bluuebunny/crossref_metadata_2025 huggingface dataset:
Closing the gaps in patient management of dyslipidemia: stepping into cardiovascular precision diagnostics with apolipoprotein profiling
Authors: Reijnders Esther , van der Laarse Arnoud , Ruhaak L. Renee , Cobbaert Christa M.
Published: March 2024

In persons with dyslipidemia, a high residual risk of cardiovascular disease remains despite lipid lowering therapy. Current cardiovascular risk prediction mainly focuses on low-density lipoprotein cholesterol (LDL-c) levels, neglecting other contributing risk factors. Moreover, the efficacy of LDL-c lowering by statins resulting in reduced cardiovascular risk is only partially effective. Secondly, from a metrological viewpoint LDL-c falls short as a reliable measurand. Both direct and calculated LDL-c tests produce inaccurate test results at the low end under aggressive lipid lowering therapy. As LDL-c tests underperform both clinically and metrologically, there is an urging need for molecularly defined biomarkers. Over the years, apolipoproteins have emerged as promising biomarkers in the context of cardiovascular disease as they are the functional workhorses in lipid metabolism. Among these, apolipoprotein B (ApoB), present on all atherogenic lipoprotein particles, has demonstrated to clinically outperform LDL-c. Other apolipoproteins, such as Apo(a) - the characteristic apolipoprotein of the emerging risk factor lipoprotein(a) -, and ApoC-III - an inhibitor of triglyceride-rich lipoprotein clearance -, have attracted attention as well. To support personalized medicine, we need to move to molecularly defined risk markers, like the apolipoproteins. Molecularly defined diagnosis and molecularly targeted therapy require molecularly measured biomarkers. This review provides a summary of the scientific validity and (patho)physiological role of nine serum apolipoproteins, Apo(a), ApoB, ApoC-I, ApoC-II, ApoC-III, ApoE and its phenotypes, ApoA-I, ApoA-II, and ApoA-IV, in lipid metabolism, their association with cardiovascular disease, and their potential as cardiovascular risk markers when measured in a multiplex apolipoprotein panel.
A Synthetic Microbiome Based on Dominant Microbes in Wild Rice Rhizosphere to Promote Sulfur Utilization
Authors: Wang Changji , Chang Jingjing , Tian Lei , Sun Yu , Wang Enze , Yao Zongmu , Ye Libo , Zhang Hengfei , Pang Yingnan , Tian Chunjie
Published: March 2024

Sulfur (S) is one of the main components of important biomolecules, which has been paid more attention in the anaerobic environment of rice cultivation. In this study, 12 accessions of rice materials, belonging to two Asian rice domestication systems and one African rice domestication system, were used by shotgun metagenomics sequencing to compare the structure and function involved in S cycle of rhizosphere microbiome between wild and cultivated rice. The sulfur cycle functional genes abundances were significantly different between wild and cultivated rice rhizosphere in the processes of sulfate reduction and other sulfur compounds conversion, implicating that wild rice had a stronger mutually-beneficial relationship with rhizosphere microbiome, enhancing sulfur utilization. To assess the effects of sulfate reduction synthetic microbiomes, Comamonadaceae and Rhodospirillaceae, two families containing the genes of two key steps in the dissimilatory sulfate reduction, aprA and dsrA respectively, were isolated from wild rice rhizosphere. Compared with the control group, the dissimilatory sulfate reduction in cultivated rice rhizosphere was significantly improved in the inoculated with different proportions groups. It confirmed that the synthetic microbiome can promote the S-cycling in rice, and suggested that may be feasible to construct the synthetic microbiome step by step based on functional genes to achieve the target functional pathway. In summary, this study reveals the response of rice rhizosphere microbial community structure and function to domestication, and provides a new idea for the construction of synthetic microbiome.
Qualitative hydrology: a review of the last quarter century and a glimpse into the future from the perspective of the Division G of the Federal Institute of Hydrology
Authors: Duester Lars , Breitung Vera , Brinke Marvin , Buchinger Sebastian , Dierkes Georg , Dietrich Christian , Hahn Jens , Jewell Kevin S. , Kleisinger Carmen , Loeffler Dirk , Radny Dirk , Reifferscheid Georg , Schäfer Sabine , Schluesener Michael P. , Schmidt Axel , Schwandt Daniel , Schüttler Andreas , Stoffels Matthias , Voelpel Rike , Wick Arne , Wiederhold Jan G. , Zavarsky Alexander , Ternes Thomas A.
Published: March 2024

With the nationwide introduction of wastewater treatment the overall water quality improved significantly, but challenges remain, including diffuse pollution, historical sediment contamination and the presence of a multitude of anthropogenic chemical species. The implementation of several EU directives in the twenty-first century led to a stronger focus on improving water and sediment quality and the sustainable management of sediments at river basin scale. Hence, in the last 25 years, not only have the regulatory frameworks significantly changed, but also the scientific backbone of our products, delivered to Germany’s federal ministries, practitioners from the German Waterways and Shipping Administration, German federal states and the public. In this respect, approaches such as non-target screening, multi-element analysis, effect-based methods, novel approaches in microplastic and nanoparticle analysis and the benefits from the increase in digitalization and automation are key methods and processes to face future challenges, especially those connected to the global climate crisis.
Systematic identification and expression analysis of bHLH gene family reveal their relevance to abiotic stress response and anthocyanin biosynthesis in sweetpotato
Authors: Guo Fen , Meng Xiaoqing , Hong Haiting , Liu Siyuan , Yu Jing , Huang Can , Dong Tingting , Geng Huixue , Li Zongyun , Zhu Mingku
Published: March 2024

Background

bHLH transcription factors play significant roles in regulating plant growth and development, stress response, and anthocyanin biosynthesis. Sweetpotato is a pivotal food and industry crop, but little information is available on sweetpotato bHLH genes.

Results

Herein, 227 putative IbbHLH genes were defined on sweetpotato chromosomes, and fragment duplications were identified as the dominant driving force for IbbHLH expansion. These IbbHLHs were divided into 26 subfamilies through phylogenetic analysis, as supported by further analysis of exon-intron structure and conserved motif composition. The syntenic analysis between IbbHLHs and their orthologs from other plants depicted evolutionary relationships of IbbHLHs. Based on the transcriptome data under salt stress, the expression of 12 IbbHLHs was screened for validation by qRT-PCR, and differential and significant transcriptions under abiotic stress were detected. Moreover, IbbHLH123 and IbbHLH215, which were remarkably upregulated by stress treatments, had obvious transactivation activity in yeasts. Protein interaction detections and yeast two-hybrid assays suggested an intricate interaction correlation between IbbHLHs. Besides, transcriptome screening revealed that multiple IbbHLHs may be closely related to anthocyanin biosynthesis based on the phenotype (purple vs. white tissues), which was confirmed by subsequent qRT-PCR analysis.

Conclusions

These results shed light on the promising functions of sweetpotato IbbHLHs in abiotic stress response and anthocyanin biosynthesis.
A Bayesian Bernoulli-Exponential joint model for binary longitudinal outcomes and informative time with applications to bladder cancer recurrence data
Authors: Oduro Michael Safo
Published: March 2024

Background

A variety of methods exist for the analysis of longitudinal data, many of which are characterized with the assumption of fixed visit time points for study individuals. This, however is not always a tenable assumption. Phenomenon that alter subject visit patterns such as adverse events due to investigative treatment administered, travel or any other emergencies may result in unbalanced data and varying individual visit time points. Visit times can be considered informative, because subsequent or current subject outcomes can change or be adapted due to previous subject outcomes.

Methods

In this paper, a Bayesian Bernoulli-Exponential model for analyzing joint binary outcomes and exponentially distributed informative visit times is developed. Via statistical simulations, the influence of controlled variations in visit patterns, prior and sample size schemes on model performance is assessed. As an application example, the proposed model is applied to a Bladder Cancer Recurrence data.

Results and conclusions

Results from the simulation analysis indicated that the Bayesian Bernoulli-Exponential joint model converged in stationarity, and performed relatively better for small to medium sample size scenarios with less varying time sequences regardless of the choice of prior. In larger samples, the model performed better for less varying time sequences. This model’s application to the bladder cancer data showed a statistically significant effect of prior tumor recurrence on the probability of subsequent recurrences.
Flexible Bayesian semiparametric mixed-effects model for skewed longitudinal data
Authors: Ferede Melkamu M. , Dagne Getachew A. , Mwalili Samuel M. , Bilchut Workagegnehu H. , Engida Habtamu A. , Karanja Simon M.
Published: March 2024

Background

In clinical trials and epidemiological research, mixed-effects models are commonly used to examine population-level and subject-specific trajectories of biomarkers over time. Despite their increasing popularity and application, the specification of these models necessitates a great deal of care when analysing longitudinal data with non-linear patterns and asymmetry. Parametric (linear) mixed-effect models may not capture these complexities flexibly and adequately. Additionally, assuming a Gaussian distribution for random effects and/or model errors may be overly restrictive, as it lacks robustness against deviations from symmetry.

Methods

This paper presents a semiparametric mixed-effects model with flexible distributions for complex longitudinal data in the Bayesian paradigm. The non-linear time effect on the longitudinal response was modelled using a spline approach. The multivariate skew-t distribution, which is a more flexible distribution, is utilized to relax the normality assumptions associated with both random-effects and model errors.

Results

To assess the effectiveness of the proposed methods in various model settings, simulation studies were conducted. We then applied these models on chronic kidney disease (CKD) data and assessed the relationship between covariates and estimated glomerular filtration rate (eGFR). First, we compared the proposed semiparametric partially linear mixed-effect (SPPLM) model with the fully parametric one (FPLM), and the results indicated that the SPPLM model outperformed the FPLM model. We then further compared four different SPPLM models, each assuming different distributions for the random effects and model errors. The model with a skew-t distribution exhibited a superior fit to the CKD data compared to the Gaussian model. The findings from the application revealed that hypertension, diabetes, and follow-up time had a substantial association with kidney function, specifically leading to a decrease in GFR estimates.

Conclusions

The application and simulation studies have demonstrated that our work has made a significant contribution towards a more robust and adaptable methodology for modeling intricate longitudinal data. We achieved this by proposing a semiparametric Bayesian modeling approach with a spline smoothing function and a skew-t distribution.
Downregulation of SMOC1 is associated with progression of colorectal traditional serrated adenomas
Authors: Aoki Hironori , Takasawa Akira , Yamamoto Eiichiro , Niinuma Takeshi , Yamano Hiro-o , Harada Taku , Kubo Toshiyuki , Yorozu Akira , Kitajima Hiroshi , Ishiguro Kazuya , Kai Masahiro , Katanuma Akio , Shinohara Toshiya , Nakase Hiroshi , Sugai Tamotsu , Osanai Makoto , Suzuki Hiromu
Published: March 2024

Background

Aberrant DNA methylation is prevalent in colorectal serrated lesions. We previously reported that the CpG island of SMOC1 is frequently methylated in traditional serrated adenomas (TSAs) and colorectal cancers (CRCs) but is rarely methylated in sessile serrated lesions (SSLs). In the present study, we aimed to further characterize the expression of SMOC1 in early colorectal lesions.

Methods

SMOC1 expression was analyzed immunohistochemically in a series of colorectal tumors (n = 199) and adjacent normal colonic tissues (n = 112).

Results

SMOC1 was abundantly expressed in normal colon and SSLs while it was significantly downregulated in TSAs, advanced adenomas and cancers. Mean immunohistochemistry scores were as follows: normal colon, 24.2; hyperplastic polyp (HP), 18.9; SSL, 23.8; SSL with dysplasia (SSLD)/SSL with early invasive cancer (EIC), 15.8; TSA, 5.4; TSA with high grade dysplasia (HGD)/EIC, 4.7; non-advanced adenoma, 21.4; advanced adenoma, 11.9; EIC, 10.9. Higher levels SMOC1 expression correlated positively with proximal colon locations and flat tumoral morphology, reflecting its abundant expression in SSLs. Among TSAs that contained both flat and protruding components, levels of SMOC1 expression were significantly lower in the protruding components.

Conclusion

Our results suggest that reduced expression of SMOC1 is associated with progression of TSAs and conventional adenomas and that SMOC1 expression may be a biomarker for diagnosis of serrated lesions and risk prediction in colorectal tumors.
Craniofacial phenotyping with fetal MRI: a feasibility study of 3D visualisation, segmentation, surface-rendered and physical models
Authors: Matthew Jacqueline , Uus Alena , De Souza Leah , Wright Robert , Fukami-Gartner Abi , Priego Gema , Saija Carlo , Deprez Maria , Collado Alexia Egloff , Hutter Jana , Story Lisa , Malamateniou Christina , Rhode Kawal , Hajnal Jo , Rutherford Mary A.
Published: March 2024

This study explores the potential of 3D Slice-to-Volume Registration (SVR) motion-corrected fetal MRI for craniofacial assessment, traditionally used only for fetal brain analysis. In addition, we present the first description of an automated pipeline based on 3D Attention UNet trained for 3D fetal MRI craniofacial segmentation, followed by surface refinement. Results of 3D printing of selected models are also presented.

Qualitative analysis of multiplanar volumes, based on the SVR output and surface segmentations outputs, were assessed with computer and printed models, using standardised protocols that we developed for evaluating image quality and visibility of diagnostic craniofacial features. A test set of 25, postnatally confirmed, Trisomy 21 fetal cases (24–36 weeks gestational age), revealed that 3D reconstructed T2 SVR images provided 66–100% visibility of relevant craniofacial and head structures in the SVR output, and 20–100% and 60–90% anatomical visibility was seen for the baseline and refined 3D computer surface model outputs respectively. Furthermore, 12 of 25 cases, 48%, of refined surface models demonstrated good or excellent overall quality with a further 9 cases, 36%, demonstrating moderate quality to include facial, scalp and external ears. Additional 3D printing of 12 physical real-size models (20–36 weeks gestational age) revealed good/excellent overall quality in all cases and distinguishable features between healthy control cases and cases with confirmed anomalies, with only minor manual adjustments required before 3D printing.

Despite varying image quality and data heterogeneity, 3D T2w SVR reconstructions and models provided sufficient resolution for the subjective characterisation of subtle craniofacial features. We also contributed a publicly accessible online 3D T2w MRI atlas of the fetal head, validated for accurate representation of normal fetal anatomy.

Future research will focus on quantitative analysis, optimizing the pipeline, and exploring diagnostic, counselling, and educational applications in fetal craniofacial assessment.
A cost-benefit analysis of genetic screening test for breast cancer in Iran
Authors: Meshkani Zahra , Moradi Najmeh , Aboutorabi Ali , Farabi Hiro , Moini Nazi
Published: March 2024

Background

This study aimed to evaluate the implementation of the population- and family history (FH) -based screening for BReast CAncer (BRCA) in Iran, a country where less than 10% of breast cancer cases are attributable to a gene mutation.

Methods

This was an economic evaluation study. The Benefit-Cost Ratio (BCR) for genetic screening test strategies in Iranian women older than 30 was calculated. To this end, the monetary value of the test was estimated using the willingness-to-pay (WTP) approach using the contingent valuation method (CVM) by payment card. From a healthcare perspective, direct medical and non-medical costs were considered and a decision model for the strategies was developed to simulate the costs. A one-way sensitivity analysis assessed the robustness of the analysis. The data were analyzed using Excel 2010.

Results

660 women were included for estimating WTP and 2,176,919 women were considered in the costing model. The cost per genetic screening test for population- and FH-based strategies was $167 and $8, respectively. The monetary value of a genetic screening test was $20 and it was $27 for women with a family history or gene mutation in breast cancer. The BCR for population-based and FH-based screening strategies was 0.12 and 3.37, respectively. Sensitivity analyses confirmed the robustness of the results.

Conclusions

This study recommends the implementation of a FH-based strategy instead of a population-based genetic screening strategy in Iran, although a cascade genetic screening test strategy should be evaluated in future studies.
AMPKα2 promotes tumor immune escape by inducing CD8+ T-cell exhaustion and CD4+ Treg cell formation in liver hepatocellular carcinoma
Authors: Ouyang Yan , Gu Yan , Zhang Xinhai , Huang Ya , Wei Xianpeng , Tang Fuzhou , Zhang Shichao
Published: March 2024

Background

Adenosine monophosphate-activated protein kinase (AMPK) is associated with the development of liver hepatocellular carcinoma (LIHC). AMPKα2, an α2 subunit of AMPK, is encoded by PRKAA2, and functions as the catalytic core of AMPK. However, the role of AMPKα2 in the LIHC tumor immune environment is unclear.

Methods

RNA-seq data were obtained from the Cancer Genome Atlas and Genotype-Tissue Expression databases. Using the single-cell RNA-sequencing dataset for LIHC obtained from the China National Genebank Database, the communication between malignant cells and T cells in response to different PRKAA2 expression patterns was evaluated. In addition, the association between PRKAA2 expression and T-cell evolution during tumor progression was explored using Pseudotime analysis, and the role of PRKAA2 in metabolic reprogramming was explored using the R “scMetabolis” package. Functional experiments were performed in LIHC HepG2 cells.

Results

AMPK subunits were expressed in tissue-specific and substrate-specific patterns. PRKAA2 was highly expressed in LIHC tissues and was associated with poor patient prognosis. Tumors with high PRKAA2 expression displayed an immune cold phenotype. High PRKAA2 expression significantly promoted LIHC immune escape. This result is supported by the following evidence: 1) the inhibition of major histocompatibility complex class I (MHC-I) expression through the regulation of interferon-gamma activity in malignant cells; 2) the promotion of CD8+ T-cell exhaustion and the formation of CD4+ Treg cells in T cells; 3) altered interactions between malignant cells and T cells in the tumor immune environment; and 4) induction of metabolic reprogramming in malignant cells.

Conclusions

Our study indicate that PRKAA2 may contribute to LIHC progression by promoting metabolic reprogramming and tumor immune escape through theoretical analysis, which offers a theoretical foundation for developing PRKAA2-based strategies for personalized LIHC treatment.
Study of myopia progression and risk factors in Hubei children aged 7–10 years using machine learning: a longitudinal cohort
Authors: Li Wenping , Tu Yuyang , Zhou Lianhong , Ma Runting , Li Yuanjin , Hu Diewenjie , Zhang Cancan , Lu Yi
Published: March 2024

Background

To investigate the trend of refractive error among elementary school students in grades 1 to 3 in Hubei Province, analyze the relevant factors affecting myopia progression, and develop a model to predict myopia progression and the risk of developing high myopia in children.

Methods

Longitudinal study. Using a cluster-stratified sampling method, elementary school students in grades 1 to 3 (15,512 in total) from 17 cities in Hubei Province were included as study subjects. Visual acuity, cycloplegic autorefraction, and height and weight measurements were performed for three consecutive years from 2019 to 2021. Basic information about the students, parental myopia and education level, and the students’ behavioral habits of using the eyes were collected through questionnaires.

Results

The baseline refractive errors of children in grades 1 ~ 3 in Hubei Province in 2019 were 0.20 (0.11, 0.27)D, −0.14 (−0.21, 0.06)D, and − 0.29 (−0.37, −0.22)D, respectively, and the annual myopia progression was − 0.65 (−0.74, −0.63)D, −0.61 (−0.73, −0.59)D and − 0.59 (−0.64, −0.51)D, with the prevalence of myopia increasing from 17.56%, 20.9%, and 34.08% in 2019 to 24.16%, 32.24%, and 40.37% in 2021 (Χ2 = 63.29, P < 0.001). With growth, children’s refractive error moved toward myopia, and the quantity of myopic progression gradually diminished. (F = 291.04, P = 0.027). The myopia progression in boys was less than that in girls in the same grade (P < 0.001). The change in spherical equivalent refraction in myopic children was smaller than that in hyperopic and emmetropic children (F = 59.28, P < 0.001), in which the refractive change in mild myopia, moderate myopia, and high myopia children gradually increased (F = 73.12, P < 0.001). Large baseline refractive error, large body mass index, and high frequency of eating sweets were risk factors for myopia progression, while parental intervention and strong eye-care awareness were protective factors for delaying myopia progression. The nomogram graph predicted the probability of developing high myopia in children and found that baseline refraction had the greatest predictive value.

Conclusion

Myopia progression varies by age, sex, and myopia severity. Baseline refraction is the most important factor in predicting high myopia in childhood. we should focus on children with large baseline refraction or young age of onset of myopia in clinical myopia prevention and control.
Social and behavior change communication competency among front-line healthcare system actors in Ethiopia: a cross-sectional study
Authors: Handebo Simegnew , Sharma Rachana , Simireta Tesfaye , Addissie Hailemariam , Endalew Getnet Bayih , Girma Eshetu , Mossa Kenzudin Assfa
Published: March 2024

Introduction

Social and Behavior Change Communication (SBCC) plays a critical role in improving behavior and health outcomes across the continuum of healthcare. Failing to implement tailored SBCC strategies continues to pose a risk of ill health, increase disease burden, and impact the quality life of people. In Ethiopia, front-line healthcare system actors’ knowledge and skills about SBCC have not been rigorously assessed. Thus, the current study aimed to assess healthcare system actors’ competencies in designing, implementing, monitoring, and evaluating SBCC interventions in Ethiopia.

Methods

A cross-sectional study was conducted between 01 August and 31 October, 2020. Five hundred twenty-eight frontline healthcare system actors in SBCC in Ethiopia were included using simple random sampling technique. Data was collected using a self-administered structured questionnaire adopted from Communication for Change; SBCC capacity assessment tool. Descriptive analysis frequencies, percentages, mean, median, standard deviation (SD), interquartile range (IQR) were employed. Besides correlations and linear regression with robust standard errors were carried out. A 95% confidence interval and a p-value of less than 0.05 were used to declare significant statistical association.

Results

A total of 488 frontline workers participated in the study, with a response rate of 92.4%. The mean SBCC knowledge score was 13.2 ± standard deviation (SD) 3.99 and 59.2% scored below 60% of the expected maximum score. The standard mean score of overall skill in SBCC intervention was 2.36 (SD ± 0.98) and 52.6% of them scored below mean score. The SBCC knowledge was significantly predicted by the service year and the regional variation. On the other hand, SBCC skills was significantly predicted by sex, service year, profession, regional variation, and SBCC knowledge. The regional variation was the main predictor of both knowledge and skill on SBCC. The regression models explained 23.1% and 50.2% of the variance in knowledge and skill of SBCC, respectively.

Conclusion

Front-line healthcare system actors in Ethiopia has low knowledge and skills in SBCC. Variations in SBCC knowledge and skill were observed based on demographic and professionals experience related characteristics. Hence, continuous capacity building activities need to be given to frontline healthcare system actors to enhance their knowledge and skill on SBCC program and achieve the intended health results.
Contextualizing medications for opioid use disorder and peer support service provision in the probation system with implementation science
Authors: Kang Augustine W. , Bailey Amelia , Napoleon Siena , Martin Rosemarie
Published: March 2024

Background

Medications for opioid use disorder (MOUD) is an evidence-based approach that reduces opioid-related mortality, particularly among criminal legal-involved persons who are at increased risk of adverse outcomes related to OUD. Implementing evidence-based approaches in the context of probation settings requires an in-depth understanding of specific contexts to improve intervention efficacy and effectiveness. Here, we use the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to understand implementation contexts for MOUD provision in the probation setting.

Methods

In-depth individual interviews were conducted with key programmatic stakeholders (treatment providers and probation staff involved in service provision for people on probation). The study examined stakeholder perspectives regarding MOUD and Peer Support Service (PSS) implementation among people who are involved in community supervision. Deductive and inductive thematic analysis was conducted, and subsequently the codes, subcodes, and themes were mapped onto the EPIS framework to better understand implementation contexts.

Results

We deduced key inner, outer, and bridging contexts that shape treatment service provision for individuals with OUD who are on probation. Inner contexts include a strong organizational climate that supports MOUD implementation and enthusiasm for peer support services. Outer contexts include difficulty navigating insurance among providers, treatment costs, and systemic stigma towards MOUD. Bridging contexts include a lack of collaboration/communication between relevant agencies (e.g., probation and courts).

Conclusions

Findings indicate the implementation is complex and requires a coordinated effort between correctional systems, probation agencies, and community-based treatment providers.
Efficient organized colorectal cancer screening in Shenzhen: a microsimulation modelling study
Authors: Zhu Minmin , Zhong Xuan , Liao Tong , Peng Xiaolin , Lei Lin , Peng Ji , Cao Yong
Published: March 2024

Background

Colorectal cancer (CRC) is a global health issue with noticeably high incidence and mortality. Microsimulation models offer a time-efficient method to dynamically analyze multiple screening strategies. The study aimed to identify the efficient organized CRC screening strategies for Shenzhen City.

Methods

A microsimulation model named CMOST was employed to simulate CRC screening among 1 million people without migration in Shenzhen, with two CRC developing pathways and real-world participation rates. Initial screening included the National Colorectal Polyp Care score (NCPCS), fecal immunochemical test (FIT), and risk-stratification model (RS model), followed by diagnostic colonoscopy for positive results. Several start-ages (40, 45, 50 years), stop-ages (70, 75, 80 years), and screening intervals (annual, biennial, triennial) were assessed for each strategy. The efficiency of CRC screening was assessed by number of colonoscopies versus life-years gained (LYG).

Results

The screening strategies reduced CRC lifetime incidence by 14–27 cases (30.9–59.0%) and mortality by 7–12 deaths (41.5–71.3%), yielded 83–155 LYG, while requiring 920 to 5901 colonoscopies per 1000 individuals. Out of 81 screening, 23 strategies were estimated efficient. Most of the efficient screening strategies started at age 40 (17 out of 23 strategies) and stopped at age 70 (13 out of 23 strategies). Predominant screening intervals identified were annual for NCPCS, biennial for FIT, and triennial for RS models. The incremental colonoscopies to LYG ratios of efficient screening increased with shorter intervals within the same test category. Compared with no screening, when screening at the same start-to-stop age and interval, the additional colonoscopies per LYG increased progressively for FIT, NCPCS and RS model.

Conclusion

This study identifies efficient CRC screening strategies for the average-risk population in Shenzhen. Most efficient screening strategies indeed start at age 40, but the optimal starting age depends on the chosen willingness-to-pay threshold. Within insufficient colonoscopy resources, efficient FIT and NCPCS screening strategies might be CRC initial screening strategies. We acknowledged the age-dependency bias of the results with NCPCS and RS.
Evaluation of FamMed essentials: a blended-learning program for capacity building of general practitioners in Pakistan
Authors: Khan Unab I , Farazdaq Hamida , Naseem Azra , Suleman Waseem , Saleem Sania , Qadir Muskaan Abdul , Fatima Komal
Published: March 2024

Background

To provide access to primary care and universal health coverage, Pakistan requires 60,000 trained family physicians by 2030. At present, most primary care is provided by general practitioners (GPs) who do not have any post-graduate training. Empowering GPs through competency–based programs, that strengthen their knowledge and skills, may be a cost-effective strategy for improving healthcare quality. We describe the development and evaluation of FamMed Essentials, a modular, blended-learning program to improve clinical knowledge and skills of GPs.

Methods

This is a mixed method study. We used the CIPP (content, input, process and product) framework for course development and evaluation. We describe the steps used in content development, strategies for teaching and assessments, and evaluation of strengths and weaknesses of the program. In depth focus group discussions were conducted to gather insight on participants’ and faculty’s perceptions regarding the program’s effectiveness.

Results

Of the 137 participants who have completed the program, 72% were women and 49% had been practicing for more than five years. We saw a significant improvement in knowledge across all modules (p = < 0.001) and perceived confidence in clinical skills (p = < 0.001). An objective assessment showed participants’ competence in patient management. Participants reported a high level of satisfaction (4.4 ± 0.83 on a 5-point Likert Scale). Focus group discussions revealed a positive impact on clinical practice. Flexibility and use of different teaching and learning strategies were additional strengths. In addition, participants reported an interest in further training. Power outages were highlighted as a major challenge.

Conclusion

In resource-constrained health systems, a modular, blended-learning, competency-based program is helpful to upgrade GPs knowledge without impacting their busy schedules. Accreditation of such programs and provision of a career trajectory for the trained GPs are pivotal to expansion of such initiatives.
Nursing strategies in antimicrobial stewardship in the hospital environment: a qualitative systematic review
Authors: Camerini Flavia Giron , Cunha Tonia Lourenço , Fassarella Cintia Silva , de Mendonça Henrique Danielle , Fortunato Juliana Gerhardt Soares
Published: March 2024

Background

Antimicrobial resistance has become one of the world’s most important public health problems. Accordingly, nursing strategies to manage antimicrobials in hospital environments are fundamental to promoting patient health. The aim of this study was to summarise the best evidence available on nursing strategies for the safe management of antimicrobials in hospital environments.

Methods

This qualitative systematic review used meta-aggregation in accordance with the recommendations of the Joanna Briggs Institute. The protocol was registered in the data base of the Prospective Register of Systematic Reviews under No. CRD42021224804. The literature search was conducted, in April and May 2021, in the following data bases and journal repositories: Latin American and Caribbean Health Sciences Literature (LILACS) via the Virtual Health Library (VHL), Medical Literature Analysis and Retrieval System on-line (Medline) via PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scientific Electronic Library Online (SciELO) and Excerpta Medica Database (EMBASE). The findings of each study were summarized and the results were meta-aggregated in JBI SUMARI software.

Results

The search resulted in a total of 447 studies and, after selection, the review included 26 studies, in which 42 nursing strategies were identified. The strategies were first categorised as care- or stewardship-related and then into the subcategories: Screening, Administration, Monitoring and Discharge, Nursing Team, Multi-professional Teams, Patients and Institutional Leadership. The 42 strategies were meta-aggregated and represented in flow diagrams. The best evidence was synthesized related to nursing strategies in the safe management of antimicrobials in the hospital environment.

Conclusions

Nurses play an indispensable function in antimicrobial stewardship in the hospital environment, because they work directly at the core of safe patient care. Significant contributions by nursing towards reducing antimicrobial resistance were found in care-related practice, education activities, research and policy.
What factors are associated with the research productivity of primary care researchers in Canada? A qualitative study
Authors: Aggarwal Monica , Hutchison Brian , Wong Sabrina T. , Katz Alan , Slade Steve , Snelgrove Deirdre
Published: March 2024

Background

Research evidence to inform primary care policy and practice is essential for building high-performing primary care systems. Nevertheless, research output relating to primary care remains low worldwide. This study describes the factors associated with the research productivity of primary care researchers.

Methods

A qualitative, descriptive key informant study approach was used to conduct semi-structured interviews with twenty-three primary care researchers across Canada. Qualitative data were analyzed using reflexive thematic analysis.

Results

Twenty-three primary care researchers participated in the study. An interplay of personal (psychological characteristics, gender, race, parenthood, education, spousal occupation, and support), professional (mentorship before appointment, national collaborations, type of research, career length), institutional (leadership, culture, resources, protected time, mentorship, type), and system (funding, systematic bias, environment, international collaborations, research data infrastructure) factors were perceived to be associated with research productivity. Research institutes and mentors facilitated collaborations, and mentors and type of research enabled funding success. Jurisdictions with fewer primary care researchers had more national collaborations but fewer funding opportunities. The combination of institutional, professional, and system factors were barriers to the research productivity of female and/or racialized researchers.

Conclusions

This study illuminates the intersecting and multifaceted influences on the research productivity of primary care researchers. By exploring individual, professional, institutional, and systemic factors, we underscore the pivotal role of diverse elements in shaping RP. Understanding these intricate influencers is imperative for tailored, evidence-based interventions and policies at the level of academic institutions and funding agencies to optimize resources, promote fair evaluation metrics, and cultivate inclusive environments conducive to diverse research pursuits within the PC discipline in Canada.
“We have to change our mindsets”: a qualitative study of barriers and facilitators in research collaboration across integrated care system organisations
Authors: Gidlow Christopher J. , Sams Lorna , Buckless Kim , Ellis Naomi J. , Duffy Helen C. , Lambley-Burke Ruth , Campbell Paul , Cooke Alison , Dziedzic Krysia , Brookes Matthew , Chockalingam Nachiappan , Devall Pam , Mallen Christian
Published: March 2024

The introduction of Integrated Care Systems (ICS) in England aimed to increase joint planning and delivery of health and social care, and other services, to better meet the needs of local communities. There is an associated duty to undertake collaborative research across ICS partners to inform this new integrated approach, which might be challenging given that organisations span health, local authority, voluntary and community sector, and research. This study aimed to explore the appetite for collaborative Research and Innovation (R&I) across ICSs, potential barriers and solutions. This qualitative study involved semi-structured interviews with 24 stakeholders who held senior positions within organisations across two ICS areas (Staffordshire and Stoke-on-Trent; Shropshire, Telford and Wrekin). Interview transcripts were analysed using inductive and deductive analysis, first mapping to the Theoretical Domains Framework (TDF), then considering key influences on organisational behaviour in terms of Capability, Opportunity and Motivation from the COM-B Behaviour Change Wheel. There were fundamental limitations on organisational opportunities for collaborative R&I: a historical culture of competition (rather than collaboration), a lack of research culture and prioritisation, compounded by a challenging adverse economic environment. However, organisations were motivated to undertake collaborative R&I. They recognised the potential benefits (e.g., skill-sharing, staff development, attracting large studies and funding), the need for collaborative research that mirrors integrated care, and subsequent benefits for care recipients. Related barriers included negative experiences of collaboration, fear of failing and low confidence. Capability varied across organisations in terms of research skills and confidence, which reflected the range of partners (from local authorities to NHS Trusts, primary care, and academic institutions). These findings indicate a need to shift from a culture of competition to collaboration, and to help organisations across ICS to prioritise research, and share resources and skills to mitigate the limiting effects of a constrained economic environment. This could be further explored using a systems change approach, to develop the collaborative research efforts alongside the overarching move towards integrated care.
Engineering Escherichia coli for increased Und-P availability leads to material improvements in glycan expression technology
Authors: Kay Emily J. , Dooda Manoj K. , Bryant Joseph C. , Reid Amanda J. , Wren Brendan W. , Troutman Jerry M. , Jorgenson Matthew A.
Published: March 2024

Background

Bacterial surface glycans are assembled by glycosyltransferases (GTs) that transfer sugar monomers to long-chained lipid carriers. Most bacteria employ the 55-carbon chain undecaprenyl phosphate (Und-P) to scaffold glycan assembly. The amount of Und-P available for glycan synthesis is thought to be limited by the rate of Und-P synthesis and by competition for Und-P between phosphoglycosyl transferases (PGTs) and GTs that prime glycan assembly (which we collectively refer to as PGT/GTs). While decreasing Und-P availability disrupts glycan synthesis and promotes cell death, less is known about the effects of increased Und-P availability.

Results

To determine if cells can maintain higher Und-P levels, we first reduced intracellular competition for Und-P by deleting all known non-essential PGT/GTs in the Gram-negative bacterium Escherichia coli (hereafter called ΔPGT/GT cells). We then increased the rate of Und-P synthesis in ΔPGT/GT cells by overexpressing the Und-P(P) synthase uppS from a plasmid (puppS). Und-P quantitation revealed that ΔPGT/GT/puppS cells can be induced to maintain 3-fold more Und-P than wild type cells. Next, we determined how increasing Und-P availability affects glycan expression. Interestingly, increasing Und-P availability increased endogenous and recombinant glycan expression. In particular, ΔPGT/GT/puppS cells could be induced to express 7-fold more capsule from Streptococcus pneumoniae serotype 4 than traditional E. coli cells used to express recombinant glycans.

Conclusions

We demonstrate that the biotechnology standard bacterium E. coli can be engineered to maintain higher levels of Und-P. The results also strongly suggest that Und-P pathways can be engineered to increase the expression of potentially any Und-P-dependent polymer. Given that many bacterial glycans are central to the production of vaccines, diagnostics, and therapeutics, increasing Und-P availability should be a foremost consideration when designing bacterial glycan expression systems.
Promoting collateral formation in type 2 diabetes mellitus using ultra-small nanodots with autophagy activation and ROS scavenging
Authors: Wang Yixuan , Li Feifei , Mao Linshuang , Liu Yu , Chen Shuai , Liu Jingmeng , Huang Ke , Chen Qiujing , Wu Jianrong , Lu Lin , Zheng Yuanyi , Shen Weifeng , Ying Tao , Dai Yang , Shen Ying
Published: March 2024

Background

Impaired collateral formation is a major factor contributing to poor prognosis in type 2 diabetes mellitus (T2DM) patients with atherosclerotic cardiovascular disease. However, the current pharmacological treatments for improving collateral formation remain unsatisfactory. The induction of endothelial autophagy and the elimination of reactive oxygen species (ROS) represent potential therapeutic targets for enhancing endothelial angiogenesis and facilitating collateral formation. This study investigates the potential of molybdenum disulfide nanodots (MoS2 NDs) for enhancing collateral formation and improving prognosis.

Results

Our study shows that MoS2 NDs significantly enhance collateral formation in ischemic tissues of diabetic mice, improving effective blood resupply. Additionally, MoS2 NDs boost the proliferation, migration, and tube formation of endothelial cells under high glucose/hypoxia conditions in vitro. Mechanistically, the beneficial effects of MoS2 NDs on collateral formation not only depend on their known scavenging properties of ROS (H2O2, •O2-, and •OH) but also primarily involve a molecular pathway, cAMP/PKA-NR4A2, which promotes autophagy and contributes to mitigating damage in diabetic endothelial cells.

Conclusions

Overall, this study investigated the specific mechanism by which MoS2 NDs mediated autophagy activation and highlighted the synergy between autophagy activation and antioxidation, thus suggesting that an economic and biocompatible nano-agent with dual therapeutic functions is highly preferable for promoting collateral formation in a diabetic context, thus, highlighting their therapeutic potential.

Graphical Abstract
Comparative effectiveness and safety of DOACs vs. VKAs in treatment of left ventricular thrombus- a meta-analysis update
Authors: Hu Tong , Chen Changli , Maduray Kellina , Han Wenqiang , Chen Tongshuai , Zhong Jingquan
Published: March 2024

Background and objective

Left ventricular thrombus (LVT) formation in patients with acute myocardial infarction (AMI) or cardiomyopathies is not uncommon. The optimal oral anticoagulation therapy for resolving LVT has been under intense debate. Vitamin K antagonists (VKAs) remain the anticoagulant of choice for this condition, according to practice guidelines. Evidence supporting the use of direct oral anticoagulants (DOACs) in the management of LVT continues to grow. We performed a systematic review and meta-analysis to compare the efficacy and safety of DOACs versus VKAs.

Methods

A comprehensive literature search was carried out in PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases in July 2023. The efficacy outcomes of this study were thrombus resolution, ischemic stroke, systemic embolism, stroke/systemic embolism, all-cause mortality, and adverse cardiovascular events. The safety outcomes were any bleeding, major bleeding, and intracranial hemorrhage. A total of twenty-seven eligible studies were included in the meta-analysis. Data were analyzed utilizing Stata software version 15.1.

Results

There was no significant difference between DOACs and VKAs with regard to LVT resolution (RR = 1.00, 95% CI 0.95–1.05, P = 0.99). In the overall analysis, DOACs significantly reduced the risk of stroke (RR = 0.74, 95% CI 0.57–0.96, P = 0.021), all-cause mortality (RR = 0.70, 95% CI 0.57–0.86, P = 0.001), any bleeding (RR = 0.75, 95% CI 0.61–0.92, P = 0.006) and major bleeding (RR = 0.67, 95% CI 0.52–0.85, P = 0.001) when compared to VKAs. Meanwhile, in the sub-analysis examining randomized controlled trials (RCTs), the aforementioned outcomes no longer differed significantly between the DOACs and VKAs groups. The incidences of systemic embolism (RR = 0.81, 95% CI 0.54–1.22, P = 0.32), stroke/systemic embolism (RR = 0.85, 95% CI 0.72–1.00, P = 0.056), intracranial hemorrhage (RR = 0.59, 95% CI 0.23–1.54, P = 0.28), and adverse cardiovascular events (RR = 0.99, 95% CI 0.63–1.56, P = 0.92) were comparable between the DOACs and VKAs groups. A subgroup analysis showed that patients treated with rivaroxaban had a significantly lower risk of stroke (RR = 0.24, 95% CI 0.08–0.72, P = 0.011) than those in the VKAs group.

Conclusion

With non-inferior efficacy and superior safety, DOACs are promising therapeutic alternatives to VKAs in the treatment of LVT. Further robust investigations are warranted to confirm our findings.