bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimizing IP issues associated with gene constructs encoding the Bt toxin - a case study
Authors: Hassan Md Mahmudul , Tenazas Francis , Williams Adam , Chiu Jing-wen , Robin Charles , Russell Derek A. , Golz John F. 
Published: June 2024

Abstract
Background
As part of a publicly funded initiative to develop genetically engineered Brassicas (cabbage, cauliflower, and canola) expressing Bacillus thuringiensis Crystal (Cry)-encoded insecticidal (Bt) toxin for Indian and Australian farmers, we designed several constructs that drive high-level expression of modified Cry1B and Cry1C genes (referred to as Cry1BM and Cry1CM; with M indicating modified). The two main motivations for modifying the DNA sequences of these genes were to minimise any licensing cost associated with the commercial cultivation of transgenic crop plants expressing CryM genes, and to remove or alter sequences that might adversely affect their activity in plants.

Results
To assess the insecticidal efficacy of the Cry1BM/Cry1CM genes, constructs were introduced into the model Brassica Arabidopsis thaliana in which Cry1BM/Cry1CM expression was directed from either single (S4/S7) or double (S4S4/S7S7) subterranean clover stunt virus (SCSV) promoters. The resulting transgenic plants displayed a high-level of Cry1BM/Cry1CM expression. Protein accumulation for Cry1CM ranged from 5.18 to 176.88 µg Cry1CM/g dry weight of leaves. Contrary to previous work on stunt promoters, we found no correlation between the use of either single or double stunt promoters and the expression levels of Cry1BM/Cry1CM genes, with a similar range of Cry1CM transcript abundance and protein content observed from both constructs. First instar Diamondback moth (Plutella xylostella) larvae fed on transgenic Arabidopsis leaves expressing the Cry1BM/Cry1CM genes showed 100% mortality, with a mean leaf damage score on a scale of zero to five of 0.125 for transgenic leaves and 4.2 for wild-type leaves.

Conclusions
Our work indicates that the modified Cry1 genes are suitable for the development of insect resistant GM crops. Except for the PAT gene in the USA, our assessment of the intellectual property landscape of components presents within the constructs described here suggest that they can be used without the need for further licensing. This has the capacity to significantly reduce the cost of developing and using these Cry1M genes in GM crop plants in the future.
The need for and acceptability of a cancer training course for medical and nursing students in Tanzania: a convergent mixed methods study
Authors: Mushy Stella Emmanuel , Mkoka Dickson A. , Lukumay Gift G. , Massae Agnes F. , Rohloff Corissa T. , Mgopa Lucy R. , Mwakawanga Dorkasi L. , Kohli Nidhi , Ross Michael W. , Mkonyi Ever , Trent Maria , Athumani Kibwanda , Kulasingam Shalini , Rosser B. R. Simon 
Published: June 2024

Abstract
Background
The cancer burden in Africa is on the rise. A Cancer Training Course on screening, prevention, care, and community education is crucial for addressing a wide range of cancer health issues. When appropriately educated healthcare providers on cancer provide care, patient care improves, and healthcare costs decrease. However, in Tanzania, doctors and nurses receive little or no training in primary cancer care in their bachelor’s program.

Aim
This study assessed the need and acceptability of a cancer training course for nursing and medical doctor students at the Muhimbili University of Health and Allied Sciences (MUHAS) in Dar es Salaam, Tanzania.

Methods
This study was a cross-sectional parallel mixed method study during the 3-month follow-up within the larger study on sexual health training for health professionals. The study was a randomized controlled (RCT), single-blind, parallel trial of sexual health training versus a waitlist control among health students at MUHAS in Tanzania. Descriptive analysis was performed to analyze the participants’ demographic information, need, and acceptability of the cancer training courseto determine the frequencies and percentages of their distribution between disciplines. In addition, inductive thematic analysis was performed for the qualitative data. The RCT study was registered at Clinical Trial.gov (NCT03923582; 01/05/2021).

Results
Data were collected from 408 students (272 medical doctors and 136 nursing students). The median age of the participants was 23 years. Most (86.0%) medical and 78.1% of nursing students reported receiving little to no cancer training. On the other hand, most (92.3%) medical and nursing (92.0%) students were interested in receiving cancer training. Furthermore, 94.1% of medical and 92.0% of nursing students needed a cancer training course in their undergraduate program. In addition, participants said a cancer training course would be important because it would help them improve the quality of cancer care and enhance the quality of life for patients by ensuring early diagnosis and treatment.

Conclusion
A cancer training course is both highly needed and acceptable to medical and nursing students. Implementation of this cancer training course will improve students’ knowledge and skills and eventually improve the quality of cancer care and patients’ quality of life by ensuring early diagnosis and management.
Evaluating competency-based medical education: a systematized review of current practices
Authors: Alharbi Nouf Sulaiman 
Published: June 2024

Abstract
Background
Few published articles provide a comprehensive overview of the available evidence on the topic of evaluating competency-based medical education (CBME) curricula. The purpose of this review is therefore to synthesize the available evidence on the evaluation practices for competency-based curricula employed in schools and programs for undergraduate and postgraduate health professionals.

Method
This systematized review was conducted following the systematic reviews approach with minor modifications to synthesize the findings of published studies that examined the evaluation of CBME undergraduate and postgraduate programs for health professionals.

Results
Thirty-eight articles met the inclusion criteria and reported evaluation practices in CBME curricula from various countries and regions worldwide, such as Canada, China, Turkey, and West Africa. 57% of the evaluated programs were at the postgraduate level, and 71% were in the field of medicine. The results revealed variation in reporting evaluation practices, with numerous studies failing to clarify evaluations’ objectives, approaches, tools, and standards as well as how evaluations were reported and communicated. It was noted that questionnaires were the primary tool employed for evaluating programs, often combined with interviews or focus groups. Furthermore, the utilized evaluation standards considered the well-known competencies framework, specialized association guidelines, and accreditation criteria.

Conclusion
This review calls attention to the importance of ensuring that reports of evaluation experiences include certain essential elements of evaluation to better inform theory and practice.
Exploring the relationship between cyberloafing and innovativeness among nurses in research hospitals: a cross-sectional study in Turkey
Authors: Aciksoz Semra , Sendir Merdiye , Atar Nurdan Yalcin , Simsekoglu Nesibe , Baydili Kursad Nuri 
Published: June 2024

Abstract
Background
Although cyberloafing, which refers to employees' use of the internet for private purposes outside of work, is seen as a negative behavior; Positive effects on areas such as individual development, learning opportunity, job satisfaction, productivity, change, organizational output, and innovation have also been reported. This study aims to investigate whether there is a significant relationship between cyberloafing and the innovativeness levels of nurses working in research hospitals in Turkey.

Methods
This analytical study consisted of 230 nurses. Data were collected using a nurse information form, Cyberloafing Scale, and Individual Innovativeness Scale. Data analysis was carried out using descriptive, comparative, and correlational statistics.

Results
Nurses had low levels of minor and severe cyberloafing scores and skeptical innovativeness. There was no correlation between cyberloafing and individual innovativeness.

Conclusions
More conscious cyberloafing should be encouraged through institutional arrangements, which can improve nurses' individual and innovative professional aspects.
Employing a serious game intervention to promote adolescent school children’s perceptions of nursing and midwifery professions
Authors: Mitchell Gary , Rainey Debbie , Healy Maria , Anderson Tara , Stark Patrick , Kalu Felicity Agwu , Monaghan Catherine , Linden Mark A 
Published: June 2024

Abstract
Aim
To test a serious game intervention about nursing and midwifery perceptions among adolescent school children.

Background
Nursing and midwifery professions face challenges in recruitment, with persistent gender stereotypes and a lack of clarity regarding the roles contributing to this issue. This study addresses the need for innovative approaches to reshape perceptions and encourage career exploration in adolescent school children.

Design
Employing a pre/post-test design, this study involved 137 post-primary students aged sixteen or seventeen in the United Kingdom.

Methods
Data collection occurred between November 2022 to April 2023, involving three post-primary schools. Participants engaged with a digital serious game designed to address misconceptions and promote a more accurate understanding of nursing and midwifery. Participants completed pre- and post-intervention questionnaires, including an adapted version of the Nursing as a Career Choice Questionnaire. Statistical analyses included descriptive statistics, paired t-tests, and independent groups t-tests.

Results
The serious game intervention resulted in statistically significant improvements in students’ perceptions across multiple domains. Overall, participants showed higher mean post-test scores (M = 139.57, SD = 15.10) compared to their mean pre-test score (M = 131.06, SD = 14.73) on the questionnaire. The domains of self-efficacy (p < .001), job prospects (p < .001) and social influences (p < .001) exhibited the most substantial positive changes. Female participants showed higher perceptions than males in pre- and post-tests and students from all-girls schools consistently scored higher than those from all-boys and mixed-gender schools.

Conclusions
A serious game about the nursing and midwifery professions appears to be capable of changing perceptions of self-efficacy and job prospects related to nursing and midwifery professions. The study suggests that a serious game intervention may have the potential to change adolescent perceptions of nursing and midwifery professions which may lead to their considering of these when making future career choices.
Genome-wide in vivo CRISPR screen identifies TGFβ3 as actionable biomarker of palbociclib resistance in triple negative breast cancer
Authors: Poulet Sophie , Dai Meiou , Wang Ni , Yan Gang , Boudreault Julien , Daliah Girija , Guillevin Alan , Nguyen Huong , Galal Soaad , Ali Suhad , Lebrun Jean-Jacques 
Published: June 2024

AbstractTriple negative breast cancer (TNBC) remains exceptionally challenging to treat. While CDK4/6 inhibitors have revolutionized HR + breast cancer therapy, there is limited understanding of their efficacy in TNBC and meaningful predictors of response and resistance to these drugs remain scarce. We conducted an in vivo genome-wide CRISPR screen using palbociclib as a selection pressure in TNBC. Hits were prioritized using microarray data from a large panel of breast cancer cell lines to identify top palbociclib sensitizers. Our study defines TGFβ3 as an actionable determinant of palbociclib sensitivity that potentiates its anti-tumor effects. Mechanistically, we show that chronic palbociclib exposure depletes p21 levels, contributing to acquired resistance, and that TGFβ3 treatment can overcome this. This study defines TGFβ3 as an actionable biomarker that can be used to improve patient stratification for palbociclib treatment and exploits the synergistic interaction between CDK4/6 and TGFβ3 to propose a new combinatorial treatment for TNBC.
The association between the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio and the risk of osteoporosis among U.S. adults: analysis of NHANES data
Authors: Wang Jinzhou , Li Shanshan , Pu Hongyu , He Jiangtao 
Published: June 2024

Abstract
Background
Osteoporosis and atherosclerosis frequently afflict older adults, and recent insights suggest a deeper connection between these conditions that surpasses mere aging effects. The ratio of non-high-density to high-density lipoprotein cholesterol (NHHR) has emerged as a novel lipid marker for evaluating the risk of cardiovascular diseases. Nonetheless, investigations into the correlation of the NHHR with the risk of developing osteoporosis remain unexplored.

Methods
We collected NHHR and bone mineral density (BMD) data from 11,024 National Health and Nutrition Examination Survey (NHANES) participants between 2011 and 2018. Multivariate linear regression was employed to examine the correlation between BMD and NHHR. Smooth curves were employed to deal with the nonlinearity. To further account for the nonlinear link, we used a two-part linear regression model. The threshold effects were estimated using two components of a linear regression model. Subgroup and sensitivity analyses were carried out to ascertain the stability of the findings.

Results
We discovered a negative relationship between the NHHR and lumbar spine BMD in all three models. An L-shaped curvilinear association existed between the NHHR and lumbar spine BMD, with a key inflection point of 6.91. The fully adjusted model showed that the BMD of the lumbar spine fell by 0.03 g/cm2 in those who were in the fourth quartile as opposed to the lowest quartile. The sensitivity analysis using unweighted logistic analysis verified the stability of the results. In addition, BMD in the nondiabetic group was more significantly affected by the negative effect of the NHHR in the subgroup analysis.

Conclusions
According to this research, there appears to be a negative correlation between BMD and NHHR in US Adults. To clarify the precise physiological mechanisms by which the NHHR contributes to the onset of osteoporosis, more research is necessary.
Dual-mode nanoprobe strategy integrating ultrasound and near-infrared light for targeted and synergistic arterial thrombolysis
Authors: Wang Zhiwen , Jiang Nan , Jiang Zhixin , Wang Hao , Guo Yuxin , Zhong Fanglu , Gui Bin , Chen Yueying , Deng Qing , Zhou Qing , Hu Bo 
Published: June 2024

AbstractEfficient thrombolysis in time is crucial for prognostic improvement of patients with acute arterial thromboembolic disease, while limitations and complications still exist in conventional thrombolytic treatment methods. Herein, our study sought to investigate a novel dual-mode strategy that integrated ultrasound (US) and near-infrared light (NIR) with establishment of hollow mesoporous silica nanoprobe (HMSN) which contains Arginine-glycine-aspartate (RGD) peptide (thrombus targeting), perfluoropentane (PFP) (thrombolysis with phase-change and stable cavitation) and indocyanine green (ICG) (thrombolysis with photothermal conversion). HMSN is used as the carrier, the surface is coupled with targeted RGD to achieve high targeting and permeability of thrombus, PFP and ICG are loaded to achieve the collaborative diagnosis and treatment of thrombus by US and NIR, so as to provide a new strategy for the integration of diagnosis and treatment of arterial thrombus. From the in vitro and in vivo evaluation, RGD/ICG/PFP@HMSN can aggregate and penetrate at the site of thrombus, and finally establish the dual-mode directional development and thrombolytic treatment under the synergistic effect of US and NIR, providing strong technical support for the accurate diagnosis and treatment of arterial thrombosis.
Graphical Abstract
Systematic review of fatigue severity in ME/CFS patients: insights from randomized controlled trials
Authors: Park Jae-Woong , Park Byung-Jin , Lee Jin-Seok , Lee Eun-Jung , Ahn Yo-Chan , Son Chang-Gue 
Published: June 2024

Abstract
Background
Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a debilitating illness medically unexplained, affecting approximately 1% of the global population. Due to the subjective complaint, assessing the exact severity of fatigue is a clinical challenge, thus, this study aimed to produce comprehensive features of fatigue severity in ME/CFS patients.

Methods
We systematically extracted the data for fatigue levels of participants in randomized controlled trials (RCTs) targeting ME/CFS from PubMed, Cochrane Library, Web of Science, and CINAHL throughout January 31, 2024. We normalized each different measurement to a maximum 100-point scale and performed a meta-analysis to assess fatigue severity by subgroups of age, fatigue domain, intervention, case definition, and assessment tool, respectively.

Results
Among the total of 497 relevant studies, 60 RCTs finally met our eligibility criteria, which included a total of 7088 ME/CFS patients (males 1815, females 4532, and no information 741). The fatigue severity of the whole 7,088 patients was 77.9 (95% CI 74.7–81.0), showing 77.7 (95% CI 74.3–81.0) from 54 RCTs in 6,706 adults and 79.6 (95% CI 69.8–89.3) from 6 RCTs in 382 adolescents. Regarding the domain of fatigue, ‘cognitive’ (74.2, 95% CI 65.4–83.0) and ‘physical’ fatigue (74.3, 95% CI 68.3–80.3) were a little higher than ‘mental’ fatigue (70.1, 95% CI 64.4–75.8). The ME/CFS participants for non-pharmacological intervention (79.1, 95% CI 75.2–83.0) showed a higher fatigue level than those for pharmacological intervention (75.5, 95% CI 70.0–81.0). The fatigue levels of ME/CFS patients varied according to diagnostic criteria and assessment tools adapted in RCTs, likely from 54.2 by ICC (International Consensus Criteria) to 83.6 by Canadian criteria and 54.2 by MFS (Mental Fatigue Scale) to 88.6 by CIS (Checklist Individual Strength), respectively.

Conclusions
This systematic review firstly produced comprehensive features of fatigue severity in patients with ME/CFS. Our data will provide insights for clinicians in diagnosis, therapeutic assessment, and patient management, as well as for researchers in fatigue-related investigations.
Whole genome sequencing of HER2-positive metastatic extramammary Paget’s disease: a case report
Authors: Lim Boon Yee , Guo Zexi , Lim Jing Quan , Ko Tun Kiat , Lee Elizabeth Chun Yong , Kannan Bavani , Lee Jing Yi , Lim Abner Herbert , Li Zhimei , Ng Cedric Chuan-Young , Busmanis Inny , Chan Jason Yongsheng 
Published: June 2024

Abstract
Background
Extramammary Paget’s disease (EMPD) is a rare cancer that occurs within the epithelium of the skin, arising predominantly in areas with high apocrine gland concentration such as the vulva, scrotum, penis and perianal regions. Here, we aim to integrate clinicopathological data with genomic analysis of aggressive, rapidly-progressing de novo metastatic EMPD responding to HER2-directed treatment in combination with other agents, to attain a more comprehensive understanding of the disease landscape.

Methods
Immunohistochemical staining on the scrotal wall tumor and bone marrow metastasis demonstrated HER2 overexpression. Whole genome sequencing of the tumor and matched blood was performed.

Results
Notable copy number gains (log2FC > 0.9) on chromosomes 7 and 8 were detected (n = 81), with 92.6% of these unique genes specifically located on chromosome 8. Prominent cancer-associated genes include ZNF703, HOOK3, DDHD2, LSM1, NSD3, ADAM9, BRF2, KAT6A and FGFR1. Interestingly, ERBB2 gene did not exhibit high copy number gain (log2FC = 0.4) although 90% of tumor cells stained HER2-positive. Enrichment in pathways associated with transforming growth factor-beta (TGFβ) (FDR = 0.0376, Enrichment Ratio = 8.12) and fibroblast growth factor receptor (FGFR1) signaling (FDR = 0.0082, Enrichment Ratio = 2.3) was detected. Amplicon structure analysis revealed that this was a simple-linear amplification event.

Conclusion
Whole genome sequencing revealed the underlying copy number variation landscape in HER2-positive metastatic EMPD. The presence of alternative signalling pathways and genetic variants suggests potential interactions with HER2 signalling, which possibly contributed to the HER2 overexpression and observed response to HER2-directed therapy combined with other agents in a comprehensive treatment regimen.
Implementation of a point-of-care ultrasound archiving system and governance framework in a UK physician-paramedic staffed helicopter emergency medical service
Authors: Aziz Shadman , Edmunds Christopher T. , Barratt Jon 
Published: June 2024

Abstract
Introduction
There has been a rapid expansion in the use of point-of-care ultrasonography (POCUS) by emergency medical services (EMS). However, less than a third of UK EMS utilise imaging archiving for POCUS, and fewer review saved images as part of a clinical governance structure. This paper describes the implementation of a novel image archiving system and a robust clinical governance framework in our UK physician-paramedic staffed helicopter emergency medical service (HEMS).

Methods
A retrospective database review was conducted of all patients attended by East Anglian Air Ambulance (EAAA) between the introduction of a new POCUS device and image archiving system on 1 December 2020 to 31 January 2024. All patients with recorded POCUS examinations were included. Images from POCUS examinations at EAAA are archived on a cloud-based server, and retrospectively reviewed within 24 h by an EAAA POCUS supervisor. Image quality is graded using a 5-point Likert-type scale, agreement between reviewer and clinician is recorded and feedback is provided on scanning technique. T-tests were used to assess the difference in image quality between physicians and paramedics. Inter-rater reliability between reviewers and clinicians was assessed using Cohen’s kappa (κ).

Results
During the study period, 5913 patients were attended by EAAA. Of these, 1097 patients had POCUS images recorded. The prevalence of POCUS during the study period was 18.6%. 1061 patient examinations underwent quality assurance (96.7%). The most common POCUS examination was echocardiography (60%), predominantly during cardiac arrest. The primary scanning clinician was a paramedic in 25.4% of POCUS examinations. Across all examination types; image quality was not significantly different between physicians and paramedics and agreement between reviewers and clinicians was strong (κ > 0.85).

Conclusions
In this service evaluation study, we have described outcomes following the introduction of a new POCUS device, image archiving system and governance framework in our HEMS. Paramedics were the primary scanning clinician in a quarter of scans, with image quality comparable to physicians. Almost all scans underwent quality assurance and inter-rater reliability was strong between clinicians and reviewers. Further research is required to investigate the diagnostic accuracy of POCUS and to demonstrate the effect of utilising prehospital POCUS to refine diagnosis on clinical outcomes.