bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractIn 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

Abstract
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

AbstractInfluenza 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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundThe 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.MethodsA 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.ResultsA 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.ConclusionsThrough 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

AbstractBackgroundHallux 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.MethodsTwenty‐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.ResultsBetween 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.ConclusionIn 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 registrationAustralian 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

AbstractPolycystic 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.