bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractThis 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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

AbstractBackgroundTo 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.MethodsThis 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.ResultsOf 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.ConclusionIn 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

Abstract
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.