bluuebunny/crossref_metadata_2025_split huggingface dataset:
Control of myopia using diffusion optics spectacle lenses: 4-year results of a multicentre randomised controlled, efficacy and safety study (CYPRESS)
Authors: Laughton Deborah , Hill Jennifer S , McParland Marcella , Tasso Vanessa , Woods Jill , Zhu Xiaoying , Young Graeme , Craven Ruth , Hunt Chris , Neitz Jay , Neitz Maureen , Chalberg Thomas W , Jones Deborah , Wolffsohn James S 
Published: October 2024

AimsTo evaluate the myopia control efficacy of Diffusion Optics Technology (DOT) spectacle lenses in children over a 4-year treatment period.MethodsCYPRESS Part 1 (NCT03623074) was a 3-year multicentre, randomised, controlled, double-masked trial comparing two investigational spectacle lens DOT designs (Test 1, Test 2) and standard single vision Control lenses in 256 North American children aged 6–10 years. Children completing Part 1 (n=200) were invited to enrol in CYPRESS Part 2 (NCT04947735) for an additional 1-year period. In Part 2, Test 1 (n=35) and Control groups (n=42) continued with their original lens assignment and the Test 2 group (n=21) were crossed over to Test 1 (DOT 0.2) lenses. The co-primary endpoints were change from baseline in axial length (AL) and cycloplegic spherical equivalent refraction (cSER).ResultsTest 1 spectacle lenses demonstrated superiority to the Control in both co-primary endpoints: with a difference between means (Test 1−Control) of −0.13 mm for AL (p=0.018) and 0.33 D for cSER (p=0.008) in Part 1 and −0.05 mm for AL (p=0.038) and 0.13 D for cSER (p=0.043) in Part 2. Comparing treatment effects in Part 1 and 2 suggests that COVID-19 public health restrictions negatively impacted treatment efficacy in study years 2 and 3.ConclusionDOT 0.2 spectacle lenses are safe and effective at reducing myopia progression, with additional benefit evident in year 4 of wear. These results support the hypothesis that a mild reduction in retinal contrast can slow myopia progression in young children. The unprecedented disruption in participant schooling and lifestyle during the COVID-19 pandemic may have depressed treatment efficacy in Part 1.
Impact of the asylum determination process on mental health in the UK and EU+: a systematic review and thematic synthesis
Authors: Mulcaire Jessie , Smetham Dom , Holt Leah , Zard Sana , Brady Francesca , O'Driscoll Ciarán 
Published: October 2024

IntroductionPeople seeking asylum are at increased risk of mental health difficulties due to premigration and postmigration experiences. The objective of this review was to understand how asylum determination process in the EU+ and UK influences the mental health of asylum seekers.MethodsWeb of Science, MEDLINE, PsycINFO, PsychArticles and Scopus were searched, with no start date specified, up to 24 August 2023. Peer-reviewed studies were eligible if they provided a qualitative analysis of primary data from adult asylum seekers and refugees regarding lived experience of asylum determination procedures in the UK and EU+, and contextual factors associated with the mental health and well-being. The protocol was not preregistered. From a total of 4902 articles, duplicates were removed, 3235 abstracts were assessed and of the remaining 113 identified for full-screen articles, 39 relevant qualitative studies were retrieved. Six further studies were identified through citation searches.Results45 studies were included in the qualitative thematic synthesis, representing the perspectives of 1158 asylum seekers and refugees. Themes demonstrate high levels of psychological distress during and after the asylum process. This was associated with the hostile environments created by policies and procedures. Participants’ mental health was affected by being caught in a stalemate while awaiting the outcome of their claim. The procedures exacerbated previous mental health difficulties. External and internal protective factors were identified, such as non-governmental organisations, religion and cognitive strategies.ConclusionsThe accumulation of each step of the asylum process contributes to psychological distress and exacerbates mental health difficulties, leading to longer-term consequences for asylum seekers and refugees. Preventive strategies and policy changes are recommended. To minimise the impact of asylum procedures, clinicians should consider peer-led groups, interventions that cultivate a sense of autonomy and meaning and reduce a sense of alienation and isolation.
County-level racial bias is associated with worse care for white and especially black older US adults: a cross-sectional observational study
Authors: Mizel Matthew L , Haas Ann , Adams John L , Martino Steven C , Haviland Amelia M , Ghosh-Dastidar Bonnie , Dembosky Jacob W , Williams Malcolm , Abel Gary , Maksut Jessica , Gildner Jennifer , Elliott Marc N 
Published: October 2024

ObjectiveTo assess the association of county-level bias about black and white people with patient experience, influenza immunisation, and quality of clinical care for black and white older US adults (age 65+ years).DesignLinear multivariable regression measured the cross-sectional association of county-level estimates of implicit and explicit bias about black and white people with patient experiences, influenza immunisation, and clinical quality-of-care for black and white older US adults.ParticipantsWe used data from 1.9 million white adults who completed implicit and explicit bias measures during 2003–2018, patient experience and influenza immunisation data from respondents to the 2009–2017 Medicare Consumer Assessment of Healthcare Providers and Systems (MCAHPS) Surveys, and clinical quality-of-care data from patients whose records were included in 2009–2017 Healthcare Effectiveness Data and Information Set (HEDIS) submissions (n=0.8–2.9 million per measure).Main outcome measuresThree patient experience measures and patient-reported influenza immunisation from the MCAHPS Survey; five HEDIS measures.ResultsIn county-level models, higher pro-white implicit bias was associated with lower immunisation rates and worse scores for some patient experience measures for black and white adults as well as larger-magnitude black-white disparities. Higher pro-white implicit bias was associated with worse scores for some HEDIS measures for black and white adults but not with black-white disparities in clinical quality of care. Most significant associations were small in magnitude (effect sizes of 0.2–0.3 or less).ConclusionsTo the extent that county-level pro-white implicit bias is indicative of bias among healthcare providers, there may be a need for interventions designed to prevent such bias from adversely affecting the experiences and preventive care of black patients and the clinical quality of care for all patients.
Factors associated with failure of intraosseous access in prehospital trauma treatment by military medical personnel
Authors: Rittblat Mor , Kotovich D , Tsur N , Beer Z , Radomislensky I , Gendler S , Almog O , Tsur A M , Avital G , Talmy T 
Published: October 2024

IntroductionIntraosseous devices have become an alternative to peripheral intravenous (PIV) access. Despite the established success of intraosseous devices in laboratory and simulator studies, there is a lack of data regarding their real-world utilisation in prehospital settings. Therefore, this study aims to evaluate the success rates of intraosseous access in a prehospital military context and identify factors associated with failure.MethodsUsing the Israel Defense Forces (IDF) Trauma Registry, we retrospectively collected data from 2010 to 2023. The primary outcome was the first pass success rate of intraosseous access, and logistic regression models were applied to identify variables associated with first pass failure.ResultsThe study included 172 trauma patients who underwent attempted intraosseous access with 46.5% cases which were classified as military events. The median age was 22 years, and 17.3% were paediatric patients. First pass success was achieved in 67.4% of cases, with a cumulative success rate of 80.8% after multiple attempts. Moreover, significant differences were noted when examining the success rate of the three intraosseous devices used by the IDF teams, with the highest success rate being documented for the NIO Adult versus the EZ-IO or the BIG (81.4%; 76.7%; 62.4%). However, logistic regression analysis revealed that the number of PIV access attempts was the only variable significantly associated with decreased odds of achieving first pass intraosseous access.ConclusionThese findings suggest that intraosseous devices are a viable alternative for establishing vascular access in prehospital military settings. However, success rates were slightly lower than previous reports, potentially due to the severity of injuries in the study cohort. Our analyses revealed a higher number of PIV access attempts correlated with reduced first pass intraosseous success, possibly stemming from caregiver proficiency in obtaining vascular access. Further research is needed to explore additional factors affecting intraosseous access success rates.
Cardiovascular risk according to genetic predisposition to gout, lifestyle and metabolic health across prospective European and Korean cohorts
Authors: Moon Ki Won , Jung Sang‑Hyuk , Do Hyunsue , Son Chang-Nam , Kim Jaeyoung , Nam Yonghyun , Yun Jae-Seung , Park Woong-Yang , Won Hong-Hee , Kim Dokyoon 
Published: October 2024

ObjectiveRecent studies have reported that gout is associated with a risk of cardiovascular disease (CVD) later in life. However, the predictive value of genetic predisposition to gout combined with lifestyle habits for CVD risk remains unclear. This study aimed to examine the association between genetic predisposition to gout and lifestyle habits and the risk of developing CVD in two diverse prospective cohorts from different ancestries.MethodsA total of 224 689 participants of European descent from the UK Biobank and 50 364 participants of East Asian descent from the Korean Genome and Epidemiology Study were included. The genetic risk for gout was assessed using a polygenic risk score (PRS) derived from a meta-genome-wide association study (n=444 533). The incident CVD risk was evaluated according to genetic risk, lifestyle and metabolic syndrome (MetS).ResultsIndividuals at high genetic risk for gout had a higher risk of incident CVD than those with low genetic risk across ancestry. Notably, a reduction in CVD risk by up to 62% (HR 0.38; 95% CI 0.31 to 0.46; p <0.001) was observed in individuals at both low and high genetic risk for gout when they maintained ideal MetS and favourable lifestyle habits.ConclusionsOur findings indicate that a higher genetic risk of gout is significantly associated with an increased risk of CVD. Moreover, adherence to a favourable lifestyle can significantly reduce CVD risk, particularly in individuals with high genetic risk. These results underscore the potential of PRS-based risk assessment to improve clinical outcomes through tailored preventative strategies.
Testing and results of an open-source radiation epidemiology model using the Goiânia accident
Authors: Quaranta Riccardo , Ludovici Gian Marco , Romano Luca , Manenti Guglielmo , Malizia Andrea 
Published: October 2024

AbstractIn the event of dispersed radioactive materials, whether from accidental orphan sources or deliberate use of radiological dispersal devices (RDD) or radiological exposure devices (RED), free open-source modelling codes can greatly assist in forecasting the dispersion of the radiation following the event. Several codes are currently available to quickly calculate the progression of radiological dispersion. However, most of these codes can only simulate the evolution of the threat for limited times after the event and over relatively short distances from the location. In order to predict the transport of radioactive material over long distances and for long times, and thus prevent its expected effects on the exposed population, specific epidemiological codes can be used, taking into account the characteristic of the radiation. If it is considered that radioactive material can be deposited on unsuspecting people who continue their daily activities after exposure, it can be assumed that these people unintentionally carry this radioactive material over long distances. This scenario is comparable to viral vectors of a hypothetical virus designed to mimic the physical characteristics of radiation. In this work, the free open-source spatio-temporal epidemiological modeller (STEM) tool is used to simulate the spread of a chimeric viral agent with specific characteristics of Ebola and COVID-19, designed to replicate the biological conditions caused by exposure to a Cs-137 source for an individual unaware of the risk. The goal is to predict the territorial spread of radioactive material caused by a CBRNe event, such as orphan sources or the use of a RDD or a RED, and its possible effects on the affected population. This supports decision-makers in forecasting the consequences of radioactive material spread and thus helps in reducing the risk. The code was tested comparing its results with the real case of the famous 1987 Goiânia radiological accident. The results show that the developed code was indeed able to accurately represent the number of contaminated individuals and the number of casualties within a month of the initial exposure, with a distribution of radioactive material in the territory similar to that actually caused by the Goiânia accident.
Loss of PI5P4Kα Slows the Progression of a Pten Mutant Basal Cell Model of Prostate Cancer
Authors: Triscott Joanna , Lehner Marika , Benjak Andrej , Reist Matthias , Emerling Brooke M. , Ng Charlotte K.Y. , de Brot Simone , Rubin Mark A. 
Published: October 2024

Abstract
Although early prostate cancer depends on the androgen receptor signaling pathway, which is predominant in luminal cells, there is much to be understood about the contribution of epithelial basal cells in cancer progression. Herein, we observe cell type–specific differences in the importance of the metabolic enzyme phosphatidylinositol 5-phosphate 4-kinase alpha (PI5P4Kα; gene name PIP4K2A) in the prostate epithelium. We report the development of a basal cell–specific genetically engineered mouse model targeting Pip4k2a alone or in combination with the tumor suppressor phosphatase and tensin homolog (Pten). PI5P4Kα is enriched in basal cells, and no major histopathologic changes were detectable following gene deletion. Notably, the combined loss of Pip4k2a slowed the development of Pten mutant mouse prostatic intraepithelial neoplasia. Through the inclusion of a lineage tracing reporter, we utilize single-cell RNA sequencing to evaluate changes resulting from in vivo downregulation of Pip4k2a and characterize cell populations influenced in the established Probasin-Cre– and cytokeratin 5-Cre–driven genetically engineered mouse model. Transcriptomic pathway analysis points toward the disruption of lipid metabolism as a mechanism for reduced tumor progression. This was functionally supported by shifts of carnitine lipids in LNCaP prostate cancer cells treated with siPIP4K2A. Overall, these data nominate PI5P4Kα as a target for PTEN mutant prostate cancer.
Implications: PI5P4Kα is enriched in prostate basal cells, and its targeted loss slows the progression of a model of advanced prostate cancer.
Abstract Mo007: Molecular Basis of Sepsis-Induced Cardiomyopathy Under Anthracycline Treatment: Insights from Mouse Model
Authors: Markandran Kasturi , Wang Rina , Lim Yi Peng , Chen Ching Kit 
Published: October 2024

Anthracyclines constitute a fundamental component in numerous paediatric chemotherapy regimens. However, its myelosuppressive & cardiotoxic nature put patients at risk of sepsis and sepsis-induced cardiomyopathy (SIC). When anthracycline-treated patients develop SIC, successful treatment of sepsis is sufficient for the restoration of cardiac function, giving rise to the 'transient cardiac dysfunction' phenomenon. Although transient it poses compromised clinical outcomes & the mechanism driving this phenomenon remains elusive.
We hypothesise that the molecular regulators of the phenomenon lie within cardiac cell populations & is controlled by transcriptional activation. Thus, we aim to model 'transient cardiac dysfunction' in mice and conduct transcriptomics on their heart tissues.
‘Transient cardiac dysfunction’ was modelled in male juvenile C57BL6 mice treated with a cumulative of 10mg/kg doxorubicin followed by sepsis induction via cecal ligation & perforation (CLP) to induce SIC. To recapitulate ‘transient cardiac dysfunction’, antibiotics were administered 20h post-CLP to treat sepsis & restore cardiac function. Controls against doxorubicin (saline treatment) was established. Echocardiography and biological sample curation were conducted at pre-SIC (before CLP), onset-SIC (10h post-CLP) & post-SIC (60h post-CLP).
Sepsis was verified based on procalcitonin fold change as compared to pre-SIC (n=3-6). Procalcitonin was 15±1.6 folds higher in dox- (n=3) & 10±0.39 folds higher in saline-treated (n=3) mice at onset-SIC. The infection was more aggressive in dox-treated mice as procalcitonin remained elevated at post-SIC (17.1±2.0, n=4), whereas in saline-treated mice, procalcitonin was reduced by post-SIC (7.9±1.0, n=3). In saline-treated mice, LVEF(%) was reduced at onset-SIC (49.0%±3.0, n=7) from pre-SIC (58.1±1.1, n=7) and recovered to baseline by post-SIC (61.8±1.7, n=5). In the contrary, LVEF in dox-treated mice (n=7) was increased at onset-SIC (62.5±1.7) from pre-SIC (56.0±0.8) & sustained till post-SIC (60.1±1.0), suggesting cardioprotection. Normal distribution was verified before statistical hypothesis testing.
In conclusion, ‘transient cardiac dysfunction’ was modelled in saline-treated mice, & novel cardio protective effect was observed in dox-treated mice. Moving forward, longitudinal snRNA-seq will be conducted on whole hearts to identify cardiac cell populations & genes responsible for ‘transient cardiac dysfunction’ & cardioprotection.
Abstract Mo012: Optimizing Mouse Models of Doxorubicin Cardiomyopathy
Authors: Curtin Casie , Liu Jing , Basu Sandeep , Weitzman Benjamin , Wieke Jakob , Asnani Aarti 
Published: October 2024

Introduction:
Anthracyclines such as doxorubicin (Dox) are effective chemotherapies that treat various cancers, including breast, lymphoma, and leukemia. While effective, their use is limited due to cardiac toxicity, leading to cardiomyopathy and heart failure.

Background:
Several Dox treatment regimens in mice have been reported in the literature, from acute high-dose models to chronic low-dose models. Many of these regimens cause fulminant cardiomyocyte apoptosis and heart failure within days, and they do not accurately recapitulate the human toxicity phenotype.

Objective:
Our goal was to identify a Dox dosing regimen in mice that causes the most consistent subacute/chronic cardiomyopathy, as seen in patients, with the least systemic toxicity.

Methods:
We administered four different Dox dosing regimens to C57BL/6N female and male mice, based on published protocols and our laboratory’s prior studies (
Fig. 1
):

#1: Dox 3mg/kg intraperitoneally (IP) every other day for two weeks (cumulative dose of 24mg/kg) or saline
#2: Dox 5mg/kg IP twice a week for two and a half weeks (cumulative dose of 25mg/kg) or saline
#3: Dox 5mg/kg IP once a week for five weeks (cumulative dose of 25mg/kg) or saline
#4: Dox 5mg/kg intravenously (IV) once a week for four weeks (cumulative dose of 20mg/kg) or saline
Cardiac function was assessed after five to seven weeks by echocardiography, prior to sacrifice. Hearts and blood were isolated for molecular analyses. Regimens were compared using a one-way ANOVA and multiple comparisons analysis.

Results:
Protocol #3 (Dox 5mg/kg IP once a week for five weeks; cumulative dose of 25mg/kg) demonstrated the most consistent difference in fractional shortening between male mice treated with saline compared to those treated with Dox, as assessed by echocardiography (
Fig. 2
). This protocol resulted in the lowest mortality, as well as the least amount of systemic toxicity (
Fig. 3
). Protocol #1 (Dox 3mg/kg IP every other day for two weeks; cumulative dose of 24mg/kg) was the only protocol that elicited a decline in fractional shortening in female mice treated with Dox compared to those treated with saline, as assessed by echocardiography.

Conclusion:
Going forward, protocol #3 (5mg/kg IP once a week for five weeks) will be implemented as the standard dosing regimen in our laboratory. Ensuring consistency in cardiac phenotypes will allow us to better understand the effects of modulating cardioprotective pathways on the development of Dox cardiac toxicity.
Abstract Mo021: Role of Estrogen and Testosterone in promoting Sex Dimorphism in Doxorubicin Cardiotoxicity.
Authors: Trampel Katy , De Melo Amaral Paloma , Efimov Igor , George Sharon Ann 
Published: October 2024

Background:
Doxorubicin (DOX), a cancer chemotherapeutic agent, causes sex-specific cardiotoxicity. Lower cardiotoxicity in females compared to males is typically attributed to the cardioprotective effects of estrogen (E2). However, the role of the sex hormones, E2 and testosterone (T), in modulating DOX induced cardiac dysfunction and its underlying mechanisms are not known.

Methods:
C57BL/6J mice were divided into four groups, 1) Control, 2) DOX (5 mg/kg/week for 6 weeks), 3) Reverse hormone profile (RevH, castrated males+E2 and ovariectomized females+T), and 4) RevH + DOX. Mouse morbidity was tracked daily. Total body weight and cardiac function was assessed biweekly for 6 weeks by echocardiography, ECG and optical mapping. Dependence on fatty acid versus glucose for metabolism was measured by seahorse analysis.

Results:
DOX treatment reduced total body weight (11%) in males, and increased morbidity in males and females. This was associated with reduced mechanical function (15% decrease in stroke volume) in males and electrical remodeling (29% action potential duration prolongation) in females.

In RevH mice, no changes in morbidity or cardiac function were observed compared to Control.
In RevH+DOX males, the onset of morbidity was delayed by two weeks compared to DOX males. This cardioprotective effect was associated with preserved mechanical and electrical function. On the other hand, in RevH+DOX females, morbidity was increased, and this correlated with mechanical (20% reduction in cardiac output) and electrical remodeling (22% increase in action potential duration). Comparing RevH+DOX males to females, males had greater fatty acid dependency while females had greater glucose dependency for metabolism.

Conclusions:
These results suggest that sex hormones play a significant role in modulating specific aspects of DOX cardiotoxicity. While E2 has a critical role in preserving cardiac mechanics during DOX therapy, high T levels were associated with mechanical dysfunction in both males and RevH females. Switching of metabolic substrates with greater preference for fatty acid metabolism in mice with higher E2 could underlie cardiac mechanics preservation. Finally, DOX induced electrical remodeling was not altered by sex hormones.