bluuebunny/crossref_metadata_2025 huggingface dataset:
The NEW Soul Study: Implementation and Evaluation Impact From the Secular Trend of the COVID-19 Pandemic
Authors: Bernhart John A. , Turner-McGrievy Gabrielle M. , Davey Marty , Okpara Nkechi , Harrell E. Grace , Bailey Shiba , Wilcox Sara
Published: October 2024

Context:

In process evaluation research, secular trends refer to external factors unrelated to an intervention that impact implementation. The COVID-19 pandemic was a secular trend that affected the implementation of the Nutritious Eating with Soul (NEW Soul) study.

Objective:

This paper describes steps taken in modifying intervention delivery due to the secular trend of the pandemic. This paper also addresses process evaluation measures of dose delivered, dose received, and satisfaction.

Design:

This study is a longitudinal study.

Setting:

The study took place in Columbia, SC, from 2018 to 2021.

Participants:

African American adults between 18 and 65 years old.

Intervention:

The NEW Soul study, a dietary lifestyle intervention, lasted 24 months.

Main Outcome Measure(s):

Process evaluation variables of dose delivered, dose received, and satisfaction.

Results:

The study team shifted intervention delivery and maintained the timeline of classes for participants and intervention activities. Dose delivered was higher in-person (7.0 out of 8) compared to online (6.4 out of 8; t = −3.92, P = .002). Attendance was higher in-person compared to online (t = 2.80, P = .006). Overall, satisfaction of the intervention was favorable in-person and online. Helpfulness of nutrition information in the class was rated lower online compared to in-person (t = 2.05, P = .04).

Conclusions:

Even though the study team successfully shifted intervention delivery online, dose delivered was higher in-person. Evaluations of classes remained high across cohorts and for in-person and online classes. Future lifestyle interventions working with African American adults requires consistent flexibility in intervention delivery.
High-quality PacBio draft genome sequences of 17 free-living Bradyrhizobium and four related Nitrobacteraceae strains isolated from arid soils in the Santa Catalina Mountains of Southern Arizona.
Authors: Kridler Melanie R , Howe Amanda , Legins Jimaree A , Guerrero Christina , Bartelme Ryan P. , Taylor Bridget , Carini Paul
Published: October 2024

Non-symbiotic Bradyrhizobium are among the most abundant and ubiquitous microbes in bulk soils globally. Despite this, most available genomic resources for Bradyrhizobium are derived from plant-associated strains. We present high-quality draft genomes for 17 Bradyrhizobium and four Nitrobacteraceae cultures isolated from bulk semiarid soils in Arizona, USA. The genome sizes range from 5.99 to 10.4 Mbp. Phylogenomic analysis of the 21 genomes indicates they fall into four clades. Two of the clades are nested within the Bradyrhizobium genus. The other two clades were associated with Nitrobacteraceae outgroups basal to Bradyrhizobium. All genomes lack genes coding for molybdenum or vanadium nitrogenases, and nod genes that code for proteins involved in nodulation, suggesting these isolates are free-living, non-symbiotic, and do not fix dinitrogen gas. These genomes offer new resources for investigating free-living Bradyrhizobium lineages.
Comparative Genomics Analysis of six Cutibacterium acnes Strains Isolated from Contaminated Platelet Concentrates
Authors: Flint Annika , Kumaran Dilini , Weedmark Kelly , Pagotto Franco , Ramirez-Arcos Sandra
Published: October 2024

Cutibacterium acnes is a bacterial skin commensal that is often isolated during routine testing of blood products like platelet concentrates (PCs). Due to the slow growing nature of this bacterium in culture media, C. acnes contaminated PCs are often transfused into vulnerable patients before retrieval of these units can be initiated. This study aimed at obtaining the whole genome sequence of six C. acnes isolates derived from contaminated PCs and to phylotype, compare, and assess their genetic backgrounds. Furthermore, the whole genomes of the PC isolates were compared to clinical isolates obtained from different sites and types of infection. The results indicate that the PC isolates assessed belonged to four phylotypes namely: IA, IB, II and III. Whole genome comparisons identified differences in the virulence profiles of the isolates, providing insight into the potential enhanced risk to patients transfused with C. acnes contaminated PCs.
Modelling the epidemiological and economic impact of digital adherence technologies with differentiated care for tuberculosis treatment in Ethiopia
Authors: Goscé Lara , Tadesse Amare Worku , Foster Nicola , Van Kalmthout Kristian , van Rest Job , .vanderwal jense , Harker Martin , Madden Norma , Abdurhman Tofik , Gadissa Demekech , Bedru Ahmed , Dube Tanyaradzwa Nicolette , Alacapa Jason , Mganga Andrew , Deyanova Natasha , Charalambous Salome , Letta Taye , Jerene Degu , White Richard , Fielding Katherine , Houben Rein M G J , McQuaid Christopher Finn
Published: October 2024

Background Digital adherence technologies (DATs) with associated differentiated care are potential tools to improve tuberculosis (TB) treatment outcomes and reduce associated costs for both patient and healthcare providers. However, the balance between epidemiological and economic benefits remains unclear. Here, we used data from a large trial (PACTR202008776694999) to estimate the potential long – term epidemiological and economic impact of DAT interventions in Ethiopia. Methods We developed a compartmental transmission model for TB, calibrated to Ethiopia and parameterised with patient and provider costs. We compared the epidemiological and economic impact of two DAT interventions, a digital pillbox and medication labels, to the current standard of care, assuming each was introduced at scale in 2023. We projected long – term TB incidence, mortality and costs to 2035, and conducted a threshold analysis to identify the maximum possible epidemiological impact of a DAT intervention by assuming 100% treatment completion for patients on DAT. Findings We estimated small and uncertain epidemiological benefits of the pillbox intervention compared to the standard of care in Ethiopia, with a difference of – 0.4% ( – 1.1; +2.0) incident TB episodes and – 0.7% (– 2.2; +3.6) TB deaths. However, our analysis also found large total provider and patient cost savings [$163 ($118; $211) and $3 ($1; $5) million respectively over 2023 – 2035], translating to a 50.2% (35.9%; 65.2%) reduction in total cost of treatment. Results were similar for the medication label intervention. The maximum possible epidemiological impact a theoretical DAT intervention could achieve over the same timescale would be a 3% (1.4; 5.5%) reduction in incident TB and a 8.2% (4.4; 12.8) reduction in TB deaths. Interpretation DAT interventions, while showing limited epidemiological impact, could substantially reduce TB treatment costs for both patients and the healthcare provider.
Pipeasm: a tool for automated large chromosome-scale genome assembly and evaluation
Authors: Silva Bruno Marques , Trindade Fernanda de Jesus , Canesin Lucas Eduardo Costa , Souza Giordano Bruno Soares , Aleixo Alexandre , Nunes Gisele Lopes , Oliveira Renato R. M.
Published: October 2024

Motivation: With increasing initiatives to study biodiversity through high-quality reference genomes and the growing capacity of sequencing a wide range of organisms, there is a pressing need for an accessible, reproducible, and user-friendly tool that incorporates state-of-the-art methodologies for large genome assembly. Results: We introduce Pipeasm, a Snakemake pipeline designed for assembling vertebrate genomes using HiFi PacBio, ONT, and HiC data. By setting a configuration file with input information and suggested parameters, Pipeasm was able to assemble multiple-sized diploid genomes ready for manual curation. Availability and Implementation: Pipeasm requires an environment with Snakemake and Singularity and is available at https://github.com/itvgenomics/pipeasm.
Revealing the hidden sequence distribution of epitope-specific TCR repertoires and its influence on machine learning model performance
Authors: Gielis Sofie , Chernigovskaya Maria , Pavlovic Milena , Van Deuren Vincent , Vandoren Romi , Valkiers Sebastiaan , Laukens Kris , Greiff Victor , Meysman Pieter
Published: October 2024

Numerous efforts have been made to decipher the epitope-T cell receptor (TCR) recognition code. Both simple machine learning techniques and deep learning strategies have been used to train models to predict the binding of epitopes by TCR sequences. A good training data set rests at the basis of every accurate prediction model, yet little attention has been given to the composition of these data sets. In this paper, we studied the natural distribution of TCR sequences within epitope-specific TCR repertoires, i.e. a set of TCRs binding the same epitope, and its impact on the predictability of TCR-epitope interactions. We found that the observed diversity of these repertoires can result from a smaller set of core binding motifs constrained by TCR generation. Moreover, a clear relationship was found between the sequence distribution of the training data and performance metrics, emphasizing the importance of the used ground-truth data when using machine learning models in this domain. Taken together, these findings inform data set composition to help push epitope-TCR prediction models to the next level.
PolSpec: polarisation-based detection for spectral classification of optical signals
Authors: Liu H. , Kumar S. , Garcia E. , French P.M.W.
Published: October 2024

Spectrally resolved imaging is typically realised using bandpass filters, which are inefficient when they reject “out-of-band” photons or using angularly dispersive devices with at least one image dimension requiring scanning to acquire a full hyperspectral dataset and therefore sequential data acquisition, unless cascades of dichroic beamsplitters are employed, for which cost and experimental complexity scale with the number of spectral channels. Here we present a new approach, “PolSpec”, to realise rapid and flexible widefield hyperspectral imaging with lower cost and complexity using polarisation optics instead of dielectric coatings or dispersive devices.PolSpecutilises Lyot filters that provide continuously varying transmission across the desired spectral range to generate orthogonal “spectral modulation vectors” that can represent specific spectral signatures with significantly lower data volumes than full spectral profiles. We demonstrate single-shot widefield hyperspectral imaging using a polarisation-resolving camera and rapid, electronically reconfigurable, more photon efficient, hyperspectral imaging using a liquid crystal variable retarder.
Structural identification of the RY12 domain of RyR1 as an ADP sensor and the target of the malignant hyperthermia therapeutic dantrolene
Authors: Kim Kookjoo , Li Huan , Yuan Qi , Melville Zephan , Zalk Ran , des Georges Amédée , Frank Joachim , Hendrickson Wayne A. , Marks Andrew R. , Clarke Oliver B.
Published: October 2024

Malignant hyperthermia (MH) is a life-threatening pharmacogenetic condition triggered by volatile anesthetics, which activate pathogenic RyR1 mutants. The small molecule therapeutic dantrolene has long been used to treat MH. However, the binding site and mechanism of dantrolene remain unclear. Here, we present cryo-EM structures of RyR1 bound to dantrolene and the MH trigger agent 4-chloro-m-cresol (4CmC), revealing the dantrolene and 4CmC binding sites in atomic detail. Dantrolene binds stacked with ATP or ADP in the RY12 domain at the corner of the receptor, inducing a conformational change in this domain which is allosterically coupled to pore closure. Functional analyses revealed that ATP or ADP was required for dantrolene inhibition, and a single point mutation that disrupts the peripheral ATP binding site abolished ATP/ADP-dependent dantrolene inhibition. Strikingly, in the absence of dantrolene, this site selectively binds two ADP molecules, suggesting a possible role in ATP/ADP ratio sensing.
ProteoSeeker: A Feature-Rich Metagenomic Analysis Tool for Accessible and Comprehensive Metagenomic Exploration
Authors: Filis Georgios , Bezantakou Dimitra , Rigkos Konstantinos , Noti Despina , Saridis Pavlos , Zarafeta Dimitra , Skretas Georgios
Published: October 2024

Metagenomics have served as a key driver of biotechnology advancements through, among others, the identification of novel proteins. The lack of standardized guidelines and benchmarks in the field, however, complicates the selection of appropriate bioinformatics tool ensembles and hinders faster progress. This study introducesProteoSeeker, an automated pipeline designed for accessible and comprehensive metagenomic exploration of whole-genome sequencing data.ProteoSeekeridentifies proteins within user-defined protein families and uncovers the taxonomy of the host organisms. It is implemented as a command-line tool to facilitate metagenomic dataset analysis for non-expert users, thus enabling facilitated and streamlined protein discovery.
Fast-lived Vertebrate Hosts Exhibit Higher Potential for Mosquito-borne Parasite Transmission
Authors: Dahlin Kyle J.-M. , O’Regan Suzanne M. , Schmidt John Paul , Han Barbara A. , Drake John M.
Published: October 2024

The emergence of mosquito-borne zoonoses has continually increased over the past decade, posing a significant global public health challenge. Ecological theory can point to the characteristics of populations that make them more likely to form reservoirs of disease. The pace of life hypothesis posits that species with more rapid reproduction and shorter lifespans are more likely to be disease reservoirs than their slower-living cousins. Mathematical modeling suggests theoretical conditions under which this hypothesis is correct for directly- and environmentally-transmitted pathogens but its applicability to mosquito-borne disease systems has yet to be examined. We parameterized a mechanistic model with host trait data to investigate the link between the position of a species on the fast-slow life history continuum and the potential for it to spread mosquitoborne diseases. We evaluated the resulting relationships for four medically important mosquito species across their thermal niches and for four pathogens characterized by infection duration and the level of susceptibility of the focal host to infection. Finally, because the fast-slow life history continuum differs across taxonomic ranks, we considered the theory in the context of two orders of vertebrate hosts, Rodentia and Primates. After parameterizing our model, we found that, near universally across all the axes of variation considered, fast-lived hosts have higher transmission potential than slow-lived hosts. There was one exception: slower-lived hosts have higher transmission potential for parasites that cause long-enduring infections to which these hosts are highly susceptible. Generally, however, these connections hinge on the often unknown links between immunological traits, population density, and pace of life. Our analyses highlight immunological traits as a key knowledge gap with strong influence over the potential for transmission. Further investigation of the pace of life hypothesis will require a better understanding of how, for mosquito-borne parasitic infections, susceptibility and infection duration vary across the members of a taxonomic order.
CADET: Enhanced transcriptome-wide association analyses in admixed samples using eQTL summary data
Authors: Head S. Taylor , Dai Qile , Schildkraut Joellen , Cutler David J. , Yang Jingjing , Epstein Michael P.
Published: October 2024

A transcriptome-wide association study (TWAS) is a popular statistical method for identifying genes whose genetically-regulated expression (GReX) component is associated with a trait of interest. Most TWAS approaches fundamentally assume that the training dataset (used to fit the gene expression prediction model) and testing GWAS dataset are from the same ancestrally homogenous population. If this assumption is violated, studies have shown a marked negative impact on expression prediction accuracy as well as reduced power of the downstream genetrait association test. These issues pose a particular problem for admixed individuals, whose genomes represent a mosaic of multiple continental ancestral segments. To resolve these issues, we present CADET, which enables powerful TWAS of admixed cohorts leveraging the local-ancestry (LA) information of the cohort along with summary-level eQTL data from reference panels of different ancestral groups. CADET combines multiple polygenic risk score models based on the summary-level eQTL reference data to predict LA-aware GReX components in admixed test samples. Using simulated data, we compare the imputation accuracy, power, and type I error rate of our proposed LA-aware approach to LA-unaware methods for performing TWASs. We show that CADET performs optimally in nearly all settings regardless of whether the genetic architecture of gene expression is dependent or independent of ancestry. We further illustrate CADET by performing a TWAS of 29 common blood biochemistry phenotypes within an admixed cohort from the UK Biobank and identify 18 hits unique to our LA-aware strategy with the majority of hits supported by existing GWAS findings.
Polyphosphate Discriminates Protein Conformational Ensembles More Efficiently than DNA Promoting Diverse Assembly and Maturation Behaviors
Authors: Goyal Saloni , Rajendran Divya , Mani Anup Kumar , Naganathan Athi N.
Published: October 2024

Disordered proteins and domains often assemble into condensates with polyanionic nucleic acids, primarily via charge complementarity, regulating numerous cellular functions. However, the assembly mechanisms associated with the other abundant and ubiquitous, anionic, stress-response regulating polymer, polyphosphate (polyP), is less understood. Here, we employ the intrinsically disordered DNA binding domain (DBD) of cytidine repressor (CytR) fromE.colito study the nature of assembly processes with polyP and DNA. CytR forms metastable liquid-like condensates with polyP and DNA, while undergoing liquid-to-solid transition in the former and solubilizing in the latter. On mutationally engineering the ensemble to exhibit more or less structure and dimensions than the WT, the assembly process with polyP is directed to either condensates with partial time-dependent solubilization or spontaneous aggregation, respectively. On the other hand, the CytR variants formonlyliquid-like but metastable droplets with DNA which solubilize within a few hours. Polyphosphate induces large secondary-structure changes, with two of the mutants adopting polyproline II-like structures within droplets, while DNA has only minimal structural effects. Our findings reveal how polyphosphate can more efficiently discern conformational heterogeneity in the starting protein ensemble, its structure, and compactness, with broad implications in assembly mechanisms involving polyP and stress response in bacterial systems.
Aerobic capacity and exercise mediate protection against hepatic steatosis via enhanced bile acid metabolism
Authors: Kugler Benjamin A. , Maurer Adrianna , Fu Xiaorong , Franczak Edziu , Ernst Nick , Schwartze Kevin , Allen Julie , Li Tiangang , Crawford Peter A. , Koch Lauren G. , Britton Steven L. , Burgess Shawn C. , Thyfault John P.
Published: October 2024

High cardiorespiratory fitness and exercise show evidence of altering bile acid (BA) metabolism and are known to protect or treat diet-induced hepatic steatosis, respectively. Here, we tested the hypothesis that high intrinsic aerobic capacity and exercise both increase hepatic BA synthesis measured by the incorporation of2H2O. We also leveraged mice with inducible liver-specific deletion ofCyp7a1(LCyp7a1KO), which encodes the rate-limiting enzyme for BA synthesis, to test if exercise-induced BA synthesis is critical for exercise to reduce hepatic steatosis. The synthesis of hepatic BA, cholesterol, andde novolipogenesis was measured in rats bred for either high (HCR) vs. low (LCR) aerobic capacity consuming acute and chronic high-fat diets. HCR rats had increased synthesis of cholesterol and certain BA species in the liver compared to LCR rats. We also found that chronic exercise with voluntary wheel running (VWR) (4 weeks) increased newly synthesized BAs of specific species in male C57BL/6J mice compared to sedentary mice. Loss ofCyp7a1resulted in fewer new BAs and increased liver triglycerides compared to controls after a 10-week high-fat diet. Additionally, exercise via VWR for 4 weeks effectively reduced hepatic triglycerides in the high-fat diet-fed control male and female mice as expected; however, exercise in LCyp7a1KO mice did not lower liver triglycerides in either sex. These results show that aerobic capacity and exercise increase hepatic BA metabolism, which may be critical for combatting hepatic steatosis.

Highlights

Rats with intrinsic high aerobic capacity have more significant reductions inde novolipogenesis and increased cholesterol and bile acid synthesis on a high-fat diet compared to rats with low aerobic capacity.

Chronic exercise increases hepatic bile acid synthesis in mice.

Loss ofCyp7a1blunts the capacity for exercise to increase bile acid synthesis and treat hepatic steatosis in male and female mice fed a high-fat diet.
Bur1-driven G1-to-S phase transition induces hydroxyurea sensitivity in yeast checkpoint mutants
Authors: da Silva Stefany Cristine Rodrigues , Bastos de Oliveira Francisco Meirelles
Published: October 2024

InSaccharomyces cerevisiae, the cyclin-dependent kinase Bur1 is known for its role in promoting transcription elongation and histone modifications, thereby regulating gene expression. In this study, we investigated the genetic interactions between a hypomorphicBUR1allele (bur1-107) and null mutants of the checkpoint kinases Mec1 and Rad53. Our findings show that thebur1-107allele suppresses hydroxyurea (HU) sensitivity inmec1andrad53mutants, indicating that Bur1 activity may be detrimental in the absence of functional checkpoint signaling. Additionally, thebur1-107mutation delays the G1-to-S phase transition, indicating a key role for Bur1 in cell cycle progression. Notably,bur1-107reduces γ-H2A accumulation, facilitates S-phase resumption, and supresses the sub-G1 population in HU-treatedmec1mutants. These findings suggest that Bur1-driven G1-to-S phase progression exacerbates DNA damage and cell death in checkpoint-deficient cells exposed to HU. This study highlights a novel role for Bur1 in modulating the cellular response to replication stress in checkpoint-compromised cells.
Antagonistic activity of AEA on TAT treated Human Astrocytes identify Inflammaging pathways
Authors: Duraikkannu Durairaj , Khatak Kamini , Nagarajan Hemavathy , Sudharshan Sridharan , Chatterjee Nivedita
Published: October 2024

Physiologically, the endocannabinoids are known to reduce inflammation by decreasing production of inflammatory factors in immune and glial cells. Astrocytes secrete soluble inflammatory mediators and prolonged activation of astrocytes is associated with accelerated aging in Central Nervous System. Many reports show miRNAs as critical gene regulators in inflammation and astrogliosis in astrocytes. The aim of this study is to investigate the microRNA changes affected by Anandamide on HIV1 TAT (Trans-activator of transcription protein) stimulated normal human astrocytes. We performed global microRNA profile in TAT activated astrocytes and analysed changes on exposure to AEA. To delineate the mechanism of action we assessed with bioinformatic tools miRWalk, KEGG and Cytoscape the global microarray for significantly impacted miRNAs, and their gene targets. TAT activation in astrocytes upregulated 122 miRNAs significantly (p < 0.05). Addition of AEA in activated astrocytes downregulate the expression of 57 miRNAs significantly. Out of 122 upregulated miRNAs on TAT treatment, 37 miRNAs which were common in TAT and TAT+AEA cells showed reversal suggesting clues to critical miRNAs for the AEA-induced mitigation of neuroinflammation. Reversal in expression of selected group of miRNAs identify antagonistic pathways which are promoting anti-inflammatory environment. Pathway analysis of key 37 miRNAs show gene targets that regulate inflammation and senescence.
Outcomes of children with serious traumatic brain injury treated in pediatric vs. adult departments
Authors: Bruns Nora , Hojeij Rayan , Brensing Pia , Nonnemacher Michael , Dammann Philipp , Dudda Marcel , Felderhoff-Müser Ursula , Stang Andreas , Dohna-Schwake Christian
Published: October 2024

The impact of treatment in a non-pediatric department on mortality and outcomes of children with traumatic brain injury (TBI) is unknown. This study aimed to quantify the impact of the treating department (pediatric (PD) or adult (AD)) on in-hospital case fatality and functional short-term outcomes in children with serious TBI who survived the initial 12 hours after hospital admission.

A Nationwide retrospective cohort study was conducted from a dataset that comprises all discharges from German hospitals from 2016 to 2021. Disease and procedural codes were used to retrieve clinical and outcome information. Hierarchical multilevel logistic regression modeling was performed to quantify the effect of the treating department on the outcomes of interest. Eligibility criteria were age < 18 years and hospital admission with serious TBI.

The main outcome was in-hospital death and secondary outcomes were pediatric complex chronic conditions category (PCCC) ≥ 2 in survivors, composite outcome (death or PCCC ≥ 2), and adjusted mean PCCC in survivors.

Of 13,492,528 pediatric cases, 12,275 were included. The adjusted odds ratio (OR) for death was 3.00 (95 % confidence interval 1.93–4.68) for children treated in ADs compared to PDs. The OR for PCCC ≥ 2 was 0.93 (0.78–1.12) and 1.04 (0.87–1.25) for the composite outcome.

Adjusted average PCCC were 0.40 (0.37–0.44) in ADs and 0.44 (0.42–0.46) in PDs.

This comprehensive nationwide study found increased odds for in-hospital death but similar functional outcomes at discharge among surviving children with serious TBI who were treated outside of PDs.
A systematised review of seasonal influenza case-fatality risk
Authors: Filipe Johnny A N , Wong Carlos K H , van Leeuwen Edwin , Goodfellow Lucy , Procter Simon R , Jit Mark
Published: October 2024

Case-fatality risk (CFR) is an important indicator of disease severity for influenza infection. However, estimates based on laboratory-confirmed cases (cCFR) are more-highly sensitive to features of the local health-care system and surveillance. Estimates based on diagnosed-symptomatic cases (sCFR) are more consistent across health systems but less commonly reported. We present a systematised review of sCFR for seasonal influenza. We identified 10 studies reporting sCFR, or primary data for its direct estimation, resulting in 40 location and season-specific point estimates (range 0.3-908 per 100,000 cases). The wide variation across studies and lack of studies in many world regions point to the need for standardised protocols and more data collection.
Frequency-specific hemispheric bias in phase entrainment of neural oscillations in unilateral spatial neglect
Authors: Okazaki Yuka O. , Hattori Noriaki , Kawano Teiji , Hatakenaka Megumi , Miyai Ichiro , Kitajo Keiichi
Published: October 2024

Left unilateral spatial neglect (USN), typically caused by a right hemisphere lesion, impairs left-side stimulus perception. Attention influences perception via cortical oscillations, shown as phase shifts and power changes in electroencephalography (EEG). Given this relationship, USN may stem from hemispheric imbalance in synchronizing cortical oscillations internally and externally. We studied this using steady-state visual evoked potentials (SSVEPs) from flickering stimuli of various frequencies. Our study included USN and non-USN patients with a right hemisphere lesion, but no hemianopsia, as well as healthy controls. Importantly, we confirmed that the affected hemisphere’s visual cortex in both patient groups responded to all flickering frequencies, ensuring a valid comparison. Comparing SSVEP power between the intact and affected hemispheres revealed no differences in non-USN patients. In USN patients, both hemispheres responded equally to most frequencies; however, SSVEP power was enhanced in the intact visual cortex with 9-Hz stimulation, resulting in a significant hemispheric bias. This bias was not caused by deficiencies in generating oscillations (we observed no significant differences in spontaneous pre-stimulus alpha oscillations) but rather by abnormal alpha-band synchronization with external inputs. Further analyses revealed increased phase-amplitude coupling between alpha phase and gamma amplitude in the intact hemisphere and elevated transfer entropy from the right visual cortex to the left frontal cortex in USN patients. These results reveal that USN involves complex alterations in neural synchronization stemming from imbalanced entrainment of oscillators to alpha-frequency stimuli, beyond merely local damage. This alpha-specific effect provides insights into frequency-specific synchronization in spatial attention, potentially guiding targeted therapies.

Significance Statement

This study provides crucial insight into the neural mechanisms underlying unilateral spatial neglect (USN), a sequela of stroke. By examining the frequency-specific hemispheric bias in neural synchronization, we identified a significant imbalance in brain activity, particularly in the alpha frequency range. This imbalance was not merely a result of local deficits but involved complex compensatory mechanisms at both the local and global network levels. Our findings highlight how disrupted neural oscillations and impairments in the capacity to modulate these oscillations for synchronization contribute to cognitive deficits in patients with USN. This research addresses gaps in our understanding of attention function and disorders, which will aid the development of more targeted therapeutic interventions and rehabilitation strategies.
The effectiveness of medical face masks and respirators in reducing SARS-CoV-2 transmission in community settings: a scoping review
Authors: Vardavas Constantine I. , Marou Valia , Aslanoglou Katerina , Manta Anastasia , Lagou Ioanna , Plyta Zinovia , Leonardi-Bee Jo , Lamb Favelle , Cenciarelli Orlando , Baka Agoritsa
Published: October 2024

Background

During the COVID-19 pandemic, various public health and social measures (PHSM) were implemented with the primary objective of curtailing the transmission of SARS-CoV-2. This review aims to synthesise existing evidence on the effectiveness of medical facemasks and/or respirators (FFP2/KN95/N95) in reducing SARS-CoV-2 transmission/infection in community settings.

Methods

A scoping literature review adhering to PRISMA was performed. All relevant study designs within community settings, excluding modelling studies, published between January 2000 and January 2023 and indexed in Medline and Embase were included with no geographical limitation. Studies not specifying facemask/respirator type or not presenting isolated outcomes for specific facemask/respirator types were excluded.

Results

Of the 10,185 studies identified, two randomised controlled trials (RCT) and two case-control studies met all inclusion criteria. The largest RCT identified an adjusted prevalence ratio of 0.89 (95%CI: 0.78-1.00) for medical vs. cloth masks. In a smaller RCT, the between-group difference favoured the mask vs no mask group (-0.3 percentage points; 95%CI: -1.2 to 0.4). Within one case-control study, N95/KN95 respirators (aOR 0.17; 95%CI: 0.05-0.64) or medical masks (aOR 0.34; 95%CI: 0.13-0.90) were associated with statistically significant lower adjusted odds of a positive test result compared to no facemask use. A second case-control study associated medical mask use with reduced COVID-19 risk in unadjusted models (OR 0.25; 95% CI: 0.12-0.53) but this effect was not independently associated with infection in multivariable models (aOR 0.61; 95%CI: 0.25-1.49).

Conclusions

Limited published evidence exists on the effectiveness of medical facemask use in community settings. Medical masks and respirators (compared to cloth masks) may reduce SARS-CoV-2 transmission, but interpretation requires caution. Mask use in community settings was rarely implemented in isolation to other PHSMs so deciphering whether the effect is solely because of mask-wearing or a combined effect is extremely challenging necessitating additional studies.
Performance of deep-learning based approaches to improve polygenic scores
Authors: Kelemen Martin , Xu Yu , Jiang Tao , Hua Zhao Jing , Anderson Carl , Wallace Chris , Butterworth Adam , Inouye Michael
Published: October 2024

Background/Objectives

Polygenic scores (PGS), which estimate an individual’s genetic propensity for a disease or trait, have the potential to become part of genomic healthcare. In maximising the predictive performance of PGS, neural-network (NN) based deep learning has emerged as a method of intense interest to model complex, nonlinear phenomena, which may be adapted to exploit gene-gene (GxG) and gene-environment (GxE) interactions.

Methods

To infer the amount of nonlinearity present in a phenotype, we present a framework for using NNs, which controls for the potential confounding effect of correlation between genetic variants, i.e. linkage disequilibrium (LD). We fit NN models to both simulated traits and 28 real disease and anthropometric traits in the UK Biobank.

Results

Simulations confirmed that our framework adequately controls LD and can infer nonlinear effects, when such effects genuinely exist. Using this approach on real data, we found evidence for small amounts of nonlinearity due to GxG and GxE which mildly improved prediction performance (r2) by ∼7% and ∼4%, respectively. Despite evidence for nonlinear effects, NN models were outperformed by linear regression models for both genetic-only and genetic+environmental input scenarios with ∼7% and ∼5% differences in r2, respectively. Importantly, we found substantial evidence for confounding by joint tagging effects, whereby inferred GxG was actually LD with due to unaccounted for additive genetic variants.

Conclusion

Our results indicate that the usefulness of NNs for generating polygenic scores for common traits and diseases may currently be limited and may be confounded by joint tagging effects due to LD.
Residential exposure to green and blue spaces over childhood and cardiometabolic health outcomes: The Generation XXI birth cohort
Authors: Valente Berta , Araújo B. , Pereira Rita , Ribeiro Ana Isabel , Barros Henrique , Santos Susana
Published: October 2024

Background

Evidence on the effects of exposure to green and blue spaces on childhood cardiometabolic health is inconsistent, limited and mostly cross-sectional.

Objectives

To assess the associations of exposure to green and blue spaces, at birth, 4, 7, and 10 years (to identify vulnerable periods of exposure) and as longitudinal trajectories (to identify the longitudinal effect over time), with cardiometabolic health outcomes at 10 years.

Methods

Participants are from Generation XXI, a population-based birth cohort from Porto Metropolitan Area, Portugal (n=4669). Residential normalized difference vegetation index (NDVI) and Euclidian distance to the nearest urban green and blue space were assessed at birth, 4, 7 and 10 years using geographic information systems and standardized by dividing the observed value by the standard deviation. Longitudinal trajectories of exposures from birth to 10 years were derived using latent class mixed models. At 10 years, we measured body mass index, fat mass index and android-to-gynoid fat ratio, blood pressure, and metabolic outcomes. We defined overweight/obesity by the World Health Organization, high blood pressure by the American Academy of Pediatrics and metabolic syndrome by the IDEFICS study.

Results

No significant associations were observed between natural spaces exposure and body mass index, body fat content and distribution. We found an inverse association between distance to nearest blue space at birth and systolic blood pressure z-scores, and a positive association between distance to nearest green space at 7 and 10 years and metabolic syndrome score (p-values<0.05). Also, compared to children in the high stable trajectory of NDVI500m, those in the descending trajectory of NDVI500m presented a lower diastolic blood pressure z-score and metabolic syndrome score (p-values<0.05). However, after multiple testing correction, all associations lost statistical significance.

Discussion

This study did not find robust associations between the exposure to natural spaces over key developmental periods and cardiometabolic health.
“Evaluating the Impact of Artificial Intelligence on Vaccine Development: Lessons Learned from the COVID-19 Pandemic”
Authors: Farahani Arshia Farmahini , Kasraei Nika
Published: October 2024

The integration of artificial intelligence (AI) into the field of vaccine development has revolutionized the discovery and production processes, particularly during the COVID-19 pandemic. AI technologies played an instrumental role in accelerating the identification of viable vaccine candidates, optimizing clinical trial designs, and expediting regulatory approvals. This review critically examines the impact of AI-driven approaches on the development of COVID-19 vaccines, highlighting case studies such as the Pfizer-BioNTech and Moderna vaccines. By employing machine learning algorithms and sophisticated data analytics, AI significantly reduced traditional vaccine development timelines from years to mere months, all while enhancing precision, safety, and efficacy.

Our analysis reveals that AI facilitated real-time monitoring of clinical trial data, improving patient stratification, and dynamically addressing adverse events, leading to faster approvals without compromising regulatory standards. Furthermore, AI-powered models optimized vaccine distribution strategies, overcoming logistical challenges associated with global deployment during the pandemic. This review also explores the ethical and technical challenges posed by AI, such as algorithmic biases, data privacy concerns, and the need for transparent governance frameworks. The lessons drawn from the COVID-19 pandemic underscore the transformative potential of AI in accelerating future vaccine research and pandemic preparedness. We conclude that continued interdisciplinary collaboration between AI experts, immunologists, and public health authorities will be essential in shaping the future of vaccine innovation.
The Impact of the Temperature on Extracting Information From Clinical Trial Publications Using Large Language Models
Authors: Windisch Paul , Dennstädt Fabio , Koechli Carole , Schröder Christina , Aebersold Daniel M. , Förster Robert , Zwahlen Daniel R.
Published: October 2024

Introduction

The application of natural language processing (NLP) for extracting data from biomedical research has gained momentum with the advent of large language models (LLMs). However, the effect of different LLM parameters, such as temperature settings, on biomedical text mining remains underexplored and a consensus on what settings can be considered “safe” is missing. This study evaluates the impact of temperature settings on LLM performance for a named-entity recognition and a classification task in clinical trial publications.

Methods

Two datasets were analyzed using GPT-4o and GPT-4o-mini models at nine different temperature settings (0.00–2.00). The models were used to extract the number of randomized participants and classified abstracts as randomized controlled trials (RCTs) and/or as oncology-related. Different performance metrics were calculated for each temperature setting and task.

Results

Both models provided correctly formatted predictions for more than 98.7% of abstracts across temperatures from 0.00 to 1.50. While the number of correctly formatted predictions started to decrease afterwards with the most notable drop between temperatures 1.75 and 2.00, the other performance metrics remained largely stable.

Conclusion

Temperature settings at or below 1.50 yielded consistent performance across text mining tasks, with performance declines at higher settings. These findings are aligned with research on different temperature settings for other tasks, suggesting stable performance within a controlled temperature range across various NLP applications.
Biological Age as a Predictor of Arterial Stiffness in Young and Early Midlife Black and White Women
Authors: Spikes Telisa A. , Alonso Alavaro , Thorpe Roland J. , Pelkmans Jordan , Higgins Melinda K. , Sullivan Samaah , Dunbar Sandra B. , Lewis Tene T. , Searles Charles , Mehta Puja K. , Pemu Priscilla E. , Taylor Herman A. , Quyyumi Arshed A.
Published: October 2024

Background: Arterial stiffness is a precursor of hypertension and hallmark of vascular aging. Chronological age (CA), a robust determinant of arterial stiffness, is considered an insufficient indicator of aging and disparities associated with disease risk. Biological age (BA), the true age based on physiological decline, is recognized as a better indicator of disease risk however the interplay among BA, CA, and arterial stiffness remains inconclusive. We investigated the associations between BA, CA, and arterial stiffness as a potential pathway for higher cardiovascular risk among Black women and whether race modified these associations. Methods: In 230 women (n=150 White, n=80 Black) enrolled in the Predictive Health Institute cohorts (age range 25-49), arterial stiffness was assessed using carotid-femoral pulse wave velocity (cfPWV), measured by applanation tonometry (SphygmoCor®). BA was estimated using the Klemera-Doubal method from 11 different clinical biomarkers and CA. Accelerated age (AccA) was calculated as the difference between BA and CA. Overall and race-specific associations between BA and arterial stiffness adjusting for sociodemographics, health behaviors, and clinical factors were estimated using multiple linear regression. Results: Overall mean (SD) for CA and BA was 40 (6.1), and 38 (12.1) years, respectively. Mean (SD) for BA, AccA, and cfPWV were 43 (13.1), 1.6 (12.9), and 7.3 (1.1) in Black women and 36 (10.8), -3.2 (10.6), and 6.3 (0.8) in White women (Black-White difference in BA: 6.4 years, P=<0.001). Overall, BA (β=0.02 m/s per year, 95%CI: 0.00, 0.03) predicted cfPWV even after adjustment for CA, without a significant interaction by race (P=0.65). Conclusions: BA is a predictor of arterial stiffness after accounting for CA and additional relevant factors. Although there were no racial differences in this association, both BA and arterial stiffness were higher among Black compared to White women. Longitudinal studies are needed to identify BA patterns and CVD risk in Black women.
Detecting Potential Mediators of the Causal Effect of Education Level on The Risk of Stroke: A Two-Step, Two-Sample Multivariable Mendelian Randomization Study
Authors: Ken C , Ying Z , Zheng W , Ying Y
Published: October 2024

Background

The effect of education level on the risk of stroke is not fully understood. The present study aimed to reveal the genetic and modifiable mediators for the effect of education level on the risk of stroke.

Methods

Summary-level genetic data were obtained from GWAS consortia. Two-sample Mendelian Randomization (MR) analysis was performed to uncover the causal effect of education level on the risk of stroke, and regression-based multivariable MR (MVMR) analyses were used to explore potential mediators.

Results

Genome-wide MR analyses showed that genetically determined higher education level was associated with reduced risk of stroke (Odds ratio (OR) per standard deviation (SD) increase: 0.74[95% confidence interval (CI): 0.58 to 0.94]; p = 0.013). We found instant coffee intake, never smoking status, body mass index (BMI), waist circumference (WC), waist-hip- ratio (WHR), Type-2 diabetes mellitus (T2DM), Diastolic pressure (DBP), Systolic pressure (SBP), Alanine aminotransferase (ALT), Platelet (PLT) and CTRP-1 (complement c1q tumor necrosis factor-related protein 1) had significant mediation roles in the effect of education level on the risk of stroke. The proportion of total effect mediated by these modifiable factors was 79%.

Conclusion

We found many modifiable mediators had essential mediation roles in the effect of education level on the risk of stroke. Intervention on these mediators might have protective effect on the risk of stroke, which highlighted novel therapeutic targets.
Expression of sex steroid receptors and sex differences of Otp glutamatergic neurons of the medial extended amygdala
Authors: González-Alonso Alba , Morales Lorena , Sanz Elisenda , Medina Loreta , Desfilis Ester
Published: October 2024

The medial extended amygdala (EAme) is part of the social behavior network and its subdivisions show expression of sex steroid receptors, which participate in the regulation of sexually dimorphic behaviors. However, EAme subdivisions are highly heterogeneous in terms of neuron subtypes, with different subpopulations being involved in regulation of different aspects of social and non-social behaviors. To further understand the role of the different EAme neurons and their contribution to sexual differences, here we studied one of its major subtypes of glutamatergic neurons, those derived from the telencephalon-opto-hypothalamic domain that coexpressOtpandFoxg1genes during development. Our results showed that the vast majority of the Otp glutamatergic neurons of the medial amygdala and BSTM in both sexes expressAr,Esr1 (ERα)andEsr2 (ERβ) mRNA. Moreover, the high percentage of receptors expression in the Otp neurons (between 93 and 100%) indicates that probably the majority of the Otp neurons of EAme are coexpressing the three receptors. In addition, Otp neurons of the posterodorsal medial amygdala have a larger soma and occupy more space in males than in females. These and other features of the Otp neurons regarding their expression of sex steroid receptors likely contribute to some of the sexually-dimorphic behaviors regulated by EAme.
Rewired type I IFN signaling is linked to age-dependent differences in COVID-19
Authors: Petrov Lev , Brumhard Sophia , Wisniewski Sebastian , Georg Philipp , Hillus David , Hiller Anna , Astaburuaga-García Rosario , Blüthgen Nils , Wyler Emanuel , Vogt Katrin , Dey Hannah-Philine , von Stillfried Saskia , Iwert Christina , Bülow Roman D. , Märkl Bruno , Maas Lukas , Langner Christine , Meyer Tim , Loske Jennifer , Eils Roland , Lehmann Irina , Ondruschka Benjamin , Ralser Markus , Trimpert Jakob , Boor Peter , Bedoui Sammy , Meisel Christian , Mall Marcus A. , Corman Victor M. , Sander Leif Erik , Röhmel Jobst , Sawitzki Birgit
Published: October 2024

Advanced age is the most important risk factor for severe disease or death from COVID-19, but a thorough mechanistic understanding of the molecular and cellular underpinnings is lacking. Multi-omics analysis of samples from SARS-CoV-2 infected persons aged 1 to 84 years, revealed a rewiring of type I interferon (IFN) signaling with a gradual shift from signal transducer and activator of transcription 1 (STAT1) to STAT3 activation in monocytes, CD4+T cells and B cells with increasing age. Diversion of interferon IFN signaling was associated with increased expression of inflammatory markers, enhanced release of inflammatory cytokines, and delayed contraction of infection-induced CD4+T cells. A shift from IFN-responsive germinal center B (GCB) cells towards CD69highGCB and atypical B cells corresponded to the formation of IgA in children while complement fixing IgG was dominant in adults. Our data provide a mechanistic basis for inflammation-prone responses to infections and associated pathology during aging.

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