bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humoral immune responses against SARS-CoV-2 variants including omicron in solid organ transplant recipients after three doses of a COVID-19 mRNA vaccine
Authors: Saharia Kapil K. , Husson Jennifer S. , Niederhaus Silke V. , Iraguha Thierry , Avila Stephanie V. , Yoo Youngchae J. , Hardy Nancy M. , Fan Xiaoxuan , Omili Destiny , Crane Alice , Carrier Amber , Xie Wen Y. , Vander Mause Erica , Hankey Kim , Bauman Sheri , Lesho Patricia , Mannuel Heather D. , Ahuja Ashish , Mathew Minu , Avruch James , Baddley John , Goloubeva Olga , Shetty Kirti , Dahiya Saurabh , Rapoport Aaron P. , Luetkens Tim , Atanackovic Djordje 
Published: January 2022

ABSTRACTBackgroundSolid organ transplant recipients (SOTR), who typically receive post-transplant immunosuppression, show increased COVID-19-related mortality. It is unclear whether an additional dose of COVID-19 vaccines in SOTR can overcome the reduced immune responsiveness against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants.MethodsWe performed a prospective cohort study of 53 SOTR receiving SARS-CoV-2 vaccination into a prospective cohort study performing detailed immunoprofiling of humoral immune responses against SARS-CoV-2 and its variants.ResultsPrior to the additional vaccine dose, 60.3% of SOTR showed no measurable neutralization and only 18.9% demonstrated neutralizing activity of >90% following two vaccine doses. More intensive immunosuppression, antimetabolites in particular, negatively impacted antiviral immunity. While absolute IgG levels were lower in SOTR than controls, antibody titers against microbial recall antigens were in fact higher. In contrast, SOTR showed reduced vaccine-induced IgG/IgA antibody titers against SARS-CoV-2 and its delta variants. Vaccinated SOTR showed a markedly fewer linear B cell epitopes, indicating reduced B cell diversity. Importantly, a third vaccine dose led to an increase in anti-SARS-CoV-2 antibody titers and neutralizing activity across alpha, beta and delta variants. However, we observed a significant decrease in anti-spike antibody titers with the omicron variant.ConclusionsOnly a small subgroup of SOTR generated functionally relevant antibodies after completing the initial vaccine series based on dysfunctional priming of immune responses against novel antigens. An additional dose of the vaccine results in dramatically improved antibody responses against all SARS-CoV-2 variants except omicron.
Increased Risk of Poor Clinical Outcome in COVID-19 Patients with Diabetes Mellitus and in-hospital Mortality Predictors: A Retrospective Cohort from a Tertiary Hospital in Indonesia
Authors: Mokoagow Md Ikhsan , Harbuwono Dante Saksono , Kshanti Ida Ayu , Rumende C Martin , Subekti Imam , Harimurti Kuntjoro , Lie Khie Chen , Shatri Hamzah 
Published: January 2022

AbstractAimTo determine association between diabetes in confirmed cases of COVID-19 and intensive care admission and in-hospital mortality, evaluate several laboratory parameters as mortality predictor, and develop predictors of in-hospital mortality among diabetics with COVID-19.MethodsThis retrospective cohort recruited all cases of COVID-19 hospitalized in Fatmawati General Hospital during March to October 2020. Inclusion criteria was RT-PCR confirmed cases of COVID-19 who aged 18 years and older while exclusion criteria were incomplete medical record or cannot be found and pregnant women.ResultsWe enrolled 506 participants to this study with median age of 51 years (IQR:22), female (56.32%), and diabetes (28.46%). Diabetes increased intensive care admission (adjusted OR:6.07;95%CI:3.52-10,43) and in-hospital mortality (adjusted OR:50;95%CI:1.61-3.89). In predicting in-hospital mortality, ferritin and lactate dehydrogenase offered an acceptable discrimination, AUC:0.71 (95%CI: 0.62-0.79) and AUC:0.70 (95%CI: 0.61-0.78), respectively. The optimal cut-off of predicting mortality for ferritin was 786 g/mL and for LDH was 514.94 u/L. Factors include age above 70 years old, RBGs level on admission above 250 mg/dL or below 140 mg/dL, ferritin level above 786 ng/mL, and presence of ARDS increased the odds of mortality among individuals with diabetes.ConclusionsDiabetes increases risk of intensive care admission and in hospital mortality in COVID-19. Multivariate analysis showed that older age, RBG on admission, high ferritin level, presence of ARDS increased the odds of mortality among individuals with diabetes.
Identifying the critical time window for the association of the early-life gut microbiome and metabolome with childhood neurodevelopment
Authors: Sun Zheng , Lee-Sarwar Kathleen , Kelly Rachel S. , Lasky-Su Jessica A. , Litonjua Augusto A. , Weiss Scott T. , Liu Yang-Yu 
Published: January 2022

ABSTRACTIt has been widely recognized that a critical time window for neurodevelopment occurs in early life, and that the host’s gut microbiome plays an important role in neurodevelopment. While murine models have demonstrated that the maternal gut microbiome also influences offspring brain development, for humans it is still unclear if the critical time window for the association between the gut microbiome and neurodevelopment is prenatal, postnatal or both. Here we leverage a large-scale human study and compare the associations between the gut microbiota and metabolites from mothers and their children with the children’s neurodevelopment. We show, for the first time, that the maternal gut microbiome is more relevant than the children’s gut microbiome to the children’s neurodevelopment in the first year of life. Interestingly, the roles of the same taxa with respect to neurodevelopment can be opposite at the two stages of fetal neurodevelopment. These findings shed light on potential therapeutic interventions to prevent neurodevelopmental disorders.
Sample Size Calculations for Variant Surveillance in the Presence of Biological and Systematic Biases
Authors: Wohl Shirlee , Lee Elizabeth C. , DiPrete Bethany L. , Lessler Justin 
Published: January 2022

SUMMARYAs demonstrated during the SARS-CoV-2 pandemic, detecting and tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. Pathogen genome sequencing has emerged as the primary tool for variant characterization, so it is important to consider the number of sequences needed when designing surveillance programs or studies, both to ensure accurate conclusions and to optimize use of limited resources. However, current approaches to calculating sample size for variant monitoring often do not account for the biological and logistical processes that can bias which infections are detected and which samples are ultimately selected for sequencing. In this manuscript, we introduce a framework that models the full process— including potential sources of bias—from infection detection to variant characterization, and we demonstrate how to use this framework to calculate appropriate sample sizes for sequencing-based surveillance studies. We consider both cross-sectional and continuous sampling, and we have implemented our method in a publicly available tool that allows users to estimate necessary sample sizes given a specific aim (e.g., variant detection or measuring variant prevalence) and sampling method. Our framework is designed to be easy to use, while also flexible enough to be adapted to other pathogens and surveillance scenarios.
Viral cultures, PCR Cycle threshold values and viral load estimation for COVID-19 infectious potential assessment in transplant patients: systematic review - Protocol Version 30 December 2021
Authors: Jefferson Tom , Spencer Elizabeth A. , Maltoni Susanna , Brassey Jon , Onakpoya Igho J. , Rosca Elena C. , Plüddemann Annette , Evans David H. , Conly John M. , Heneghan Carl J. 
Published: January 2022

AbstractThis is the protocol for a systematic review focussing on people receiving solid organ or hematopoietic stem cell transplants.Our research questions are as follows:What is the relationship between serial PCR Ct value or other measures of viral burden, and the likelihood and duration of the presence of infectious virus from viral culture, among transplant recipients with SARS-CoV-2 infection?What is the influence of age, sex, underlying pathologies, degree of immunosuppression, vaccination status, COVID-19 symptoms and COVID-19 disease course on viral burden and the likelihood of presence of infectious SARS-CoV-2?We will include single studies reporting serial Cts from sequential rt-PCR testing or other measures of viral burden such as RNA gene copies of respiratory samples (from nasopharyngeal specimens) along with viral culture data on the same samples, from patients about to receive a transplant or who are post transplant with SARS-CoV-2 infection.
Interictal SEEG resting-state connectivity localizes seizure onset zone and predicts seizure outcome
Authors: Jiang Haiteng , Kokkinos Vasileios , Ye Shuai , Urban Alexandra , Bagić Anto , Richardson Mark , He Bin 
Published: January 2022

AbstractStereotactic-electroencephalography (SEEG) is a common neurosurgical method to localize epileptogenic zone in drug resistant epilepsy patients and inform treatment recommendations. In the current clinical practice, localization of epileptogenic zone typically requires prolonged recordings to capture seizure, which may take days to weeks. Although epilepsy surgery has been proven to be effective in general, the percentage of unsatisfactory seizure outcomes is still concerning. We developed a method to identify the seizure onset zone (SOZ) and predict seizure outcome using short-time resting-state SEEG data. In a cohort of 43 drug resistant epilepsy patients, we estimated the information flow via directional connectivity and inferred the excitation-inhibition ratio from the 1/f power slope. We hypothesized that the antagonism of information flow at multiple frequencies between SOZ and non-SOZ underlying the relatively stable epilepsy resting state could be related to the disrupted excitation-inhibition balance. We found higher excitability in non-SOZ regions compared to the SOZ, with dominant information flow from non-SOZ to SOZ regions, probably reflecting inhibitory input from non-SOZ to prevent seizure initiation. Greater differences in information flow between SOZ and non-SOZ regions were associated with favorable seizure outcome. By integrating a balanced random forest model with resting-state connectivity, our method localized the SOZ with an accuracy of 85% and predicted the seizure outcome with an accuracy of 77% using clinically determined SOZ. Overall, our study suggests that brief resting-state SEEG data can significantly facilitate the identification of SOZ and may eventually predict seizure outcomes without requiring long-term ictal recordings.
Point-of-care lung ultrasound predicts severe disease and death due to COVID-19: a prospective cohort study
Authors: Blair Paul W. , Siddharthan Trishul , Liu Gigi , Bai Jiawei , East Joshua , Herrera Phabiola , Anova Lalaine , Mahadevan Varun , Hossen Shakir , Seo Stefanie , Sonuga Olamide , Lawrence Joshua , Peters Jillian , Cox Andrea , Manabe Yukari C. , Fenstermacher Katherine , Shea Sophia , Rothman Richard E. , Hansoti Bhakti , Sauer Lauren , Crainiceanu Ciprian , Clark Danielle V. 
Published: January 2022

AbstractObjectiveThe clinical utility of point-of-care lung ultrasound (LUS) for disease severity triage of hospitalized patients with COVID-19 is unclear.DesignProspective cohort studySettingA large tertiary care center in Maryland, USA between April 2020 to September 2021.PatientsHospitalized adults (≥18 years of age) with positive SARS-CoV-2 RT-PCR results.InterventionsNone.Measurements and Main ResultsAll patients were scanned using a standardized protocol including 12 lung zones and followed to determine clinical outcomes until hospital discharge and vital status at 28-days. Ultrasounds were independently reviewed for lung and pleural line artifacts and abnormalities, and the mean Lung Ultrasound Score (ranging from 0 to 3) across lung zones (mLUSS) was determined. The primary outcome was time to ICU-level care, defined as high flow oxygen, noninvasive, or mechanical ventilation, within 28-days of the initial ultrasound. Cox proportional hazards regression models adjusted for age and sex were fit for mLUSS and each ultrasound covariate. A total of 264 participants were enrolled in the study; the median age was 59 years and 114 (43.2) % of participants were female. The median mLUSS was 1 (interquartile range: 0.5 to 1.3). Following enrollment, 29 (11.0%) participants went on to require ICU-level care and 14 (5.3%) subsequently died by 28 days. Each increase in mLUSS at enrollment was associated with disease progression to ICU-level care (aHR = 3.63; 95% CI: 1.23 to 10.65) and 28-day mortality (aHR = 4.50; 95% CI: 1.52 to 13.31). Pleural line abnormalities were independently associated with disease progression to ICU-level care (aHR = 18.86; CI: 1.57 to 226.09).ConclusionsParticipants with a mLUSS ≥1 or pleural line changes on LUS had an increased likelihood of subsequent requirement of high flow oxygen or greater. LUS is a promising tool for assessing risk of COVID-19 progression at the bedside.
Memory persistence and differentiation into antibody-secreting cells accompanied by positive selection in longitudinal BCR repertoires
Authors: Mikelov Artem I. , Alekseeva Evgeniia I. , Komech Ekaterina A. , Staroverov Dmitriy B. , Turchaninova Maria A. , Shugay Mikhail , Chudakov Dmitriy M. , Bazykin Georgii A. , Zvyagin Ivan V. 
Published: January 2022

AbstractThe stability and plasticity of B cell-mediated immune memory ensures the ability to respond to the repeated challenges. We have analyzed the longitudinal dynamics of immunoglobulin heavy chain repertoires from memory B cells, plasmablasts, and plasma cells from the peripheral blood of generally healthy volunteers. We reveal a high degree of clonal persistence in individual memory B cell subsets, with inter-individual convergence in memory and antibody-secreting cells (ASCs). ASC clonotypes demonstrate clonal relatedness to memory B cells, and are transient in peripheral blood. We identify two clusters of expanded clonal lineages with differing prevalence of memory B cells, isotypes, and persistence. Phylogenetic analysis revealed signs of reactivation of persisting memory B cell-enriched clonal lineages, accompanied by new rounds of affinity maturation during proliferation and differentiation into ASCs. Negative selection contributes to both persisting and reactivated lineages, preserving the functionality and specificity of BCRs to protect against current and future pathogens.
Escherichia coli chemotaxis to competing stimuli in a microfluidic device with a constant gradient
Authors: Zhao Xueying , Ford Roseanne M. 
Published: January 2022

AbstractIn natural systems bacteria are exposed to many chemical stimulants; some attract chemotactic bacteria as they promote survival, while others repel bacteria because they inhibit survival. When faced with a mixture of chemoeffectors, it is not obvious which direction the population will migrate. Predicting this direction requires an understanding of how bacteria process information about their surroundings. We used a multiscale mathematical model to relate molecular level details of their two-component signaling system to the probability that an individual cell changes its swimming direction to the chemotactic velocity of a bacterial population. We used a microfluidic device designed to maintain a constant chemical gradient to compare model predictions to experimental observations. We obtained parameter values for the multiscale model of Escherichia coli chemotaxis to individual stimuli, α-methylaspartate and nickel ion, separately. Then without any additional fitting parameters, we predicted the response to chemoeffector mixtures. Migration of E. coli toward α-methylaspartate was modulated by adding increasing concentrations of nickel ion. Thus, the migration direction was controlled by the relative concentrations of competing chemoeffectors in a predictable way. This study demonstrated the utility of a multiscale model to predict the migration direction of bacteria in the presence of competing chemoeffectors.
A systematic characterization of intrinsically formed microglia-like cells during retinal organoid differentiation
Authors: Bartalska Katarina , Hübschmann Verena , Korkut-Demirbaş Medina , Cubero Ryan John A. , Venturino Alessandro , Rössler Karl , Czech Thomas , Siegert Sandra 
Published: January 2022

AbstractBrain organoids differentiated from human induced pluripotent stem cells provide a unique opportunity to investigate the development, organization and connectivity of neurons in a complex cellular environment. However, organoids usually lack microglia, brain-resident immune cells which are both present in the early human embryonic brain and participate in neuronal circuit development.Here, we find that microglia innately develop in unguided retinal organoid differentiation between week 3 and 4 in 2.5D culture and appear later in floating, non-pigmented, 3D-cystic compartments. We enriched for cystic structures using a low-dosed BMP4 application and performed mass spectrometry, thus defining the protein composition of microglia-containing compartments. We found that cystic compartments expressed both mesenchymal and epithelial markers with microglia enriched in the mesenchymal region. Interestingly, microglia-like cells started to express the border-associated macrophage marker CD163. The preferential localization of human microglia to a mesenchymal compartment provides insight into the behavior and migration of microglia. The model will ultimately allow detailed study of these enigmatic cells and how they enter and distribute within the human brain.
Intermittent compression increases flow through a gel: a mechanical model perhaps relevant to flow of cerebrospinal fluid
Authors: Hale Michael G. , Coles Jonathan A. 
Published: January 2022

AbstractExchange of molecules between cerebrospinal fluid (CSF) and brain cells contributes to brain function and protection from dementia. Despite widespread acceptance of the ‘glymphatic’ theory, the route by which CSF is brought close enough to the neural tissue for solutes to be exchanged by extracellular diffusion is not entirely clear. Exogenous molecules injected into CSF are observed to reach the basement lamina that surrounds the dense capillary network. Transport of solutes by diffusion along the basement lamina, a gel of macromolcules about 100 nm thick, would be too slow; bulk flow in a static geometry would require unphysiologically high pressures. However, it is known that the pulsation of blood aids transport of CSF, and we hypothesized that this is because the pulsation intermittently squeezes the pericapillary lamina. In a primitive mimicry, we have tested whether intermittent squeezing increases flow through an agar gel. In all but one of 216 tests, pulsation caused a reversible increase, sometimes by a factor of 100 or more. The enhancement was greatest for frequencies 5-11 Hz and, over the tested range of pressure heads (20 - 50 cmH2O), was greatest for the lowest pressure. The results suggest a reason why exercise slows the aging of the brain.
Structure-function relationships in mitochondrial transcriptional condensates
Authors: Feric Marina , Sarfallah Azadeh , Dar Furqan , Temiakov Dmitry , Pappu Rohit V. , Misteli Tom 
Published: January 2022

AbstractPhase separation organizes many membraneless structures in cells. The functional consequences of concentrating cellular machinery into biomolecular condensates, however, are largely unclear. One fundamental cellular function that has been linked to condensate formation is transcription. Here, we have reconstituted mitochondrial transcription in condensates from purified components. We find that the core components of the mttranscriptional machinery form multi-phasic, viscoelastic condensatesin vitro. Strikingly, the rates of condensate-mediated transcription are substantially lower than equivalent reactions in bulk solution. These condensate-mediated decreases in transcriptional rates are associated with the formation of dynamically arrested vesicular structures that are driven by the production and accumulation of RNA during transcription. Using coarse-grained, equilibrium simulations, we show that the generation of RNA alters the phase behavior and the organization of transcriptional components within condensates and that thein vitromtcondensates are non-equilibrium structures. Together, ourin vitroandin silicoapproaches shed light on how proteins and (ribo)nucleic acids biophysically self-assemble within mitochondriain vivo. Our results highlight the complex morphologies of transcribing, multicomponent condensates and they illustrate the interdependent structure-function relationships in condensates.Significance StatementMitochondria condense their genome into transcriptionally active mt-nucleoids. These structures fit the definition of biomolecular condensates that form via macromolecular phase separation. We take advantage of the ability to reconstitute mitochondrial transcriptional condensates in vitro from minimal components. We find that the production and accumulation of RNA alters the phase behavior of transcriptional condensates. The altered phase behavior is linked to the formation of arrested, non-equilibrium vesicular structures. Similar changes to phase behavior of proteins and (ribo)nucleic acids can be recapitulated in live mitochondria through knockdown of mt-nucleoid core components. Computer simulations help identify biophysical mechanisms that are needed to maintain the steady-state structures of transcriptional condensates.
White-matter degradation and dynamical compensation support age-related functional alterations in human brain
Authors: Petkoski Spase , Ritter Petra , Jirsa Viktor K. 
Published: January 2022

AbstractStructural connectivity of the brain at different ages is analyzed using diffusion-weighted Magnetic Resonance Imaging (MRI) data. The largest decrease of the number and average length of streamlines is found for the long inter-hemispheric links, with the strongest impact for frontal regions. From the BOLD functional MRI (fMRI) time series we identify age-related changes of dynamic functional connectivity (dFC) and spatial covariation features of the FC links captured by metaconnectivity (MC). They indicate more constant dFC, but wider range and variance of MC. Finally we applied computational whole-brain network model based on oscillators, which mechanistically expresses the impact of the spatio-temporal structure of the brain (weights and the delays) to the dynamics. With this we tested several hypothesis, which revealed that the spatio-temporal reorganization of the brain with ageing, supports the observed functional fingerprints only if the model accounts for: (i) compensation of the individual brains for the overall loss of structural connectivity, and (ii) decrease of propagation velocity due to the loss of myelination. We also show that having these two conditions, it is sufficient to decompose the time-delays as bimodal distribution that only distinguishes between intra- and inter-hemispheric delays, and that the same working point also captures the static FC the best.