bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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

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

Ferroptosis 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

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

Background

Persons 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.

Methods

We 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.

Results

Of 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.

Conclusion

Persons 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

The 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.
Comparative immunological landscape between pre- and early-stage LUAD manifested as ground-glass nodules revealed by scRNA and scTCR integrated analysis
Authors: Wang Ziqi , Yang Li , Wang Wenqiang , Zhou Huanhuan , Chen Juan , Ma Zeheng , Wang Xiaoyan , Zhang Quncheng , Liu Haiyang , Zhou Chao , Guo Zhiping , Zhang Xiaoju
Published: November 2023

Background

Mechanism underlying the malignant progression of precancer to early-stage lung adenocarcinoma (LUAD) as well as their indolence nature remains elusive.

Methods

Single-cell RNA sequencing (scRNA) with simultaneous T cell receptor (TCR) sequencing on 5 normal lung tissues, 3 precancerous and 4 early-stage LUAD manifested as pulmonary ground-glass nodules (GGNs) were performed.

Results

Through this integrated analysis, we have delineated five key modules that drive the malignant progression of early-stage LUAD in a disease stage-dependent manner. These modules are related to cell proliferation and metabolism, immune response, mitochondria, cilia, and cell adhesion. We also find that the tumor micro-environment (TME) of early-stage LUAD manifested as GGN are featured with regulatory T (Tregs) cells accumulation with three possible origins, and loss-functional state (decreased clonal expansion and cytotoxicity) of CD8 + T cells. Instead of exhaustion, the CD8 + T cells are featured with a shift to memory phenotype, which is significantly different from the late stage LUAD. Furthermore, we have identified monocyte-derived macrophages that undergo a lipid-phenotype transition and may contribute to the suppressive TME. Intense interaction between stromal cells, myeloid cells including lipid associated macrophages and LAMP3 + DCs, and lymphocytes were also characterized.

Conclusions

Our work provides new insight into the molecular and cellular mechanism underlying malignant progression of LUAD manifested as GGN, and pave way for novel immunotherapies for GGN.
Liquid-based biomarkers in breast cancer: looking beyond the blood
Authors: Shuai You , Ma Zhonghua , Ju Jie , Wei Tong , Gao Songlin , Kang Yikun , Yang Zixuan , Wang Xue , Yue Jian , Yuan Peng
Published: November 2023

In recent decades, using circulating tumor cell (CTC), circulating tumor DNA (ctDNA), circulating tumor RNA (ctRNA), exosomes and etc. as liquid biomarkers has received enormous attention in various tumors, including breast cancer (BC). To date, efforts in the area of liquid biopsy predominantly focus on the analysis of blood-based markers. It is worth noting that the identifications of markers from non-blood sources provide unique advantages beyond the blood and these alternative sources may be of great significance in offering supplementary information in certain settings. Here, we outline the latest advances in the analysis of non-blood biomarkers, predominantly including urine, saliva, cerebrospinal fluid, pleural fluid, stool and etc. The unique advantages of such testings, their current limitations and the appropriate use of non-blood assays and blood assays in different settings are further discussed. Finally, we propose to highlight the challenges of these alternative assays from basic to clinical implementation and explore the areas where more investigations are warranted to elucidate its potential utility.
Lesion-specific cortical activation following sensory stimulation in patients with subacute stroke
Authors: Li Wei , Li Chong , Liu Aixian , Lin Ping-Ju , Mo Linhong , Zhao Hongliang , Xu Quan , Meng Xiangzun , Ji Linhong
Published: November 2023

Background

Sensory stimulation can play a fundamental role in the activation of the primary sensorimotor cortex (S1-M1), which can promote motor learning and M1 plasticity in stroke patients. However, studies have focused mainly on investigating the influence of brain lesion profiles on the activation patterns of S1-M1 during motor tasks instead of sensory tasks. Therefore, the objective of this study is to explore the lesion-specific activation patterns due to different brain lesion profiles and types during focal vibration (FV).

Methods

In total 52 subacute stroke patients were recruited in this clinical experiment, including patients with basal ganglia hemorrhage/ischemia, brainstem ischemia, other subcortical ischemia, cortical ischemia, and mixed cortical–subcortical ischemia. Electroencephalograms (EEG) were recorded following a resting state lasting for 4 min and three sessions of FV. FV was applied over the muscle belly of the affected limb’s biceps for 3 min each session. Beta motor-related EEG power desynchronization overlying S1-M1 was used to indicate the activation of S1-M1, while the laterality coefficient (LC) of the activation of S1-M1 was used to assess the interhemispheric asymmetry of brain activation.

Results

(1) Regarding brain lesion profiles, FV could lead to the significant activation of bilateral S1-M1 in patients with basal ganglia ischemia and other subcortical ischemia. The activation of ipsilesional S1-M1 in patients with brainstem ischemia was higher than that in patients with cortical ischemia. No activation of S1-M1 was observed in patients with lesions involving cortical regions. (2) Regarding brain lesion types, FV could induce the activation of bilateral S1-M1 in patients with basal ganglia hemorrhage, which was significantly higher than that in patients with basal ganglia ischemia. Additionally, LC showed no significant correlation with the modified Barthel index (MBI) in all patients, but a positive correlation with MBI in patients with basal ganglia lesions.

Conclusions

These results reveal that sensory stimulation can induce lesion-specific activation patterns of S1-M1. This indicates FV could be applied in a personalized manner based on the lesion-specific activation of S1-M1 in stroke patients with different lesion profiles and types. Our study may contribute to a better understanding of the underlying mechanisms of cortical reorganization.
Phillyrin ameliorates influenza a virus-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation
Authors: Zhang Shanyu , Sun Fengzhi , Zhu Jinlu , Qi Jianhong , Wang Wenjing , Liu Ziming , Li Wenqian , Liu Chuanguo , Liu Xuehuan , Wang Nonghan , Song Xinyu , Zhang Dan , Qi Dongmei , Wang Xiaolong
Published: November 2023

Influenza is an acute viral respiratory illness with high morbidity rates worldwide. Excessive pulmonary inflammation is the main characteristic of lethal influenza A virus (IAV) infections. Therapeutic options for managing influenza are limited to vaccines and some antiviral medications. Phillyrin is one of the major bioactive components of the Chinese herbal medicine Forsythia suspensa, which has the functions of sterilization, heat clearing and detoxification. In this work, the effect and mechanism of phillyrin on H1N1 influenza (PR8)-induced pneumonia were investigated. We reported that phillyrin (15 mg/kg) treatment after viral challenge significantly improved the weight loss, ameliorated pulmonary inflammation and inhibited the accumulation of multiple cytokines and chemokines in bronchoalveolar lavage fluid on 7 days post infection (dpi). In vitro, phillyrin suppressed influenza viral replication (Matrixprotein and nucleoprotein messenger RNA level) and reduced influenza virus-induced cytopathic effect (CPE). Furthermore,chemokine receptor CXCR2 was confirmed to be markedly inhibited by phillyrin. Surface plasmon resonance results reveal that phillyrin exhibits binding affinity to CXCR2, having a binding affinity constant (KD) value of 1.858e-5 M, suggesting that CXCR2 is a potential therapeutic target for phillyrin. Moreover, phillyrin inhibited the mRNA and protein expression levels of Caspase1, ASC and NLRP3 in the lungs of mice with H1N1-induced pneumonia.This study reveals that phillyrin ameliorates IAV-induced pulmonary inflammation by antagonizing CXCR2 and inhibiting NLRP3 inflammasome activation partly.
Rapid detection of avian influenza virus based on CRISPR-Cas12a
Authors: Zhou Xu , Wang Siwen , Ma Yue , Li Yanbing , Deng Guohua , Shi Jianzhong , Wang Xiurong
Published: November 2023

Background

Avian influenza (AI) is a disease caused by the avian influenza virus (AIV). These viruses spread naturally among wild aquatic birds worldwide and infect domestic poultry, other birds, and other animal species. Currently, real-time reverse transcription polymerase chain reaction (rRT-PCR) is mainly used to detect the presence of pathogens and has good sensitivity and specificity. However, the diagnosis requires sophisticated instruments under laboratory conditions, which significantly limits point-of-care testing (POCT). Rapid, reliable, non-lab-equipment-reliant, sensitive, and specific diagnostic tests are urgently needed for rapid clinical detection and diagnosis. Our study aimed to develop a reverse transcription recombinase polymerase amplification (RT-RPA)/CRISPR method which improves on these limitations.

Methods

The Cas12a protein was purified by affinity chromatography with Ni-agarose resin and observed using sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE). Specific CRISPR RNA (crRNA) and primers targeting the M and NP genes of the AIV were designed and screened. By combining RT-RPA with the Cas12a/crRNA trans-cleavage system, a detection system that uses fluorescence readouts under blue light or lateral flow strips was established. Sensitivity assays were performed using a tenfold dilution series of plasmids and RNA of the M and NP genes as templates. The specificity of this method was determined using H1–H16 subtype AIVs and other avian pathogens, such as newcastle disease virus (NDV), infectious bursal disease virus (IBDV), and infectious bronchitis virus (IBV).

Results

The results showed that the method was able to detect AIV and that the detection limit can reach 6.7 copies/μL and 12 copies/μL for the M and NP gene, respectively. In addition, this assay showed no cross-reactivity with other avian-derived RNA viruses such as NDV, IBDV, and IBV. Moreover, the detection system presented 97.5% consistency and agreement with rRT-PCR and virus isolation for detecting samples from poultry. This portable and accurate method has great potential for AIV detection in the field.

Conclusion

An RT-RPA/CRISPR method was developed for rapid, sensitive detection of AIV. The new system presents a good potential as an accurate, user-friendly, and inexpensive platform for point-of-care testing applications.
What is the purpose of ultra-processed food? An exploratory analysis of the financialisation of ultra-processed food corporations and implications for public health
Authors: Wood Benjamin , Robinson Ella , Baker Phillip , Paraje Guillermo , Mialon Mélissa , van Tulleken Christoffer , Sacks Gary
Published: November 2023

Background

In recent decades there has been a global rise in consumption of ultra-processed foods (UPFs) to the detriment of population health and the environment. Large corporations that have focused heavily on low-cost manufacturing and extensive marketing of UPFs to maximise profits have driven this dietary transition. The same corporations claim to serve the interests of multiple ‘stakeholders’, and that they are contributing to sustainable development. This paper aimed to test these claims by examining the degree to which UPF corporations have become ‘financialised’, focusing on the extent to which they have prioritised the financial interests of their shareholders relative to other actors, as well as the role that various types of investors have played in influencing their governance. Findings were used to inform discussion on policy responses to improve the healthiness of population diets.

Methods

We adopted an exploratory research design using multiple methods. We conducted quantitative analysis of the financial data of U.S. listed food and agricultural corporations between 1962 and 2021, share ownership data of a selection of UPF corporations, and proxy voting data of a selection of investors between 2012 and 2022. We also conducted targeted narrative reviews using structured and branching searches of academic and grey literature.

Results

Since the 1980s, corporations that depend heavily on manufacturing and marketing UPFs to generate profits have been increasingly transferring money to their shareholders relative to their total revenue, and at a level considerably higher than other food and agricultural sectors. In recent years, large hedge fund managers have had a substantial influence on the governance of major UPF corporations in their pursuit of maximising short-term returns. In comparison, shareholders seeking to take steps to improve population diets have had limited influence, in part because large asset managers mostly oppose public health-related shareholder proposals.

Conclusions

The operationalisation of ‘shareholder primacy’ by major UPF corporations has driven inequity and undermines their claims that they are creating ‘value’ for diverse actors. Measures that protect population diets and food systems from the extractive forces of financialisation are likely needed as part of efforts to improve the healthiness of population diets.
Built to last? Barriers and facilitators of healthcare program sustainability: a systematic integrative review
Authors: Zurynski Yvonne , Ludlow Kristiana , Testa Luke , Augustsson Hanna , Herkes-Deane Jessica , Hutchinson Karen , Lamprell Gina , McPherson Elise , Carrigan Ann , Ellis Louise A. , Dharmayani Putu Novi Arfirsta , Smith Carolynn L. , Richardson Lieke , Dammery Genevieve , Singh Nehal , Braithwaite Jeffrey
Published: November 2023

Objective

To identify barriers and facilitators associated with the sustainability of implemented and evaluated improvement programs in healthcare delivery systems.

Data sources and study setting

Six academic databases were searched to identify relevant peer-reviewed journal articles published in English between July 2011 and June 2022. Studies were included if they reported on healthcare program sustainability and explicitly identified barriers to, and facilitators of, sustainability.

Study design

A systematic integrative review guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Study quality was appraised using Hawker’s Quality Assessment Tool.

Data collection/extraction methods

A team of reviewers screened eligible studies against the inclusion criteria and extracted the data independently using a purpose-designed Excel spreadsheet. Barriers and facilitators were extracted and mapped to the Integrated Sustainability Framework (ISF). Frequency counts of reported barriers/facilitators were performed across the included studies.

Results

Of the 124 studies included in this review, almost half utilised qualitative designs (n = 52; 41.9%) and roughly one third were conducted in the USA (n = 43; 34.7%). Few studies (n = 29; 23.4%) reported on program sustainability beyond 5 years of program implementation and only 16 of them (55.2%) defined sustainability. Factors related to the ISF categories of inner setting (n = 99; 79.8%), process (n = 99; 79.8%) and intervention characteristics (n = 72; 58.1%) were most frequently reported. Leadership/support (n = 61; 49.2%), training/support/supervision (n = 54; 43.5%) and staffing/turnover (n = 50; 40.3%) were commonly identified barriers or facilitators of sustainability across included studies. Forty-six (37.1%) studies reported on the outer setting category: funding (n = 26; 56.5%), external leadership by stakeholders (n = 16; 34.8%), and socio-political context (n = 14; 30.4%). Eight studies (6.5%) reported on discontinued programs, with factors including funding and resourcing, poor fit, limited planning, and intervention complexity contributing to discontinuation.

Conclusions

This review highlights the importance of taking into consideration the inner setting, processes, intervention characteristics and outer setting factors when sustaining healthcare programs, and the need for long-term program evaluations. There is a need to apply consistent definitions and implementation frameworks across studies to strengthen evidence in this area.

Trial registration

https://bmjopen.bmj.com/content/7/11/e018568.
“I know what I'm supposed to do, but I don't do it”: patient‐perceived risk factors that lead to their lower extremity amputations
Authors: Ben chmo Marcelle , Matricciani Lisa , Kumar Saravana , Graham Kristin
Published: November 2023

Background

The purpose of this study is to extend on our previous research by exploring patient‐perceived factors that lead to their Lower Extremity Amputations (LEA). LEA are a serious complication of Type 2 Diabetes Mellitus (T2DM), LEA are thought to be preventable with early detection and management of risk factors. Our previous study identified that these factors extend beyond the typical biological and modifiable risk factors and may also extend to patient awareness and competing priorities. Therefore, this research explored these issues in further detail, identifying patient‐perceived factors that lead to their LEA.

Methods

A qualitative descriptive methodology involving non‐probability purposive sampling was used to recruit inpatients at a tertiary metropolitan hospital in South Australia. Semi‐structured interviews were conducted, and data were transcribed verbatim. Data from the interviews were analysed using thematic analysis and the constant comparison approach.

Results

A total of 15 participants shared their perspectives of risk factors for LEA. Two main themes emerged: intrinsic and extrinsic factors. Intrinsic factors identified in this study included identity, ambivalence, denial, inevitability, and helplessness. Extrinsic factors related to resources, rapport with healthcare professionals, and management of care.

Conclusions

Through identifying that a combination of perceived personal attributes (intrinsic) and system‐level (extrinsic) factors likely contribute to LEA, this study highlights the complexity of factors that contribute to patients’ perceptions of what led to their diabetes related LEA. These findings support the importance of a nuanced approach in managing patients with diabetes who are at risk of LEA as it's likely patients' personal circumstances, day‐to‐day life's requirements and responsibilities, their interaction with healthcare professionals all seemingly contribute to how risks are viewed and managed. Tackling this challenge will require reimagining diabetes care, acknowledgement of risk factors beyond the obvious and addressing persistent access and workforce issues.
Nonsurgical management of hallux valgus: findings of a randomised pilot and feasibility trial
Authors: Menz Hylton B. , Lim Polly Q. X. , Hurn Sheree E. , Mickle Karen J. , Buldt Andrew K. , Cotchett Matthew P. , Roddy Edward , Wluka Anita E. , Erbas Bircan , Batra Mehak , Munteanu Shannon E.
Published: November 2023

Background

Hallux valgus is a common and disabling condition. This randomised pilot and feasibility trial aimed to determine the feasibility of conducting a parallel group randomised trial to evaluate the effectiveness of a nonsurgical intervention for reducing pain associated with hallux valgus.

Methods

Twenty‐eight community‐dwelling women with painful hallux valgus were randomised to receive either a multifaceted, nonsurgical intervention (footwear, foot orthoses, foot exercises, advice, and self‐management) or usual care (advice and self‐management alone). Outcome measures were obtained at baseline, 4, 8 and 12 weeks. The primary outcome was feasibility, evaluated according to demand (recruitment rate and conversion rate), acceptability, adherence, adverse events, and retention rate. Limited efficacy testing was conducted on secondary outcome measures including foot pain, foot muscle strength, general health‐related quality of life, use of cointerventions, and participants' perception of overall treatment effect.

Results

Between July 8, 2021, and April 22, 2022, we recruited and tested 28 participants (aged 44 to 80 years, mean 60.7, standard deviation 10.7). This period encompassed two COVID‐related stay‐at‐home orders (July 16 to July 27, and August 5 to October 21, 2021). The predetermined feasibility thresholds were met for retention rate, foot pain, mental health‐related quality of life, and use of cointerventions, partly met for acceptability, adverse events, and muscle strength, and not met for demand (recruitment rate or conversion rate), adherence, physical health‐related quality of life and perception of overall treatment effect.

Conclusion

In its current form, a randomised trial of footwear, foot orthoses, foot exercises, advice and self‐management for relieving pain associated with hallux valgus is not feasible, particularly due to the low adherence with the intervention. However, it is difficult to determine whether the trial would be feasible under different circumstances, particularly due to COVID‐19 stay‐at‐home orders. Future trials will need to consider improving the aesthetics of the footwear and making the exercise program less burdensome.

Trial registration

Australian and New Zealand Clinical Trial Registry (ACTRN12621000645853).
Causal pathways linking polycystic ovary syndrome to distinct breast cancer subtypes through mediator factors: a multivariable mendelian randomization analysis
Authors: Cao Runxiang , Chen Lanlan , Liu Yutong , Wang Xuyutian , Ma Ruolin , Zhao Qian , Du Ye
Published: November 2023

Polycystic ovary syndrome (PCOS) is an endocrine disorder characterized by ovarian cysts, high androgen levels, and irregular menstruation. The causality between PCOS and breast cancer (BC) has been widely discussed as they share a significant intersection in clinical manifestations. Previous epidemiological studies have not provided consistent conclusions in association between PCOS and BC, while mendelian randomization (MR) analyses have confirmed the causality between PCOS and estrogen receptor-positive breast cancer (ER + BC), but among a series of clinical manifestations resulting from PCOS, which related traits mediate the causal effect remains unknown. In this study, we conducted multivariable mendelian randomization (MVMR) analysis to explore the potential mediator variables in the mechanism linking PCOS to distinct subtypes of BC, and calculated the mediating effects proportion. We analyzed 13 PCOS-related traits and found that age at menopause may mediate PCOS-induced ER + BC (with -4.82% proportion) with a weak protective effect through the repair of DNA double-strand breaks by homologous recombination. This study helps to better comprehend the shared mechanisms contributing to the development of both PCOS and BC, and to screen high-risk populations for BC and take appropriate preventive measures.
Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial
Authors: Zhang Meng-Qiu , Xu Ming-Zhe , He Yi , Su Yong-Wei , Ma Jun , Zuo Yun-Xia
Published: November 2023

Background

Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear.

Methods

This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers’ and anaesthesia care providers’ satisfaction, and mask compliance.

Discussion

This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery.

Trial registration

ChiCTR2300069998. Registered on 30 March 2023.
Divergent brain regional atrophy and associated fiber disruption in amnestic and non-amnestic MCI
Authors: Du Chao , Dang Mingxi , Chen Kewei , Chen Yaojing , Zhang Zhanjun
Published: November 2023

Background

Understanding the pathological characteristics of various mild cognitive impairment (MCI) subtypes is crucial for the differential diagnosis of dementia. The purpose of this study was to feature divergent symptom-deficit profiles in amnestic MCI (aMCI) and non-amnestic MCI (naMCI).

Methods

T1 and DTI MRI data from a total of 158 older adults with 50 normal controls, 56 aMCI, and 52 naMCI were included. The voxel-wise gray matter volumes and the number of seed-based white matter fiber bundles were compared among these three groups. Furthermore, correlation and mediation analyses between the neuroimaging indices and cognitive measures were performed.

Results

The aMCI with specific memory abnormalities was characterized by volumetric atrophy of the left hippocampus but not by damage in the linked white matter fiber bundles. Conversely, naMCI was characterized by both the altered volume of the right inferior frontal gyrus and the significant damage to fiber bundles traversing the region in all three directions, not only affecting fibers around the atrophied area but also distant fibers. Mediation analyses of gray matter-white matter-cognition showed that gray matter atrophy affects the number of fiber bundles and further affects attention and executive function. Meanwhile, fiber bundle damage also affects gray matter volume, which further affects visual processing and language.

Conclusions

The divergent structural damage patterns of the MCI subtypes and cognitive dysfunctions highlight the importance of detailed differential diagnoses in the early stages of pathological neurodegenerative diseases to deepen the understanding of dementia subtypes and inform targeted early clinical interventions.
Evaluation of imaging findings in gastrointestinal anisakiasis in emergency CT and ultrasound
Authors: Fornell-Perez Roberto , Urizar-Gorosarri Maite , Martinez-Urabayen Uxue , Perez-Bea Marta
Published: November 2023

Background

To assess the frequency of appearance of various signs (isolated and grouped) in emergency imaging tests in patients with anisakiasis, according to the location of gastrointestinal tract involvement.

Methods

Retrospective review by two experienced radiologists of emergency ultrasounds and CTs performed on patients admitted in the Emergency Department of our hospital with later confirmed anisakiasis (2010–2021), assessing the presence of signs suggesting anisakiasis. Calculation of the frequency of appearance according to the gastric or intestinal location, as well as the most common grouped signs.

Results

Out of 231 total patients with anisakiasis, imaging studies were performed in 144: abdominopelvic ultrasound in 43 cases and CT in 111 (both techniques in 31). In cases with gastric occurrence (34), in CT the wall stratification (100%), wall thickening (97%), fat stranding (91%) and ascitic fluid (82%) were predominant. In the intestinal cases (105), in CT (95) the wall thickening (100%), fat stranding (92%) and mesenteric vessel engorgement (83%) were usual; in ultrasound (40), ascitic fluid and wall thickening (70% in both cases) were frequently observed. The frequency of grouped appearance of the mentioned signs was 82% in gastric cases, 80% in intestinal cases and 50% in ultrasounds. Multisegment involvement in CT reached 28% (gastric + intestinal) and 11% (only intestinal) of cases.

Conclusions

The most frequent CT findings in patients with gastric anisakiasis are wall stratification and thickening, fat stranding and ascitic fluid. In the intestinal cases, wall thickening, fat oedema and vessel engorgement are the most often observed findings.

Critical relevance statement

The presence of different radiological signs makes it advisable to include anisakiasis in the differential diagnosis of acute abdomen. Intestinal and multifocal involvement rates are greater than previously reported.

Key points

• In gastric anisakiasis, CT frequently shows wall stratification and thickening, fat stranding and ascitic fluid.

• In intestinal anisakiasis, CT often presents wall thickening, fat stranding and vessel engorgement.

• In intestinal anisakiasis, ultrasounds most frequently show ascitic fluid and wall thickening.

Graphical Abstract