bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of the chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale: a prospective cohort study
Authors: Gu Zhancheng , Chen Chen , Gu Jialin , Song Ziwei , Wei Guoli , Cai Guoxiang , Shu Qijin , Zhu Lingjun , Zhu Weiyou , Deng Haibin , Li Sheng , Chen Aifei , Yin Yue , Wu Qiulan , Zhu Hongyu , Li Guochun , Dai Anwei , Huo Jiege
Published: November 2023

Background

Current chemotherapy-induced peripheral neuropathy (CIPN) assessment tools mostly have poor sensitivity and weak anti-interference, so that it is sometimes difficult to provide substantive guidance for clinical intervention. This study aimed to develop an assessment tool dedicated for oxaliplatin to address these limitations.

Methods

This study screened 445 OIPN-related literatures for producing a symptom list, and developed the questionnaire module through expert supplement, item generation, content correlation analysis, pre-testing, and item improvement. The validation phase used a Chinese population-based prospective cohort study from June 2021 to July 2022. Patients were requested to complete the tested questionnaire, QLQ-CIPN20 and the CTCAE grading one day before cycles 2–6 of chemotherapy. Cronbach’s α coefficient and intraclass correlation coefficient (ICC) were calculated for the internal consistency and stability analysis, respectively. Exploratory factor analysis was conducted to investigate the construct validity. The correlations among the tested questionnaire, QLQ-CIPN20 and CTCAE were compared for the criterion validity analysis. Wilcoxon signed-rank sum test was utilized to compare the sensitivity between the tested questionnaire and QLQ-CIPN20.

Result

A 20-item CIPN assessment tool named chemotherapy-induced peripheral neuropathy integrated assessment – oxaliplatin subscale (CIPNIA-OS) was developed. The validation phase included 186 patients. Cronbach's α coefficient of CIPNIA-OS was 0.764 (> 0.7), and ICC was 0.997 (between 0.9 and 1). The structure of CIPNIA-OS containing seven factors was examined. The correlation coefficient between CIPNIA-OS and CTCAE was 0.661 (95%CI 0.623 to 0.695), which was significantly higher than that between QLQ-CIPN20 and CTCAE (0.417, 95%CI 0.363 to 0.469, p < 0.01). Besides, the total score of CIPNIA-OS was mostly higher than QLQ-CIPN20, with an average difference of 2.189 (CI 95% 2.056 to 2.322), and the difference gradually expanded with the progress of chemotherapy (p < 0.05).

Conclusion

This study developed an original CIPN questionnaire which was dedicated for OIPN assessment. It was a comprehensive tool that covered acute OIPN symptoms and integrated features from several proven CIPN assessment tools. The validation results supported that CIPNIA-OS had satisfactory reliability, stability, construct, criterion validity, and was more accuracy and sensitive than QLQ-CIPN20 in the evaluation of OIPN.
ANKRD49 promotes the metastasis of NSCLC via activating JNK-ATF2/c-Jun-MMP-2/9 axis
Authors: Sun Jia , Hu Jin-rui , Liu Chao-feng , Li Yuan , Wang Wei , Fu Rong , Guo Min , Wang Hai-long , Pang Min
Published: November 2023

Background

Ankyrin repeat domain 49 (ANKRD49) has been found to be highly expressed in multiple cancer including lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). However, the function of ANKRD49 in the pathogenesis of NSCLC still remains elusive. Previously, ANKRD49 has been demonstrated to promote the invasion and metastasis of A549 cells, a LUAD cell line, via activating the p38-ATF-2-MMP2/MMP9 pathways. Considering the heterogeneity of tumor cells, the function and mechanism of ANKRD49 in NSCLC need more NSCLC-originated cells to clarify.

Methods

Real-time qPCR was employed to test ANKRD49 expression levels in nine pairs of fresh NSCLC tissues and the corresponding adjacent normal tissues. The function of ANKRD49 was investigated using overexpression and RNA interference assays in lung adenocarcinoma cell line (NCI-H1299) and lung squamous carcinoma cell line (NCI-H1703) through gelatin zymography, cell counting kit-8, colony formation, wound healing, migration and invasion assays mmunoprecipitation was performed to in vitro. Immunoprecipitation was performed to test the interaction of c-Jun and ATF2. Chromatin immunoprecipitation was conducted to assess the transcriptional regulation of ATF2/c-Jun on MMP-2/9. Moreover, the tumorigenicity of ANKRD49 was evaluated in nude mice models and the involved signal molecular was also measured by immunohistochemical method.

Results

We found that the levels of ANKRD49 in cancerous tissues were higher than those in adjacent normal tissues. in vitro assay showed that ANKRD49 promoted the migration and invasion of NCI-H1299 and NCI-H1703 cells via enhancing the levels of MMP-2 and MMP-9. Furthermore, ANKRD49 elevated phosphorylation of JNK and then activated c-Jun and ATF2 which interact in nucleus to promote the binding of ATF2:c-Jun with the promoter MMP-2 or MMP-9. In vivo assay showed that ANKRD49 promoted lung metastasis of injected-NSCLC cells and the high metastatic rate was positively correlated with the high expression of ANKRD49, MMP-2, MMP-9, p-JNK, p-c-Jun and p-ATF2.

Conclusion

The present study indicated that ANKRD49 accelerated the invasion and metastasis of NSCLC cells via JNK-mediated transcription activation of c-Jun and ATF2 which regulated the expression of MMP-2/MMP-9. The molecular mechanisms of ANKRD49’s function is different from those found in A549 cells. The current study is a supplement and improvement to the previous research.
Prevalence of insomnia and its association with quality of life in caregivers of psychiatric inpatients during the COVID-19 pandemic: a network analysis
Authors: Chen Pan , Zhao Yan-Jie , An Feng-Rong , Li Xiao-Hong , Lam Mei Ieng , Lok Ka-In , Wang Yue-Ying , Li Jia-Xin , Su Zhaohui , Cheung Teris , Ungvari Gabor S. , Ng Chee H. , Zhang Qinge , Xiang Yu-Tao
Published: November 2023

Background

Studies on sleep problems among caregivers of psychiatric patients, especially during the COVID-19 pandemic, are limited. This study examined the prevalence and correlates of insomnia symptoms (insomnia hereafter) among caregivers of psychiatric inpatients during the COVID-19 pandemic as well as the association with quality of life (QoL) from a network analysis perspective.

Methods

A multi-center cross-sectional study was conducted on caregivers of inpatients across seven tertiary psychiatric hospitals and psychiatric units of general hospitals. Network analysis explored the structure of insomnia using the R program. The centrality index of “Expected influence” was used to identify central symptoms in the network, and the “flow” function was adopted to identify specific symptoms that were directly associated with QoL.

Results

A total of 1,101 caregivers were included. The overall prevalence of insomnia was 18.9% (n = 208; 95% CI = 16.7–21.3%). Severe depressive (OR = 1.185; P < 0.001) and anxiety symptoms (OR = 1.099; P = 0.003), and severe fatigue (OR = 1.320; P < 0.001) were associated with more severe insomnia. The most central nodes included ISI2 (“Sleep maintenance”), ISI7 (“Distress caused by the sleep difficulties”) and ISI1 (“Severity of sleep onset”), while “Sleep dissatisfaction” (ISI4), “Distress caused by the sleep difficulties” (ISI7) and “Interference with daytime functioning” (ISI5) had the strongest negative associations with QoL.

Conclusion

The insomnia prevalence was high among caregivers of psychiatric inpatients during the COVID-19 pandemic, particularly in those with depression, anxiety and fatigue. Considering the negative impact of insomnia on QoL, effective interventions that address insomnia and alteration of sleep dissatisfaction should be developed.
Correlates of cannabis use in a sample of mental health treatment-seeking Canadian armed forces members and veterans
Authors: St. Cyr Kate , Nazarov Anthony , Le Tri , Nouri Maede , Saha Priyonto , Forchuk Callista A , Soares Vanessa , Wanklyn Sonya G. , Bird Brian M. , Davis Brent D. , King Lisa , Ketcheson Felicia , Richardson J. Don
Published: November 2023

Objective

Canadian Armed Forces (CAF) members and Veterans are more likely to experience mental health (MH) conditions, such as posttraumatic stress disorder (PTSD), than the general Canadian population. Previous research suggests that an increasing number of individuals are employing cannabis for MH symptom relief, despite a lack of robust evidence for its effectiveness in treating PTSD. This research aimed to: (1) describe the prevalence of current cannabis use among MH treatment-seeking CAF members and Veterans; and (2) estimate the association between current cannabis use and a number of sociodemographic, military, and MH-related characteristics.

Method

Using cross-sectional intake data from 415 CAF members and Veterans attending a specialized outpatient MH clinic in Ontario, Canada, between January 2018 and December 2020, we estimated the proportion of CAF members and Veterans who reported current cannabis use for either medical or recreational purposes. We used multivariable logistic regression to estimate adjusted odds ratios for a number of sociodemographic, military, and MH-related variables and current cannabis use.

Results

Almost half of the study participants (n = 187; 45.1%) reported current cannabis use. Respondents who reported current cannabis use for medical purposes had a higher median daily dose than those who reported current cannabis use for recreational purposes. The multivariable logistic regression identified younger age, lower income, potentially hazardous alcohol use, and increased bodily pain as statistically significant correlates of current cannabis use among our MH treatment-seeking sample. PTSD severity, depressive severity, sleep quality, and suicide ideation were not statistically associated with current cannabis use.

Conclusions

Almost half of our treatment-seeking sample reported current cannabis use for medical or recreational purposes, emphasizing the importance of screening MH treatment-seeking military members and Veterans for cannabis use prior to commencing treatment. Future research building upon this study could explore the potential impact of cannabis use on MH outcomes.
Correlation analysis between physical activity and depressive tendencies among occupational groups: an isotemporal substitution approach
Authors: Liu Yihua , Lin Haoxiang , Zhang Hao , Zhang Xiaoyue , Yin Shengli
Published: November 2023

Objectives

Sedentary behaviour (SB) and physical activity (PA) have been shown to be associated with depression. However, behaviours, such as PA, occupy a portion of an individual’s 24-h day. Thus, an increase in time for one behaviour takes away time from another. Previous evidence suggests that it would be more appropriate to shift the focus to the importance of reallocating time spent in sedentary behaviour to time spent in physical activity. The aim of this study was to analyse the mutual replacement effect of different health behaviours on depressive tendencies by isotemporal substitution modelling (ISM) under the objective condition of considering a limited 24-h day. Second, we aimed to further explore the potential association between excessive or insufficient sleep duration and depressive symptoms.

Methods

A total of 10656 employees from 79 companies in four provinces of China participated in this survey.

The Center for Epidemiological Studies Depression Scale (CES-D) was used to measure workers’ depressive tendencies. The duration of various types of physical activity was self-reported by workers based on the International Physical Activity Questionnaire (IPAQ). ISM was used to assess the associations of time spent in different activities on displacement of equivalent time spent on other activities with depression risk.

Results

A total of 10656 participants (89.5% of the sample) were included in the analysis.

The ISM found that a 30-min unit of SB replaced with walking (OR, 95% CI: 0.83, 0.77–0.88), sleep (≤ 8 h) (OR, 95% CI: 0.77, 0.74–0.79), moderate physical activity (MPA) (OR, 95% CI: 0.87, 0.81–0.93) and vigorous physical activity (VPA) (OR, 95% CI: 0.91, 0.84–0.99) was significantly and negatively associated with the risk of depressive tendencies. When sleep duration was less than 8 h, each additional half hour of sleep time was significantly associated with a lower risk of depressive tendencies, and this association was no longer significant after 8 h.

Conclusion

Prolonged SB is common in the current workplace in China. Replacing an average of 30 min per day of SB with VPA and MPA, even walking is associated with less depression among workers. In addition, insufficient daily sleep is also an important risk factor for workers' depressive tendencies. These findings provide valuable evidence to promote mental health among occupational groups and support the development of healthy workplaces.
Views on sharing mental health data for research purposes: qualitative analysis of interviews with people with mental illness
Authors: Watson Emily , Fletcher-Watson Sue , Kirkham Elizabeth Joy
Published: November 2023

Background

Improving the ways in which routinely-collected mental health data are shared could facilitate substantial advances in research and treatment. However, this process should only be undertaken in partnership with those who provide such data. Despite relatively widespread investigation of public perspectives on health data sharing more generally, there is a lack of research on the views of people with mental illness.

Methods

Twelve people with lived experience of mental illness took part in semi-structured interviews via online video software. Participants had experience of a broad range of mental health conditions including anxiety, depression, schizophrenia, eating disorders and addiction. Interview questions sought to establish how participants felt about the use of routinely-collected health data for research purposes, covering different types of health data, what health data should be used for, and any concerns around its use.

Results

Thematic analysis identified four overarching themes: benefits of sharing mental health data, concerns about sharing mental health data, safeguards, and data types. Participants were clear that health data sharing should facilitate improved scientific knowledge and better treatments for mental illness. There were concerns that data misuse could become another way in which individuals and society discriminate against people with mental illness, for example through insurance premiums or employment decisions. Despite this there was a generally positive attitude to sharing mental health data as long as appropriate safeguards were in place.

Conclusions

There was notable strength of feeling across participants that more should be done to reduce the suffering caused by mental illness, and that this could be partly facilitated by well-managed sharing of health data. The mental health research community could build on this generally positive attitude to mental health data sharing by following rigorous best practice tailored to the specific concerns of people with mental illness.
Reducing prescribing of antibiotics for acute respiratory infections using a frontline nurse-led EHR-Integrated clinical decision support tool: protocol for a stepped wedge randomized control trial
Authors: Stevens Elizabeth R. , Agbakoba Ruth , Mann Devin M. , Hess Rachel , Richardson Safiya I. , McGinn Thomas , Smith Paul D. , Halm Wendy , Mundt Marlon P. , Dauber-Decker Katherine L. , Jones Simon A. , Feldthouse Dawn M. , Kim Eun Ji , Feldstein David A.
Published: November 2023

Background

Overprescribing of antibiotics for acute respiratory infections (ARIs) remains a major issue in outpatient settings. Use of clinical prediction rules (CPRs) can reduce inappropriate antibiotic prescribing but they remain underutilized by physicians and advanced practice providers. A registered nurse (RN)-led model of an electronic health record-integrated CPR (iCPR) for low-acuity ARIs may be an effective alternative to address the barriers to a physician-driven model.

Methods

Following qualitative usability testing, we will conduct a stepped-wedge practice-level cluster randomized controlled trial (RCT) examining the effect of iCPR-guided RN care for low acuity patients with ARI. The primary hypothesis to be tested is: Implementation of RN-led iCPR tools will reduce antibiotic prescribing across diverse primary care settings. Specifically, this study aims to: (1) determine the impact of iCPRs on rapid strep test and chest x-ray ordering and antibiotic prescribing rates when used by RNs; (2) examine resource use patterns and cost-effectiveness of RN visits across diverse clinical settings; (3) determine the impact of iCPR-guided care on patient satisfaction; and (4) ascertain the effect of the intervention on RN and physician burnout.

Discussion

This study represents an innovative approach to using an iCPR model led by RNs and specifically designed to address inappropriate antibiotic prescribing. This study has the potential to provide guidance on the effectiveness of delegating care of low-acuity patients with ARIs to RNs to increase use of iCPRs and reduce antibiotic overprescribing for ARIs in outpatient settings.

Trial registration

ClinicalTrials.gov Identifier: NCT04255303, Registered February 5 2020, https://clinicaltrials.gov/ct2/show/NCT04255303.
Quitting one’s job or leaving one’s profession: unexplored consequences of workplace violence and discrimination against health professionals
Authors: Hämmig Oliver
Published: November 2023

Background

Although workplace violence and discrimination against healthcare workers are global and universal phenomena, and violence at work is recognized as a serious and growing problem, in Switzerland, hardly anything is known about the related consequences on job changes and career endings, which are two major staffing challenges present in the notoriously understaffed healthcare sector.

Method

Data collected from a written survey conducted among 1,840 hospital employees, of which 1,441 were health professionals, were used to evaluate and estimate the prevalence and impact of specific and cumulated forms of workplace violence and discrimination on the work climate and particularly on subsequent turnover intentions and career endings. Established multi- and single-item measures were used as predicting, intervening and outcome variables. Relative frequencies stratified for nurses, physicians and therapists were calculated to estimate and differentiate the size of the phenomena under study. Furthermore, crosstabulations, as well as multivariate regression analyses, were performed to explore the associations of interest.

Results

Every fifth to sixth nurse and every seventh to eighth physician reported having had intentions to change jobs or leave the profession within the past year. These intentions become much more prevalent across all health professions when one or even two or more different forms of violence and/or discrimination at work are experienced and reported. Accordingly, the relative risks for intending to quit one’s job or leave one’s profession increase significantly and steadily with a growing number (1, 2 +) of different experienced forms of violence and/or discrimination at work compared to the reference group of those who are nonaffected (aOR from 2.5 up to 5.4). This fairly strong association was only slightly reduced (aOR from 2.1 to 4.0) when work climate was additionally taken into account as a potential intervening variable. Although work climate only partly accounted for the association under study, a poor work climate was an additional strong predictor and independent risk factor for intentions to turnover (aOR = 6.4) or leave the profession (aOR = 4.2).

Conclusions

Experiences of workplace violence and discrimination and the resulting poor work climate both together and independent of each other seem to be important causes of job changes and career endings among healthcare workers in Switzerland.
Transitions in health care settings for frequent and infrequent users of emergency departments: a population-based retrospective cohort study
Authors: Rosychuk Rhonda J. , Chen Anqi A. , Ospina Maria B. , McRae Andrew D. , Hu X. Joan , McLane Patrick
Published: November 2023

Background

Efforts to reduce emergency department (ED) volumes often target frequent users. We examined transitions in care across ED, hospital, and community settings, and in-hospital death, for high system users (HSUs) compared to controls.

Methods

Population-based databases provided ED visits and hospitalizations in Alberta and Ontario, Canada. The retrospective cohort included the top 10% of all the ED users during 2015/2016 (termed HSUs) and a random sample of controls (4 per each HSU) from the bottom 90% per province. Rates of transitions among ED, hospitalization, community settings, and in-hospital mortality were adjusted for sociodemographic and ED variables in a multistate statistical model.

Results

There were 2,684,924 patients and 579,230 (21.6%) were HSUs. Patient characteristics associated with shorter community to ED transition times for HSUs included Alberta residence (ratio of hazard ratio [RHR] = 1.11, 95% confidence interval [CI] 1.11,1.12), living in areas in the lower income quintile (RHR = 1.06, 95%CI 1.06,1.06), and Ontario residents without a primary health care provider (RHR = 1.13, 95%CI 1.13,1.14). Once at the ED, characteristics associated with shorter ED to hospital transition times for HSUs included higher acuity (e.g., RHR = 1.70, 95% CI 1.61, 1.81 for emergent), and for many diagnoses including chest pain (RHR = 1.71, 95%CI 1.65,1.76) and gastrointestinal (RHR = 1.66, 95%CI 1.62,1.71). Once admitted to hospital, HSUs did not necessarily have longer stays except for conditions such as chest pain (RHR = 0.90, 95% CI 0.86, 0.95). HSUs had shorter times to death in the ED if they presented for cancer (RHR = 2.51), congestive heart failure (RHR = 1.93), myocardial infarction (RHR = 1.53), and stroke (RHR = 1.84), and shorter times to death in-hospital if they presented with cancer (RHR = 1.29).

Conclusions

Differences between HSUs and controls in predictors of transitions among care settings were identified. Co-morbidities and limitations in access to primary care are associated with more rapid transitions from community to ED and hospital among HSUs. Interventions targeting these challenges may better serve patients across health systems..

Trial registration

Not applicable.
Acts of negotiation: toward a grounded theory of nursing practice in chronic wound care in Austria
Authors: Drgac Deborah , Himmelsbach Raffael
Published: November 2023

Background

Demographic change and the rise of diabetes mellitus are leading to a projected increase in the prevalence of chronic wounds. People suffering from chronic wounds experience significant losses in their health-related quality of life. Health systems struggle to meet the needs of these persons, even in high-income countries. This paper explores wound nurses’ perspectives on their professional practice in Austria. They play a key role as they do much of the treatment work, contribute to advancing the field, and enable interprofessional coordination. Their perspectives enable insights into how a health system provides care for elderly and chronically ill people.

Methods

We used the Constructivist Grounded Theory framework to analyse transcripts of 14 semi-structured qualitative interviews with nurses who work in different treatment settings.

Results

We identified three themes. Firstly, the interviewees characterise working with patients as a balancing act between offering enough support to build a trustful relationship while protecting themselves against the overwhelming situation of caring for a chronically ill person. Secondly, the interviewees compensate for nonexistent care pathways by building informal networks with doctors, which requires delicate relationship work. Thirdly, the study participants must prove their competence in every new professional encounter. Their need for professional autonomy clashes with the traditional doctor-nurse hierarchy. Based on these insights, we propose a grounded theory that conceives of nursing practice in terms of ‘acts of negotiations’.

Conclusion

Our results demonstrate that wound nurses in Austria operate in an institutional environment whose outdated imagination of the nursing role is at odds with the care demands that arise from a growing number of elderly and chronically ill people. We detailed the ‘acts of negotiation’ nurses deploy to compensate for this situation. We identify areas for policy intervention to strengthen the autonomy of wound nurses, including access to statutory health insurance billing.
Neuromolecular responses in disrupted mutualistic cleaning interactions under future environmental conditions
Authors: Ramírez-Calero S. , Paula J. R. , Otjacques E. , Ravasi T. , Rosa R. , Schunter C.
Published: November 2023

Background

Mutualistic interactions, which constitute some of the most advantageous interactions among fish species, are highly vulnerable to environmental changes. A key mutualistic interaction is the cleaning service rendered by the cleaner wrasse, Labroides dimidiatus, which involves intricate processes of social behaviour to remove ectoparasites from client fish and can be altered in near-future environmental conditions. Here, we evaluated the neuromolecular mechanisms behind the behavioural disruption of cleaning interactions in response to future environments. We subjected cleaner wrasses and surgeonfish (Acanthurus leucosternon, serving as clients) to elevated temperature (warming, 32 °C), increased levels of CO2 (high CO2, 1000 ppm), and a combined condition of elevated CO2 and temperature (warming and high CO2, 32 °C, and 1000 ppm) for 28 days.

Results

Each of these conditions resulted in behavioural disruptions concerning the motivation to interact and the quality of interaction (high CO2 − 80.7%, warming − 92.6%, warming and high CO2 − 79.5%, p < 0.001). Using transcriptomics of the fore-, mid-, and hindbrain, we discovered that most transcriptional reprogramming in both species under warming conditions occurred primarily in the hind- and forebrain. The associated functions under warming were linked to stress, heat shock proteins, hypoxia, and behaviour. In contrast, elevated CO2 exposure affected a range of functions associated with GABA, behaviour, visual perception, thyroid hormones and circadian rhythm. Interestingly, in the combined warming and high CO2 condition, we did not observe any expression changes of behaviour. However, we did find signs of endoplasmic reticulum stress and apoptosis, suggesting not only an additive effect of the environmental conditions but also a trade-off between physiological performance and behaviour in the cleaner wrasse.

Conclusions

We show that impending environmental shifts can affect the behaviour and molecular processes that sustain mutualistic interactions between L. dimidiatus and its clients, which could have a cascading effect on their adaptation potential and possibly cause large-scale impacts on coral reef ecosystems.
Biomineralized tetramethylpyrazine-loaded PCL/gelatin nanofibrous membrane promotes vascularization and bone regeneration of rat cranium defects
Authors: Wu Xiaoyu , Ni Su , Dai Ting , Li Jingyan , Shao Fang , Liu Chun , Wang Jiafeng , Fan Shijie , Tan Yadong , Zhang Linxiang , Jiang Qiting , Zhao Hongbin
Published: November 2023

Conventional electrospinning produces nanofibers with smooth surfaces that limit biomineralization ability. To overcome this disadvantage, we fabricated a tetramethylpyrazine (TMP)-loaded matrix-mimicking biomineralization in PCL/Gelatin composite electrospun membranes with bubble-shaped nanofibrous structures. PCL/Gelatin membranes (PG), PCL/Gelatin membranes containing biomineralized hydroxyapatite (HA) (PGH), and PCL/Gelatin membranes containing biomineralized HA and loaded TMP (PGHT) were tested. In vitro results indicated that the bubble-shaped nanofibrous surface increased the surface roughness of the nanofibers and promoted mineralization. Furthermore, sustained-release TMP had an excellent drug release efficiency. Initially released vigorously, it reached stabilization at day 7, and the slow-release rate stabilized at 61.0 ± 1.8% at 28 days. All membranes revealed an intact cytoskeleton, cell viability, and superior adhesion and proliferation when stained with Ghost Pen Cyclic Peptide, CCK-8, cell adhesion, and EdU. In PGHT membranes, the osteogenic and vascularized gene expression of BMSCs and human vascular endothelial cells was significantly upregulated compared with that in other groups, indicating the PGHT membranes exhibited an effective vascularization role. Subsequently, the membranes were implanted in a rat cranium defect model for 4 and 8 weeks. Micro-CT and histological analysis results showed that the PGHT membranes had better bone regenerative patterns. Additionally, the levels of CD31 and VEGF significantly increased in the PGHT membrane compared with those in other membranes. Thus, PGHT membranes could accelerate the repair of cranium defects in vivo via HA and TMP synergistic effects.

Graphical Abstract
Intervening in hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p for tumor microenvironment regulation and cancer therapy
Authors: Zhou Xueqing , Hong Yiling , Liu Yupeng , Wang Li , Liu Xuan , Li Yi , Yuan Hong , Hu Fuqiang
Published: November 2023

Background

Despite being a common malignant tumor, the molecular mechanism underlying the initiation and progression of triple-negative breast cancers (TNBCs) remain unclear. Tumor-associated macrophages (TAMs) are often polarized into a pro-tumor phenotype and are associated with a poor prognosis of TNBCs. Exosomes, important mediators of cell-cell communication, can be actively secreted by donor cells to reprogram recipient cells. The functions and molecular mechanisms of tumor cell-derived exosomes in TNBCs progression and TAMs reprogramming urgently need to be further explored.

Results

We demonstrated that tumor cell-derived exosomes enriched with miR-184-3p were taken up by macrophages to inhibit JNK signaling pathway by targeting EGR1, thereby inducing M2 polarization of macrophages and synergistically promoting tumor progression. Nanoparticles loaded with oncogene c-Myc inhibitor JQ1 could suppress the polarization process by reducing Rac1-related exosome uptake by macrophage. More importantly, it was found for the first time that tumor-suppressive miR-184-3p was actively sorted into exosomes by binding to RNA-binding protein heterogeneous nuclear ribonucleoprotein A2B1 (hnRNPA2B1), thus facilitating tumor cell proliferation and metastasis by relieving the inhibitory effect of miR-184-3p on Mastermind-like 1 (MAML1). Overexpressing miR-184-3p in tumor cells and simultaneously knocking down hnRNPA2B1 to block its secretion through exosomes could effectively inhibit tumor growth and metastasis.

Conclusions

Our study revealed that hnRNPA2B1-mediated exosomal transfer of tumor-suppressive miR-184-3p from breast cancer cells to macrophages was an important mediator of TNBCs progression, providing new insights into TNBCs pathogenesis and therapeutic strategies.

Graphical Abstract
Prediction of the SF-6D utility score from Lung cancer FACT-L: a mapping study in China
Authors: Yang Qing , Jiang Long Lin , Li Yin Feng , Huang Deyu
Published: November 2023

Objective

To develop a mapping algorithm for generating the Short Form Six-Dimension (SF-6D) utility score based on the Functional Assessment of Cancer Therapy-Lung (FACT-L) of lung cancer patients.

Methods

Data were collected from 625 lung cancer patients in mainland China. The Spearman rank correlation coefficient and principal component analysis were used to evaluate the conceptual overlap between the FACT-L and SF-6D. Five model specifications and four statistical techniques were used to derive mapping algorithms, including ordinary least squares (OLS), Tobit and beta-mixture regression models, which were used to directly estimate health utility, and ordered probit regression was used to predict the response level. The prediction performance was evaluated using the correlations between the root mean square error (RMSE), mean absolute error (MAE), concordance correlation coefficient (CCC), Akaike information criterion (AIC) and Bayesian information criterion (BIC) and the observed and predicted SF-6D scores. A five-fold cross-validation method was used to test the universality of each model and select the best model.

Results

The average FACT-L score was 103.024. The average SF-6D score was 0.774. A strong correlation was found between FACT-L and SF-6D scores (ρ = 0.797). The ordered probit regression model with the total score of each dimension and its square term, as well as age and sex as covariates, was most suitable for mapping FACT-L to SF-6D scores (5-fold cross-validation: RMSE = 0.0854; MAE = 0.0655; CCC = 0.8197; AEs > 0.1 (%) = 53.44; AEs > 0.05 (%) = 21.76), followed by beta-mixture regression for direct mapping. The Bland‒Altman plots showed that the ordered probit regression M5 had the lowest proportion of prediction scores outside the 95% agreement limit (-0.166, 0.163) at 4.96%.

Conclusions

The algorithm reported in this paper enables lung cancer data from the FACT-L to be mapped to the utility of the SF-6D. The algorithm allows the calculation of quality-adjusted life years for cost-utility analyses of lung cancer.
Developing and validating a multi-criteria decision analytic tool to assess the value of cancer clinical trials: evaluating cancer clinical trial value
Authors: Gillett Piers , Mahar Robert K , Tran Nancy R , Rosenthal Mark , IJzerman Maarten
Published: November 2023

Background

Demonstrating safety and efficacy of new medical treatments requires clinical trials but clinical trials are costly and may not provide value proportionate to their costs. As most health systems have limited resources, it is therefore important to identify the trials with the highest value. Tools exist to assess elements of a clinical trial such as statistical validity but are not wholistic in their valuation of a clinical trial. This study aims to develop a measure of clinical trials value and provide an online tool for clinical trial prioritisation.

Methods

A search of the academic and grey literature and stakeholder consultation was undertaken to identify a set of criteria to aid clinical trial valuation using multi-criteria decision analysis. Swing weighting and ranking exercises were used to calculate appropriate weights of each of the included criteria and to estimate the partial-value function for each underlying metric. The set of criteria and their respective weights were applied to the results of six different clinical trials to calculate their value.

Results

Seven criteria were identified: ‘unmet need’, ‘size of target population’, ‘eligible participants can access the trial’, ‘patient outcomes’, ‘total trial cost’, ‘academic impact’ and ‘use of trial results’. The survey had 80 complete sets of responses (51% response rate). A trial designed to address an ‘Unmet Need’ was most commonly ranked as the most important with a weight of 24.4%, followed by trials demonstrating improved ‘Patient Outcomes’ with a weight of 21.2%. The value calculated for each trial allowed for their clear delineation and thus a final value ranking for each of the six trials.

Conclusion

We confirmed that the use of the decision tool for valuing clinical trials is feasible and that the results are face valid based on the evaluation of six trials. A proof-of-concept applying this tool to a larger set of trials with an external validation is currently underway.
Insights into the regulatory role of RNA methylation modifications in glioma
Authors: Long Shengrong , Yan Yu , Xu Hongyu , Wang Lesheng , Jiang Jiazhi , Xu Ziyue , Liu Runming , Zhou Qiangqiang , Huang Xiaopeng , Chen Jincao , Li Zhiqiang , Wei Wei , Li Xiang
Published: November 2023

Epitranscriptomic abnormalities, which are highly prevalent in primary central nervous system malignancies, have been identified as crucial contributors to the development and progression of gliomas. RNA epitranscriptomic modifications, particularly the reversible modification methylation, have been observed throughout the RNA cycle. Epitranscriptomic modifications, which regulate RNA transcription and translation, have profound biological implications. These modifications are associated with the development of several cancer types. Notably, three main protein types—writers, erasers, and readers, in conjunction with other related proteins, mediate these epitranscriptomic changes. This review primarily focuses on the role of recently identified RNA methylation modifications in gliomas, such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), N7-methylguanosine (m7G), and N1-methyladenosine (m1A). We delved into their corresponding writers, erasers, readers, and related binding proteins to propose new approaches and prognostic indicators for patients with glioma.
Deletion of voltage-gated calcium channels in astrocytes decreases neuroinflammation and demyelination in a murine model of multiple sclerosis
Authors: Denaroso G. E. , Smith Z. , Angeliu C. G. , Cheli V. T. , Wang C. , Paez P. M.
Published: November 2023

The experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis was used in combination with a Cav1.2 conditional knock-out mouse (Cav1.2KO) to study the role of astrocytic voltage-gated Ca++ channels in autoimmune CNS inflammation and demyelination. Cav1.2 channels were specifically ablated in Glast-1-positive astrocytes by means of the Cre-lox system before EAE induction. After immunization, motor activity was assessed daily, and a clinical score was given based on the severity of EAE symptoms. Cav1.2 deletion in astrocytes significantly reduced the severity of the disease. While no changes were found in the day of onset and peak disease severity, EAE mean clinical score was lower in Cav1.2KO animals during the chronic phase of the disease. This corresponded to better performance on the rotarod and increased motor activity in Cav1.2KO mice. Furthermore, decreased numbers of reactive astrocytes, activated microglia, and infiltrating lymphocytes were found in the lumbar section of the spinal cord of Cav1.2KO mice 40 days after immunization. The degree of myelin protein loss and size of demyelinated lesions were also attenuated in Cav1.2KO spinal cords. Similar results were found in EAE animals treated with nimodipine, a Cav1.2 Ca++ channel inhibitor with high affinity to the CNS. Mice injected with nimodipine during the acute and chronic phases of the disease exhibited lower numbers of reactive astrocytes, activated microglial, and infiltrating immune cells, as well as fewer demyelinated lesions in the spinal cord. These changes were correlated with improved clinical scores and motor performance. In summary, these data suggest that antagonizing Cav1.2 channels in astrocytes during EAE alleviates neuroinflammation and protects the spinal cord from autoimmune demyelination.
“Sex without fear”: exploring the psychosocial impact of oral HIV pre-exposure prophylaxis on gay men in England
Authors: Hayes Rosalie , Nutland Will , Rayment Michael , Wayal Sonali , Apea Vanesa , Clarke Amanda , McOwan Alan , Sullivan Ann , Desai Monica , Jajja Andrew , Rice Brian , Horne Rob , McCormack Sheena , Gafos Mitzy
Published: November 2023

Gay, bisexual, and other men who have sex with men (GBMSM) experience a high prevalence of psychosocial health problems, such as harmful substance use and depression, as well as being disproportionately affected by HIV. HIV Pre-Exposure Prophylaxis (PrEP) may provide psychosocial benefits beyond its intended purpose of reducing HIV infection. We explore the psychosocial impact of oral PrEP use on gay men in England using qualitative data from the PROUD study. From February 2014 to January 2016, semi-structured in-depth interviews were conducted with 40 gay men and one trans woman. Participants were purposively recruited based on trial arm allocation, adherence, and sexual risk behaviours. By removing HIV risk from sex, PrEP improves users’ wellbeing by reducing HIV-related anxiety and internalised stigma and increasing HIV prevention self-efficacy, sexual pleasure, and intimacy. In turn, these psychological changes may influence behaviour in the form of greater sexual freedom, reduced harmful drug use, and more protective sexual health behaviours. However, PrEP may create internal conflict for some gay men, due to its disruption of social norms around condom use and its perceived influence on their sexual behaviour leading to reduced condom self-efficacy. These findings provide a baseline of PrEP’s psychosocial impact amongst some of the first PrEP users in England and supports calls to consider the psychosocial impact of PrEP in prescribing guidelines.
Maintaining quality of life after major lung resection for carcinoid tumor
Authors: Abdel Jalil Riad , Abdallah Farah A. , Obeid Zeinab , Abou Chaar Mohamad K. , Harb Ahmad Khaled , Shannies Tariq Bassam , El-Edwan Ahed , Haddad Hussam , Ghraibeh Azza , Abu-Shanab Ahmad
Published: November 2023

Background

Pulmonary carcinoid is a rare diagnosis with surgery remaining the standard treatment of choice. However, resection may impact patients’ daily activities due to decreased lung volume reserve and postoperative pain. Our study aims to compare the impact of different types of surgical resection on the post-operative quality of life with the application of a strict peri-operative pulmonary care program.

Methods

Patients who underwent surgery for bronchopulmonary carcinoid tumors in a tertiary cancer center between August, 2017 and March, 2020 were identified and demographic data was collected. Patients were contacted via phone for the qualitative and quantitative assessment of pain and quality of life, utilizing the Arabic version of Short-form McGill Pain Questionnaire and Activity of Daily Living (ADL) instrument respectively. Lung reserve was assessed before and after surgery. Statistical analysis used Chi-Square for categorical variables and ANOVA for continuous variables.

Results

A total of 16 patients underwent different type of resection. The majority were male (n = 10; 63%) with a mean age of 44 years (19–81). Most common clinical stage was stage I (n = 12, 75%) with typical carcinoid features recorded in more than half of the cases (n = 11, 69%). Almost all patients underwent surgical excision (n = 15, 94%) with negative resection margin and no major post-operative complications. Bilobectomy was the most frequent procedure (n = 6, 40%) and video-assisted thoracoscopic surgery (VATS) was utilized in 8 patients (50%). Expected changes were recorded in pre- and postoperative pulmonary function test with an average drop of 10 in FEV1 and 14 mL/min/mmHg in DLCO. The majority of patients (n = 15, 94%) were totally independent doing daily activities. Mild intermittent pain was found in 7 patients (44%) who scored an average intensity of 1.6 out of 10.

Conclusions

Excellent long-term outcomes can be achieved following surgical resection of pulmonary carcinoid tumors with little to no effect on patients’ lung function and quality of life in regard to performance status and post-operative pain when a good peri-operative pulmonary, physical rehabilitation, and pain management programs are adopted and strictly implemented.
Formation of an invasion-permissive matrix requires TGFβ/SNAIL1-regulated alternative splicing of fibronectin
Authors: Franco-Valls Héctor , Tusquets-Uxó Elsa , Sala Laura , Val Maria , Peña Raúl , Iaconcig Alessandra , Villarino Álvaro , Jiménez-Arriola Martín , Massó Pere , Trincado Juan L. , Eyras Eduardo , Muro Andrés F. , Otero Jorge , García de Herreros Antonio , Baulida Josep
Published: November 2023

Background

As in most solid cancers, the emergence of cells with oncogenic mutations in the mammary epithelium alters the tissue homeostasis. Some soluble factors, such as TGFβ, potently modify the behavior of healthy stromal cells. A subpopulation of cancer-associated fibroblasts expressing a TGFβ target, the SNAIL1 transcription factor, display myofibroblastic abilities that rearrange the stromal architecture. Breast tumors with the presence of SNAIL1 in the stromal compartment, and with aligned extracellular fiber, are associated with poor survival prognoses.

Methods

We used deep RNA sequencing and biochemical techniques to study alternative splicing and human tumor databases to test for associations (correlation t-test) between SNAIL1 and fibronectin isoforms. Three-dimensional extracellular matrices generated from fibroblasts were used to study the mechanical properties and actions of the extracellular matrices on tumor cell and fibroblast behaviors. A metastatic mouse model of breast cancer was used to test the action of fibronectin isoforms on lung metastasis.

Results

In silico studies showed that SNAIL1 correlates with the expression of the extra domain A (EDA)-containing (EDA+) fibronectin in advanced human breast cancer and other types of epithelial cancers. In TGFβ-activated fibroblasts, alternative splicing of fibronectin as well as of 500 other genes was modified by eliminating SNAIL1. Biochemical analyses demonstrated that SNAIL1 favors the inclusion of the EDA exon by modulating the activity of the SRSF1 splicing factor. Similar to Snai1 knockout fibroblasts, EDA- fibronectin fibroblasts produce an extracellular matrix  that does not sustain TGFβ-induced fiber organization, rigidity, fibroblast activation, or tumor cell invasion. The presence of EDA+ fibronectin changes the action of metalloproteinases on fibronectin fibers. Critically, in an mouse orthotopic breast cancer model, the absence of the fibronectin EDA domain completely prevents lung metastasis.

Conclusions

Our results support the requirement of EDA+ fibronectin in the generation of a metastasis permissive stromal architecture in breast cancers and its molecular control by SNAIL1. From a pharmacological point of view, specifically blocking EDA+ fibronectin deposition could be included in studies to reduce the formation of a pro-metastatic environment.