bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning predictive models and risk factors for lymph node metastasis in non-small cell lung cancer
Authors: Wu Bo , Zhu Yihui , Hu Zhuozheng , Wu Jiajun , Zhou Weijun , Si Maoyan , Cao Xiying , Wu Zhicheng , Zhang Wenxiong 
Published: October 2024

Abstract
Background
The prognosis of non-small cell lung cancer (NSCLC) is substantially affected by lymph node metastasis (LNM), but there are no noninvasive, inexpensive methods of relatively high accuracy available to predict LNM in NSCLC patients.

Methods
Clinical data on NSCLC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for LNM were recognized LASSO and multivariate logistic regression. Six predictive models were constructed with machine learning based on risk factors. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the model. Subgroup analysis with different T-stages was performed on an optimal model. A webpage LNM risk calculator for optimal model was built using the Shinyapps.io platform.

Results
We enrolled 64,012 NSCLC patients, of whom 26,611 (41.57%) had LNM. Using multivariate logistic regression, we finally identified 10 independent risk factors for LNM: age, sex, race, histology, primary site, grade, T stage, M stage, tumor size, and bone metastases. GLM is the optimal model among all six machine learning models in both the training and validation cohorts. Subgroup analyses revealed that GLM has good predictability for populations with different T staging. A webpage LNM risk calculator based on GLM was posted on the shinyapps.io platform (https://wubopredict.shinyapps.io/dynnomapp/).

Conclusion
The predictive model based on GLM can be used to precisely predict the probability of LNM in NSCLC patients, which was proven effective in all subgroup analyses according to T staging.
The relationship between cyberchondria and health literacy among first-year nursing students: the mediating effect of health anxiety
Authors: Ali Samira Saad , Hendawi Nourhan Essam , El-Ashry Ayman Mohamed , Mohammed Manal Saeed 
Published: October 2024

Abstract
Background
First-year nursing students are at a critical juncture in their education. They are transitioning from laypersons to healthcare professionals, and students are frequently exposed to medical information in academic settings and through personal research. This exposure can sometimes lead to cyberchondria; improving health literacy and managing health anxiety are critical strategies for reducing the incidence of cyberchondria.

Aim
Investigate the mediating effect of health anxiety on cyberchondria and health literacy among first-year nursing students.

Methods
A cross-sectional correlational research design was used in this study. The study was conducted with 475 students in October 2023 during the first semester of the academic year 2023–2024.

Results
Cyberchondria and health literacy levels were both moderate. In addition, the degree of health anxiety among first-year Nursing Students was mild, too. The results showed that the association between Cyberchondria and Health Literacy was partially mediated by health anxiety.

Conclusion and implications
This study highlights the sophisticated relationship between cyberchondria, health literacy, and anxiety among first-year nursing students. It demonstrates that lower health literacy can lead to increased health anxiety, which in turn exacerbates cyberchondria. To mitigate these issues, it is essential to enhance health literacy and provide support for managing health anxiety within nursing education programs. By doing so, we can help nursing students navigate online health information effectively and reduce unnecessary health-related anxieties, promoting better educational outcomes and overall well-being.
Employer support for health and social care registered professionals, their patients and service users involved in regulatory fitness to practise regulatory proceedings
Authors: Wallace Louise M , Greenfield Mari 
Published: October 2024

Abstract
Background
Health and social care employees may be involved in professional regulatory proceedings because their alleged behaviour raises health or conduct concerns. Employees, patients or service users may also be involved in a regulatory tribunal as witnesses. This study is about the role of employers in supporting them in this process.

Methods
Taking an organisational support perspective, we interviewed 25 senior employees in health and social care organisations in the UK who are responsible for managing the employer’s role in the proceedings. Template analysis was used to analyse the transcripts.

Results
Support for patients was limited to that offered during an employer’s complaints process, and only one employer gave some support during the regulatory process if the patient or service user initiated regulatory proceedings. Support for employees in tribunals was little different to that offered during an initial investigation by the employer. However, where additional support for being involved in a regulatory tribunal was offered to employees, it most often came from the senior employees’ own experience of the stressfulness of being a witness in these proceedings. Employers were not aware of training resources that would better support their employees to engage with professional regulatory proceedings.

Conclusions
Employers offer limited support to employees who are involved in professional regulatory proceedings, and the support offered may depend more on senior employee’s individual experience of involvement in regulatory proceedings to exercise this discretion. Patients, service users and other public witnesses receive almost no support from health and social care employers during professional regulatory proceedings.
Comprehensive neurosurgical and visceral surgical therapy of retroperitoneal nerve tumors: a descriptive and retrospective analysis
Authors: Petkov Martin , Kornmann Marko , Bäzner Ute Marlies , Minzenmay Lena , Pala Andrej , Pedro Maria Teresa , Wirtz Christian Rainer , Antoniadis Gregor 
Published: October 2024

AbstractNerve tumors in the retroperitoneal space are a rarity. Radical surgery according to soft tissue tumors can lead to persistent pain and neurological deficits. This study aims to evaluate clinical outcomes of patients treated by a visceral- / neurosurgical approach. 33 patients with a retroperitoneal nerve tumor underwent surgery between 01/2002 and 12/2022 at our department. A visceral surgeon provided access to the retroperitoneal space, followed by micro-neurosurgical tumor preparation under neuromonitoring. Clinical examination and MRI were performed 12 weeks after surgery and further 3 months (WHO grade > 1) or 12 months (WHO grade 1). Further examinations were based on MRI findings and residual symptoms with median follow-up time of 24 months. One patient was treated for two distinct masses resulting in a total of 34 histological findings. Schwannomas (n = 15; 44.1%) and neurofibromas (n = 10; 29.4%) were the most common tumors. Long-term improvements were noted in radicular pain (15/18 patients; 83.3%), motor deficits (7/16 patients; 43.8%), abdominal discomfort and pain (5/7 patients; 71.4%). Recurrences were observed in 3/33 (9,1%) patients. This study represents the largest series of retroperitoneal BPNSTs treated with microsurgical techniques. Prospective multicenter studies are warranted to establish standardized treatment guidelines.
The effectiveness and acceptability of physical activity interventions amongst older adults with lower socioeconomic status: a mixed methods systematic review
Authors: Harris Danielle , Dlima Schenelle Dayna , Gluchowski Ashley , Hall Alex , Elliott Emma , Munford Luke 
Published: October 2024

Abstract
Background
Older adults with lower socioeconomic status are less likely to be physically active than those with higher socioeconomic status. To inform future intervention development, this review explored: [i] how effective are physical activity interventions at increasing levels of physical activity amongst older adults with lower socioeconomic status?; [ii] what factors are associated with the acceptability of physical activity interventions amongst older adults with lower socioeconomic status?; [iii] what are the implications for developing physical activity interventions for older adults with lower socioeconomic status?

Methods
This mixed methods systematic review followed PRISMA guidelines. MEDLINE, CENTRAL, Embase, Scopus, Web of Science, PsycINFO, CINAHL, ASSIA and Sports Medicine and Education Index were searched up to May 2023, to identify quantitative, qualitative and mixed methods primary research studies measuring the effectiveness of and/or experiences of physical activity interventions for older adults (aged ≥ 65 years) with lower socioeconomic status. No limits on country were applied. Included studies were assessed for methodological quality using the Mixed Methods Appraisal Tool. Results were synthesised using a results-based convergent synthesis approach with narrative synthesis of quantitative findings and thematic synthesis of qualitative findings.

Results
Thirty studies were included. Mixed effects were found for the effectiveness of physical activity interventions, with positive effects for increases in utilitarian walking (i.e. for transport) but not for leisure, mixed effects for objectively measured physical activity and no effects for self-reported total physical activity or muscle strengthening and flexibility activities. Engaging in physical activity interventions was perceived as offering many benefits, social familiarity was important to intervention acceptability and interventions were seen as more acceptable when they were compatible with the lifestyles of older adults with lower socioeconomic status.

Conclusions
Future development of physical activity interventions for older adults with lower socioeconomic status should foster social connections, emphasise health benefits of physical activity, hold interventions in locations that are accessible and familiar to older adults with lower socioeconomic status, minimise costs to participants, employ individuals who share participant characteristics to lead interventions, and combine physical activity with other activities older adults with lower socioeconomic status already do to make more efficient use of time.

Trial registration
PROSPERO CRD42023417312; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=417312.
Combining ERAP1 silencing and entinostat therapy to overcome resistance to cancer immunotherapy in neuroblastoma
Authors: Tempora Patrizia , D’Amico Silvia , Gragera Paula , Damiani Verena , Krol Kamila , Scaldaferri Valentina , Pandey Kirti , Chung Shanzou , Lucarini Valeria , Giorda Ezio , Scarsella Marco , Volpe Gabriele , Pezzullo Marco , De Stefanis Cristiano , D’Oria Valentina , De Angelis Lorenzo , Giovannoni Roberto , De Ioris Maria Antonietta , Melaiu Ombretta , Purcell Anthony W. , Locatelli Franco , Fruci Doriana 
Published: October 2024

Abstract
Background
Checkpoint immunotherapy unleashes tumor control by T cells, but it is undermined in non-immunogenic tumors, e.g. with low MHC class I expression and low neoantigen burden, such as neuroblastoma (NB). Endoplasmic reticulum aminopeptidase 1 (ERAP1) is an enzyme that trims peptides before loading on MHC class I molecules. Inhibition of ERAP1 results in the generation of new antigens able of inducing potent anti-tumor immune responses. Here, we identify a novel non-toxic combinatorial strategy based on genetic inhibition of ERAP1 and administration of the HDAC inhibitor (HDACi) entinostat that increase the immunogenicity of NB, making it responsive to PD-1 therapy.

Methods
CRISPR/Cas9-mediated gene editing was used to knockout (KO) the ERAP1 gene in 9464D NB cells derived from spontaneous tumors of TH-MYCN transgenic mice. The expression of MHC class I and PD-L1 was evaluated by flow cytometry (FC). The immunopeptidome of these cells was studied by mass spectrometry. Cocultures of splenocytes derived from 9464D bearing mice and tumor cells allowed the assessment of the effect of ERAP1 inhibition on the secretion of inflammatory cytokines and activation and migration of immune cells towards ERAP1 KO cells by FC. Tumor cell killing was evaluated by Caspase 3/7 assay and flow cytometry analysis. The effect of ERAP1 inhibition on the immune content of tumors was analyzed by FC, immunohistochemistry and multiple immunofluorescence.

Results
We found that inhibition of ERAP1 makes 9464D cells more susceptible to immune cell-mediated killing by increasing both the recall and activation of CD4+ and CD8+ T cells and NK cells. Treatment with entinostat induces the expression of MHC class I and PD-L1 molecules in 9464D both in vitro and in vivo. This results in pronounced changes in the immunopeptidome induced by ERAP1 inhibition, but also restrains the growth of ERAP1 KO tumors in vivo by remodelling the tumor-infiltrating T-cell compartment. Interestingly, the absence of ERAP1 in combination with entinostat and PD-1 blockade overcomes resistance to PD-1 immunotherapy and increases host survival.

Conclusions
These findings demonstrate that ERAP1 inhibition combined with HDACi entinostat treatment and PD-1 blockade remodels the immune landscape of a non-immunogenic tumor such as NB, making it responsive to checkpoint immunotherapy.
Uptake of health economic evaluations alongside clinical trials in Australia: an observational study
Authors: Carrandi Alayna , Wells Cynthia , Morton Rachael L. , Norman Richard , Skouteris Helen , Grove Amy , Higgins Alisa M. 
Published: October 2024

Abstract
Background
Australia’s clinical trials sector is highly productive with continued sector investment needed to enhance research impact. Generating economic evidence alongside trials has the potential to facilitate the implementation of trial results into practice. Ascertaining the use of health economic evaluations alongside clinical trials can assist in determining whether clinical trials fully realize and operationalize their potential to change policy and practice. The aims of this study were to ascertain the uptake of health economic evaluations alongside Australian-led clinical trials and explore associations between uptake and trial characteristics.

Methods
This observational study comprised a descriptive analysis of clinical trials registries, a cross-sectional survey of Australian Clinical Trials Alliance (ACTA) networks, and a subgroup analysis of completed acute care trials. Descriptive analyses of trial registrations were conducted, with logistic regressions used to identify predictors of proposing and subsequently publishing a health economic evaluation alongside acute care trials.

Results
Few randomized Australian-led clinical trials (11% of 9251) and ACTA network trials (43% of 227) proposed a health economic evaluation. In the subgroup analysis, 22% of the 324 acute care trials and 53% of the 38 ACTA network acute care trials proposed a health economic evaluation. Acute care trials funded by government bodies were significantly more likely to propose and publish a health economic evaluation than those funded by hospitals, universities, and other funders, after adjusting for phase, registration year, primary sponsor type, and comparator.

Conclusions
Current uptake of health economic evaluations alongside Australian-led clinical trials is low, with uptake higher among the subset of ACTA network trials. This is despite economic evidence playing an increasingly prominent role in health system management, as well as rising health expenditure, limited budgets, and competing demands. There is significant opportunity to embed health economic evaluations alongside clinical trials, particularly phase 3 trials, to increase research outputs and optimize research translation. Investing in clinical trial networks that support funding for a health economist or a health economic evaluation may be an effective strategy to increase the uptake of health economic evaluations alongside trials.
Strengthening lung cancer screening in Europe: fostering participation, improving outcomes, and addressing health inequalities through collaborative initiatives in the SOLACE consortium
Authors: Kauczor Hans-Ulrich , von Stackelberg Oyunbileg , Nischwitz Emily , Chorostowska-Wynimko Joanna , Hierath Monika , Mathonier Coline , Prosch Helmut , Zolda Pamela , Revel Marie-Pierre , Horváth Ildikó , Vašáková Martina Koziar , Powell Pippa , Samarzija Miroslav , Blum Torsten Gerriet ,   and SOLACE Consortium
Published: October 2024

Abstract
The Strengthening the Screening of Lung Cancer in Europe (SOLACE) initiative, supported by Europe’s Beating Cancer Plan, is dedicated to advancing lung cancer screening. This initiative brings together the most extensive pan-European network of respiratory and radiology experts, involving 37 partners from 15 countries. SOLACE aims to enhance equitable access to lung cancer screening by developing targeted recruitment strategies for underrepresented and high-risk populations. Through comprehensive work packages, SOLACE integrates scientific research, pilot studies, and sustainability efforts to bolster regional and national screening efforts across EU member states.

Critical relevance statement
The SOLACE project aims to facilitate the optimization and implementation of equitable lung cancer screening programs across the heterogeneous healthcare landscape in EU member states.

Key Points

The effectiveness of lung cancer screening is supported by both scientific evidence and now increasing legislative support.

SOLACE aims to develop, test, and disseminate tools to facilitate the realization of lung cancer screening at both a national and regional level.

Previously underrepresented populations in lung cancer screening will be targeted by tailored recruitment strategies.

SOLACE forms the first pan-European network of experts poised to drive real-world implementation of lung cancer screening.
Reproducibility of ultrasound-derived fat fraction in measuring hepatic steatosis
Authors: Song Danlei , Wang Pingping , Han Jiahao , Chen Huihui , Gao Ruixia , Li Ling , Li Jia 
Published: October 2024

Abstract
Purpose
Steatotic liver disease (SLD) has become the most common cause of chronic liver disease. Nevertheless, the non-invasive quantitative diagnosis of steatosis is still lacking in clinical practice. This study aimed to evaluate the reproducibility of the new parameter for steatosis quantification named ultrasound-derived fat fraction (UDFF).

Materials and methods
The UDFF values were independently executed by two operators in two periods. In the process, repeated measurements of the same patient were performed by the same operator under different conditions (liver segments, respiration, positions, and dietary). Finally, the results of some subjects (28) were compared with the MRI-derived proton density fat fraction (PDFF). The concordance analysis was mainly achieved by the intraclass correlation coefficient (ICC) and Bland–Altman.

Results
One hundred-five participants were included in the study. UDFF had good reliability in measuring the adult liver (ICCintra-observer = 0.96, ICCinter-observer = 0.94). Meanwhile, the ICC of the two operators increased over time. The variable measurement states did not influence the UDFF values on the surface, but they affected the coefficient of variation (Cov) of the results. Segment 8 (S8), end-expiratory, supine, and fasting images had the most minor variability. On the other hand, the UDFF value of S8 displayed satisfied consistency with PDFF (mean difference, −0.24 ± 1.44), and the results of both S5 (mean difference: −0.56 ± 3.95) and S8 (mean difference: 0.73 ± 1.87) agreed well with the whole-liver PDFF.

Conclusion
UDFF measurements had good reproducibility. Furthermore, the state of S8, end-expiration, supine, and fasting might be the more stable measurement approach.

Critical relevance statement
UDFF is the quantitative ultrasound parameter of hepatic steatosis and has good reproducibility. It can show more robust performance under specific measurement conditions (S8, end-expiratory, supine, and fasting).

Trial registration
The research protocol was registered at the Chinese Clinical Trial Registry on October 9, 2023 (http://www.chictr.org.cn/). The registration number is ChiCTR 2300076457.

Key Points

There is a lack of non-invasive quantitative measurement options for hepatic steatosis.

UDFF demonstrated excellent reproducibility in measuring hepatic steatosis.

S8, end-expiratory, supine, and fasting may be the more stable measuring condition.

Training could improve the operators’ measurement stability.

Variable measurement state affects the repeatability of the UDFF values (Cov).

Graphical Abstract
Optimizing CD8+ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators
Authors: Zhou Zihao , Zheng Jiarong , Lu Ye , Mai Zizhao , Lin Yunfan , Lin Pei , Zheng Yucheng , Chen Xu , Xu Rongwei , Zhao Xinyuan , Cui Li 
Published: October 2024

AbstractCD8+ T cells are integral to the effective management of cancer and infectious diseases due to their cytotoxic functions. The efficacy of these cells is profoundly influenced by their metabolic state, which regulates their activation, differentiation, and longevity. Accordingly, the modulation of metabolic pathways within CD8+ T cells is crucial for enhancing the effectiveness of T cell-based immunotherapy. Precise metabolic control is paramount in optimizing therapeutic outcomes and minimizing potential toxicities associated with treatment. Importantly, the potential of exogenous metabolites to augment CD8+ T cell responses is critically evaluated, especially through in vivo evidence that underscores their therapeutic promise. This review also addresses current challenges, including the need for precise control of metabolic modulation to avoid adverse effects, the development of targeted delivery systems to ensure efficient metabolite delivery to CD8+ T cells, and the inherent variability of metabolic states among patients that may influence treatment outcomes. Addressing these hurdles will be crucial for the successful integration of metabolic interventions into established immunotherapeutic regimens.