bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG coherence as a marker of Alzheimer’s disease
Authors: Radinskaia Dina , Radinski Crystal 
Published: July 2022

AbstractBackgroundProgressive deterioration of synaptic plasticity and synaptic connectivity between neurons is a neurophysiological hallmark of brain ageing and has been linked to the severity of dementia. We hypothesized that if synaptic disconnection as the neuropathology of Alzheimer’s disease (AD) is responsible for the failure of the brain to integrate various regions into effective networks, then electroencephalographic evidence of the disruption of functional connectivity might be used to diagnose Alzheimer’s dementia. We proposed that changes in EEG coherence, a measure of functional interaction between the brain collaborating areas, can be detected in a clinical setting and serve as a marker of neuronal disconnection. Improving the accuracy and reducing the time needed to diagnose AD could allow timely interventions, treatments, and care cost reduction.MethodsThis study examined group differences in EEG coherence within global cortical networks at rest and during executive challenges among patients with AD, individuals with mild cognitive impairment, and healthy controls.ResultsDecreased EEG coherence has been discovered in cross-hemisphere frontal, temporal, parietal and occipital pairs in the AD group at rest and when challenged with tasks requiring comprehension, analysis, perceptual-motor response, and executive functioning. The most notable changes were detected in F3-F4 Beta with the visual-spatial task challenge, P7-P8 Beta during the writing task, T7-T8 Gamma during a task requiring speech understanding and O1-O2 Alpha during orientation in space task.ConclusionsThe study identified several potential EEG biomarkers of AD. More research is needed to identify sensitivity and specificity of the markers.
Antibiotic choice for Group B Streptococcus prophylaxis in mothers with documented penicillin allergies and associated newborn outcomes
Authors: Snider Josephine B. , Mithal Leena B. , Kwah Jason H. , Rhodes Nathaniel J. , Son Moeun 
Published: July 2022

ABSTRACTObjectiveTo evaluate intrapartum Group B Streptococcus (GBS) prophylaxis in women with documented penicillin allergy compared to women without penicillin allergy, and to investigate associated differences in neonatal outcomes.Study DesignThis retrospective cohort study included GBS positive pregnant women who had a vaginal delivery or cesarean section after trial of labor at >35 weeks of gestation at a high-volume urban hospital (2005-2018). Management of women who reported penicillin allergy was compared to women without a reported penicillin allergy. Maternal outcome was type of antibiotic administered for GBS prophylaxis (beta-lactam antibiotic prophylaxis defined as administration of penicillin, ampicillin, or cefazolin; alternative antibiotic prophylaxis defined as vancomycin or clindamycin). Neonatal outcomes included number of blood draws, antibiotic administration, neonatal intensive care unit (NICU) admission, and length of stay. Univariate analyses were performed.ResultsOf the 11,334 mother-neonate pairs meeting eligibility criteria, 1170 (10.3%) women had a documented penicillin allergy, and of these women 51 (4.4%) had a co-existing cephalosporin allergy. Among women with a reported penicillin allergy (n=1170), 49 (4.2%) received penicillin or ampicillin, 259 (22.1%) received cefazolin, 449 (38.4%) received clindamycin and 413 (35.3%) received vancomycin. Women with documented penicillin allergy were significantly more likely to receive alternative GBS prophylaxis compared to women without penicillin allergy (73.7% vs. 0.2%, p<0.01). Neonates of women who received alternative GBS prophylaxis had more lab draws compared to neonates of women who received beta-lactam antibiotic agents (20.8% vs. 17.3%, p<0.01).ConclusionPregnant women with documented penicillin allergy received alternative antibiotics for GBS prophylaxis at a significantly higher frequency than women without a penicillin allergy. This was associated with an increased frequency of blood draws among neonates of mothers with penicillin allergy.
SARS-CoV-2 BA.5 vaccine breakthrough risk and severity compared with BA.2: a case-case and cohort study using Electronic Health Records in Portugal
Authors: Kislaya Irina , Casaca Pedro , Borges Vítor , Sousa Carlos , Ferreira Bibiana I. , Fernandes Eugénia , Dias Carlos Matias , Duarte Sílvia , Almeida José Pedro , Grenho Inês , Coelho Luís , Ferreira Rita , Ferreira Patrícia Pita , Isidro Joana , Pinto Miguel , Menezes Luís , Sobral Daniel , Nunes Alexandra , Santos Daniela , Gonçalves António Maia , Vieira Luís , Gomes João Paulo , Leite Pedro Pinto , Nunes Baltazar , Machado Ausenda , Peralta-Santos André 
Published: July 2022

AbstractBackgroundIn a context of multiple Omicron lineages circulation, it is relevant to clarify the effect of vaccination and previous infections on the risk of infection and severe post-infection outcomes.MethodsUsing electronic health records and SARS-CoV-2 laboratory surveillance data, we conducted a case-case and a cohort study covering the period of Omicron BA.2/BA.5 lineage replacement in Portugal, to compare vaccine effectiveness of complete primary and booster dose against infection, COVID-19 hospitalization, and mortality. Variant classification was performed through whole-genome sequencing (WGS) or Spike Gene Target Failure (SGTF).FindingsBetween April 25 and June 10, 2022, within a total of 27702 collected samples, 55.5% were classified as BA.2 and the remaining as BA.5. We observed no evidence of reduced vaccine effectiveness for the primary complete vaccination (OR=1.07, CI95%:0.93-1.23) or booster dose vaccination (OR=0.96, CI95%:0.84-1.09) against BA.5 infection compared with BA.2. The protection against reinfection was inferior in BA.5 cases when compared with BA.2 (OR=1.44; CI95%:1.30-1.60). Among those infected with BA.5, booster vaccination was associated with 77% and 88% of reduction in risk of COVID-19 hospitalization and death, respectively, while higher risk reduction was found for BA.2 cases, with 93% and 94%, respectively.InterpretationThis study shows that the SARS-CoV-2 Omicron BA.5 lineage is associated with higher odds of reinfection compared with Omicron BA.2, regardless of the vaccination status.Although less effective compared with BA.2, COVID-19 booster vaccination still offers substantial protection against severe outcomes following BA.5 infection.
Leveraging large-scale genetics of PTSD and cardiovascular disease demonstrates robust shared risk and improves risk prediction accuracy
Authors: Seligowski Antonia V. , Misganaw Burook , Duffy Lucie A. , Ressler Kerry J. , Guffanti Guia 
Published: July 2022

AbstractIndividuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD; e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the current literature, including the need for large-scale genomic studies to identify shared genetic risk. The current study used a large healthcare biobank dataset ofN= 36,412 individuals, combined with GWAS summary statistics from publicly available, large-scale PTSD and CVD studies. We found significant genetic correlations between PTSD and CVD (rG=0.24, S.E.= 0.05982,p=5.09E-05), and Mendelian randomization analyses indicated a potential causal link from PTSD to hypertension (β=0.20, S.E.= 0.04,p=5.97e-6), but not the reverse. PTSD summary statistics significantly predicted PTSD diagnostic status (R2=0.27%,p=5.31E-08), and this was significantly improved by incorporating summary statistics from CVD and major depressive disorder (R2=1.30%,p=2.16E-32). Further, pathway enrichment analyses indicated that genetic variants involved in shared PTSD-CVD risk included those involved in postsynaptic structure (p=0.00001), synapse organization (p=0.0001), and interleukin-7 (IL-7) mediated signaling pathways (p=0.0002). While additional research is needed to determine the clinical utility of these findings, these data further support the biological shared risk for stress-related disorders of mental health and cardiovascular illness.
Health impacts of COVID-19 disruptions to primary cervical screening by time since last screen: A model-based analysis for current and future disruptions
Authors: Burger Emily A. , de Kok Inge M.C.M. , O’Mahony James F , Rebolj Matejka , Jansen Erik E.L. , de Bondt Daniel D. , Killen James , Hanley Sharon J. , Castanon Alejandra , Kim Jane J. , Canfell Karen , Smith Megan A. , Regan Mary Caroline 
Published: July 2022

ABSTRACTBackgroundWe evaluated how temporary disruptions to primary cervical cancer (CC) screening services may differentially impact women due to heterogeneity in their screening history and test modality.MethodsWe used three CC models to project the short- and long-term health impacts assuming an underlying primary screening frequency (i.e., 1, 3, 5, or 10 yearly) under three alternative COVID-19-related screening disruption scenarios (i.e., 1-, 2- or 5-year delay) versus no delay, in the context of both cytology-based and HPV-based screening.ResultsModels projected a relative increase in symptomatically-detected cancer cases during a 1-year delay period that was 38% higher (Policy1-Cervix), 80% higher (Harvard) and 170% higher (MISCAN-Cervix) for under-screened women whose last cytology screen was 5 years prior to the disruption period compared with guidelines-compliant women (i.e., last screen three years prior to disruption). Over a woman’s lifetime, temporary COVID-19-related delays had less impact on lifetime risk of developing CC than screening frequency and test modality; however, CC risks increased disproportionately the longer time had elapsed since a woman’s last screen at the time of the disruption. Excess risks for a given delay period were generally lower for HPV-based screeners than for cytology-based screenersConclusionsOur independent models predicted that the main drivers of CC risk were screening frequency and screening modality, and the overall impact of disruptions from the pandemic on CC outcomes may be small. However, screening disruptions disproportionately affect under-screened women, underpinning the importance of reaching such women as a critical area of focus, regardless of temporary disruptions.FundingThis study was supported by funding from the National Cancer Institute (U01CA199334). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. Megan A Smith receives salary support from the National Health and Medical Research Council, Australia (APP1159491) and Cancer Institute NSW (ECF181561). Matejka Rebolj is funded by Cancer Research UK (reference: C8162/A27047). James O’Mahony is funded by Ireland’s Health Research Board (EIA2017054). Karen Canfell receives salary support from the National Health and Medical Research Council, Australia (APP1194679). Emily A. Burger receives salary support from the Norwegian Cancer Society.
Integrated Machine Learning Approaches Highlight the Heterogeneity of Human Myeloid-Derived Suppressor Cells in Acute Sepsis
Authors: Bonavia Anthony S. , Samuelsen Abigail , Halstead E. Scott 
Published: July 2022

AbstractHighly heterogeneous cell populations require multiple flow cytometric markers for appropriate phenotypic characterization. This exponentially increases the complexity of 2D scatter plot analysis and exacerbates human errors due to variations in manual gating of flow data. We describe a workflow involving the stepwise integration of several, newly available machine learning tools for the analysis of myeloid-derived suppressor cells (MDSCs) in septic and non-septic critical illness. Unsupervised clustering of flow cytometric data showed good correlation with, but significantly different numbers of, MDSCs as compared with the cell numbers obtained by manual gating. However, both quantification methods revealed a significant difference between numbers of PMN-MDSC at day 1 in healthy volunteers and critically ill patients having septic or non-septic illness. Numbers of PMN-MDSC obtained by machine learning positively correlated with 30 days hospital readmission following critical illness, whereas manual gating of this cell population distinguished between septic and non-septic critical illness. Neither gating strategy found a correlation between number of MDSCs and 30-day mortality or hospital length of stay.
A genome-wide association study of mammographic texture variation
Authors: Liu Yuxi , Chen Hongjie , Heine John , Lindstroem Sara , Turman Constance , Warner Erica T. , Winham Stacey J. , Vachon Celine M. , Tamimi Rulla M. , Kraft Peter , Jiang Xia 
Published: July 2022

AbstractBackgroundBreast parenchymal texture features, including gray scale variation (V), capture the patterns of texture variation on a mammogram and are associated with breast cancer risk, independent of mammographic density (MD). However, our knowledge on the genetic basis of these texture features is limited.MethodsWe conducted a genome-wide association study of V in 7,040 European-ancestry women. Four V assessments representing different amounts of breast edge erosion and image resolutions were generated from digitized film mammograms. We used linear regression to test the single-nucleotide polymorphism (SNP)-phenotype associations adjusting for age, body mass index (BMI), MD phenotypes, and the top four genetic principal components. Multivariate phenotype association tests combining all four V assessments were performed. We further calculated genetic correlations and performed SNP-set tests of V with MD, breast cancer risk, and other breast cancer risk factors.ResultsWe identified three genome-wide significant loci associated with V: rs138141444 (6q24.1) inECT2L, rs79670367 (8q24.22) inLINC01591, and rs113174754 (12q22) nearPGAM1P5. 6q24.1 and 8q24.22 have not previously been associated with MD phenotypes or breast cancer risk, whilst 12q22 is a known locus for both MD and breast cancer risk. Among known MD and breast cancer risk SNPs, we identified four variants that were associated with V at the Bonferroni-corrected thresholds accounting for the number of SNPs tested: rs335189 (5q23.2) inPRDM6, rs13256025 (8p21.2) inEBF2, rs11836164 (12p12.1) nearSSPN, and rs17817449 (16q12.2) inFTO. We observed significant genetic correlations between V and mammographic dense area (rg= 0.79,P= 5.91 × 10−5), percent density (rg= 0.73,P= 1.00 × 10−4), and adult BMI (rg= -0.36,P= 3.88 × 10−7). Additional significant relationships were observed for nondense area (z = -4.14,P= 3.42 × 10−5), estrogen receptor-positive breast cancer (z = 3.41,P= 6.41 × 10−4), and childhood body fatness (z = -4.91,P= 9.05 × 10−7) from the SNP-set tests.ConclusionsThese findings provide new insights into the genetic basis of mammographic texture variation and their associations with MD, breast cancer risk, and other breast cancer risk factors.
Determination of significant immunological timescales from mRNA-LNP-based vaccines in humans
Authors: Moyles Iain R. , Korosec Chapin S. , Heffernan Jane M. 
Published: July 2022

AbstractA compartment model for an in-host liquid nanoparticle delivered mRNA vaccine is presented. Through non-dimensionalisation, five timescales are identified that dictate the lifetime of the vaccine in-host: decay of interferon gamma, antibody priming, autocatalytic growth, antibody peak and decay, and interleukin cessation. Through asymptotic analysis we are able to obtain semi-analytical solutions in each of the time regimes which allows us to predict maximal concentrations and better understand parameter dependence in the model. We compare our model to 22 data sets for the BNT162b2 and mRNA-1273 mRNA vaccines demonstrating good agreement. Using our analysis, we estimate the values for each of the five timescales in each data set and predict maximal concentrations of plasma B-cells, antibody, and interleukin. Through our comparison, we do not observe any discernible differences between vaccine candidates and sex. However, we do identify an age dependence, specifically that vaccine activation takes longer and that peak antibody occurs sooner in patients aged 55 and greater.
Glutamine synthetase mRNA releases sRNA from its 3’UTR to regulate carbon/nitrogen metabolic balance
Authors: Miyakoshi Masatoshi , Morita Teppei , Kobayashi Asaki , Berger Anna , Takahashi Hiroki , Gotoh Yasuhiro , Hayashi Tetsuya , Tanaka Kan 
Published: July 2022

ABSTRACTGlutamine synthetase is the key enzyme of nitrogen assimilation, which is encoded in the first cistron ofglnALGoperon and is induced under nitrogen limiting conditions through transcriptional activation by NtrBC inSalmonellaandE. coli. 2-oxoglutarate serves as the carbon skeleton of glutamate and glutamine, but how 2-oxoglutarate fluctuation is controlled in response to nitrogen availability remained unknown. We show that theglnAmRNA produces an Hfq-dependent GlnZ sRNA from its 3’ sUTR through RNase E-mediated cleavage. Through a base-pairing mechanism, GlnZ primarily regulatessucA, encoding the E1o component of 2-oxoglutarate dehydrogenase. In the cells grown on glutamine as the nitrogen source, the endogenous GlnZ represses the expression of SucA to redirect the carbon flow from the TCA cycle to the nitrogen assimilation pathway. This study also clarifies that the release of GlnZ sRNA from theglnAmRNA by RNase E is essential for the post-transcriptional regulation ofsucA, and thus the mRNA coordinates the two independent functions to balance the supply and demand of the fundamental metabolites.
Early pre-neural serotonin modulates balance of late monoamines and behavioral patterns in fish model system
Authors: Ivashkin Evgeny , Spulber Stefan , Zinovyev Andrei , Yoshitake Takashi , Yoshitake Shimako , Kharchenko Olga , Khabarova Marina Yu. , Theofilopoulos Spyridon , Kehr Jan , Arenas Ernest , Ceccatelli Sandra , Voronezhskaya Elena E. , Adameyko Igor 
Published: July 2022

SummaryThe presence of serotonergic system during early pre-neural development is enigmatic and conserved amongst all studied invertebrate and vertebrate animals. We took advantage of zebrafish model system to address what is the role of early serotonin before first neurons form. Unexpectedly, we experimentally revealed the existence of delayed developmental neurogenic and behavioral effects resulting from the manipulations of pre-neural (zygote, blastula and gastrula) serotonergic system. In particular, the delayed effects included differences in the synthesis of serotonin in early serotonergic neurons in the central nervous system as well as in behavioral alterations after habituation in zebrafish larvae. These effects appeared as highly specific and did not coincide with any major abnormalities. The same manipulations of the serotonergic system at neural developmental stages did not show such effects, which confirms that early effects of serotonergic system manipulation are not based on retained serotonin in embryonic cells. Accordingly, gene expression analysis demonstrated specific changes only in response to the elevation of early pre-neural serotonin, which included the delayed and pre-mature onsets of different gene expression programs. Taken together, our results introduce a novel function of early pre-neural serotonergic system in a vertebrate embryo – tuning and fine control of specific mechanisms at later neural developmental stages that result in a mild variation of a behavioral adaptive spectrum.
Stromal Interaction Molecule 1 Maintains β Cell Identity and Function in Female Mice through Preservation of G Protein-Coupled Estrogen Receptor 1 Signaling
Authors: Sohn Paul , McLaughlin Madeline R. , Krishnan Preethi , Lee Chih-Chun , Kono Tatsuyoshi , Evans-Molina Carmella 
Published: July 2022

SummaryLoss of pancreatic β cell mass, identity, and function contribute to the development of diabetes. Here, we show that the endoplasmic reticulum (ER) calcium sensor, stromal interaction molecule 1 (STIM1), is critical for the maintenance of β cell function in female mice. When mice with β cell-specific deletion of STIM1 (STIM1Δβ) were challenged with high-fat diet, β cell dysfunction was observed in female, but not male, mice. Impaired glucose tolerance was accompanied by reductions in β cell mass, a concomitant increase in α cell mass, and significant reductions in the expression of markers of β cell maturity, including MafA and UCN3. Mechanistic assays demonstrated that the sexually dimorphic phenotype observed in STIM1Δβ mice was due in part to loss of signaling through the noncanonical 17-β estradiol receptor, GPER1. Together, these data suggest that STIM1 orchestrates pancreatic β cell function and identity through GPER1-mediated estradiol signaling.
Nuclear Location Bias of HCAR1 Drives Cancer Malignancy through Numerous Routes
Authors: Nezhady Mohammad Ali Mohammad , Cagnone Gael , Bajon Emmanuel , Chaudhari Prabhas , Modaresinejad Monir , Hardy Pierre , Maggiorani Damien , Quiniou Christiane , Joyal Jean-Sébastien , Beauséjour Christian , Chemtob Sylvain 
Published: July 2022

AbstractThe involvement of G-Protein-Coupled Receptors’ (GPCR) location bias in diverse cellular functions and their misregulation in pathology is an underexplored territory. HCAR1, a GPCR for lactate is linked to cancer progression, mainly due to Warburg effect, but its mechanism of action remains elusive. Here, we show HCAR1 has a nuclear localization, capable of signaling intranuclearly to induce nuclear-ERK and AKT phosphorylation concomitant with higher cancer cell proliferation and survival. We determine its nuclear interactome, proving its involvement in protein-translation and DNA-damage repair. Nuclear HCAR1 (N-HCAR1) directly interacts with chromatin/DNA promoting expression of genes involved in cellular migration. Notably, we show N-HCAR1 particularly regulates a broader transcriptomic signature than its PM counterpart, emphasizing on the facts that functional output of N-HCAR1 is larger than PM localized HCAR1. Our study presents several unprecedented processes by which a GPCR through location-biased activity regulate various cellular functions and how cancer cells exploit these.
Comprehensively characterizing evolutionarily conserved differential dosage compensations of the X chromosome during development and in diseases
Authors: Guo Mengbiao , Fang Zhengwen , Chen Bohong , Songyang Zhou , Xiong Yuanyan 
Published: July 2022

AbstractThe active X chromosome in mammals is upregulated to balance its dosage to autosomes during evolution. However, it is elusive why the currently known dosage compensation machinery showed uneven and small influence on X genes, necessitating systemic investigation of X dosage in different angles and identification of new dosage regulators. Here, based on >20,000 transcriptomes, we identified two X gene groups (genome ploidy-sensitive [PSX] and ploidy-insensitive [PIX] genes), showing distinct but evolutionarily-conserved (in both primates and mouse) dosage compensations (termed X-over-Autosome dosage Ratio, or XAR). We then explored XAR in diseases and in stem cells, where XAR is potentially important. We demonstrated that XAR-PIX was downregulated while XAR-PSX upregulated across cancer types at both RNA and protein levels. In contrast, XAR-PIX was upregulated while XAR-PSX downregulated during stem cell differentiation. Interestingly, XAR-PIX, but not XAR-PSX, was significantly lower and associated with autoantibodies and inflammation in lupus patients, suggesting that insufficient dosage of PIX genes may contribute to lupus pathogenesis. We further identified and experimentally validated two new XAR regulators,TP53andATRX. Collectively, we provided insights to further unravel the mystery of X dosage compensation in mammals and its pathophysiological roles in human diseases.