, this work improves our understanding of selection on human genes and validates approaches for interpreting genetic variants in human 3’ UTRs.