bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trainees as Agents of Change: A Theory-Informed Model for Trainee-Driven Curricular Advocacy in Medical Education
Authors: Clarke Lauren 
Published: May 2024

Abstract
Trainees (medical students, residents, and fellows) are beginning to make strides in pushing for changes to their education. While there are many examples of successful trainee-led curriculum reform efforts, the path to success remains unclear. To better understand the process of trainee-driven curricular advocacy, the author analyzes this process through the lens of ecological systems theory (EST) not only to provide readers with context for the barriers and facilitators to trainee-driven curricular advocacy but also to further medical education’s understanding of the sociopolitical forces influencing the process of trainee-driven curricular advocacy and reform through the lens of the trainee. EST explains how individuals are influenced by a complex web of social and environmental forces. The theory outlines 5 ecological systems of influence: the microsystem, mesosystem, exosystem, macrosystem, and chronosystem. Using EST to explore the process of trainee-driven curricular advocacy therefore clarifies the many layers of influence that trainees must navigate while advocating for curriculum change. The author then draws on this theory and their own experience as a medical student advocating for local and national curriculum reform to develop a model to facilitate trainee-driven curricular advocacy in medical education. The proposed model outlines concrete steps trainees can take while going through the process of curricular advocacy both within their own institutions and on a national level. Through developing this model, the author hopes not only to empower trainees to become agents of change in medical education but also to encourage faculty members and administrators within health professional training programs to support trainees in these efforts.
A Guiding Model for Undergraduate Medical Education Well-Being Programs
Authors: Lawrence Elizabeth C. , Sheridan Chantal , Hurtado Alicia , Lee Wei Wei , Lizotte-Waniewski Michelle , Rea Margaret , Zehle Christa 
Published: May 2024

Abstract
Most medical schools have instituted undergraduate medical education (UME) well-being programs in recent years in response to high rates of medical student distress, but there is currently significant variability in the structure of UME well-being programs and limited guidance on how to best structure such programs to achieve success. In this article, the authors, all leaders of medical student well-being programs at their home institutions and members of the Association of American Medical Colleges Group on Student Affairs Committee on Student Affairs Working Group on Medical Student Well-Being between 2019 and 2023 offer guidance to the national community on how best to structure a UME well-being program. They use the current literature and their professional experiences leading well-being efforts at 7 different institutions to review the case for addressing medical student well-being, propose a guiding model, and make recommendations for strategies to implement this model.
The proposed guiding model emphasizes the importance of the learning environment and efficiency of learning to medical student well-being, as well as personal resilience. Based on this model, the authors recommend specific and tangible well-being strategies to implement systemic interventions to improve the learning environment, efficiency of learning, and personal resilience, including formalizing the well-being program; hiring qualified, dedicated, and empowered well-being leadership with clear responsibilities; acting as a central hub for resources and as a liaison with mental health care; and establishing robust program evaluation methods.
Ligamentous Augmentation to Prevent Proximal Junctional Kyphosis and Failure
Authors: Weng Chong , Niemeier Thomas , Mohammed Zuhair J. , Eberhardt Alan , Theiss Steven M. , Rajaram Manoharan Sakthivel R. 
Published: May 2024

Study Design:
Biomechanical cadaveric study (level V).

Objective:
To evaluate the effectiveness of polyethylene bands looped around the supra-adjacent spinous process (SP) or spinal lamina (SL) in providing strength to the cephalad unfused segment and reducing junctional stress.

Background:
Proximal junctional kyphosis (PJK) is a pathologic kyphotic deformity adjacent to posterior spinal instrumentation after fusion constructs. Recent studies demonstrate a mismatch in stiffness between the instrumented construct and nonfused adjacent levels to be a causative factor in the development of PJK and proximal junction failure. To our knowledge, no biomechanical studies have addressed the effect of different methods of polyethylene band placement at the proximal junction.

Materials and Methods:
Twelve fresh frozen cadavers were divided into 3 groups of 4: pedicle screw-based instrumentation from T10 to L5 (“control”), T10–L5 instrumentation with a polyethylene band to the T9 “SP,” T10–L5 instrumentation with 2 polyethylene bands to the T9 “SL.” Specimens were tested with an eccentric (10 mm anterior) load at 5 mm/min for 15 mm or until failure occurred. Failure was defined by the inflection point on the load versus deformation curves. Linear regression was utilized to evaluate the effect of augmentation on the load-to-failure. Significance was set at 0.05.

Results:
Fractures occurred in all specimens tested. The mean peak load to failure was 2148 N (974–3322) for the SP group, and 1248 N (742–1754) for the control group (P > 0.05) and 1390 N (1080–2004) for the SL group. No difference existed between the control group and the SP group in terms of fracture level (P > 0.05). Net kyphotic angulation shows no differences among these 3 groups (P > 0.05).

Conclusion:
Although statistical significance was not achieved, ligament augmentation to the SP increased mean peak load-to-failure in a cadaveric PJK model.
Feasibility of Using Intraoperative Neurophysiological Monitoring for Detecting Bone Layer of Cervical Spine Surgery
Authors: Zuo Weiyang , Yu Lingjia , Tan Haining , Li Xiang , Zhu Bin , Liu Yuquan , Peng Xuan , Yang Yong , Fei Qi 
Published: May 2024

Study Design:
Intraoperative neurophysiological monitoring (IONM) as a guide to bone layer estimation was examined during posterior cervical spine lamina grinding.

Objective:
To explore the feasibility of IONM to estimate bone layer thickness.

Summary of Background Data:
Cervical laminoplasty is a classic operation for cervical spondylosis. To increase safety and accuracy, surgery-assistant robots are currently being studied. It combines the advantages of various program awareness methods to form a feasible security strategy. In the field of spinal surgery, robots have been successfully used to help place pedicle screws. IONM is used to monitor intraoperative nerve conditions in spinal surgery. This study was designed to explore the feasibility of adding IONM to robot safety strategies.

Methods:
Chinese miniature pig model was used. Electrodes were placed on the lamina, and the minimum stimulation threshold of DNEP for each lamina was measured (Intact lamina, IL). The laminae were ground to measure the DNEP threshold after incomplete grinding (Inner cortical bone preserved, ICP) and complete grinding (Inner cortical bone grinded, ICG). Subsequently, the lateral cervical mass screw canal drilling was performed, and the t-EMG threshold of the intact and perforated screw canals was measured and compared.

Result:
The threshold was significantly lower than that of the recommended threshold of DENP via percutaneous cervical laminae measurement. The DNEP threshold decreases with the process of laminae grinding. The DNEP threshold of the IL group was significantly higher than ICP and ICG group, while there was no significant difference between the ICP group and the ICG group. There was no significant relationship between the integrity of the cervical spine lateral mass screw path and t-EMG threshold.

Conclusions:
It is feasible to use DENP threshold to estimate lamina thickness. Cervical lateral mass screw canals by t-EMG showed no help to evaluate the integrity.
Cortisol Levels During First Admission Day Are Associated With Clinical Outcomes in Surgical Critically Ill Patients
Authors: Goder Noam , Gerstenhaber Fabian , Gal Oz Amir , Stavi Dekel , Angel Yoel , Nini Asaph , Lichter Yael , Sold Oded 
Published: May 2024

IMPORTANCE:
To explore the correlation between cortisol levels during first admission day and clinical outcomes.

OBJECTIVES:
Although most patients exhibit a surge in cortisol levels in response to stress, some suffer from critical illness-related corticosteroid insufficiency (CIRCI). Literature remains inconclusive as to which of these patients are at greater risk of poor outcomes.

DESIGN:
A retrospective study.

SETTING:
A surgical ICU (SICU) in a tertiary medical center.

PARTICIPANTS:
Critically ill patients admitted to the SICU who were not treated with steroids.

MAIN OUTCOMES AND MEASURES:
Levels of cortisol taken within 24 hours of admission (day 1 [D1] cortisol) in 1412 eligible patients were collected and analyzed. Results were categorized into four groups: low (0–10 µg/dL), normal (10–25 µg/dL), high (25–50 µg/dL), and very high (above 50 µg/dL) cortisol levels. Primary endpoint was 90-day mortality. Secondary endpoints were the need for organ support (use of vasopressors and mechanical ventilation [MV]), ICU length of stay (LOS), and duration of MV.

RESULTS:
The majority of patients (63%) had high or very high D1 cortisol levels, whereas 7.6% had low levels and thus could be diagnosed with CIRCI. There were statistically significant differences in 90-day mortality between the four groups and very high levels were found to be an independent risk factor for mortality, primarily in patients with Sequential Organ Failure Assessment (SOFA) less than or equal to 3 or SOFA greater than or equal to 7. Higher cortisol levels were associated with all secondary endpoints. CIRCI was associated with favorable outcomes.

CONCLUSIONS AND RELEVANCE:
In critically ill surgical patients D1 cortisol levels above 50 mcg/dL were associated with mortality, need for organ support, longer ICU LOS, and duration of MV, whereas low levels correlated with good clinical outcomes even though untreated. D1 cortisol level greater than 50 mcg/dL can help discriminate nonsurvivors from survivors when SOFA less than or equal to 3 or SOFA greater than or equal to 7.
Direct reprogramming of fibroblasts into functional hepatocytes via CRISPRa activation of endogenous Gata4 and Foxa3
Authors: Li Jiacheng , Li Ruopu , Bai Xue , Zhang Wenlong , Nie Yu , Hu Shengshou 
Published: May 2024

Abstract

Background:
The ability to generate functional hepatocytes without relying on donor liver organs holds significant therapeutic promise in the fields of regenerative medicine and potential liver disease treatments. Clustered regularly interspaced short palindromic repeats (CRISPR) activator (CRISPRa) is a powerful tool that can conveniently and efficiently activate the expression of multiple endogenous genes simultaneously, providing a new strategy for cell fate determination. The main purpose of this study is to explore the feasibility of applying CRISPRa for hepatocyte reprogramming and its application in the treatment of mouse liver fibrosis.

Method:
The differentiation of mouse embryonic fibroblasts (MEFs) into functional induced hepatocyte-like cells (iHeps) was achieved by utilizing the CRISPRa synergistic activation mediator (SAM) system, which drove the combined expression of three endogenous transcription factors—Gata4, Foxa3, and Hnf1a—or alternatively, the expression of two transcription factors, Gata4 and Foxa3. In vivo, we injected adeno-associated virus serotype 6 (AAV6) carrying the CRISPRa SAM system into liver fibrotic Col1a1-Cre

ER
; Cas9

fl/
fl
mice, effectively activating the expression of endogenous Gata4 and Foxa3 in fibroblasts. The endogenous transcriptional activation of genes was confirmed using real-time quantitative polymerase chain reaction (RT-qPCR) and RNA-seq, and the morphology and characteristics of the induced hepatocytes were observed through microscopy. The level of hepatocyte reprogramming in vivo is detected by immunofluorescence staining, while the improvement of liver fibrosis is evaluated through Sirius red staining, alpha-smooth muscle actin (α-SMA) immunofluorescence staining, and blood alanine aminotransferase (ALT) examination.

Results:
Activation of only two factors, Gata4 and Foxa3, via CRISPRa was sufficient to successfully induce the transformation of MEFs into iHeps. These iHeps could be expanded in vitro and displayed functional characteristics similar to those of mature hepatocytes, such as drug metabolism and glycogen storage. Additionally, AAV6-based delivery of the CRISPRa SAM system effectively induced the hepatic reprogramming from fibroblasts in mice with live fibrosis. After 8 weeks of induction, the reprogrammed hepatocytes comprised 0.87% of the total hepatocyte population in the mice, significantly reducing liver fibrosis.

Conclusion:
CRISPRa-induced hepatocyte reprogramming may be a promising strategy for generating functional hepatocytes and treating liver fibrosis caused by hepatic diseases.
SIRT3 protects endometrial receptivity in patients with polycystic ovary syndrome
Authors: Zeng Zhonghong , Shan Hongying , Lin Mingmei , Bao Siyu , Mo Dan , Deng Feng , Yu Yang , Yang Yihua , Zhou Ping , Li Rong 
Published: May 2024

Abstract

Background:
The sirtuin family is well recognized for its crucial involvement in various cellular processes. Nevertheless, studies on its role in the human endometrium are limited. This study aimed to explore the expression and localization of the sirtuin family in the human endometrium, focusing on sirtuin 3 (SIRT3) and its potential role in the oxidative imbalance of the endometrium in polycystic ovary syndrome (PCOS).

Methods:
Endometrial specimens were collected from both patients with PCOS and controls undergoing hysteroscopy at the Center for Reproductive Medicine, Peking University Third Hospital, from July to August 2015 and used for cell culture. The protective effects of SIRT3 were investigated, and the mechanism of SIRT3 in improving endometrial receptivity of patients with PCOS was determined using various techniques, including cellular bioenergetic analysis, small interfering ribonucleic acid (siRNA) silencing, real-time quantitative polymerase chain reaction, Western blot, immunofluorescence, immunohistochemistry, and flow cytometry analysis.

Results:
The sirtuin family was widely expressed in the human endometrium, with SIRT3 showing a significant increase in expression in patients with PCOS compared with controls (P <0.05), as confirmed by protein and gene assays. Concurrently, endometrial antioxidant levels were elevated, while mitochondrial respiratory capacity was reduced, in patients with PCOS (P <0.05). An endometrial oxidative stress (OS) model revealed that the downregulation of SIRT3 impaired the growth and proliferation status of endometrial cells and reduced their receptivity to day 4 mouse embryos. The results suggested that SIRT3 might be crucial in maintaining normal cellular state by regulating antioxidants, cell proliferation, and apoptosis, thereby contributing to enhanced endometrial receptivity.

Conclusions:
Our findings proposed a significant role of SIRT3 in improving endometrial receptivity in patients with PCOS by alleviating OS and regulating the balance between cell proliferation and apoptosis. Therefore, SIRT3 could be a promising target for predicting and improving endometrial receptivity in this patient population.
Oncologic Outcomes for Squamous Cell Carcinoma In Situ With a Clinically Resolved Biopsy Site Managed by Watchful Waiting
Authors: Logan Sam , Porter Hannah J. , Lowry Joy , Carpenter Cari , Seward David J. , Holmes Todd , Goldman Glenn , Bui Melanie R. 
Published: May 2024

BACKGROUND
Treatment option decisions for low-risk squamous cell carcinoma in situ (SCCIS) are hampered by a paucity of management-type–specific outcomes data.

OBJECTIVE
Describe SCCIS tumor outcomes managed by watchful waiting and risk factors associated with poor cancer outcomes.

MATERIALS AND METHODS
Retrospective cohort study. Setting: Single academic hospital in a rural setting. Patients: Adults with SCCIS diagnosed between January 01, 2014, and December 31, 2016. Main Outcomes and Measures: Hazard ratios (HRs) for local recurrence (LR), nodal metastases (NM), distant metastases (DM), and disease-specific death (DSD).

RESULTS
A total of 411 consecutive SCCIS tumors that were considered clinically resolved at follow-up and managed with watchful waiting were included. Seventeen tumors recurred locally. No instances of NM, DM, or DSD were identified. Multivariate analysis found that solid-organ transplant recipient status conferred the highest risk of local recurrence [HR, 9.979 (95% CI, 2.249–39.69)]. Additional risk factors predicting LR include anatomic location on the vermilion lip or ear [HR, 9.744 (95% CI, 1.420–69.28)], anatomic location on the head and neck [HR, 6.687 (95% CI, 1.583–36.15)], and a biopsy with tumor extending to the deep edge [HR, 6.562 (95% CI, 1.367–39.04)].

CONCLUSION
Watchful waiting for SCCIS with a clinically resolved biopsy site has a local recurrence rate of 4%.
Growing Adoption of Immunohistochemistry by Mohs Micrographic Surgeons: A National Medicare Trend Analysis
Authors: Gronbeck Christian , Feng Hao , Knackstedt Thomas 
Published: May 2024

BACKGROUNDImmunohistochemical (IHC) staining can be used alongside Mohs micrographic surgery to aid in margin assessment of subtle tumors, yet existing estimates of IHC utilization have primarily relied on survey or older data that lacks stratification.OBJECTIVETo characterize national IHC utilization trends by Mohs surgeons, stratifying by surgeon characteristics and modeling future adoption.METHODSLongitudinal analysis of 2014 to 2021 Medicare Public Use Files.RESULTSIn 2021, 158 of 2,058 Mohs surgeons (7.7%) used IHC as compared with 4.0% in 2014 (average annual growth rate [AAGR] +3.6%). Adoption change was highest in the Northeast (AAGR +19.9%), whereas volume growth was greatest in the West (AAGR +25.2%). Multivariable regression revealed significantly greater utilization propensity among Mohs surgeons in academics (adjusted odds ratio [aOR] 3.36), American College of Mohs Surgery (ACMS) members (aOR 2.12), and Micrographic Dermatologic Surgery (MDS)-certified surgeons (aOR 1.66).CONCLUSIONMohs surgeons are steadily incorporating IHC into practice across all regions, with volume growth driven by higher adoption rates. Greater utilization among ACMS members, recipients of MDS certification, and those in academics suggests value of formalized training in enhancing comfort. Additional educational opportunities at conferences may aid in recognition of value and help identify solutions to address integration challenges.
Nonsurgical Gluteal Volume Correction with Hyaluronic Acid: A Retrospective Study to Assess Long-term Safety and Efficacy
Authors: Crabai Piero , Marchetti Francesco , Santacatterina Fulvio , Fontenete Silvia , Galera Teresa 
Published: May 2024

Background:
Augmentation and reshaping of body volume, particularly in the gluteal area, presents a significant challenge in aesthetic surgery. Hyaluronic acid (HA) fillers have emerged as an effective and safe tool for such indications, but literature examining nonsurgical gluteal reshaping with HA remains limited. This study aims to evaluate the long-term safety of using recommended volumes of HA body fillers for nonsurgical gluteal augmentation.

Methods:
A retrospective, observational study was carried out across multiple centers in Italy and the United Arab Emirates. The study involved participants between 22 and 53 years of age who underwent gluteal augmentation using HA body filler (HYAcorp MLF1/2) between 2017 and 2021, with up to 4 years and 7 months of follow-up. Participants and investigators independently evaluated the procedure’s effectiveness by comparing pre- and posttreatment photographs. The Global Aesthetic Improvement Scale was used to assess posttreatment satisfaction by both participants and investigators. All adverse effects (AEs) were recorded.

Results:
The study included a diverse group of 91 participants. No serious adverse events were reported, with the majority of AE occurring shortly after treatment and resolving in 1 week. AEs were more frequently observed in participants with previous treatments using different substances in the treatment area.

Conclusions:
The real-world application of HA body filler (HYAcorp MLF1/2) for gluteal augmentation in the participants of this study showed the treatment’s effectiveness, with no severe adverse events reported among the participants. High levels of satisfaction were reported among both participants and investigators.
Overview of Mycotic Keratitis
Authors: Arboleda Alejandro , Ta Christopher N. 
Published: May 2024

Abstract:
Keratomycosis is a serious corneal infection associated with high ocular morbidity that can lead to severe vision loss. It is estimated to affect more than 1 million patients annually, most commonly occurring in tropical climates, and represents a growing threat to patients worldwide. Despite aggressive medical management, fungal infections have a higher rate of perforation requiring surgical intervention compared with other infectious etiologies. Early diagnosis and appropriate treatment are keys to preserving vision and saving patients' eyes.
Timely diagnosis of fungal keratitis helps minimize corneal damage and scarring and increases the likelihood of a favorable outcome. Studies have shown that correct identification of fungal infections is often delayed up to 2 to 3 weeks after initial presentation. This leads to incorrect or ineffective treatment for many patients. Diagnostic techniques explored in this study include corneal scrapings with staining and culture, visualization with in vivo confocal microscopy, molecular diagnostic techniques including polymerase chain reaction, and recently developed omics-based technologies.
Treatment of fungal keratitis begins with topical antifungals. Medical management has been proven to be effective, but with limitations including poor drug penetration and low bioavailability. Cases that do not respond to topical therapy require more invasive and novel treatments to control the infection. We review the clinical trials that have shaped current practice patterns, with focus on the efficacy of topical natamycin as the primary therapy for filamentous fungal keratitis. We explore additional management strategies such as localized intrastromal and intracameral injections of antifungal medications, photodynamic therapy, and surgical intervention.