bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy of bougie first approach for endotracheal intubation with video laryngoscopy during continuous chest compression: a randomized crossover manikin trial
Authors: Xu Xiaohan , Ma Haobo , Zhang Yuelun , Liu Wei , Jung Boris , Li Xu , Shen Le
Published: May 2024

Background

Endotracheal intubation is challenging during cardiopulmonary resuscitation, and video laryngoscopy has showed benefits for this procedure. The aim of this study was to compare the effectiveness of various intubation approaches, including the bougie first, preloaded bougie, endotracheal tube (ETT) with stylet, and ETT without stylet, on first-attempt success using video laryngoscopy during chest compression.

Methods

This was a randomized crossover trial conducted in a general tertiary teaching hospital. We included anesthesia residents in postgraduate year one to three who passed the screening test. Each resident performed intubation with video laryngoscopy using the four approaches in a randomized sequence on an adult manikin during continuous chest compression. The primary outcome was the first-attempt success defined as starting ventilation within a one minute.

Results

A total of 260 endotracheal intubations conducted by 65 residents were randomized and analyzed with 65 procedures in each group. First-attempt success occurred in 64 (98.5%), 57 (87.7%), 56 (86.2%), and 46 (70.8%) intubations in the bougie-first, preloaded bougie, ETT with stylet, and ETT without stylet approaches, respectively. The bougie-first approach had a significantly higher possibility of first-attempt success than the preloaded bougie approach [risk ratio (RR) 8.00, 95% confidence interval (CI) 1.03 to 62.16, P = 0.047], the ETT with stylet approach (RR 9.00, 95% CI 1.17 to 69.02, P = 0.035), and the ETT without stylet approach (RR 19.00, 95% CI 2.62 to 137.79, P = 0.004) in the generalized estimating equation logistic model accounting for clustering of intubations operated by the same resident. In addition, the bougie first approach did not result in prolonged intubation or increased self-reported difficulty among the study participants.

Conclusions

The bougie first approach with video laryngoscopy had the highest possibility of first-attempt success during chest compression. These results helped inform the intubation approach during CPR. However, further studies in an actual clinical environment are warranted to validate these findings.

Trial registration

Clinicaltrials.gov; identifier: NCT05689125; date: January 18, 2023.
Exploring the factors influencing evidence-based approaches to advanced chronic kidney disease: a qualitative study involving nurses and physicians
Authors: Pintado-Outumuro Elena , Morin-Fraile Victoria , Salvador-González Betlem , Benito Llúcia , Julve-Ibáñez Maricel , Sancho-Campos M.-Pilar , Alves-Tafur Carolina , Lumillo-Gutiérrez Iris
Published: May 2024

Background

Advanced chronic kidney disease (ACKD) is associated with a high risk of adverse cardiovascular and renal events and has a significant impact on quality of life and life expectancy. Several studies have identified areas for improvement in their management in primary care. Some professional and environmental factors can act as key barriers to appropriate care.

Objective

To analyse attitudes, subjective norms, and perceived behavioural control among primary care professionals related to the implementation of an evidence-based approach for individuals with ACKD in primary care.

Methodology

This was a qualitative study using an interpretative phenomenological approach based on the theory of planned behaviour. Two aspects of the evidence-based approach were explored: the implementation of clinical practice guidelines and the utilisation of electronic kidney disease records within the scope of this study. Primary care nurses and physicians participated in a previous pilot interview and five focus groups. Subsequently, a thematic analysis of the gathered data was conducted.

Findings

Thirty-three primary care professionals participated. The emerging themes included: experiences in the management of ACKD (highlighting a distinct profile of older, frail patients with comorbidities masking CKD and a CKD follow-up primarily focused on analytical monitoring and drug adjustment); factors in the professional environment influencing the use of scientific evidence (such as time constraints, excessive electronic health records, and unfamiliar reference guidelines); attitudes towards the application of recommendations on ACKD (recognising limitations of computer systems despite considering them as guidance); and capacities to implement evidence-based recommendations (acknowledging formative needs and challenges in coordinating care with nephrology services).

Conclusions

Several psychological elements identified through the TBP hinder the adequate implementation of an evidence-based approach for individuals with CKD. Attitudes have been identified as factors modulating the use of standardised electronic records. Instead, subjective norms (influences from the professional environment) and perceived behavioral control (perception of capabilities) acted as barriers to the proper application of clinical practice guidelines and standardised records.

Implications for practice

Strategies aimed at optimising the management of people with ACKD should focus not only on training but also on improving attitudes, organisational structures, IT systems and coordination between primary care and nephrology.
Goal setting in later life: an international comparison of older adults’ defined goals
Authors: Burton Elissa , Chonody Jill , Teater Barbra , Alford Sabretta
Published: May 2024

Background

Studies of goal setting in later life tend to focus on health-related goal setting, are pre-determined by the researcher (i.e., tick box), and/or are focused on a specific geographical area (i.e., one country). This study sought to understand broader, long-term goals from the perspective of older adults (65 + years) from Australia, New Zealand (NZ), United Kingdom (UK), Ireland, Canada, and the United States of America (USA).

Methods

Through a cross-sectional, online survey (N = 1,551), this exploratory study examined the qualitative goal content of older adults. Thematic analysis was used to analyze the qualitative data, and bivariate analyses were used to compare thematic differences between regions and by participants’ sex.

Results

Over 60% of the participants reported setting goals, and participants from the Australia-NZ and Canada-USA regions were more likely to set goals than the UK-Ireland region. The following six overarching themes were identified from the 946 goals reported: health and well-being; social connections and engagement; activities and experiences; finance and employment; home and lifestyle; and attitude to life.

Conclusions

This study supports previous research that demonstrates that older adults can and do set personal goals that are wide ranging. These findings support the need for health professionals to consider different methods for elucidating this important information from older adults that builds rapport and focuses on aspects viewed as more important by the older adult and therefore potentially produces improved health outcomes.
Strategies aiming to improve statin therapy adherence in older adults: a systematic review
Authors: Frieden Philipp , Gagnon Rose , Bénard Élodie , Cossette Benoît , Bergeron Frédéric , Talbot Denis , Guertin Jason Robert
Published: May 2024

Background

Randomized clinical trials have shown that, under optimal conditions, statins reduce the risk of cardiovascular events in older adults. Given the prevalence and consequences of suboptimal adherence to statin among older adults, it is essential to document strategies designed to increase statin adherence in this population. The objective of this systematic review is to describe and summarize the effectiveness of interventions to improve statin adherence in older adults (≥ 65 years old).

Methods

This review followed PRISMA guidelines. Studies were identified from PubMed, PsycINFO, Embase, CINAHL and Web of Science. Study selection was conducted independently by four reviewers working in pairs. Included studies reported data on interventions designed to increase adherence to statin therapy in older adults and were original trials or observational studies. Interventions were pragmatically regrouped into 8 different categories going from patient to administrative level. Two reviewers extracted study data and assessed study quality independently. Given the heterogeneity between the included studies, a narrative critique and summary was conducted.

Results

Twelve out of the 2889 identified articles were included in the review. Our review showed that simplifying patients’ drug regimen, administrative improvements and large-scale pharmacy-led automated telephone interventions show positive effects on patient adherence to statin therapy, with odds ratios between > 1.0 and 3.0, while education-based strategies and intensified patient care showed mixed results.

Conclusions

Current evidence suggests that some interventions can increase statin adherence in older adults, which could help in the reduction of the risk of a cardiovascular event in this population.
Development and validation of a nomogram for predicting in-hospital death in cirrhotic patients with acute kidney injury
Authors: Li Xiang , Li Xunliang , Zhao Wenman , Wang Deguang
Published: May 2024

Background

The purpose of this study was to develop a nomogram for predicting in-hospital mortality in cirrhotic patients with acute kidney injury (AKI) in order to identify patients with a high risk of in-hospital death early.

Methods

This study collected data on cirrhotic patients with AKI from 2008 to 2019 using the Medical Information Mart for Intensive Care IV. Multivariate logistic regression was used to identify confounding factors related to in-hospital mortality, which were then integrated into the nomogram. The concordance index (C-Index) was used to evaluate the accuracy of the model predictions. The area under the curve (AUC) and decision curve analysis (DCA) was used to assess the predictive performance and clinical utility of the nomogram.

Results

The final study population included 886 cirrhotic patients with AKI, and 264 (29.8%) died in the hospital. After multivariate logistic regression, age, gender, cerebrovascular disease, heart rate, respiration rate, temperature, oxygen saturation, hemoglobin, blood urea nitrogen, serum creatinine, international normalized ratio, bilirubin, urine volume, and sequential organ failure assessment score were predictive factors of in-hospital mortality. In addition, the nomogram showed good accuracy in estimating the in-hospital mortality of patients. The calibration plots showed the best agreement with the actual presence of in-hospital mortality in patients. In addition, the AUC and DCA curves showed that the nomogram has good prediction accuracy and clinical value.

Conclusions

We have created a prognostic nomogram for predicting in-hospital death in cirrhotic patients with AKI, which may facilitate timely intervention to improve prognosis in these patients.
Machine learning models on a web application to predict short-term postoperative outcomes following anterior cervical discectomy and fusion
Authors: Karabacak Mert , Bhimani Abhiraj D. , Schupper Alexander J. , Carr Matthew T. , Steinberger Jeremy , Margetis Konstantinos
Published: May 2024

Background

The frequency of anterior cervical discectomy and fusion (ACDF) has increased up to 400% since 2011, underscoring the need to preoperatively anticipate adverse postoperative outcomes given the procedure’s expanding use. Our study aims to accomplish two goals: firstly, to develop a suite of explainable machine learning (ML) models capable of predicting adverse postoperative outcomes following ACDF surgery, and secondly, to embed these models in a user-friendly web application, demonstrating their potential utility.

Methods

We utilized data from the National Surgical Quality Improvement Program database to identify patients who underwent ACDF surgery. The outcomes of interest were four short-term postoperative adverse outcomes: prolonged length of stay (LOS), non-home discharges, 30-day readmissions, and major complications. We utilized five ML algorithms - TabPFN, TabNET, XGBoost, LightGBM, and Random Forest - coupled with the Optuna optimization library for hyperparameter tuning. To bolster the interpretability of our models, we employed SHapley Additive exPlanations (SHAP) for evaluating predictor variables’ relative importance and used partial dependence plots to illustrate the impact of individual variables on the predictions generated by our top-performing models. We visualized model performance using receiver operating characteristic (ROC) curves and precision-recall curves (PRC). Quantitative metrics calculated were the area under the ROC curve (AUROC), balanced accuracy, weighted area under the PRC (AUPRC), weighted precision, and weighted recall. Models with the highest AUROC values were selected for inclusion in a web application.

Results

The analysis included 57,760 patients for prolonged LOS [11.1% with prolonged LOS], 57,780 for non-home discharges [3.3% non-home discharges], 57,790 for 30-day readmissions [2.9% readmitted], and 57,800 for major complications [1.4% with major complications]. The top-performing models, which were the ones built with the Random Forest algorithm, yielded mean AUROCs of 0.776, 0.846, 0.775, and 0.747 for predicting prolonged LOS, non-home discharges, readmissions, and complications, respectively.

Conclusions

Our study employs advanced ML methodologies to enhance the prediction of adverse postoperative outcomes following ACDF. We designed an accessible web application to integrate these models into clinical practice. Our findings affirm that ML tools serve as vital supplements in risk stratification, facilitating the prediction of diverse outcomes and enhancing patient counseling for ACDF.
Predictive Value of Jugulo-omohyoid Lymph Nodes in Lateral Lymph Node Metastasis of Papillary Thyroid Cancer
Authors: Cai Huizhu , Zhuge Lingdun , Huang Zehao , Wang Shixu , Shi Ping , Yan Dangui , Wei Minghui , Niu Lijuan , Li Zhengjiang
Published: May 2024

Background

Jugulo-omohyoid lymph nodes (JOHLN) metastasis has proven to be associated with lateral lymph node metastasis (LLNM). This study aimed to reveal the clinical features and evaluate the predictive value of JOHLN in PTC to guide the extent of surgery.

Methods

A total of 550 patients pathologically diagnosed with PTC between October 2015 and January 2020, all of whom underwent thyroidectomy and lateral lymph node dissection, were included in this study.

Results

Thyroiditis, tumor location, tumor size, extra-thyroidal extension, extra-nodal extension, central lymph node metastasis (CLNM), and LLMM were associated with JOHLN. Male, upper lobe tumor, multifocality, extra-nodal extension, CLNM, and JOHLN metastasis were independent risk factors from LLNM. A nomogram based on predictors performed well. Nerve invasion contributed the most to the prediction model, followed by JOHLN metastasis. The area under the curve (AUC) was 0.855, and the p-value of the Hosmer-Lemeshow goodness of fit test was 0.18. Decision curve analysis showed that the nomogram was clinically helpful.

Conclusion

JOLHN metastasis could be a clinically sensitive predictor of further LLM. A high-performance nomogram was established, which can provide an individual risk assessment of LNM and guide treatment decisions for patients.
Malignant transformation of white sponge nevus: a case report of a novel keratin 4 mutation
Authors: Liu Dan , Zhang Tianyu , Zhou Hangfan , Wu Chuanji , Li Taiwen , Jiang Lu
Published: May 2024

Background

White Sponge Nevus (WSN) is traditionally considered a benign genetic disorder affecting the oral mucosa, primarily caused by pathogenic mutations in keratin 4 (KRT4) or keratin 13 (KRT13). Despite its benign nature, recent evidence has begun to question the malignant potential of WSN.

Case presentation

We report a case involving a 70-year-old man who presented with a white lesion on the right floor of his mouth. Initial diagnostic evaluations confirmed the lesion as WSN. Over a one-year follow-up, the lesion underwent malignant transformation, evolving into local epithelial moderate-to-severe dysplasia. Exome sequencing identified a novel insertion mutation in exon 1 of the KRT4 gene, resulting in a deletion-insertion amino acid mutation involving glycine. Single-cell RNA sequencing further revealed altered epithelial proliferation and differentiation dynamics within the lesion.

Conclusions

This case not only expands the known genetic spectrum of KRT4 mutations associated with WSN but also provides preliminary evidence suggesting the malignant potential of WSN. The novel pathogenic mutation in KRT4 is postulated to alter epithelial proliferation and differentiation, thereby raising concerns about the malignant transformation of WSN. Further studies are warranted to confirm these findings.
Analgesic effects of oral Yokukansan on acute postoperative pain and involvement of the serotonin nervous system: a mouse model study
Authors: Kurita Shuichiro , Sasaki Mika , Tanaka Moegi , Kuwabara Yoshinori , Ogasawara Yukino , Baba Hiroshi , Kamiya Yoshinori
Published: May 2024

Background

Yokukansan, a traditional Japanese medicine (Kampo), has been widely used to treat neurosis, dementia, and chronic pain. Previous in vitro studies have suggested that Yokukansan acts as a partial agonist of the 5-HT1A receptor, resulting in amelioration of chronic pain through inhibition of nociceptive neuronal activity. However, its effectiveness for treating postoperative pain remains unknown, although its analgesic mechanism of action has been suggested to involve serotonin and glutamatergic neurotransmission. This study aimed to investigate the effect of Yokukansan on postoperative pain in an animal model.

Methods

A mouse model of postoperative pain was created by plantar incision, and Yokukansan was administered orally the day after paw incision. Pain thresholds for mechanical and heat stimuli were examined in a behavioral experiment. In addition, to clarify the involvement of the serotonergic nervous system, we examined the analgesic effects of Yokukansan in mice that were serotonin-depleted by para-chlorophenylalanine (PCPA) treatment and intrathecal administration of NAN-190, 5-HT1A receptor antagonist.

Results

Orally administered Yokukansan increased the pain threshold dose-dependent in postoperative pain model mice. Pretreatment of para-chlorophenylalanine dramatically suppressed serotonin immunoreactivity in the spinal dorsal horn without changing the pain threshold after the paw incision. The analgesic effect of Yokukansan tended to be attenuated by para-chlorophenylalanine pretreatment and significantly attenuated by intrathecal administration of 2.5 µg of NAN-190 compared to that in postoperative pain model mice without para-chlorophenylalanine treatment and NAN-190 administration.

Conclusion

This study demonstrated that oral administration of Yokukansan has acute analgesic effects in postoperative pain model mice. Behavioral experiments using serotonin-depleted mice and mice intrathecally administered with a 5-HT1A receptor antagonist suggested that Yokukansan acts as an agonist at the 5-HT1A receptor, one of the serotonin receptors, to produce analgesia.
Health profession education hackathons: a scoping review of current trends and best practices
Authors: Rooholamini Azadeh , Salajegheh Mahla
Published: May 2024

Background

While the concept of hacking in education has gained traction in recent years, there is still much uncertainty surrounding this approach. As such, this scoping review seeks to provide a detailed overview of the existing literature on hacking in health profession education and to explore what we know (and do not know) about this emerging trend.

Methods

This was a scoping review study using specific keywords conducted on 8 databases (PubMed, Embase, Scopus, Web of Science, ERIC, PsycINFO, Education Source, CINAHL) with no time limitation. To find additional relevant studies, we conducted a forward and backward searching strategy by checking the reference lists and citations of the included articles. Studies reporting the concept and application of hacking in education and those articles published in English were included. Titles, abstracts, and full texts were screened and the data were extracted by 2 authors.

Results

Twenty-two articles were included. The findings are organized into two main categories, including (a) a Description of the interventions and expected outcomes and (b) Aspects of hacking in health profession education.

Conclusion

Hacking in health profession education refers to a positive application that has not been explored before as discovering creative and innovative solutions to enhance teaching and learning. This includes implementing new instructional methods, fostering collaboration, and critical thinking to utilize unconventional approaches.
The progress test as a structuring initiative for programmatic assessment
Authors: Alavarce Débora Cristina , de Medeiros Melyssa Lima , de Araújo Viana Danylo , Abade Flávia , Vieira Joaquim Edson , Machado José Lúcio Martins , Collares Carlos Fernando
Published: May 2024

Background

The Progress Test is an individual assessment applied to all students at the same time and on a regular basis. The test was structured in the medical undergraduate education of a conglomerate of schools to structure a programmatic assessment integrated into teaching. This paper presents the results of four serial applications of the progress test and the feedback method to students.

Methods

This assessment comprises 120 items offered online by means of a personal password. Items are authored by faculty, peer-reviewed, and approved by a committee of experts. The items are classified by five major areas, by topics used by the National Board of Medical Examiners and by medical specialties related to a national Unified Health System. The correction uses the Item Response Theory with analysis by the “Rasch” model that considers the difficulty of the item.

Results

Student participation increased along the four editions of the tests, considering the number of enrollments. The median performances increased in the comparisons among the sequential years in all tests, except for test1 – the first test offered to schools. Between subsequent years of education, 2nd-1st; 4th-3rd and 5th-4th there was an increase in median scores from progress tests 2 through 4. The final year of undergraduate showed a limited increase compared to the 5th year. There is a consistent increase in the median, although with fluctuations between the observed intervals.

Conclusion

The progress test promoted the establishment of regular feedback among students, teachers and coordinators and paved the road to engagement much needed to construct an institutional programmatic assessment.
Ethical perspectives regarding Euthanasia, including in the context of adult psychiatry: a qualitative interview study among healthcare workers in Belgium
Authors: Verhofstadt Monica , Moureau Loïc , Pardon Koen , Liégeois Axel
Published: May 2024

Introduction

Previous research has explored euthanasia’s ethical dimensions, primarily focusing on general practice and, to a lesser extent, psychiatry, mainly from the viewpoints of physicians and nurses. However, a gap exists in understanding the comprehensive value-based perspectives of other professionals involved in both somatic and psychiatric euthanasia. This paper aims to analyze the interplay among legal, medical, and ethical factors to clarify how foundational values shape the ethical discourse surrounding euthanasia in both somatic and psychiatric contexts. It seeks to explore these dynamics among all healthcare professionals and volunteers in Belgium.

Methods

Semi-structured interviews were conducted with 30 Dutch-speaking healthcare workers who had encountered patients requesting euthanasia for psychiatric conditions, in Belgium, from August 2019 to August 2020. Qualitative thematic analysis was applied to the interview transcripts.

Findings

Participants identified three pivotal values and virtues: religious values, professional values, and fundamental medical values encompassing autonomy, beneficence, and non-maleficence, linked to compassion, quality care, and justice. These values interwove across four tiers: the patient, the patient’s inner circle, the medical realm, and society at large. Irrespective of their euthanasia stance, participants generally displayed a blend of ethical values across these tiers. Their euthanasia perspective was primarily shaped by value interpretation, significance allocation to key components, and tier weighting. Explicit mention of varying ethical values, potentially indicating distinct stances in favor of or against euthanasia, was infrequent.

Conclusion

The study underscores ethical discourse’s central role in navigating euthanasia’s intricate landscape. Fostering inclusive dialogue, bridging diverse values, supports informed decision-making, nurturing justice, and empathy. Tailored end-of-life healthcare in psychiatry is essential, acknowledging all involved actors’ needs. The study calls for interdisciplinary research to comprehensively grasp euthanasia’s multifaceted dimensions, and guiding policy evolution. While contextualized in Belgium, the implications extend to the broader euthanasia discourse, suggesting avenues for further inquiry and cross-cultural exploration.
Sustainability consciousness among nursing students in Egypt: a cross-sectional study
Authors: Mohamed Marwa Ahmed El-Sayed , Ghallab Eman , Hassan Ragaa Abdullah Ahmed , Amin Shaimaa Mohamed
Published: May 2024

Background

Recognizing nurses as pivotal change agents and urgent preparation for the next generation is crucial for addressing sustainability issues and cultivating a sustainable healthcare system. Reports highlight gaps in the integration of sustainable development goals (SDGs) into nursing curricula, prompting the International Council of Nurses to stress the importance of sustainable development in nursing education. The extent to which nursing students are aware of sustainability issues remains to be determined. This study addresses a global and Egyptian research gap by evaluating and comparing Sustainability Consciousness (SC) levels among nursing students at three universities, providing insights into awareness, attitudes, and behaviors related to sustainability.

Methods

This descriptive comparative study was conducted across three nursing faculties within three Egyptian public universities. The target population for this study was undergraduate nursing students enrolled in these universities during the academic year 2022-2023. This study used the extended version of the Sustainability Consciousness Questionnaire (SCQ-L) to measure individuals' knowingness, attitudes, and behaviors related to the three dimensions of sustainable development: environmental, social, and economic.

Results

More than half of the nursing students across the three universities expressed unfamiliarity with the SDGs. Social media was the most common source of information across the three universities. Sohag University recorded the highest median (IQR) scores in sustainability knowingness (72.0, IQR: 70.0-81.0), attitudes (56.0, IQR: 53.0-61.5), and behavior (65.0, IQR: 60.0-69.0) across their respective dimensions, as well as in overall SC (195, IQR: 184.5-208.5). This was followed by Damanhour University, with a median score of 179.0 (IQR: 124.5-194), and then Alexandria University, with a median score of 116.0 (IQR: 85.5-153), all of which were significantly different (all with p values=0.000). Older students from rural areas exhibited higher SC median scores, while students with insufficient family income and no familiarity with the SDGs had lower SC scores.

Conclusions

This study highlighted the prevalent reliance on social media for information among nursing students across these universities, emphasizing the pivotal role of academic institutions in integrating sustainability development concepts in nursing education. Sohag University's notable commitment to sustainability practices has contributed to the higher SC of its students compared to Alexandria and Damanhour Universities. The study also identified age, place of residence, family income, and familiarity with the SDGs as consistent predictors of sustainability consciousness.
The mediating effects of self-efficacy and study engagement on the relationship between specialty identity and career maturity of Chinese nursing students: a cross-sectional study
Authors: Liu Yanjia , Chong Mei Chan , Han Yanhong , Wang Hui , Xiong Lijuan
Published: May 2024

Background

Career maturity is a crucial indicator of career preparedness and unpreparedness can cause the turnover of new nurses. Considerable empirical work demonstrates the potential associations between specialty identity, self-efficacy, study engagement, and career maturity. This study aimed to explore the mediation role of self-efficacy and study engagement on the relationships between specialty identity and career maturity among Chinese nursing students.

Methods

Four hundred twenty-six Chinese nursing students were recruited between September 11 and October 30, 2022. The online survey was conducted following the CHERRIES checklist. Electronic questionnaires assessed their perceived specialty identity, self-efficacy, study engagement, and career maturity. The descriptive analysis, Harman single-factor analysis, Pearson correlation tests, structural equation modeling, and the bootstrap method were employed in data analysis.

Results

Bivariate correlation analysis identified a positive correlation between specialty identity, self-efficacy, study engagement, and career maturity (r = 0.276–0.440, P < 0.001). Self-efficacy and study engagement partially mediated the relationship between specialty identity and career maturity. Self-efficacy and study engagement played a chain mediating role between specialty identity and career maturity.

Conclusions

The underlying mechanism can explain the relationships between specialty identity and career maturity: a direct predictor and an indirect effect through self-efficacy and study engagement. Policymakers and educators should emphasize the importance of specialty identity and provide tailored strategies for improving care maturity depending on nursing students’ specialty identity, self-efficacy, study engagement in the early stages of career development.
New-generation advanced PROTACs as potential therapeutic agents in cancer therapy
Authors: Wang Chao , Zhang Yujing , Chen Wujun , Wu Yudong , Xing Dongming
Published: May 2024

Proteolysis-targeting chimeras (PROTACs) technology has garnered significant attention over the last 10 years, representing a burgeoning therapeutic approach with the potential to address pathogenic proteins that have historically posed challenges for traditional small-molecule inhibitors. PROTACs exploit the endogenous E3 ubiquitin ligases to facilitate degradation of the proteins of interest (POIs) through the ubiquitin–proteasome system (UPS) in a cyclic catalytic manner. Despite recent endeavors to advance the utilization of PROTACs in clinical settings, the majority of PROTACs fail to progress beyond the preclinical phase of drug development. There are multiple factors impeding the market entry of PROTACs, with the insufficiently precise degradation of favorable POIs standing out as one of the most formidable obstacles. Recently, there has been exploration of new-generation advanced PROTACs, including small-molecule PROTAC prodrugs, biomacromolecule-PROTAC conjugates, and nano-PROTACs, to improve the in vivo efficacy of PROTACs. These improved PROTACs possess the capability to mitigate undesirable physicochemical characteristics inherent in traditional PROTACs, thereby enhancing their targetability and reducing off-target side effects. The new-generation of advanced PROTACs will mark a pivotal turning point in the realm of targeted protein degradation. In this comprehensive review, we have meticulously summarized the state-of-the-art advancements achieved by these cutting-edge PROTACs, elucidated their underlying design principles, deliberated upon the prevailing challenges encountered, and provided an insightful outlook on future prospects within this burgeoning field.
Lipoproteins and metabolites in diagnosing and predicting Alzheimer’s disease using machine learning
Authors: Wang Fenglin , Wang Aimin , Huang Yiming , Gao Wenfeng , Xu Yaqi , Zhang Wenjing , Guo Guiya , Song Wangchen , Kong Yujia , Wang Qinghua , Wang Suzhen , Shi Fuyan
Published: May 2024

Background

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder that poses a substantial economic burden. The Random forest algorithm is effective in predicting AD; however, the key factors influencing AD onset remain unclear. This study aimed to analyze the key lipoprotein and metabolite factors influencing AD onset using machine-learning methods. It provides new insights for researchers and medical personnel to understand AD and provides a reference for the early diagnosis, treatment, and early prevention of AD.

Methods

A total of 603 participants, including controls and patients with AD with complete lipoprotein and metabolite data from the Alzheimer’s disease Neuroimaging Initiative (ADNI) database between 2005 and 2016, were enrolled. Random forest, Lasso regression, and CatBoost algorithms were employed to rank and filter 213 lipoprotein and metabolite variables. Variables with consistently high importance rankings from any two methods were incorporated into the models. Finally, the variables selected from the three methods, with the participants’ age, sex, and marital status, were used to construct a random forest predictive model.

Results

Fourteen lipoprotein and metabolite variables were screened using the three methods, and 17 variables were included in the AD prediction model based on age, sex, and marital status of the participants. The optimal random forest modeling was constructed with “mtry” set to 3 and “ntree” set to 300. The model exhibited an accuracy of 71.01%, a sensitivity of 79.59%, a specificity of 65.28%, and an AUC (95%CI) of 0.724 (0.645–0.804). When Mean Decrease Accuracy and Gini were used to rank the proteins, age, phospholipids to total lipids ratio in intermediate-density lipoproteins (IDL_PL_PCT), and creatinine were among the top five variables.

Conclusions

Age, IDL_PL_PCT, and creatinine levels play crucial roles in AD onset. Regular monitoring of lipoproteins and their metabolites in older individuals is significant for early AD diagnosis and prevention.
Mapping the needs of healthcare workers caring for COVID-19 patients using the socio-ecological framework: a rapid scoping review
Authors: Konstantinou Pinelopi , Theofanous Vaso , Karekla Maria , Kassianos Angelos P.
Published: May 2024

Undoubtedly, the mental health of healthcare workers (HCWs) was negatively affected because of caring for patients during the COVID-19 pandemic. However, literature is limited on mapping the challenges and needs of HCWs during COVID-19 pandemic. A widely used framework in public health for mapping evidence includes the socio-ecological models, suggesting behavior can be influenced by individual, interpersonal, organizational, and community factors. The aim of this rapid scoping review was to use the socio-ecological model to map and compile lessons learnt from the literature regarding primarily the challenges and needs and secondly available psychological interventions for HCWs caring for COVID-19 patients. PubMed, CINAHL and Scopus databases were searched, with 21 studies finally included examining challenges and needs of HCWs and 18 studies presenting psychological interventions. Organizational-level challenges and needs such as inadequate staff preparation and supplies of protective equipment, flexible work policies and paid rest periods were the most reported. Individual-level challenges and needs included COVID-19-related fears and reduced mental health, whereas interpersonal-related needs included support provision. Community-level challenges included societal stigma. Certain psychological interventions were found to be promising for HCWs, but these were utilized to address only individual-level challenges and needs. Given that well-being entails an interaction of factors, multi-level interventions addressing multiple socio-ecological levels (interpersonal, organizational, community) and that place HCWs in their social context should be administrated to increase and maintain intervention’ effects long-term and possibly aid in better coping with future pandemics.
Effects of marketing claims on toddler food products on parents’ product preferences, perceptions and purchasing intentions: an online experiment
Authors: Dixon Helen Gwenda , Awoke Mamaru Ayenew , Scully Maree , McCann Jennifer , Martin Jane , Morley Belinda , Rhodes Anthea , McAleese Alison , Schmidtke Andrea
Published: May 2024

Background

The retail market for toddler-specific packaged foods is growing. Many of these products are ultra-processed and high in nutrients of concern for health, yet marketed in ways that may make them appear wholesome. This study aims to assess parents’ responses to claims on unhealthy, ultra-processed toddler food products and test whether removing such claims promotes more accurate product perceptions and healthier product preferences.

Methods

Parents of toddlers aged 12 to < 36 months (N = 838) were recruited for an online experiment testing four on-pack claim conditions: control (no claim); 'contains "good" ingredient'; 'free from "bad" ingredient'; and unregulated 'child-related' claim. Participants were randomly assigned to one condition, then viewed images of toddler food products that varied in nutrition content and the claims displayed. Participants completed tasks assessing product preferences (unhealthy product displaying claim vs. a healthier option with no claim, across four food categories (banana bars, strawberry snacks, blueberry yogurt snacks and veggie snacks)), purchase intentions and product perceptions. Poisson regression (count variable) and linear regression (continuous outcomes) analyses were employed to test for mean differences by marketing claim conditions.

Results

For the overall sample, brief exposure to ‘free from "bad" ingredient’ claims increased participant’s intentions to purchase unhealthy food products for their toddlers, but there was no clear evidence that ‘contains "good" ingredient’ claims and ‘child-related’ claims significantly impacted parent’s preferences, purchase intentions and perceptions of toddler foods. However, certain claims influenced particular parent subgroups. Notably, parents with three or more children chose more unhealthy products when these products displayed ‘contains "good" ingredient’ or ‘free from "bad" ingredient’ claims; the latter claims also promoted stronger purchase intentions and enhanced product perceptions among this subgroup.

Conclusions

Findings indicate that ‘free from "bad" ingredient’ claims on unhealthy toddler foods are of most concern, as they boost the appeal of these products to parents. ‘Contains "good" ingredient’ claims and ‘child-related’ claims showed limited effects in this study. Considering available evidence, we recommend claims should not be permitted on child-oriented foods, as they may promote inaccurate product perceptions and unhealthy product choices by parents, that can detract from their children’s diets and health.
Adherence to the Mediterranean Diet and its association with gastric cancer: health benefits from a Planeterranean perspective
Authors: Reytor-González Claudia , Zambrano Ana Karina , Montalvan Martha , Frias-Toral Evelyn , Simancas-Racines Alison , Simancas-Racines Daniel
Published: May 2024

The Mediterranean Diet (MD) has garnered increasing attention for its potential protective effects against gastric cancer (GC). The MD’s rich content of antioxidants, polyphenols, and other bioactive compounds contributes to its ability to modulate gene expression, inhibit tumor growth, and regulate apoptosis. Studies have shown significant reductions in inflammatory markers such as C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) among individuals adhering to the MD, suggesting its pivotal role in mitigating chronic inflammation-associated with cancer development. Furthermore, the MD’s anti-angiogenic properties, particularly in components like olive oil, red wine, fish, and tomatoes, offer promising avenues for reducing GC risk by inhibiting tumor angiogenesis. Additionally, the MD’s influence on intestinal microbiota composition underscores its potential in maintaining immune homeostasis and reducing systemic inflammation, factors crucial in GC prevention. Despite challenges such as variability in dietary adherence scoring systems and the need for further gender and geographical-specific studies, evidence supports the MD as a cost-effective and holistic approach to GC prevention. Emphasizing the role of nutrition in public health is a promising strategy with broad implications for global health and cancer prevention initiatives. Therefore, this review explores the multifaceted impacts of the MD on GC prevention, delving into its anti-inflammatory, anti-angiogenic, and molecular mechanisms.
In silico analysis of the wild-type and mutant-type of BRCA2 gene
Authors: Li Jingjing , Ge Rui , Lu Guanming , Cai Yuanxuan , Teng Yuan , Fan Zhe , Liao Liangyan , Kong Lingjie , Zhang Jinze , Wei Tao , Li Qian , Long Tianzhu , Yu Hongyan , Li Jie
Published: May 2024

Background

The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure–function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC).

Methods

A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient’s whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein–protein docking (HADDOCK) algorithm and protein–ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC.

Results

Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1.

Conclusion

Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.
Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics
Authors: Li Hongzhe , Wang Yuwen , Liu Rongrong , Li Xiaoxiao , Zhang Ping , Chen Ping , Zhao Ning , Li Bing , Wang Jie , Tang Yongmin
Published: May 2024

Background

Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application.

Methods

We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro.

Results

In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them.

Conclusions

We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.