bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of carotid plaques with high-risk features in embolic stroke of undetermined source: Systematic review and meta-analysis
Authors: Rapillo Costanza Maria , Giuricin Alessandro , Sarti Cristina , Nesi Mascia , Marcheselli Simona , Lombardo Ivano , Pascarella Rosario , Zedde Marialuisa , Arba Francesco 
Published: January 2025

Introduction: Recent evidence suggests a possible role of non-stenotic carotid atherosclerotic plaques in the etiology of embolic stroke of undetermined source (ESUS). Methods: We conducted a systematic review and meta-analysis of prevalence and characteristics of non-stenotic carotid plaques (NSPs) with high-risk features (complicated NSP) in internal carotid artery in unilateral ESUS in the anterior circulation. We searched MEDLINE and Ovid-Embase databases. High-risk features were intraplaque hemorrhage, thickness ⩾ 3 mm, ulceration, and hypodensity. We assessed the risk of bias (RoB), extracted the data, calculated the pooled prevalence and 95% confidence intervals (CI) using Inverse Variance Weighting method, and Random Effect models. Results: We included 16 studies and 1406 patients with different imaging for NSP assessment (1 ultrasound, 11 computed tomography (CT)-angiography, 4 magnetic resonance (MR) angiography). The RoB was moderate to low in most studies. Definition of complicated NSP differed across studies. The combined prevalence of any complicated NSP was 31% (95% CI = 27–36%) ipsilateral and 14% (95% CI = 9–19%) contralateral to the index stroke, the finding of any high-risk NSP was fourfold higher ipsilateral to the index stroke (OR = 3.63; 95% CI = 2.09–6.33). The prevalence of single high-risk features ipsilateral to ESUS was as follows: 35% (95% CI = 30–41%) for thickness ⩾ 3 mm; 24% (95% CI = 8–39%) for ulceration; 45% (95% CI = −2; 93%) for hypodensity, 16% (95% CI = 5–26%) for intraplaque hemorrhage. Conclusion: Complicated NSPs are present in around a third of all ESUS, and are four times more frequent ipsilaterally to the index stroke. Our results confirm the possible causal role in ESUS and highlight the need for greater diagnostic uniformity of plaque at risk.
Comparison of Glenoid Bone Loss After Unidirectional Versus Combined Shoulder Instability in a Military Population
Authors: Yoon Annette H. , Sandler Alexis B. , Scanaliato John P. , Klahs Kyle J. , Hurley Eoghan T. , Tyler John , Parnes Nata 
Published: January 2025

Background: While glenoid bone loss (GBL) after anterior shoulder instability correlates with poor functional outcomes, the specific effects of GBL in posterior and combined-type shoulder instability remain poorly characterized, especially in a high-risk military population. Purpose/Hypothesis: The purpose of this study was to compare GBL between unidirectional anterior or posterior instability versus combined-type instability in active-duty servicemembers. It was hypothesized that total GBL and GBL in the direction of instability would be greater in those with combined-type instability compared with unidirectional instability. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Active-duty servicemembers who underwent shoulder stabilization surgery between January 2010 and December 2019 were eligible for inclusion. Patients with multidirectional instability, concomitant rotator cuff tears, osteochondritis dissecans of the glenoid or humeral head, superior labral anterior-posterior tears, biceps pathologies, and humeral avulsion of the glenohumeral ligament were excluded. Patients were grouped according to direction of instability (anterior, posterior, or combined), and patient characteristics, instability characteristics, suture anchor use, and GBL were compared between the 3 cohorts. Results: In total, 117 patients met the study inclusion criteria. The mean patient age was 29 years, 89.7% were male, the dominant extremity was involved in 63.2%, 65.8% attributed their injuries to a singular traumatic event, and the mean follow-up was 7.9 years. There was no significant difference regarding patient characteristics, injury mechanism, or follow-up time between the 3 cohorts. As compared with the combined-type instability cohort, mean anterior GBL was greater in the anterior instability cohort (8.00% ± 4.40% vs 4.98% ± 5.26% for combined; P = .012), while mean posterior GBL was greater in the posterior instability cohort (7.44% ± 4.54% vs 4.86% ± 5.69% for combined; P = .024). There was no significant difference in mean total GBL between the combined-type (9.84% ± 7.82%) and either of the unidirectional cohorts (anterior: 8.00% ± 4.40% [ P = .231]; posterior: 7.44% ± 4.54% [ P = .082]). Conclusion: GBL in the direction of instability was found to be significantly greater in the unidirectional versus combined-type instability cohorts.
Synergistic attenuation of complete freund’s adjuvant-induced inflammation in mice using shinbaro-pelubiprofen: a novel therapeutic complex
Authors: Kim Hyunseong , Hong Jin Young , Jeon Wan-Jin , Kim Hyun , Yeo Changhwan , Lee Junseon , Lee Yoon Jae , Ha In-Hyuk 
Published: January 2025

Abstract

Background
Inflammation is a critical protective response in the body, essential for combating infections and healing injuries. However, chronic inflammation can be harmful and significantly contribute to the development and progression of chronic diseases, with macrophage-mediated responses being central to these processes. This study presents “SBR-Pel,” a new therapeutic blend of Shinbaro tab (SBR), a traditional herbal formula, and pelubiprofen (Pel), a non-steroidal anti-inflammatory drug, and investigated their combined anti-inflammatory effects to create a treatment that both improves efficacy and reduces side effects.

Methods
To this end, we performed both in vitro and in vivo analyses, utilizing a mouse model of inflammation. Viability and cytotoxicity assays, immunohistochemistry, enzyme-linked immunosorbent assays, real-time polymerase chain reaction assays, nociception assays, writhing tests, and blood biochemical analyses were performed.

Results
In vitro, SBR-Pel synergistically reduced the production of nitric oxide and reactive oxygen species and the expression of pro-inflammatory cytokines. SBR-Pel also significantly attenuated paw edema in vivo in a Complete Freund’s adjuvant-induced inflammation model in adult mice. Furthermore, immunohistochemical analyses showed that treatment with SBR-Pel reduced both the infiltration of CD68+ macrophages and the expression of pro-inflammatory cytokines in inflamed tissues. Additionally, compared with individual treatment alone, SBR-Pel enhanced the expression of anti-inflammatory cytokines CD206, TGF-β, and IL-10, indicating a synergistic effect. Our research demonstrates that SBR-Pel effectively diminishes inflammatory pain by reducing macrophage infiltration and pro-inflammatory cytokine secretion. Additionally, while 1.5 mg/kg of Pel alone increases levels of liver and kidney toxicity markers, such as aspartate aminotransferase, alanine aminotransferase, and creatinine, combining it with SBR at a reduced dosage of 0.5 mg/kg maintains these markers at normal levels.

Conclusions
This combined effect highlights SBR-Pel’s potential as an effective treatment for inflammatory diseases driven by heightened macrophage activity, while also minimizing side effects by reducing the Pel dosage.
Synergistic activity of Pitstop-2 and 1,6-hexanediol in aggressive human lung cancer cells
Authors: Stefanello Sílvio Terra , Mizdal Caren Rigon , da Silva Aline Franzen , Todesca Luca Matteo , Soares Félix Alexandre Antunes , Shahin Victor 
Published: January 2025

Abstract
Metastatic cancer cells undergo metabolic reprogramming, which involves changes in the metabolic fluxes, including endocytosis, nucleocytoplasmic transport, and mitochondrial metabolism, to satisfy their massive demands for energy, cell division, and proliferation compared to normal cells. We have previously demonstrated the ability of two different types of compounds to interfere with linchpins of metabolic reprogramming, Pitstop-2 and 1,6-hexanediol (1,6-HD). 1,6-HD disrupts glycolysis enzymes and mitochondrial function, enhancing reactive oxygen species production and reducing cellular ATP levels, while Pitstop-2 impedes clathrin-mediated endocytosis and small GTPases activity. Besides, both compounds interfere with the integrity of nuclear pore complexes, the gatekeepers for all nucleocytoplasmic transport. Herein, we investigate the possible synergistic effects of both compounds on lowly, highly metastatic, and erlotinib-resistant non-small cell lung cancer. We observe a synergistic cytotoxic effect on erlotinib-resistant cells. Moreover, motility assays show that the compounds combination significantly impedes the motility of all cells. Drug safety and tolerability assessments were validated using the in vivo model organism Caenorhabditis elegans, where fairly high doses showed negligible impact on survival, development, or behavioral parameters. Our findings propose that the 1,6-HD and Pitstop-2 combination may usher in the design of potent strategies for treating advanced lung cancer.
Exploring peer learning module vs. conventional tutorials: effects on engagement and learning outcomes among first-year medical students
Authors: Arasappa Vishwanath Vinay , Raghuramaiah Sindhu , Rasalkar Kavita 
Published: January 2025

Abstract

Background
In contemporary medical education, it is essential to raise student involvement and active participation in the learning process. By contrasting small-group peer learning modules with teacher-led conventional tutorial sessions, we aim to provide insights into their respective influences on learning outcomes and the overall learning experience among 150 first-year medical students.

Methods
Each group consisted of 50 students. These students were further divided into two groups and a pretest was administered on the day of the session. One group engaged in conventional tutorials, while the other participated in a peer learning module. Post-tests and session feedback were provided after each session.

Results
Results from the posttest revealed advancement in both learning approaches compared to the pretest. Compared to tutorials, the level of progress was much higher following peer learning with a p-value of < 0.05. Participants felt that while the tutorials helped them cover the full subject and saved time, they occasionally got monotonous and there was little active engagement. Students who participated in the peer learning method said that while interaction aided in a better learning experience, improved communication skills, and had more active participation, there was less time for discussion and some group members were reticent and ineffective in explaining the concepts.

Conclusions
The peer learning module is thought to be superior to conventional tutorial classes since it promises active involvement from all students, promotes greater learning, and aids in skill improvement, thus assisting students to help each other in gaining insight into the process of active learning.
How do staff work in NHS hospital operations management meetings to support resilience in everyday service delivery? A qualitative study
Authors: Sutton L. , Tarrant C. , Willars J. , Coats T. , Simmonds M. , Mclean D. , Boyle A. , Dreesbeimdiek K. , Richter S. , Oyedijo A. , Roland D. 
Published: January 2025

Abstract

Background
Operations Management meetings in NHS hospitals provide an opportunity for operational and clinical staff to monitor demand and capacity and manage patient flow. These meetings play an important role in the achievement of resilient performance over time. However, little is known about the work that takes place within these meetings in the United Kingdom’s National Health Service.

Methods
We conducted a qualitative study observing 29 Operations Management meetings across three English hospitals between June and October 2023. The observations focused on: who was present; how meetings were organised and conducted; what data were used; how decision-making took place; and the types of work that were undertaken. We also conducted 17 semi-structured interviews with divisional leads and meeting chairs. A grounded theory analytic approach involved exploring the data in two sites to identify key themes, and then testing these themes through a third comparator site.

Results
We identified the type and extent of work that took place in these meetings to maintain flow and enable resilient service delivery. Operations Management meetings provided an opportunity for staff to come together to engage in collective sense-making, to develop a shared mental model of the state of the hospital and to build a collective understanding of where action was needed. Review of centralised data, formally encoded and recorded in numerical form, played an important role, but staff also drew on local intelligence to make sense of and adapt to often pressurised situations. We identified three types of work: Sense-making and Interpretation, and Risk work (which together contributed to maintaining organisational function) and Maintaining morale (which supported individual staff resilience).

Conclusions
The work that went on in Operations Management meetings functioned to support organisational and individual resilience, through staff repeatedly sharing and assessing information on capacity and demand, taking action to address these continually changing pressures, and having their efforts recognised.
Advances in nucleic acid-based cancer vaccines
Authors: Liao Hung-Chun , Liu Shih-Jen 
Published: January 2025

Abstract
Nucleic acid vaccines have emerged as crucial advancements in vaccine technology, particularly highlighted by the global response to the COVID-19 pandemic. The widespread administration of mRNA vaccines against COVID-19 to billions globally marks a significant milestone. Furthermore, the approval of an mRNA vaccine for Respiratory Syncytial Virus (RSV) this year underscores the versatility of this technology. In oncology, the combination of mRNA vaccine encoding neoantigens and immune checkpoint inhibitors (ICIs) has shown remarkable efficacy in eliciting protective responses against diseases like melanoma and pancreatic cancer. Although the use of a COVID-19 DNA vaccine has been limited to India, the inherent stability at room temperature and cost-effectiveness of DNA vaccines present a viable option that could benefit developing countries. These advantages may help DNA vaccines address some of the challenges associated with mRNA vaccines. Currently, several trials are exploring the use of DNA-encoded neoantigens in combination with ICIs across various cancer types. These studies highlight the promising role of nucleic acid-based vaccines as the next generation of immunotherapeutic agents in cancer treatment. This review will delve into the recent advancements and current developmental status of both mRNA and DNA-based cancer vaccines.
Association of high complement and low immunoglobulins with the clinical symptoms of patients with fibromyalgia
Authors: Izuno Satoshi , Hosoi Masako , Anno Kozo , Kato Takahiro A. , Sudo Nobuyuki , Yoshihara Kazufumi 
Published: January 2025

Abstract

Background
Fibromyalgia (FM) is a disease characterized by chronic widespread pain concomitant with various symptoms such as fatigue and anxiety. Although chronic inflammation has been implicated in the immunological abnormalities of FM, there are few human studies on complement and immunoglobulins. In this study, we investigated the immunological characteristics of FM patients and the association between their clinical symptoms and immunological indices, including complement and immunoglobulins.

Methods
1) The serum 50% hemolytic complement activity (CH50), C3, C4, IgG, IgM, and hsCRP of 36 FM patients and 30 healthy sex- and age-matched controls (HC) were measured and compared. 2) Data from the Brief Pain Inventory (pain intention and pain interference subscales), the visual analog scale (VAS) (low back pain, knee pain, and fatigue), the State-Trait Anxiety Inventory and the Center for Epidemiologic Studies Depression Scale (anxiety and depression), and CH50, IgG, and hsCRP as immunological indices were acquired for 41 FM patients. Correlation analysis was done of the clinical symptom and immunological indices.

Results
1) The FM group had significantly higher CH50 and lower IgG and IgM than the HC group after adjusting for body mass index (BMI). 2) Correlation analysis of immunological indices and clinical symptoms showed a positive, partial correlation between CH50 and fatigue and trait anxiety after adjusting for sex, age, and BMI.

Conclusions
FM patients had higher CH50 and lower immunoglobulin levels than HCs. CH50 was also associated with the fatigue and trait anxiety of FM patients. Further studies are needed to determine whether changes in these immunological indices can be used as biomarkers and/or therapeutic targets for FM.
Examining the integration of refugees into the national health system in Uganda: an analysis using the policy triangle framework
Authors: Komakech Henry , Elnakib Shatha , Karroum Lama Bou , Nyachwo Evelyn , Adoch Winnie , Sali Sarah , Okeny Godfrey Goddie , Orach Christopher Garimoi 
Published: January 2025

Abstract

Background
Uganda has been confronted with a sustained influx of refugees for decades. This prompted the government to explore opportunities to integrate refugees into local service structures including its national health system. This paper chronicles the history of policies and strategies that have influenced the integration of refugees into the national health system in Uganda and investigates factors that impacted policy evolution and progression.

Methods
We used a case study approach that drew on a document review and key informant interviews with 28 respondents at national and subnational levels. Interviews were analyzed using thematic qualitative analysis and findings were organized using Walt and Gilson’s Policy Triangle Framework. Data from the literature review, media review, and key informant interviews were triangulated.

Results
Uganda’s experience with the integration of refugee’s dates to 1999 when the country first implemented the Self-reliance strategy. Since then, policy learning and evolution have taken place, with policies around integration evolving and improving over time, moving the country towards more effective implementation of integrated health services. A conducive policy environment was key as a set of legislations at national and district-levels and sector-specific plans and budgets that included refugees have provided the foundation for implementation. The integration received support and buy-in from the highest levels of government including the President and the Office of The Prime Minister. This was coupled with deliberate efforts by the government to mainstream refugee response in local plans and budgets, allowing implementation at district and sub-district levels. These factors were pivotal to the implementation of the integration agenda.

Conclusion
Our study highlights the complex, dynamic, evolving, and multifaceted nature of the multisectoral health policy process in the integration of health services in refugee settings. The findings shed light on the importance of collaboration between stakeholders, mobilization of legal and political frameworks to shape the integration of refugee health services into the national health system, and the importance of ensuring that high-level commitments translate to action and development plans at local levels.
TREM2 promotes the formation of a tumor-supportive microenvironment in hepatocellular carcinoma
Authors: Guo Hanrui , Wang Meiling , Ni Caiya , Yang Chun , Fu Chunxue , Zhang Xiaoman , Chen Xueling , Wu Xiangwei , Hou Jun , Wang Lianghai 
Published: January 2025

Abstract

Background
Triggering receptor expressed on myeloid cells 2 (TREM2), a surface receptor predominantly expressed on myeloid cells, is a major hub gene in pathology-induced immune signaling. However, its function in hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the role of TREM2 in the tumor microenvironment in the context of HCC progression.

Methods
HCC was experimentally induced in wild-type (WT) and Trem2-deficient (Trem2
−/−) mice, and clinical sample analysis and in vitro studies on macrophages were conducted. HCC cells were treated with conditioned medium from WT or Trem2
−/− macrophages, and their malignant phenotypes and underlying mechanisms were analyzed.

Results

TREM2 deficiency reduced liver tumor burden in orthotopic and subcutaneous HCC models by altering CD8+ T cell infiltration. Trem2-deficient macrophages presented increased chemokine secretion. TGF-β1 was found to be positively correlated with TREM2 expression in HCC, and TGF-β blockade reversed TREM2 induction. On the other hand, TREM2+ macrophages were found to be associated with glycolysis and PKM2 expression in HCC cells; this association may be related to the secretion of IL-1β, which enhances the malignant phenotypes of HCC cells.

Conclusions
These results reveal that TREM2+ macrophages play a driving role in HCC progression by suppressing CD8+ T cell infiltration and promoting tumor cell glycolysis, providing a new therapeutic target for HCC.
Large simple randomized controlled trials—from drugs to medical devices: lessons from recent experience
Authors: Buccheri Sergio , James Stefan , Mafham Marion , Landray Martin , Melvin Tom , Oldgren Jonas , Bulbulia Richard , Bowman Louise , Hoogervorst Lotje Anna , de Mheen Perla J. Marang-van , Juni Peter , McCulloch Peter , Fraser Alan G. 
Published: January 2025

Abstract

Randomized controlled trials (RCTs) are the cornerstone of modern evidence-based medicine. They are considered essential to establish definitive evidence of efficacy and safety for new drugs, and whenever possible they should also be the preferred method for investigating new high-risk medical devices. Well-designed studies robustly inform clinical practice guidelines and decision-making, but administrative obstacles have made it increasingly difficult to conduct informative RCTs. The obstacles are compounded for RCTs of high-risk medical devices by extra costs related to the interventional procedure that is needed to implant the device, challenges with willingness to randomize patients throughout a trial, and difficulties in ensuring proper blinding even with sham procedures. One strategy that may help is to promote the wider use of simpler and more streamlined RCTs using data that are collected routinely during healthcare delivery. Recent large simple RCTs have successfully compared the performance of drugs and of high-risk medical devices, against alternative treatments; they enrolled many patients in a short time, limited costs, and improved efficiency, while also achieving major impact. From a task conducted within the CORE-MD project, we report from our combined experience of designing and conducting large pharmaceutical trials during the COVID-19 pandemic, and of planning and coordinating large registry-based RCTs of cardiovascular devices. We summarize the essential principles and utility of large simple RCTs, likely applicable to all interventions but especially in order to promote their wider adoption to evaluate new medical devices.