bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preparing clinicians for practice: effectiveness and design of on-call simulation
Authors: Priest Sebastian , Wells Lucy , Huszka Hajnalka , Tovell Nick , Okorie Michael 
Published: June 2024

Abstract
Background
Final year medical students and postgraduate doctors regularly contend with feelings of under-preparedness when transitioning into new areas of clinical practice. This lack of confidence is most evident in the context of on-call work which frequently requires sound clinical prioritisation, rigorous decision making and the management of acutely unwell patients, often with reduced senior support and staffing. This has prompted the emergence of on-call simulation which seeks to enhance participant confidence in performing on-call tasks and facilitate the development of key clinical and non-technical skills. This narrative review examined the use of on-call simulation in medical student and newly qualified doctor cohorts, its effectiveness in achieving its stated outcomes and to identify novel areas for the development of existing models.

Method
A search strategy was developed in conjunction with a specialist medical librarian. OVID Medline and Embase searches identified articles related to the use and design of on-call simulation in medical education with no restrictions placed upon date or language of publication. Key findings from articles were summarised to develop comprehensive themes for discussion.

Results
Twenty Three unique publications were reviewed which unanimously reported that on-call simulation had a positive effect on self-reported participant confidence in performing on-call roles. Furthermore the value on-call simulation when used as an induction activity was also evident. However, there was limited evidence around improved patient and performance outcomes following simulation. It also remains resource intensive as an educational tool and there is a distinct absence of interprofessional education in current models.

Conclusions
We concluded that on-call simulation must adopt an interprofessional educational approach, incorporating other clinical roles. Further studies are needed to characterise the impact on patient outcomes. It remains highly useful as a confidence-boosting induction activity, particularly in specialities where clinical exposure is limited. Virtual and tabletop simulation formats, could potentially address the resource burden of manikin-based models, particularly with ever growing demands on medical educators and the expansion of training posts.
Current status and ongoing needs for the teaching and assessment of clinical reasoning – an international mixed-methods study from the students` and teachers` perspective
Authors: Wagner F. L , Sudacka M. , Kononowicz A. A , Elvén M. , Durning S. J , Hege I. , Huwendiek S. 
Published: June 2024

Abstract
Background
Clinical reasoning (CR) is a crucial ability that can prevent errors in patient care. Despite its important role, CR is often not taught explicitly and, even when it is taught, typically not all aspects of this ability are addressed in health professions education. Recent research has shown the need for explicit teaching of CR for both students and teachers. To further develop the teaching and learning of CR we need to improve the understanding of students' and teachers' needs regarding content as well as teaching and assessment methods for a student and trainer CR curriculum.

Methods
Parallel mixed-methods design that used web-surveys and semi-structured interviews to gather data from both students (nsurvey = 100; ninterviews = 13) and teachers (nsurvey = 112; ninterviews = 28). The interviews and surveys contained similar questions to allow for triangulation of the results. This study was conducted as part of the EU-funded project DID-ACT (https://did-act.eu).

Results
Both the surveys and interview data emphasized the need for content in a clinical reasoning (CR) curriculum such as “gathering, interpreting and synthesizing patient information”, “generating differential diagnoses”, “developing a diagnostic and a treatment plan” and “collaborative and interprofessional aspects of CR”. There was high agreement that case-based learning and simulations are most useful for teaching CR. Clinical and oral examinations were favored for the assessment of CR. The preferred format for a train-the-trainer (TTT)-course was blended learning. There was also some agreement between the survey and interview participants regarding contents of a TTT-course (e.g. teaching and assessment methods for CR). The interviewees placed special importance on interprofessional aspects also for the TTT-course.

Conclusions
We found some consensus on needed content, teaching and assessment methods for a student and TTT-course in CR. Future research could investigate the effects of CR curricula on desired outcomes, such as patient care.
Experiences of medical students and faculty regarding the use of long case as a formative assessment method at a tertiary care teaching hospital in a low resource setting: a qualitative study
Authors: Kumakech Jacob , Munabi Ian Guyton , Mubuuke Aloysius Gonzaga , Kiguli Sarah 
Published: June 2024

Abstract
Introduction
The long case is used to assess medical students’ proficiency in performing clinical tasks. As a formative assessment, the purpose is to offer feedback on performance, aiming to enhance and expedite clinical learning. The long case stands out as one of the primary formative assessment methods for clinical clerkship in low-resource settings but has received little attention in the literature.

Objective
To explore the experiences of medical students and faculty regarding the use of the Long Case Study as a formative assessment method at a tertiary care teaching hospital in a low-resource setting.

Methodology
A qualitative study design was used. The study was conducted at Makerere University, a low-resource setting. The study participants were third- and fifth-year medical students as well as lecturers. Purposive sampling was utilized to recruit participants. Data collection comprised six Focus Group Discussions with students and five Key Informant Interviews with lecturers. The qualitative data were analyzed by inductive thematic analysis.

Results
Three themes emerged from the study: ward placement, case presentation, and case assessment and feedback. The findings revealed that students conduct their long cases at patients’ bedside within specific wards/units assigned for the entire clerkship. Effective supervision, feedback, and marks were highlighted as crucial practices that positively impact the learning process. However, challenges such as insufficient orientation to the long case, the super-specialization of the hospital wards, pressure to hunt for marks, and inadequate feedback practices were identified.

Conclusion
The long case offers students exposure to real patients in a clinical setting. However, in tertiary care teaching hospitals, it’s crucial to ensure proper design and implementation of this practice to enable students’ exposure to a variety of cases. Adequate and effective supervision and feedback create valuable opportunities for each learner to present cases and receive corrections.
Development of machine learning models to predict perioperative blood transfusion in hip surgery
Authors: Zang Han , Hu Ai , Xu Xuanqi , Ren He , Xu Li 
Published: June 2024

Abstract
Background
Allogeneic Blood transfusion is common in hip surgery but is associated with increased morbidity. Accurate prediction of transfusion risk is necessary for minimizing blood product waste and preoperative decision-making. The study aimed to develop machine learning models for predicting perioperative blood transfusion in hip surgery and identify significant risk factors.

Methods
Data of patients undergoing hip surgery between January 2013 and October 2021 in the Peking Union Medical College Hospital were collected to train and test predictive models. The primary outcome was perioperative red blood cell (RBC) transfusion within 72 h of surgery. Fourteen machine learning algorithms were established to predict blood transfusion risk incorporating patient demographic characteristics, preoperative laboratory tests, and surgical information. Discrimination, calibration, and decision curve analysis were used to evaluate machine learning models. SHapley Additive exPlanations (SHAP) was performed to interpret models.

Results
In this study, 2431 hip surgeries were included. The Ridge Classifier performed the best with an AUC = 0.85 (95% CI, 0.81 to 0.88) and a Brier score = 0.21. Patient-related risk factors included lower preoperative hemoglobin, American Society of Anesthesiologists (ASA) Physical Status > 2, anemia, lower preoperative fibrinogen, and lower preoperative albumin. Surgery-related risk factors included longer operation time, total hip arthroplasty, and autotransfusion.

Conclusions
The machine learning model developed in this study achieved high predictive performance using available variables for perioperative blood transfusion in hip surgery. The predictors identified could be helpful for risk stratification, preoperative optimization, and outcomes improvement.
ARID1A loss promotes RNA editing of CDK13 in an ADAR1-dependent manner
Authors: Zhu Tianyu , Li Qian , Zhang Zhe , Shi Jiahao , Li Yongyun , Zhang Feng , Li Lingjie , Song Xin , Shen Jianfeng , Jia Renbing 
Published: June 2024

Abstract
Background
ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, is thought to play a significant role both in tumor suppression and tumor initiation, which is highly dependent upon context. Previous studies have suggested that ARID1A deficiency may contribute to cancer development. The specific mechanisms of whether ARID1A loss affects tumorigenesis by RNA editing remain unclear.

Results
Our findings indicate that the deficiency of ARID1A leads to an increase in RNA editing levels and alterations in RNA editing categories mediated by adenosine deaminases acting on RNA 1 (ADAR1). ADAR1 edits the CDK13 gene at two previously unidentified sites, namely Q113R and K117R. Given the crucial role of CDK13 as a cyclin-dependent kinase, we further observed that ADAR1 deficiency results in changes in the cell cycle. Importantly, the sensitivity of ARID1A-deficient tumor cells to SR-4835, a CDK12/CDK13 inhibitor, suggests a promising therapeutic approach for individuals with ARID1A-mutant tumors. Knockdown of ADAR1 restored the sensitivity of ARID1A deficient cells to SR-4835 treatment.

Conclusions
ARID1A deficiency promotes RNA editing of CDK13 by regulating ADAR1.
Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination
Authors: Nguyen Ngoc Pouplin Julie , Kaendiao Thoopmanee , Rahimi Bilal Ahmad , Soni Mayur , Basopia Hensi , Shah Darshana , Patil Jitendra , Dholakia Vyom , Suthar Yash , Tarning Joel , Mukaka Mavuto , Taylor Walter R. 
Published: June 2024

Abstract
Background
With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination.

Methods
A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18–45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5–30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration–time (AUC0–t) were within 80.00 to 125.00%.

Results
47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92–111.96%); the corresponding GM AUC0–t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76–112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0–t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h.

Conclusion
IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination.
Trial registration The trial registration reference is ISRCTN 54640699
Comparing the EQ-5D-5L and stroke impact scale 2.0 in stroke patients: an analysis of measurement properties
Authors: Schmidt Juliana , Düvel Juliane Andrea , Elkenkamp Svenja , Greiner Wolfgang 
Published: June 2024

Abstract
Background
Stroke has evolved to become a chronic disease and a major public health challenge. To adequately capture the full disease burden of stroke patients, the assessment of health-related quality of life (HRQoL) and thus the performance of respective measures is increasingly relevant. The aim of this analysis was to compare the measurement properties of two self-report instruments, the EQ-5D-5L and the Stroke Impact Scale 2.0.

Methods
The data used for the analysis was derived from a quasi-experimental case management study for mildly to moderately affected incident stroke and transient ischemic attack (TIA) patients aged ≥ 18 in Germany. Data was collected patient-individually at 3, 6 and 12 months after initial stroke. The EQ-5D-5L and SIS 2.0 were compared in terms of feasibility, ceiling and floor effects, responsiveness and known-groups validity (Kruskal-Wallis H and Wilcoxon rank-sum test).

Results
A response for all three follow-ups is available for n = 855 patients. The feasibility of the EQ-5D-5L is determined as good (completion rate: 96.4–96.6%, ≥ one item missing: 3.2 − 3.3%), whereas the SIS 2.0 is moderately feasible (overall completion rate: 44.9–46.1%, ≥ one item missing in domains: 4.7 − 28.7%). The SIS 2.0 shows substantial ceiling effects in comparable domains (physical function: 10.4 − 13%, others: 3.5–31.3%) which are mainly larger than ceiling effects in the EQ-5D-5L index (17.1–21.5%). In terms of responsiveness, the EQ-5D-5L shows small to moderate change while the SIS 2.0 presents with moderate to large responsiveness. The EQ-5D-5L index, mobility, usual activities and Visual Analogue Scale show known-groups validity (p < 0.05). Content-related domains of the SIS 2.0 show known-groups validity as well (p < 0.05). However, it is compromised in the emotion domain in both measures (p > 0.05).

Conclusions
The EQ-5D-5L seems to be slightly more suitable for this cohort. Nonetheless, the results of both measures indicate limited suitability for TIA patients. Large-scale studies concerning responsiveness and known-groups validity are encouraged.

Trial registration
The study was registered in the German Clinical Trials Register, retrospective registration on 21.09.2022. Registration ID: DRKS00030297.
Implementation of health-related quality of life in the German TraumaRegister DGU® – first results of a pilot study
Authors: Jaekel Carina , Nienaber Ulrike , Neubert Anne , Kamp Oliver , Wienhöfer Lisa , Nohl Andre , Maegele Marc , Duesing Helena , Erichsen Christoph J. , Frenzel Stephan , Lefering Rolf , Flohe Sascha , Bieler Dan ,   Outcome Study Group of the Committee on Emergency Medicine, Intensive Care, Trauma Management (Sektion NIS) of the German Trauma Society (DGU), Gnass I. , Heining S. M. , Kaske S. , Kollig E. , Polak U. , Simmel S. , Sturm J. , Thelen S. , Volland R. 
Published: June 2024

Abstract
Background
Approximately 30,000 people are affected by severe injuries in Germany each year. Continuous progress in prehospital and hospital care has significantly reduced the mortality of polytrauma patients. With increasing survival rates, the functional outcome, health-related quality (hrQoL) of life and ability to work are now gaining importance. Aim of the study is, the presentation of the response behavior of seriously injured patients on the one hand and the examination of the factors influencing the quality of life and ability to work 12 months after major trauma on the other hand. Building on these initial results, a standard outcome tool shall be integrated in the established TraumaRegister DGU® in the future.

Methods
In 2018, patients [Injury Severity Score (ISS) ≥ 16; age:18–75 years] underwent multicenter one-year posttraumatic follow-up in six study hospitals. In addition to assessing hrQoL by using the Short-Form Health Survey (SF-12), five additional questions (treatment satisfaction; ability to work; trauma-related medical treatment; relevant physical disability, hrQoL as compared with the prior to injury status) were applied.

Results
Of the 1,162 patients contacted, 594 responded and were included in the analysis. The post-injury hrQoL does not show statistically significant differences between the sexes. Regarding age, however, the younger the patient at injury, the better the SF-12 physical sum score. Furthermore, the physically perceived quality of life decreases statistically significantly in relation to the severity of the trauma as measured by the ISS, whereas the mentally perceived quality of life shows no differences in terms of injury severity. A large proportion of severely injured patients were very satisfied (42.2%) or satisfied (39.9%) with the treatment outcome. It should be emphasized that patients with a high injury severity (ISS > 50) were on average more often very satisfied with the treatment outcome (46.7%). A total of 429 patients provided information on their ability to work 12 months post-injury. Here, 194 (45.2%) patients had a full employment, and 58 (13.5%) patients were had a restricted employment.

Conclusion
The present results show the importance of a structured assessment of the postinjury hrQoL and the ability to work after polytrauma. Further studies on the detection of influenceable risk factors on hrQoL and ability to work in the intersectoral course of treatment should follow to enable the best possible outcome of polytrauma survivors.
Sex-dependent effects of carbohydrate source and quantity on caspase-1 activity in the mouse central nervous system
Authors: Valiauga Rasa , Talley Sarah , Khemmani Mark , Fontes Noronha Melline , Gogliotti Rocco , Wolfe Alan J. , Campbell Edward 
Published: June 2024

Abstract
Background
Mounting evidence links glucose intolerance and diabetes as aspects of metabolic dysregulation that are associated with an increased risk of developing dementia. Inflammation and inflammasome activation have emerged as a potential link between these disparate pathologies. As diet is a key factor in both the development of metabolic disorders and inflammation, we hypothesize that long term changes in dietary factors can influence nervous system function by regulating inflammasome activity and that this phenotype would be sex-dependent, as sex hormones are known to regulate metabolism and immune processes.

Methods
5-week-old male and female transgenic mice expressing a caspase-1 bioluminescent reporter underwent cranial window surgeries and were fed control (65% complex carbohydrates, 15% fat), high glycemic index (65% carbohydrates from sucrose, 15% fat), or ketogenic (1% complex carbohydrates, 79% fat) diet from 6 to 26 weeks of age. Glucose regulation was assessed with a glucose tolerance test following a 4-h morning fast. Bioluminescence in the brain was quantified using IVIS in vivo imaging. Blood cytokine levels were measured using cytokine bead array. 16S ribosomal RNA gene amplicon sequencing of mouse feces was performed to assess alterations in the gut microbiome. Behavior associated with these dietary changes was also evaluated.

Results
The ketogenic diet caused weight gain and glucose intolerance in both male and female mice. In male mice, the high glycemic diet led to increased caspase-1 biosensor activation over the course of the study, while in females the ketogenic diet drove an increase in biosensor activation compared to their respective controls. These changes correlated with an increase in inflammatory cytokines present in the serum of test mice and the emergence of anxiety-like behavior. The microbiome composition differed significantly between diets; however no significant link between diet, glucose tolerance, or caspase-1 signal was established.

Conclusions
Our findings suggest that diet composition, specifically the source and quantity of carbohydrates, has sex-specific effects on inflammasome activation in the central nervous system and behavior. This phenotype manifested as increased anxiety in male mice, and future studies are needed to determine if this phenotype is linked to alterations in microbiome composition.
The role of blood related inflammatory factors on age-related macular degeneration (AMD)
Authors: Ojaghi Habib , Poorsheykhian Shirin , Najafi Amin , Iranpour Sohrab 
Published: June 2024

Abstract
Background
Age-related macular degeneration (AMD) is a significant retinal disease that leads to irreversible low vision, particularly in developing countries. The variation in AMD prevalence among different racial groups and highlighted role of inflammation on disease pathology from previous studies which yielded in inconsistent findings, It seems to be of great importance to do more investigation in this field.

Methods
This case control study involved 204 participants, divided into four groups of equal size (51 individuals per group). Three groups represented AMD cases of varying severity according to Beckman classification (3 groups) and one healthy control group. Sampling was conducted exhaustively until the desired sample size was reached. The control group comprised healthy individuals without any infectious or inflammatory systemic, ophthalmic disease. Blood samples were collected to measure inflammatory factors, including lymphocytes, monocytes, neutrophils, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP). Collected data were analyzed by statistical methods in SPSS version 21.

Results
Of the participants, 51% were women, and their ages ranged from 47 to 89 years (62.2 ± 8). According to multiple logistic regression analysis, age exhibited a statistically significant positive association with AMD severity (P = 0.038, odds ratio [OR] = 1.034). ANOVA results indicated a significant association between neutrophil count and AMD severity (P < 0.001). As the disease severity increased, the number of neutrophils decreased. The mean ± SD neutrophil counts for early, intermediate and advanced AMD were 3849 ± 800, 3702 ± 734, and 3342 ± 823, respectively. No statistically significant associations were found between lymphocyte count, monocyte count, neutrophil-to-lymphocyte ratio, CRP, and AMD.

Conclusion
There was a significant relationship between the number of neutrophils in peripheral blood and the severity of AMD in study participants which needs more evaluation for the potential utility of this factor in the prognosis of AMD. There was not any significant relationship among the other factors and AMD.