bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adhesion of Candida Albicans to digital versus conventional acrylic resins: a systematic review and meta-analysis
Authors: Alhajj Mohammed Nasser , Halboub Esam , Yacob Norlela , Al-Maweri Sadeq Ali , Ahmad Siti Fauzza , Celebić Asja , Al-Mekhlafi Hesham M. , Salleh Nosizana Mohd 
Published: March 2024

Abstract
Background
The present systematic review and meta-analysis investigated the available evidence about the adherence of Candida Albicans to the digitally-fabricated acrylic resins (both milled and 3D-printed) compared to the conventional heat-polymerized acrylic resins.

Methods
This study followed the guidelines of the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA). A comprehensive search of online databases/search tools (Web of Science, Scopus, PubMed, Ovid, and Google Scholar) was conducted for all relevant studies published up until May 29, 2023. Only in-vitro studies comparing the adherence of Candida albicans to the digital and conventional acrylic resins were included. The quantitative analyses were performed using RevMan v5.3 software.

Results
Fourteen studies were included, 11 of which were meta-analyzed based on Colony Forming Unit (CFU) and Optical Density (OD) outcome measures. The pooled data revealed significantly lower candida colonization on the milled digitally-fabricated compared to the heat-polymerized conventionally-fabricated acrylic resin materials (MD = − 0.36; 95%CI = − 0.69, − 0.03; P = 0.03 and MD = − 0.04; 95%CI = − 0.06, − 0.01; P = 0.0008; as measured by CFU and OD respectively). However, no differences were found in the adhesion of Candida albicans between the 3D-printed digitally-fabricated compared to the heat-polymerized conventionally-fabricated acrylic resin materials (CFU: P = 0.11, and OD: P = 0.20).

Conclusion
The available evidence suggests that candida is less likely to adhere to the milled digitally-fabricated acrylic resins compared to the conventional ones.
Analyzing the application of mixed method methodology in medical education: a qualitative study
Authors: Alhassan Abdulaziz Ibrahim 
Published: March 2024

Abstract
Background
Interest in mixed methods methodology within medical education research has seen a notable increase in the past two decades, yet its utilization remains less prominent compared to quantitative methods. This study aimed to investigate the application and integration of mixed methods methodology in medical education research, with a specific focus on researchers’ perceptions, strategies, and readiness, including the necessary skills and expertise. This study adheres to the COREQ guidelines for reporting qualitative research.

Methods
Faculty members from King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Saudi Arabia, across its three campuses in Riyadh, Jeddah, and Al Ahsa, participated in this study during the 2021–2022 academic year. We conducted 15 in-depth, one-on-one interviews with researchers who had previously used mixed methods in their medical education research. Theoretical saturation was reached with no refusals or dropouts. Data were collected using a semi-structured interview guide developed from literature review and mixed methods guidelines. Thematic analysis was employed to analyze the data, enabling a comprehensive understanding of the participants’ perspectives.

Results
The thematic analysis of the interviews yielded three key themes. The first theme, ‘Understanding and Perceptions of Mixed Methods in Medical Education Research,’ delved into researchers’ depth of knowledge and conceptualization of mixed methods. The second theme, ‘Strategies and Integration in Mixed Methods Implementation,’ explored how these methodologies are applied and the challenges involved in their integration. The final theme, ‘Mastery in Mixed Methods: Prerequisites and Expert Consultation in Research,’ highlighted the gaps in readiness and expertise among researchers, emphasizing the importance of expert guidance in this field.

Conclusion
Findings indicate a varied understanding of mixed methods among participants. Some lacked a comprehensive grasp of its application, while others perceived mixed methods primarily as a means to enhance the publication prospects of their studies. There was a general lack of recognition of mixed methods as a guiding methodology for all study aspects, pointing to the need for more in-depth training and resources in this area.
High-risk pooling for mitigating risk selection incentives in health insurance markets with sophisticated risk equalization: an application based on health survey information
Authors: Withagen-Koster A. A. , van Kleef R. C. , Eijkenaar F. 
Published: March 2024

Abstract
Background
Despite sophisticated risk equalization, insurers in regulated health insurance markets still face incentives to attract healthy people and avoid the chronically ill because of predictable differences in profitability between these groups. The traditional approach to mitigate such incentives for risk selection is to improve the risk-equalization model by adding or refining risk adjusters. However, not all potential risk adjusters are appropriate. One example are risk adjusters based on health survey information. Despite its predictiveness of future healthcare spending, such information is generally considered inappropriate for risk equalization, due to feasibility challenges and a potential lack of representativeness.

Methods
We study the effects of high-risk pooling (HRP) as a strategy for mitigating risk selection incentives in the presence of sophisticated– though imperfect– risk equalization. We simulate a HRP modality in which insurers can ex-ante assign predictably unprofitable individuals to a ‘high risk pool’ using information from a health survey. We evaluate the effect of five alternative pool sizes based on predicted residual spending post risk equalization on insurers’ incentives for risk selection and cost control, and compare this to the situation without HRP.

Results
The results show that HRP based on health survey information can substantially reduce risk selection incentives. For example, eliminating the undercompensation for the top-1% with the highest predicted residual spending reduces selection incentives against the total group with a chronic disease (60% of the population) by approximately 25%. Overall, the selection incentives gradually decrease with a larger pool size. The largest marginal reduction is found moving from no high-risk pool to HRP for the top 1% individuals with the highest predicted residual spending.

Conclusion
Our main conclusion is that HRP has the potential to considerably reduce remaining risk selection incentives at the expense of a relatively small reduction of incentives for cost control. The extent to which this can be achieved, however, depends on the design of the high-risk pool.
Novel polymorphisms in CYP4A22 associated with susceptibility to coronary heart disease
Authors: Huang Kang , Ma Tianyi , Li Qiang , Zhong Zanrui , Zhou Yilei , Zhang Wei , Qin Ting , Tang Shilin , Zhong Jianghua , Lu Shijuan 
Published: March 2024

Abstract
Background
Coronary heart disease (CHD) has become a worldwide public health problem. Genetic factors are considered important risk factors for CHD. The aim of this study was to explore the correlation between CYP4A22 gene polymorphism and CHD susceptibility in the Chinese Han population.

Methods
We used SNPStats online software to complete the association analysis among 962 volunteers. False-positive report probability analysis was used to confirm whether a positive result is noteworthy. Haploview software and SNPStats were used for haplotype analysis and linkage disequilibrium. Multi-factor dimensionality reduction was applied to evaluate the interaction between candidate SNPs.

Results
In overall and some stratified analyses (male, age ≤ 60 years or CHD patients complicated with hypertension), CYP4A22-rs12564525 (overall, OR = 0.83, p-value is 0.042) and CYP4A22-rs2056900 (overall, OR = 1.22, p-value is 0.032) were associated with the risk of CHD. CYP4A22-4926581 was associated with increased CHD risk only in some stratified analyses. FPRP indicated that all positive results in our study are noteworthy findings. In addition, MDR showed that the single-locus model composed of rs2056900 is the best model for predicting susceptibility to CHD.

Conclusion
There are significant associations between susceptibility to CHD and CYP4A22 rs12564525, and rs2056900.
Values, challenges, and responses associated with high-priced potential cures: perspectives of diverse stakeholders in South Korea
Authors: Hong Jihyung , Bae Eun-Young , Lee Hye-Jae , Lee Tae-Jin , Clarke Philip 
Published: March 2024

Abstract
Background
The emergence of high-priced potential cures has sparked significant health policy discussions in South Korea, where the healthcare system is funded through a single-payer National Health Insurance model. We conducted focus group interviews (FGIs) and accompanying surveys with diverse stakeholders to comprehensively understand related issues and find better solutions to the challenges brought by these technologies.

Methods
From October to November 2022, 11 FGIs were conducted with stakeholders from various sectors, including government payers, policy and clinical experts, civic and patient organisations, and the pharmaceutical industry, involving a total of 25 participants. These qualitative discussions were supplemented by online surveys to effectively capture and synthesise stakeholder perspectives.

Results
Affordability was identified as a critical concern by 84% of stakeholders, followed by clinical uncertainty (76%) and limited value for money (72%). Stakeholders expressed a preference for both financial-based controls and outcome-based pricing strategies to mitigate these challenges. Despite the support for outcome-based refunds, payers raised concerns about the feasibility of instalment payment models, whether linked to outcomes or not, due to the specific challenges of the Korean reimbursement system and the potential risk of ‘cumulative liabilities’ from ongoing payments for previously administered treatments. In addition, the FGIs highlighted the need for clear budgetary limits for drugs with high uncertainties, with mixed opinions on the creation of special silo funds (64.0% agreement). Less than half (48%) endorsed the use of external reference pricing, currently applied to such essential drugs in South Korea. A significant majority (84%), predominantly non-pharma stakeholders, advocated for addressing cost-effectiveness uncertainty through re-assessment once long-term clinical data become available.

Conclusions
This study uncovers a broad agreement among stakeholders on the need for more effective value assessment methodologies for high-priced potential cures, stressing the importance of more robust and comprehensive re-assessment supported by long-term data collection, rather than primarily relying on external reference pricing. Each type of stakeholders exhibited a cautious approach to their specific uncertainties, suggesting that new funding strategies should accommodate these uncertainties with predefined guidelines and agreements prior to the initiation of managed entry agreements.
Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells
Authors: Al Tarrass Mohammad , Belmudes Lucid , Koça Dzenis , Azemard Valentin , Liu Hequn , Al Tabosh Tala , Ciais Delphine , Desroches-Castan Agnès , Battail Christophe , Couté Yohann , Bouvard Claire , Bailly Sabine 
Published: March 2024

Abstract
Background
BMP9 and BMP10 are two major regulators of vascular homeostasis. These two ligands bind with high affinity to the endothelial type I kinase receptor ALK1, together with a type II receptor, leading to the direct phosphorylation of the SMAD transcription factors. Apart from this canonical pathway, little is known. Interestingly, mutations in this signaling pathway have been identified in two rare cardiovascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension.

Methods
To get an overview of the signaling pathways modulated by BMP9 and BMP10 stimulation in endothelial cells, we employed an unbiased phosphoproteomic-based strategy. Identified phosphosites were validated by western blot analysis and regulated targets by RT-qPCR. Cell cycle analysis was analyzed by flow cytometry.

Results
Large-scale phosphoproteomics revealed that BMP9 and BMP10 treatment induced a very similar phosphoproteomic profile. These BMPs activated a non-canonical transcriptional SMAD-dependent MAPK pathway (MEKK4/P38). We were able to validate this signaling pathway and demonstrated that this activation required the expression of the protein GADD45β. In turn, activated P38 phosphorylated the heat shock protein HSP27 and the endocytosis protein Eps15 (EGF receptor pathway substrate), and regulated the expression of specific genes (E-selectin, hyaluronan synthase 2 and cyclooxygenase 2). This study also highlighted the modulation in phosphorylation of proteins involved in transcriptional regulation (phosphorylation of the endothelial transcription factor ERG) and cell cycle inhibition (CDK4/6 pathway). Accordingly, we found that BMP10 induced a G1 cell cycle arrest and inhibited the mRNA expression of E2F2, cyclinD1 and cyclinA1.

Conclusions
Overall, our phosphoproteomic screen identified numerous proteins whose phosphorylation state is impacted by BMP9 and BMP10 treatment, paving the way for a better understanding of the molecular mechanisms regulated by BMP signaling in vascular diseases.
The proteome of the blood–brain barrier in rat and mouse: highly specific identification of proteins on the luminal surface of brain microvessels by in vivo glycocapture
Authors: Tremblay Tammy-Lynn , Alata Wael , Slinn Jacqueline , Baumann Ewa , Delaney Christie E. , Moreno Maria , Haqqani Arsalan S. , Stanimirovic Danica B. , Hill Jennifer J. 
Published: March 2024

Abstract
Background
The active transport of molecules into the brain from blood is regulated by receptors, transporters, and other cell surface proteins that are present on the luminal surface of endothelial cells at the blood–brain barrier (BBB). However, proteomic profiling of proteins present on the luminal endothelial cell surface of the BBB has proven challenging due to difficulty in labelling these proteins in a way that allows efficient purification of these relatively low abundance cell surface proteins.

Methods
Here we describe a novel perfusion-based labelling workflow: in vivo glycocapture. This workflow relies on the oxidation of glycans present on the luminal vessel surface via perfusion of a mild oxidizing agent, followed by subsequent isolation of glycoproteins by covalent linkage of their oxidized glycans to hydrazide beads. Mass spectrometry-based identification of the isolated proteins enables high-confidence identification of endothelial cell surface proteins in rats and mice.

Results
Using the developed workflow, 347 proteins were identified from the BBB in rat and 224 proteins in mouse, for a total of 395 proteins in both species combined. These proteins included many proteins with transporter activity (73 proteins), cell adhesion proteins (47 proteins), and transmembrane signal receptors (31 proteins). To identify proteins that are enriched in vessels relative to the entire brain, we established a vessel-enrichment score and showed that proteins with a high vessel-enrichment score are involved in vascular development functions, binding to integrins, and cell adhesion. Using publicly-available single-cell RNAseq data, we show that the proteins identified by in vivo glycocapture were more likely to be detected by scRNAseq in endothelial cells than in any other cell type. Furthermore, nearly 50% of the genes encoding cell-surface proteins that were detected by scRNAseq in endothelial cells were also identified by in vivo glycocapture.

Conclusions
The proteins identified by in vivo glycocapture in this work represent the most complete and specific profiling of proteins on the luminal BBB surface to date. The identified proteins reflect possible targets for the development of antibodies to improve the crossing of therapeutic proteins into the brain and will contribute to our further understanding of BBB transport mechanisms.
Point-of-care ultrasound to inform antiviral treatment initiation in chronic hepatitis B virus infection in low-resource settings – the PUSH protocol
Authors: Heller Tom , Phiri Veronica , Kumwenda Tapiwa , Mzumara Wongani , Vinikoor Michael Jeffrey , Rambiki Ethel , Wallrauch Claudia 
Published: March 2024

Abstract
Background
Chronic Hepatitis B (CHB) is prevalent worldwide and most related deaths occur in low-resource settings. Antiviral treatment of CHB is indicated in those with significant liver disease and markers of viral replication. However, recommended diagnostics such as elastography (a non-invasive imaging measure of fibrosis/cirrhosis) or HBV viral load are often lacking in these settings, which creates barriers to treatment. Point-of-care clinical B-mode ultrasound (US) has potential to overcome implementation barriers in HBV care programs in low-resource settings.

Methods
We describe a Point-of-care US protocol for Hepatitis (“PUSH”) to check for signs of cirrhosis and hepatocellular carcinoma in the liver of people with CHB. We performed a prospective observational study applying the protocol, first by trainee clinicians and then by trainers, in consecutive patients referred to our clinic for CHB treatment eligibility assessment. All patients additionally underwent physical examination, liver function tests (LFTs) and platelet counts. We describe the PUSH training approach and performance of the protocol.

Results
Four clinicians and 111 adult patients with HBV infection were included in the development of PUSH. Using US, liver complications of HBV were documented in 31 (27.9%) patients; including cirrhosis in 15 patients, HCC with cirrhosis in 13, and HCC without cirrhosis in 3. Patients with sonographic findings had significantly more clinical symptoms also their LFTs were higher and more frequently indicative for HBV treatment. Of 28 patients with sonographic diagnosis of cirrhosis, 23 (82.1%) showed a nodular liver surface, 24 (85.7%) a coarse echotexture, 20 (71.4%) scarce vessels, and 9 (32.1%) an enlarged caudate lobe. Overall concordance of the findings between assessment of trainees and experienced sonographers was high, ranging from 90 to 95%; trainees were not blinded to clinical and laboratory findings.

Conclusion
Ultrasound can facilitate same-day initiation of antiviral therapy for chronic HBV monoinfection in a resource-limited setting and a streamlined protocol-driven liver ultrasound can be feasibly used by front line clinicians managing HBV.
Developing a broad perspective of future work and career in medical students through field trips to a disaster area: a qualitative study
Authors: Hidaka Tomoo , Endo Shota , Kasuga Hideaki , Masuishi Yusuke , Kakamu Takeyasu , Fukushima Tetsuhito 
Published: March 2024

Abstract
Objective
Field trips to disaster-affected areas (FTDAs) without a specific purpose, such as medical cooperation, are widely used in medical education. However, what medical students gain from FTDAs remains unclear. The present study aimed to clarify what medical students gain from FTDAs. Five medical students who had visited the Fukushima nuclear power plant in Japan participated in a semi-structured group interview to ask what they gained from such a visit. The narratives were analysed using open coding.

Results
The following four themes emerged: “Spirit of scientific inquiry”, “Foundation for lifelong education and personal growth”, “Broadened understanding of the medical profession”, and “Importance of practicing medicine in the community setting”. The ambiguity of medical students’ specific roles in the field trip compared to the fieldwork may have encouraged them to make sense of the experience from their perspective. As a result, students may have gained a broader perspective of their future work and career through the FTDA. If medical educators can gain consensus from the residents of a disaster site, different disaster-affected areas can be potential sites for medical education using FTDAs.
AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial
Authors: Bao Xiaodong , Kumar Sathish S. , Shah Nirav J. , Penning Donald , Weinstein Mitchell , Malhotra Gaurav , Rose Sydney , Drover David , Pennington Matthew W. , Domino Karen , Meng Lingzhong , Treggiari Mariam , Clavijo Claudia , Wagener Gebhard , Chitilian Hovig , Maheshwari Kamal ,   The HPI Study Team, Cody Kathryn , Muller Ariel , Christensen Anna L. 
Published: March 2024

Abstract
Background
Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient’s likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min.

Methods
Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. Measurements: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg.

Results
Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: − 0.35 (95%CI − 0.43, − 0.27); p < 0.001].

Conclusions
The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes.

Trial registration
Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217. Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.