bluuebunny/crossref_metadata_2025_split huggingface dataset:
TONSILS ARE MAJOR SITES OF PROLONGED SARS-COV-2 INFECTION IN CHILDREN
Authors: Lima Thais M. , Martins Ronaldo B. , Miura Carolina S. , Souza Maria V. O. , Cassiano Murilo H. A. , Rodrigues Tamara S. , Veras Flávio P. , Sousa Josane F. , Gomes Rogério , Almeida Glaucia M. , Melo Stella R. , Silva Gabriela C. , Dias Matheus , Capato Carlos F. , Silva Maria L. , Barros Veridiana E. D. , Carenzi Lucas R. , Zamboni Dario S. , Jorge Daniel M. M. , Tamashiro Edwin , Anselmo-Lima Wilma T. , Valera Fabiana C. P. , Arruda Eurico 
Published: January 2023

ABSTRACTIn the present study, we show that SARS-CoV-2 can infect palatine tonsils and adenoids in children without symptoms of COVID-19, with no history of recent upper airway infection. We studied 48 children undergoing tonsillectomy due to snoring/OSA or recurrent tonsillitis between October 2020 and September 2021. Briefly, nasal cytobrush (NC), nasal wash (NW) and tonsillar tissue fragments obtained at surgery were tested by RT-PCR, immunohistochemistry (IHC), flow cytometry and neutralization assay. We detected the presence of SARS-CoV-2 in at least one specimen tested in 25% of patients (20% in palatine tonsils and 16.27% in adenoids, 10.41% of NC and 6.25% of NW). Importantly, in 2 of the children there was evidence of laboratory-confirmed acute infection 2 and 5 months before surgery. IHC revealed the presence of SARS-CoV-2 nucleoprotein in epithelial surface and in lymphoid cells in both extrafollicular and follicular regions, in adenoids and palatine tonsils. Flow cytometry showed that CD20+B lymphocytes were the most infected phenotypes by SARS-CoV-2 NP, followed by CD4+ and CD8+ T lymphocytes, and CD14+ macrophages and dendritic cells. Additionally, IF indicated that SARS-CoV-2-infected tonsillar tissues had increased expression of ACE2 and TMPRSS2. NGS sequencing demonstrated the presence of different SARS CoV-2 variants in tonsils from different tissues. SARS-CoV-2 antigen detection was not restricted to tonsils, but was also detected in nasal cells from the olfactory region. In conclusion, palatine tonsils and adenoids are sites of prolonged infection by SARS-CoV-2 in children, even without COVID-19 symptoms.
Predicting vasospasm risk using first presentation aneurysmal subarachnoid haemorrhage volume: a semi-automated CT image segmentation analysis in ITK-SNAP
Authors: Street James S , Pandit Anand S , Toma Ahmed K 
Published: January 2023

AbstractPurposeCerebral vasospasm following aneurysmal subarachnoid haemorrhage (aSAH) is a significant complication associated with poor neurological outcomes. We present a novel, semi-automated pipeline in ITK-SNAP to segment subarachnoid blood volume from initial CT head (CTH) scans and use this to predict future radiological vasospasm.Methods42 patients were admitted between February 2020 and December 2021 to our tertiary neurosciences centre, and whose initial referral CTH scan was used for this retrospective cohort study. Blood load was segmented using a semi-automated random forest classifier and active contour evolution implemented in the open-source medical imaging analysis software ITK-SNAP. Clinical data were extracted from electronic healthcare records in order to fit models aimed at predicting radiological vasospasm risk.ResultsSemi-automated segmentations demonstrated excellent agreement with manual, expert-derived volumes (mean Dice coefficient=0.92). Total normalised blood volume, extracted from CTH images at first presentation, was significantly associated with greater odds of later radiological vasospasm, increasing by approximately 7% for each additional cm3of blood (OR=1.069, 95% CI: 1.021-1.120; p<.005). Greater blood volume was also significantly associated with vasospasm of a higher Lindegaard ratio, of longer duration, and a greater number of discrete episodes. Total blood volume predicted radiological vasospasm with a greater accuracy as compared to the modified Fisher scale (AUC= 0.86 vs 0.70), and was of independent predictive value.ConclusionSemi-automated methods provide a plausible pipeline for the segmentation of blood from CT head images in aSAH, and total blood volume is a robust, extendable predictor of radiological vasospasm, outperforming the modified Fisher scale. Greater subarachnoid blood volume significantly increases the odds of subsequent vasospasm, its time course and its severity.
Within-person Relationships of Sleep Duration with Next-Day Stress and Affect in the Daily Life of Adults with Type-1 Diabetes
Authors: Jin Haomiao , Gonzalez Jeffrey S , Pyatak Elizabeth , Schneider Stefan , Hoogendoorn Claire J , Hernandez Raymond , Lee Pey-Jiuan , Spruijt-Metz Donna 
Published: January 2023

AbstractObjectiveThe objective of this study is to examine the within-person relationships between sleep duration and next-day stress and affect in the daily life of individuals with T1D.MethodsStudy participants were recruited in the Function and Emotion in Everyday Life with Type 1 Diabetes (FEEL-T1D) study. Sleep duration was derived by synthesizing objective (actigraphy) and self-report measures. General and diabetes-specific stress and positive and negative affect were measured using ecological momentary assessment. Multilevel regression was used to examine the within-person relationships between sleep duration and next-day stress and affect. Cross-level interactions were used to explore whether gender and baseline depression and anxiety moderated these within-person relationships.ResultsAdults with T1D (n=166) completed measurements for 14 days. The average age was 40.99 years, and 91 participants (54.82%) were female. The average sleep duration was 7.29 hours (SD=1.18 hours). Longer sleep was significantly associated with lower general stress (p<0.001) but not diabetes-specific stress (p=0.18) on the next day. There were significant within-person associations of longer sleep with lower levels on next-day negative affect (overall, p=0.002, disappoint, p=0.05; sad, p=0.05; tense, p<0.001; upset, p=0.008; anxious, p=0.04). There were no significant associations with positive affect. Examination of the interaction effects did not reveal significant differential relationships for men and women and for individuals with and without depression or anxiety at baseline.ConclusionFindings from this study suggest optimizing sleep duration as an important interventional target for better managing general stress and improving daily emotional wellbeing of individuals with T1D.
The impact of COVID-19 lockdown on a cohort of adults with recurrent major depressive disorder from Catalonia: a decentralized longitudinal study using remote measurement technology
Authors: Lavalle R. , Condominas E. , Haro JM , Giné-Vázquez I. , Bailon R , Laporta E , Garcia E , Kontaxis S , Riquelme G. , Lombardini F. , Preti A. , Peñarrubia-María MT , Coromina M. , Arranz B. , Vilella E. , Rubio E. ,   RADAR-MDD-Spain, Matcham F. , Lamers F , Hotopf M. , Penninx BWJH , Annas P. , Narayan V , Simblett S. , Siddi S 
Published: January 2023

AbstractBackgroundThe present study analyzes the effects of each containment phase of the first COVID-19 wave on depression levels in a cohort of adults with a history of major depressive disorder (MDD).MethodsThis analysis is part of the Remote Assessment of Disease and Relapse-MDD (RADAR-MDD) study. Individuals included had a diagnosis of DSM-5 major depressive disorder (MDD), at least two episodes of major depression (MDE), one of them in the previous two years. Depression was evaluated with the Patient Health Questionnaire-8 (PHQ-8) and anxiety with the Generalized Anxiety Disorder-7 (GAD-7). A total of 121 participants recruited from Catalonia were registered from November 1, 2019, to October 16, 2020. Levels of depression were explored across the phases (pre-lockdown, lockdown, four post-lockdown phases) of the restrictions imposed by the Spanish/Catalan governments. Then, a mixed model was fitted to estimate how depression varied over the phases.ResultsA small but statistically significant rise in the depressive severity was found during the lockdown and phase 0 (early post-lockdown), as compared with the pre-lockdown phase in this sample with a history of MDD. Those with low pre-lockdown depression experienced an increase in depression levels during the “new normality”. We observed a significant decrease in the depression levels during the “new normality” in those with high pre-lockdown depression, compared to the pre-lockdown period.ConclusionThese findings suggest that COVID-19 restrictions impacted on the depression of individuals diagnosed with MDD, depending on their pre-lockdown depression severity. Furthermore, these subjects worsened when the restrictions were harder, during the lockdown and the early post-lockdown.
TERTexpression is associated with metastasis from thin primaries, exhausted CD4+ T cells in melanoma and with DNA repair across cancer entities
Authors: Kuhn Christina Katharina , Meister Jaroslawna , Kreft Sophia , Stiller Mathias , Puppel Sven-Holger , Zaremba Anne , Scheffler Björn , Ullrich Vivien , Schöneberg Torsten , Schadendorf Dirk , Horn Susanne 
Published: January 2023

AbstractTelomerase reverse transcriptase (TERT) promoter mutations occur frequently in cancer, have been associated with increasedTERTexpression and cell proliferation, and could potentially influence therapeutic regimens for melanoma. As the role ofTERTexpression in malignant melanoma and the non-canonical functions of TERT remain understudied, we aimed to extend the current knowledge on both types ofTERTalterations with respect to survival, further clinical and molecular parameters. Using multivariate models,TERTalterations were not consistently associated with survival in melanoma cohorts under immune checkpoint inhibition. The presence of CD4+ T cells increased withTERTexpression and correlated with the expression of exhaustion markers. While the frequency of promoter mutations did not change with Breslow thickness,TERTexpression was increased in metastases arising from thinner primaries. Enrichment analyses of single-cell RNA-seq showedTERTexpression is associated with genes involved in cell migration and dynamics of the extracellular matrix, supporting the role ofTERTduring invasion and metastasis. Co-regulated genes in several bulk tumors and single-cell RNA-seq cohorts also indicated non-canonical functions ofTERTrelated to mitochondrial DNA stability and nuclear DNA repair in line with increasedTERTexpression during chromothripsis (PCAWG cohort) and under hypoxic conditions (PCAWG and SKCM cohorts). Also in glioblastoma (Klughammer and PCAWG cohorts),TERTwas co-expressed with DNA repair genes. Our results thus indicate a relevance ofTERTexpression in melanoma metastasis, T cell dysfunction and DNA repair across cancer entities.SignificanceIn addition to the frequently occurringTERTpromoter mutations, we testTERTexpression with respect to clinical and molecular associates, extending the canonical role ofTERTin melanoma and other cancer entities.
A targeted isotope dilution mass spectrometry assay for Osteopontin quantification in plasma of metastatic breast cancer patients
Authors: Leslie Andrew , Teh Eve , Druker Arik , Pinto Devanand M. 
Published: January 2023

AbstractOsteopontin (OPN) is a secreted glycophosphoprotein that derives its name from its high abundance in bone and secretion by osteoblasts. It is also secreted by a number of immune cells and, therefore, is present in human plasma at nanogram per millilitre levels where it affects cell adhesion and motility. These properties implicate OPN as a promotor of tumor progression. Plasma OPN is primarily measured by enzyme-linked immunosorbent assay (ELISA). However, due to the complexity of the various OPN isoforms, conflicting results have been obtained on the use of OPN as a biomarker even in the same disease condition. These discrepant results may result from the difficulty in comparing ELISA results obtained with different antibodies that target unique OPN epitopes. Mass spectrometry can be used to quantify proteins in plasma and, by targeting OPN regions that do not bear post-translational modifications, may provide more consistent quantification. However, the low (ng/mL) levels in plasma present a significant analytical challenge. In order to develop a sensitive assay for plasma OPN, we explored a single-step precipitation method using a recently developed spin-tube format. Quantification was performed using isotope-dilution mass spectrometry. The concentration detection limit of this assay was 39 ± 15 ng/mL. The assay was applied to the analysis of plasma OPN in metastatic breast cancer patients.
Homeostasis at different backgrounds: The roles of overlayed feedback structures in vertebrate photoadaptation
Authors: Grini Jonas V. , Nygård Melissa , Ruoff Peter 
Published: January 2023

AbstractWe have studied the resetting behavior of eight basic integral controller motifs with respect to different but constant backgrounds. We found that the controllers split symmetrically into two classes: one class, based on derepression of the compensatory flux, leads to more rapid resetting kinetics as backgrounds increase. The other class, which directly activates the compensatory flux, shows a slowing down in the resetting at increased backgrounds. We found a striking analogy between the resetting kinetics of vertebrate photoreceptors and controllers based on derepression, i.e. vertebrate rod or cone cells show decreased sensitivities and accelerated response kinetics as background illuminations increase. The central molecular model of vertebrate photoadaptation consists of an overlay of three negative feedback loops with cytosolic calcium, cyclic guanosine monophosphate (cGMP) and cyclic nucleotide-gated (CNG) channels as components. While in one of the feedback loops the extrusion ofby potassium-dependent sodium-calcium exchangers (NCKX) can lead to integral control with cGMP as the controlled variable, the expected robust perfect adaptation of cGMP is lost, because of the two other feedback loops. They avoid thatlevels become too high and toxic. Looking at psychophysical laws, we found that in all of the above mentioned basic controllers Weber’s law is followed when a “just noticeable difference” (threshold) of 1% of the controlled variable’s set-point was considered. Applying comparable threshold pulses or steps to the photoadaptation model we find, in agreement with experimental results, that Weber’s law is followed for relatively high backgrounds, while Stephens’ power law gives a better description when backgrounds are low. Limitations of our photoadaption model, in particular with respect to potassium/sodium homeostasis, are discussed. Finally, we discuss possible implication of background perturbations in biological controllers when compensatory fluxes are based on activation.
Using Mechanistic Models and Machine Learning to Design Single-Color Multiplexed Nascent Chain Tracking Experiments
Authors: Raymond William S. , Ghaffari Sadaf , Aguilera Luis U. , Ron Eric , Morisaki Tatsuya , Fox Zachary R. , May Michael P. , Stasevich Timothy J. , Munsky Brian 
Published: January 2023

ABSTRACTmRNA translation is the ubiquitous cellular process of reading messenger-RNA strands into functional proteins. Over the past decade, large strides in microscopy techniques have allowed observation of mRNA translation at a single-molecule resolution for self-consistent time-series measurements in live cells. Dubbed Nascent chain tracking (NCT), these methods have explored many temporal dynamics in mRNA translation uncaptured by other experimental methods such as ribosomal profiling, smFISH, pSILAC, BONCAT, or FUNCAT-PLA. However, NCT is currently restricted to the observation of one or two mRNA species at a time due to limits in the number of resolvable fluorescent tags. In this work, we propose a hybrid computational pipeline, where detailed mechanistic simulations produce realistic NCT videos, and machine learning is used to assess potential experimental designs for their ability to resolve multiple mRNA species using a single fluorescent color for all species. Through simulation, we show that with careful application, this hybrid design strategy could in principle be used to extend the number of mRNA species that could be watched simultaneously within the same cell. We present a simulated example NCT experiment with seven different mRNA species within the same simulated cell and use our ML labeling to identify these spots with 90% accuracy using only two distinct fluorescent tags. The proposed extension to the NCT color palette should allow experimentalists to access a plethora of new experimental design possibilities, especially for cell signalling applications requiring simultaneous study of multiple mRNAs.
Increments in Visual Motion Coherence are More Readily Detected than Decrements
Authors: Wei Lai , Mitchell Autumn O. , Maunsell John H.R. 
Published: January 2023

AbstractUnderstanding the circuits that access and read out information in the cerebral cortex to guide behavior remains a challenge for systems-level neuroscience. Recent optogenetic experiments targeting specific cell classes in mouse primary visual cortex (V1) have shown that mice are sensitive to optically-induced increases in V1 spiking, but are relatively insensitive to decreases in neuronal spiking of similar magnitude and time course. This asymmetry suggests that the readout of signals from cortex depends preferentially on increases in spike rate. We investigated whether humans display a similar asymmetry by measuring thresholds for detecting changes in the motion coherence of dynamic random dot stimuli. The middle temporal visual area (MT) has been shown to play an important role in discriminating random dot stimuli, and the responses of its individual neurons to dynamic random dots are well characterized. While both increments and decrements in motion coherence have heterogeneous effects on MT responses, increments cause on average more increases in firing rates. Consistent with this, we found that subjects are far more sensitive to increments of random dot motion coherence than to decrements of coherence. The magnitude of the difference in detectability was largely consistent with the expected difference in effectiveness of coherence increments and decrements in producing increases in MT spike rates. The results add strength to the notion that the circuit mechanisms that read out cortical signals are relatively insensitive to decrements in cortical spiking.
AI-assisted selection of mating pairs through simulation-based optimized progeny allocation strategies in plant breeding
Authors: Hamazaki Kosuke , Iwata Hiroyoshi 
Published: January 2023

AbstractEmerging technologies such as genomic selection have been applied to modern plant and animal breeding to increase the speed and efficiency of variety release. However, breeding requires decisions regarding parent selection and mating pairs, which significantly impact the ultimate genetic gain of a breeding scheme. The selection of appropriate parents and mating pairs to increase genetic gain while maintaining genetic diversity is still an urgent need that breeders are facing. This study aimed to determine the best progeny allocation strategies by combining future-oriented simulations and numerical black-box optimization for an improved selection of parents and mating pairs. In this study, we focused on optimizing the allocation of progenies, and the breeding process was regarded as a black-box function whose input is a set of parameters related to the progeny allocation strategies and whose output is the ultimate genetic gain of breeding schemes. The allocation of progenies to each mating pair was parameterized according to a softmax function of multiple selection criteria. Different selection criteria are weighted in the function to balance genetic gains and genetic diversity optimally. The weighting parameters were then optimized by the black-box optimization algorithm called StoSOO via future-oriented breeding simulations. Simulation studies to evaluate the potential of our novel method revealed that the breeding strategy based on optimized weights attained almost 10% higher genetic gain than that with an equal allocation of progenies to all mating pairs within just four generations. Among the optimized strategies, those considering the expected genetic variance of progenies could maintain the genetic diversity throughout the breeding process, leading to a higher ultimate genetic gain than those without considering it. These results suggest that our novel method can significantly improve the speed and efficiency of variety development through optimized decisions regarding the selection of parents and mating pairs. In addition, by changing simulation settings, our future-oriented optimization framework for progeny allocation strategies can be easily implemented into general breeding schemes, contributing to accelerated plant and animal breeding with high efficiency.
Astrocytic connection to engram neurons Increased after learning
Authors: Kim Jooyoung , Sung Yongmin , Park HyoJin , Choi Dong Il , Kim Ji-il , Lee Hoonwon , Jung Min Kyo , Noh Seulgi , Ye Sanghyun , Lee Jiah , Islam Md Ariful , Chun Heejung , Mun Ji Young , Kaang Bong-Kiun 
Published: January 2023

AbstractAstrocytes directly participate in learning and memory. However, the structural association between astrocytes and memory-encoding engram neurons after learning remains to be elucidated. We developed astrocyte-enhanced green fluorescent protein reconstitution across synaptic partners (eGRASP) to examine tripartite synapses between astrocytes and engram neurons. Using astrocyte-eGRASP, we found that astrocytes had increased connections to engram neurons after learning. Dendritic spines with astrocytic contacts showed enhanced morphology. Live-cell imaging of astrocyte-eGRASP revealed that astrocytic connections are stabilized by neuronal activity. These results indicate that astrocytes distinguish contact between engram neurons and generate engram-specific contact patterns during learning.