bluuebunny/crossref_metadata_2025_split huggingface dataset:
Participation in Social and Community Life Before and After Spinal Cord Injury/Disease
Authors: Gross-Hemmi Mirja H. , Gangwisch Anita , Brinkhof Martin W.G. , Eriks Hoogland Inge , Schwegler Urban , Staubli Stefan , Galvis Aparicio Mayra 
Published: November 2024

Objectives
Examining changes in participation frequency (productive, leisure, and social activities) from pre–spinal cord injury/disorder to at least 2 yrs post–spinal cord injury/disorder and identifying sociodemographic and spinal cord injury/disorder characteristics associated with significant shifts in participation frequency.

Design
The study used a longitudinal design, using data from the Swiss Spinal Cord Injury Cohort study. Pre–spinal cord injury/disorder participation frequency was assessed retrospectively 12 wks after spinal cord injury/disorder and prospectively 1 and at least 2 yrs after spinal cord injury/disorder. Linear mixed-effects model trees were used to identify subgroups with participation changes and related sociodemographic and spinal cord injury/disorder characteristics.

Results
The study involved 550 individuals (median age at spinal cord injury/disorder onset: 53 yrs, 30% female, 63.9% with traumatic etiology, and 5.6 yrs since onset). Pronounced decrease was observed prominently in productive activities. Education and age at spinal cord injury/disorder onset served as initial variables to split the tree at first level for each of the participation dimensions.

Conclusions
This research identified participation dimensions most susceptible to changes during the initial years after spinal cord injury/disorder and pinpointed subgroups displaying clinically meaningful longitudinal variations across productive, leisure, and social activities. These findings have the potential to enhance the efficiency of rehabilitation programs, leading to improvements in long-term participation levels for individuals with spinal cord injury/disorder.
Determinants of Between-Person Variation in Shoulder Pain in Individuals With Spinal Cord Injury
Authors: Bossuyt Fransiska Marie , Eriks-Hoogland Inge , Schubert Martin , Minder Ursina , Brinkhof Martin W.G. , Arnet Ursina 
Published: November 2024

Objective
The aim of the study was to evaluate determinants of between-person variation in shoulder pain (“yes”/“no”) in individuals with spinal cord injury living in Switzerland.

Design
This longitudinal study used data from the Swiss Spinal Cord Injury Cohort community surveys 2012, 2017, and 2022. Logistic regression analyses were used to identify determinants of between-person variability in shoulder pain while controlling for within-person variability.

Results
The prevalence of shoulder pain was 34.4% (95% CI = 33.0–35.9) when studying 4393 completed questionnaires. Significant determinants for between-subject variability revealed higher likelihoods for shoulder pain in females as compared with males (odds ratio: 1.57; 95% CI = 1.21–2.05), and when spasticity (1.49; 1.14–1.95), contractures (2.77; 2.21–3.48), and depression (1.39; 1.02–3.48) were present. In addition, shoulder pain presented highest likelihoods in individuals with incomplete tetraplegia (1.81; 1.32–2.48) versus incomplete paraplegia, in individuals over 26 yrs since injury (1.65; 1.15–2.37) versus up to 5 yrs since injury, and in individuals using a manual (2.17; 1.53–3.08) or electrical (2.16; 1.41–3.31) wheelchair versus no aids. There were significant interaction effects for gender with time since injury, contractures, and depression.

Conclusions
Determinants of between-subject variability in shoulder pain were female gender, lesion severity, time since injury, specific health conditions, and wheelchair use.
Changes in Secondary Health Conditions Among Individuals With Spinal Cord Injury After Transition From Inpatient Rehabilitation to Community Living
Authors: Glisic Marija , Stoyanov Jivko , Mueller Gabi , Schubert Martin , Jordan Xavier , Hund-Georgiadis Margret , Pannek Juergen , Eriks-Hoogland Inge 
Published: November 2024

Objective
The aim of the study is to examine the changes in the burden of secondary health conditions and their risk factors among newly injured individuals with spinal cord injury after discharge from inpatient rehabilitation to community living.

Design
This is a prospective cohort study.

Results
Among 280 included persons, the majority were men with traumatic spinal cord injury and paraplegia. The most common secondary health conditions at discharge from rehabilitation and in the community setting were pain (60.8% vs. 75.9%), urinary tract infections (27.8% vs. 47.6%), and pressure sores (9.9% vs. 27.5%). There was also a significant increase in reported heart disease (9.3% vs. 14.8%) and diabetes (0% vs. 4.2%). The odds of experiencing pain, pressure sores, depression and urinary tract infections increased after discharge from rehabilitation, whereas the odds of respiratory problems decreased significantly during the observation period. Factors such as sex, injury severity, activity limitations, and duration of follow-up were identified as potential risk factors influencing secondary health condition occurrence.

Conclusions
Our study emphasizes a significant rise in secondary health conditions after the transition to community living. Future research should prioritize development of targeted intervention programs tailored to address the unique needs of affected individuals at this pivotal stage in the continuum of spinal cord injury care.
Impact of Psychosocial Resources on Mental Health During the Transition From the Initial Rehabilitation to Community
Authors: Lüscher Janina , Galvis Mayra , Schwegler Urban , Diener Martina , Debnar Caroline 
Published: November 2024

Objectives
This study aims to examine the change in mental health from the clinical to community setting in persons with spinal cord injury and to identify the role of psychosocial resources for this transition.

Design
Longitudinal survey self-report data from N = 240 persons with spinal cord injury from the Swiss Spinal Cord Injury Cohort study.

Results
Latent profile analysis identified three profiles for each the clinical and the community setting: low, medium, and high mental health load. Latent transition analysis revealed that persons with spinal cord injury were most likely to stay in the same profile from discharge of initial rehabilitation to community, followed by a decrease from a high mental health load to a medium mental health load and an increase from a low mental health load to a medium mental health load. Individuals staying in the low mental health load profile showed significantly higher levels of psychosocial resources compared to individuals increasing to the medium mental health load profile, whereas individuals who stayed in the high mental health load profile showed lower levels of psychosocial resources compared to individuals decreasing to the medium mental health load profile.

Conclusions
This study highlights a positive role of psychosocial resources on mental health transitions, underlining the need for strengthening psychosocial resources beyond initial rehabilitation.
Prediction of Severe Acute Pancreatitis at a Very Early Stage of the Disease Using Artificial Intelligence Techniques, Without Laboratory Data or Imaging Tests
Authors: Villasante Sara , Fernandes Nair , Perez Marc , Cordobés Miguel Angel , Piella Gemma , Martinez María , Gomez-Gavara Concepción. , Blanco Laia , Alberti Piero , Charco Ramón , Pando Elizabeth ,   Pancreatia Study Collaborators
Published: November 2024

Objective:
To evaluate machine learning models’ performance in predicting acute pancreatitis severity using early-stage variables while excluding laboratory and imaging tests.

Summary Background Data:
Severe acute pancreatitis (SAP) affects approximately 20% of acute pancreatitis (AP) patients and is associated with high mortality rates. Accurate early prediction of SAP and in-hospital mortality is crucial for effective management. Traditional scores such as APACHE-II and BISAP are complex and require laboratory tests, while early predictive models are lacking. Machine learning (ML) has shown promising results in predictive modelling, potentially outperforming traditional methods.

Methods:
We analysed data from a prospective database of AP patients admitted to Vall d’Hebron Hospital from November 2015 to January 2022. Inclusion criteria were adults diagnosed with AP according to the 2012 Atlanta classification. Data included basal characteristics, current medication, and vital signs. We developed machine learning models to predict SAP, in-hospital mortality, and intensive care unit (ICU) admission. The modelling process included two stages: Stage 0, which used basal characteristics and medication, and Stage 1, which included data from Stage 0 and vital signs.

Results:
Out of 634 cases, 594 were analysed. The Stage 0 model showed AUC values of 0.698 for mortality, 0.721 for ICU admission, and 0.707 for persistent organ failure. The Stage 1 model improved performance with AUC values of 0.849 for mortality, 0.786 for ICU admission, and 0.783 for persistent organ failure. The models demonstrated comparable or superior performance to APACHE-II and BISAP scores.

Conclusions:
The ML models showed good predictive capacity for SAP, ICU admission, and mortality using early-stage data without laboratory or imaging tests. This approach could revolutionise AP patients’ initial triage and management, providing a personalised prediction method based on early clinical data.
Regulation of Necroptosis and the Type Interferon Response by Monkeypox/mpox Virus
Authors: Williams Jacqueline , Bonner James , Jacobs Bertram L. 
Published: November 2024

AbstractMonkeypox/mpox virus (MPXV) has re-emerged as the most important orthopoxvirus infection of humans. Despite being pathogenic, it contains a natural truncation at the N-terminus of its homologue of the vaccinia virus (VACV) innate immune evasion protein, E3, leading to the loss of the first 37 amino acids. Our previous data have shown that VACV E3 protein is required for interferon-resistance of VACV. The N-terminal Z-nucleic acid binding domain is necessary to inhibit induction of necroptosis, as VACV containing an N-terminal deletion (VACV-E3LΔ37N) undergoes rapid ZBP1-dependent necroptotic cell death, through activation of RIPK3, and subsequent phosphorylation and trimerization of the executioner of necroptosis, MLKL. Despite lacking parts of the N-terminus, MPXV has evolved ways in circumventing necroptotic cell death in mouse L929 cells. Our data shows that MPXV infection inhibits phosphorylation of MLKL and does not lead to MLKL trimerization, nor cell death. We show that MPXV inhibits necroptosis in two steps: by degrading RIPK3 through either a caspase-dependent pathway or through the “viral inducer of RIPK3 degradation” (vIRD) and by inhibiting MLKL aggregation. Additionally, MPXV shows interferon sensitivity that is fully ZBP1- and RIPK3- and MLKL-dependent, but independent of necroptosis. Addition of a pancaspase inhibitor (zVAD), or a proteasome inhibitor (MLN4924) does not increase cell death but leads to an increase in interferon sensitivity comparable to VACV-E3LΔ37N. Thus, treatment with an interferon inducer along with a pancaspase or proteasome inhibitor could potentially be a beneficial treatment against MPXV infections.
The Experience of Automated Home Oxygen Therapy for Patients with COPD – a Qualitative Study
Authors: Kofod Linette Marie , Laursen Louise Bolvig , Westerdahl Elisabeth , Hansen Ejvind Frausing , Brocki Barbara Cristina , Kristensen Morten Tange , Bove Dorthe Gaby 
Published: November 2024

AbstractThe present study included the first patients with COPD on long-term oxygen therapy who experienced second-by-second oxygen adjustments in their homes based on oxygen saturation. A device capable of automatically titrating the patient’s oxygen was installed in the patients’ home aiming at increasing the time spent within target saturation. We explored patients’ experiences with this automated home oxygen titration, focusing on how maintaining target saturation affected daily life.Semi-structured interviews were conducted with eight men and four women after installation. Systematic text condensation was used in the analysis.Three main themes emerged from patient narratives: 1) “This is my life” – Patients preferred maintaining stable oxygen saturation, associating hypoxemia with dyspnea, discomfort, and difficulties with daily tasks. 2) “Getting the oxygen, I need” – Many patients reported improved ability to perform daily activities when oxygen was automatically adjusted. 3) “New technology gives hope for my life” – Patients expressed optimism about the potential of home-based technology, offering suggestions to improve usability, mainly by reducing concentrator noise.Our findings suggested high acceptability of the automated oxygen in the patients’ home, as they believed it to increase the time spend with sufficient oxygen, especially during daily activities. Integrating patient insights is essential for implementation and acceptance of automated home oxygen therapy.
Seasonal influenza vaccination in people who have contact with birds
Authors: Thomas Amy , Gokool Suzanne , Whitlow Harry , Clapp Genevieve , Moore Peter , Puleston Richard , Smith Louise E , Pae Riinu , Brooks-Pollock Ellen 
Published: November 2024

AbstractBackgroundFollowing the 2021-2022 avian influenza panzootic in birds and wildlife, seasonal influenza vaccines have been advised to occupationally high-risk groups to reduce the likelihood of coincidental infection in humans with both seasonal and avian influenza A viruses.MethodsWe developed and launched a questionnaire aimed at poultry workers and people in direct contact with birds to understand awareness and uptake of seasonal influenza vaccination. We collected responses in-person at an agricultural trade event and online.FindingsThe questionnaire was completed by 225 individuals from across the UK. The most commonly reported reason for vaccination was protection against seasonal influenza (82%, 63 of 77). Nearly all individuals aged ≥65 years reported that the vaccine was recommended for them (24 of 28). There was no difference in recommendation for occupational groups. Most vaccinees were aged over 60 years (60%, 29 of 48), however coverage was lower than expected in the ≥65 target group. Vaccination in those exposed to avian influenza was low (32%, 9 of 28). Not having enough time was the single most reported reason for not getting vaccinated in those intending to. Individuals unintending to be vaccinated perceived natural immunity to be better than receiving the vaccine as well as lack of awareness and time.ConclusionsOur findings suggest that targeted campaigns in occupationally exposed groups need to be undertaken to improve communication of information and access to vaccine clinics. We recommend co-production methods to optimise this public health strategy for increased knowledge and future vaccine uptake.
Blood DNA Methylation Signature for Incident Dementia: Evidence from Longitudinal Cohorts
Authors: Zhang Wei , Young Juan I. , Gomez Lissette , Schmidt Michael A. , Lukacsovich David , Kunkle Brian W. , Chen Xi , Martin Eden R. , Wang Lily 
Published: November 2024

ABSTRACTINTRODUCTIONDistinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies.METHODSWe studied blood DNA methylation (DNAm) differences and incident dementia in two large longitudinal cohorts: the Offspring cohort of the Framingham Heart Study (FHS) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. We analyzed blood DNAm samples from over 1,000 cognitively unimpaired subjects.RESULTSMeta-analysis identified 44 CpGs and 44 differentially methylated regions consistently associated with time to dementia in both cohorts. Our integrative analysis identified early processes in dementia, such as immune responses and metabolic dysfunction. Furthermore, we developed a Methylation-based Risk Score, which successfully predicted future cognitive decline in an independent validation set, even after accounting for age, sex, APOE ε4, years of education, baseline diagnosis, and baseline MMSE score.DISCUSSIONDNA methylation offers a promising source of biomarker for early detection of dementia.
Cell-based assay for blood-based diagnostics enhances prediction of lung cancer in patients with lung nodules
Authors: Berndt Jason D. , Duffy Fergal J. , D’Ascenzo Mark D. , Miller Leslie R. , Qi Yijun , Whitney G. Adam , Danziger Samuel A. , Vachani Anil , Massion Pierre P. , Deppen Stephen A. , Lipshutz Robert J. , Aitchison John D. , Smith Jennifer J. 
Published: November 2024

AbstractThe iCAP is a tool for blood-based diagnostics that addresses the low signal-to-noise ratio of blood biomarkers by using cells as biosensors. The assay exposes small volumes of patient serum to standardized cells in culture and classifies disease by AI analysis of gene-expression readouts from the cells. It simplifies the complexity of blood into a concise readout in a scalable cell-based assay. We developed the LC-iCAP as a rule-out test for nodule management in CT-based lung cancer screening. The assay achieved an AUC of 0.63 (95% CI 0.50-0.75) in retrospective-blind-temporal validation. When integrated with CT data after validation, it demonstrated potential to reduce unnecessary follow-up procedures by significantly outperforming the Mayo Clinic model with 90% sensitivity, 67% specificity and 95% NPV using an estimated 25% prevalence. Analytical validation established LC-iCAP reproducibility and identified unwanted variation from long-term serum storage suggesting a prospective study design could enhance performance.
Sex differences in ACE2, TMPRSS2, and HLA-DQA2 expression in gray matter: Implications for post-COVID-19 neurological symptoms
Authors: Kesler Shelli R. , De La Torre Schutz Alexa , Rocha Oscar Y. Franco , Lewis Kimberly 
Published: November 2024

AbstractCOVID-19 has been associated with sex differences in terms of mortality and morbidity. Viral entry proteins including those regulated by ACE2 and TMPRSS2 may play a role, but few studies have been conducted to date and none have examined sex differences in brain expression. Additionally, HLA-DQA2 expression has emerged as a potential moderator of COVID-19 outcomes. Using non-invasive imaging transcriptomics, we measured ACE2, TMPRSS2, and HLA-DQA2 mRNA expression in gray matter volumes using MRI scans obtained from 1,045 healthy adults aged 21-35 years (44% male) imaged prior to the COVID-19 pandemic. ACE2 (t = 9.24, p < 0.001, d = 0.576), TMPRSS2 (t = 24.66, p < 0.001, d = 1.54), and HLA-DQA2 (t = 3.70, p < 0.001, d = 0.231) expression was significantly higher in males compared to females. Bayesian network analysis indicated significant (p < 0.05) positive causal paths from ACE2 to HLA-DQA2 (B = 0.282), ACE2 to TMPRSS2 (B = 0.357), and TMPRSS2 to HLA-DQA1 (B = 0.139) and a negative causal path from sex (males = -1, females = 1) to TMPRSS2 (B = -0.607). Our results have important implications for neurological symptoms associated with COVID-19 and long COVID including complex interactions between viral entry proteins and immune responses, sex-related disparities in symptom reporting and diagnosis, assessment of neurological problems after COVID-19, and potential COVID-19 related syndemics. However, further research is needed to determine gene expression patterns by sex and COVID-19 outcomes, to evaluate additional genes that may influence neurologic status, and studies that include objective assessments of neurologic outcomes.
Constitutive activity of an atypical chemokine receptor revealed by inverse agonistic nanobodies
Authors: Perez Almeria Claudia V. , Otun Omolade , Schlimgen Roman , Lamme Thomas D. , Crudden Caitrin , Youssef Noureldine , Musli Lejla , Jenjak Shawn , Bobkov Vladimir , Drube Julia , Hoffmann Carsten , Volkman Brian F. , Granier Sébastien , Bechara Cherine , Siderius Marco , Heukers Raimond , Schafer Christopher T. , Smit Martine J. 
Published: November 2024

AbstractChemokine stimulation of atypical chemokine receptor 3 (ACKR3) does not activate G proteins but recruits arrestins. It is a chemokine scavenger that indirectly influences responses by restricting the availability of CXCL12, an agonist shared with the canonical receptor CXCR4. ACKR3 is upregulated in numerous disorders. Due to limited insights in chemokine-activated ACKR3 signaling, it is unclear how ACKR3 contributes to pathological phenotypes. One explanation may be that high constitutive activity of ACKR3 drives non-canonical signaling through a basal receptor state. Here we characterize the constitutive action of ACKR3 using novel inverse agonistic nanobodies to suppress basal activity. These new tools promote an inactive receptor conformation which decreased arrestin engagement and inhibited constitutive internalization. Basal, non-chemotactic, breast cancer cell motility was also suppressed, suggesting a role for ACKR3 in this process. The basal receptor activity in pathophysiology may provide a new therapeutic approach for targeting ACKR3.
Small molecule modulator of neuronal lysosome positioning and function resolves Alzheimer’s Disease-linked pathologies in cultured human neurons
Authors: Snead Amanda M. , Patel Sruchi , Krout Mia , Hippman Ryan S. , Smith Gabrielle , Dileep Diya , Chagoor Nitya , Shi Rachel , Linares Ricardo , Dobria Andrew , Cologna Stephanie M. , Crowder Camerron , Aldrich Leslie N. , Gowrishankar Swetha 
Published: November 2024

AbstractAbnormal increase in axonal lysosome abundance is associated with multiple neurodegenerative diseases including Alzheimer’s disease. However, the underlying mechanisms and disease relevance are not fully understood. We have recently identified RH1115 as a small molecule modulator of the autophagy-lysosomal pathway that regulates lysosome positioning in neurons. This allowed us to manipulate neuronal lysosome distribution including in axons and interrogate its contribution to both optimal neuronal functioning and to disease pathology. We demonstrate that the small molecule not only rescues aberrant buildup of both axonal autophagic and lysosomal intermediates but also reduces secreted Aβ42 levels in human iPSC-derived neurons lacking the lysosomal adaptor, JIP3. We thus demonstrate that restoring efficient axonal lysosome transport has an anti-amyloidogenic effect in human neurons and is a promising therapeutic strategy for Alzheimer’s disease. Furthermore, we show that the small molecule enhances neuronal lysosome degradation, requires the lysosomal adaptor JIP4 to rescue the axonal lysosome pathology in the JIP3 KO neurons and increases levels of the JIP4-interacting lysosomal membrane protein, TMEM55B. Lastly, treatment with the small molecule led to a striking rescue of locomotor defects in JIP3 KO zebrafish larvae. Thus, we have identified a small molecule which can be impactful in neurodegenerative diseases that have a lysosomal pathology and have determined its molecular targets in modulating axonal lysosome abundance.