bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study
Authors: Zhang Lu , Chen Lizhi , Liu Xiaohong , Huang Zhijun , Zheng Yifan , Tang Kejing , Jiang Xiaoyun , Chen Pan 
Published: May 2024

Abstract

Objectives
Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients.

Method
This was a population-based observational cohort study. A total of 86 pediatric LN patients treated with mycophenolate mofetil (MMF) for induction therapy were enrolled. The area-under the concentration-time curve (AUC) was calculated using MPA concentrations according to a limited sampling strategy. Receiver operating characteristic analysis was performed to assess the MPA-AUC threshold values. The cumulative incidence of renal remission and inactive systemic lupus erythematosus (SLE) over time was evaluated by Kaplan–Meier’s analysis.

Results
MPA-AUC was identified as an independent factor associated with renal remission and lupus activity at 6 and 12 months after MMF treatment, and the improved renal remission rates were correlated with higher MPA-AUC, with thresholds of 29.81 and 30.63 μg·h·mL−1 at 6 months and 12 months, respectively. Furthermore, the thresholds for maintaining the hypoactive state of LN were 30.96 and 31.19 μg·h·mL−1at 6 months and 12 months, respectively. Patients reaching target thresholds for MPA-AUC achieved renal response or stable disease earlier. In addition, the MPA-AUC threshold for decreasing MMF-related adverse reactions was 50.80 μg·h·mL−1.

Conclusion
The initial and long-term treatments of pediatric LN patients with MMF should be individualized according to the MPA-AUC, and the recommended MPA exposure is 31.19–50.80 μg·h·mL−1.
Endothelial progenitor cells for diabetic cardiac and kidney disease
Authors: Raleigh Matthew J , Pasricha Sachin V , Nauth Aaron , Ward Michael R , Connelly Kim A 
Published: May 2024

Abstract
The management of diabetes mellitus and its resultant end organ dysfunction represents a major challenge to global health-care systems. Diabetic cardiac and kidney disease commonly co-occur and are significant contributors to the morbidity and mortality of patients with diabetes, carrying a poor prognosis. The tight link of these parallel end organ manifestations suggests a deeper common underlying pathology. Here, we outline the mechanistic link between diabetic cardiac and kidney disease, providing evidence for the role of endothelial dysfunction in both processes and the potential for cellular therapy to correct these disorders. Specifically, we review the preclinical and clinical evidence for endothelial progenitor cell therapy in cardiac, kidney, and cardio-renal disease applications. Finally, we outline novel approaches to endothelial progenitor cell therapy through cell enhancement and the use of extracellular vesicles, discussing published and future work.
Comparative toxicological assessment of 2 bisphenols using a systems approach: evaluation of the behavioral and transcriptomic responses of Danio rerio to bisphenol A and tetrabromobisphenol A
Authors: Morash Michael G , Kirzinger Morgan W , Achenbach John C , Venkatachalam Ananda B , Nixon Jessica , Penny Susanne , Cooper Joëlle Pinsonnault , Ratzlaff Deborah E , Woodland Cindy L A , Ellis Lee D 
Published: May 2024

Abstract
The zebrafish (Danio rerio) is becoming a critical component of new approach methods (NAMs) in chemical risk assessment. As a whole organism in vitro NAM, the zebrafish model offers significant advantages over individual cell-line testing, including toxicokinetic and toxicodynamic competencies. A transcriptomic approach not only allows for insight into mechanism of action for both apical endpoints and unobservable adverse outcomes, but also changes in gene expression induced by lower, environmentally relevant concentrations. In this study, we used a larval zebrafish model to assess the behavioral and transcriptomic alterations caused by subphenotypic concentrations of 2 chemicals with the same structural backbone, the endocrine-disrupting chemicals bisphenol A and tetrabromobisphenol A. Following assessment of behavioral toxicity, we used a transcriptomic approach to identify molecular pathways associated with previously described phenotypes. We also determined the transcriptomic point of departure for each chemical by modeling gene expression changes as continuous systems which allows for the identification of a single concentration at which toxic effects can be predicted. This can then be investigated with confirmatory cell-based testing in an integrated approach to testing and assessment to determine risk to human health and the environment with greater confidence. This paper demonstrates the impact of using a multi-faceted approach for evaluating the physiological and neurotoxic effects of exposure to structurally related chemicals. By comparing phenotypic effects with transcriptomic outcomes, we were able to differentiate, characterize, and rank the toxicities of related bisphenols, which demonstrates methodological advantages unique to the larval zebrafish NAM.
Bringing a Structural Competency Framework to the (Simulated) Bedside: The Premature Discharge Objective Structured Clinical Exam
Authors: Ramsdell Amanda K. , Hupert Nathaniel , Abramson Erika , Safdieh Joseph E. , Katz Sydney 
Published: May 2024

Abstract

Problem
Structural competency is increasingly valued as a framework to address health equity within undergraduate medical education. As of academic year 2023–2024, the Liaison Committee on Medical Education (LCME) requires that medical schools have content regarding basic principles of structurally competent health care. Despite encouraging data about the effectiveness of structural competency curricula, most occur within the walls of a classroom and do not enter the authentic or simulated clinical space.

Approach
From 2022 to 2023, an objective structured clinical exam (OSCE) focused on premature discharge, previously known as discharge against medical advice, was integrated into the required fourth-year Health Policy course at Weill Cornell Medical College, which uses the framework of structural competency. After a simulated clinical encounter, students completed a reflection assignment and participated in group debriefing to reflect on how policy coursework affected their simulated clinical experience. Students completed an evaluation about their OSCE experience, and OSCE checklist performance was analyzed.

Outcomes
Of 82 students who participated in the curriculum, 68 completed a curricular evaluation, and 62 consented to have their OSCE performance evaluated for research. Mean overall OSCE checklist performance evaluating students’ patient-centered communication skills, harm reduction skills, and discharge planning and counseling was 14.3/16 (89.6%; standard deviation, 9.8%). Students reported it was valuable to focus on structural factors affecting care within the simulated clinical encounter by using the structural competency framework.

Next Steps
To the authors’ knowledge, this is the first OSCE for medical students designed to deepen their understanding of structural competency by embedding the experience into an existing course using the framework. Future work should explore how this curriculum affects students’ attitudes toward structurally vulnerable patients. With structural competency as an LCME requirement, the use of OSCEs may give educators a means to teach and assess fundamental concepts.
Building a Physician-Scientist Pathway for Underrepresented Medical Students Through a Summer Research Experience
Authors: Duncan Andrea F. , Sukra Liza , Portugues Alexandra , Fields British , Patton Kiara , Aredas Brenna , Ellison Angela M. 
Published: May 2024

Abstract

Problem
There is a need to increase the number of physician-scientists from underrepresented in medicine (URiM) groups. To engage URiM medical students, a committee of pediatric departmental leaders at the Children’s Hospital of Philadelphia created the Summer Underrepresented in Medicine Medical Student Research program. This 8-week, onsite research and clinical experience takes place during the summer between students’ first and second years of medical school.

Approach
Applications were solicited between 2019 and 2023 through nationwide outreach to medical school deans and members of URiM student organizations. Accepted students were assigned a mentor to lead their research and clinical exposure. A curriculum highlighting aspects of academic medicine was developed. Students received a $3,000–$5,500 stipend for in-person participation. In 2020 and 2021, adjustments were made (e.g., virtual programming) to avoid interruptions during the COVID-19 pandemic.

Outcomes
In the 2019–2023 application cycles, 298 students applied. Of 128 students who participated, 78 (61%) completed a postprogram survey. Students’ survey feedback was positive. They indicated the program met expectations (mean rating = 1.3; scale: 1 = strongly agree to 5 = strongly disagree). Students reported they learned valuable information/skills (mean = 1.3) and that participation was worth time spent away from other responsibilities (mean = 1.3). The 2019 cohort (n = 12) achieved a 100% residency match rate. In addition, 4 (33%) of these students reported they are obtaining additional degrees or are performing research. After the program, many mentors continued to include students in their research projects.

Next Steps
Next steps include incorporating a standardized, scored rubric for selecting applicants; adding 3 lead mentors, an executive committee, and a faculty advisory board; establishing earlier pathway programming (e.g., at elementary and middle school levels); continuing to track/support alumni throughout their careers; and pursuing federal funding to expand the program.
Magnetic sphincter augmentation in the management of gastro-esophageal reflux disease: a systematic review and meta-analysis
Authors: Fadel Michael G. , Tarazi Munir , Dave Madhav , Reddy Marcus , Khan Omar , Fakih-Gomez Naim , Ashrafian Hutan , Fehervari Matyas 
Published: May 2024

Background:
Magnetic sphincter augmentation (MSA) through placement of the LINX device is an alternative to fundoplication in the management of gastro-esophageal reflux disease (GERD). This systematic review and meta-analysis aimed to assess efficacy, quality of life, and safety in patients that underwent MSA, with a comparison to fundoplication.

Methods:
A literature search of MEDLINE, Embase, Emcare, Scopus, Web of Science, and Cochrane library databases was performed for studies that reported data on outcomes of MSA, with or without a comparison group undergoing fundoplication, for GERD from January 2000 to January 2023. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed.

Results:
Thirty-nine studies with 8075 patients were included: 6983 patients underwent MSA and 1092 patients had laparoscopic fundoplication procedure. Ten of these studies (seven retrospective and three prospective) directly compared MSA with fundoplication. A higher proportion of individuals successfully discontinued proton-pump inhibitors (P<0.001; WMD 0.83; 95% CI: 0.72–0.93; I
2=96.8%) and had higher patient satisfaction (P<0.001; WMD 0.85; 95% CI: 0.78–0.93; I
2=85.2%) following MSA when compared to fundoplication. Functional outcomes were better after MSA than after fundoplication including ability to belch (P<0.001; WMD 0.96; 95% CI: 0.93–0.98; I
2=67.8) and emesis (P<0.001; WMD 0.92; 95% CI: 0.89–0.95; I
2=42.8%), and bloating (P=0.003; WMD 0.20; 95% CI: 0.07–0.33; I
2=97.0%). MSA had higher rates of dysphagia (P=0.001; WMD 0.41; 95% CI: 0.17–0.65; I
2=97.3%) when compared to fundoplication. The overall erosion and removal rate following MSA was 0.24% and 3.9%, respectively, with no difference in surgical reintervention rates between MSA and fundoplication (P=0.446; WMD 0.001; 95% CI: −0.001–0.002; I
2=78.5%).

Conclusions:
MSA is a safe and effective procedure at reducing symptom burden of GERD and can potentially improve patient satisfaction and functional outcomes. However, randomized controlled trials directly comparing MSA with fundoplication are necessary to determine where MSA precisely fits in the management pathway of GERD.
Does an aptitude for surgery exist and can we predict it? An experimental study
Authors: Ruchay Zino , Pape Julian , Cordt Julia-Sophie , Kerres Carolina , Siehl Sebastian , Jansone Karina , Ackermann Johannes , Guenther Veronika , Mettler Liselotte , Allahqoli Leila , Maass Nicolai , Nees Frauke , Alkatout Ibrahim 
Published: May 2024

Background:
The selection and allocation of surgeons with a greater potential for high surgical performance are essential aspects of improving the quality, safety, and effectiveness of surgical procedures. Objective of this trial was to determine the existence of basic skills and traits that would predict better performance in surgery, and those predictive factors that constitute a driving force in different stages of training.

Materials and methods:
The randomized crossover training trial took place from January 2021 to December 2021 and was conducted at an educational training center for minimally invasive surgery. A total of n=87 physicians (residents and experts) from surgical disciplines and n=239 fifth-year medical students were studied. The participants underwent extensive neuropsychological testing and surgical training, which was performed with conventional as well as robot-assisted laparoscopy by way of identical brief tasks conducted six times in a randomized crossover setting. Main Outcome was the latent factor structure of ‘psychomotor skills’, ‘personality’, and ‘motivation’ based on structural equation modeling.

Results:
The training performance of both students and physicians was significantly explained by the interaction of the three factors (explained variance: 8.2% for students, 23.8% for physicians). In students, motivation (explained variance 8.4%) and personality (explained variance 4.5%) revealed the highest contribution to surgical training performance (explained variance through psychomotor skills 1.1%). In physicians, psychomotor skills (explained variance 27.4%) made the greatest contribution to surgical training performance (explained variance through motivation 2.3%; explained variance through personality 10.5%).

Conclusion:
The study showed that surgical performance is sensitive to, and fragile in regard of nonsurgery-related general individual traits. This aligns with the notion that early selection of surgeons with prospects of high surgical performance is possible, and perhaps even necessary in order to keep up with future demands on the medical system.
MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study
Authors: Lan Tianjun , Kuang Shijia , Liang Peisheng , Ning Chenglin , Li Qunxing , Wang Liansheng , Wang Youyuan , Lin Zhaoyu , Hu Huijun , Yang Lingjie , Li Jintao , Liu Jingkang , Li Yanyan , Wu Fan , Chai Hua , Song Xinpeng , Huang Yiqian , Duan Xiaohui , Zeng Dong , Li Jinsong , Cao Haotian 
Published: May 2024

Introduction:
The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20–30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions.

Aim:
To construct and evaluate a preoperative diagnostic method to predict OCLNM in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features.

Methods:
A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA), and survival analysis.

Results:
Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881–0.975), 0.878 (95% CI: 0.766–0.990), 0.796 (95% CI: 0.666–0.927), and 0.834 (95% CI: 0.721–0.947) in the training, test, external validation set1, and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC.

Conclusion:
The proposed MRI-based Resnet50 DL model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.
Estimating the Proportion of People Living With HIV Who May Benefit From the Reverse Algorithm for the Diagnosis of Incident Syphilis
Authors: Menza Timothy W. , Berry Stephen A. , Dombrowski Julia C. , Cachay Edward , Crane Heidi M. , Mayer Kenneth H. 
Published: May 2024

AbstractAmong 8455 people engaged in HIV care in 4 US cities, 4925 (58%) had treponemal testing at care entry. Of the 4925 tested, 3795 (77%) had a nonreactive result and might benefit from the reverse algorithm for a future incident syphilis diagnosis. Furthermore, low-barrier treponemal testing as a first step in the reverse algorithm may increase syphilis screening and decrease time to treatment.
Response to Antibiotic Treatment of Bacterial Vaginosis Predicts the Effectiveness of LACTIN-V (Lactobacillus crispatus CTV-05) in the Prevention of Recurrent Disease
Authors: Hemmerling Anke , Wierzbicki Michael R. , Armstrong Eric , Cohen Craig R. 
Published: May 2024

Objectives
Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment.

Methods
A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks.

Results
At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35–0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47–2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure.

Conclusions
LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.
Rescuing DNMT1 Fails to Fully Reverse the Molecular and Functional Repercussions of Its Loss in Mouse Embryonic Stem Cells
Authors: Elder Elizabeth , Lemieux Anthony , Legault Lisa-Marie , Caron Maxime , Bertrand-Lehouillier Virginie , Dupas Thomas , Raynal Noël J-M , Bourque Guillaume , Sinnett Daniel , Gévry Nicolas , McGraw Serge 
Published: May 2024

SUMMARYEpigenetic mechanisms are crucial for developmental programming and can be disrupted by environmental stressors, increasing susceptibility to disease. This has sparked interest in therapies for restoring epigenetic balance, but it remains uncertain whether disordered epigenetic mechanisms can be fully corrected. Disruption of DNA methyltransferase 1 (DNMT1), responsible for DNA methylation maintenance, has particularly devastating biological consequences. Therefore, here we explored if rescuing DNMT1 activity is sufficient to reverse the effects of its loss utilizing mouse embryonic stem cells. However, only partial reversal could be achieved. Extensive changes in DNA methylation, histone modifications and gene expression were detected, along with transposable element de-repression and genomic instability. Reduction of cellular size, complexity and proliferation rate were observed, as well as lasting effects in germ layer lineages and embryoid bodies. Interestingly, by analyzing the impact on imprinted regions, we uncovered 20 regions exhibiting imprinted-like signatures. Notably, while many permanent effects persisted throughoutDnmt1inactivation and rescue, others arose from the rescue intervention. Lastly, rescuing DNMT1 after differentiation initiation worsened outcomes, reinforcing the need for early intervention. Our findings highlight the far-reaching functions of DNMT1 and provide valuable perspectives on the repercussions of epigenetic perturbations during early development and the challenges of rescue interventions.HIGHLIGHTS-Extensive changes to epigenomic landscapes and gene expression following transient loss of DNMT1 activity-Dysregulation of known imprinted regions and identification of 20 regions with imprinted-like signatures-De-repression of MERVL and MT2 LTRs with evidence of chimeric gene transcript generation-Shorter telomeres, DNA damage accumulation and reduction of cell size, internal complexity and proliferation rate-Lasting effects upon differentiation toward germ layer lineages and embryoid bodies-Worsened molecular and cellular outcomes when delayingDnmt1rescue until after differentiation initiationGRAPHICAL ABSTRACT