bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivo PET of synaptic density as potential diagnostic marker for cognitive disorders: prospective comparison with current imaging markers for neuronal dysfunction and relation to symptomatology - study protocol
Authors: Vanderlinden Greet , Carron Charles , Vandenberghe Rik , Vandenbulcke Mathieu , Van Laere Koen
Published: February 2024

Background

18F-FDG brain PET is clinically used for differential diagnosis in cognitive dysfunction of unclear etiology and for exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. 18F-FDG PET measures regional glucose metabolism, which represents a combination of neuronal/synaptic activity but also astrocytic activity and neuroinflammation. Recently, imaging of synaptic vesicle protein 2 A (SV2A) has become available and was shown to be a proxy of synaptic density. This prospective study will investigate the use of 18F-SynVesT-1 for imaging SV2A and its discriminative power for differential diagnosis in cognitive disorders in a head-to-head comparison to 18F-FDG PET. In addition, simultaneous PET/MR allows an evaluation of contributing factors and the additional value of advanced MRI imaging to FDG/SV2A PET imaging will be investigated. In this work, the study design and protocol are depicted.

Methods

In this prospective, multimodal imaging study, 110 patients with uncertain diagnosis of cognitive impairment who are referred for 18F-FDG PET brain imaging in their diagnostic work-up in a tertiary memory clinic will be recruited. In addition, 40 healthy volunteers (HV) between 18 and 85 years (M/F) will be included. All study participants will undergo simultaneous 18F-SynVesT-1 PET/MR and an extensive neuropsychological evaluation. Amyloid status will be measured by PET using 18FNAV4694, in HV above 50 years of age. Structural T1-weighted and T2-weighted fluid-attenuated inversion recovery MR images, triple-tagging arterial spin labeling (ASL) and resting-state functional MRI (rs-fMRI) will be obtained. The study has been registered on ClinicalTrials.gov (NCT05384353) and is approved by the local Research Ethics Committee.

Discussion

The main endpoint of the study will be the comparison of the diagnostic accuracy between 18F-SynVesT-1 and 18F-FDG PET in cognitive disorders with uncertain etiology and in exclusion of a neurodegenerative cause in patients with cognitive impairment in late-life psychiatric disorders. The strength of the relationship between cognition and imaging data will be assessed, as well as the potential incremental diagnostic value of including MR volumetry, ASL perfusion and rs-fMRI.
Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing
Authors: Śmieszek Agnieszka , Marcinkowska Klaudia , Małas Zofia , Sikora Mateusz , Kępska Martyna , Nowakowska Beata A. , Deperas Marta , Smyk Marta , Rodriguez-Galindo Carlos , Raciborska Anna
Published: February 2024

Background

Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing.

Methods

Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay.

Results

Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) and osteopontin (OPN). In subsequent cultures, cells remain viable and metabolically active, and the mitochondrial network is well developed, with some distinctive morphotypes noted in each cell line. Cell-specific transcriptome profile was noted, providing information on potential new biomarkers (non-coding RNAs) with diagnostic and prognostic features. The cells showed different sensitivity to vemurafenib and trametinib.

Conclusion

Obtained and characterized cellular models of stromal-like cells derived from histiocytic lesions can be used for studies on histiocytosis biology and drug testing.
Efficacy and safety of temozolomide-based regimens in advanced pancreatic neuroendocrine tumors: a systematic review and meta-analysis
Authors: Taherifard Erfan , Bakhtiar Muhammad , Mahnoor Mahnoor , Ahmed Rabeea , Cavalcante Ludimila , Zhang Janie , Saeed Anwaar
Published: February 2024

Background

Recent advances in the management of pancreatic neuroendocrine tumors (pNETs) highlight the potential benefits of temozolomide, an alkylating agent, for these patients. In this meta-analysis, we aimed to assess the outcome of temozolomide, alone or in combination with other anticancer medications in patients with advanced pNET.

Methods

Online databases of PubMed, Web of Science, Embase, the Cochrane Library, and ClinicalTrials.gov were searched systematically for clinical trials that reported the efficacy and safety of temozolomide in patients with advanced pNET. Random-effect model was utilized to estimate pooled rates of outcomes based on Response Evaluation Criteria in Solid Tumors criteria, biochemical response, and adverse events (AEs).

Results

A total of 14 studies, providing details of 441 individuals with advanced pNET, were included. The quantitative analyses showed a pooled objective response rate (ORR) of 41.2% (95% confidence interval, CI, of 32.4%-50.6%), disease control rate (DCR) of 85.3% (95% CI of 74.9%-91.9%), and a more than 50% decrease from baseline chromogranin A levels of 44.9% (95% CI of 31.6%-49.0%). Regarding safety, the results showed that the pooled rates of nonserious AEs and serious AEs were 93.8% (95% CI of 88.3%-96.8%) and 23.7% (95% CI of 12.0%-41.5%), respectively. The main severe AEs encompassed hematological toxicities.

Conclusions

In conclusion, our meta-analysis suggests that treatment with temozolomide, either as a monotherapy or in combination with other anticancer treatments might be an effective and relatively safe option for patients with advanced locally unresectable and metastatic pNET. However, additional clinical trials are required to further strengthen these findings. This study has been registered in PROSPERO (CRD42023409280).

Graphical Abstract
High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma
Authors: Tao Shanchun , Cui Di , Cheng Huimin , Liu Xiaofei , Jiang Zhaobin , Chen Hongwei , Gao Yong
Published: February 2024

Background

Hepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms.

Method

Downloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4.

Results

Bioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1.

Conclusion

TBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3β signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.
Inflammatory markers predict survival in patients with postoperative urothelial carcinoma receiving tislelizumab (PD-1 inhibitor) adjuvant therapy
Authors: Yang Meng , Zhang Jingwen , Wei Dongqun , Yu Tianyi , Chen Zeyu , Liu Xin , Zhu Haitao
Published: February 2024

Background

In the management of urothelial carcinoma, patient selection for immunotherapy, particularly with immune checkpoint inhibitors such as PD-1 (programmed cell death protein 1), is important for treatment efficacy. Inflammatory markers are useful for predicting treatment outcomes and immune-related adverse events (irAEs). This study aims to retrospectively explore the associations between inflammatory markers and outcomes in patients with postoperative urothelial carcinoma undergoing tislelizumab (PD-1 inhibitor) adjuvant therapy.

Methods

A retrospective analysis was conducted on 133 patients with postoperative urothelial carcinoma who received tislelizumab adjuvant therapy at the Affiliated Hospital of Xuzhou Medical University from April 2020 to August 2023. The prognostic effects of the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) on disease-free survival (DFS) and overall survival (OS) were assessed using Cox regression models. The correlation between inflammatory markers and the onset of irAEs was analyzed using logistic regression models.

Results

NLR < 5 and MLR < 0.31 were significantly associated with better outcomes compared to NLR >5 and MLR >0.31, respectively. Multivariate analysis revealed that an NLR < 5 was independently associated with better DFS and OS. However, there was no significant effect on the DFS and OS between PLR < 135 and PLR >135. Patients who experienced irAEs had longer DFS and OS. Multivariate analysis demonstrated that irAEs were an independent prognostic risk factor for DFS and OS. There was no significant difference in the occurrence of irAEs among different NLR, PLR, and MLR groups.

Conclusion

In patients with postoperative urothelial carcinoma receiving tislelizumab adjuvant therapy, the assessment of NLR and MLR before treatment may serve as valuable predictive markers of clinical outcome.
Non-pharmacological interventions for delirium in the pediatric population: a systematic review with narrative synthesis
Authors: Kim Kyua , Jeong Ju Hee , Choi Eun Kyoung
Published: February 2024

Background

Delirium is a serious complication experienced by hospitalized children. Therefore, preventive management strategies are recommended for these patients. However, comprehensive analyses of delirium interventions in children remain insufficient. Specifically, this systematic review aimed to summarize non-pharmacological interventions for pediatric delirium, addressing the urgent need for a comprehensive understanding of effective strategies. We also explored frequently measured outcome variables to contribute evidence for future research on delirium outcomes in children.

Methods

This systematic review searched articles from PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medica databases. The eligibility criteria were formed under the population, intervention, comparator, outcome, and study design framework. Studies were included if they involved (1) children aged under 18 years receiving hospital care, (2) non-pharmacological delirium interventions, (3) comparators involving no intervention or pharmacological delirium interventions, and (4) outcomes measuring the effectiveness of non-pharmacological delirium interventions. Only peer-reviewed articles published in English were included.

Results

Overall, 16 studies were analyzed; of them, 9 assessed non-pharmacological interventions for emergence delirium and 7 assessed interventions for pediatric delirium. The intervention types were grouped as follows: educational (n = 5), multicomponent (n = 6), and technology-assisted (n = 5). Along with pediatric and emergence delirium, the most frequently measured outcome variables were pain, patient anxiety, parental anxiety, pediatric intensive care unit length of stay, agitation, analgesic consumption, and postoperative maladaptive behavior.

Conclusions

Non-pharmacological interventions for children are effective treatments without associated complications. However, determining the most effective non-pharmacological delirium intervention for hospitalized children based on current data remains challenging.
The perceived impact of climate change on mental health and suicidality in Kenyan high school students
Authors: Ndetei David M. , Wasserman Danuta , Mutiso Victoria , Shanley Jenelle R. , Musyimi Christine , Nyamai Pascalyne , Munyua Timothy , Swahn Monica H. , Weisz John R. , Osborn Tom L. , Bhui Kamaldeep , Johnson Natalie E. , Pihkala Panu , Memiah Peter , Gilbert Sonja , Javed Afzal , Sourander Andre
Published: February 2024

Background

Climate change has psychological impacts but most of the attention has been focused on the physical impact. This study was aimed at determining the association of climate change with adolescent mental health and suicidality as reported by Kenyan high school students.

Methods

This was a cross sectional study with a sample size of 2,652. The participants were high school students selected from 10 schools in 3 regions of Kenya. A questionnaire was used to assess climate change experiences, mental health problems, and suicidality of the youth. Data were analyzed descriptively and with logistic regression to determine various associations of the different variables and the predictors of the various scores of SDQ and suicidality at 95% CI.

Results

Significant differences were observed between gender and two of the threats of climate change – worry and being afraid as subjectively experienced by the participants. Females were more worried and afraid of climate change than males. On univariate and multivariate logistic regression, we found that various experiences of climate change were significantly associated with various scores of SDQ and much fewer of the experiences predicted SDQ scores. The same pattern was reflected in suicidality.

Conclusion

Climate change appears to be associated with mental health concerns and suicidality according to Kenyan high school students’ reports with gender differences in some associations.
Association between sexual violence and multiple high-risk fertility behaviours among women of reproductive age in sub-Saharan Africa
Authors: Aboagye Richard Gyan , Donkoh Irene Esi , Okyere Joshua , Seidu Abdul-Aziz , Ahinkorah Bright Opoku , Yaya Sanni
Published: February 2024

Background

Intimate partner violence has adverse outcomes on the sexual and reproductive health of women. In this study, we examined the association between sexual violence and multiple high-risk fertility behaviours (MHRFB) among women in sub-Saharan Africa (SSA).

Methods

We conducted a cross-sectional analysis of data pooled from the most recent Demographic and Health Surveys of 20 countries in SSA. We included countries with most recent datasets conducted from 2015 to 2021 and had data on all variables included in the study. A weighted sample of 88,011 was included in the study. We used a multilevel binary logistic regression to examine the association between sexual violence and MHRFB, controlling for other covariates. The regression results were presented using adjusted odds ratio (aOR) with 95% confidence interval (CI). Statistical significance was set at p < 0.05.

Results

The overall prevalence of MHRFB was 22.53% (95% CI: 22.26–22.81), which ranged from 9.94% in South Africa to 30.38% in Chad. For sexual violence, the pooled prevalence was 7.02% (95% CI: 6.86–7.19). Burundi (20.58%) and the Gambia (2.88%) reported the highest and lowest proportions, respectively. Women who experienced sexual violence were more likely to engage in MHRFB compared to those who did not experience sexual violence [aOR = 1.11, 95% CI: 1.02, 1.21].

Conclusion

There is a positive association between sexual violence and the risk of MHRFB. Our findings underscore a need for sub-Saharan African countries to strengthen their efforts to reduce the occurrence of sexual violence in intimate partner relationships. To augment efforts and accelerate social change, sub-Saharan African countries can introduce pro-poor policies and interventions to improve the wealth status of women. Also, empowering women through the encouragement of attaining higher education would be a useful step in lowering the risk of MHRFB in SSA.
Preference for primary care in Chinese homebound patients
Authors: Zhang Jinxin , Sun Xiaojie , Yao Aaron
Published: February 2024

Objective

This study aims to describe the preference for primary healthcare (PHC) and investigate associated factors among homebound residents in both rural and urban areas of China. It provides valuable insights to facilitate the rational allocation of healthcare resources and promote the utilization of PHC.

Methods

In this nationally representative cross-sectional study, we utilized the most recent data (2020) from the China Family Panel Studies (CFPS). Participants were recruited from 25 provincial-level administrative regions in both rural and urban areas of China. Homebound patients were asked to provide details about their individual characteristics, variables related to family caregiving, and preferences for PHC. Multivariable logistic models were used to analyze potential factors associated with preference for PHC. Estimates of association were reported as odds ratios (OR) and their 95% confidence intervals (CI).

Results

The study found that 58.43% of rural patients reported a preference for PHC, while 42.78% of urban patients favored PHC. Compared to rural participants who did not received inpatient care in the past year, those who received inpatient care in the past year had 67% lower odds of choosing PHC (OR:0.33, 95% CI:0.19–0.59); Compared to rural participants who did not received family caregiving when ill, those who received family caregiving when ill had 59% lower odds of choosing PHC (OR: 0.41, 95% CI:0.21–0.77). Correspondingly, Compared to urban participants who did not received inpatient care in the past year, those who had received inpatient care in the past year had 75% lower odds of choosing PHC (OR: 0.25, 95% CI: 0.10–0.56); Compared to urban participants who did not received family caregiving when ill, those who received family caregiving when ill had 73% lower odds of choosing PHC (OR: 0.27, 95% CI: 0.11–0.63); Compared to urban participants who with agricultural Hukou, those with Non-agricultural Hukou had 61% lower odds of choosing PHC (OR: 0.39, 95% CI:0.18–0.83); Compared to urban participants living in the eastern part of mainland China, those living in the central part of China had 188% higher odds of choosing PHC (OR: 2.88, 95% CI: 1.14–7.29).

Conclusion

Policymakers should focus on tailoring PHC to vulnerable populations and prioritizing family-based public health strategies for enhancing homebound patients’ perceptions of PHC. Furthermore, further study is needed on whether the Hukou registration system affects the barriers that homebound patients experience in choosing healthcare providers.
Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study
Authors: Guan Jianbin , Liu Tao , Chen Hao , Yang Kaitan
Published: February 2024

Background

Observational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses.

Methods

We collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package.

Results

We identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD.

Conclusion

In two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.
Immunohistochemical expression of SPARC in odontogenic keratocysts: a comparative study with other odontogenic cysts
Authors: Poomsawat Sopee , Choakdeewanitthumrong Sirada , Sanguansin Sirima , Meesakul Ounruean , Kosanwat Theerachai
Published: February 2024

Background

Secreted protein acidic and rich in cysteine (SPARC) has been shown to modulate aggressive behavior in several benign and malignant tumors. Little is known about SPARC expression in odontogenic keratocyst (OKC), an odontogenic cyst with an aggressive nature. To the best of our knowledge, only one study has been investigated the expression of this protein in OKCs. This study aimed to characterize SPARC expression in OKCs. Additionally, to determine whether SPARC is associated with aggressive behavior in OKCs, SPARC expression in OKCs was compared with radicular cysts (RCs), dentigerous cysts (DCs) and calcifying odontogenic cysts (COCs). These odontogenic cysts showed no or less aggressive behavior.

Methods

SPARC expression was evaluated in 38 OKCs, 39 RCs, 35 DCs and 14 COCs using immunohistochemistry. The percentages of positive cells and the intensities of immunostaining in the epithelial lining and the cystic wall were evaluated and scored.

Results

Generally, OKCs showed similar staining patterns to RCs, DCs and COCs. In the epithelial lining, SPARC was not detected, except for ghost cells in all COCs. In the cystic wall, the majority of positive cells were fibroblasts. Compared between 4 groups of odontogenic cysts, SPARC expression in OKCs was significantly higher than those of RCs (P < 0.001), DCs (P < 0.001) and COCs (P = 0.001).

Conclusions

A significant increase of SPARC expression in OKCs compared with RCs, DCs and COCs suggests that SPARC may play a role in the aggressive behavior of OKCs.
Resting energy expenditure, body composition, and metabolic alterations in breast cancer survivors vs. healthy controls: a cross-sectional study
Authors: Van Soom Timia , Tjalma Wiebren , Van Daele Ulrike , Gebruers Nick , van Breda Eric
Published: February 2024

Purpose

This study aimed to investigate the difference in absolute and fat free mass (FFM)-adjusted resting energy expenditure (mREE) and body composition (body weight, fat mass (FM), FFM) between breast cancer survivors (BCs) and controls. Correlations with body composition were analyzed. We examined if survival year, or being metabolically dysfunctional were predictive variables.

Methods

A cross-sectional analysis was conducted on 32 BCs ≤5 years post treatment and 36 healthy controls. Indirect calorimetry measured absolute mREE. Body composition was determined by BOD POD. FFM-adjusted mREE was calculated (mREE/FFM). The Harris-Benedict equation was used to predict REE and determine hyper−/hypometabolism (mREE/pREE). The database of the multidisciplinary breast clinic of the University Hospital of Antwerp was consulted for survival year and metabolic dysfunctions.

Results

BCs have similar absolute mREE and greater FFM-adjusted mREE compared to controls. Absolute mREE and body composition between BCs differed; adjusted mREE was similar. FFM correlated significantly with absolute mREE in BCs. A significant interaction term was found between survival year and FM for absolute mREE.

Conclusion

BCs have similar absolute mREE, but higher FFM-adjusted mREE. Differences in body composition between BCs are suggested to cause inter-individual variations. We suggest that increased FFM-adjusted mREE is caused by metabolic stress related to cancer/treatment. Accurate measurement of REE and body composition is advised when adapting nutritional strategies, especially in patients at risk for developing metabolic dysfunctions.
A comparative study on the effectiveness of online and in-class team-based learning on student performance and perceptions in virtual simulation experiments
Authors: Shen Jing , Qi Hongyan , Mei Ruhuan , Sun Cencen
Published: February 2024

Background

The swift transition to online teaching in medical education has presented the challenge of replicating in-class engagement and interaction essential for active learning. Despite online team-based learning (TBL) offering potential solutions through structured cooperative activities, its efficacy in virtual simulation experiment courses remains scantily researched. This study investigates the effectiveness of online TBL for teaching virtual patient experiments in a basic medical laboratory course and contrasts it with traditional offline teaching in terms of student performance and perceptions.

Methods

A comparative analysis involved 179 Year 3 medical students using online TBL, face-to-face TBL (FTF-TBL), and the flipped classroom (FC) approach. The learning outcomes were assessed based on experiment reports, IRAT scores, TRAT scores, and final exam performance. Students’ perceptions of both online and in-class TBL methodologies were also surveyed.

Results

Both online and in-class TBL groups demonstrated comparable academic outcomes and surpassed the FC group in academic performance. Students displayed a marked preference for the TBL format (whether online or in-class), valuing its enhancement of learning interest and practical knowledge application. Nevertheless, refinements in discussion efficiency, platform convenience, and student-instructor interaction were indicated as potential areas of improvement in the online setting.

Conclusions

Online TBL, along with its in-class counterpart, showed superior academic performance and a more positive learning experience compared to the FC group. These findings underscore the potential of online TBL in adapting to modern pedagogical challenges and enriching medical education through virtual simulation experiments.
Development of low back pain curriculum content standards for entry-level clinical training
Authors: Jenkins Hazel J. , Brown Benjamin T. , O’Keeffe Mary , Moloney Niamh , Maher Chris G. , Hancock Mark
Published: February 2024

Background

The management of low back pain (LBP) is highly variable and patients often receive management that is not recommended and/or miss out on recommended care. Clinician knowledge and behaviours are strongly influenced by entry-level clinical training and are commonly cited as barriers to implementing evidence-based management. Currently there are no internationally recognised curriculum standards for the teaching of LBP content to ensure graduating clinicians have the appropriate knowledge and competencies to assess and manage LBP. We formed an international interdisciplinary working group to develop curriculum content standards for the teaching of LBP in entry-level clinical training programs.

Methods

The working group included representatives from 11 countries: 18 academics and clinicians from healthcare professions who deal with the management of LBP (medicine, physiotherapy, chiropractic, osteopathy, pharmacology, and psychology), seven professional organisation representatives (medicine, physiotherapy, chiropractic, spine societies), and one healthcare consumer. A literature review was performed, including database and hand searches of guidelines and accreditation, curricula, and other policy documents, to identify gaps in current LBP teaching and recommended entry-level knowledge and competencies. The steering group (authors) drafted the initial LBP Curriculum Content Standards (LBP-CCS), which were discussed and modified through two review rounds with the working group.

Results

Sixty-two documents informed the draft standards. The final LBP-CCS consisted of four broad topics covering the epidemiology, biopsychosocial contributors, assessment, and management of LBP. For each topic, key knowledge and competencies to be achieved by the end of entry-level clinical training were described.

Conclusion

We have developed the LBP-CCS in consultation with an interdisciplinary, international working group. These standards can be used to inform or benchmark the content of curricula related to LBP in new or existing entry-level clinical training programs.
Varying (preferred) levels of involvement in treatment decision-making in the intensive care unit before and during the COVID-19 pandemic: a mixed-methods study among relatives
Authors: Renckens Sophie C. , Pasman H. Roeline , Jorna Zina , Klop Hanna T. , Perron Chantal du , van Zuylen Lia , Steegers Monique A.H. , ten Tusscher Birkitt L. , van Mol Margo M.C. , Vloet Lilian C.M. , Onwuteaka-Philipsen Bregje D.
Published: February 2024

Background

In the intensive care unit (ICU) relatives play a crucial role as surrogate decision-makers, since most patients cannot communicate due to their illness and treatment. Their level of involvement in decision-making can affect their psychological well-being. During the COVID-19 pandemic, relatives’ involvement probably changed. We aim to investigate relatives’ involvement in decision-making in the ICU before and during the pandemic and their experiences and preferences in this regard.

Methods

A mixed-methods study among relatives of ICU patients admitted to an ICU before or during the COVID-19 pandemic. Relatives in six ICUs completed a questionnaire (n = 329), including two items on decision-making. These were analysed using descriptive statistics and logistic regression analyses. Subsequently, relatives (n = 24) were interviewed about their experiences and preferences regarding decision-making. Thematic analysis was used for analysing the qualitative data.

Results

Nearly 55% of the relatives indicated they were at least occasionally asked to be involved in important treatment decisions and of these relatives 97.1% reported to have had enough time to discuss questions and concerns when important decisions were to be made. During the first COVID-19 wave relatives were significantly less likely to be involved in decision-making compared to relatives from pre-COVID-19. The interviews showed that involvement varied from being informed about an already made decision to deliberation about the best treatment option. Preferences for involvement also varied, with some relatives preferring no involvement due to a perceived lack of expertise and others preferring an active role as the patient’s advocate. Discussing a patient’s quality of life was appreciated by relatives, and according to relatives healthcare professionals also found this valuable. In some cases the preferred and actual involvement was in discordance, preferring either a larger or a smaller role.

Conclusions

As treatment alignment with a patient’s values and preferences and accordance between preferred and actual involvement in decision-making is very important, we suggest that the treatment decision-making process should start with discussions about a patient’s quality of life, followed by tailoring the process to relatives’ preferences as much as possible. Healthcare professionals should be aware of relatives’ heterogeneous and possibly changing preferences regarding the decision-making process.
Care quality and satisfaction at the cancer hospital – a questionnaire study of older patients with cancer and their family members
Authors: Launonen Minna , Vehviläinen-Julkunen Katri , Mikkonen Santtu , Kvist Tarja
Published: February 2024

Background

The unique life situations of older patients with cancer and their family members requires that health care professionals take a holistic approach to achieve quality care. The aim of this study was to assess the perceptions of older patients with cancer and family members about the quality of care received and evaluate differences between their perceptions. A further aim was to examine which factors explain patients’ and family members’ levels of satisfaction with the care received.

Methods

The study was descriptive and cross-sectional in design. Data were collected from patients (n = 81) and their family members (n = 65) on four wards in a cancer hospital, using the Revised Humane Caring Scale (RHCS). Data were analysed using descriptive statistics, crosstabulation, Wilcoxon signed rank test, and multivariable Analysis of Covariance (ANCOVA).

Results

Family members had more negative perceptions of the quality of care than patients did. Dissatisfaction was related to professional practice (p < 0.001), interaction between patient and health care professionals (p < 0.001), cognition of physical needs (p = 0.024), and human resources (p < 0.001). Satisfaction with overall care was significantly lower among those patients and family members who perceived that they had not been involved in setting clear goals for the patient's care with staff (p = 0.002).

Conclusions

It is important that older patients with cancer and family members receive friendly, respectful, individual care based on their needs and hopes, and that they can rely on professionals. Health care professionals need more resources and education about caring for older cancer patients to provide quality care.
Experiences of delivering and receiving mental healthcare in the acute hospital setting: a qualitative study
Authors: Romeu Daniel , Guthrie Elspeth , Saraiva Sonia , Czoski-Murray Carolyn , Hewison Jenny , House Allan
Published: February 2024

Background

Recent investment in UK liaison psychiatry services has focused on expanding provision for acute and emergency referrals. Little is known about the experiences of users and providers of these services. The aim of this study was to explore the experiences of users of acute liaison mental health services (LMHS) and those of NHS staff working within LMHS or referring to LMHS. A secondary aim was to explore the potential impact of a one-hour service access target on service delivery.

Methods

Cross-sectional qualitative study. Individual interviews were audio-recorded, transcribed verbatim and interpreted using framework analysis.

Results

Service users reported mixed experiences of LMHS, with some reporting positive experiences and some reporting poor care. Most service users described the emergency department (ED) environment as extremely stressful and wished to be seen as quickly as possible. Staff described positive benefits of the one-hour access target but identified unintended consequences and trade-offs that affected other parts of the liaison service.

Conclusions

The assessment and treatment of people who attend ED with mental health problems needs to improve and particular attention should be given to the stressful nature of the ED environment for those who are extremely agitated or distressed.
Association of the triglyceride glucose index with all-cause and cardiovascular mortality in a general population of Iranian adults
Authors: Alavi Tabatabaei Ghazaal , Mohammadifard Noushin , Rafiee Hamed , Nouri Fatemeh , Maghami mehr Asieh , Najafian Jamshid , Sadeghi Masoumeh , Boshtam Maryam , Roohafza Hamidreza , Haghighatdoost Fahimeh , Taheri Marzieh , Sarrafzadegan Nizal
Published: February 2024

Background

The triglyceride glucose (TyG) index is a new and low-cost marker to determine insulin resistant which may be a predictor of cardiovascular disease (CVD). Although available evidence showed that its association with CVD mortality (CVM) and all-cause mortality (ACM) may differ in different populations, scarce data are available in this regard specially in low and middle-income countries.

Purpose

To examine the association between TyG index and risk of CVM and ACM in Iranians.

Methods

This prospective cohort study included 5432 adults (age ≥ 35 years) with no history of CVD events. Fasting glucose and triglyceride were measured at baseline in all participants and TyG index was calculated. Cox frailty model was used to calculate hazard ratios (HRs) for CVM and ACM across the tertiles of TyG index.

Results

After a median follow-up of 11.25 years, a total number of 191 cardiovascular deaths, and 487 all-cause mortality was recorded. The risk of both CVM and ACM increased across the tertiles of TyG index. In the adjusted model for lifestyle and metabolic variables, the risks of ACM and CVM increased by 41% (95% CI 1.11, 1.81; P for trend = 0.005) and 64% (95% CI 1.07, 2.50; P for trend = 0.024), respectively. However, adjustment for diabetes mellitus disappeared the significance for both ACM and CVM. These associations may vary by sex. TyG was not related to the risk of non-CVD mortality.

Conclusion

The predicting value of TyG index for ACM and CVM might be mediated by diabetes status. Further studies are required to confirm these findings.
Scalable production of recombinant three-finger proteins: from inclusion bodies to high quality molecular probes
Authors: Xu Jiang , Lei Xiao , Li Ao , Li Jun , Li Shuxing , Chen Lin
Published: February 2024

Background

The three-finger proteins are a collection of disulfide bond rich proteins of great biomedical interests. Scalable recombinant expression and purification of bioactive three-finger proteins is quite difficult.

Results

We introduce a working pipeline for expression, purification and validation of disulfide-bond rich three-finger proteins using E. coli as the expression host. With this pipeline, we have successfully obtained highly purified and bioactive recombinant α-Βungarotoxin, k-Bungarotoxin, Hannalgesin, Mambalgin-1, α-Cobratoxin, MTα, Slurp1, Pate B etc. Milligrams to hundreds of milligrams of recombinant three finger proteins were obtained within weeks in the lab. The recombinant proteins showed specificity in binding assay and six of them were crystallized and structurally validated using X-ray diffraction protein crystallography.

Conclusions

Our pipeline allows refolding and purifying recombinant three finger proteins under optimized conditions and can be scaled up for massive production of three finger proteins. As many three finger proteins have attractive therapeutic or research interests and due to the extremely high quality of the recombinant three finger proteins we obtained, our method provides a competitive alternative to either their native counterparts or chemically synthetic ones and should facilitate related research and applications.
Evaluation of the malaria elimination programme in Muara Enim Regency: a qualitative study from Indonesia
Authors: Hasyim Hamzah , Marini Heni , Misnaniarti Misnaniarti , Flora Rostika , Liberty Iche Andriyani , Elagali Ahmed , Hartoni Hartoni , Maharani Fadhilah Eka
Published: February 2024

Background

Malaria remains an enduring public health concern in Indonesia, exacerbated by its equatorial climate that fosters the proliferation of Anopheles mosquitoes. This study seeks to assess the performance of the malaria elimination programme comprehensively.

Methods

Between May and August 2022, a qualitative study was conducted in Muara Enim Regency, South Sumatra Province, involving 22 healthcare professionals from diverse backgrounds. These informants were strategically chosen for their pivotal roles in providing profound insights into various facets of the malaria elimination programme. This encompasses inputs such as human resources, budgetary allocation, and infrastructural support; processes like case identification and management, capacity enhancement, epidemiological surveillance, prevention measures, outbreak control, and enhanced communication and educational initiatives; and, notably, the programme’s outcomes. Data were collected through 3-h Focus Group Discussions (FGDs) divided into two groups, each with 12 participants: healthcare professionals and programme managers. Additionally, in-depth interviews (IDIs) were conducted with ten informants. Employing the Input-Process-Output (IPO) model, this study meticulously analysed the healthcare system dynamics and the interventions’ efficacy.

Results

The study unveiled many challenges during the input phase, including the absence of entomologists and a shortage of diagnostic tools. Despite these obstacles, it documented remarkable accomplishments in the output domain, marked by significant advancements in the distribution of mosquito nets and the successful implementation of the Early Warning System (EWS). Despite the adversities, the programme has made substantial strides towards malaria elimination.

Conclusions

Urgent action is imperative to bolster the effectiveness of the malaria elimination programme. Key measures encompass augmenting the entomologist workforce, optimizing resource allocation, and ensuring stringent adherence to regional regulations. Addressing these concerns will enhance programme efficacy, yielding enduring public health benefits. This research substantially contributes to Indonesia’s ongoing malaria elimination endeavours, furnishing actionable insights for programme enhancement. Consequently, this research holds significant importance for the malaria elimination drive.
Two promising candidates for paratransgenesis, Elizabethkingia and Asaia, increase in both sexes of Anopheles gambiae mosquitoes after feeding
Authors: Egyirifa Richardson K. , Akorli Jewelna
Published: February 2024

Background

The male mosquito microbiome may be important for identifying ideal candidates for disease control. Among other criteria, mosquito-associated symbionts that have high localization in both male and female mosquitoes and are transmissible through both vertical and sexual routes are desirable. However, mosquito microbiome studies have mainly been female-focused. In this study, the microbiota of male and female Anopheles gambiae sensu lato (s.l.) were compared to identify shared or unique bacteria.

Methods

Late larval instars of Anopheles mosquitoes were collected from the field and raised to adults. Equal numbers of males and females of 1-day-old non-sugar-fed, 4–5-day-old sugar-fed and post-blood-fed females were randomly selected for whole-body analyses of bacteria 16S rRNA.

Results

Results revealed that male and female mosquitoes generally share similar microbiota except when females were blood-fed. Compared to newly emerged unfed mosquitoes, feeding on sugar and/or blood increased variability in microbial composition (⍺-diversity), with a higher disparity among females (39% P = 0.01) than in males (29% P = 0.03). Elizabethkingia meningoseptica and Asaia siamensis were common discriminants between feeding statuses in both males and females. While E. meningoseptica was particularly associated with sugar-fed mosquitoes of both sexes and sustained after blood feeding in females, A. siamensis was also increased in sugar-fed mosquitoes but decreased significantly in blood-fed females (LDA score > 4.0, P < 0.05). Among males, A. siamensis did not differ significantly after sugar meals.

Conclusions

Results indicate the opportunities for stable infection in mosquitoes should these species be used in bacteria-mediated disease control. Further studies are recommended to investigate possible host-specific tissue tropism of bacteria species which will inform selection of the most appropriate microbes for effective transmission-blocking strategies.
Mesenchymal stem cell-derived extracellular vesicles exert pro-angiogenic and pro-lymphangiogenic effects in ischemic tissues by transferring various microRNAs and proteins including ITGa5 and NRP1
Authors: Łabędź-Masłowska Anna , Vergori Luisa , Kędracka-Krok Sylwia , Karnas Elżbieta , Bobis-Wozowicz Sylwia , Sekuła-Stryjewska Małgorzata , Sarna Michał , Andriantsitohaina Ramaroson , Zuba-Surma Ewa K.
Published: February 2024

Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis.

Graphical Abstract