bluuebunny/crossref_metadata_2025 huggingface dataset:
Implications of GCLC in prognosis and immunity of lung adenocarcinoma and multi-omics regulation mechanisms
Authors: Huang Zhong , Liang Feifei , Wu Jiangtao , Huang Zichong , Li Yinglian , Huang Xiaoyuan , Liu Zhenyu
Published: May 2024

Background

Ferroptosis is an iron-dependent type of regulated cell death, and has been implicated in lung adenocarcinoma (LUAD). Evidence has proved the key role of glutamate-cysteine ligase catalytic subunit (GCLC) in ferroptosis, but its role in LUAD remains unclear. Herein, we explored the implications of GCLC and relevant genes in LUAD prognosis and immunity as well as underlying molecular mechanisms.

Methods

This work gathered mRNA, miRNA, DNA methylation, somatic mutation and copy-number variation data from TCGA-LUAD. WGCNA was utilized for selecting GCLC-relevant genes, and a GCLC-relevant prognostic signature was built by uni- and multivariate-cox regression analyses. Immune compositions were estimated via CIBERSORT, and two immunotherapy cohorts of solid tumors were analyzed. Multi-omics regulatory mechanisms were finally assessed.

Results

Our results showed that GCLC was overexpressed in LUAD, and potentially resulted in undesirable survival. A prognostic model was generated, which owned accurate and independent performance in prognostication. GCLC, and relevant genes were notably connected with immune compositions and immune checkpoints. High GCLC expression was linked with better responses to anti-PD-L1 and anti-CTLA-4 treatment. Their possible DNA methylation sites were inferred, e.g., hypomethylation in cg19740353 might contribute to GCLC up-regulation. Frequent genetic mutations also affected their expression. Upstream transcription factors (E2F1/3/4, etc.), post-transcriptional regulation of miRNAs (hsa-mir-30c-1, etc.), lncRNAs (C8orf34-AS1, etc.), and IGF2BP1-mediated m6A modification were identified. It was also found NOP58-mediated SUMOylation post-translational modification.

Conclusions

Together, we show that GCLC and relevant genes exert crucial roles in LUAD prognosis and immunity, and their expression can be controlled by complex multi-omics mechanisms.
Exploring the usage of learning resources by medical students in the basic science stage and their effect on academic performance
Authors: Ranabhat Sabin Kumar , Kunjukrishnan Mohan Lal , Dubey Muskan , Curran Vernon , Dubey Arun Kumar , Dwivedi Neelam
Published: May 2024

Background

The United States Medical Licensing Examination (USMLE) step 1 is one of the two examinations written after completion of the first two years (basic science stage) of medical school to be eligible to apply for residency training in the USA. A huge number and types of study materials are available to prepare for the exam which might confuse students choosing a resource.

We investigated learning resources being used by the third and fifth-semester medical students and their association with academic performance. We also compared learning resources and exam scores of high-performing and low-performing students.

Methods

Data collection was done using structured (quantitative study) and semi-structured (qualitative study) questionnaires during a face-to-face interview. This article is about the quantitative part which was designed as a correlational study. Single factor one-way analysis of variance (ANOVA), Pearson correlation coefficient test, T-test, and Fisher’s exact test were used to analyze the data.

Results

About half of all students used three or more commercial resources dealing with the same content. A weak negative correlation was observed between the number of commercial resources and the exam scores, especially when the number of these resources was three or more (r = -0.26). The mean exam score of textbook users was statistically significantly higher than the mean score of textbook non-users (p = 0.01). The usage of textbooks was statistically significantly higher in the cohort of top performers in comparison to the rest of the students (p = 0.006). In addition to less usage of textbooks, the mean number of review books was higher in the group of weakest students (2.84 versus 3.7; p = 0.75).

Conclusions

Most students did not use professional textbooks and about half used too many commercial review resources. While the former fact was significantly associated with poor academic performance, the later fact had weak negative correlation with exam score.

Pedagogical interventions are urgently needed to make the right type of learning resources available by making professional textbooks more USMLE-oriented and helping the students choose the best and right number of resources for optimum academic performance. By fulfilling the observed needs of the students in this way, they might feel empowered because of self-determination which will motivate studies.
Competency gap among graduating nursing students: what they have achieved and what is expected of them
Authors: Purabdollah Majid , Zamanzadeh Vahid , Ghahramanian Akram , Valizadeh Leila , Mousavi Saeid , Ghasempour Mostafa
Published: May 2024

Background

Nurses’ professional competencies play a significant role in providing safe care to patients. Identifying the acquired and expected competencies in nursing education and the gaps between them can be a good guide for nursing education institutions to improve their educational practices.

Methods

In a descriptive-comparative study, students’ perception of acquired competencies and expected competencies from the perspective of the Iranian nursing faculties were collected with two equivalent questionnaires consisting of 85 items covering 17 competencies across 5 domains. A cluster sampling technique was employed on 721 final-year nursing students and 365 Iranian nursing faculties. The data were analyzed using descriptive statistics and independent t-tests.

Results

The results of the study showed that the highest scores for students’ acquired competencies and nursing faculties’ expected competencies were work readiness and professional development, with mean of 3.54 (SD = 0.39) and 4.30 (SD = 0.45), respectively. Also, the lowest score for both groups was evidence-based nursing care with mean of 2.74 (SD = 0.55) and 3.74 (SD = 0.57), respectively. The comparison of competencies, as viewed by both groups of the students and the faculties, showed that the difference between the two groups’ mean scores was significant in all 5 core-competencies and 17 sub-core competencies (P < .001). Evidence-based nursing care was the highest mean difference (mean diff = 1) and the professional nursing process with the lowest mean difference (mean diff = 0.70).

Conclusion

The results of the study highlight concerns about the gap between expected and achieved competencies in Iran. Further research is recommended to identify the reasons for the gap between the two and to plan how to reduce it. This will require greater collaboration between healthcare institutions and nursing schools.
The prevalence and mortality risks of PRISm and COPD in the United States from NHANES 2007–2012
Authors: Cadham Christopher J. , Oh Hayoung , Han MeiLan K. , Mannino David , Cook Steven , Meza Rafael , Levy David T. , Sánchez-Romero Luz María
Published: May 2024

Background

We estimated the prevalence and mortality risks of preserved ratio impaired spirometry (PRISm) and chronic obstructive pulmonary disease (COPD) in the US adult population.

Methods

We linked three waves of pre-bronchodilator spirometry data from the US National Health and Nutritional Examination Survey (2007–2012) with the National Death Index. The analytic sample included adults ages 20 to 79 without missing data on age, sex, height, BMI, race/ethnicity, and smoking status. We defined COPD (GOLD 1, 2, and 3–4) and PRISm using FEV1/FVC cut points by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). We compared the prevalence of GOLD stages and PRISm by covariates across the three waves. We estimated adjusted all-cause and cause-specific mortality risks by COPD stage and PRISm using all three waves combined.

Results

Prevalence of COPD and PRISm from 2007–2012 ranged from 13.1%-14.3% and 9.6%-10.2%, respectively. We found significant differences in prevalence by sex, age, smoking status, and race/ethnicity. Males had higher rates of COPD regardless of stage, while females had higher rates of PRISm. COPD prevalence increased with age, but not PRISm, which was highest among middle-aged individuals. Compared to current and never smokers, former smokers showed lower rates of PRISm but higher rates of GOLD 1. COPD prevalence was highest among non-Hispanic White individuals, and PRISm was notably higher among non-Hispanic Black individuals (range 31.4%-37.4%). We found associations between PRISm and all-cause mortality (hazard ratio [HR]: 2.3 95% CI: 1.9—2.9) and various cause-specific deaths (HR ranges: 2.0–5.3). We also found associations between GOLD 2 (HR: 2.1, 95% CI: 1.7–2.6) or higher (HR: 4.2, 95% CI: 2.7–6.5) and all-cause mortality. Cause-specific mortality risk varied within COPD stages but typically increased with higher GOLD stage.

Conclusions

The prevalence of COPD and PRISm remained stable from 2007–2012. Greater attention should be paid to the potential impacts of PRISm due to its higher prevalence in minority groups and its associations with mortality across various causes including cancer.
HPV16-miRNAs exert oncogenic effects through enhancers in human cervical cancer
Authors: Wang Yunuan , Wang Xueying , Liu Yiting , He Yuxin , Duan Xiaoling , Li Qinmei , Huang Yanchun , Xu Guoxiong , Lu Qi
Published: May 2024

Background

Cervical cancer is a human papillomavirus (HPV)-related disease. HPV type 16 (HPV16), which is the predominant cause of cervical cancer, can encode miRNAs (HPV16-miRNAs). However, the role of HPV16-miRNAs in the pathogenesis of cervical cancer remains unclear.

Methods

Human cervical cancer cell lines SiHa (HPV16-positive) and C33A (HPV-negative), and cervical cancer tissues were collected to investigate the expression levels of two HPV16-miRNAs (HPV16-miR-H1 and HPV16-miR-H6). The overexpression and knockdown of HPV16-miR-H1 and HPV16-miR-H6 were performed using the lentiviral vector system and miRNA inhibitors, respectively. RNA-sequencing (RNA-seq) analysis and H3K27ac chromatin immunoprecipitation and sequencing (CHIP-seq) experiments were utilized to explore the roles of HPV16-miR-H1 and HPV16-miR-H6 facilitated by enhancers. CCK8, EdU, transwell, and wound healing assays were performed to verify the effects of HPV16-miR-H1 and HPV16-miR-H6 on cell proliferation and migration.

Results

HPV16-miR-H1 and HPV16-miR-H6 were highly expressed in both SiHa cells and tissue samples from HPV16-positive cervical cancer patients. RNA-seq analysis showed that HPV16-miR-H1 and HPV16-miR-H6 induced the upregulation of numerous tumor progression-associated genes. H3K27ac CHIP-seq experiments further revealed that HPV16-miR-H1 and HPV16-miR-H6 modulated the expression of critical genes by regulating their enhancer activity. The functional study demonstrated that HPV16-miR-H1 and HPV16-miR-H6 increased the migratory capacity of SiHa cells.

Conclusions

Our data shed light on the role of HPV16-encoded miRNAs in cervical cancer, particularly emphasizing their involvement in the miRNA-enhancer-target gene system. This novel regulatory mechanism of HPV16-miRNAs provides new insights and approaches for the development of therapeutic strategies by targeting HPV16-positive cervical cancer.
Alzheimer blood biomarkers: practical guidelines for study design, sample collection, processing, biobanking, measurement and result reporting
Authors: Zeng Xuemei , Chen Yijun , Sehrawat Anuradha , Lee Jihui , Lafferty Tara K. , Kofler Julia , Berman Sarah B. , Sweet Robert A. , Tudorascu Dana L. , Klunk William E. , Ikonomovic Milos D. , Pfister Anna , Zetterberg Henrik , Snitz Beth E. , Cohen Anne D. , Villemagne Victor L. , Pascoal Tharick A. , Kamboh M. llyas , Lopez Oscar I. , Blennow Kaj , Karikari Thomas K.
Published: May 2024

Alzheimer’s disease (AD), the most common form of dementia, remains challenging to understand and treat despite decades of research and clinical investigation. This might be partly due to a lack of widely available and cost-effective modalities for diagnosis and prognosis. Recently, the blood-based AD biomarker field has seen significant progress driven by technological advances, mainly improved analytical sensitivity and precision of the assays and measurement platforms. Several blood-based biomarkers have shown high potential for accurately detecting AD pathophysiology. As a result, there has been considerable interest in applying these biomarkers for diagnosis and prognosis, as surrogate metrics to investigate the impact of various covariates on AD pathophysiology and to accelerate AD therapeutic trials and monitor treatment effects. However, the lack of standardization of how blood samples and collected, processed, stored analyzed and reported can affect the reproducibility of these biomarker measurements, potentially hindering progress toward their widespread use in clinical and research settings. To help address these issues, we provide fundamental guidelines developed according to recent research findings on the impact of sample handling on blood biomarker measurements. These guidelines cover important considerations including study design, blood collection, blood processing, biobanking, biomarker measurement, and result reporting. Furthermore, the proposed guidelines include best practices for appropriate blood handling procedures for genetic and ribonucleic acid analyses. While we focus on the key blood-based AD biomarkers for the AT(N) criteria (e.g., amyloid-beta [Aβ]40, Aβ42, Aβ42/40 ratio, total-tau, phosphorylated-tau, neurofilament light chain, brain-derived tau and glial fibrillary acidic protein), we anticipate that these guidelines will generally be applicable to other types of blood biomarkers. We also anticipate that these guidelines will assist investigators in planning and executing biomarker research, enabling harmonization of sample handling to improve comparability across studies.
Work-related problems and the psychosocial characteristics of individuals with irritable bowel syndrome: an updated literature review
Authors: Sugaya Nagisa
Published: May 2024

Background

Irritable bowel syndrome (IBS) is a common, functional gastrointestinal disorder. Because IBS often develops and worsens with stress, it requires treatment from both physical and mental perspectives. Recent years have seen increasing reports of its impact on the daily performance and productivity of workers with IBS, leading to sick leaves and lower quality of life. Therefore, this narrative review aimed to summarize the work and psychosocial characteristics of individuals with IBS.

Main body

Workers with IBS report greater occupational stressors and work productivity impairments, including presenteeism or absenteeism, in addition to suffering from psychological distress, low quality of life, and medical and economic problems, similar to those with IBS in the general population. Anxiety about abdominal symptoms, as well as the severity of IBS, is related to the degree of interference with one’s work. Regarding the association between characteristics of work and IBS, shift work and job demands/discretion have been associated with IBS. Studies on specific occupations have revealed associations between IBS and various occupational stressors in healthcare workers, firefighters, and military personnel. Telecommuting, which has become increasingly popular during the coronavirus disease pandemic, has not found to improve IBS. Moreover, the effectiveness of medication, diet, and a comprehensive self-management program, including cognitive behavioral therapy, in improving the productivity of workers with IBS have been examined.

Conclusion

As mentioned above, the IBS of workers is related not only to their problematic physical and mental health but also to work-related problems; workers with IBS exhibit severe occupational stress factors and work productivity impairment. Further research is required to develop efficient and appropriate interventions for workers.
Efficacy of massage versus massage with post isometric relaxation in temporomandibular disorders: a randomized controlled trial
Authors: Tariq Mahnoor , Fatima Kainaat , Khan Shahzada Faiz Ahmad , Mahmood Wajeeha , Mahmood Tahir , Khurshaid Sarma , Khalid Masooma , Khoosa Mehrunisa , Babur Muhammad Naveed
Published: May 2024

Background

Temporomandibular joint disorder (TMD) is a common condition affecting the masticatory muscles and joint mobility.

Objectives

The primary objective was to compare the effects of massage therapy alone and massage therapy combined with post-isometric relaxation exercises in patients with TMD for pain and maximal mouth opening.

Design

Assessor-blinded randomized controlled trial.

Setting

Sir Ganga Ram Hospital, Chaudhry Muhammad Akram Dental Hospital, Lahore Medical and Dental Hospital.

Subjects

Temporomandibular joint disorder patients.

Intervention

Group A (n = 23) received conventional treatment including massage and therapeutic exercises consecutively for 2 weeks. Group B (n = 23) received post-isometric relaxation technique along with conventional treatment for consecutive 2 weeks.

Main measures

The main outcome measures were pain and maximal mouth opening. Pain was measured using the Visual Analogue Scale (VAS) and maximal mouth opening (MMO) was measured using the TheraBite Scale.

Results

Both groups demonstrated significant improvements in pain and MMO scores post-treatment. However, Group B (massage with post-isometric relaxation exercises) showed significantly better outcomes compared to Group A (massage alone). There was a statistically significant difference in post-treatment pain scores (P = 0.000) and MMO scores (P = 0.000) between the two groups.

Conclusion

The results suggest that massage therapy combined with post-isometric relaxation is more effective than massage therapy alone in managing pain and improving mouth opening in TMD patients. The study provides evidence supporting the use of these therapies in TMD management.

Trial registry number

NCT05810831. Date of registration/First submission: 15 March 2023.
Modeling brain sex in the limbic system as phenotype for female-prevalent mental disorders
Authors: Matte Bon Gloria , Kraft Dominik , Comasco Erika , Derntl Birgit , Kaufmann Tobias
Published: May 2024

Background

Sex differences exist in the prevalence and clinical manifestation of several mental disorders, suggesting that sex-specific brain phenotypes may play key roles. Previous research used machine learning models to classify sex from imaging data of the whole brain and studied the association of class probabilities with mental health, potentially overlooking regional specific characteristics.

Methods

We here investigated if a regionally constrained model of brain volumetric imaging data may provide estimates that are more sensitive to mental health than whole brain-based estimates. Given its known role in emotional processing and mood disorders, we focused on the limbic system. Using two different cohorts of healthy subjects, the Human Connectome Project and the Queensland Twin IMaging, we investigated sex differences and heritability of brain volumes of limbic structures compared to non-limbic structures, and subsequently applied regionally constrained machine learning models trained solely on limbic or non-limbic features. To investigate the biological underpinnings of such models, we assessed the heritability of the obtained sex class probability estimates, and we investigated the association with major depression diagnosis in an independent clinical sample. All analyses were performed both with and without controlling for estimated total intracranial volume (eTIV).

Results

Limbic structures show greater sex differences and are more heritable compared to non-limbic structures in both analyses, with and without eTIV control. Consequently, machine learning models performed well at classifying sex based solely on limbic structures and achieved performance as high as those on non-limbic or whole brain data, despite the much smaller number of features in the limbic system. The resulting class probabilities were heritable, suggesting potentially meaningful underlying biological information. Applied to an independent population with major depressive disorder, we found that depression is associated with male–female class probabilities, with largest effects obtained using the limbic model. This association was significant for models not controlling for eTIV whereas in those controlling for eTIV the associations did not pass significance correction.

Conclusions

Overall, our results highlight the potential utility of regionally constrained models of brain sex to better understand the link between sex differences in the brain and mental disorders.
In vivo assessment of safety, biodistribution, and radiation dosimetry of the [18F]Me4FDG PET-radiotracer in adults
Authors: Geist Barbara Katharina , Ramirez Juan Carlos , Binder Patrick , Einspieler Holger , Ibeschitz Harald , Langsteger Werner , Nics Lukas , Rausch Ivo , Diemling Markus , Sohlberg Antti , Hacker Marcus , Rasul Sazan
Published: May 2024

Background

Approaches targeting the sodium-glucose cotransporter (SGLT) could represent a promising future therapeutic strategy for numerous oncological and metabolic diseases. In this study, we evaluated the safety, biodistribution and radiation dosimetry of the glucose analogue positron emission tomography (PET) agent [18F] labeled alpha-methyl-4-deoxy-4-[18F]fluoro-D-glucopyranoside ([18F]Me4FDG) with high sodium-glucose cotransporter and low glucose transporter (GLUT) affinity. For this purpose, five healthy volunteers (1 man, 4 women) underwent multiple whole-body PET/computed tomography (CT) examinations starting with injection and up to 4 h after injection of averaged (2.4 ± 0.1) MBq/kg (range: 2.3–2.5 MBq/kg) administered activity. The PET/CT scans were conducted in 5 separate sessions, blood pressure and temperature were measured, and blood and urine samples were collected before the scans and one hour after injection to assess toxicity. Measurements of [18F]Me4FDG radioactivity in organs of interest were determined from the PET/CT scans at 5 time points. Internal dosimetry was performed on voxel level using a fast Monte Carlo approach.

Results

All studied volunteers could well tolerate the [18F]Me4FDG and no adverse event was reported. The calculated effective dose was (0.013 ± 0.003) mSv/MBq. The organs with the highest absorbed dose were the kidneys with 0.05 mSv/MBq per kidney. The brain showed almost no uptake. After 60 min, (12 ± 15) % of the administered dose was excreted into the bladder.

Conclusion

Featuring an effective dose of only 0.013 ± 0.003 mSv/MBq and no occurrence of side effects, the glucose analogue [18F]Me4FDG seems to be a safe radio-tracer with a favorable biodistribution for PET imaging and also within several consecutive scans.

Trial registration number

NCT03557138, Registered 22 February 2017, https://ichgcp.net/clinical-trials-registry/NCT03557138.
Porcine lung tissue slices: a culture model for PRCV infection and innate immune response investigations
Authors: Li Shuxian , Lu Yabin , Yang Shanshan , Wang Caiying , Yang Jing , Huang Xin , Chen Guohui , Shao Yongheng , Li Maolin , Yu Haoyuan , Fu Yuguang , Liu Guangliang
Published: May 2024

Respiratory coronaviruses (RCoVs) significantly threaten human health, necessitating the development of an ex vivo respiratory culture system for investigating RCoVs infection. Here, we successfully generated a porcine precision-cut lung slices (PCLSs) culture system, containing all resident lung cell types in their natural arrangement. Next, this culture system was inoculated with a porcine respiratory coronavirus (PRCV), exhibiting clinical features akin to humans who were infected by SARS-CoV-2. The results demonstrated that PRCV efficiently infected and replicated within PCLSs, targeting ciliated cells in the bronchioles, terminal bronchioles, respiratory bronchioles, and pulmonary alveoli. Additionally, through RNA-Seq analysis of the innate immune response in PCLSs following PRCV infection, expression levels of interferons, inflammatory cytokines and IFN stimulated genes were significantly upregulated. This ex vivo model may not only offer new insights into PRCV infection in the porcine respiratory tract but also serve as a valuable tool for studying human respiratory CoVs infection.
Evaluating the OpenAI’s GPT-3.5 Turbo’s performance in extracting information from scientific articles on diabetic retinopathy
Authors: Gue Celeste Ci Ying , Rahim Noorul Dharajath Abdul , Rojas-Carabali William , Agrawal Rupesh , RK Palvannan , Abisheganaden John , Yip Wan Fen
Published: May 2024

We aimed to compare the concordance of information extracted and the time taken between a large language model (OpenAI’s GPT-3.5 Turbo via API) against conventional human extraction methods in retrieving information from scientific articles on diabetic retinopathy (DR). The extraction was done using GPT3.5 Turbo as of October 2023. OpenAI’s GPT-3.5 Turbo significantly reduced the time taken for extraction. Concordance was highest at 100% for the extraction of the country of study, 64.7% for significant risk factors of DR, 47.1% for exclusion and inclusion criteria, and lastly 41.2% for odds ratio (OR) and 95% confidence interval (CI). The concordance levels seemed to indicate the complexity associated with each prompt. This suggests that OpenAI’s GPT-3.5 Turbo may be adopted to extract simple information that is easily located in the text, leaving more complex information to be extracted by the researcher. It is crucial to note that the foundation model is constantly improving significantly with new versions being released quickly. Subsequent work can focus on retrieval-augmented generation (RAG), embedding, chunking PDF into useful sections, and prompting to improve the accuracy of extraction.
Online dissemination of Cochrane reviews on digital health technologies: a cross-sectional study
Authors: De Santis Karina Karolina , Kirstein Mathia , Kien Christina , Griebler Ursula , McCrabb Sam , Jahnel Tina
Published: May 2024

Background

This cross-sectional study investigated the online dissemination of Cochrane reviews on digital health technologies.

Methods

We searched the Cochrane Database of Systematic Reviews from inception up to May 2023. Cochrane reviews with any population (P), intervention or concept supported by any digital technology (I), any or no comparison (C), and any health outcome (O) were included. Data on review characteristics (bibliographic information, PICO, and evidence quality) and dissemination strategies were extracted and processed. Dissemination was assessed using review information on the Cochrane website and Altmetric data that trace the mentions of academic publications in nonacademic online channels. Data were analysed using descriptive statistics and binary logistic regression analysis.

Results

Out of 170 records identified in the search, 100 Cochrane reviews, published between 2005 and 2023, were included. The reviews focused on consumers (e.g. patients, n = 86), people of any age (n = 44), and clinical populations (n = 68). All reviews addressed interventions or concepts supported by digital technologies with any devices (n = 73), mobile devices (n = 17), or computers (n = 10). The outcomes focused on disease treatment (n = 56), health promotion and disease prevention (n = 27), or management of care delivery (n = 17). All reviews included 1–132 studies, and half included 1–10 studies. Meta-analysis was performed in 69 reviews, and certainty of evidence was rated as high or moderate for at least one outcome in 46 reviews.

In agreement with the Cochrane guidelines, all reviews had a plain language summary (PLS) that was available in 3–14 languages. The reviews were disseminated (i.e. mentioned online) predominantly via X/Twitter (n = 99) and Facebook (n = 69). Overall, 51 reviews were mentioned in up to 25% and 49 reviews in 5% of all research outputs traced by Altmetric data. Dissemination (i.e. higher Altmetric scores) was associated with bibliographic review characteristics (i.e. earlier publication year and PLS available in more languages), but not with evidence quality (i.e. certainty of evidence rating, number of studies, or meta-analysis performed in review).

Conclusions

Online attention towards Cochrane reviews on digital health technologies is high. Dissemination is higher for older reviews and reviews with more PLS translations. Measures are required to improve dissemination of Cochrane reviews based on evidence quality.

Systematic review registration

The study was prospectively registered at the Open Science Framework (https://osf.io/mpw8u/).
Retention of people who inject drugs enrolled in a ‘medications for opioid use disorder’ (MOUD) programme in Uganda
Authors: Mudiope Peter , Mutamba Brian Byamah , Komuhangi Liz , Nangendo Joan , Alamo Stella , Mathers Bradley , Makumbi Fredrick , Wanyenze Rhoda
Published: May 2024

Background

Injection Drug use is associated with increased HIV risk behaviour that may result in the transmission of HIV and poor access to HIV prevention and treatment. In 2020, Uganda introduced the ‘medication for opioid use disorder (MOUD) treatment’ for People who inject drugs (PWID). We analysed the 12-month retention and associated factors among PWID enrolled on MOUD treatment in Kampala, Uganda.

Methods

We conducted a retrospective analysis of 343 PWID with OUD who completed 14 days of methadone induction from September 2020 to July 2022. Retention was defined as the number of individuals still in the programme divided by the total number enrolled, computed at 3-, 6-, 9-, and 12 months using lifetable and Kaplan-Meier survival analyses. Cox proportional regression analyses were conducted to assess factors associated with retention in the programme in the first 12 months.

Results

Overall, 243 (71%) of 343 participants stabilized at a methadone dose of 60 mg or more. The majority of participants were males (n = 284, 82.8%), and the median (interquartile range, IQR) age was 31 (26–38) years. Most participants (n = 276, 80.5%) lived 5 km or more away from the MOUD clinic. Thirty (8.8%) were HIV-positive, 52 (15.7%) had a major mental illness and 96 (27.9%) had a history of taking alcohol three months before enrollment. The cumulative retention significantly declined from 83.4% (95%CI = 79.0–87.0) at 3months to 71.9% (95%CI = 67.2–76.6) at 6months, 64% 95%CI = 58.7–68.9) at 9months, and 55.2%; 95% CI (49.8–60.3% at 12months. The 12-month retention was significantly higher for participants on methadone doses of 60 mg or more (adj.HR = 2.1, 95%CI = 1.41–3.22), while participants resident within 5 km of the MOUD clinic were 4.9 times more likely to be retained at 12 months, compared to those residing 5 km or more, (adj. HR = 4.81, 95%CI = 1.54-15). Other factors, including predisposing, need, and enabling factors, were not associated with retention.

Conclusion

Our study demonstrates acceptable 12-month retention rates for people who inject drugs, comparable to previous studies done in both developing and developed countries. Sustaining and improving retention may require enhanced scaling up of MOUD dose to an optimal level in the first 14 days and reducing the distance between participant locale and MOUD clinics.
13C-Stable isotope resolved metabolomics uncovers dynamic biochemical landscape of gut microbiome-host organ communications in mice
Authors: Xiao Xia , Zhou Yixuan , Li Xinwei , Jin Jing , Durham Jerika , Ye Zifan , Wang Yipeng , Hennig Bernhard , Deng Pan
Published: May 2024

Background

Gut microbiome metabolites are important modulators of host health and disease. However, the overall metabolic potential of the gut microbiome and interactions with the host organs have been underexplored.

Results

Using stable isotope resolved metabolomics (SIRM) in mice orally gavaged with 13C-inulin (a tracer), we first observed dynamic enrichment of 13C-metabolites in cecum contents in the amino acids and short-chain fatty acid metabolism pathways. 13C labeled metabolites were subsequently profiled comparatively in plasma, liver, brain, and skeletal muscle collected at 6, 12, and 24 h after the tracer administration. Organ-specific and time-dependent 13C metabolite enrichments were observed. Carbons from the gut microbiome were preferably incorporated into choline metabolism and the glutamine-glutamate/GABA cycle in the liver and brain, respectively. A sex difference in 13C-lactate enrichment was observed in skeletal muscle, which highlights the sex effect on the interplay between gut microbiome and host organs. Choline was identified as an interorgan metabolite derived from the gut microbiome and fed the lipogenesis of phosphatidylcholine and lysophosphatidylcholine in host organs. In vitro and in silico studies revealed the de novo synthesis of choline in the human gut microbiome via the ethanolamine pathway, and Enterococcus faecalis was identified as a major choline synthesis species. These results revealed a previously underappreciated role for gut microorganisms in choline biosynthesis.

Conclusions

Multicompartmental SIRM analyses provided new insights into the current understanding of dynamic interorgan metabolite transport between the gut microbiome and host at the whole-body level in mice. Moreover, this study singled out microbiota-derived metabolites that are potentially involved in the gut-liver, gut-brain, and gut-skeletal muscle axes.
Effectiveness of Recovery Strategies After Training and Competition in Endurance Athletes: An Umbrella Review
Authors: Li Shuting , Kempe Matthias , Brink Michel , Lemmink Koen
Published: May 2024

Background

Recovery strategies are used to enhance performance and reduce injury risk in athletes. In previous systematic reviews, individual recovery strategies were investigated to clarify their effectiveness for mixed groups of athletes. However, the current evidence is ambiguous, and a clear overview of (training) recovery for endurance athletes is still lacking.

Methods

We conducted an umbrella review based on a literature search in PubMed, Cochrane Database of Systematic Reviews, and Web of Science. Reviews published in English and before December 2022 were included. Systematic reviews and meta-analyses were eligible if they investigated the effectiveness of one or more recovery strategies compared with a placebo or control group after a training session in endurance athletes.

Results

Twenty-two reviews (nine systematic reviews, three meta-analyses, and ten systematic reviews with meta-analyses included) met the inclusion criteria. In total, sixty-three studies with 1100 endurance athletes were included in our umbrella review. Out of the sixty-three studies, eight provided information on training recovery time frame for data synthesis. Among them, cryotherapy and compression garments showed positive effects, while applying massage showed no effect. In general, none of the included recovery strategies showed consistent benefits for endurance athletes.

Conclusion

There is no particular recovery strategy that can be advised to enhance recovery between training sessions or competitions in endurance athletes. However, individual studies suggest that compression garments and cryotherapy are effective training recovery strategies. Further research should improve methodology and focus on the different time courses of the recovery process.

Registration

The review protocol was registered with the International Prospective Register of Systematic Reviews with the number CRD42021260509.
Equity, diversity and inclusion in simulation-based education: constructing a developmental framework for medical educators
Authors: Mutch Jennifer , Golden Shauna , Purdy Eve , Chang Chloe Hui Xin , Oliver Nathan , Tallentire Victoria Ruth
Published: May 2024

Background

Themes of equity, diversity and inclusion (EDI) arise commonly within healthcare simulation. Though faculty development guidance and standards include increasing reference to EDI, information on how faculty might develop in this area is lacking. With increasingly formal expectations being placed on simulation educators to adhere to EDI principles, we require a better understanding of the developmental needs of educators and clear guidance so that teams can work towards these expectations. Our study had two aims: Firstly, to explore the extent to which an existing competency framework for medical teachers to teach ethnic and cultural diversity is relevant for simulation educator competency in EDI, and secondly, informed by the data gathered, to construct a modified competency framework in EDI for simulation educators.

Methods

We engaged our participants (10 simulation faculty) in a 5-month period of enhanced consideration of EDI, using the SIM-EDI tool to support faculty debriefing conversations focussed on EDI within a pre-existing programme of simulation. We interviewed participants individually at two timepoints and analysed transcript data using template analysis. We employed an existing competency framework for medical teachers as the initial coding framework. Competencies were amended for the simulation context, modified based on the data, and new themes were added inductively, to develop a new developmental framework for simulation educators.

Results

Interview data supported the relevance of the existing competency framework to simulation. Modifications made to the framework included the incorporation of two inductively coded themes (‘team reflection on EDI’ and ‘collaboration’), as well as more minor amendments to better suit the healthcare simulation context. The resultant Developmental Framework for Simulation Educators in EDI outlines 10 developmental areas we feel are required to incorporate consideration of EDI into simulation programmes during the design, delivery and debriefing phases. We propose that the framework acts as a basis for simulation faculty development in EDI.

Conclusions

Simulation faculty development in EDI is important and increasingly called for by advisory bodies. We present a Developmental Framework for Simulation Educators in EDI informed by qualitative data. We encourage simulation teams to incorporate this framework into faculty development programmes and report on their experiences.
Being in-between “to return or to stay”: exploring the experiences of urban displaced people in Mozambique’s Pemba
Authors: Tivane Nelson
Published: May 2024

The province of Cabo Delgado, located in the north of Mozambique, has been inflicted by the conflict and terrorist actions since 2017. The threats they pose, and the unfolding fragility of the security situation have forced over 1.4 million people to flee their homes and communities. While thousands of displaced people are reluctant to risk their lives and return, over five hundred thousand displaced people made their spontaneous way back “home,” and the country continues to struggle with such a reality. In the face of violent disruption and displacement, this paper offers an exploratory review of return from the perspective of encountering and giving meaning to places. Leaving culture (reflexivity again) a bit out, the paper closely looks at the (social and economic) experiences people have developed and carried with them through their displacement (and return) narratives as the main factors influencing the decision to or not to return. This article would then have a twofold purpose. On the one hand, it contributes to the existing debate on conflict, displacement, place and place-making. On the other hand, it would be beneficial to enrich the ongoing research further.
Artificial intelligence generated clinical score sheets: looking at the two faces of Janus
Authors: Berce Cristian
Published: May 2024

In vivo experiments are increasingly using clinical score sheets to ensure minimal distress to the animals. A score sheet is a document that includes a list of specific symptoms, behaviours and intervention guidelines, all balanced to for an objective clinical assessment of experimental animals. Artificial Intelligence (AI) technologies are increasingly being applied in the field of preclinical research, not only in analysis but also in documentation processes, reflecting a significant shift towards more technologically advanced research methodologies. The present study explores the application of Large Language Models (LLM) in generating score sheets for an animal welfare assessment in a preclinical research setting. Focusing on a mouse model of inflammatory bowel disease, the study evaluates the performance of three LLM – ChatGPT-4, ChatGPT-3.5, and Google Bard – in creating clinical score sheets based on specified criteria such as weight loss, stool consistency, and visible fecal blood. Key parameters evaluated include the consistency of structure, accuracy in representing severity levels, and appropriateness of intervention thresholds. The findings reveal a duality in LLM-generated score sheets: while some LLM consistently structure their outputs effectively, all models exhibit notable variations in assigning numerical values to symptoms and defining intervention thresholds accurately. This emphasizes the dual nature of AI performance in this field—its potential to create useful foundational drafts and the critical need for professional review to ensure precision and reliability. The results highlight the significance of balancing AI-generated tools with expert oversight in preclinical research.
Predicted roles of long non-coding RNAs in abiotic stress tolerance responses of plants
Authors: Imaduwage IUH , Hewadikaram Madhavi
Published: May 2024

The plant genome exhibits a significant amount of transcriptional activity, with most of the resulting transcripts lacking protein-coding potential. Non-coding RNAs play a pivotal role in the development and regulatory processes in plants. Long non-coding RNAs (lncRNAs), which exceed 200 nucleotides, may play a significant role in enhancing plant resilience to various abiotic stresses, such as excessive heat, drought, cold, and salinity. In addition, the exogenous application of chemicals, such as abscisic acid and salicylic acid, can augment plant defense responses against abiotic stress. While how lncRNAs play a role in abiotic stress tolerance is relatively well-studied in model plants, this review provides a comprehensive overview of the current understanding of this function in horticultural crop plants. It also delves into the potential role of lncRNAs in chemical priming of plants in order to acquire abiotic stress tolerance, although many limitations exist in proving lncRNA functionality under such conditions.
Gravity and magnetic joint imaging based on Gramian constraints
Authors: Shu Yiming , Liu Shuang , Wang Tianchi , Cai Hongzhu , Hu Xiangyun
Published: May 2024

Gravity and magnetic imaging produce numerical images proportional to the density and magnetization source distribution through the upward continuation of potential field data. However, the inherent ambiguity and nonuniqueness in gravity or magnetic imaging restrict the reliability of the imaging model. We develop a joint iterative imaging framework for gravity and magnetic data based on Gramian constraints. The imaging fields of gravity and magnetic fields are initially calculated by the depth from extreme points imaging method. With the recovered magnetization and density distribution, the gradient directions of the Gramian function for these model parameters are calculated and used to regularize the joint imaging directions for gravity and magnetic fields. The introduction of Gramian constraints achieves mutual complementarity of the gravity and magnetic data and generates density and magnetization models with more distinct boundaries and improved structural coherence. Our approach is tested with two synthetic examples and applied to field data from the Galinge iron deposit in Qinghai, China. The real case results are verified by information from drillholes and physical properties measurements of ore and rock samples. Joint imaging provides an alternative to joint inversion with improved resolution and reliability of imaging models compared with separate imaging through the complementarity of gravity and magnetic data.
Impact of Genomic Alterations on Efficacy of Trastuzumab Deruxtecan Against Human Epidermal Growth Factor Receptor-2–Positive Advanced Gastric Cancer
Authors: Yamaguchi Kyoko , Ito Mamoru , Isobe Taichi , Koreishi Sakuya , Taguchi Ryosuke , Uehara Koki , Ueno Shohei , Imajima Takashi , Kitazono Takafumi , Tsuchihashi Kenji , Ohmura Hirofumi , Yoshihiro Tomoyasu , Tanoue Kenro , Nishiyori Satoshi , Iwama Eiji , Maeda Takahiro , Akashi Koichi , Baba Eishi
Published: May 2024

PURPOSE

The impact of genomic alterations on response and resistance to trastuzumab deruxtecan (T-DXd) has not been elucidated. Thus, we sought to identify factors predicting sensitivity to T-DXd in gastric or gastroesophageal junction (G/GEJ) cancer.

METHODS

We conducted a retrospective study using real-world clinical data and next-generation sequencing–based comprehensive genomic profiling (CGP) data from patients with advanced G/GEJ cancers, collected by the nationwide database in Japan. We analyzed the associations between genomic alterations and the patients' survivals after T-DXd treatment.

RESULTS

In 114 patients with human epidermal growth factor receptor-2 (HER2)–positive G/GEJ cancer treated with T-DXd, the most frequently altered genes were TP53 (82%), ERBB2 (80%), and CCNE1 (36%). Multivariate Cox regression analysis revealed CCNE1 amplification to be a significant predictor of shorter progression-free survival (PFS) after T-DXd treatment among 91 patients whose CGP samples were obtained before T-DXd (median PFS, 131 days v 189 days; hazard ratio [HR], 1.90 [95% CI, 1.02 to 3.53]; P = .044). Analyses of 1,450 G/GEJ cancers revealed significant CCNE1/ ERBB2 coamplification (41% relative to 11% CCNE1 amplification in ERBB2-nonamplified tumors; P < .0001). ERBB2-activating mutations were also detected in 3.7% of G/GEJ cancers and in 8.8% of HER2-positive G/GEJ cancers treated with T-DXd. Patients with ERBB2-mutated tumors showed shorter PFS than those without ERBB2 mutations after T-DXd treatment (mPFS, 105 v 180 days; P = .046).

CONCLUSION

CCNE1 amplification may confer primary resistance to T-DXd in HER2-positive G/GEJ cancer, suggesting that the cell cycle could be a potential therapeutic target in CCNE1/ERBB2 coamplified tumors. ERBB2-activating mutation may also attenuate T-DXd efficacy in HER2-positive G/GEJ cancer.