bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and safety of heterologous Omicron BA.1 and bivalent SARS-CoV-2 recombinant spike protein booster vaccines: a phase 3, randomized, clinical trial
Authors: Bennett Chijioke , Rivers E Joy , Woo Wayne , Bloch Mark , Cheung King , Griffin Paul , Mohan Rahul , Deshmukh Sachin , Arya Mark , Cumming Oscar , Neville A. Munro , Pardey Toni McCallum , Plested Joyce S , Cloney-Clark Shane , Zhu Mingzhu , Kalkeri Raj , Patel Nita , Buchanan Agi , Marcheschi Alex , Swan Jennifer , Smith Gale , Cho Iksung , Glenn Gregory M. , Walker Robert , Mallory Raburn M. 
Published: July 2023

AbstractBackgroundMutations present in emerging SARS-CoV-2 variants permit evasion of neutralization with prototype vaccines. A novel Omicron BA.1 subvariant-specific vaccine (NVX-CoV2515) was tested alone, or as a bivalent preparation in combination with the prototype vaccine (NVX-CoV2373), to assess antibody responses to SARS-CoV-2.MethodsParticipants aged 18 to 64 years immunized with 3 doses of prototype mRNA vaccines were randomized 1:1:1 to receive a single dose of NVX-CoV2515, NVX-CoV2373, or bivalent mixture in a phase 3 study investigating heterologous boosting with SARS-CoV-2 recombinant spike protein vaccines. Immunogenicity was measured 14 and 28 days after vaccination for the SARS-CoV-2 Omicron BA.1 sublineage and ancestral strain. Safety profiles of vaccines were assessed.ResultsOf participants who received trial vaccine (N=829), those administered NVX-CoV2515 (n=286) demonstrated superior neutralizing antibody response to BA.1 versus NVX-CoV2373 (n=274) at Day 14 (geometric mean titer ratio [95% CI]: 1.6 [1.33, 2.03]). Seroresponse rates [n/N; 95% CI] were 73.4% [91/124; 64.7, 80.9] for NVX-CoV2515 versus 50.9% [59/116; 41.4, 60.3] for NVX-CoV2373. All formulations were similarly well-tolerated.ConclusionsNVX-CoV2515 elicited a superior neutralizing antibody response against the Omicron BA.1 subvariant compared with NVX-CoV2373 when administered as a fourth dose. Safety data were consistent with the established safety profile of NVX-CoV2373.
Validation of a HIV Whole Genome Sequencing Method for HIV Drug Resistance Testing in an Australian Clinical Microbiology Laboratory
Authors: Jenkins Frances , Le Thomas , Farhat Rima , Pinto Angie , Anzari M Azim , Bonsall David , Golubchik Tanya , Bowden Rory , Lee Frederick J , Van Hal Sebastiaan 
Published: July 2023

AbstractDetection of HIV drug resistance is vital to successful anti-retroviral therapy (ART). HIV drug resistance (HIVDR) testing to determine drug resistance mutations (DRMs) is routinely performed in Australia to guide ART choice in either newly diagnosed people living with HIV or in cases of treatment failure. In 2022, our Australian clinical microbiology laboratory sought to validate a Next-generation sequencing (NGS)-based HIVDR assay to replace the previous Sanger sequencing (SS)-based ViroSeq assay. NGS solutions for HIVDR offer higher throughput, lower costs and higher sensitivity for variant detection. We sought to validate the previously described low-cost probe-based NGS method (veSEQ-HIV) for HIV-1 recovery and HIVDR testing in a diagnostic setting. The implemented veSEQ-HIV assay displayed 100% and 98% accuracy in major and minor mutation detection respectively and 100% accuracy of subtyping (provided >1000 mapped reads were obtained). Pairwise comparison exhibited low inter-and intra-run variability across the whole genome (Jaccard similarity coefficient [J] =0.993; J=0.972) and limited to the Pol gene only (J=0.999; J=0.999) respectively. The veSEQ-HIV assay met all our pre-set criteria based on the WHO “Recommended methods for validating an in-house genotyping assay for surveillance of HIV drug resistance” and has successfully replaced the ViroSeq assay in our laboratory.Scaling-down the veSEQ-HIV assay to a limited batch size and sequencing on the Illumina iSeq100, allowed easy implementation of the assay into the workflow of a small sequencing laboratory with minimal staff and equipment and the ability to meet clinically relevant test turn-around times.
Generalization Challenges in ECG Deep Learning: Insights from Dataset Characteristics and Attention Mechanism
Authors: Huang Zhaojing , MacLachlan Sarisha , Yu Leping , Herbozo Contreras Luis Fernando , Truong Nhan Duy , Ribeiro Antônio Horta , Kavehei Omid 
Published: July 2023

AbstractThis research investigates the influence of dataset characteristics on the performance and generalization capabilities of deep learning models, on ECG data. The study evaluates multiple subsets of the TNMG dataset with varying levels of curated characteristics to assess their impact on model performance. Additionally, an attention mechanism is introduced to enhance model accuracy and generalization. The experimental results reveal that models trained on balanced subsets and incorporating the attention mechanism consistently outperform those trained on unbalanced data or without attention, emphasizing the critical importance of dataset balance and attention mechanism for achieving improved model performance.Surprisingly, the largest ECG dataset, TNMG, proved less effective in generalization than smaller, curated subsets. The study demonstrates that a well-balanced and thoughtfully curated dataset, combined with the attention mechanism, can lead to competitive model performance, even with a significantly smaller size.This research on ECG data underscores the critical importance of dataset curation, balance, and attention mechanisms in biomedical machine learning. It highlights that well-balanced, thoughtfully curated datasets with attention mechanisms can outperform larger, unbalanced datasets, challenging conventional notions and offering potential advancements in medical data analysis and patient care.
Analysis and perception of Instagram posts referring to diastasis recti abdominis, exercise and sports-related content: a mixed-method study protocol
Authors: Giagio S , Rial Rebullido T , Salvioli S , Innocenti T , Pillastrini P , Moore IS , Donnelly GM 
Published: July 2023

ABSTRACTObjectivesThis study will evaluate the health information posted in Instagram (IG) concerning in diastasis recti abdominis (DRA), exercise and sports, and it will explore how IG content is perceived and impacts the daily lives of women with DRA.MethodsA convergent parallel mixed methods design will be used. Through an observational study, public IG posts content written in English language will be descriptively analysed and reviewed using the QUality Evaluation Scoring Tool (QUEST) criteria. We will extract data on exercise and sport suggestions for women with DRA, along with any proposed indications and contraindications.Eligible women with a diagnosis of DRA will be recruited via a worldwide e-survey using Qualtrics, and invited to take part to one-to-one interviews via Microsoft Teams. Semi-structured interviews will aim to explore their IG use and their perceptions on information related to DRA, exercise, and sports. Descriptive and thematic analysis will be conducted.ImplicationsThe availability and quality of information on social media are becoming increasingly important aspects of patient care. For sports medicine and women’s health clinicians, the findings of the present study will give an overview of DRA content that are easily accessible to women, underscoring the related posts characteristics. Furthermore, results could impact clinical practice by providing clinicians with a better understanding of patients’ perceptions and beliefs from IG DRA content, with the ultimate aim of better engaging with them and dispelling any potential misconceptions.
Plasma cfDNA analysis can be facilitated by membrane based filtration of whole blood regardless of additive
Authors: Marra Amanda N. , van den Boom Dirk , Ehrich Mathias , Ellison Christopher K. 
Published: July 2023

AbstractCell-free DNA (cfDNA) has emerged as a pivotal biomarker for various noninvasive screening applications such as noninvasive prenatal screening, minimum residual disease monitoring, and transplant rejection prediction. However, the efficacy of these applications is heavily reliant on the detection of minority nucleic acid species amidst a vast background of host DNA. Therefore, it is crucial to prevent the dilution of the desired cfDNA signal with genomic DNA originating from white blood cell (WBC) degradation. The most commonly adopted sample collection methods prevent WBC lysis by either adding a stabilizing agent to the collection tube, like Streck, or through immediate centrifugation following the collection of whole blood. In this study, we propose an alternative for plasma sample collection that involves membrane based filtration of plasma from cellular blood components at the point of collection. Our findings demonstrate that cfDNA recovered using this method performs equally or better compared to conventional methods and enables the implementation of novel and more accessible blood collection procedures.
Rare GPR37L1 variants reveal potential roles in anxiety and migraine disorders
Authors: Breitwieser Gerda E. , Cippitelli Andrea , Wang Yingcai , Pelletier Oliver , Dershem Ridge , Wei Jianning , Toll Lawrence , Fakhoury Bianca , Brunori Gloria , Metpally Raghu , Carey David J. ,   the Regeneron Genetics Center, Robishaw Janet 
Published: July 2023

AbstractGPR37L1 is an orphan receptor that couples through heterotrimeric G-proteins to regulate physiological functions. Since its role in humans is not fully defined, we used an unbiased computational approach to assess the clinical significance of rareGPR37L1genetic variants found among 51,289 whole exome sequences from the DiscovEHR cohort. Briefly, rareGPR37L1coding variants were binned according to predicted pathogenicity, and analyzed by Sequence Kernel Association testing to reveal significant associations with disease diagnostic codes for epilepsy and migraine, among others. Since associations do not prove causality, rareGPR37L1variants were then functionally analyzed in SK-N-MC cells to evaluate potential signaling differences and pathogenicity. Notably, receptor variants exhibited varying abilities to reduce cAMP levels, activate MAPK signaling, and/or upregulate receptor expression in response to the agonist prosaptide (TX14(A)), as compared to the wild-type receptor. In addition to signaling changes, knockout of GPR37L1 or expression of certain rare variants altered cellular cholesterol levels, which were also acutely regulated by administration of the agonist TX14(A) via activation of the MAPK pathway. Finally, to simulate the impact of rare nonsense variants found in the large patient cohort, a knockout (KO) mouse line lackingGpr37L1was generated, revealing loss of this receptor produced sex-specific changes implicated in migraine-related disorders. Collectively, these observations define the existence of rare GPR37L1 variants in the human population that are associated with neuropsychiatric conditions and identify the underlying signaling changes that are implicated in thein vivoactions of this receptor in pathological processes leading to anxiety and migraine.SIGNIFICANCE STATEMENTG-protein coupled receptors (GPCRs) represent a diverse group of membrane receptors that contribute to a wide range of diseases and serve as effective drug targets. However, a number of these receptors have no identified ligands or functions, i.e., orphan receptors. Over the past decade, advances have been made, but there is a need for identifying new strategies to reveal their roles in health and disease. Our results highlight the utility of rare variant analyses of orphan receptors for identifying human disease associations, coupled with functional analyses in relevant cellular and animal systems, to ultimately reveal their roles as novel drug targets for treatment of neurological disorders that lack wide-spread efficacy.
Pan-cancer analysis reveals embryonic and hematopoietic stem cell signatures to distinguish different cancer subtypes
Authors: Lei Jiali , Luo Jiangti , Liu Qian , Wang Xiaosheng 
Published: July 2023

AbstractPurposeStem cells-like properties in cancer cells may confer cancer development and therapy resistance. With the advancement of multi-omics technology, the multi-omics-based exploration of cancer stemness has attracted certain interests. However, subtyping of cancer based on the combination of different types of stem cell signatures remains scarce.MethodsIn this study, 10,323 cancer specimens from 33 TCGA cancer types were clustered based on the enrichment scores of six stemness gene sets, representing two types of stem cell backgrounds: embryonic stem cells (ESCs) and hematopoietic stem cells (HSCs).ResultsWe identified four subtypes of pan-cancer, termed StC1, StC2, StC3 and StC4, which displayed distinct molecular and clinical features, including stemness, genome integrity, intratumor heterogeneity, methylation levels, tumor microenvironment, tumor progression, chemotherapy and immunotherapy responses, and survival prognosis. This subtyping method for pan-cancer is reproducible at the protein level.ConclusionOur findings indicate that the ESC signature is an adverse prognostic factor, while the HSC signature and ratio of HSC/ESC signatures are positive prognostic factors in cancer. The ESC and HSC signatures-based subtyping of cancer may provide insights into cancer biology and clinical implications of cancer.
Validating models of TMS effects with concurrent TMS/fMRI
Authors: Petrov Petar I. , Vink Jord , Mandija Stefano , van den Berg Nico A.T. , Dijkhuizen Rick M. , Neggers Sebastiaan F.W. 
Published: July 2023

AbstractThe exact dose and spatial pattern of brain activation induced by transcranial magnetic stimulation (TMS) is of importance to all applications of TMS, both clinical and for investigational use. How TMS coils induce electrical fields has been investigated and validated by several groups, but models of how evoked currents interact with neuronal tissue and where activation is induced have hardly been validated empirically.Here we propose a detailed model of TMS induced currents in the brain building on our previous work on different TMS coil models, taking into account various electromagnetic head tissue properties with finite element modeling and several competing macroscopic models of how brain activation is achieved by the TMS induced electrical field. Importantly, we validate these models using TMS coil discharges administered to the brain of 6 healthy volunteers inside a 3T MRI scanner, while acquiring functional MRI scans at the same time.We conclude that the mere magnitude of the electric field in the cortical gray matter tissue near the stimulation site provides the best metric to predict neuronal activation as measured by BOLD fMRI, whereas models of brain activation taking into account orientation of E-fields with respect to the cortical columns and layers do not (yet) yield better predictions of neuronal activation induced by TMS.This report is relevant for neuronavigated TMS approaches attempting to take into account evoked E-fields and neuronal activation to improve precision of TMS administration for clinical and investigational purposes.
Enhanced cellular longevity arising from environmental fluctuations
Authors: Liu Yuting , Zhou Zhen , Wu Songlin , Ni Gavin , Zhang Alex , Tsimring Lev S. , Hasty Jeff , Hao Nan 
Published: July 2023

SummaryCellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions, but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity - the creation of a stable fixed point in the “healthy” state of the cell and the dynamic stabilization of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms.
High red/far-red ratio promotes root colonization ofSerratia plymuthicaA21-4 in tomato by root exudates-stimulated chemotaxis and biofilm formation
Authors: Guo Zhixin , Qin Yanping , Lv Jingli , Wang Xiaojie , Ye Ting , Dong Xiaoxing , Du Nanshan , Zhang Tao , Piao Fengzhi , Dong Han , Shen Shunshan 
Published: July 2023

AbstractEffective colonization on plant roots is a prerequisite for plant growth promoting rhizobacterias (PGPR) to exert beneficial activities. Light is essential for plant growth, development and stress response. However, how light modulates root colonization of PGPR remains unclear. Here, we found that high red/far red(R/FR) light promoted and low R/FR light inhibited the colonization and growth enhancement ofSerratia plymuthicaA21-4 on tomato. Non-targeted metabolomic analysis of root exudates collected from different R/FR ratio treated tomato seedlings with A21-4 inoculation by ultra performance liquid chromatography-tandem mass spectrometry showed that 64 primary metabolites including amino acids, sugars and organic acids in high R/FR light-grown plants significantly increased compared with those determined for low R/FR light-grown plants. Among them, 7 amino acids, 1 organic acid and 1 sugar obviously induced the chemotaxis and biofilm formation of A21-4 compared to the control. Furthermore, exogenous addition of five artificial root exudate compontents (leucine, methionine, glutamine, 6-aminocaproic acid and melezitose) regained and further increased the colonization and growth promoting ability of A21-4 in tomato under low R/FR light and high R/FR light, respectively, indicating their involvement in high R/FR light-regulated the interaction of tomato root and A21-4. Taken together, our results, for the first time, clearly demonstrate that high R/FR light-induced root exudates play a key role in chemotaxis, biofilm formation and root colonization of A21-4. This study provides new insights into the interactions of plant-PGPR under different light conditions and can help promote the combined application of light supplementation and PGPR to facilitate crop growth and health in green agricultural production.
Near infrared-light treatment alters mitochondrial homeostasis to induce senescence in breast cancer cells
Authors: Kalampouka I , Mould R R , Botchway S W , Mackenzie A , Nunn A V , Thomas E L , Bell J D 
Published: July 2023

ABSTRACTThe application of near infrared (NIR)-light to living systems has been suggested as a potential method to enhance tissue repair, decrease inflammation, and possibly mitigate cancer therapy-associated side effects. In this study, we examined the effect of exposing three cell lines: breast cancer (MCF7), non-cancer breast cells (MCF10A), and lung fibroblasts (IMR-90), to 734 nm NIR-light for 20 minutes per day for six days, and measuring changes in cellular senescence. Positive senescent populations were induced using doxorubicin. Flow cytometry was used to assess relative levels of senescence together with mitochondria-related variables. Exposure to NIR-light significantly increased the level of senescence in MCF7 cells (13.5%; P<0.01), with no observable effects on MCF10A or IMR-90 cell lines. NIR-induced senescence was associated with significant changes in mitochondria homeostasis, including raised ROS level (36.0%; P<0.05) and mitochondrial membrane potential (14.9%; P<0.05), with no changes in mitochondrial Ca2+. These results suggest that NIR-light exposure can significantly arrest the proliferation of breast cancer cells via inducing senescence, while leaving non-cancerous cell lines unaffected.
Cooperative conformational transitions and the temperature dependence of enzyme catalysis
Authors: Walker Emma J. , Hamill Carlin J. , Crean Rory , Connolly Michael S. , Warrender Annmaree K. , Kraakman Kirsty L. , Prentice Erica J. , Steyn-Ross Alistair , Steyn-Ross Moira , Pudney Christopher R. , van der Kamp Marc W. , Schipper Louis A. , Mulholland Adrian J. , Arcus Vickery L. 
Published: July 2023

AbstractMany enzymes display non-Arrhenius behaviour with curved Arrhenius plots in the absence of denaturation. There has been significant debate about the origin of this behaviour and recently the role of the activation heat capacityhas been widely discussed. If enzyme-catalysed reactions occur with appreciable negative values of(arising from narrowing of the conformational space along the reaction coordinate), then curved Arrhenius plots are a consequence. To investigate these phenomena in detail, we have collected high precision temperature-rate data over a wide temperature interval for a model glycosidase enzyme MalL, and a series of mutants that change the temperature-dependence of the enzyme-catalysed rate. We use these data to test a range of models including macromolecular rate theory (MMRT) and an equilibrium model. In addition, we have performed extensive molecular dynamics (MD) simulations to characterise the conformational landscape traversed by MalL in the enzyme-substrate complex and an enzyme-transition state complex. We have crystallised the enzyme in a transition state-like conformation in the absence of a ligand and determined an X-ray crystal structure at very high resolution (1.10 Å). We show (using simulation) that this enzyme-transition state conformation has a more restricted conformational landscape than the wildtype enzyme. We coin the term “transition state-like conformation (TLC)” to apply to this state of the enzyme. Together, these results imply a cooperative conformational transition between an enzyme-substrate conformation (ES) and a transition-state-like conformation (TLC) that precedes the chemical step. We present a two-state model as an extension of MMRT (MMRT-2S) that describes the data along with a convenient approximation with linear temperature dependence of the activation heat capacity (MMRT-1L) that can be used where fewer data points are available. Our model rationalises disparate behaviour seen for MalL and a thermophilic alcohol dehydrogenase and is consistent with a raft of data for other enzymes. Our model can be used to characterise the conformational changes required for enzyme catalysis and provides insights into the role of cooperative conformational changes in transition state stabilisation that are accompanied by changes in heat capacity for the system along the reaction coordinate. TLCs are likely to be of wide importance in understanding the temperature dependence of enzyme activity, and other aspects of enzyme catalysis.