bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between aerobic capacity and left atrial size in healthy young males: An observational study
Authors: Camkiran Volkan , Yurtseven Ece , Aslan Gamze , Ozyigit Tolga
Published: July 2024

Aerobic capacity, defined as peak oxygen uptake (peakVO2), is a marker for aerobic fitness and is associated with left ventricular (LV) systolic and diastolic function. The aim of the study was to explore the relation between left atrial (LA) volume index (LAVI) and aerobic capacity in healthy young male adults. One hundred three healthy young male subjects (mean age: 34.2 ± 5.5years) were consecutively included in the study. All subjects underwent echocardiography to assess LAVI, LV systolic and diastolic functions. Aerobic capacity was assessed by cardiopulmonary exercise testing. All patients had normal left ventricular ejection fraction (LVEF). One hundred one subjects had normal LAVI (≤34 mL/m2) while 2 subjects had mildly increased LAVI (35–41 mL/m2). Mean peakVO2 predicted was 82.2 ± 14.4%. 64subjects (62.1%) had a peakVO2 < 85% of age-predicted and sex-predicted values and they had higher LAVI compared to those who had a peakVO2 higher than 85% of age-predicted and sex-predicted values (22.0 ± 4.8 mL/m2 vs 20.3 ± 4.1 mL/m2, P = .055). Notably, only LAVI showed a significant correlation with peakVO2 and predicted breathing reserve (BR), while anaerobic threshold correlated with both LAVI and LVEF. Age was also a significant factor, negatively impacting peakVO2 (r = −0.265, P = .007) and predicted BR (r = −0.282, P = .004). Multivariate analysis revealed that both LAVI and age were independent predictors of peakVO2 and predicted BR. This study suggests that LAVI can be a valuable indicator of aerobic capacity in apparently healthy young males.
The effect of emergency department history on health literacy level and role of digital literacy: An observational study
Authors: Boğa Erkan , Yilmaz Kadir
Published: July 2024

In this research, it was aimed to evaluate the effect of emergency department history on health literacy level and the role of digital literacy. A total of 454 participants were subjected to survey including health literacy scale, the digital literacy scale, and the demographic information form. Participants were divided into 2 groups as emergency medicine service (EMS) history (n = 269) and no EMS history (n = 185) groups. Health literacy, attitude, cognitive, and total digital literacy level of EMS history group were significantly higher than no EMS history group (P < .05). Social dimension of digital literacy scale was significantly higher in no EMS history group (P < .05). In no EMS history group, health literacy was significantly correlated with attitude (r = 0.298; P < .01), technical (r = 0.157; P < .01), cognitive (r = 0.369; P < .01), social (r = −0.302; P < .01) dimensions, and total score of digital literacy (r = 0.213; P < .01). In EMS history group, health literacy was significantly correlated with attitude (r = 0.553; P < .01), technical (r = 0.488; P < .01), cognitive (r = 0.555; P < .01) dimensions, and total score of digital literacy (r = 0.514; P < .01). Digital literacy had significant and positive effect on health literacy for all participants (OR = 0.126; P < .01), no EMS history (OR = 0.059; P < .01) and EMS history group (OR = 0.191; P < .01). People’s health literacy skills are positively impacted if they have ever received medical attention from EMS units, regardless of the reason. Furthermore, among those who have used emergency medical services in the past, the impact of digital literacy on health literacy is statistically substantially larger.
Optimizing intubation technique using a single-use video laryngoscope: A comparative study in a simulation model
Authors: Chen Hui-Chin , Liu Jui-Fang , Chi Miao-Ching , Cheng Hsiu-Lan
Published: July 2024

Tracheal intubation poses a high risk of infection to medical staff due to Coronavirus disease 2019 (COVID-19) highly infectious nature. To mitigate this risk, various medical devices, including video laryngoscopy, have been developed to assist intubation. This study compared conventional laryngoscopy (Macintosh) and disposable video laryngoscopes (Medcaptain VS-10s and Honestmc Laryngoscope_LA10000) in terms of their use and operation processes. We designed a questionnaire to assess the operator perception of performing intubation with the devices, and statistical analysis was performed on 50 clinical staff members from 2 hospitals who had performed intubation or had learned intubation techniques. The primary outcomes were time to glottic visualization, intubation time, intubation success rate, distance between the operator and training model, and time from glottic visualization to tube insertion. The secondary outcomes were as follows: overall laryngoscope quality, operative feel, maneuverability, ease of use, and video quality. This study showed that video laryngoscopes were superior to conventional laryngoscopes in terms of quality, operative feel, and ease of use. When LA10000 was employed, the intubation success rate was higher, and the operator risk of infection was lower because of the greater distance from the training model. However, the use of video laryngoscopes requires appropriate education and training use of the devices. This study also demonstrated that when participants viewed a simple operation video prior to using video laryngoscopes, tube insertion time was shorter. Overall, video laryngoscopy can provide a safer and more convenient option for clinical medical personnel during pandemics.
Paradoxical cognitive and language function recovery by zolpidem in a patient with traumatic brain injury: A case report
Authors: Li Jia , Li Haozheng , Peng Cheng , Xu Weijian , Chen Qiang , Liu Gang
Published: July 2024

Background:

Traumatic brain injury (TBI) is a significant public health issue, often resulting from traffic accidents and falls, leading to a wide spectrum of outcomes from mild concussions to severe brain damage. The neurorehabilitation of TBI focuses on enhancing recovery and improving quality of life. Zolpidem, traditionally used for short-term management of insomnia, has shown potential in improving cognitive functions and language in TBI patients. Advances in neuroimaging techniques, such as functional near-infrared spectroscopy (fNIRS), have facilitated the exploration of the effects of therapeutic interventions on brain activity and functional connectivity in TBI patients.

Case summary:

We present the case of a 34-year-old male who sustained a TBI from a traffic collision. Despite severe impairments in cognitive and language functions, administration of 10 mg of zolpidem resulted in temporary but significant improvements in these areas, as evidenced by increased Mini-Mental State Examination scores and observed behavioral changes. fNIRS assessments before and after zolpidem administration revealed notable changes in cerebral cortex activity, including increased left hemisphere activation and a shift in functional connectivity to the bilateral frontal lobes, corresponding with the patient’s improvement.

Conclusion:

This case study highlights the potential of zolpidem, a medication traditionally used for insomnia, in enhancing cognitive and verbal functions in a patient with TBI, suggesting a potential therapeutic role for zolpidem in neurorehabilitation, supported by changes in brain activity and connectivity observed through fNIRS. However, further investigation is warranted to validate these findings and elucidate zolpidem’s long-term effects on cognitive and functional outcomes in TBI patients.
Identifying discriminant factors between phantom limb pain, residual limb pain, and both in people with lower limb amputations: a cross-sectional study
Authors: Pournajaf Sanaz , Damiani Carlo , Agostini Francesco , Morone Giovanni , Proietti Stefania , Casale Roberto , Franceschini Marco , Goffredo Michela
Published: July 2024

Postamputation pain is a common condition in patients with lower limb amputation (LLA), which compromises amputees’ rehabilitation, use of the prosthesis, and quality of life. The aim of our study was to investigate the prevalence of phantom limb pain (PLP), residual limb pain (RLP), or both types of pain among individuals with LLA, and to identify the factors associated with the presence of one type of pain versus the other. Patients who underwent amputation for traumatic or vascular reasons and who reported on RLP or PLP were analyzed and divided into three groups: PLP, RLP, or a group of subjects that presented both pains. We searched for factors that affect the occurrence of limb pain using univariate analyses, followed by multinomial logistic regression. Among the 282 participants with transtibial and transfemoral amputations, 192 participants (150 male and 42 female) presented PLP, RLP, or both types of pain, while 90 participants declared to perceive no pain. The estimated prevalence of any type of pain after transfemoral and transtibial amputation was therefore 68% (27% PLP, 10% RLP, and 31% both). Among the studied characteristics, only amputation level was associated with the type of pain (P = 0.001). Multinomial logistic regression identified transfemoral amputation as the only statistically significant predictor for PLP (odds ratio = 2.8; P = 0.002). Hence, it was estimated that individuals with transfemoral amputation have nearly three times higher odds of experiencing PLP compared with those with transtibial amputation.
The effectiveness of mindfulness-based cognitive therapy during poststroke rehabilitation: a randomized controlled trial
Authors: Udvardi Veronika , Szabo Gabor , Takacs Johanna , Fazekas Gabor
Published: July 2024

Stroke can have a range of physical, psychological, cognitive, and social impacts that are challenging for survivors. This study aimed to evaluate the efficacy of a group-based mindfulness intervention integrated into an inpatient rehabilitation program compared to standard care. A single-center, randomized, controlled trial was conducted in 93 poststroke patients. The intervention group received 6-weeks of mindfulness-based cognitive therapy (MBCT) and standard care; the control group received standard care. Primary outcomes were depression and trait anxiety; secondary outcomes were trait mindfulness and attention. Participants completed questionnaires at baseline, and postintervention (6 weeks). Mixed-effect model repeated measures analysis of variance was conducted between groups and across time. A total of 80 participants (intervention n = 43; standard care n = 37) were included in the postintervention analysis. There were no statistically significant differences in the primary outcomes between the groups over time. An improvement was found, however, on the trait mindfulness observing subscale in favor of the intervention group. Eight sessions of MBCT integrated into an inpatient stroke rehabilitation program over 6 weeks was not effective in improving depression and anxiety compared to standard care. Lack of follow-up and low to moderate pathological symptoms at baseline may have limited the effectiveness of this intervention.
The Impact of an Online Preceptorship Training Program on Preceptor Self-Efficacy Among Nurse Case Managers Working in an Acute Care Setting
Authors: O’Connor Jonelle M. , MacCulloch Patricia
Published: July 2024

Purpose/Objectives:

The U.S. health care system is experiencing a critical workforce shortage of nurse case managers exacerbated by an older workforce and looming retirements and the growth of this specialty. This quality improvement project aimed to develop an online case manager preceptor training program and examine its impact on the nurse case manager preceptors’ self-efficacy.

Practice Setting:

This project was implemented at a 395-bed acute care, community-based hospital in the northeast.

Methodology and Sample:

The target population for the intervention included a convenience sample of 13 nurse case managers who were assigned a preceptor role. The intervention was an abbreviated version of an online preceptorship program by Lippincott. The Preceptor Self-Efficacy Questionnaire (PSEQ), with a Cronbach’s alpha of 0.96, measured nurse preceptors’ confidence in various skills including fostering critical thinking and providing feedback. Data from pre- and post-intervention PSEQ surveys were analyzed using a Wilcoxon rank sum test in SPSS version 28.

Results:

The Wilcoxon rank sum test revealed a statistically significant improvement in preceptor confidence scores (p = .043) between pre- and post-intervention PSEQ results.

Implications for Case Management Practice:

This project demonstrated feasibility of an online nurse case manager preceptor training program while also identifying improved preceptors’ self-efficacy. Future research can include investigating the impact of a preceptor training program on the nurse case manager learners receiving role training from the trained case manager preceptor.
How Does Standing Anteroposterior Stability Limits Correlate to Foot/ankle Functions in Bilateral Spastic Cerebral Palsy?
Authors: Tomita Hidehito , Takahashi Shuhei , Kawaguchi Daisuke , Aoki Yumi , Yamamoto Yoshiji , Asai Hitoshi
Published: July 2024

Purpose:

To determine whether foot and ankle functions are correlated with the limits of stability (LoS) while standing in individuals with bilateral spastic cerebral palsy (BSCP).

Methods:

Eighteen people who could walk and with BSCP and 18 people without disability participated. Anteroposterior LoS was measured using a force platform. To quantify ankle and foot functions, spasticity, isometric muscle strength, passive range of motion, and plantar light touch-pressure sensation were assessed.

Results:

In the BSCP group, anteroposterior LoS was significantly decreased, and anterior LoS reduction was correlated with decreases in plantar flexor and toe flexor strength and in sensitivity of the forefoot to light touch-pressure sensation, whereas the posterior LoS reduction was correlated with reduced dorsiflexor strength.

Conclusions:

The present findings suggest that improvement in these foot and ankle functions in BSCP may increase LoS while standing.
The thin red line: Blood planning factors and the enduring need for a robust military blood system to support combat operations
Authors: Gurney Jennifer M. , Cap Andrew P. , Holcomb John B. , Staudt Amanda M. , Tadlock Matthew D. , Polk Travis M. , Davis Crystal , Corley Jason B. , Schreiber Martin A. , Beckett Andrew , Spott Mary Ann , Shackelford Stacy A. , Van Gent Jan-Michael , Stallings Jonathan D. , Martin Matthew J. , Riggs Leslie E.
Published: July 2024

Battlefield lessons learned are forgotten; the current name for this is the Walker Dip. Blood transfusion and the need for a Department of Defense Blood Program are lessons that have cycled through being learned during wartime, forgotten, and then relearned during the next war. The military will always need a blood program to support combat and contingency operations. Also, blood supply to the battlefield has planning factors that have been consistent over a century. In 2024, it is imperative that we codify these lessons learned. The linchpins of modern combat casualty care are optimal prehospital care, early whole blood transfusion, and forward surgical care. This current opinion comprised of authors from all three military Services, the Joint Trauma System, the Armed Services Blood Program, blood SMEs and the CCC Research Program discuss two vital necessities for a successful military trauma system: (1) the need for an Armed Services Blood Program and (2) Planning factors for current and future deployed military ere is no effective care for wounded soldiers, and by extension there is no effective military medicine.
Waitlist Time, Age, and Social Vulnerability: Impact on the Survival Benefit of Deceased Donor Kidney Transplantation Versus Long-term Dialysis Among Patients With End-stage Renal Disease
Authors: Yang Jason , Endo Yutaka , Munir Muhammad Musaab , Woldesenbet Selamawit , Altaf Abdulla , Limkemann Ashley , Schenk Austin , Washburn Kenneth , Pawlik Timothy M.
Published: July 2024

Background.

We sought to define the survival benefit of kidney transplantation versus long-term dialysis relative to waitlist time on dialysis, social vulnerability, and age among end-stage renal transplant candidates.

Methods.

End-stage renal disease patients who were candidates for their first deceased donor kidney transplantation between 2008 and 2020 were identified using the US Renal Data System. Survival probabilities for patient survival were compared using the restricted mean survival times (RMSTs) across different age and social vulnerability index (SVI) ranges.

Results.

Among 149 923 patients, 68 795 (45.9%) patients underwent a kidney transplant and 81 128 (54.1%) remained on dialysis. After propensity-score matching (n = 58 035 in each cohort), the 5-y RMST difference between kidney transplant and dialysis demonstrated an increasing trend in mean life-years gained within 5 y of follow-up relative to advancing age (<30 y: 0.40 y, 95% confidence interval, 0.36-0.44 y versus >70 y: 0.75 y, 95% confidence interval, 0.70-0.80 y). Conversely, disparities in 5-y RMSTs remained consistent relative to social vulnerability (median 5-y RMST difference: 0.62 y comparing low versus high SVI). When considering waitlist duration, stratified analyses demonstrated increasing trends across different age groups with the largest RMST differences observed among older patients aged ≥70 y. Notably, longer waitlist durations (>3 y) yielded more pronounced RMST differences compared with shorter durations (<1 y).

Conclusions.

These data underscore the survival benefit associated with kidney transplantation over long-term dialysis across various age and SVI ranges. Transplantation demonstrated a greater advantage among older patients who had a longer waitlist duration.
Psychotropic drugs, eating behaviour and weight gain
Authors: Arniotis-Streat Shalika , Fonte Anthony , Ziauddeen Hisham
Published: July 2024

Purpose of review

Psychotropic drug related weight gain is a common side-effect of significant concern to both clinicians and patients. Recent studies and treatment guidelines strongly support taking preventive and early treatment approaches to psychotropic drug-related weight gain (PDWG). Arguably the main pathway that PDWG occurs is via changes in eating behaviour leading to increased caloric intake.

Recent findings

Systematic reviews and meta-analyses have provided good data on the nature and prevalence of alterations in eating behaviour with psychotropic treatment including increased hunger, night eating and binge eating. These changes are unsurprisingly more prominent with agents like olanzapine and clozapine that have high propensity to cause weight gain.

Altered eating behaviour can serve as an earlier measure of the risk of weight gain and can be examined easily in clinical practice. Detecting these changes can enable earlier action in terms of switching treatments and starting pharmacological and nonpharmacological preventive strategies.
Genome sequencing and analysis of Salmonella enterica subsp. enterica serotype Enteritidis PT4 578: Insights into pathogenicity and virulence
Authors: Carneiro Deisy Guimarães , Vidigal Pedro Marcus , Morgan Túlio , Vanetti Maria Cristina Dantas
Published: July 2024

Salmonella enterica serotype Enteritidis is a generalist serotype that adapts to different hosts and transmission niches. It has significant epidemiological relevance and is among the most prevalent serotypes distributed in several countries. Salmonella Enteritidis causes self-limited gastroenteritis in humans, which can progress to systemic infection in immunocompromised individuals. The Salmonella pathogenicity mechanism is multifactorial and complex, including the presence of virulence factors that are encoded by virulence genes. Poultry products are considered significant reservoirs of many Salmonella serotypes, and Salmonella Enteritidis infections are often related to the consumption of chicken meat and eggs. This study reports the whole-genome sequence of Salmonella Enteritidis PT4 strain 578. A total of 165 genes (3.66%) of the 4,506 coding sequences (CDS) predicted in its genome are virulence factors associated with cell invasion, intestinal colonization, and intracellular survival. The genome harbors twelve Salmonella pathogenicity islands (SPIs), with the SPI-1 and SPI-2 genes encoding type III secretion systems (T3SS) showing high conservation. Six prophage-related sequences were found, with regions of intact prophages corresponding to Salmon_118970_sal3 and Gifsy-2. The genome also contains two CRISPR systems. Comparative genome analysis with Salmonella Enteritidis ATCC 13076, Salmonella Typhimurium ATCC 13311, and Salmonella Typhimurium ATCC 14028 demonstrates that most unshared genes are related to metabolism, membrane, and hypothetical proteins. Finally, the phenotypic characterization evidenced differences among Salmonella Enteritidis PT4 578 and the other three serotypes regarding the expression of the red, dry, and rough (rdar) morphotype and biofilm formation. Overall, the genomic characterization and phenotypic properties expand knowledge of the mechanisms of pathogenicity in Salmonella Enteritidis PT4 578.
A transcriptome-wide Mendelian randomization study in isolated human immune cells highlights risk genes involved in viral infections and potential drug repurposing opportunities for schizophrenia
Authors: Stacey David , Gaziano Liam , Eldi Preethi , Toben Catherine , Benyamin Beben , Lee S Hong , Hyppönen Elina
Published: July 2024

Background

Schizophrenia is a neurodevelopmental psychiatric disorder characterised by symptoms of psychosis, thought disorder, and flattened affect. Immune mechanisms are associated with schizophrenia, though the precise nature of this relationship (i.e., causal, correlated, consequential) and the mechanisms involved are not fully understood.

Methods

To elucidate these mechanisms, we conducted a transcriptome-wide Mendelian randomization study using gene expression exposures from 29 humancis-eQTL datasets encompassing 11 unique immune cell types, all publicly available from the eQTL catalogue.

Results

These analyses highlighted 196 genes, including 67 located within the human leukocyte antigen (HLA) region. Enrichment analyses indicated an over-representation of immune genes, which was driven by the HLA genes. Stringent validation and replication steps retained 61 candidate genes, 27 of which were the sole causal signals at their respective loci, thereby representing strong candidate effector genes at known risk loci. We highlightedL3HYPDHas a potential novel schizophrenia risk gene andDPYDandMAPK3as candidate drug repurposing targets. Futhermore, we performed follow-up analyses focused on one of the candidate effectors, interferon regulatory transcription factor 3 (IRF3), which coordinates interferon responses to viral infections. We found evidence of shared genetic aetiology between schizophrenia and autoimmune diseases at theIRF3locus, and a significant enrichment of IRF3 chromatin binding at known schizophrenia risk loci.

Conclusions

Our findings highlight a novel schizophrenia risk gene, potential drug repurposing opportunities, and provide support forIRF3as a schizophrenia hub gene, which may play critical roles in mediating schizophrenia-autoimmune comorbidities and the impact of viral infections on schizophrenia risk.
Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF
Authors: Verhaege Daan , De Nolf Clint , Castelein Jonas , Claeys Wouter , Van Wonterghem Elien , Van Imschoot Griet , Dujardin Pieter , De Spiegelaere Ward , Hoste Esther , Boone Fleur , Lidov Hart G. W. , Neil Dani , Derk Julia , Kremer Anna , Van Hamme Evelien , Borghgraef Peter , Lippens Saskia , Lehtinen Maria K , Siegenthaler Julie , Van Hoecke Lien , Vandenbroucke Roosmarijn E.
Published: July 2024

The choroid plexus (ChP) is a highly understudied structure of the central nervous system (CNS). The structure hangs in the brain ventricles, is composed of an epithelial cell layer, which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. It encapsulates a stromal mix of fenestrated capillaries, fibroblasts and a broad range of immune cells. Here, we report that the ChP base region harbors unique fibroblasts that cluster together, are connected by tight junctions and seal the ChP stroma from brain and CSF, thereby forming ChP base barrier cells (ChP BBCs). ChP BBCs are derived from meningeal mesenchymal precursors, arrive early during embryonic development, are maintained throughout life and are conserved across species. Moreover, we provide transcriptional profiles and key markers to label ChP BBCs and observe a striking transcriptional similarity with meningeal arachnoid barrier cells (ABCs). Finally, we provide evidence that this fibroblast cluster functions as a barrier to control communication between CSF and the ChP stroma and between the latter and the brain parenchyma. Moreover, loss of barrier function was observed during an inflammatory insult. Altogether, we have identified a novel barrier that provides functional compartmentalization of ChP, brain and CSF.

GRAPHICAL ABSTRACT

Newly discovered base barrier cells provide compartmentalization of choroid plexus, brain and CSF

The choroid plexus (ChP) hangs in the brain ventricles and is composed of an epithelial cell layer which produces the cerebrospinal fluid (CSF) and forms the blood-CSF barrier. The ChP epithelial cells are continuous with the ependymal cells lining the ventricle wall. At this base region, we identified and characterized a novel subtype of fibroblasts coined the ChP base barrier cells (BBCs). ChP BBCs express tight junctions (TJs), cluster together and seal the ChP stroma from CSF and brain parenchyma. The subarachnoid space (SAS) CSF penetrates deep into choroid plexus invaginations where it is halted by ChP BBCs.

Abbreviations: E9-16.5 (embryonic day 9-16.5); P1-4 (postnatal day 1-4).
On the replicability of diffusion weighted MRI-based brain-behavior models
Authors: Kotikalapudi Raviteja , Kincses Balint , Gallitto Giuseppe , Englert Robert , Hoffschlag Kevin , Li Jialin , Bingel Ulrike , Spisak Tamas
Published: July 2024

Establishing replicable inter-individual brain-wide associations is key to advancing our understanding of the crucial links between brain structure, function, and behavior, as well as applying this knowledge in clinical contexts. While the replicability and sample size requirements for anatomical and functional MRI-based brain-behavior associations have been extensively discussed recently, systematic replicability assessments are still lacking for diffusion-weighted imaging (DWI), despite it being the dominant non-invasive method to investigate white matter microstructure and structural connectivity. We report results of a comprehensive evaluation of the replicability of various DWI-based multivariate brain-behavior models. This evaluation is based on large-scale data from the Human Connectome Project, including five different DWI-based brain features (from fractional anisotropy to structural connectivity) and 58 different behavioral phenotypes. Our findings show an overall moderate replicability, with 24-31% of phenotypes replicable with sample sizes of fewer than 500. As DWI yields trait-like brain features, we restricted the analysis to trait-like phenotypes, such as cognitive and motor skills, and found much more promising replicability estimates, with 67-75% of these phenotypes replicable with n<500. Contrasting our empirical results to analytical replicability estimates substantiated that the replicability of DWI-based models is primarily a function of the true, unbiased effect size. Our work highlights the potential of DWI to produce replicable brain-behavior associations. However, it shows that achieving replicability with small-to-moderate samples requires stable, reliable and neurobiologically relevant target phenotypes. Our work highlights the potential of DWI to produce replicable brain-behavior associations, but only for stable, reliable and neurobiologically relevant target phenotypes.

HIGHLIGHTS

Moderate replicability in DWI-based models:Overall replicability of DWI-based brain-behavior associations ranges from 24-31% with sample sizes under 500.

Improved replicability for trait-like phenotypes:Trait-like phenotypes e.g., cognitive and motor skills exhibit higher replicability estimates of 67-75%, compared to state-like phenotypes such as emotion.

Effect size as a key factor:Replicability is primarily influenced by the true, unbiased effect size, highlighting the importance of targeting stable and reliable phenotypes.

Promise of -based multivariate associations:DWI-based brain-behaviour models should focus on phenotypes that display a sufficient temporal stability and test-retest reliability.
Global thermal tolerance of freshwater invertebrates and fish
Authors: Bayat Helena S. , He Fengzhi , Madariaga Graciela M. , Escobar-Sierra Camilo , Prati Sebastian , Jupke Jonathan F. , Peters Kristin , Chen Xing , Spaak Jurg W. , Manfrin Alessandro , Juvigny-Khenafou Noel P.D. , Schäfer Ralf B.
Published: July 2024

Scientists have investigated the thermal tolerance of organisms for centuries, yet the field has not lost relevance as the environmental threats of thermal pollution and global change sharpen the need to understand the thermal vulnerability of organisms in landscapes increasingly subjected to multiple stressors. Freshwater fish and especially invertebrates are greatly underrepresented in recent large-scale compilations of thermal tolerance, despite the importance of freshwater habitats as a crucial resource and biodiversity havens. This inspired us to create a thermal tolerance database for these organisms that includes literature from 1900 until the present day sourced from five languages to counteract geographic bias, and 395 thermal tolerance tests conducted with additional stressors present. The database contains over 5000 records for over 800 species, including 452 invertebrates, providing a valuable resource to test hypotheses on thermal risks to freshwater organisms in present and future environments, and how these might change in multiple stressor scenarios.
Phylogenetic analysis reveals how selection and mutation shape the coevolution of mRNA and protein abundances
Authors: Cope Alexander L. , Schraiber Joshua G. , Pennell Matt
Published: July 2024

The regulatory mechanisms that shape mRNA and protein abundances are intensely studied. Much less is known about the evolutionary processes that shape the relationship between these two levels of gene expression. To disentangle the contributions of mutational and selective processes, we derive a novel phylogenetic model and fit it to multi-species data from mammalian skin tissue. We find that over macroevolutionary time: 1) there has been strong stabilizing selection on protein abundances; 2) mutations impacting mRNA abundances have minimal influence on protein abundances; 3) mRNA abundances are under selection to track protein abundances, and 4) mRNA abundances adapt more quickly than protein abundances due to increased mutational opportunity. We find additional support for these findings by comparing gene-specific parameter estimates from our model to human functional genomic data. More broadly, our new phylogenetic approach provides a foundation for testing hypotheses about the processes that led to divergence in gene expression.
Detrimental Influence of Arginase-1 in Infiltrating Macrophages on Post-Stroke Functional Recovery and Inflammatory Milieu
Authors: Kim Hyung Soon , Jee Seung Ah , Einisadr Ariandokht , Seo Yeojin , Seo Hyo Gyeong , Jang Byeong Seong , Park Hee Hwan , Chung Won-Suk , Kim Byung Gon
Published: July 2024

Post-stroke inflammation critically influences functional outcomes following ischemic stroke. Arginase-1 (Arg1) is conventionally understood as a marker for anti-inflammatory macrophages, associated with the resolution of inflammation and promotion of tissue repair in various pathological conditions. However, its specific role in post-stroke recovery remains to be elucidated. This study investigates the functional impact of Arg1 expressed in macrophages on post-stroke recovery and inflammatory milieu. We observed a time-dependent increase in Arg1 expression, peaking at 7 days after photothrombotic stroke in mice. Cellular mapping analysis revealed that Arg1 was predominantly expressed in LysM-positive infiltrating macrophages. Using a conditional knockout (cKO) mouse model, we examined the role of Arg1 expressed in infiltrating macrophages. Contrary to its presumed beneficial effects, Arg1 cKO in LysM-positive macrophages significantly improved skilled forelimb motor function recovery after stroke. Mechanistically, Arg1 cKO attenuated fibrotic scar formation, enhanced peri-infarct remyelination, and increased synaptic density while reducing microglial synaptic elimination in the peri-infarct cortex. Gene expression analysis of FACS-sorted microglia revealed decreased TGF-beta signaling and pro-inflammatory cytokine activity in peri-infarct microglia from Arg1 cKO animals. In vitro co-culture experiments demonstrated that Arg1 activity in macrophages modulates microglial synaptic phagocytosis, providing evidence for macrophage-microglia interaction. These findings provide new insights into Arg1 function in CNS injury and highlight an interaction between infiltrating macrophages and resident microglia in shaping the post-stroke inflammatory milieu. Our study identifies Arg1 in macrophages as a potential therapeutic target for modulating post-stroke inflammation and improving functional recovery.
Population density drives increased parasitism via greater exposure and reduced resource availability in wild hosts
Authors: Hasik Adam Z. , Butt Shane , Maris Katie , Morris Sean , Morris Ali , Turner Richard S. , Pemberton Josephine M. , Albery Gregory F.
Published: July 2024

Exposure to environmental parasites should increase with host population density due to the accumulation of infective parasites in space. However, competition for resources also increases with density, lowering condition and increasing susceptibility, which offers an alternative pathway for density-dependent infection to act. To test how these two processes act independently or together to drive greater parasite counts, we used a long-term study of red deer to examine associations between host density, resource availability, and counts of three common helminth parasites. We found that greater density correlated with reduced resource availability, and while density was positively associated with both strongyle and tissue worm burdens, resource availability was independently and negatively associated with the same burdens, supporting separate roles of density-dependent exposure and susceptibility in driving infection. This study provides evidence that competition for resources is an important driver of infection in higher-density areas, exacerbating the effects of density-dependent increases in exposure.
ANASFV: a workflow for ASFV whole genome sequencing, assembly, and evaluation
Authors: Li Ke , Han Xu , Shao Yanwen , Zhang Yiwen , Zhao Xiaomin , Johnson Eager Wayne , Li Runsheng
Published: July 2024

African Swine Fever Virus (ASFV) poses an ongoing threat with widespread outbreaks affecting both domestic and wild pig populations globally. Effective management of ASFV outbreaks necessitates a deep understanding of its genetic diversity and evolutionary dynamics. Despite the advantages of nanopore sequencing for genome analysis, its application to ASFV genomes encounters specific challenges, such as high host DNA contamination that reduces viral genome coverage and an inherently higher error rate producing small insertions and deletions (indels). Another notable issue is the lack of standardized methods for assessing the quality of ASFV genomes. Furthermore, an increasing number of recombinant isolates of genotype I and II, have been observed, further complicating the task of phylogenetic analysis. To overcome these obstacles, we developed the ANASFV (analysis of an ASFV) pipeline. The pipeline is used to solve four tasks: In the first task, the pipeline introduces an amplicon sequencing approach that significantly improves genomic coverage, enabling reliable genome assembly. The pipeline also introduce reference-aided polishing techniques to correct small indels caused by nanopore sequencing errors. Moving on to the second task, a genome quality assessment system was established to evaluate the completeness and accuracy of the assembled genomes. For the third task, a method to rapidly analyze whether an isolate is a recombinant between genotype I and II, as well as to determine the pattern of recombination, based on gene similarity. Lastly, a comprehensive phylogenetic analysis based on coding sequences (CDS) was conducted, allowing us to generate a refined phylogenetic tree that includes all known ASFV genomes. The ANASFV pipeline will facilitate ASFV full genome sequencing using the nanopore platform. The pipeline will also support robust downstream bioinformatic analyses to assess genome integrity and conduct detailed phylogenetic studies based on whole-genome data.
Aberrant remodelling of astrocytic architecture in acute hepatic encephalopathy: complexity of oedematic atrophic astrocytes
Authors: Popek Mariusz , Obara-Michlewska Marta , Szewczyk Łukasz , Kołodziej Marcin , Verkhratsky Alexei , Albrecht Jan , Zielińska Magdalena
Published: July 2024

Hepatic encephalopathy (HE) following acute liver failure (ALF) is a primary toxic astrocytopathy, although in-depth characterisation of underlying pathogenesis is far from complete. Among the multitude of astrocyte-specific proteins guiding brain functionality, plasmalemma-cytoskeletal linker ezrin, actin-binding protein profilin-1, and water channel aquaporin 4 (AQP4) contribute to astrocytic morphological plasticity through regulation of cell shape, volume, complexity of primary and terminal processes, and positioning astrocytes against other CNS constituents. Changes in these proteins might contribute to the brain oedema and astrocytic morphological remodelling in the HE. Using transmission electron microscopy, confocal fluorescent microscopy, and 3D reconstruction, we found complex morphological alterations of cortical astrocytes in mice with azoxymethane-induced ALF. Astrocytic primary branches demonstrated hypertrophy, whereas terminal leaflets showed atrophy quantified by the reduced area occupied by astrocytes, decreased number and the length of leaflets, decreased leaflets volume fraction, and altered astrocyte-to-neurone landscape. These morphological changes correlat with decreased expression of AQP4, phosphorylated leaflet-associated ezrin, and the actin dynamics regulator, profilin 1, suggesting the contribution of these proteins to astrocytic pathological remodelling. Pathological changes in astrocytes develop in parallel, and are likely causally linked to, the HE-linked neurological decline, manifested by a reduction in electroencephalography power and by excessive glutamate in the brain microdialysates.

Abstract Figure

Graphical abstract:

Hepatic encephalopathy is associated with astrocyte remodelling manifested by swelling of the soma and primary branches together with atrophy of distal branches and leaflets; the latter retract from synapses thus affecting neurotransmission and contribute to the reduced neuronal activity. Astrocyte remodelling was linked to (and probably instigated by) a decrease of plasmalemma-cytoskeleton linker phosphorylated ezrin (Phos-ezrin), actin modulator profilin-1 (PFN1) and water channel aquaporin 4 (AQP4).
A robust relationship between robustness and evolvability
Authors: Hardy Nate B
Published: July 2024

Here, I consolidate and extend simple models of how genetic robustness affects the evolvability of phenotypes with discrete states. I share three main insights. (1) What we already know about the effects of mutational robustness on evolvability can be readily transferred to environmental robustness. (2) Even without a hard genotype-level trade-off between robustness and evolvability, the optimal level of phenotypic robustness depends on the rate of environmental change. But counter-intuitively, when adaptive landscapes are complex, an increase in environmental stability can increase the frequency of environmentally-robust but mutationally-sensitive genotypes. (3) Even with a fixed probability that a mutation is neutral, populations can evolve along the spectrum of robustness and evolvability by evolving the genotype-determined neighborhood of mutationally-accessible phenotypes. Indeed, because it allows for the evolution of increased evolvability without a concomitant increase in genetic load, selection should favor changes in the phenotypic neighborhood over changes in mutational sensitivity.

Teaser Text

Models of the evolution of discrete phenotypes show that their evolvability is highest when environments fluctuate at intermediate rates, and with intermediate levels of mutational robustness. By merging previous models and relaxing previous assumptions, I show that previous insights are robust. I also show that the same models tell us very different things about the evolvability of discrete traits, namely, that what applies to robustness against mutation is readily transferable to robustness against environmental perturbation, and that selection for evolvability will preferentially work on the neighborhood of mutationally-accessible phenotypes rather than the probability of non-neutral mutation.
Entangled and non-modular enhancer sequences producing independent spatial activities
Authors: Museridze Mariam , Ceolin Stefano , Mühling Bettina , Ramanathan Srishti , Barmina Olga , Sekhar Pallavi Santhi , Gompel Nicolas
Published: July 2024

The modularity of transcriptional enhancers (1, 2) is central to our understanding of morphological evolution, as it allows specific changes to a gene expression pattern component, without affecting others (3). Enhancer modularity refers to physically separated stretches of regulatory sequence producing discrete spatiotemporal transcriptional activity. This concept stems mainly from assays that test the sufficiency of a DNA segment (4) to drive spatial reporter expression resembling that of the corresponding gene. Focusing on sufficiency to produce spatial patterns, it overlooks quantitative aspects of gene expression, underestimating the regulatory sequence actually required to reach full endogenous expression levels. Here we show that five regulatory activities of the pigmentation geneyellowinDrosophila, classically described as modular (5–7), result from extensively overlapping sequences, with broadly distributed regulatory information. Nevertheless, the independent regulatory activities of these entangled enhancers appear to be nucleated by specific segments that we called enhancer cores. Our work calls for a reappraisal of enhancer definition and properties, as well as of the consequences on regulatory evolution.
A multi-region recurrent circuit for evidence accumulation in rats
Authors: Gupta Diksha , Kopec Charles D. , Bondy Adrian G. , Luo Thomas Z. , Elliott Verity A. , Brody Carlos D.
Published: July 2024

Decision-making based on noisy evidence requires accumulating evidence and categorizing it to form a choice. Here we evaluate a proposed feedforward and modular mapping of this process in rats: evidence accumulated in anterodorsal striatum (ADS) is categorized in prefrontal cortex (frontal orienting fields, FOF). Contrary to this, we show that both regions appear to be indistinguishable in their encoding/decoding of accumulator value and communicate this information bidirectionally. Consistent with a role for FOF in accumulation, silencing FOF to ADS projections impacted behavior throughout the accumulation period, even while nonselective FOF silencing did not. We synthesize these findings into a multi-region recurrent neural network trained with a novel approach. In-silico experiments reveal that multiple scales of recurrence in the cortico-striatal circuit rescue computation upon nonselective FOF perturbations. These results suggest that ADS and FOF accumulate evidence in a recurrent and distributed manner, yielding redundant representations and robustness to certain perturbations.
Host-use Drives Convergent Evolution in Clownfish and Disentangles the Mystery of an Iconic Adaptive Radiation
Authors: Gaboriau T. , Marcionetti A. , Garcia Jimenez A. , Schmid S. , Fitzgerald L. M. , Micheli B. , Titus B. , Salamin N.
Published: July 2024

Clownfishes (Amphiprioninae) are a fascinating example of marine radiation. From a central Pacific ancestor, they quickly colonized the coral reefs of the Indo-Pacific and diversified independently on each side of the Indo-Australian Archipelago. Their association with venomous sea anemones is often thought to be the key innovation that enabled the clownfish radiation. However, this intuition has little empirical or theoretical support given our current knowledge of the clade. To date, no ecological variable has been identified that can explain clownfish niche partitioning, phenotypic evolution, species co-occurrence, and thus, the adaptive radiation of the group. Our synthetic work solves this long-standing mystery by testing the influence of sea anemone host use on phenotypic divergence. We provide the first major revision to the known clownfish-sea anemone host associations in over 30 years, accounting for host associations in a biologically relevant way. We gathered whole-genome data for all 28 clownfish species and reconstructed a fully supported species tree for the Amphiprioninae. Integrating this new data into comparative phylogenomic approaches, we demonstrate for the first time, that the host sea anemones are the drivers of convergent evolution in clownfish color pattern and morphology. During the adaptive radiation of this group, clownfishes in different regions that associate with the same hosts have evolved the same phenotypes. Comparative genomics also reveals several genes under convergent positive selection linked to host specialisation events. Our results identify the sea anemone host as the key ecological variable that disentangles the entire adaptive radiation. As one of the most recognizable animals on the planet and an emerging model organism in the biological sciences, our findings bear on the interpretation of dozens of prior studies on clownfishes and will radically reshape research agendas for these iconic organisms.
Multi-dataset Integration and Residual Connections Improve Proteome Prediction from Transcriptomes using Deep Learning
Authors: Cranney Caleb W. , Meyer Jesse G.
Published: July 2024

Proteomes are well known to poorly correlate with transcriptomes measured from the same sample. While connected, the complex processes that impact the relationships between transcript and protein quantities remains an open research topic. Many studies have attempted to predict proteomes from transcriptomes with limited success. Here we use publicly available data from the Clinical Proteomics Tumor Analysis Consortium to show that deep learning models designed by neural architecture search (NAS) achieve improved prediction accuracy of proteome quantities from transcriptomics. We find that this benefit is largely due to including a residual connection in the architecture that allows input information to be remembered near the end of the network. Finally, we explore which groups of transcripts are functionally important for protein prediction using model interpretation with SHAP.