bluuebunny/crossref_metadata_2025 huggingface dataset:
Culture change and lessons learned from ten years in the VA centers of excellence in primary care education
Authors: Weppner William G. , Singh Mamta K. , Wipf Joyce E. , Shunk Rebecca , Woodard LeChauncy , Brienza Rebecca
Published: April 2024

Background

Team-based care is critical to achieving health care value while maximizing patient outcomes. Few descriptions exist of graduate-level team training interventions and practice models. Experience from the multisite, decade-long Veterans Affairs (VA) Centers of Excellence in Primary Care Education provides lessons for developing internal medicine training experiences in interprofessional clinical learning environments.

Methods

A review of multisite demonstration project transforming traditional silo-model training to interprofessional team-based primary care. Using iterative quality improvement approaches, sites evaluated curricula with learner, faculty and staff feedback. Learner- and patient-level outcomes and organizational culture change were examined using mixed methods, within and across sites. Participants included more than 1600 internal medicine, nurse practitioner, nursing, pharmacy, psychology, social work and physical therapy trainees. This took place in seven academic university-affiliated VA primary care clinics with patient centered medical home design

Results

Each site developed innovative design and curricula using common competencies of shared decision making, sustained relationships, performance improvement and interprofessional collaboration. Educational strategies included integrated didactics, workplace collaboration and reflection. Sites shared implementation best practices and outcomes. Cross-site evaluations of the impacts of these educational strategies indicated improvements in trainee clinical knowledge, team-based approaches to care and interest in primary care careers. Improved patient outcomes were seen in the quality of chronic disease management, reduction in polypharmacy, and reduced emergency department and hospitalizations. Evaluations of the culture of training environments demonstrated incorporation and persistence of interprofessional learning and collaboration.

Conclusions

Aligning education and practice goals with cross-site collaboration created a robust interprofessional learning environment. Improved trainee/staff satisfaction and better patient care metrics supports use of this model to transform ambulatory care training.

Trial registration

This evaluation was categorized as an operation improvement activity by the Office of Academic Affairs based on Veterans Health Administration Handbook 1058.05, in which information generated is used for business operations and quality improvement (Title 38 Code of Federal Regulations Part 16 (38 CFR 16.102(l)). The overall project was subject to administrative oversight rather Human Subjects Institutional Review Board, as such informed consent was waived as part of the project implementation and evaluation.
3D visualization technology for Learning human anatomy among medical students and residents: a meta- and regression analysis
Authors: Wang Junming , Li Wenjun , Dun Aishe , Zhong Ning , Ye Zhen
Published: April 2024

Background

3D visualization technology applies computers and other devices to create a realistic virtual world for individuals with various sensory experiences such as 3D vision, touch, and smell to gain a more effective understanding of the relationships between real spatial structures and organizations. The purpose of this study was to comprehensively evaluate the effectiveness of 3D visualization technology in human anatomy teaching/training and explore the potential factors that affect the training effects to better guide the teaching of classroom/laboratory anatomy.

Methods

We conducted a meta-analysis of randomized controlled studies on teaching human anatomy using 3D visualization technology. We extensively searched three authoritative databases, PubMed, Web of Science, and Embase; the main outcomes were the participants’ test scores and satisfaction, while the secondary outcomes were time consumption and enjoyment. Heterogeneity by I² was statistically determined because I²> 50%; therefore, a random-effects model was employed, using data processing software such as RevMan, Stata, and VOSviewer to process data, apply standardized mean difference and 95% confidence interval, and subgroup analysis to evaluate test results, and then conduct research through sensitivity analysis and meta-regression analysis.

Results

Thirty-nine randomized controlled trials (2,959 participants) were screened and included in this study. The system analysis of the main results showed that compared with other methods, including data from all regions 3D visualization technology moderately improved test scores as well as satisfaction and enjoyment; however, the time that students took to complete the test was not significantly reduced. Meta-regression analysis also showed that regional factorsaffected test scores, whereas other factors had no significant impact. When the literature from China was excluded, the satisfaction and happiness of the 3D virtual-reality group were statistically significant compared to those of the traditional group; however, the test results and time consumption were not statistically significant.

Conclusion

3D visualization technology is an effective way to improve learners’ satisfaction with and enjoyment of human anatomical learning, but it cannot reduce the time required for testers to complete the test. 3D visualization technology may struggle to improve the testers’ scores. The literature test results from China are more prone to positive results and affected by regional bias.
Overcoming barriers to equality, diversity, inclusivity, and sense of belonging in healthcare education: the Underrepresented Groups’ Experiences in Osteopathic Training (UrGEnT) mixed methods study
Authors: Draper-Rodi Jerry , Abbey Hilary , Hammond John , Thomson Oliver P. , Brownhill Kevin , MacMillan Andrew , Fabusuyi Yinka , Vogel Steven
Published: April 2024

Background

Individuals from minority groups have historically faced social injustices. Those from underrepresented groups have been less likely to access both healthcare services and higher education. Little is known about the experiences of underrepresented students during their undergraduate studies in osteopathy in the UK. The aim of this project was to explore awareness of cultural diversity and beliefs about patients from underrepresented groups in current osteopathic educational environments and evaluate students’ preparedness to manage patients from diverse groups. The project also aimed to investigate the educational experiences of students from underrepresented backgrounds during their training and their opinions on changes that could support better levels of recruitment and achievement. The findings were discussed with stakeholders in interactive workshops with the aim to develop recommendations for action and change.

Methods

A transformative action research paradigm informed this mixed methods project. It included: 1/ a survey of students from all seven osteopathic educational providers in the UK using the Multidimensional Cultural Humility Scale (MCHS); 2/ a series of focus groups with students from underrepresented groups (women, students with disabilities, students from minority ethnic backgrounds, and students identifying as LGBTQIA+); and 3/ a workshop forum to discuss findings.

Results

A total of 202 participants completed the MCHS and demographic questionnaire and seven focus groups were conducted. A model was developed to describe participants’ training experiences comprising two main themes: institutional contextual obstacles (with four sub-themes) and underrepresented students’ conceptual understanding of Equity, Diversity and Inclusion (EDI). Recommendations for change identified in the workshops were based on three topics: institutions, staff, and students.

Conclusion

Our findings confirm conclusions from other institutions that staff education is urgently needed to create and maintain equitable, inclusive environments in osteopathic educational institutions in the UK to support all students, particularly those from underrepresented groups. Institutional EDI processes and policies also need to be clarified or modified to ensure their usefulness, accessibility, and implementation.
Intercultural sensitivity in Chilean healthcare profession students
Authors: Pineda Patricia , Klenner Maura , Espinoza Gerardo , Mariño Rodrigo , Zaror Carlos
Published: April 2024

Each culture has unique health care related values, habits, perceptions, expectations, norms, etc., that makes cultural competence an important attribute to be developed by healthcare professionals, to ensure they provide effective treatment. Intercultural sensitivity (IS) is the affective dimension of cultural competence. The objective of this study is to explore the self-perceived level of IS in first and last year students of three health sciences professions (i.e., Dentistry, Medicine, and Nursing) at the Universidad de la Frontera, Temuco, Chile. This study adopted a cross-sectional design and a group comparison (e.g., year of study). 312 students completed the Intercultural Sensitivity Scale (ISS). Findings showed that overall ISS scores ranged from 1.83 to 4.94, with a mean score of 4.11 (s.d. 0.43). Group comparison between first and final year students showed statistically significant differences (4.18 vs. 4.00; p < 0.001). Medical and nursing students had a significantly higher overall mean IS score compared to dental students (4.21 and 4.16, respectively vs. 4.02; p < 0.01). There were also significant differences between three factors (interaction engagement; interaction confidence; and interaction enjoyment) by healthcare profession. These findings allow for discussion of the need for explicit incorporation and development of cultural competence in on health care professional curricula. Longitudinal research is needed to explore how IS changes over time, along with generating qualitative data from the student populations IS experiences and exposure.
A randomized controlled trial comparison of PTEBL and traditional teaching methods in “Stop the Bleed” training
Authors: Zhao Wanchen , Cao Yangbo , Hu Liangrong , Lu Chenxiao , Liu Gaoming , Gong Matthew , He Jinshen
Published: April 2024

Background

The Stop the Bleed (STB) training program was launched by the White House to minimize hemorrhagic deaths. Few studies focused on the STB were reported outside the United States. This study aimed to evaluate the effectiveness of a problem-, team- and evidence-based learning (PTEBL) approach to teaching, compared to traditional teaching methods currently employed in STB courses in China.

Methods

This study was a parallel group, unmasked, randomised controlled trial. We included third-year medical students of a five-year training program from the Xiangya School of Medicine, Central South University who voluntarily participated in the trial. One hundred fifty-three medical students were randomized (1:1) into the PTEBL group (n = 77) or traditional group (n = 76). Every group was led by a single instructor. The instructor in the PTEBL group has experienced in educational reform. However, the instructor in the traditional group follows a traditional teaching mode. The teaching courses for both student groups had the same duration of four hours. Questionnaires were conducted to assess teaching quality before and after the course. The trial was registered in the Central South University (No. 2021JY188).

Results

In the PTEBL group, students reported mastery in three fundamental STB skills—Direct Finger Compression (61/77, 79.2%), Packing (72/77, 93.8%), and Tourniquet Placement (71/77, 92.2%) respectively, while 76.3% (58/76), 89.5% (68/76), and 88.2% (67/76) of students in the traditional group (P > 0.05 for each pairwise comparison). 96.1% (74/77) of students in the PTEBL group felt prepared to help in an emergency, while 90.8% (69/76) of students in the traditional group (P > 0.05). 94.8% (73/77) of students reported improved teamwork skills after the PTEBL course, in contrast with 81.6% (62/76) of students in the traditional course (P = 0.011). Furthermore, a positive correlation was observed between improved clinical thinking skills and improved teamwork skills (R = 0.82, 95% CI: 0.74–0.88; P < 0.001).

Conclusions

Compared with the traditional teaching method, the PTEBL method was superior in teaching teamwork skills, and has equally effectively taught hemostasis techniques in the emergency setting. The PTEBL method can be introduced to the STB training in China.
The caregiver contribution to self-care of stroke inventory (CC-SCSI): evaluation of psychometric characteristics
Authors: Wang Wenna , Zhang Zhenxiang , Mei Yongxia , Zhou Bing , Zhang Dudu , Liu Lamei
Published: April 2024

Background

The caregiver contribution to self-care plays an important role in improving the health outcomes of chronic patients, which needs urgent attention. However, it has been hindered by the lack of a tailored instrument that assesses the caregiver contribution to self-care of stroke.

Objectives

To test the psychometric characteristics of the caregiver contribution to self-care of stroke Inventory (CC-SCSI) in health care practice.

Methods

Participants were recruited in Henan Province from March 2021 to October 2022, utilizing a multicenter stratified sampling approach. A 23-item self-report CC-SCSI with 3 separate scales measuring caregiver contribution to self-care maintenance of stroke, caregiver contribution to self-care monitoring of stroke and caregiver contribution to self-care management of stroke was tested for validity through discriminant validity, confirmatory factor analysis, concurrent validity and convergent validity. The reliability was tested by Cronbach’s α coefficient and test-retest reliability. Qualitative data were analysed using thematic analysis. A STROBE checklist was used.

Results

The three scales of the CC-SCSI exhibited good discriminant validity. Confirmatory factor analysis supported the three-factor structure of the Caregiver Contribution to Stroke Self-Care Maintenance and Management scales and the one-factor structure of the Caregiver Contribution to Stroke Self-Care Monitoring scale. The moderate correlation between the CC-SCSI and the Self-Care of Stroke Inventory indicated acceptable concurrent validity. The moderate correlation between the CC-SCSI and the Caregiver Contribution to Self-Care of Chronic Illness Inventory indicated acceptable convergent validity. Cronbach’s αs for the Caregiver Contribution to Self-Care Maintenance, Self-Care Monitoring, and Self-Care Management scales ranged from 0.876 to 0.974. Test-retest reliability showed average ICC values ranging from 0.828 to 0.903 (P < 0.001).

Conclusions

The 23-item CC-SCSI presents good psychometric properties and could be used to explore the caregiver contribution to stroke self-care in health care practice and research.
Barriers and facilitators to the implementation of prehabilitation for elderly frail patients prior to elective surgery: a qualitative study with healthcare professionals
Authors: Fuchs Tamina Isabel , Pfab Carina , Kiselev Jörn , Schaller Stefan J , Spies Claudia , Rombey Tanja
Published: April 2024

Background

Prehabilitation aims to enhance functional capacity before surgery, minimise complications and achieve a better postoperative outcome. This can be particularly useful for older, frail patients to better tolerate surgery. The aim of this study was to identify what barriers and facilitators healthcare professionals in Germany experienced in the implementation and delivery of the multimodal prehabilitation programme “PRAEP-GO” for (pre-)frail adults aged 70 years and older to inform the implementation of prehabilitation into standard care.

Methods

A nested descriptive qualitative study was conducted using semi-structured face-to-face interviews with healthcare professionals involved in the PRAEP-GO trial from the Berlin and Brandenburg region in Germany. Transcripts were analysed using Kuckartz’ qualitative content analysis. Results were interpreted and synthesised using the Consolidated Framework for Implementation Research, a theoretical framework to allow their application to a more general context.

Results

A total of 14 interviews were conducted. Seven therapists (physio-, ergo-, sports therapy), five physicians and two employees from other professions with mainly administrative and organisational tasks in the project. All identified barriers and facilitating factors could be assigned to the themes of organisation, prehabilitation, cooperation and communication between healthcare professionals and with patients. Much optimisation potential was found regarding organisational aspects, e.g. addressing perceived staff shortages and optimising the patient pathway. Furthermore, it became apparent that communication and cooperation between professionals but also with patients need to be improved. More evidence regarding prehabilitation should be provided to convince professionals more. Prehabilitation should be multimodal and individualised, including the programme duration. Officially introducing prehabilitation into standard care would facilitate its delivery.

Discussion

These findings underscore the fact that successful implementation of prehabilitation programmes, such as PRAEP-GO, requires sufficient organisational infrastructure, human resources, access to knowledge, an adaptable and individualised programme design as well as good communication among professionals and with patients. The transferability of the findings is limited by the absence of nutritionists and resulting overrepresentation of other therapists in the sample. To further convince professionals and patients of the concept of prehabilitation, more research is needed to build a solid evidence base that will ensure greater awareness and, thus, more motivation and cooperation among professionals and patients.

Trial registration

Open Science Framework (osf.io/ksfgj).
Improving medication dispensing and counselling for patients with vision impairment: a qualitative study of pharmacist-reported barriers and facilitators
Authors: Kentab Basma Y. , Barry Heather E. , Al-Aqeel Sinaa A. , Hughes Carmel M.
Published: April 2024

Background

People with vision impairment encounter many difficulties when it comes to medicines use. However, evidence indicates that there are major gaps in pharmaceutical care service provision worldwide and limited research on interventions to optimise medication use for this patient population. The Theoretical Domains Framework (TDF) provides a method for theoretically understanding individuals’ behaviour and informing development of interventions. The aim of this research was to (a) identify the barriers and facilitators to the provision of medication dispensing and counselling services by pharmacists to patients with vision impairment, and (b) identify key TDF domains to be targeted in a future intervention.

Methods

Semi-structured interviews were conducted with pharmacists from different pharmacy practice settings/areas in Saudi Arabia. The 14-domain TDF was utilised as the theoretical lens through which pharmacists’ behaviours were examined. Interviews were conducted in Arabic or English, either face-to-face or over the telephone based on the participant’s preference. Following transcription, interviews conducted in Arabic were translated into English before analysis. Data analysis involved using the framework method and content analysis to identify important barriers and facilitators to the provision of dispensing and counselling services to those with vision impairment. Key TDF domains that could be targeted in a future intervention were then identified using a consensus-based approach.

Results

Twenty-six pharmacists were interviewed. Pharmacists’ experience in pharmacy practice ranged from two to 28 years. A range of barriers and facilitators were highlighted as important in providing services to those with vision impairment. Eight domains were identified as ‘key domains’ including: ‘Knowledge’, ‘Skills’, ‘Beliefs about capabilities’, ‘Goals’, ‘Memory, attention, and decision processes’, ‘Environmental context and resources’, ‘Social influences’, and ‘Behavioural regulation’.

Conclusions

Barriers and facilitators identified by pharmacists will inform the development of an intervention to ensure its applicability to everyday practice. Future research will focus on the process of developing the proposed intervention through targeting key TDF domains to improve medication dispensing and counselling by pharmacists to patients with vision impairment.
Systematic review on the frequency and quality of reporting patient and public involvement in patient safety research
Authors: Hammoud Sahar , Alsabek Laith , Rogers Lisa , McAuliffe Eilish
Published: April 2024

Background

In recent years, patient and public involvement (PPI) in research has significantly increased; however, the reporting of PPI remains poor. The Guidance for Reporting Involvement of Patients and the Public (GRIPP2) was developed to enhance the quality and consistency of PPI reporting. The objective of this systematic review is to identify the frequency and quality of PPI reporting in patient safety (PS) research using the GRIPP2 checklist.

Methods

Searches were performed in Ovid MEDLINE, EMBASE, PsycINFO, and CINAHL from 2018 to December, 2023. Studies on PPI in PS research were included. We included empirical qualitative, quantitative, mixed methods, and case studies. Only articles published in peer-reviewed journals in English were included. The quality of PPI reporting was assessed using the short form of the (GRIPP2-SF) checklist.

Results

A total of 8561 studies were retrieved from database searches, updates, and reference checks, of which 82 met the eligibility criteria and were included in this review. Major PS topics were related to medication safety, general PS, and fall prevention. Patient representatives, advocates, patient advisory groups, patients, service users, and health consumers were the most involved. The main involvement across the studies was in commenting on or developing research materials. Only 6.1% (n = 5) of the studies reported PPI as per the GRIPP2 checklist. Regarding the quality of reporting following the GRIPP2-SF criteria, our findings show sub-optimal reporting mainly due to failures in: critically reflecting on PPI in the study; reporting the aim of PPI in the study; and reporting the extent to which PPI influenced the study overall.

Conclusions

Our review shows a low frequency of PPI reporting in PS research using the GRIPP2 checklist. Furthermore, it reveals a sub-optimal quality in PPI reporting following GRIPP2-SF items. Researchers, funders, publishers, and journals need to promote consistent and transparent PPI reporting following internationally developed reporting guidelines such as the GRIPP2. Evidence-based guidelines for reporting PPI should be encouraged and supported as it helps future researchers to plan and report PPI more effectively.

Trial registration

The review protocol is registered with PROSPERO (CRD42023450715).
Methionine inducing carbohydrate esterase secretion of Trichoderma harzianum enhances the accessibility of substrate glycosidic bonds
Authors: Liu Yang , Li Tuo , Zhu Han , Cao Linhua , Liang Lebin , Liu Dongyang , Shen Qirong
Published: April 2024

Background

The conversion of plant biomass into biochemicals is a promising way to alleviate energy shortage, which depends on efficient microbial saccharification and cellular metabolism. Trichoderma spp. have plentiful CAZymes systems that can utilize all-components of lignocellulose. Acetylation of polysaccharides causes nanostructure densification and hydrophobicity enhancement, which is an obstacle for glycoside hydrolases to hydrolyze glycosidic bonds. The improvement of deacetylation ability can effectively release the potential for polysaccharide degradation.

Results

Ammonium sulfate addition facilitated the deacetylation of xylan by inducing the up-regulation of multiple carbohydrate esterases (CE3/CE4/CE15/CE16) of Trichoderma harzianum. Mainly, the pathway of ammonium-sulfate's cellular assimilates inducing up-regulation of the deacetylase gene (Thce3) was revealed. The intracellular metabolite changes were revealed through metabonomic analysis. Whole genome bisulfite sequencing identified a novel differentially methylated region (DMR) that existed in the ThgsfR2 promoter, and the DMR was closely related to lignocellulolytic response. ThGsfR2 was identified as a negative regulatory factor of Thce3, and methylation in ThgsfR2 promoter released the expression of Thce3. The up-regulation of CEs facilitated the substrate deacetylation.

Conclusion

Ammonium sulfate increased the polysaccharide deacetylation capacity by inducing the up-regulation of multiple carbohydrate esterases of T. harzianum, which removed the spatial barrier of the glycosidic bond and improved hydrophilicity, and ultimately increased the accessibility of glycosidic bond to glycoside hydrolases.
The Anopheles coluzzii range extends into Kenya: detection, insecticide resistance profiles and population genetic structure in relation to conspecific populations in West and Central Africa
Authors: Kamau Luna , Bennett Kelly L. , Ochomo Eric , Herren Jeremy , Agumba Silas , Otieno Samson , Omoke Diana , Matoke-Muhia Damaris , Mburu David , Mwangangi Joseph , Ramaita Edith , Juma Elijah O. , Mbogo Charles , Barasa Sonia , Miles Alistair
Published: April 2024

Background

Anopheles coluzzii is a primary vector of malaria found in West and Central Africa, but its presence has hitherto never been documented in Kenya. A thorough understanding of vector bionomics is important as it enables the implementation of targeted and effective vector control interventions. Malaria vector surveillance efforts in the country have tended to focus on historically known primary vectors. The current study sought to determine the taxonomic status of samples collected from five different malaria epidemiological zones in Kenya as well as describe the population genetic structure and insecticide resistance profiles in relation to other An. coluzzii populations.

Methods

Mosquitoes were sampled as larvae from Busia, Kwale, Turkana, Kirinyaga and Kiambu counties, representing the range of malaria endemicities in Kenya, in 2019 and 2021 and emergent adults analysed using Whole Genome Sequencing (WGS) data processed in accordance with the Anopheles gambiae 1000 Genomes Project phase 3. Where available, historical samples from the same sites were included for WGS. Comparisons were made with An. coluzzii cohorts from West and Central Africa.

Results

This study reports the detection of An. coluzzii for the first time in Kenya. The species was detected in Turkana County across all three time points from which samples were analyzed and its presence confirmed through taxonomic analysis. Additionally, there was a lack of strong population genetic differentiation between An. coluzzii from Kenya and those from the more northerly regions of West and Central Africa, suggesting they represent a connected extension to the known species range. Mutations associated with target-site resistance to DDT and pyrethroids and metabolic resistance to DDT were found at high frequencies up to 64%. The profile and frequencies of the variants observed were similar to An. coluzzii from West and Central Africa but the ace-1 mutation linked to organophosphate and carbamate resistance present in An. coluzzii from coastal West Africa was absent in Kenya.

Conclusions

These findings emphasize the need for the incorporation of genomics in comprehensive and routine vector surveillance to inform on the range of malaria vector species, and their insecticide resistance status to inform the choice of effective vector control approaches.
Longitudinal leisure-time physical activity profiles throughout adulthood and related characteristics: a 36-year follow-up study of the older Finnish Twin Cohort
Authors: Berntzen Bram J. , Tolvanen Asko , Kujala Urho M. , Silventoinen Karri , Vuoksimaa Eero , Kaprio Jaakko , Aaltonen Sari
Published: April 2024

Background

Personalized interventions aiming to increase physical activity in individuals are effective. However, from a public health perspective, it would be important to stimulate physical activity in larger groups of people who share the vulnerability to be physically inactive throughout adulthood. To find these high-risk groups, we identified 36-year leisure-time physical activity profiles from young adulthood to late midlife in females and males. Moreover, we uncovered which anthropometric-, demographic-, lifestyle-, and health-related characteristics were associated with these physical activity profiles.

Methods

We included 2,778 females and 1,938 males from the population-based older Finnish Twin Cohort Study, who responded to health and behavior surveys at the mean ages of 24, 30, 40 and 60. Latent profile analysis was used to identify longitudinal leisure-time physical activity profiles.

Results

We found five longitudinal leisure-time physical activity profiles for both females and males. Females’ profiles were: 1) Low increasing moderate (29%), 2) Moderate stable (23%), 3) Very low increasing low (20%), 4) Low stable (20%) and 5) High increasing high (9%). Males’ profiles were: 1) Low increasing moderate (29%), 2) Low stable very low (26%), 3) Moderate decreasing low (21%), 4) High fluctuating high (17%) and 5) Very low stable (8%). In both females and males, lower leisure-time physical activity profiles were associated with lower education, higher body mass index, smoking, poorer perceived health, higher sedentary time, high blood pressure, and a higher risk for type 2 diabetes. Furthermore, lower leisure-time physical activity was linked to a higher risk of depression in females.

Conclusions

We found several longitudinal leisure-time physical activity profiles with unique changes in both sexes. Fewer profiles in females than in males remained or became low physically active during the 36-year follow-up. We observed that lower education, higher body mass index, and more smoking already in young adulthood were associated with low leisure-time physical activity profiles. However, the fact that several longitudinal profiles demonstrated a change in their physical activity behavior over time implies the potential for public health interventions to improve leisure-time physical activity levels.
Deciphering the role of FUS::DDIT3 expression and tumor microenvironment in myxoid liposarcoma development
Authors: Ranji Parmida , Jonasson Emma , Andersson Lisa , Filges Stefan , Luna Santamaría Manuel , Vannas Christoffer , Dolatabadi Soheila , Gustafsson Anna , Myklebost Ola , Håkansson Joakim , Fagman Henrik , Landberg Göran , Åman Pierre , Ståhlberg Anders
Published: April 2024

Background

Myxoid liposarcoma (MLS) displays a distinctive tumor microenvironment and is characterized by the FUS::DDIT3 fusion oncogene, however, the precise functional contributions of these two elements remain enigmatic in tumor development.

Methods

To study the cell-free microenvironment in MLS, we developed an experimental model system based on decellularized patient-derived xenograft tumors. We characterized the cell-free scaffold using mass spectrometry. Subsequently, scaffolds were repopulated using sarcoma cells with or without FUS::DDIT3 expression that were analyzed with histology and RNA sequencing.

Results

Characterization of cell-free MLS scaffolds revealed intact structure and a large variation of protein types remaining after decellularization. We demonstrated an optimal culture time of 3 weeks and showed that FUS::DDIT3 expression decreased cell proliferation and scaffold invasiveness. The cell-free MLS microenvironment and FUS::DDIT3 expression both induced biological processes related to cell-to-cell and cell-to-extracellular matrix interactions, as well as chromatin remodeling, immune response, and metabolism. Data indicated that FUS::DDIT3 expression more than the microenvironment determined the pre-adipocytic phenotype that is typical for MLS.

Conclusions

Our experimental approach opens new means to study the tumor microenvironment in detail and our findings suggest that FUS::DDIT3-expressing tumor cells can create their own extracellular niche.
Recent advances in the discovery and development of drugs targeting the kallikrein-kinin system
Authors: Wisniewski Petra , Gangnus Tanja , Burckhardt Bjoern B.
Published: April 2024

Background

The kallikrein-kinin system is a key regulatory cascade involved in blood pressure maintenance, hemostasis, inflammation and renal function. Currently, approved drugs remain limited to the rare disease hereditary angioedema. However, growing interest in this system is indicated by an increasing number of promising drug candidates for further indications.

Methods

To provide an overview of current drug development, a two-stage literature search was conducted between March and December 2023 to identify drug candidates with targets in the kallikrein-kinin system. First, drug candidates were identified using PubMed and Clinicaltrials.gov. Second, the latest publications/results for these compounds were searched in PubMed, Clinicaltrials.gov and Google Scholar. The findings were categorized by target, stage of development, and intended indication.

Results

The search identified 68 drugs, of which 10 are approved, 25 are in clinical development, and 33 in preclinical development. The three most studied indications included diabetic retinopathy, thromboprophylaxis and hereditary angioedema. The latter is still an indication for most of the drug candidates close to regulatory approval (3 out of 4). For the emerging indications, promising new drug candidates in clinical development are ixodes ricinus-contact phase inhibitor for thromboprophylaxis and RZ402 and THR-149 for the treatment of diabetic macular edema (all phase 2).

Conclusion

The therapeutic impact of targeting the kallikrein-kinin system is no longer limited to the treatment of hereditary angioedema. Ongoing research on other diseases demonstrates the potential of therapeutic interventions targeting the kallikrein-kinin system and will provide further treatment options for patients in the future.
CAV3 alleviates diabetic cardiomyopathy via inhibiting NDUFA10-mediated mitochondrial dysfunction
Authors: Guo Ping , Hu Shuiqing , Liu Xiaohui , He Miaomiao , Li Jie , Ma Tingqiong , Huang Man , Fang Qin , Wang Yan
Published: April 2024

Background

The progression of diabetic cardiomyopathy (DCM) is noticeably influenced by mitochondrial dysfunction. Variants of caveolin 3 (CAV3) play important roles in cardiovascular diseases. However, the potential roles of CAV3 in mitochondrial function in DCM and the related mechanisms have not yet been elucidated.

Methods

Cardiomyocytes were cultured under high-glucose and high-fat (HGHF) conditions in vitro, and db/db mice were employed as a diabetes model in vivo. To investigate the role of CAV3 in DCM and to elucidate the molecular mechanisms underlying its involvement in mitochondrial function, we conducted Liquid chromatography tandem mass spectrometry (LC–MS/MS) analysis and functional experiments.

Results

Our findings demonstrated significant downregulation of CAV3 in the cardiac tissue of db/db mice, which was found to be associated with cardiomyocyte apoptosis in DCM. Importantly, cardiac-specific overexpression of CAV3 effectively inhibited the progression of DCM, as it protected against cardiac dysfunction and cardiac remodeling associated by alleviating cardiomyocyte mitochondrial dysfunction. Furthermore, mass spectrometry analysis and immunoprecipitation assays indicated that CAV3 interacted with NDUFA10, a subunit of mitochondrial complex I. CAV3 overexpression reduced the degradation of lysosomal pathway in NDUFA10, restored the activity of mitochondrial complex I and improved mitochondrial function. Finally, our study demonstrated that CAV3 overexpression restored mitochondrial function and subsequently alleviated DCM partially through NDUFA10.

Conclusions

The current study provides evidence that CAV3 expression is significantly downregulated in DCM. Upregulation of CAV3 interacts with NDUFA10, inhibits the degradation of lysosomal pathway in NDUFA10, a subunit of mitochondrial complex I, restores the activity of mitochondrial complex I, ameliorates mitochondrial dysfunction, and thereby protects against DCM. These findings indicate that targeting CAV3 may be a promising approach for the treatment of DCM.
An implementation analysis of a quality improvement project to reduce cesarean section in Brazilian private hospitals
Authors: Torres Jacqueline Alves , Leite Tatiana Henriques , Fonseca Thaís Cristina Oliveira , Domingues Rosa Maria Soares Madeira , Figueiró Ana Claudia , Pereira Ana Paula Esteves , Theme-Filha Mariza Miranda , da Silva Ayres Bárbara Vasques , Scott Oliver , de Cássia Sanchez Rita , Borem Paulo , de Maio Osti Maria Carolina , Rosa Marcos Wengrover , Andrade Amanda S. , Filho Fernando Maia Peixoto , Nakamura-Pereira Marcos , do Carmo Leal Maria
Published: April 2024

Background

Brazil has one of the highest prevalence of cesarean sections in the world. The private health system is responsible for carrying out most of these surgical procedures. A quality improvement project called Adequate Childbirth Project (“Projeto Parto Adequado”- PPA) was developed to identify models of care for labor and childbirth, which place value on vaginal birth and reduce the frequency of cesarean sections without a clinical indication. This research aims to evaluate the implementation of PPA in private hospitals in Brazil.

Method

Evaluative hospital-based survey, carried out in 2017, in 12 private hospitals, including 4,322 women. We used a Bayesian network strategy to develop a theoretical model for implementation analysis. We estimated and compared the degree of implementation of two major driving components of PPA—“Participation of women” and “Reorganization of care” – among the 12 hospitals and according to type of hospital (belonging to a health insurance company or not). To assess whether the degree of implementation was correlated with the rate of vaginal birth data we used the Bayesian Network and compared the difference between the group “Exposed to the PPA model of care” and the group “Standard of care model”.

Results

PPA had a low degree of implementation in both components “Reorganization of Care” (0.17 – 0.32) and “Participation of Women” (0.21 – 0.34). The combined implementation score was 0.39–0.64 and was higher in hospitals that belonged to a health insurance company. The vaginal birth rate was higher in hospitals with a higher degree of implementation of PPA.

Conclusion

The degree of implementation of PPA was low, which reflects the difficulties in changing childbirth care practices. Nevertheless, PPA increased vaginal birth rates in private hospitals with higher implementation scores. PPA is an ongoing quality improvement project and these results demonstrate the need for changes in the involvement of women and the care offered by the provider.
Yu Linzhu alleviates primary ovarian insufficiency in a rat model by improving proliferation and energy metabolism of granulosa cells through hif1α/cx43 pathway
Authors: Ruan Xin , Wang Pengxu , Wei Maolin , Yang Qingqing , Dong Xiaoying
Published: April 2024

Background

Yu Linzhu (YLZ) is a classical Chinese traditional formula, which has been used for more than 600 years to regulate menstruation to help pregnancy. However, the mechanism of modern scientific action of YLZ needs to be further studied.

Methods

Thirty SD female rats were divided into three groups to prepare the blank serum and drug-containing serum, and then using UHPLC-QE-MS to identify the ingredients of YLZ and its drug-containing serum. Twenty-four SD female rats were divided into four groups, except the control group, 4-vinylcyclohexene dicycloxide (VCD) was intraperitoneally injected to establish a primary ovarian insufficiency (POI) model of all groups. Using vaginal smear to show that the estrous cycle of rats was disturbed after modeling, indicates that the POI model was successfully established. The ELISA test was used to measure the follicle-stimulating hormone (FSH), estradiol (E2), and anti-Mullerian hormone (AMH) levels in the serum of rats. HE stain was used to assess the morphology of ovarian tissue. The localization and relative expression levels of CX43 protein were detected by tissue immunofluorescence. Primary ovarian granulosa cells (GCs) were identified by cellular immunofluorescence. CCK8 was used to screen time and concentration of drug-containing serum and evaluate the proliferation effect of YLZ on VCD-induced GCs. ATP kit and Seahorse XFe24 were used to detect energy production and real-time glycolytic metabolism rate of GCs. mRNA and protein expression levels of HIF1α, CX43, PEK, LDH, HK1 were detected by RT-PCR and WB.

Results

UHPLC-QE-MS found 1702 ingredients of YLZ and 80 constituents migrating to blood. YLZ reduced the FSH while increasing the AMH and E2 levels. In ovarian tissues, YLZ improved ovarian morphology, follicle development, and the relative expression of CX43. In vitro studies, we found that YLZ increased the proliferative activity of GCs, ATP levels, glycolytic metabolic rate, HIF1α, CX43, PEK, HK1, LDH mRNA, and protein levels.

Conclusions

The study indicated that YLZ increased the proliferation and glycolytic energy metabolism of GCs to improve follicular development further alleviating ovarian function.
The association between triglyceride glucose-body Mass Index and in vitro fertilization outcomes in women with polycystic ovary syndrome: a cohort study
Authors: Li Xin , Luan Ting , Wei Yi , Zhang JuanJuan , Zhao Chun , Ling Xiufeng
Published: April 2024

Background

Polycystic Ovary Syndrome (PCOS) is a common reproductive disorder that frequently affects fertility. The TyG-BMI (Triglyceride glucose-body mass) index is a newly explored parameter that may be linked to reproductive results in individuals with PCOS. Nevertheless, its connection with outcomes in In Vitro Fertilization (IVF) procedures remains uncertain.

Methods

This study included a total of 966 females who underwent IVF treatments for PCOS. At the baseline, the participants were categorized into four groups according to the quartiles of TyG-BMI measured prior to oocyte retrieval. Subsequently, the study compared the differences in clinical and laboratory outcomes among these four groups.

Results

Patients in higher TyG-BMI quartiles exhibited a decreased number of retrieved oocytes, 2PN embryos, and available/high-quality embryos (P < 0.05 for Q1-Q4). Additionally, the multivariable regression analysis revealed that individuals in the top quartile of TyG-BMI had a lower count of accessible embryos (β = -0.224, P = 0.257) and a decreased number of high-quality embryos (β = -0.352, P = 0.028) in comparison to those in the lowest quartile. Nevertheless, there were no notable variances detected in the rates of pregnancy or live births among these quartiles. Furthermore, a linear correlation was noted between the TyG-BMI index and the quantity of accessible embryos (P-non-linear = 0.6, P-overall < 0.001), along with high-quality embryos (P-nonlinear = 0.026, P-overall = 0.006). In contrast, there was no notable linear correlation found between the TyG-BMI index and the available embryo rate (P-nonlinear = 0.60, P-overall = 0.8).

Conclusions

The results of this research emphasize the notable correlation between TyG-BMI and IVF results in females diagnosed with PCOS. The interplay of insulin resistance and disorders of lipid metabolism may indeed play a pivotal role in influencing the assisted reproductive outcomes of patients with PCOS. Considering these findings, TyG-BMI proves to be a valuable indicator for exploring this potential association.
NextDenovo: an efficient error correction and accurate assembly tool for noisy long reads
Authors: Hu Jiang , Wang Zhuo , Sun Zongyi , Hu Benxia , Ayoola Adeola Oluwakemi , Liang Fan , Li Jingjing , Sandoval José R. , Cooper David N. , Ye Kai , Ruan Jue , Xiao Chuan-Le , Wang Depeng , Wu Dong-Dong , Wang Sheng
Published: April 2024

Long-read sequencing data, particularly those derived from the Oxford Nanopore sequencing platform, tend to exhibit high error rates. Here, we present NextDenovo, an efficient error correction and assembly tool for noisy long reads, which achieves a high level of accuracy in genome assembly. We apply NextDenovo to assemble 35 diverse human genomes from around the world using Nanopore long-read data. These genomes allow us to identify the landscape of segmental duplication and gene copy number variation in modern human populations. The use of NextDenovo should pave the way for population-scale long-read assembly using Nanopore long-read data.
Enhancing prime editor flexibility with coiled-coil heterodimers
Authors: Mu Shuangshuang , Chen Huangyao , Li Qianru , Gou Shixue , Liu Xiaoyi , Wang Junwei , Zheng Wei , Chen Menglong , Jin Qin , Lai Liangxue , Wang Kepin , Shi Hui
Published: April 2024

Background

Prime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency.

Results

Herein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target thePcsk9gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol.

Conclusions

Our innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.