bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Disruption Persists and Relates to Memory Disability After Traumatic Brain Injury: A Cross-Sectional Study of Adults in the Chronic Phase of Injury
Authors: Morrow Emily L. , Duff Melissa C.
Published: May 2024

Objective:

To examine sleep disruption in chronic traumatic brain injury (TBI) across 3 aims: (1) to examine differences in self-reported sleep disruption between adults with and without a chronic history of TBI; (2) to query reported changes in sleep after TBI; and (3) to explore the relationship between self-reported sleep disruption and memory failures in daily life.

Setting:

Community-dwelling participants completed self-report sleep and memory surveys as part of their participation in a larger patient registry.

Participants:

This study included 258 participants, and half (n = 129) of them have a chronic history of moderate-severe TBI (mean time since injury is 5.1 [SD 6.5] years).

Design:

We report descriptive statistics from this matched cross-sectional study on sleep in the chronic phase of injury. We also used planned Wilcoxon ranked-sum tests and exploratory correlations to examine the relationships of sleep disruption with TBI diagnosis, injury chronicity, and memory.

Main Measures:

We used the Pittsburgh Sleep Quality Index to measure sleep disruption and the Epworth Sleepiness Scale to measure daytime sleepiness. Participants answered questions about postinjury sleep and responded to the Everyday Memory Questionnaire as a measure of memory failures in daily life.

Results:

Individuals with TBI had significantly higher rates of sleep disruption than those without TBI, as measured by the Pittsburgh Sleep Quality Index but not on the Epworth Sleepiness Scale. Sleep disruption in TBI manifested more in sleep quality than quantity. Half of the participants with TBI reported a negative change in sleep postinjury. In an exploratory analysis, sleep disruption was related to memory failure in daily life in the TBI sample.

Conclusions:

Sleep disruption persists long after TBI but may be under-recognized in people with chronic TBI. Given that sleep is critical for memory and rehabilitation outcomes well into the chronic phase of injury, steps to improve the identification and management of sleep disruption are needed. Key words:
chronic, memory, sleep, traumatic brain injury
Trauma-Informed Care Education Initiative Explores Impact on Perinatal Nurse Secondary Traumatic Stress and Workforce Challenges
Authors: Runyon Maggie C. , Irby Mandy N. , Rojas Landivar Paula
Published: May 2024

Background:

Psychological trauma refers to long-lasting adverse effects on well-being precipitated by the experience of a distressing event or a combination of events. High rates of psychological birth trauma in patients contribute to secondary traumatic stress (STS) in perinatal nurses, creating workplace challenges and resulting in dissatisfaction, apathy, and attrition. Perinatal nurses experience high rates of STS, and researchers have called for a universal standard of trauma-informed care (TIC). However, there is a lack of published results on effectively creating TIC education in this nurse population.

Methods:

A pre/posttest design evaluated an online pilot evidence-based practice project addressing a perinatal nurse education initiative on STS and its correlation with nurse attitudes toward TIC. Participants include perinatal nurses in the United States (n = 29). Two scales measured the program’s effect on nurses: the Secondary Traumatic Stress Scale (STSS) and the Attitudes Related to Trauma-Informed Care (ARTIC) scale.

Results:

A paired t test evaluating pre- and postprogram levels of the STSS showed a decrease in STS (t
28 = −3.28, P = .003, Cohen’s d = 0.609), the ARTIC scale results showed an increased receptiveness to TIC (t
28 = 3.8, P < .001, Cohen’s d = 0.706], and a not significant correlation was found between pretest STS and ARTIC scores (Spearman’ ρ = −0.248, P = .194).

Conclusion:

This program supported a significant reduction in nurses’ identification of STS. Future perinatal nurse education can expand to build a standard of TIC that is patient-centered and reduces nurse STS.
Ovarian cancer
Authors: Pullen Richard L.
Published: May 2024

Ovarian cancer, a leading cause of cancer deaths, poses challenges due to insidious development and vague signs and symptoms. Risk factors include age, reproductive history, genetic mutations, and environmental factors. Treatment involves surgery, chemotherapy, and targeted therapy, with nursing interventions focusing on symptom management and supportive care.
Sepsis best practices
Authors: Seckel Maureen A.
Published: May 2024

Sepsis remains a complex and costly disease with high morbidity and mortality. This article discusses Sepsis-2 and Sepsis-3 definitions, highlighting the 2021 Surviving Sepsis International guidelines as well as the regulatory requirements and reimbursement for the Severe Sepsis and Septic Shock Management Bundle (SEP-1) measure.
Can artificial intelligence help ED nurses more accurately triage patients?
Authors: Regan Melinda
Published: May 2024

The Emergency Severity Index (ESI) is the most popular tool used to triage patients in the US and abroad. Evidence has shown that ESI has its limitations in correctly assigning acuity. To address this, AI can be incorporated into the triage process, decreasing the likelihood of assigning an incorrect ESI level.
Radiation-Induced Cellular Plasticity: A Strategy for Combatting Glioblastoma
Authors: He Ling , Azizad Daria , Bhat Kruttika , Ioannidis Angeliki , Hoffmann Carter J. , Arambula Evelyn , Bhaduri Aparna , Kornblum Harley I. , Pajonk Frank
Published: May 2024

Glioblastoma is the deadliest brain cancer in adults and almost all patients succumb to the tumor. While surgery followed by chemo-radiotherapy significantly delays disease progression, these treatments do not lead to long-term tumor control and targeted therapies or biologics have so far failed to further improve survival.

Utilizing a transient radiation-induced state of multipotency we used the adenylcyclase activator forskolin to alter the cellular fate of glioma cells in response to radiation. The combined treatment induced the expression of neuronal markers in glioma cells, reduced proliferation and led to a distinct gene expression profile. scRNAseq revealed that the combined treatment forced glioma cells into a microglia- and neuron-like phenotypes.In vivothis treatment led to a loss of glioma stem cells and prolonged median survival in mouse models of glioblastoma. Collectively, our data suggest that revisiting a differentiation therapy with forskolin in combination with radiation could lead to clinical benefit.
ninjaCap: A fully customizable and 3D printable headgear for fNIRS and EEG brain imaging
Authors: von Lühmann Alexander , Kura Sreekanth , O’Brien W. Joseph , Zimmermann Bernhard B. , Duwadi Sudan , Rogers De’Ja , Anderson Jessica E. , Farzam Parya , Snow Cameron , Chen Anderson , Yücel Meryem A. , Perkins Nathan , Boas David A.
Published: May 2024

Significance

Accurate sensor placement is vital for non-invasive brain imaging, particularly for functional near infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT), which lack standardized layouts like EEG. Custom, manually prepared probe layouts on textile caps are often imprecise and labor-intensive.

Aim

We introduce a method for creating personalized, 3D-printed headgear, enabling accurate translation of 3D brain coordinates to 2D printable panels for custom fNIRS and EEG sensor layouts, reducing costs and manual labor.

Approach

Our approach uses atlas-based or subject-specific head models and a spring-relaxation algorithm for flattening 3D coordinates onto 2D panels, using 10-5 EEG coordinates for reference. This process ensures geometrical fidelity, crucial for accurate probe placement. Probe geometries and holder types are customizable and printed directly on the cap, making the approach agnostic to instrument manufacturers and probe types.

Results

Our ninjaCap method offers 2.2±1.5 mm probe placement accuracy. Over the last five years, we have developed and validated this approach with over 50 cap models and 500 participants. A cloud-based ninjaCap generation pipeline along with detailed instructions is now available at openfnirs.org.

Conclusions

The ninjaCap marks a significant advancement in creating individualized neuroimaging caps, reducing costs and labor while improving probe placement accuracy, thereby reducing variability in research.
Needs Assessment for the Development of a Sustainability Curriculum for Surgical Residents
Authors: Matthys Madeline , Wang Jane , Sathe Tejas S. , Wang Kaiyi , Gandhi Seema , Lee Hanmin , Alseidi Adnan ,   the Sustainability Curriculum Working Group
Published: May 2024

Introduction

The healthcare sector accounts for 8.5% of United States (U.S.) greenhouse gas emissions, of which one-third comes from operating rooms (ORs). As a result, there is great interest in decarbonizing the OR and surgical care. However, surgical residents are not routinely educated on the negative environmental impact of surgery or how to reduce it. In this paper, we present a formal needs assessment for a sustainability curriculum geared towards surgical residents.

Methods

Using Kern’s Six-Step Framework for curriculum development, we conducted focus groups with surgical residents to perform a targeted needs assessment on three main topics: 1) the current state of surgical sustainability curricula; 2) resident knowledge regarding the environmental impact of surgery and barriers to sustainable practice; and 3) preferred educational methods and topics within sustainability education. We recorded all focus groups and performed thematic analysis using anonymized transcripts.

Results

Fourteen residents participated in three focus groups, from which a qualitative analysis revealed four themes. First, surgery residents receive limited formal teaching on the negative environmental impact of surgical care or how to reduce this impact. Second, surgery residents have variable levels of prior education about and interest in sustainability in surgery. Third, several barriers prevent the implementation of sustainable changes in surgical practice, including a lack of institutional initiative, cultural inertia, concerns about workflow efficiency, and limited formal education. Finally, residents prefer to learn about practical ways to reduce waste, specifically through interactive approaches such as quality improvement initiatives.

Conclusions

Given the increasing importance of sustainability in surgery, there is an urgent need for formal resident education on this topic. This needs assessment provides a valuable foundation for future sustainability curriculum development.
The effects of white matter hyperintensities on MEG power spectra in cognitively healthy aging
Authors: Torres-Simón Lucia , Cuesta Pablo , del Cerro Alberto , Doval Sandra , Chino Brenda , Hernández Lucía , Marsh Elizabeth B. , Maestú Fernando
Published: May 2024

Objective

This study sought to identify magnetoencephalography (MEG) power spectra patterns associated with cerebrovascular damage (white matter hyperintensities - WMH) and their relationship with cognitive performance and brain structure integrity in aging individuals without cognitive impairment.

Methods

We hypothesized a “slowness” pattern characterized by increased power in δ and θ bands and decreased power in the β band associated with the severity of vascular damage. MEG signals were analyzed in cognitively healthy older adults to investigate these associations.

Results

Contrary to expectations, we did not observe an increase in δ and θ power. However, we found a significant negative correlation between β band power and WMH volume. This β power reduction was linked to structural brain changes, such as larger lateral ventricles, reduced white matter volume, and decreased fractional anisotropy in critical white matter tracts, but not to cognitive performance. This suggests that β band power reduction may serve as an early marker of vascular damage before the onset of cognitive symptoms.

Conclusion

Our findings partially confirm our initial hypothesis by demonstrating a decrease in β band power with increased vascular damage but not the anticipated increase in slow band power. The lack of correlation between the βpow marker and cognitive performance suggests its potential utility in early identification of at-risk individuals for future cognitive impairment due to vascular origins. These results contribute to understanding the electrophysiological signatures of preclinical vascular damage and highlight the importance of MEG in detecting subtle brain changes associated with aging.
Cell-free RNA Liquid Biopsy to Monitor Hematopoietic Stem Cell Transplantation
Authors: Loy Conor , Cheng Matthew P. , Gonzalez-Bocco Isabel H. , Lenz Joan , Belcher Emma , Bliss Andrew , Eweis-LaBolle Daniel , Chu Tinyi , Ritz Jerome , De Vlaminck Iwijn
Published: May 2024

Hematopoietic Stem Cell Transplantation (HSCT) is one of the oldest and most successful immunotherapies. Yet, despite long-standing success in the use of HSCT for the treatment of blood cancers and severe immune disorders, monitoring post-transplant complications remains a challenge due to a lack of informative diagnostic tests. Here, we investigate the utility of cell-free RNA (cfRNA) in plasma as a liquid biopsy to monitor allogeneic HSCT recipients during and after treatment. We assayed longitudinal samples from 92 HSCT recipients by cfRNA sequencing and show that cfRNA provides insight into treatment and recovery trajectories, immune dynamics in response to transplantation, infection, and solid-tissue injury associated with Graft-Versus-Host Disease. Collectively, our results provide support for the use of plasma cfRNA profiling to monitor complications of HSCT.
Efficacy and Safety of Habitual Consumption of a Food Supplement Containing Miraculin in Malnourished Cancer Patients: the CLINMIR Pilot Study
Authors: López-Plaza Bricia , Álvarez-Mercado Ana Isabel , Arcos-Castellanos Lucía , Plaza-Diaz Julio , Ruiz-Ojeda Francisco Javier , Brandimonte-Hernández Marco , Feliú-Batlle Jaime , Hummel Thomas , Gil Ángel , Milla Samara Palma
Published: May 2024

Taste disorders (TDs) are common among systemically treated cancer patients and negatively impact their nutritional status and quality of life. A food supplement containing the natural taste-modifying protein miraculin (DMB®) has emerged as a possible alternative treatment for TDs. The present study aimed to evaluate the efficacy and safety of habitual DMB consumption in malnourished cancer patients undergoing active treatment. An exploratory clinical trial was carried out in which 31 cancer patients were randomized into three arms [standard dose of DMB (150 mg DMB/tablet), high dose of DMB (300 mg DMB/tablet) or placebo (300 mg freeze-dried strawberry)] for three months. Patients consumed an intervention DMB tablet or placebo before each main meal. Throughout the five main visits, electrochemical taste perception, nutritional status, dietary intake, quality of life and the fatty acid profile of erythrocytes were evaluated. Patients consuming a standard dose of DMB exhibited improved taste acuity over time (% change right/left side: ‒52.8 ± 38.5 / ‒58.7 ± 69.2%) and salty taste perception (2.29 ± 1.25vs.high dose: 2.17 ± 1.84vs.placebo: 1.57 ± 1.51 points, p < 0.05). They also had higher energy intake (p = 0.075) and covered better energy expenditure (107 ± 19%). The quality of life evaluated by symptom scales improved in patients receiving the standard dose of DMB (constipation, p = 0.048). The levels of arachidonic (13.1 ± 1.8; 14.0 ± 2.8, 12.0 ± 2.0%; p = 0.004) and do-cosahexaenoic (4.4 ± 1.7; 4.1 ± 1.0; 3.9 ± 1.6%; p = 0.014) acids in erythrocytes increased over time after DMB intake. The standard dose of DMB increased fat‒free massvs. placebo (47.4 ± 9.3 vs. 44.1 ± 4.7 kg, p = 0.007). Importantly, habitual patients with DMB did not experience any adverse events, and metabolic parameters remained stable and within normal ranges. In conclusion, habitual consumption of a standard 150 mg dose of DMB improves electrochemical food perception, nutritional status (energy intake, fat quantity and quality, fat-free mass) and quality of life in malnourished cancer patients receiving antineoplastic treatment. Additionally, DMB consumption appears to be safe, with no changes in major biochemical parameters associated with health status. The clinical trial was registered athttp://clinicaltrials.gov(NCT05486260).
Unveiling Tissue Structure and Tumor Microenvironment from Spatially Resolved Transcriptomics by Hypergraph Learning
Authors: Liao Yi , Zhang Chong , Wang Zhikang , Qi Fei , Huang Weitian , Cai Shangyan , Li Junyu , Yuan Zhiyuan , Song Jiangning , Cai Hongmin
Published: May 2024

Spatially resolved transcriptomics (SRT) technologies acquire gene expressions and spatial information simultaneously, reshaping the perspectives of life sciences. Identifying spatial patterns is essential for exploring organ development and tumor microenvironment. Nevertheless, emerging SRT technologies have also introduced diverse spatial resolutions, posing challenges in characterizing spatial domains with finer resolutions. Here we propose a hypergraph-based method, termed HyperSTAR to precisely recognize spatial domains across varying spatial resolutions by utilizing higher-order relationships among spatially adjacent tissue programs. Specifically, a gene expression-guided hyperedge decomposition module is incorporated to refine the structure of the hypergraph to precisely delineate the boundaries of spatial domains. A hypergraph attention convolutional neural network is designed to adaptively learn the significance of each hyperedge. With the power of capturing intricate higher-order relationships within spatially neighboring multi-spots/cells, HyperSTAR demonstrates superior performance across different technologies with various resolutions compared to existing advanced graph neural network models in multiple tasks including uncovering tissue sub-structure, inferring spatiotemporal patterns, and denoising spatially resolved gene expressions. It successfully reveals spatial heterogeneity in breast cancer section and its findings are further validated through functional and survival analyses of independent clinical data. Notably, HyperSTAR performs well with diverse spatial omics data types and seamlessly extends to large-scale datasets.
The Endoplasmic Reticulum as an Active Liquid Network
Authors: Scott Zubenelgenubi C. , Steen Samuel B. , Huber Greg , Westrate Laura M. , Koslover Elena F.
Published: May 2024

The peripheral endoplasmic reticulum (ER) forms a dense, interconnected, and constantly evolving network of membrane-bound tubules in eukaryotic cells. While individual structural elements and the morphogens that stabilize them have been described, a quantitative understanding of the dynamic large-scale network topology remains elusive. We develop a physical model of the ER as an active liquid network, governed by a balance of tension-driven shrinking and new tubule growth. This minimalist model gives rise to steady-state network structures with density and rearrangement timescales predicted from the junction mobility and tubule spawning rate. Several parameter-independent geometric features of the liquid network model are shown to be representative of ER architecture in live mammalian cells. The liquid network model connects the time-scales of distinct dynamic features such as ring closure and new tubule growth in the ER. Furthermore, it demonstrates how the steady-state network morphology on a cellular scale arises from the balance of microscopic dynamic rearrangements.

SIGNIFICANCE

The peripheral endoplasmic reticulum (ER) forms a continuous, dynamic network of tubules that plays an important role in protein sorting, export, and quality control, as well as cellular signaling and stress response. Elucidating how the unique morphology of the ER arises and supports its function is critical to developing a mechanistic understanding of the many neurological diseases associated with ER structural perturbations. We develop a physical model of the ER as an active liquid network to understand how its cellular-scale structure emerges from small-scale dynamic rearrangements. The model demon-strates how key features of ER architecture can arise from a balance of tubule growth and tension-driven sliding. This work provides insight into the fundamental physical mechanisms underlying the emergent morphology of the ER.
Functional brain networks predicting sustained attention are not specific to perceptual modality
Authors: Corriveau Anna , Ke Jin , Terashima Hiroki , Kondo Hirohito M. , Rosenberg Monica D.
Published: May 2024

Sustained attention is essential for daily life and can be directed to information from different perceptual modalities including audition and vision. Recently, cognitive neuroscience has aimed to identify neural predictors of behavior that generalize across datasets. Prior work has shown strong generalization of models trained to predict individual differences in sustained attention performance from patterns of fMRI functional connectivity. However, it is an open question whether predictions of sustained attention are specific to the perceptual modality in which they are trained. In the current study we test whether connectome-based models predict performance on attention tasks performed in different modalities. We show first that a predefined network trained to predict adults’visualsustained attention performance generalizes to predictauditorysustained attention performance in three independent datasets (N1=29, N2=60, N3=17). Next, we train new network models to predict performance on visual and auditory attention tasks separately. We find that functional networks are largely modality-general, with both model-unique and shared model features predicting sustained attention performance in independent datasets regardless of task modality. Results support the supposition that visual and auditory sustained attention rely on shared neural mechanisms and demonstrate robust generalizability of whole-brain functional network models of sustained attention.
Scale-sensitive Mouse Facial Expression Pipeline using a Surrogate Calibration Task
Authors: Telfer Andre , van Kaick Oliver , Abizaid Alfonso
Published: May 2024

Emotions are complex neuro-physiological states that influence behavior. While emotions have been instrumental to our survival, they are also closely associated with prevalent disorders such as depression and anxiety. The development of treatments for these disorders has relied on animal models, in particular, mice are often used in pre-clinical testing. To compare effects between treatment groups, researchers have increasingly used machine learning to help quantify behaviors associated with emotionality. Previous work has shown that computer vision can be used to detect facial expressions in mice. In this work, we create a novel dataset for depressive-like mouse facial expressions using varying LypoPolySaccharide (LPS) dosages and demonstrate that a machine learning model trained on this dataset was able to detect differences in magnitude via dosage amount.
iTreg mediated TGF-Β1 therapy improves functional engraftment of cell therapy in rd1 Retinitis Pigmentosa mouse model
Authors: Mohan K Varsha , Mishra Alaknanda , Sinha Prakriti , Muniyasamy Abaranjitha , Nagarajan Perumal , Chaudhary Kiran , Upadhyay Pramod
Published: May 2024

Purpose

Retinitis Pigmentosa (RP) is a progressive and hereditary disease that primarily affects the retina, leading to partial or complete vision loss. In addition to the direct impact on vision, the degeneration of the retina in RP also leads to inflammation in the eye, which can further damage the retina and make it difficult to treat the condition with cell therapy. This inflammation led to oxidative stress and cell death, creating an unfavourable environment for the introduction of new cells via cell therapy.

Methods

The potential of Transforming Growth Factor-Beta1 (TGF-B1) as an anti-inflammatory agent to treat ocular inflammation was investigated done by administering TGF-B1 intravitreally to the eyes of rd1 mice. However, due to the transient effect of TGF-B1 injection, the in-vitro-induced Treg (iTregs) cells that secrete TGF-B1, were generated and transplanted into the conjunctiva of 4 weeks old rd1 mice to achieve a sustained release of TGF-B1. After administering iTregs, Retinal Neuron-Like Cells (RNLCs) were transplanted into the rd1 mouse retina as a form of cell therapy to improve vision perception.

Flow cytometry was used to estimate the number of Qtracker labelled RNLCs post 30 days of transplantation. The potential of iTregs as an adjunct transplantation with RNLCs to improve cell therapy survival and vision rescue was investigated by conducting Electroretinography and behavioural studies.

Results

The study found that ocular inflammation can be reduced by treating with TGF-B1. After 30 days, mice transplanted with iTregs showed a significant increase in the number of transplanted RNLCs that survived compared to the mice who only received RNLCs. In the total fluid of the eye (aqueous plus vitreous), there was a significant increase in the levels of anti-inflammatory cytokines TGF-B1 and IL-10, and some decrease in the levels of pro-inflammatory cytokines Monocyte Chemoattractant Protein-1 (MCP1). The adjunct therapy of iTregs transplantation resulted in improvement in ERG wave functions and vision preservation compared to the group without adjunct iTregs.

Conclusions

The administration of TGF-B1-secreting iTregs to the affected eye reduced the inflammatory environment, which enabled transplanted RNLCs to stay longer compared to without TGF-B1. The iTregs mediated sustained anti-inflammatory adjunct therapy can improve the outcome of cell therapy for RP.
Application of observational research methods to real-world studies for rare disease drugs: a scoping review protocol
Authors: Patel Yuti P , Ghaddar Lea , Lin Yuqi , Karim Nuzat , Chan Kelvin , Dupuis Lee , Tadrous Mina
Published: May 2024

Objective

The primary objective is to identify which observational research methods have been used in the last 5 years in rare disease drug evaluation and how they are applied to generate adequate evidence regarding the real-world effectiveness or safety of rare disease drugs.

Background

Rare disease is an umbrella term for a condition which affects <200,000 people each year and despite the rarity of these conditions, collectively they encompass approximately 7000 different conditions. With the striking number of rare conditions, many pharmaceutical manufacturers are introducing an increased number of drugs to treat them. However, due to small patient populations, heterogeneity and other factors related to rare diseases, there are feasibility concerns regarding the generation of adequate efficacy and safety evidence using conventional randomized controlled trials (RCTs). Recently, real-world evidence generated through observational (or real-world) studies has been proposed to address some of the feasibility concerns with RCTs by measuring drug effectiveness or safety in the real-world setting. However, there remain methodological concerns due to a lack of randomization/masking. This proposed scoping review aims to identify which observational research methods in the last 5 years are used in rare disease drug evaluation to address methodological concerns and how they’re applied to generate evidence on drug effectiveness or safety.

Inclusion criteria

Articles must be primary observational or real-world studies reporting rare disease drug effectiveness or safety published between 2018-2023. Literature reviews, meta-analyses, randomized control trials, case series, case reports, opinion pieces, conference abstracts, and studies with unavailable full-text articles will be excluded.

Methods

The search strategy will combine the following key search concepts: rare disease, drugs for rare disease and observational/real-world studies. The search will be conducted in MEDLINE and EMBASE.

Review registration number

Open Science Framework,https://osf.io/f3wpv
Intraindividual Variability Differentiated Older Adults with Physical Frailty and the Role of Education in the Maintenance of Cognitive Intraindividual Variability
Authors: Wu Jingyi , Chen Jinyu , Wu Juncen , Hsu Chun Liang
Published: May 2024

Objectives

Physical frailty is associated with increased risk of cognitive impairment. However, its impact on sustained cognitive processing as evaluated by intraindividual variability (IIV), and factors beneficial to IIV in physically frail older adults remain unexplored. This study aimed to quantify differences in IIV between older adults with and without physical frailty, and examine whether education facilitated maintenance of IIV.

Methods

This cross-sectional study included 121 community-dwelling older adults 65-90 years with/without physical frailty (PF and non-PF; n=41 and n=80 respectively). Physical frailty was determined via Short Physical Performance Battery. Dispersion across the seven components of the Montreal Cognitive Assessment (MoCA) was computed to ascertain IIV. Multivariate analysis of covariance was used to determine group differences in total score and IIV. Four moderation models were constructed to test the effects of education on age-total score and age-IIV relationships in PF and non-PF.

Results

Compared with non-PF, PF showed greater IIV (p= .022; partial η² = 0.044). Among PF, education moderated age-total score (R-sq = 0.084, F = 5.840,p< 0.021) and age-IIV (R-sq = 0.101, F = 7.454,p= 0.010) relationships. IIV increased with age for those with five years (β = 0.313,p= 0.006) or no formal education (β = 0.610,p= 0.001). Greater than seven years of education (β = 0.217,p= 0.050) may be required to maintain IIV at older age.

Conclusion

IIV may be a sensitive method to differentiate physically frail older adults. Additionally, perceived cognitive benefits of education may be dependent on physical functioning.
Typologies of activity-related behaviours from childhood to adolescence and their transitions: A longitudinal analysis of the ELSPAC cohort
Authors: Janda David , Gába Aleš , Ayala Ana Maria Contardo , Timperio Anna , Andrýsková Lenka , Piler Pavel , Arundell Lauren
Published: May 2024

Objectives

To identify typologies of activity-related behaviours in childhood and adolescence and to explore transitions between the identified typologies. Additionally, we aimed to identify demographic indicators associated with the transitions and typology membership.

Design

Prospective cohort study

Setting

Czech Republic

Participants

Individuals involved in the Czech part of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC-CZ) study, aged 11 to 18 years. The study involved more than 563 individuals of which 380 provided complete data the analysis.

Primary outcome measures

Time spent outdoors, participation in organised physical activity (PA) and sport activities, time watching television and using personal computer, and total sleep duration. Latent variables defined by the Latent Transition Analysis.

Results

Four typologies of activity-related behaviours were identified and labelled to reflect their behavioural profiles: 1)Actives(high outdoor time and organised PA and sport participation, low screen time, optimal sleep duration), 2)Active screeners(median outdoor time, high organised PA and sport participation, high screen time, optimal sleep duration), 3)Poor sleepers(average outdoor time and organised PA and sport participation, low screen time, not meeting sleep guidelines), and 4)Averages(average duration of all behaviours and optimal sleep duration). A major shift in typology membership from 11 to 18 years was observed with a decreasing proportion of individuals in typologies characterised by a high proportion of outdoor time and participation in organised PA and sport activities (i.e.Actives;Active screeners). A high proportion of individuals also transitioned to the typology with poor sleeping habits (i.e.Poor sleepers). Sex and maternal education were associated with the typology membership and transition probabilities (p< 0.05).

Conclusions

Our findings highlight the importance of implementing lifestyle interventions in childhood to prevent possible sleep disorders and low physical activity later in life.

Strengths and limitations of this study

The longitudinal design allows an investigation of unique activity-related behaviour patterns across the transition from childhood to adolescents.

Utilising various activity-related behaviours (e.g. outdoor time or screen time) provide a comprehensive understanding of the lifestyle of children and adolescents.

Data were collected from a specific geographic region from the Central Europe, which may limit the generalisability to broader population.
PRS-GRID: A Cross and Within Ancestry Polygenic Risk Prediction Method Based on Individual Genetic Distance
Authors: Tang Liwei , You Cong , Kong Xue-jun , Napolioni Valerio , Huang Jie
Published: May 2024

Background

Two decades of genome-wide association studies (GWAS) have led to the fast-growing application of polygenic risk prediction (PRS). However, due to population structure and evolutionary path differences, the PRS substrate derived mostly from studies of European ancestry does not work equally well for other ancestries. There is an association between prediction accuracy decay and individual genetic distance (GD) to the genetic centers (GC) of various populations.

Objectives

To develop a new PRS method and software that utilizes individual GD to improve PRS risk prediction accuracy, especially for non-European populations.

Method

We hypothesize that adding a GD-based weight into PRS methods would enhance its risk prediction performance, particularly for minority groups. We explore the GD first by principal components (PC) and then by phylogenetic tree structures. Building on top of an emerging software (PRS-CSx) that achieves high prediction accuracy across multiple-ancestries, we present PGS-GRID, where “GRID” stands for “GeneticReference based onIndividualDistance”.

Results

We developed a preliminary version of PRS-GRID and pilot tested its prediction performance for a classic quantitative trait (e.g., height) and a disease trait (e.g., type-2 diabetes). We found slight but noticeable improvement of risk prediction in minority populations. We further explored a random forest approach so that the performance of PRS-GRID could be clearly explained, which is a key step for PRS to be used in clinical and public health practice.

Conclusions

The PRS-GRID philosophy and method represent an innovative and significant advancement in the field of polygenic risk prediction. Our work provides a foundation for future research and clinical applications aimed at reducing health disparities and improving population health through personalized medicine.
Tuberculosis healthcare service disruptions during the COVID-19 pandemic in Brazil, India and South Africa: A model-based analysis of country-level data
Authors: de Villiers Abigail K. , Osman Muhammad , Struchiner Claudio J. , Trajman Anete , Tumu Dheeraj , Shah Vaibhav V. , Werneck Guilherme L. , Alves Layana C. , Choudhary Megha , Verma Sunita , Mattoo Sanjay K. , Meehan Sue-Ann , Singh Urvashi B. , Hesseling Anneke C. , Marx Florian M.
Published: May 2024

Tuberculosis (TB) is the leading infectious disease cause of death worldwide. In recent years, stringent measures to contain the spread of SARS-CoV-2 have led to considerable disruptions of healthcare services for TB in many countries. The extent to which these measures have affected TB testing, treatment initiation and outcomes has not been comprehensively assessed. We aimed to estimate TB healthcare service disruptions occurring during the COVID-19 pandemic in Brazil, India, and South Africa. We obtained country-level TB programme and laboratory data and used autoregressive integrated moving average (ARIMA) time-series models to estimate healthcare service disruptions with respect to TB testing, treatment initiation, and treatment outcomes. We quantified disruptions as the percentage difference between TB indicator data observed during the COVID-19 pandemic compared with values for a hypothetical no-COVID scenario, predicted through forecasting of trends during a three-year pre-pandemic period. Annual estimates for 2020-2022 were derived from aggregated monthly data. We estimated that in 2020, the number of bacteriological tests conducted for TB diagnosis was 24.3% (95% uncertainty interval: 8.4%;36.6%) lower in Brazil, 27.8% (19.8;3 4.8%) lower in India, and 32.0% (28.9%;34.9%) lower in South Africa compared with values predicted for the no-COVID scenario. TB treatment initiations were 17.4% (13.9%;20.6%) lower than predicted in Brazil, 43.3% (39.8%;46.4%) in India, and 27.0% (15.2%;36.3%) in South Africa. Reductions in 2021 were less severe compared with 2020. The percentage deaths during TB treatment were 13.7% (8.1%; 19.7%) higher than predicted in Brazil, 1.7% (−8.9%;14.0%) in India and 21.8% (7.4%;39.2%) in South Africa. Our analysis suggests considerable disruptions of TB healthcare services occurred during the early phase of the COVID-19 pandemic in Brazil, India, and South Africa, with at least partial recovery in the following years. Sustained efforts to mitigate the detrimental impact of COVID-19 on TB healthcare services are needed.
The cost of behavioral flexibility: reversal learning driven by a spiking neural network
Authors: Ghazinouri Behnam , Cheng Sen
Published: May 2024

To survive in a changing world, animals often need to suppress an obsolete behavior and acquire a new one. This process is known as reversal learning (RL). The neural mechanisms underlying RL in spatial navigation have received limited attention and it remains unclear what neural mechanisms maintain behavioral flexibility. We extended an existing closed-loop simulator of spatial navigation and learning, based on spiking neural networks [8]. The activity of place cells and boundary cells were fed as inputs to action selection neurons, which drove the movement of the agent. When the agent reached the goal, behavior was reinforced with spike-timing-dependent plasticity (STDP) coupled with an eligibility trace which marks synaptic connections for future reward-based updates. The modeled RL task had an ABA design, where the goal was switched between two locations A and B every 10 trials. Agents using symmetric STDP excel initially on finding target A, but fail to find target B after the goal switch, persevering on target A. Using asymmetric STDP, using many small place fields, and injecting short noise pulses to action selection neurons were effective in driving spatial exploration in the absence of rewards, which ultimately led to finding target B. However, this flexibility came at the price of slower learning and lower performance. Our work shows three examples of neural mechanisms that achieve flexibility at the behavioral level, each with different characteristic costs.
Stress-induced brain extracellular vesicles ameliorate anxiety behaviour
Authors: Mizohata Yusuke , Yoshioka Yusuke , Koga Minori , Toda Hiroyuki , Ohta Hiroyuki , Kobayashi Yasunobu , Ochiya Takahiro , Morimoto Yuji
Published: May 2024

Extracellular vesicles (EVs), nano particles secreted by all types of cells, serve as a communication network, carrying information through the bloodstream to distant cells1,2. Notably, brain cells secrete EVs that play a crucial role in regulating neurological functions3-5. Meanwhile the brain detects acute stress and activates mechanisms to enhance stress resistance and maintain homeostasis6,7. However, the specific contribution of brain-derived extracellular vesicles (BDEVs) in modulating the stress response remains elusive. Here we found that administration of the acute stress-induced BDEVs to mice reduced anxiety-related behaviours, and this reduction was also induced by the administration of only three microRNAs (miRNAs) (miR-199a-3p, miR-99b-3p and miR-140-5p) included in the acute stress-induced BDEVs. Furthermore, we showed that miR-199a-3p contributes to the mechanism of the anxiolytic effect through the suppression ofMecp2in neurons. These findings elucidate the role of BDEVs in modulating mental activity under acute stress and provide insights into the underlying molecular mechanisms. Our results open up new avenues for therapeutic strategies in the treatment of anxiety disorders using EVs or miRNAs.
Effects of Concussion on the Relative Contributions of Sensorimotor Memories during Adaptation to Unpredictable Spring-Like Loads
Authors: Lantagne Devon D , Mrotek Leigh A , Ahamed Sheikh I , Beardsley Scott A , Grove Andrew J , Leigh David H , Smith Carolyn S , Thomas Danny G , Scheidt Robert A
Published: May 2024

We examined the extent to which concussion impacts how implicit sensorimotor memories are used to compensate for changes in hand-held loads during goal-directed reaching. Recently concussed individuals performed computerized cognition tests and a robotic test of sensorimotor adaptation on three occasions: as soon as possible after injury; after clearance to return to activity; three months after injury. Non-concussed individuals (controls) were tested at inter-session intervals mimicking concussed group intervals. During robotic testing, subjects grasped the handle of a horizontal planar robot while reaching repeatedly to a target. The robot exerted spring-like forces that changed unpredictably between trials; this allowed us to estimate contributions of implicit sensorimotor memories to trial-by-trial performance by fitting a computational model to the time series of reach errors and robot forces. Symptom severity varied considerably within the concussed group at the first session. Computerized cognition tests revealed longer reaction times in the concussed group relative to control group in Session 1 only. Concussed subjects likewise had slower reaction time in the reaching task during the first but not later sessions. Computational modeling found abnormally high values of effective limb compliance in concussed individuals relative to the control group in the first session only, but did not find group differences in how sensorimotor memories contribute to reach adaptation in any session. Analysis of control group models identified a practice effect affecting the memory coefficients that may have masked initial effects of concussion on how implicit memories contribute to sensorimotor adaptation. Although a practice effect and a heterogeneous concussed cohort preclude strong conclusions, our findings suggest procedural improvements that may decrease the robotic test’s sensitivity to practice effects and increase its sensitivity to concussion-related changes in how implicit memories contribute to sensorimotor adaptation to unpredictable hand-held loads during reaching.
Impact of microchannel width on axons for brain-on-chip applications
Authors: Vulić Katarina , Amos Giulia , Ruff Tobias , Kasm Revan , Ihle Stephan J. , Küchler Jöel , Vörös János , Weaver Sean
Published: May 2024

Technologies for axon guidance forin vitrodisease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designingin vitroplatforms andin vivoneural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies.
Feature selective adaptation of numerosity perception
Authors: Caponi Camilla , Castaldi Elisa , Grasso Paolo Antonino , Arrighi Roberto
Published: May 2024

Perceptual adaptation has been used to infer the existence of numerosity detectors, which allow humans to quickly estimate the number of objects in a scene. While adaptation was originally thought to affect numerosity perception regardless of the low-level features of the items, a recent study demonstrated that adaptation is more pronounced when the adapting and adapted (test) stimuli share the same color, compared to when they were colored differently. In this study we explored whether such adaptation reduction depends on a novelty effect induced by changes in stimulus features or whether this effect is observed only when implying an identity change of the stimuli. To this aim, we performed six experiments in which numerosity adaptation was investigated in conditions in which adapting and adapted stimuli were either matched or differed for several low-level (color, luminance, shape, and motion) or high-level (letters’ identity, face emotions) features. Numerosity adaptation was consistently observed across all conditions, but it was reduced when adaptor and test differed in color, luminance and shape. However, when stimuli differed in their motion profile, a very salient perceptual change that does not imply a change in items’ identity, adaptation selectivity vanished. Moreover, adaptation selectivity was not observed when items’ identity was changed by spatial rotations of the same stimulus (letters) or when stimuli were matched for the global configuration (face outline) but differed for the arrangement of local features (mouth, nose, eyes). Interestingly, image dissimilarity between test and adaptor, as quantified by Gabor filters simulating a simplified model of the primary visual cortex, nicely predicted the strength of numerosity adaptation across all conditions. Overall, changes in stimulus identity defined by low-level features, rather than novelty in general, determined the strength of the adaptation effects, provided that the changes were readily noticeable. Our findings suggest that numerosity mechanisms may be able to operate on segregated and categorized visual items in addition to the total quantity of the set, with part of the aftereffects induced by numerosity adaptation occurring after feature-binding.