bluuebunny/crossref_metadata_2025_split huggingface dataset:
“What will the doctor give me, the same painkiller?”: a qualitative study exploring health-care seeking and symptoms self-management among patients for the treatment of long-term chikungunya disease, in Curaçao
Authors: Doran Churnalisa , Duits Ashley , Gerstenbluth Izzy , Tami Adriana , Bailey Ajay 
Published: November 2023

Abstract
Background
Long-term chikungunya disease, characterized by persistent disabling rheumatic symptoms, including poly-arthralgia/arthritis of severe pain intensity, can persist for years after infection with the re-emerging mosquito-borne chikungunya virus. Although persistent symptoms and pain severity are important determinants of health-care seeking and self-management of symptoms, research on these in relation to long-term chikungunya disease is scarce. This study aimed to explore the perceived benefits and perceived barriers concerning health-care seeking, based on the Health Belief Model, and the symptoms self-management strategies used for health outcome improvement among individuals affected by long-term chikungunya disease.

Methods
An exploratory qualitative descriptive study was conducted with 20 purposively selected adults (17 females and 3 males) with persistent rheumatic symptoms, recruited from an ongoing longitudinal chikungunya cohort, in Curaçao. Semi-structured interviews were carried out, audio-recorded, and transcribed. An iterative coding process was used for themes identification through inductive thematic analyses.

Results
No perceived benefits in health-care seeking were reported. Identified themes in relation to perceived barriers were: (1) health-care seeking at disease onset; (2) general practitioners (GPs) perceptions and awareness of persistent symptoms; (3) challenges for medical referrals and support; (4) no validation of symptoms and challenges accessing therapy; (5) health system restrictions; and (6) social stigmatization of psychological help. These perceived barriers have led participants to self-manage persistent symptoms. Over-the-counter pharmacological and/or non-pharmacological treatments were used without consulting GPs. Identified themes were: (1) self-medication of symptoms; and (2) self-management true non-pharmacological treatments.

Conclusions
To promote the benefits of long-term health-care seeking and subsequently reduce the possible harmful use of analgesics, a collaborative physician-patient therapeutic relationship need to be encouraged. To facilitate this, important shifts may be needed in chikungunya sequalae education of both patients and health-care professionals, and policy makers need to revise health systems for the long-term provision of multidisciplinary care to achieve beneficial health outcomes in long-term chikungunya disease.
Gene birth in a model of non-genic adaptation
Authors: Mani Somya , Tlusty Tsvi 
Published: November 2023

Abstract
Background
Over evolutionary timescales, genomic loci can switch between functional and non-functional states through processes such as pseudogenization and de novo gene birth. Particularly, de novo gene birth is a widespread process, and many examples continue to be discovered across diverse evolutionary lineages. However, the general mechanisms that lead to functionalization are poorly understood, and estimated rates of de novo gene birth remain contentious. Here, we address this problem within a model that takes into account mutations and structural variation, allowing us to estimate the likelihood of emergence of new functions at non-functional loci.

Results
Assuming biologically reasonable mutation rates and mutational effects, we find that functionalization of non-genic loci requires the realization of strict conditions. This is in line with the observation that most de novo genes are localized to the vicinity of established genes. Our model also provides an explanation for the empirical observation that emerging proto-genes are often lost despite showing signs of adaptation.

Conclusions
Our work elucidates the properties of non-genic loci that make them fertile for adaptation, and our results offer mechanistic insights into the process of de novo gene birth.
Trends in the ability of socioeconomic position to predict individual body mass index: an analysis of repeated cross-sectional data, 1991–2019
Authors: Wright Liam , Staatz Charis Bridger , Silverwood Richard J. , Bann David 
Published: November 2023

Abstract
Background
The widening of group-level socioeconomic differences in body mass index (BMI) has received considerable research attention. However, the predictive power of socioeconomic position (SEP) indicators at the individual level remains uncertain, as does the potential temporal variation in their predictive value. Examining this is important given the increasing incorporation of SEP indicators into predictive algorithms and calls to reduce social inequality to tackle the obesity epidemic. We thus investigated SEP differences in BMI over three decades of the obesity epidemic in England, comparing population-wide (SEP group differences in mean BMI) and individual-level (out-of-sample prediction of individuals’ BMI) approaches to understanding social inequalities.

Methods
We used repeated cross-sectional data from the Health Survey for England, 1991–2019. BMI (kg/m2) was measured objectively, and SEP was measured via educational attainment, occupational class, and neighbourhood index of deprivation. We ran random forest models for each survey year and measure of SEP adjusting for age and sex.

Results
The mean and variance of BMI increased within each SEP group over the study period. Mean differences in BMI by SEP group also increased: differences between lowest and highest education groups were 1.0 kg/m2 (0.4, 1.6) in 1991 and 1.3 kg/m2 (0.7, 1.8) in 2019. At the individual level, the predictive capacity of SEP was low, though increased in later years: including education in models improved predictive accuracy (mean absolute error) by 0.14% (− 0.9, 1.08) in 1991 and 1.05% (0.18, 1.82) in 2019. Similar patterns were obtained for occupational class and neighbourhood deprivation and when analysing obesity as an outcome.

Conclusions
SEP has become increasingly important at the population (group difference) and individual (prediction) levels. However, predictive ability remains low, suggesting limited utility of including SEP in prediction algorithms. Assuming links are causal, abolishing SEP differences in BMI could have a large effect on population health but would neither reverse the obesity epidemic nor reduce much of the variation in BMI.
Periodontitis and systemic inflammation as independent and interacting risk factors for mortality: evidence from a prospective cohort study
Authors: Pink Christiane , Holtfreter Birte , Völzke Henry , Nauck Matthias , Dörr Marcus , Kocher Thomas 
Published: November 2023

Abstract

Background
Recent studies have highlighted the role of low-grade systemic inflammation in linking periodontitis to cardiovascular disease (CVD) outcomes, but many aspects remain unclear. This study examines the independent and reciprocal associations of periodontitis and low-grade systemic inflammation with all-cause and CVD mortality in a large-scale cohort.

Methods
A total of 3047 participants from the prospective, population-based Study of Health in Pomerania (SHIP-START) were followed for a period of 13.0 ± 2.4 years. For the association between various inflammation/periodontitis measures and mortality, hazard ratios (HRs) were obtained from covariate-adjusted Cox proportional hazards models. Interactions were analysed in joint models: on the multiplicative scale, HRs were reported and on the additive scale, relative excess risks due to interaction (RERI) were calculated. Subject and variable-specific interval records were used to account for time-varying exposures and covariates.

Results
During the observation period, 380 (12.5%) individuals died from CVD (n = 125) or other causes (n = 255). All markers of periodontitis and inflammation showed apparent associations with all-cause mortality (HRs per SD-increase: mean PPD: 1.068 (95% confidence interval (CI): 0.988–1.155), mean CAL: 1.205 (95% CI: 1.097–1.323), missing teeth: 1.180 (95% CI: 1.065–1.307), periodontitis score: 1.394 (95% CI: 1.202–1.616), leukocytes: 1.264 (95% CI: 1.163–1.374), fibrinogen: 1.120 (95% CI: 1.030–1.218), CRP: 1.231 (95% CI: 1.109–1.366), inflammation score: 1.358 (95% CI: 1.210–1.523)). For CVD mortality, all PPD related variables showed significant associations. Interaction modelling revealed some variation with respect to mortality type and exposure combinations. On the additive scale, RERIs for periodontitis score and inflammation score implied 18.9% and 27.8% excess mortality risk for all-cause and CVD mortality, respectively. On the multiplicative scale, the HRs for interaction were marginal.

Conclusions
Both periodontitis and inflammation were significantly associated with all-cause mortality and CVD mortality. On the additive scale, a substantial excess risk was observed due to the interaction of periodontitis and inflammation, suggesting that the greatest treatment benefit may be achieved in patients with both periodontitis and high systemic inflammation. As periodontal therapy has been reported to also reduce systemic inflammation, the possibility of a reduction in CVD mortality risk by anti-inflammatory treatments, including periodontal interventions, seems worthy of further investigation.
Advancing the communication of genetic risk for cardiometabolic diseases: a critical interpretive synthesis
Authors: Law Jing Hui , Sultan Najia , Finer Sarah , Fudge Nina 
Published: November 2023

Abstract
Background
Genetics play an important role in risk for cardiometabolic diseases—including type 2 diabetes, cardiovascular disease and obesity. Existing research has explored the clinical utility of genetic risk tools such as polygenic risk scores—and whether interventions communicating genetic risk information using these tools can impact on individuals’ cognitive appraisals of disease risk and/or preventative health behaviours. Previous systematic reviews suggest mixed results. To expand current understanding and address knowledge gaps, we undertook an interpretive, reflexive method of evidence synthesis—questioning the theoretical basis behind current interventions that communicate genetic risk information and exploring how the effects of genetic risk tools can be fully harnessed for cardiometabolic diseases.

Methods
We obtained 189 records from a combination of database, website and grey literature searches—supplemented with reference chaining and expert subject knowledge within the review team. Using pre-defined critical interpretive synthesis methods, quantitative and qualitative evidence was synthesised and critiqued alongside theoretical understanding from surrounding fields of behavioural and social sciences.

Findings
Existing interventions communicating genetic risk information focus predominantly on the “self”, targeting individual-level cognitive appraisals, such as perceived risk and perceived behavioural control. This approach risks neglecting the role of contextual factors and upstream determinants that can reinforce individuals’ interpretations of risk. It also assumes target populations to embody an “ascetic subject of compliance”—the idea of a patient who strives to comply diligently with professional medical advice, logically and rationally adopting any recommended lifestyle changes. We developed a synthesising argument—“beyond the ascetic subject of compliance”—grounded in three major limitations of this perspective: (1) difficulty applying existing theories/models to diverse populations, (2) the role of familial variables and (3) the need for a life course perspective.

Conclusions
Interventions communicating genetic risk information should account for wider influences that can affect individuals’ responses to risk at different levels—including through interactions with their family systems, socio-cultural environments and wider health provision.

Protocol registration
PROSPERO CRD42021289269
Inhibition of PKA/CREB1 pathway confers sensitivity to ferroptosis in non-small cell lung cancer
Authors: Shan Guangyao , Bi Guoshu , Zhao Guangyin , Liang Jiaqi , Bian Yunyi , Zhang Huan , Jin Xing , Hu Zhengyang , Yao Guangyu , Fan Hong , Zhan Cheng 
Published: November 2023

AbstractFerroptosis is a type of regulated cell death characterized by iron accumulation and lipid peroxidation. The molecular mechanisms underlying ferroptosis regulation in non-small cell lung cancer (NSCLC) are poorly understood. In this study, we found that protein kinase A (PKA) inhibition enhanced ferroptosis susceptibility in NSCLC cells, as evidenced by reduced cell viability and increased lipid peroxidation. We further identified cAMP-responsive element protein 1 (CREB1), a transcription factor and a substrate of PKA, as a key regulator of ferroptosis. Knockdown of CREB1 sensitized NSCLC cells to ferroptosis inducers (FINs) and abolished the effects of PKA inhibitor and agonist, revealing the pivotal role of CREB1 in ferroptosis regulation. Using a high-throughput screening approach and subsequent validation by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, we discovered that CREB1 transcriptionally activated stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the conversion of saturated fatty acids to monounsaturated fatty acids. SCD conferred ferroptosis resistance by decreasing the availability of polyunsaturated fatty acids for lipid peroxidation, and its overexpression rescued the effect of CREB1 knockdown on ferroptosis in vitro. Besides, CREB1 knockdown suppressed xenograft tumor growth in the presence of Imidazole Ketone Erastin (IKE), a potent FIN, and this effect was reversed by SCD. Finally, we showed that high expression of CREB1 was associated with poor prognosis in NSCLC patients from public datasets and our institution. Collectively, this study illustrates the effect of PKA/CREB1/SCD axis in regulating ferroptosis of NSCLC, targeting this pathway may provide new strategies for treating NSCLC patients.
Treatment with recombinant Sirt1 rewires the cardiac lipidome and rescues diabetes-related metabolic cardiomyopathy
Authors: Costantino Sarah , Mengozzi Alessandro , Velagapudi Srividya , Mohammed Shafeeq Ahmed , Gorica Era , Akhmedov Alexander , Mongelli Alessia , Pugliese Nicola Riccardo , Masi Stefano , Virdis Agostino , Hülsmeier Andreas , Matter Christian Matthias , Hornemann Thorsten , Melina Giovanni , Ruschitzka Frank , Luscher Thomas Felix , Paneni Francesco 
Published: November 2023

Abstract
Background
Metabolic cardiomyopathy (MCM), characterized by intramyocardial lipid accumulation, drives the progression to heart failure with preserved ejection fraction (HFpEF). Although evidence suggests that the mammalian silent information regulator 1 (Sirt1) orchestrates myocardial lipid metabolism, it is unknown whether its exogenous administration could avoid MCM onset. We investigated whether chronic treatment with recombinant Sirt1 (rSirt1) could halt MCM progression.

Methods
db/db mice, an established model of MCM, were supplemented with intraperitoneal rSirt1 or vehicle for 4 weeks and compared with their db/ + heterozygous littermates. At the end of treatment, cardiac function was assessed by cardiac ultrasound and left ventricular samples were collected and processed for molecular analysis. Transcriptional changes were evaluated using a custom PCR array. Lipidomic analysis was performed by mass spectrometry. H9c2 cardiomyocytes exposed to hyperglycaemia and treated with rSirt1 were used as in vitro model of MCM to investigate the ability of rSirt1 to directly target cardiomyocytes and modulate malondialdehyde levels and caspase 3 activity. Myocardial samples from diabetic and nondiabetic patients were analysed to explore Sirt1 expression levels and signaling pathways.

Results
rSirt1 treatment restored cardiac Sirt1 levels and preserved cardiac performance by improving left ventricular ejection fraction, fractional shortening and diastolic function (E/A ratio). In left ventricular samples from rSirt1-treated db/db mice, rSirt1 modulated the cardiac lipidome: medium and long-chain triacylglycerols, long-chain triacylglycerols, and triacylglycerols containing only saturated fatty acids were reduced, while those containing docosahexaenoic acid were increased. Mechanistically, several genes involved in lipid trafficking, metabolism and inflammation, such as Cd36, Acox3, Pparg, Ncoa3, and Ppara were downregulated by rSirt1 both in vitro and in vivo. In humans, reduced cardiac expression levels of Sirt1 were associated with higher intramyocardial triacylglycerols and PPARG-related genes.

Conclusions
In the db/db mouse model of MCM, chronic exogenous rSirt1 supplementation rescued cardiac function. This was associated with a modulation of the myocardial lipidome and a downregulation of genes involved in lipid metabolism, trafficking, inflammation, and PPARG signaling. These findings were confirmed in the human diabetic myocardium. Treatments that increase Sirt1 levels may represent a promising strategy to prevent myocardial lipid abnormalities and MCM development.

Graphical Abstract
Health equity for persons with disabilities: a global scoping review on barriers and interventions in healthcare services
Authors: Gréaux Mélanie , Moro Maria Francesca , Kamenov Kaloyan , Russell Amy M. , Barrett Darryl , Cieza Alarcos 
Published: November 2023

AbstractBackgroundPersons with disabilities experience health inequities in terms of increased mortality, morbidity, and limitations in functioning when compared to the rest of the population. Many of the poor health outcomes experienced by persons with disabilities cannot be explained by the underlying health condition or impairment, but are health inequities driven by unfair societal and health system factors. A synthesis of the global evidence is needed to identify the factors that hinder equitable access to healthcare services for persons with disabilities, and the interventions to remove these barriers and promote disability inclusion.MethodsWe conducted a scoping review following the methodological framework proposed by Arksey and O’Malley, Int J Soc Res Methodol 8:19–32. We searched two scholarly databases, namely MEDLINE (Ovid) and Web of Science, the websites of Organizations of Persons with Disabilities and governments, and reviewed evidence shared during WHO-led consultations on the topic of health equity for persons with disabilities. We included articles published after 2011 with no restriction to geographical location, the type of underlying impairments or healthcare services. A charting form was developed and used to extract the relevant information for each included article.ResultsOf 11,884 articles identified in the search, we included 182 articles in this review. The majority of sources originated from high-income countries. Barriers were identified worldwide across different levels of the health system (such as healthcare costs, untrained healthcare workforces, issues of inclusive and coordinated services delivery), and through wider contributing factors of health inequities that expand beyond the health system (such as societal stigma or health literacy). However, the interventions to promote equitable access to healthcare services for persons with disabilities were not readily mapped onto those needs, their sources of funding and projected sustainability were often unclear, and few offered targeted approaches to address issues faced by marginalized groups of persons with disabilities with intersectional identities.ConclusionPersons with disabilities continue to face considerable barriers when accessing healthcare services, which negatively affects their chances of achieving their highest attainable standard of health. It is encouraging to note the increasing evidence on interventions targeting equitable access to healthcare services, but they remain too few and sparce to meet the populations’ needs. Profound systemic changes and action-oriented strategies are warranted to promote health equity for persons with disabilities, and advance global health priorities.
Ultra-sensitive CTC-based liquid biopsy for pancreatic cancer enabled by large blood volume analysis
Authors: Stoecklein Nikolas H. , Fluegen Georg , Guglielmi Rosa , Neves Rui P.L. , Hackert Thilo , Birgin Emrullah , Cieslik Stefan A. , Sudarsanam Monica , Driemel Christiane , van Dalum Guus , Franken André , Niederacher Dieter , Neubauer Hans , Fehm Tanja , Rox Jutta M. , Böhme Petra , Häberle Lena , Göring Wolfgang , Esposito Irene , Topp Stefan A. , Coumans Frank A.W. , Weitz Jürgen , Knoefel Wolfram T. , Fischer Johannes C. , Bork Ulrich , Rahbari Nuh N. 
Published: November 2023

AbstractThe limited sensitivity of circulating tumor cell (CTC) detection in pancreatic adenocarcinoma (PDAC) stems from their extremely low concentration in the whole circulating blood, necessitating enhanced detection methodologies. This study sought to amplify assay-sensitivity by employing diagnostic leukapheresis (DLA) to screen large blood volumes. Sixty patients were subjected to DLA, with a median processed blood volume of ~ 2.8 L and approximately 5% of the resulting DLA-product analyzed using CellSearch (CS). Notably, DLA significantly increased CS-CTC detection to 44% in M0-patients and 74% in M1-patients, yielding a 60-fold increase in CS-CTC enumeration. DLA also provided sufficient CS-CTCs for genomic profiling, thereby delivering additional genomic information compared to tissue biopsy samples. DLA CS-CTCs exhibited a pronounced negative prognostic impact on overall survival (OS), evidenced by a reduction in OS from 28.6 to 8.5 months (univariate: p = 0.002; multivariable: p = 0.043). Additionally, a marked enhancement in sensitivity was achieved (by around 3-4-times) compared to peripheral blood (PB) samples, with positive predictive values for OS being preserved at around 90%. Prognostic relevance of CS-CTCs in PDAC was further validated in PB-samples from 228 PDAC patients, consolidating the established association between CTC-presence and reduced OS (8.5 vs. 19.0 months, p < 0.001). In conclusion, DLA-derived CS-CTCs may serve as a viable tool for identifying high-risk PDAC-patients and aiding the optimization of multimodal treatment strategies. Moreover, DLA enables comprehensive diagnostic profiling by providing ample CTC material, reinforcing its utility as a reliable liquid-biopsy approach. This high-volume liquid-biopsy strategy presents a potential pathway for enhancing clinical management in this malignancy.