bluuebunny/crossref_metadata_2025 huggingface dataset:
Aligned bodies, united hearts: embodied emotional dynamics of an Islamic ritual
Authors: Saraei Mohammadamin , Paxton Alexandra , Xygalatas Dimitris
Published: August 2024

Collective rituals involve the coordination of intentions and actions and have been shown to promote the alignment of emotional states and social identities. However, the mechanics of achieving group-level synchrony is yet unclear. We report the results of a naturalistic study in the context of an Islamic congregational prayer that involves synchronous movement. We used wearable devices to capture data on body posture, autonomic responses and spatial proximity to investigate how postural alignment and shared arousal intertwine during this ritual. The findings reveal a dual process at play: postural alignment appears to be more localized, with worshippers synchronizing their movements with their nearest neighbours, while physiological alignment operates on a broader scale, primarily driven by the central role of the religious leader. Our findings underscore the importance of interpersonal dynamics in collective gatherings and the role of physical co-presence in fostering connections among participants, with implications extending to our understanding of group dynamics across various social settings.

This article is part of the theme issue ‘Minds in movement: embodied cognition in the age of artificial intelligence’.
The impact of channel geometry and flow regime on endothelial orientation and morphology in vessel-on-chip
Authors: Jouybar Mohammad , van der Kallen Sophie , Sahebali Sheen , Bouten Carlijn , den Toonder Jaap M.J.
Published: August 2024

This study investigates the impact of channel geometry and applied flow on the morphology and function of endothelial cells (ECs) within vessel-on-chip (VoC) models. Traditional organ-on-chip models often utilize rectangular cross-section channels, resulting in flat walls, sharp corners, and non-uniform wall shear stress profiles, which do not accurately mimic physiological conditions. Tubular channels with a circular cross-section provide a more in vivo-like geometry and result in a physiological uniform wall shear stress. Here, sugar 3D-printing is used for fabricating tubular channels, and stereolithography 3D-printing is applied for making rectangular channels. Using these models, the effects of both channel geometry and various flow conditions on the orientation and morphology of ECs, from both blood and lymph vessels, is explored. The research demonstrates that ECs in tubular channels exhibit a more uniform coverage and circumferential alignment/migration compared to rectangular channels. Unidirectional and bidirectional flow conditions induce alignments parallel to flow, overruling the circumferential alignment induced by curvature in tubular channels. The combination of tubular geometry and pulsatile flow induces enhanced circumferential orientation, different from rectangular channels in which cells remain primarily aligned along the flow direction under pulsatile flow. In summary, our systematic study shows that the channel curvature determines the cell orientation in static conditions, and that adding flow results in a competing effect between geometry and flow for which the resulting cell alignment depends on the flow conditions. Additionally, the study examines the initial adhesive interactions between monocytes and ECs, revealing that EC orientation induced by different flow regimes impacts monocyte rolling velocities. This finding is important for understanding immune cell motility and adhesion in healthy and diseased states. This study underlines the importance of the combined effect of channel geometry and flow conditions in VoC models, and it provides a strong motivation for the continued development of advanced OoC systems with ever more representative geometrical designs and flow control, to maximize the potential of OoC to revolutionize biomedical research and personalized medicine by providing more accurate and functional models of human physiology.
Glucose uptake in pigment glia suppresses tau-induced inflammation and photoreceptor degeneration inDrosophila
Authors: Oka Mikiko , Nakajima Sho , Suzuki Emiko , Yamamoto Shinya , Ando Kanae
Published: August 2024

Brain inflammation contributes to the pathogenesis of neurodegenerative diseases such as Alzheimer’s disease (AD). Glucose hypometabolism and glial activation are pathological features seen in AD brains; however, the connection between the two is not fully understood. Using aDrosophilamodel of AD, we identified that glucose metabolism in glia plays a critical role in neuroinflammation under disease conditions. Expression of human Tau in the retinal cells, including photoreceptor neurons and pigment glia, causes photoreceptor degeneration accompanied by inclusion formation and swelling of the lamina cortex. We found that inclusions are formed by glial phagocytosis, and swelling of the laminal cortex correlates with the expression of antimicrobial peptides. Co-expression of human glucose transporter 3 (GLUT3) with Tau in the retina does not affect tau levels but suppresses these inflammatory responses and photoreceptor degeneration. We also found that expression ofGLUT3, specifically in the pigment glia, is sufficient to suppress inflammatory phenotypes and mitigate photoreceptor degeneration in the tau-expressing retina. Our results suggest that glial glucose metabolism contributes to inflammatory responses and neurodegeneration in tauopathy.

Summary Statement

Glucose uptake into pigment glia suppresses inflammatory responses and photoreceptor degeneration in the fly model of tauopathy.
Center of mass states render multi-joint torques throughout standing balance recovery
Authors: Jakubowski Kristen L. , Martino Giovanni , Beck Owen N. , Sawicki Gregory S. , Ting Lena H.
Published: August 2024

Successful reactive balance control requires coordinated modulation of hip, knee, and ankle torques. Stabilizing joint torques arise from feedforward neural signals that modulate the musculoskeletal system’s intrinsic mechanical properties, namely muscle short-range stiffness, and neural feedback pathways that activate muscles in response to sensory input. Although feedforward and feedback pathways are known to modulate the torque at each joint, the role of each pathway to the balance-correcting response across joints is poorly understood. Since the feedforward and feedback torque responses act at different delays following perturbations to balance, we modified the sensorimotor response model (SRM), previously used to analyze the muscle activation response to perturbations, to consist of parallel feedback loops with different delays. Each loop within the model is driven by the same information, center of mass (CoM) kinematics, but each loop has an independent delay. We evaluated if a parallel loop SRM could decompose the reactive torques into the feedforward and feedback contributions during balance-correcting responses to backward support surface translations at four magnitudes. The SRM accurately reconstructed reactive joint torques at the hip, knee, and ankle, across all perturbation magnitudes (R2>0.84 & VAF>0.83). Moreover, the hip and knee exhibited feedforward and feedback components, while the ankle only exhibited feedback components. The lack of a feedforward component at the ankle may occur because the compliance of the Achilles tendon attenuates muscle short-range stiffness. Our model may provide a framework for evaluating changes in the feedforward and feedback contributions to balance that occur due to aging, injury, or disease.

NEWS AND NOTEWORTHY

Reactive balance control requires coordination of neurally-mediated feedforward and feedback pathways to generate stabilizing joint torques at the hip, knee, and ankle. Using a sensorimotor response model, we decomposed reactive joint torques into feedforward and feedback contributions based on delays relative to center of mass kinematics. Responses across joints were driven by the same signals, but contributions from feedforward versus feedback pathways differed, likely due to differences in musculotendon properties between proximal and distal muscles.
Spiral-eyes: A soft active matter model of in vivo corneal epithelial cell migration
Authors: Kostanjevec Kaja , Sknepnek Rastko , Collinson Jon Martin , Henkes Silke
Published: August 2024

The mammalian cornea constantly regenerates its outer epithelial layer. Cells lost by abrasion are replaced by division of both corneal epithelial cells and populations of stem cells around the corneal periphery, the limbus. Limbal-derived epithelial cells migrate into the cornea, retaining equal cell loss and replacement rates (the 'XYZ hypothesis'). This process leads to a striking stable spiral cell motion pattern across the corneal surface, with a central vortex. Here, we show that the emergence of the spiral pattern can be explained by the interplay of the position of the limbus, cell division, extrusion, and collective cell migration along the curved surface of the cornea. Using dissected LacZ mosaic murine corneas, we inferred the flow field on the curved surface by following stripe edges, revealing a tightening spiral. To explain the flow fields, we developed a cell-level, in silico model of the mouse cornea. Corneal epithelial cells were treated as mechanically soft, self-propelled particles with density-dependent proliferation and extrusion rates, and noisy alignment of the direction of migration. Even without any global guidance cues, the model predicted that migration patterns form stripes and spirals closely recapitulating those in the experiment. To understand the origin and properties of this flow field, we complemented the particle-based model with a continuum description of cell flux on the cornea that generalises the XYZ hypothesis of steady-state balance between cell divisions and extrusions. The work, therefore, demonstrates how the physics of swarms on curved surfaces can provide quantitative explanations of biological processes at the tissue scale.
Epidemiological Study and Analysis of Factors Related to Skin Lesions Caused by Medical Disinfectants, and Personal Protective Equipment among Epidemic-Prevention Workers During the SARS-CoV-2 Pandemic Lockdown Period
Authors: Jingyi Hu , Xiao Xiu-Li , Lu Yi , Su Jian-Yong , Zhang Yan , Shang Ting , Zhang Chun-Hua , Guo Lian , Wang Jian-Chao
Published: August 2024

Objective: The aim of this study was to investigate the prevalence of and potential risk factors associated with skin lesions resulting from the use of medical disinfectants and personal protective equipment (PPE) among epidemic prevention workers (including healthcare professionals, temporary sampling site workers, community members and volunteers) during the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic lockdown period in China. Methods: We conducted a survey to investigate the prevalence and factors associated with skin lesions during SARS-CoV-2 pandemic lockdown period among epidemic prevention workers in Gaojing town of Baoshan distract, Shanghai, China. Results: A total of 1033 questionnaires were reviewed, with 995 deemed valid. Among the 995 respondents, 209 (21.01%) reported comorbidities, while 786 (78.99%) were considered as controls. Autoimmune diseases, family history of dermatitis, cardiovascular diseases (CVDs), palmar and plantar hyperhidrosis, allergic diseases and the total time spent on skin cleansing and antisepsis procedures were identified as independent risk factors for these skin lesions. Conclusion: During the SARS-CoV-2 pandemic lockdown period, skin lesions among epidemic prevention workers was prevalent, which was primarily attributed to the use of medical disinfectants and PPE. These skin lesions frequently manifested as a combination of various subtypes across different areas of the body. Several individual factors, along with the total time spent on skin cleansing and skin antisepsis procedures, were identified as significant risk factors for the development of these skin lesions.
Perinatal liver inflammation is associated with persistent elevation of CXCL10 and its canonical receptor CXCR3 on common myeloid progenitors
Authors: Alkhani Anas , Baskaran Suruthi , Murti Abhishek , Rapp Blaine , Levy Claire S , Wang Bruce , Nijagal Amar
Published: August 2024

Biliary atresia (BA) is a leading cause of liver failure in infants. Despite effective surgical drainage, patients with BA exhibit attenuated immune responses to childhood vaccines, suggesting there are long-lasting alterations to immune function. The perinatal liver is home to hematopoietic stem and progenitor cells (HSPCs) and serves as the epicenter for rapidly progressive and significantly morbid inflammatory diseases like BA. We have previously established the role of neonatal myeloid progenitors in the pathogenesis of perinatal liver inflammation (PLI) and hypothesize that PLI leads to long-term changes to HSPCs in mice that recovered from PLI. To test this hypothesis, we compared the changes that occur to HSPCs and mature myeloid populations in the bone marrow of adult mice during homeostasis and during PLI. Our results demonstrate that HSPCs from animals that recover from PLI (“PLI-recovered”) undergo long-term expansion with a reduced proliferative capacity. Notably, PLI leads to persistent activation of common myeloid progenitors through the involvement of CXCL10 and its canonical receptor, CXCR3. Our data suggests that the CXCR3-CXCL10 axis may mediate the changes in HSPCs that lead to altered immune function observed in BA, providing support for a targetable pathway to mitigate the detrimental long-term immune effects observed in patients with BA.
Identification of druggable targets from the interactome of the Androgen Receptor and Serum Response Factor pathways in prostate cancer.
Authors: Azam Haleema , Veale Colin , Zitzmann Kim , Marcone Simone , Gallagher William M. , Prencipe Maria
Published: August 2024

Background: The Androgen Receptor (AR) is crucial for prostate cancer (PCa) progression. Despite the introduction of second-generation AR antagonist, majority of patients develop resistance. The Serum Response Factor (SRF) was identified as a player involved in a crosstalk with AR signalling pathway and associated resistance. Elevated SRF levels in PCa patients were associated with disease progression and resistance to enzalutamide. However, the molecular mediators of the crosstalk between SRF and AR still need to be elucidated. The objective of this study was to identify common interactors of the AR/SRF crosstalk as therapeutic targets. Methods: Here we used affinity purification mass spectrometry (MS) to identify proteins that interact with both SRF and AR. Results: Seven common interactors were identified, including HSP70, HSP0AA1, HSP90AB1, HSAP5, PRDX1 and GAPDH. Pathway analysis revealed that the PI3k/AKT pathway was the most enriched in the AR/SRF network. Moreover, pharmacological inhibition of several proteins in this network, including HSP70, HSP90, PI3k and AKT, significantly decreased cellular viability of PCa cells. Conclusions: This study identified a list of AR/SRF common interactors that represent a pipeline of druggable targets for the treatment of PCa.
Bidirectional Optogenetic Modulations of Peripheral Sensory Nerve Activity: Induction vs. Suppression through Channelrhodopsin and Halorhodopsin
Authors: Kosugi Akito , Inoue Ken-ichi , Takada Masahiko , Seki Kazuhiko
Published: August 2024

In this study, we investigated the potential of optogenetics for modulating activity of peripheral sensory nerves, particularly tactile and proprioceptive afferents, which are vital for movement control. Using adeno-associated virus serotype 9 vector, we selectively transduced channelrhodopsin (ChR2) and halorhodopsin (eNpHR3.0) into large-diameter sciatic nerve afferents of rats. Diverging from conventional dorsal root ganglion (DRG) approaches, we applied optical stimulation at the distal portion of the afferent nerve. The intensity of optical stimulation varied to modulate the extent of induction and suppression of afferent activity. Then, the effect of optical stimulation was determined by the activity recorded in the dorsal root of the same afferents. Our findings show successful induction and suppression of activity in large-diameter afferents via optical stimulation. By increasing the intensity of blue (for ChR2) and yellow (for eNpHR3.0) light stimulation, the activity of fast-conducting afferent fibers was preferentially evoked or inhibited in an intensity-dependent manner. These data indicate that the activity of large-diameter afferents can systematically be regulated by optogenetics. The present innovative methodology for manipulating specific sensory modalities at the nerve level offers a targeted and accessible alternative to DRG stimulation, expanding the therapeutic scope of optogenetics for treating sensory disorders.
On the relationship between spatial environmental variability, dispersion and biodiversity
Authors: Bernardini Giulia , Roberts Gareth G. , Sutton Mark
Published: August 2024

Aim

We establish quantitative relationships between species richness and the rate of spatial change in controlled, digital, environments. We use a simplified, first-principles, stochastic, evolutionary model in which artificial organisms can evolve and disperse. We develop an understanding of how environmental variability in space influences species richness and how it is affected by organisms’ ability to disperse.

Time period

At each time step of the experiment, each organism can reproduce sexually, disperse and die. Each experiment is run for 100,000 time steps. The life span of each organism is 15 time steps.

Location

The model uses an artificial, digital, landscape consisting of a uniform (x, y) grid of cells, with a single environmental variable that changes sinusoidally in thexdirection.

Major taxa studied

Organisms are defined by a 64-bit genome and reproduce sexually. These digital organisms are designed to mimic the basic principles of biological evolution.

Methods

Each experiment starts with a single organism, which can mutate and reproduce sexually, producing offspring that can do all of the above and disperse in the environment. Monte Carlo experimentation is used to generate statistical insight into species richness by producing thousands of replicate simulations.

Results

A strong correlation is observed between mean species richness and the rate of spatial change in the environmental variable. This relationship holds true for a wide range of dispersal abilities, but diminishes when dispersal ability is very low.

Main Conclusions

We predict that the rate of change of environmental variables (e.g. the derivative of elevation) is a driver of real-world biodiversity where dispersal is sufficient. Our results suggest that the ability of organisms to disperse plays an important role in determining how biodiversity responds to environmental gradients.
Comparison of test-retest reproducibility of DESPOT and 3D-QALAS for waterT1andT2mapping
Authors: Simegn Gizeaddis Lamesgin , Gagoski Borjan , Song Yulu , Dean Douglas C. , Hupfeld Kathleen E. , Murali-Manohar Saipavitra , Davies-Jenkins Christopher W. , Simičić Dunja , Wisnowski Jessica , Yedavalli Vivek , Gudmundson Aaron T. , Zöllner Helge J. , Oeltzschner Georg , Edden Richard A. E.
Published: August 2024

Purpose

Relaxometry, specificallyT1andT2mapping, has become an essential technique for assessing the properties of biological tissues related to various physiological and pathological conditions. Many techniques are being used to estimateT1andT2relaxation times, ranging from the traditional inversion or saturation recovery and spin-echo sequences to more advanced methods. Choosing the appropriate method for a specific application is critical since the precision and accuracy ofT1andT2measurements are influenced by a variety of factors including the pulse sequence and its parameters, the inherent properties of the tissue being examined, the MRI hardware, and the image reconstruction. The aim of this study is to evaluate and compare the test-retest reproducibility of two advanced MRI relaxometry techniques (Driven Equilibrium Single Pulse Observation ofT1andT2, DESPOT, and 3D Quantification using an interleaved Look-Locker acquisition Sequence with aT2preparation pulse, QALAS), forT1andT2mapping in a healthy volunteer cohort.

Methods

10 healthy volunteers underwent brain MRI at 1.3 mm3isotropic resolution, acquiring DESPOT and QALAS data (∼11.8 and ∼5 minutes duration, including field maps, respectively), test-retest with subject repositioning, on a 3.0 Tesla Philips Ingenia Elition scanner. To reconstruct theT1andT2maps, we used an equation-based algorithm for DESPOT and a dictionary-based algorithm that incorporates inversion efficiency andB1-field inhomogeneity for QALAS. The test-retest reproducibility was assessed using the coefficient of variation (CoV), intraclass correlation coefficient (ICC) and Bland-Altman plots.

Results

Our results indicate that both the DESPOT and QALAS techniques demonstrate good levels of test-retest reproducibility forT1andT2mapping across the brain. Higher whole-brain voxel-to-voxel ICCs are observed in QALAS forT1(0.84 ± 0.039) and in DESPOT forT2(0.897 ± 0.029). The Bland-Altman plots show smaller bias and variability ofT1estimates for QALAS (mean of -0.02 s, and upper and lower limits of -0.14 and 0.11 s, 95% CI) than for DESPOT (mean of -0.02 s, and limits of -0.31 and 0.27 s). QALAS also showed less variability (mean 1.08 ms, limits –1.88 to 4.04 ms) forT2compared to DESPOT (mean of 2.56 ms, and limits -17.29 to 22.41 ms). The within-subject CoVs for QALAS range from 0.6% (T2in CSF) to 5.8% (T2in GM), while for DESPOT they range from 2.1% (T2in CSF) to 6.7% (T2in GM). The between-subject CoVs for QALAS range from 2.5% (T2in GM) to 12% (T2in CSF), and for DESPOT they range from 3.7% (T2in WM) to 9.3% (T2in CSF).

Conclusion

Overall, QALAS demonstrated better reproducibility forT1andT2measurements than DESPOT, in addition to reduced acquisition time.
The Identification of Key Genes and Biological Pathways in Cardiac Arrest by Integrated Bioinformatics and Next Generation Sequencing Data Analysis
Authors: Vastrad Basavaraj , Vastrad Chanabasayya
Published: August 2024

Cardiac arrest (CA) is a common cause of death world wide. The disease has lacks effective treatment. Efforts have been made to elucidate the molecular pathogenesis of CA, but the molecular mechanisms remain elusive. To identify key genes and pathways in CA, the next generation sequencing (NGS) GSE200117 dataset was downloaded from the Gene Expression Omnibus (GEO) database. DESeq2 tool was used to recognize differentially expressed genes (DEGs). Gene ontology (GO) and REACTOME pathway enrichment analyses were performed to analyze the DEGs and associated signal pathways in the g:Profiler database. The IID database was used to construct the protein-protein interaction (PPI) network, and modules analysis was performed using Cytoscape. A miRNA-hub gene regulatory network and TF-hub gene regulatory network were then constructed to screen miRNAs, TFs and hub genes by miRNet and NetworkAnalyst database and Cityscape software. Receiver operating characteristic curve (ROC) analysis used to verified the hub genes. In total, 844 DEGs were identified, comprising 414 up regulated genes and 430 down regulated genes. GO and REACTOME pathway enrichment analyses indicated that the DEGs for CA were mainly enriched in organonitrogen compound metabolic process, response to stimulus, translation and immune system. Ten hub genes (up-regulated: HSPA8, HOXA1, INCA1 and TP53; down-regulated: HSPB1, LMNA, SNCA, ADAMTSL4 and PDLIM7) were screened. We also predicted miRNAs (hsa-mir-1914-5p and hsa-mir-598-3p) and TFs (JUN and PRRX2) targeting hub genes. This study uses a series of bioinformatics technologies to obtain hug genes, miRNAs and TFs, and key pathways related to CA. These analysis results provide us with new ideas for finding biomarkers and treatment methods for CA.
Genetic variations associated with adaptation processes in Acrocomia palms: A comparative study across the Neotropic for future crop improvement
Authors: Morales-Marroquin Jonathan Andre , Diaz-Hernandez Brenda Gabriela , Vianna Suelen Alves , Alves-Pereira Alessandro , de Araujo-Batista Carlos Eduardo , Colombo Carlos A. , Pinheiro José Baldin , Zucchi Maria Imaculada
Published: August 2024

Population genetic research has evolved, focusing on selection processes using single nucleotide polymorphisms (SNP) genotyping techniques to study crop traits and domestication. This study explores the adaptation process of three neotropical palms of Acrocomia, a genus that has high potential for oil extraction. Our research focuses on their genetic structure, evolutionary significance, and implications of the selection signatures for breeding efforts. We employed Genotyping-by-Sequencing (GBS) with a focus on outlier SNP markers for identifying adaptive genetic processes in A. aculeata, A. totai, and A. intumescens across the Neotropic. Our results reveal two major gene pools in A. aculeata, a North American and a South American group mainly influenced by dispersal and biogeographic barriers, with putative selective signatures linked to fatty acid and carotenoid biosynthesis, pathogen resistance, and environmental stress adaptation. A. totai presented a pronounced genetic structure, with SNPs under selection indicating a recent diversification driven by climatic and geological factors, especially in the Pantanal biome. A. intumescens displays genetic structuring shaped by the endemic process of biogeographic barriers within the Caatinga biome, with potential shared ancestry with A. aculeata. Correlations between allele frequencies and climatic variables highlight adaptation to diverse environments, principally semi-arid, with the annual mean temperature being one of the most influential. Candidate genes associated with fatty acid and carotenoid biosynthesis, as well as pathogen resistance and drought tolerance, indicate targets for domestication. Despite challenges in reduced representation sequencing, this study underlines the potential of Acrocomia as a novel crop, offering prospects in oil production, biofuels, and sustainable agriculture. Future efforts should prioritize whole-genome sequencing and genotype-environment interaction studies to realize the full potential of Acrocomia in sustainable development and renewable energy production.
Neural mechanisms of awareness of action
Authors: Jin David S. , Agdali Oumayma , Yadav Taruna , Kronemer Sharif I. , Kunkler Sydney , Majumder Shweta , Khurana Maya , McCusker Marie C. , Fu Ivory , Siff Emily J. , Khalaf Aya , Christison-Lagay Kate L. , Aerts Shanae L. , Xin Qilong , Li Jing-Jing , McGill Sarah H. , Crowley Michael J. , Blumenfeld Hal
Published: August 2024

The origins of awareness of action (AoA), the ability to report an action just performed, remain elusive. Differing theories ascribe AoA to pre-action, efferent motor/volitional mechanisms versus post-action, afferent sensory/perceptual neural mechanisms. To study these two types of mechanisms and others, we developed a paradigm where very similar aware and unaware actions occur repeatedly. Aware actions demonstrated larger neurophysiological signals both preceding and following movement. The differences included well-known volitional and perceptual event related potentials (PMP, N140, P300), as well as frontal midline theta, event-related alpha/beta desynchronization, and post-move blink rates. On longer time scales, we identified a novel event related potential preceding unaware moves, and found behavioral and pupillometric evidence for decreased attention and arousal over minutes concurrent with AoA loss. Our findings suggest that both dynamic, individual action-associated volitional and perceptual neural activity, as well as long-term attention and arousal states play a role in maintaining AoA.
Low hemoglobin causes hematoma expansion and poor intracerebral hemorrhage outcomes
Authors: Cottarelli Azzurra , Mamoon Rayan , Ji Robin , Mao Eric , Boehme Amelia , Kumar Aditya , Song Sandy , Allegra Valentina , Sharma Sabrina V. , Konofagou Elisa , Spektor Vadim , Guo Jia , Connolly E. Sander , Sekar Padmini , Woo Daniel , Roh David J.
Published: August 2024

Objectives

Although lower hemoglobin levels associate with worse intracerebral hemorrhage (ICH) outcomes, causal drivers for this relationship remain unclear. We investigated the hypothesis that lower hemoglobin relates to increased hematoma expansion (HE) risk and poor outcomes using human observational data and assessed causal relationships using a translational murine model of anemia and ICH.

Methods

ICH patients with baseline hemoglobin measurements and serial CT neuroimaging enrolled between 2010-2016 to a multicenter, prospective observational cohort study were studied. Patients with systemic evidence of coagulopathy were excluded. Separate regression models assessed relationships of baseline hemoglobin with HE (≥33% and/or ≥6mL growth) and poor long-term neurological outcomes (modified Rankin Scale 4-6) after adjusting for relevant covariates. Using a murine collagenase ICH model with serial neuroimaging in anemic vs. non-anemic C57/BL6 mice, intergroup differences in ICH lesion volume, ICH volume changes, and early mortality were assessed.

Results

Among 1190 ICH patients analyzed, lower baseline hemoglobin levels associated with increased odds of HE (adjusted OR per -1g/dL hemoglobin decrement: 1.10 [1.02-1.19]) and poor 3-month clinical outcomes (adjusted OR per -1g/dL hemoglobin decrement: 1.11 [1.03-1.21]). Similar relationships were seen with poor 6 and 12-month outcomes. In our animal model, anemic mice had significantly greater ICH lesion expansion, final lesion volumes, and greater mortality, as compared to non-anemic mice.

Conclusions

These results, in a human cohort and a mouse model, provide novel evidence suggesting that anemia has causal roles in HE and poor ICH outcomes. Additional studies are required to clarify whether correcting anemia can improve these outcomes.
Could a female athlete run a 4-minute mile with improved aerodynamic drafting?
Authors: da Silva Edson Soares , Hoogkamer Wouter , Kipp Shalaya , Kram Rodger
Published: August 2024

In 2023, Faith Kipyegon set the female world record for running one mile (4:07.64). Here, we quantitively explore if improved aerodynamic drafting could allow her to run just 3.19% faster and thus break the 4-minute mile barrier. Drafting involves other athletes (pacers) running in formation around a designated athlete to reduce the aerodynamic drag force acting on the designated runner. Drafting allows the designated athlete to run faster at the same rate of metabolic energy consumption. Our overall approach was to estimate Kipyegon’s metabolic energy consumption during her mile world record performance. Then, we used empirically established relationships between horizontal resistive force, running velocity and metabolic power to estimate how much faster she could run at the same metabolic power if the aerodynamic force was reduced via drafting. Our calculations suggest that Kipyegon could run ∼3:59.37 with drafting provided by one pacer in front and one in back who change out with two other pacers at 800 m.
Analysis of university students' mental health from the perspective of occupational harmony
Authors: Liu Yijun , She Ruiqi , Xin Jing
Published: August 2024

Background: Mental health problems are common among university students. Based on the Model of Occupational Harmony, we investigated the relationship between occupational engagement and mental health among Chinese university students. Methods: A mixed methods approach was adopted. A total of 734 Chinese university students responded to online questionnaires: a socio-demographic questionnaire, the Depression Anxiety Stress Scale, the WHOQOL-BREF, and a self-designed Occupational Harmony Questionnaire. Individual interviews with 11 university students and a focus group of four students provided qualitative data. Results: Anxiety, depression, and stress were reported by 11.9%, 9.4%, and 2.9% of the participants, respectively. The level of occupational harmony was negatively correlated with depression, anxiety, and stress (p<.001). The DASS-21 score was significantly different among students who spent different amounts of time on the following activities: exercise, sleep, rest, reflective and consulting activities, study, work, and leisure and entertainment (P<.05). In the context of the COVID-19 pandemic, the key occupational factors contributing to university students' mental health problems included excessive mental engagement and insufficient physical engagement, excessive active engagement and insufficient quiet engagement, insufficient social engagement, excessive or insufficient Gong (productive) engagement, and insufficient De (virtuous) engagement, Zhi (rational) engagement, and Kang (health maintenance) engagement, lack of coherence within the family, school, social systems, as well as inadequate schedule planning and time management. Conclusions: Occupational disharmony is related to university students' mental health problems. Occupational therapy can promote university students' mental well-being by enhancing occupational harmony.
Temporal Immune Profiling in the CSF and Blood of Patients with Aneurysmal Subarachnoid Hemorrhage
Authors: Ujas Thomas A. , Anderson Katie L. , Lutshumba Jenny , Hart Samantha N. , Turchan-Cholewo Jadwiga , Hatton Kevin W , Bachstetter Adam D , Nikolajczyk Barbara S. , Stowe Ann M
Published: August 2024

Background: Delayed cerebral ischemia (DCI) is a significant complication of aneurysmal subarachnoid hemorrhage (aSAH). This study profiled immune responses after aSAH and evaluated their association with DCI onset. Methods: Twelve aSAH patients were enrolled. Leukocyte populations and cytokine levels were analyzed in cerebrospinal fluid (CSF) and peripheral blood (PB) on days 3, 5, 7, 10, and 14 post-aSAH. Peripheral blood mononuclear cells (PBMCs) were collected and their cytokine production quantified following stimulation. Results: Mixed-effects models revealed distinct immune cell dynamics in CSF compared to blood. Natural killer T cell frequency increased over time in CSF only, while monocyte/macrophage numbers increased in both CSF and PBMCs. CD4+ HLA II+ T cells increased in circulation. Unstimulated PBMCs showed increased IL-1β, IL-6, and TNFα production, peaking at 7 days post-aSAH, coinciding with typical DCI onset. Ex vivo stimulation of PBMCs showed that only IL-6 significantly changed over time. In CSF, cytokines peaked 5 days post-injury, preceding immune cell profile alterations. Conclusions: Our findings reveal a time-dependent immune response following aSAH, with distinct within-patient patterns in CSF and PB. The early CSF cytokine peak preceding immune cell changes suggests a potential mechanistic link and identifies the cytokine response as a promising therapeutic target. This cytokine surge may drive immune cell expansion and prime PBMCs for increased inflammatory activity, potentially contributing to DCI risk. Future studies should explore the importance and sources of specific cytokines in driving immune activation. These insights may inform the development of targeted immunomodulatory strategies for preventing or managing DCI in aSAH patients.
Cardiac dose-volume analysis of 9,411 patients with registry data for cardiovascular disease and overall survival.
Authors: Forbes Nora , Terrones-Campos Cynthia , Smith Abraham , Reekie Joanne , Darkner Sune , Maraldo Maja , P/ohl Mette , Risumlund Signe , Specht Lena , Bentzen Soren M , Petersen Jens , Vogelius Ivan R
Published: August 2024

Abstract Background and purpose Radiation therapy (RT) to the thorax poses risks of radiation-induced cardiotoxicity, potentially increasing cardiovascular diseases (CVD) incidence. Advances in RT strive to minimize these risks by reducing heart radiation dose exposure. This study integrates detailed 3D dosimetry on individually delineated hearts with registry-based outcome data to assess the impact of radiation dose on cardiovascular morbidity and overall survival (OS) across multiple cancer types. It also examined the influence of patient-specific factors on cardiotoxicity risk and survival outcomes. Materials and methods We analyzed data from 9,411 patients receiving RT at Rigshospitalet between 2009 and 2020 for breast, esophageal, lymphoma, and lung cancers. Cumulative incidence of CVD and death in the presence of competing risks was calculated with the Aalen-Johansen estimator. The impact of radiation dose and patient characteristics on ischemic heart disease (IHD) onset and OS were assessed using Kaplan-Meier and Cox Proportional-Hazards Models. Results Higher mean heart dose (MHD) was associated with poorer OS in breast and lung cancer patients (Hazard ratio 2.8 and 1.2), but no significant relationship was found between MHD and IHD. Established cardiac risk factors (age, sex, and existing IHD) outweighed cardiac dose as a risk factor for subsequent cardiac events for all diagnoses. The risk of death was greater than subsequent CVD, especially in esophageal and lung cancers (cumulative incidence 60% versus 17% and 60% versus 14%), despite comparatively high heart doses. Conclusion The study demonstrates that risk of death from primary cancer is of far greater concern than risk of subsequent cardiac events from cardiac radiation dose exposure in the range achievable with contemporary RT techniques, especially for lung and esophageal cancer patients. Further sparing of the heart should not be prioritized at the expense of adequate treatment of the index cancer. Highlights - Age and existing heart disease far outweighed heart dose as predictors of ischemic heart disease - Overall survival is not a useful surrogate for cardiac toxicity in dose-response studies due to confounding by disease stage - With modern RT techniques, the excess absolute risk attributable to radiotherapy is so small that a statistically significant dose-response could not be observed even in 9,411 patients - For most patients, good quality contemporary radiotherapy is sufficient to limit heart toxicity as a clinically relevant concern
Expression of C5aR1 in Cutaneous Squamous Cell Carcinoma is Associated with Invasion, Metastasis and Poor Prognosis
Authors: Heiskanen Lauri , Nissinen Liisa , Siljamaki Elina , Knuutila Jaakko , Pellinen Teijo , Kallajoki Markku , Heino Jyrki , Riihila Pilvi , Kahari Veli-Matti
Published: August 2024

Cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and the metastatic disease is associated with poor prognosis. We have examined the role of complement C5a receptor, C5aR1, in the progression and metastasis of cSCC. C5aR1 expression was increased in cSCC cells in 3D spheroid coculture model in the presence of fibroblasts, and that treatment with recombinant C5a enhanced the invasion of cSCC cells. Staining for C5aR1 was detected on the surface of tumor cells at the invasive edge of human cSCC xenografts in vivo. Staining of metastatic and nonmetastatic primary human cSCCs, premalignant and benign epidermal lesions and normal skin for C5aR1 with multiplex immunofluorescence and chromogenic immunohistochemistry revealed increased expression of C5aR1 on the surface of tumor cells and fibroblasts in invasive cSCCs and recessive dystrophic epidermolysis bullosa associated cSCCs compared to cSCC in situ, actinic keratoses, seborrheic keratoses and normal skin. Increased expression of C5aR1 on the tumor cell surface and in fibroblasts was associated with metastatic risk and poor disease specific survival of patients with primary cSCC. These findings reveal the role of C5aR1 in cSCC invasion and identify C5aR1 as a novel biomarker for metastasis risk and poor prognosis in patients with cSCC. The results also suggest that C5aR1 could be a novel therapeutic target for treatment of locally advanced and metastatic cSCC.
Antiretroviral therapy adherence interventions among persons who use alcohol and other substances in fisherfolk communities: A systematic review
Authors: Agwogie Martin Osayande , Kuester Landon , Radcliffe Polly , Gordon Andrea , Loos Mary , Williams Anna
Published: August 2024

Background: Suboptimal adherence to antiretroviral therapy (ART) is a major challenge in Human Immunodeficiency Virus (HIV) treatment interventions among persons who use alcohol and other substances (AOS) in fisherfolk communities. While studies have identified barriers to ART adherence and interventions to address these barriers in this population, no systematic review has been conducted to establish the significance of these interventions. Methods: Searches were conducted in three electronic databases: PubMed, Web of Science and PsycINFO for studies conducted in English between 1996 and April 2024 to identify relevant primary studies that included adult males or females, engages in fishing activities, use alcohol or other substances and are HIV positive. Outcomes include any measure of adherence to ART, a reduction or abstinence from alcohol and other substance use and associated consequences that could hinder ART adherence. Results: 54 studies were identified and screened against the inclusion/exclusion criteria. Five papers met the inclusion criteria (three quantitative designs, one qualitative design and one mixed methods design). Seven interventions were identified, these include counselling, peer support, screening and brief intervention, economic straightening, social network, gender transformative programmes and prescription monitoring. Conclusion: Findings highlight the significance of alcohol use reduction interventions and gender transformative programmes particularly among men to encourage ART adherence in fisherfolk communities. To achieve the universal target of an end to the HIV scourge by 2030, specific hard to reach populations like fisherfolk communities with high HIV prevalence, alcohol and other substance use needs particular attention.
The Clonal Hematopoiesis-associated GeneSrcapPlays an Essential Role in Hematopoiesis
Authors: Wong Terrence N. , Mychalowych Anna , Feldpausch Ellie R. , Carson Alexander , Karpova Darja , Link Daniel C.
Published: August 2024

Somatic mutations arising in hematopoietic stem cells (HSCs) may provide the latter with a fitness advantage, allowing the mutant HSC to clonally expand. Such mutations have been recurrently identified in the chromatin modifier,SRCAP, in both non-malignant and leukemic clones, suggesting that this gene plays a significant role in hematopoiesis. We generated a conditionalSrcaploss of function murine model and determined the consequences of hematopoietic-specific loss of this gene. We show thatSrcapis essential for normal fetal liver erythropoiesis and monocytopoiesis. InSrcapdeficient fetal livers, the number of phenotypic HSCs is similar to that of controls, but these HSCs exhibit a profound repopulating defect. Likewise, conditional deletion ofSrcapduring adult hematopoiesis results in a rapid loss of HSCs. Loss ofSrcapis associated with evidence of increased DNA damage in HSCs and lineage-restricted progenitors as assessed by y-H2AX expression. Consistent with this finding, we observed strong transcriptional upregulation of the p53 pathway inSrcapdeficient erythroid precursors. Collectively our data highlight the importance ofSrcapin maintaining HSC function and supporting hematopoietic differentiation and suggests that it plays an essential role in maintaining genomic integrity.

Key Points

(1)

Srcapplays an essential role in supporting normal hematopoietic differentiation. and in maintaining HSC function.

(2)

Loss ofSrcapis associated with evidence of increased DNA damage and transcriptional upregulation of the p53 pathway.
Cell-free chromatin particles damage genomic DNA of healthy cells via an ROS-independent mechanism
Authors: Jain Karishma , Raghuram Gorantla V. , Lopes Relestina , Khare Naveen Kumar , Shabrish Snehal , Mittra Indraneel
Published: August 2024

Several hundred billion cells die daily in the human body, releasing cell-free chromatin particles (cfChPs) in the process, which then enter the blood circulation and get taken up by healthy cells. We have previously reported that, these internalized cfChPs damage genomic DNA as well cause physical damage to mitochondria, resulting in increased mitochondrial ROS production. In the current study, we evaluated the potential damaging effects of the cfChP-induced increase in ROS production on genomic DNA. NIH3T3 mouse fibroblast cells were treated with cfChPs isolated from the sera of healthy individuals (H-cfChPs) or patients with cancer (C-cfChPs) in the presence or absence of the ROS scavenger Mito-TEMPO. The pre-incubation of cfChP-treated cells with Mito-TEMPO abolished ROS production, but did not prevent genomic DNA damage induced by H-cfChPs and C-cfChPs. Our results suggest that cfChP-induced genomic DNA damage occurs in an ROS-independent manner. These findings align with emerging evidence suggesting that mitochondrial ROS may not be a direct cause of genomic DNA damage and suggest that DNA damage attributed to ROS may in-fact be induced by cfChPs. This possibility opens up new therapeutic approaches involving deactivation of cfChPs to retard ageing and other degenerative conditions traditionally attributed to oxidative stress.
Biodiversity and riparian forests are mutual biological drivers of ecosystem functions in temperate and tropical streams
Authors: Oester Rebecca , de Omena Paula M. , da Costa Larissa Corteletti , Moretti Marcelo S. , Altermatt Florian , Bruder Andreas
Published: August 2024

Fluxes of energy, matter, and organisms sustain linkages and functions within and between ecosystems. Yet, how biological drivers influence interactions and functions at the interface between aquatic and terrestrial environments (i.e., aquatic-terrestrial ecosystem functions) locally and across regions has received little attention. To test the relative importance of biological drivers on multiple aquatic-terrestrial ecosystem functions, we subsidised local terrestrial detritus in forested and non-forested stream sites in a temperate and tropical region. We also manipulated leaf litter diversity (horizontal biodiversity of resources) and macroinvertebrate access (vertical biodiversity of consumers). We measured secondary production of aquatic fungi, in-stream leaf litter nitrogen loss, and decomposition rates. The simultaneous provision of all three ecosystem functions (i.e., multifunctionality) was positively driven by vertical biodiversity and riparian forests in both regions. In both tropical and temperate streams, nitrogen loss was associated with vertical biodiversity. Decomposition rates were also enhanced by vertical biodiversity and linked to other ecosystem functions. These results reveal strong and consistent effects of biodiversity and riparian forests on aquatic-terrestrial ecosystem functions in freshwater detrital food webs in both temperate and tropical headwater streams. Thus, disentangling the drivers of ecosystem functions in these systems requires an understanding of underlying mechanisms beyond ecosystem borders.