bluuebunny/crossref_metadata_2025 huggingface dataset:
Health Center Characteristics Associated With Hospital Care Among Medicare-Medicaid Dual Enrollees
Authors: Wright Brad , Lombardi Brianna , Akiyama Jill , Potter Andrew J. , Sabik Lindsay M. , Stehlin Grace G. , Trivedi Amal N. , Wolinsky Fredric D.
Published: November 2024

Using 2012–2018 Medicare claims and health center data, we identified factors associated with variation in rates of hospital care among Medicare–Medicaid dual enrollees receiving primary care at health centers. In our sample (n = 5961 health center-years), we found no evidence that patient-centered medical home designation or other modifiable health center characteristics were associated with reductions in hospital care use, which depends more on health center patient mix. Thus, policymakers should target efforts to health centers serving the most disadvantaged and marginalized communities.
The Development of Doctor-nurse-patient Co-construction through Evidence-based Narrative Exploration of Traditional Chinese Medicine
Authors: YU Miao , LI Bo , LIU Qian , WANG Tianyuan
Published: November 2024

Traditional Chinese medicine (TCM) is the wisdom crystallization and cultural treasure of the Chinese nation. Establishing a positive relationship among doctors, nurses, and patients is essential for promoting the sustainable development of TCM culture. As an important branch of evidence-based narrative medicine, evidence-based narrative of TCM significantly contributes to the co-construction of doctors, nurses and patients. This paper discusses the necessity and clinical practice value of promoting co-construction of doctors, nurses and patients based on the principles of evidence-based narrative TCM. By working together to select optimal diagnosis and treatment options, we aim to enhance patient compliance, alleviate tensions among the parties involved, and establish equitable collaborative relationships. Creating a harmonious medical environment is crucial for promoting the continuous development of this collaborative model in clinical practice, thereby improving patients’ overall health, increasing public recognition of TCM, and supporting its sustainable growth.
The Narrative Medicine Practice for the Treatment of Ben Tun Qi
Authors: WANG Zixu , LIU Yipin
Published: November 2024

This article takes the narrative medicine practice of traditional Chinese medicine (TCM) in the treatment of Ben Tun Qi (奔豚气) as an example to illustrate the characteristics of narrative medicine in TCM diagnosis and treatment, and strives to form a simple, easy to implement, and practical process of narrative medicine of TCM, which can help doctors provide more comprehensive, detailed, and humanistic care for diagnosis and treatment activities, and achieve doctor-patient harmony.
A Narrative Review of Congenital Syphilis in the United States: Innovative Perspectives on a Complex Public Health and Medical Disease
Authors: Lehman Alice , Olson Nehemiah , Foster Jill , Contag Stephen
Published: November 2024

Over the past two decades, congenital syphilis cases have risen 11-fold in the United States. While disparities across geography, race, and ethnicity exist, lack of timely screening or treatment is identified in 88% of cases nationally. Congenital syphilis is a public health and medical problem rooted in systematic and societal structural determinants of health and healthcare limitations. Early syphilis in pregnancy leads to congenital syphilis if untreated in 50 – 70% of cases, with risk for fetal demise, and among survivors, congenital anomalies, organ damage, and central nervous system disease. Prevention of congenital syphilis lies in early detection and treatment in pregnant persons. In this narrative review, we describe the evolving epidemiology of syphilis and congenital syphilis, highlighting unique aspects among women. We explore the role of novel screening and treatment strategies, public health policy, and medical considerations in terms of congenital syphilis prevention. Readers of this review will understand CS as a complex public health and medical disease that can be prevented through innovative and coordinated strategies in public health policy, expanded screening and research opportunities.
Exploring cognitive overload in adults with visual impairment: The association between concentration and fatigue
Authors: Veldman Manon H. J. , Adanç Beritan , van Rens Ger H. M. B. , van Nispen Ruth M. A. , van der Aa Hilde P. A.
Published: November 2024

SIGNIFICANCE

This research contributes to the concept of cognitive overload and the association between concentration and fatigue in individuals with visual impairment (VI). Gaining more insight into these and other factors explaining cognitive overload is essential for a better understanding, prevention, and treatment of fatigue severity in individuals with VI.

PURPOSE

Individuals with VI need to use additional cognitive resources to compensate for their loss of vision. These cognitive demands include increased concentration, which may put an extra burden on energy levels. This study aimed to expand upon previous research on the concept of cognitive overload by exploring the relationship between concentration and fatigue severity in individuals with VI.

METHODS

A cross-sectional study was conducted based on data from the eligibility screening of the E-nergEYEze trial (n = 213). Concentration problems were measured with the Checklist of Individual Strengths subscale Concentration, and fatigue severity was measured with the Checklist of Individual Strengths subscale Fatigue Severity. Linear regression analyses were performed to investigate the association between concentration problems and fatigue severity. Potential effect modifiers (i.e., sociodemographic and vision-related characteristics) were considered, and associations were corrected for confounding.

RESULTS

Concentration problems were directly and positively associated with fatigue severity (β = 0.47; R
2 = 0.10; 95% confidence interval, 0.28 to 0.66; adjusted model: β = 0.52; R
2 = 0.16; 95% confidence interval, 0.32 to 0.72). No relevant effect modifiers were identified. However, other factors that were not included in this study were involved in this association.

CONCLUSIONS

This study contributes to understanding the cognitive overload as experienced by adults with VI and highlights the importance of the association of concentration problems, as a reflection of the cognitive burden and perceived fatigue. It is recommended to identify and address concentration difficulties through suitable awareness and treatment strategies to prevent and reduce severe fatigue in this population.
Real-Time Dashboard for Identifying Overdose Touchpoints in Indiana
Authors: Ray Bradley , Huntsinger Douglas , Christian Kaitlyn , Gillenwater Logan , Rinderle Abigail , Dir Allyson , Aalsma Matthew C. , Reda Khairi
Published: November 2024

Indiana state government partnered with researchers to develop a real-time dashboard that brings together multiple data sources to provide state and county-level measures around overdose touchpoints, which are settings that people engaged with prior to fatal overdose. Exploration of the dashboard reveals multiple opportunities for overdose prevention and highlights its use as a tool to monitor strategies in reducing overdose deaths.
The Complexity of Health Self-Management Behavior. Beliefs and Attitudes of Individuals Living With Spinal Cord Injury in Switzerland
Authors: Diviani Nicola , Qama Enxhi , Brach Mirjam , Gemperli Armin , Jordan Xavier , Scheel-Sailer Anke , Rubinelli Sara
Published: November 2024

Objective

Within the objective of defining targets for interventions to support self-management behaviors among people living with spinal cord injury, this study aims to describe self-management attitudes and beliefs in community-dwelling people living with spinal cord injury in Switzerland and to identify their correlates in terms of personal characteristics and outcomes, such as secondary health conditions and quality of life.

Design

This is a cross-sectional, observational study using data from the third community survey of the Swiss Spinal Cord Injury Cohort Study.

Results

Out of 1158 individuals, the data revealed high endorsement in areas of prevention importance, perceived knowledge, adherence to recommendations, and proactive problem-solving. Personal and lesion characteristics were significantly associated with differing self-management beliefs and attitudes. Overall, a more positive and proactive stance toward self-management correlated with enhanced outcomes. However, readiness to renounce activities to adhere to self-management recommendations was associated with lower quality of life.

Conclusions

The findings confirm the complex nature of self-management among individuals with spinal cord injury, advocating for a tailored, person-centered approach in designing interventions. Highlighting a potential trade-off between strict self-management adherence and quality of life outcomes posits an avenue for balanced, individualized self-management strategies to ameliorate health outcomes and life quality for individuals with spinal cord injury.
Healthcare Service Utilization and Related Costs. A Comparison of the Situation of Persons With Spinal Cord Injury to the General Population
Authors: Pacheco Barzallo Diana , Oña Ana , Brach Mirjam , Gemperli Armin
Published: November 2024

Objective

The aim of the study is to investigate healthcare utilization and related costs in spinal cord injury compared to the Swiss population, addressing gaps in understanding this vulnerable group’s needs.

Design

We analyzed healthcare utilization across age groups using data from the Swiss Health Survey and the Swiss Community Survey. Employing count models, Zero-Inflated Negative Binomial, and Poisson regressions, we estimated the adjusted healthcare visits across different age groups in the sample.

Results

Persons with spinal cord injury use 11 times more healthcare services than the healthy population and 4 times more than persons with other chronic health conditions. Notably, service providers for persons with spinal cord injury include physiotherapists, nursing services, general practitioners, and specialists. The high frequency of usage of persons with spinal cord injury translates into high costs, which is 3 times higher than in the general healthy population. These patterns become more evident as persons with spinal cord injury age, where nursing care and rehabilitation services become the most demanded services.

Conclusions

Our findings show the multiple healthcare needs of people with spinal cord injury, which makes them a high-needs, high-cost group. This characteristic underscores the importance of preventive measures to reduce the incidence of spinal cord injury in older adults.
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.
Quantifying the fractal complexity of nutrient transport channels in Escherichia coli biofilms under varying cell shape and growth environment
Authors: Bottura Beatrice , Rooney Liam , Feeney Morgan , Hoskisson Paul A. , McConnell Gail
Published: November 2024

Recent mesoscopic characterization of nutrient-transporting channels in Escherichia coli has allowed the identification and measurement of individual channels in whole mature colony biofilms. However, their complexity under different physiological and environmental conditions remains unknown. Analysis of confocal micrographs of colony biofilms formed by cell shape mutants of E. coli shows that channels have high fractal complexity, regardless of cell phenotype or growth medium. In particular, colony biofilms formed by the mutant strain ΔompR, which has a wide-cell phenotype, have a higher fractal dimension when grown on rich medium than when grown on minimal medium, with channel complexity affected by glucose and agar concentrations in the medium. Osmotic stress leads to a dramatic reduction in the ΔompR cell size but has a limited effect on channel morphology. This work shows that fractal image analysis is a powerful tool to quantify the effect of phenotypic mutations and growth environment on the morphological complexity of internal E. coli biofilm structures. If applied to a wider range of mutant strains, this approach could help elucidate the genetic determinants of channel formation in E. coli colony biofilms.
Zoledronate Therapy in Osteogenesis Imperfecta: Perspectives in Indonesia Tertiary Hospital
Authors: Martanto Tri Wahyu , Japamadisaw Aliefio , Nurhayati Dian , Nelissen Rob G. H. H.
Published: November 2024

Background: Osteogenesis imperfecta (OI) is a rare disease with an estimated incidence of between 1/25,000 and 1/10,000 globally. The main treatment for OI is the administration of bisphosphonate drugs. Research on clinical, radiographic, and biochemical markers to monitor patients with OI treated with zoledronate can be challenging in countries in which patients have limited national health insurance. We aimed to examine patients with OI treated in Indonesia with a minimum follow-up period of 2 years.Methods: An observational study was conducted of all patients with OI treated with zoledronate between 2021 and 2023 at a tertiary hospital in Indonesia. We evaluated the paediatric quality of life (PedsQL), bone mineral density (BMD), and alkaline phosphatase (ALP) level before and after zoledronate treatment. To monitor safety, serum creatinine and calcium levels were also measured.Results: Eleven boys (55%) and nine girls (45%), with an average age of 6.9 years (range, 4–17 years), were included. After 2 years of zoledronate treatment, the total PedsQL score increased from 66.7 to 76.9 (P=0.0001) and the mean lumbar and total body BMD increased from 0.467 and 0.501 to 0.599 g/cm2, and 0.626 g/cm2 (P=0.001), respectively. The ALP level decreased from 310.6 to 186.4 mg/mL (P=0.0001). Neither serum creatinine (P=0.586) nor calcium (P=0.53) levels changed from the pre-treatment to 2 years post-treatment time points.Conclusions: Zoledronate was safe and effective for the treatment of OI. There were significant improvements in the quality of life and BMD in patients with OI. The ALP level decreased, but serum creatinine and calcium levels were not affected by zoledronate.
Regulation of Necroptosis and the Type Interferon Response by Monkeypox/mpox Virus
Authors: Williams Jacqueline , Bonner James , Jacobs Bertram L.
Published: November 2024

Monkeypox/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

The 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

Background

Following 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.

Methods

We 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.

Findings

The 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.

Conclusions

Our 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

INTRODUCTION

Distinguishing between molecular changes that precede dementia onset and those resulting from the disease is challenging with cross-sectional studies.

METHODS

We 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.

RESULTS

Meta-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.

DISCUSSION

DNA methylation offers a promising source of biomarker for early detection of dementia.
Designed miniproteins potently inhibit and protect against MERS-CoV
Authors: Ragotte Robert J. , Alejandra Tortorici M. , Catanzaro Nicholas J. , Addetia Amin , Coventry Brian , Froggatt Heather M. , Lee Jimin , Stewart Cameron , Brown Jack T. , Goreshnik Inna , Sims Jeremiah N. , Milles Lukas F. , Wicky Basile I.M. , Glögl Matthias , Gerben Stacey , Kang Alex , Bera Asim K. , Sharkey William , Schäfer Alexandra , Baric Ralph S. , Baker David , Veesler David
Published: November 2024

Middle-East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen with 36% case-fatality rate in humans. No vaccines or specific therapeutics are currently approved to use in humans or the camel host reservoir. Here, we computationally designed monomeric and homo-oligomeric miniproteins binding with high affinity to the MERS-CoV spike (S) glycoprotein, the main target of neutralizing antibodies and vaccine development. We show that these miniproteins broadly neutralize a panel of MERS-CoV S variants, spanning the known antigenic diversity of this pathogen, by targeting a conserved site in the receptor-binding domain (RBD). The miniproteins directly compete with binding of the DPP4 receptor to MERS-CoV S, thereby blocking viral attachment to the host entry receptor and subsequent membrane fusion. Intranasal administration of a lead miniprotein provides prophylactic protection against stringent MERS-CoV challenge in mice motivating future clinical development as a next-generation countermeasure against this virus with pandemic potential.
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

The 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

COVID-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

Chemokine 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

Abnormal 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.
Development and validation of a near-comprehensive RxNorm valueset of opioid medications
Authors: Wasz Michael , Shankar Prabhu RV , Sprouse Elizabeth , Kirchner Lyndsey , Garber Matthew H. , Jones James , Mandl Kenneth D. , McMurry Andy
Published: November 2024

Objective

Develop a near-comprehensive opioid medications valueset for population measures of opioid related treatments and outcomes. The opioid valueset should be free, open source, and conform to the RxNorm standard federally mandated in every US-certified electronic health record.

Materials and Methods

Cumulus opioid valueset was manually curated by the authors and expanded using computer assisted curation. Opioid classifier rules were developed to select opioid RxNorm concepts with known opioid receptor interactions, ingredients, keywords, and drug product formulations. Twelve publicly available valuesets were used to develop and validate the Cumulus opioid valueset. Validation accuracy was measured against a corpus of opioid medication orders and non-opioid pain relievers.

Results

Cumulus opioid valueset recall was >99.9% when measured against opioid prescription RxNorm codes from UC Davis Health and Brigham and Women’s Hospital. Cumulus opioid valueset was 100% specific compared to three valuesets of non-opioid pain relievers.

Discussion and Conclusion

To the authors’ knowledge, Cumulus opioid valueset is the largest publicly available valueset of opioid medications (8,926 RxNorm concepts). The intended use of this opioid valueset is for population health measures of opioid medications and related patient outcomes.
Reduction of arrival time jitter or energy spread with arclike variable bunch compressors
Authors: Dixon Adam , Williams Peter , Thorin Sara , Charles Tessa , Wolski Andrzej
Published: November 2024

Synchronizing free-electron laser pulses for time-resolved experiments is necessary as an unsynchronized system reduces the effective repetition rate of the experiment. Additionally, free-electron laser longitudinal coherence and spectral brightness are limited by electron beam energy spread. In this paper, a variable bunch compressor design and compression schemes were developed to: reduce klystron-induced arrival time jitter by 85% while preserving peak current and transverse emittance and to minimize electron beam correlated energy spread for potential self-seeding or HB-SASE modes.

Published by the American Physical Society
2024
Manifestation of
a1(1260)
meson in the process
e+e−→π+π−π0
Authors: Obraztsov I. V. , Rudenko A. S. , Milstein A. I.
Published: November 2024

The charge asymmetry in the process e+e−→π+π−π0 is studied taking into account a longitudinal polarization of electrons (positrons). The asymmetry arises due to interference of amplitudes corresponding to production of pions in states with charge parity odd and charge parity even. It is a manifestation of a1(1260) meson in the intermediate state. Polarization leads to additional correlations in the differential cross section, which simplifies the experimental study of the process. It is shown that the charge asymmetry can reach several percent.

Published by the American Physical Society
2024
Interpretation of recently discovered single bottom baryons in the relativistic flux tube model
Authors: Jakhad Pooja , Oudichhya Juhi , Rai Ajay Kumar
Published: November 2024

Following recent experimental progress in the study of bottom baryons, we systematically calculate the mass spectra of Λb, Ξb, Σb, Ξb′, and Ωb baryons with a quark-diquark picture in the framework of a relativistic flux tube model with spin-dependent interactions in the j-j coupling scheme. Furthermore, we calculate the strong decay width of bottom baryons decaying into a bottom baryon and a light pseudoscalar meson. Good agreement is found between the calculated masses and the experimentally available masses of singly bottom baryons. By analyzing both mass spectra and strong decay widths, we interpret

Σ

b

(

6097

)

as a 1P(3/2−) state and Ξb(6100) as a 1P(1/2−) state of the Ξb baryon. The Ξb(6227) is identified to be an orbital excitation 1P of the Ξb′ baryon with JP=3/2−. Further, we determine Ξb(6327) and Ξb(6333) as a 1P(3/2−) state and 1P(5/2−) state, respectively, of Ξb′ baryon. From the obtained mass spectra, we construct the Regge trajectories in the (J,M2) plane, which are found to be essentially linear, parallel, and equidistant. Our predictions for higher orbital and radial excited states can help experimentalists identify missing excited states of singly bottom baryons.

Published by the American Physical Society
2024
Effective Kähler and auxiliary field potentials for chiral superfield models at three loops
Authors: Martin Stephen P.
Published: November 2024

I obtain the effective Kähler potential at three-loop order for a general renormalizable supersymmetric theory containing only chiral supermultiplets. The three-loop contribution is remarkably simple, consisting of only four terms involving three distinct renormalized master integrals. In the case of the Wess-Zumino model with a single chiral superfield, I also obtain the effective auxiliary field potential at three-loop order, extending previous results at one-loop order. The method used is inferential, relying on existing knowledge of the ordinary scalar effective potential.

Published by the American Physical Society
2024
Current-vortex-sheet model of the magnetic Rayleigh-Taylor instability
Authors: Baek Seunghyeon , Sohn Sung-Ik
Published: November 2024

This study investigates the Rayleigh-Taylor instability in the magnetic field applied parallel to the interface. The motion of the interface is described using a current-vortex-sheet model. The growth rate of the interface is obtained from a linear stability analysis of the model. The interface of a single mode k=1 is linearly stable for RA≤1, where RA denotes the Alfvén number. Further, we conduct numerical computations for the evolution of the interface from the model for both regimes of RA≤1 and RA>1. For RA≤1, the interface oscillates vertically but does not intrude into the opposite phase. The amplitude of the interface and the oscillation period decrease with decrease in RA. For 1<RA≲1.5, the interface undergoes some growth at early times and then decreases. This oscillation is repeated, and no roll-ups are observed at the interface. Therefore, the nonlinear growth of the Rayleigh-Taylor instability is stabilized by a sufficiently strong magnetic field. For RA≳3 the interface is unstable and the pattern of the interface evolution differs from the density ratio. In addition, the magnetic field is greatly amplified as RA increases.

Published by the American Physical Society
2024
Optical ionization effects in kHz laser wakefield acceleration with few-cycle pulses
Authors: Monzac J. , Smartsev S. , Huijts J. , Rovige L. , Andriyash I. A. , Vernier A. , Tomkus V. , Girdauskas V. , Raciukaitis G. , Mackevičiūtė M. , Stankevic V. , Cavagna A. , Kaur J. , Kalouguine A. , Lopez-Martens R. , Faure J.
Published: November 2024

We present significant advances in laser wakefield acceleration (LWFA) operating at a 1 kHz repetition rate, employing a sub-TW, few-femtosecond laser and a continuously flowing hydrogen gas target. We conducted a comprehensive study assessing how the nature of the gas within the target influences accelerator performance. This work confirms and elucidates the superior performance of hydrogen in LWFA driven by few-cycle, low-energy laser pulses. Our system generates quasimonoenergetic electron bunches with energies up to 10 MeV, bunch charges of 2 pC, and angular divergences of 15 mrad. Notably, our scheme relying on differential pumping enables continuous operation at kHz repetition rates, contrasting with previous systems that operated in burst mode to achieve similar beam properties. Particle-in-cell simulations explain hydrogen's superior performances: the ionization effects in nitrogen and helium distort the laser pulse, negatively impacting the accelerator performance. These effects are strongly mitigated in hydrogen plasma, thereby enhancing beam quality. This analysis represents a significant step forward in optimizing and understanding kHz LWFA. It underscores the critical role of hydrogen and the imperative need to develop hydrogen-compatible target systems capable of managing high repetition rates, as exemplified by our differential pumping system. These advances lay the groundwork for further developments in high-repetition-rate laser plasma accelerator technology.

Published by the American Physical Society
2024
Run-and-tumble motion of ellipsoidal microswimmers
Authors: Anchutkin Gordei , Cichos Frank , Holubec Viktor
Published: November 2024

A hallmark of bacteria is their so-called “run-and-tumble” motion and its variants, consisting of a sequence of linear directed “runs” and distinct rotation events that constantly alternate due to biochemical feedback. It plays a crucial role in the ability of bacteria to move through chemical gradients and has inspired a fundamental active particle model. Nevertheless, synthetic active particles generally do not exhibit run-and-tumble motion but rather active Brownian motion. We show in experiments that ellipsoidal thermophoretic Janus particles, propelling along their short axis, can yield run-and-reverse motion, i.e., where rotation events flip the direction of motion, even without feedback. Their hydrodynamic wall interactions under strong confinement give rise to an effective double-well potential for the declination of the short axis. The geometry-induced timescale separation of the in-plane rotational dynamics and noise-induced transitions in the potential then yield run-and-reverse motion.

Published by the American Physical Society
2024