bluuebunny/crossref_metadata_2025_split huggingface dataset:
Expression Level Analysis of ACE2 Receptor Gene in African-American and Non-African-American COVID-19 Patients
Authors: Nyamari Marion N. , Omar Kauthar M. , Fayehun Ayorinde F. , Dachi Oumaima , Bwana Billiah Kemunto , Awe Olaitan I. 
Published: September 2023

AbstractBackgroundThe COVID-19 pandemic caused by SARS-CoV-2 has spread rapidly across the continents. While the incidence of COVID-19 has been reported to be higher among African-American individuals, the rate of mortality has been lower compared to that of non-African-Americans. ACE2 is involved in COVID-19 as SARS-CoV-2 uses the ACE2 enzyme to enter host cells. Although the difference in COVID-19 incidence can be explained by many factors such as low accessibility of health insurance among the African-American community, little is known about ACE2 expression in African-American COVID-19 patients compared to non-African-American COVID-19 patients. The variable expression of genes can contribute to this observed phenomenon.MethodologyIn this study, transcriptomes from African-American and non-African-American COVID-19 patients were retrieved from the sequence read archive and analyzed for ACE2 gene expression. HISAT2 was used to align the reads to the human reference genome, and HTseq-count was used to get raw gene counts. EdgeR was utilized for differential gene expression analysis, and enrichR was employed for gene enrichment analysis.ResultsThe datasets included 14 and 33 transcriptome sequences from COVID-19 patients of African-American and non-African-American descent, respectively. There were 24,092 differentially expressed genes, with 7,718 upregulated (log fold change > 1 and FDR 0.05) and 16,374 downregulated (log fold change −1 and FDR 0.05). The ACE2 mRNA level was found to be considerably downregulated in the African-American cohort (p-value = 0.0242, p-adjusted value = 0.038).ConclusionThe downregulation of ACE2 in the African-American cohort could indicate a correlation to the low COVID-19 severity observed among the African-American community.
Minimal circuit motifs for second-order conditioning in the insect mushroom body
Authors: Jürgensen Anna-Maria , Schmitt Felix Johannes , Nawrot Martin Paul 
Published: September 2023

AbstractIn well-established first-order conditioning experiments, the concurrence of a sensory cue with reinforcement forms an association, allowing the cue to predict future reinforcement. Once a sensory cue is established as a predictor, it can also serve as indirect reinforcement, a phenomenon referred to as second-order conditioning. In the insect mushroom body, such associations are encoded in the plasticity of the synapses between the intrinsic and output neurons of the mushroom body, a process mediated by the activity of dopaminergic neurons that encode reinforcement signals. In second-order conditioning, a new sensory cue is paired with an already established one that presumably activates dopaminergic neurons due to its predictive power of the reinforcement. We explore minimal circuit motifs in the mushroom body for their ability to support second-order conditioning. We found that dopaminergic neurons can either be activated directly by the mushroom body’s intrinsic neurons or via feedback from the output neurons via several pathways. We demonstrate that the circuit motifs differ in their computational efficiency and robustness and suggest a particular motif that relies on feedforward input of the mushroom body intrinsic neurons to dopaminergic neurons as a promising additional candidate for experimental evaluation. It differentiates well between trained and novel stimuli, demonstrating robust performance across a range of model parameters.
Examining Functional Linkages Between Conformational Dynamics, Protein Stability and Evolution of Cryptic Binding Pockets in the SARS-CoV-2 Omicron Spike Complexes with the ACE2 Host Receptor: Recombinant Omicron Variants Mediate Variability of Conserved Allosteric Sites and Binding Epitopes
Authors: Alshahrani Mohammed , Gupta Grace , Xiao Sian , Tao Peng , Verkhivker Gennady 
Published: September 2023

AbstractIn the current study, we explore coarse-grained simulations and atomistic molecular dynamics together with binding energetics scanning and cryptic pocket detection in a comparative examination of conformational landscapes and systematic characterization of allosteric binding sites in the SARS-CoV-2 Omicron BA.2, BA.2.75 and XBB.1 spike full-length trimer complexes with the host receptor ACE2. Microsecond simulations, Markov state models and mutational scanning of binding energies of the SARS-CoV-2 BA.2 and BA.2.75 receptor binding domain complexes revealed the increased thermodynamic stabilization of the BA.2.75 variant and significant dynamic differences between these Omicron variants. Molecular simulations of the SARS-CoV-2 Omicron spike full length trimer complexes with the ACE2 receptor complemented atomistic studies and enabled an in-depth analysis of mutational and binding effects on conformational dynamic and functional adaptability of the Omicron variants. Despite considerable structural similarities, Omicron variants BA.2, BA.2.75 and XBB.1 can induce unique conformational dynamic signatures and specific distributions of the conformational states. Using conformational ensembles of the SARS-CoV-2 Omicron spike trimer complexes with ACE2, we conducted a comprehensive cryptic pocket screening to examine the role of Omicron mutations and ACE2 binding on the distribution and functional mechanisms of the emerging allosteric binding sites. This analysis captured all experimentally known allosteric sites and discovered networks of inter-connected and functionally relevant allosteric sites that are governed by variant-sensitive conformational adaptability of the SARS-CoV-2 spike structures. The results detailed how ACE2 binding and Omicron mutations in the BA.2, BA.2.75 and XBB.1 spike complexes modulate the distribution of conserved and druggable allosteric pockets harboring functionally important regions. The results of are significant for understanding functional roles of druggable cryptic pockets that can be used for allostery-mediated therapeutic intervention targeting conformational states of the Omicron variants.
Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants
Authors: Qu Panke , Xu Kai , Faraone Julia N. , Goodarzi Negin , Zheng Yi-Min , Carlin Claire , Bednash Joseph S. , Horowitz Jeffrey C. , Mallampalli Rama K. , Saif Linda J. , Oltz Eugene M. , Jones Daniel , Gumina Richard J. , Liu Shan-Lu 
Published: September 2023

AbstractEvolution of SARS-CoV-2 requires the reassessment of current vaccine measures. Here, we characterized BA.2.86 and the XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, and EG.5.1 by sera from 3-dose vaccinated and bivalent vaccinated healthcare workers, XBB.1.5-wave infected first responders, and monoclonal antibody (mAb) S309. We assessed the biology of the variant Spikes by measuring viral infectivity and membrane fusogenicity. BA.2.86 is less immune evasive compared to FLip and other XBB variants, consistent with antigenic distances. Importantly, distinct from XBB variants, mAb S309 was unable to neutralize BA.2.86, likely due to a D339H mutation based on modeling. BA.2.86 had relatively high fusogenicity and infectivity in CaLu-3 cells but low fusion and infectivity in 293T-ACE2 cells compared to some XBB variants, suggesting a potentially differences conformational stability of BA.2.86 Spike. Overall, our study underscores the importance of SARS-CoV-2 variant surveillance and the need for updated COVID-19 vaccines.
MSMEG_0311 is a conserved essential polar protein involved in mycobacterium cell wall metabolism
Authors: Sodani Megha , Misra Chitra S. , Kulkarni Savita , Rath Devashish 
Published: September 2023

AbstractCell wall synthesis and cell division are two closely linked pathways in a bacterial cell which distinctly influence the growth and survival of a bacterium. This requires an appreciable coordination between the two processes, more so, in case of mycobacteria with an intricate multi-layered cell wall structure. In this study, we investigated a conserved gene cluster and show that knockdown of most of the genes in this cluster leads to growth defects. We further characterised one of the genes, MSMEG_0311. The repression of this gene not only imparts severe growth defect but also changes colony morphology. We demonstrate that the protein preferentially localises to the polar region and show its influence on the polar growth of the bacillus. A combination of permeability and drug susceptibility assay strongly suggests a cell wall associated function of this gene which is also corroborated by transcriptomic analysis of the knockdown. Considering the gene is highly conserved across mycobacterial species and appears to be essential for growth, it may serve as a potential drug target.
A systematic review on the incidence of influenza viruses in wastewater matrices: Implications for Public Health
Authors: Dlamini Mbasa , Msolo Luyanda , Ebomah Kingsley Ehi , Nontongana Nolonwabo , Okoh Anthony Ifeanyi 
Published: September 2023

AbstractInfluenza has historically been and remains a significant global health concern, causing substantial illness worldwide. Influenza is a serious public health issue in both industrialized and developing nations and it is characterized as an acute respiratory illness resulting from infection with influenza virus. Influenza viruses are RNA viruses with a negative sense and enveloped structure. These viruses possess segmented genomes, with influenza A and B viruses being the prevalent types affecting human populations. These viruses have been associated with disease outbreaks in some regions of the world as a result of excrement being introduced into the environment. Given the global implications of influenza and the limited availability of data for many countries, particularly in the African region where the prevalence and incidence of influenza remain largely unknown, there is a lack of published information regarding the detection of influenza viruses. Therefore, the purpose of this paper is to examine or review the frequency of influenza virus detection in wastewater samples, serving as an initial step toward gaining a better understanding of the burden of influenza. This includes exploring its epidemiology, the consequences of severe influenza infections, and the development of strategies to enhance supportive care and virus-specific therapies in resource-constrained, low-income settings.
Determinants ofde novoB cell responses to drifted epitopes in post-vaccination SARS-CoV-2 infections
Authors: Quirk Grace E. , Schoenle Marta V. , Peyton Kameron L. , Uhrlaub Jennifer L. , Lau Branden , Burgess Jefferey L. , Ellingson Katherine , Beitel Shawn , Romine James , Lutrick Karen , Fowlkes Ashley , Britton Amadea , Tyner Harmony L. , Caban-Martinez Alberto J. , Naleway Allison , Gaglani Manjusha , Yoon Sarang , Edwards Laura , Olsho Lauren , Dake Michael , LaFleur Bonnie J. , Nikolich Janko Ž. , Sprissler Ryan , Worobey Michael , Bhattacharya Deepta 
Published: September 2023

SummaryVaccine-induced immunity may impact subsequentde novoresponses to drifted epitopes in SARS-CoV-2 variants, but this has been difficult to quantify due to the challenges in recruiting unvaccinated control groups whose first exposure to SARS-CoV-2 is a primary infection. Through local, statewide, and national SARS-CoV-2 testing programs, we were able to recruit cohorts of individuals who had recovered from either primary or post-vaccination infections by either the Delta or Omicron BA.1 variants. Regardless of variant, we observed greater Spike-specific and neutralizing antibody responses in post-vaccination infections than in those who were infected without prior vaccination. Through analysis of variant-specific memory B cells as markers ofde novoresponses, we observed that Delta and Omicron BA.1 infections led to a marked shift in immunodominance in which some drifted epitopes elicited minimal responses, even in primary infections. Prior immunity through vaccination had a small negative impact on thesede novoresponses, but this did not correlate with cross-reactive memory B cells, arguing against competitive inhibition of naïve B cells. We conclude that dampenedde novoB cell responses against drifted epitopes are mostly a function of altered immunodominance hierarchies that are apparent even in primary infections, with a more modest contribution from pre-existing immunity, perhaps due to accelerated antigen clearance.
Digital markers from smartwatch data relate to non-motor clinical examinations of Parkinson’s disease
Authors: Schalkamp Ann-Kathrin , Harrison Neil A , Peall Kathryn J , Sandor Cynthia 
Published: September 2023

AbstractMonitoring of Parkinson’s disease (PD) has seen substantial improvement over recent years as digital sensors enable a passive and continuous collection of information in the home environment. However, the primary focus of this work has been motor symptoms, with little focus on the non-motor aspects of the disease. To address this, we combined longitudinal clinical non-motor assessment data and digital multi-sensor data from the Verily Study Watch for 85 participants from the Parkinson’s Progression Monitoring Initiative (PPMI) cohort with a diagnosis of PD. We show that digitally collected physical activity and sleep markers do significantly relate to clinical non-motor assessments of cognitive, autonomic, and daily living impairment. The observed poor predictive performance, however, highlights the need for better targeted digital markers to enable a monitoring of non-motor symptoms.
Prevalence of Long COVID-associated symptoms in adults with and without SARS-CoV-2 infection in Germany: Results of the population-based study “Corona Monitoring Nationwide 2021/22” (RKI-SOEP-2)
Authors: Poethko-Müller Christina , Ordonez-Cruickshank Ana , Nübel Julia , Sarganas Giselle , Gößwald Antje , Schmid Lorenz , Rosario Angelika Schaffrath , Hoebel Jens , Schlaud Martin , Scheidt-Nave Christa 
Published: September 2023

AbstractBackgroundControlled population-based studies on long-term health sequelae of SARS-CoV-2 can help to identify clinical signs specific to “Long COVID” and to evaluate this emerging public health challenge.AimTo examine prevalence differences of Long COVID-associated symptoms among adults with and without SARS-CoV-2 infection in Germany.MethodsThis population-based, retrospective study (11/2021-2/2022) included 7,683 working aged adults (18-65 years), a subset of the Corona Monitoring Nationwide study in Germany. Prior SARS-CoV-2 infection was defined based on self-reported PCR-confirmed infections and IgG-antibody dried blood spot testing. Participants answered a questionnaire including 19 common symptoms of Long COVID experienced in the six months preceding the survey. We estimated population-weighted prevalence of (1) individual symptoms, and (2) ≥1 symptom, with and without impact on work ability, by infection status within strata of sex, age group, income and comorbidity. We calculated model-adjusted prevalence differences and the probability that symptoms among infected are attributable to infection.Results12 of 19 symptoms showed a significantly higher prevalence in infected than non-infected participants, including fatigue (27.5% versus 18.3%; p<0.001), concentration problems (22.2% vs. 13.1%; p<0.001), shortness of breath (15.6% vs. 7.5%; p<0.001), and smell and taste disorder (10% vs. 1.2%; p<0.001). ≥1 symptom with impact on work ability was more prevalent following infection (16.0% vs. 12.2%; p=0.06) with a model-adjusted prevalence difference of 3.8% (95%-CI -0.5-8.0).ConclusionWe observed a rather small excess prevalence attributable to SARS-CoV-2 infection. However, the absolute number of persons places great demands on the health care system and may affect economic productivity.
Stress Biomarkers and Child Development in Young Children in Bangladesh
Authors: Butzin-Dozier Zachary , Mertens Andrew N. , Tan Sophia T. , Granger Douglas A. , Pitchik Helen O. , Il’yasova Dora , Tofail Fahmida , Rahman Md. Ziaur , Spasojevic Ivan , Shalev Idan , Ali Shahjahan , Karim Mohammed Rabiul , Shahriar Sunny , Famida Syeda Luthfa , Shuman Gabrielle , Shoab Abul K. , Akther Salma , Hossen Md. Saheen , Mutsuddi Palash , Rahman Mahbubur , Unicomb Leanne , Das Kishor K. , Yan Liying , Meyer Ann , Stewart Christine P. , Hubbard Alan , Naved Ruchira Tabassum , Parvin Kausar , Mamun Md. Mahfuz Al , Luby Stephen P. , Colford John M. , Fernald Lia C. H. , Lin Audrie 
Published: September 2023

BackgroundHundreds of millions of children in low-and middle-income countries are exposed to chronic stressors, such as poverty, poor sanitation and hygiene, and sub-optimal nutrition. These stressors can have physiological consequences for children and may ultimately have detrimental effects on child development. This study explores associations between biological measures of chronic stress in early life and developmental outcomes in a large cohort of young children living in rural Bangladesh.MethodsWe assessed physiologic measures of stress in the first two years of life using measures of the hypothalamic-pituitary-adrenal (HPA) axis (salivary cortisol and glucocorticoid receptor gene methylation), the sympathetic-adrenal-medullary (SAM) system (salivary alpha-amylase, heart rate, and blood pressure), and oxidative status (F2-isoprostanes). We assessed child development in the first two years of life with the MacArthur-Bates Communicative Development Inventories (CDI), the WHO gross motor milestones, and the Extended Ages and Stages Questionnaire (EASQ). We compared development outcomes of children at the 75th and 25th percentiles of stress biomarker distributions while adjusting for potential confounders (hereafter referred to as contrasts) using generalized additive models, which are statistical models where the outcome is predicted by a potentially non-linear function of predictor variables.ResultsWe analyzed data from 684 children (49% female) at both 14 and 28 months of age; we included an additional 765 children at 28 months of age. We observed 135 primary contrasts of the differences in child development outcomes at the 75thand 25thpercentiles of stress biomarkers, where we detected significant relationships in 5 out of 30 contrasts (17%) of HPA axis activity, 1 out of 30 contrasts (3%) of SAM activity, and 3 out of 75 contrasts (4%) of oxidative status. These findings revealed that measures of HPA axis activity were associated with poor development outcomes. We did not find consistent evidence that markers of SAM system activity or oxidative status were associated with developmental status.ConclusionsOur observations reveal associations between the physiological evidence of stress in the HPA axis with developmental status in early childhood. These findings add to the existing evidence exploring the developmental consequences of early life stress.
Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms
Authors: Zanoaga Mihaela-Diana , Friligkou Eleni , He Jun , Pathak Gita A. , Koller Dora , Cabrera-Mendoza Brenda , Stein Murray B. , Polimanti Renato 
Published: September 2023

AbstractBackgroundTo gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from UK Biobank (UKB; N=380,379), FinnGen Program (N=290,361), and Million Veteran Program (MVP; N=199,611) together with UKB genome-wide data (N=33,224) related to 3,935 brain imaging-derived phenotypes (IDP).MethodsA genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX–brain associations, a two-sample Mendelian randomization (MR) was performed considering multiple methods and sensitivity analyses. A subsequent multivariable MR (MVMR) was executed to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms.ResultsAfter false discovery rate correction (FDR q<0.05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UKB, FinnGen, and MVP). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent MVMR analysis, reduced area of the right posterior middle-cingulate gyrus (rpMCG; beta=-0.09, P= 8.01×10-4) and reduced gray-matter volume of the right anterior superior temporal gyrus (raSTG; beta=-0.09, P=1.55×10-3) had direct effects on ANX. In the ANX symptom-level analysis, rpMCG was negatively associated with “tense sore oraching muscles during the worst period of anxiety” (beta=-0.13, P=8.26×10-6).ConclusionsThis study identified genetically inferred effects generalizable across large cohorts, contributing to understand how changes in brain structure and function can lead to ANX.
Development and Standardization of a Classification System for Osteoradionecrosis: Implementation of a Risk-Based Model
Authors: Watson Erin E , Hueniken Katrina , Lee Junhyung , Huang Sophie H , Maghrabi A Amr El , Xu Wei , Moreno Amy C , Tsai C. Jillian , Hahn Ezra , McPartlin Andrew J , Yao Christopher MKL , Goldstein David P , De Almeida John R , Waldon John N , Fuller Clifton David , Hope Andrew J , Ruggiero Salvatore L , Glogauer Michael , Hosni Ali A 
Published: September 2023

AbstractPurposeOsteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.MethodsConsecutive head-and-neck cancer (HNC) patients treated with curative-intent IMRT (≥45Gy) in 2011-2018 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared to fifteen existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection).ResultsORN was identified in 219 out of 2732 (8%) consecutive HNC patients. Factors associated with high-risk of ORN were: oral-cavity or oropharyngeal primaries, received IMRT dose ≥60Gy, current/ex-smokers, and/or stage III-IV periodontal disease. The ORN rate for high-risk vs low-risk patients was 12.7% vs 3.1% (p<0.001) with an area-under-the-receiver-operating-curve (AUC) of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, RadORN, was proposed based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems.ConclusionWe identified risk factors for ORN, and proposed a novel ORN classification system based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN, and may facilitate clinical care and clinical trials.