bluuebunny/crossref_metadata_2025_split huggingface dataset:
Developing Competencies and Milestones: Putting the Pieces Together for Student Success
Authors: Fernandez Tanya , Dougherty Kelsey , Sivahop Jacqueline 
Published: October 2024

Abstract
Competency-based medical education has become a means in physician assistant (PA) education to ensure learner readiness for practice; align educational expectations; and assess knowledge, skills, and attitudes. Competency-based education may also serve to meet accreditation requirements. Creating program-defined competencies and associated milestones can help a PA program align with their mission and vision, developmentally guide learners through the curriculum, and ensure program assessments measure the tasks required of practice-ready graduates. This review provides an overview of a single program's process for developing program-defined competencies and associated milestones. Beginning with a literature search, the program was able to develop a working list of competencies that was then further refined into competencies with building block milestones that support the development of competency in various domains. Involving faculty in defining a program's competencies is an Accreditation Review Commission on Education for the Physician Assistant requirement that can be done from the ground up or by using previously published competencies that are refined and tailored for the program. The process of creating the competencies provides significant insight into a program's curriculum, goals and expectations for students, and assessment methods.
Clinical outcomes in patients with unintended pregnancy after liver transplantation: A multicenter registry cohort study
Authors: Walia Anjali , Yin Ophelia , Coscia Lisa , Afshar Yalda , Irani Roxanna , Constantinescu Serban , Moritz Michael , Sarkar Monika 
Published: October 2024

The consequences of unintended pregnancy in recipients of liver transplants (LTs), a growing part of the high-risk obstetric population, remain unknown. To fill this gap, we conducted a retrospective registry cohort study to describe the risk factors, obstetric and neonatal morbidity, and graft outcomes associated with unintended pregnancy after LT. This study utilized the Transplant Pregnancy Registry International and included 565 pregnancies of recipients of LT between 1967 and 2019 from 289 hospitals, primarily in North America. The primary outcome of acute cellular rejection and secondary outcomes of graft loss, severe maternal morbidity, and neonatal composite morbidity were compared by pregnancy intention. The study population included 60.9% with intended pregnancies and 39.1% with unintended pregnancies. Recipients with unintended pregnancy were more likely to self-report as Black race, to be younger, nulliparous, and to have exposure to teratogenic immunosuppression. Acute cellular rejection was more common with unintended pregnancy (3.7% vs. 1.2%, p=0.047). Unintended pregnancies had lower median birth weight (2806.6 vs. 2948.4 g, p=0.033). Unintended pregnancy was not associated with increased neonatal morbidity or severe maternal morbidity. These findings underscore the importance of family planning counseling, access to safe and effective contraceptive options, as well as multidisciplinary prenatal care in the growing population of recipients of reproductive-aged LT.
Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells
Authors: Gould Seth , Herron Ansley , Davis Jonathan , Phillips Mollie , Chakrabarti Mrinmay , Evans Colin E. 
Published: October 2024

Purpose of review
Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies. We also describe studies of metabolic interventions that aim to inhibit ALI/ARDS and/or promote post-sepsis vascular repair, including those that target endothelial cell metabolites, endothelial cell metabolic signaling pathways, and endothelial cell metabolism.

Recent findings
Endothelial cells are integral to both the injury and repair phases of ALI/ARDS. During the injury phase of ALI/ARDS, lung endothelial cell survival decreases, and lung endothelial cell-to-endothelial cell (EC-EC) junctions are weakened. During the repair phase after sepsis-induced lung injury, lung endothelial cell proliferation and lung EC-EC junction reannealing occur. These crucial aspects of ALI/ARDS and post-sepsis vascular repair, that is, endothelial cell viability, growth, and junction integrity, are controlled by a myriad of metabolites and metabolic signaling pathways in endothelial cells.

Summary
Metabolic signaling pathways in endothelial cells represent a novel class of putative targets for the prevention and treatment of sepsis-induced inflammatory lung injury. Therapies that target metabolic signaling in endothelial cells are currently being explored as potential treatments for sepsis-induced inflammatory lung injury.
Distinct roles of size-defined HDL subpopulations in cardiovascular disease
Authors: Davidson W. Sean , Vaisar Tomas , Heinecke Jay W. , Bornfeldt Karin E. 
Published: October 2024

Purpose of review
Doubts about whether high-density lipoprotein-cholesterol (HDL-C) levels are causally related to atherosclerotic cardiovascular disease (CVD) risk have stimulated research on identifying HDL-related metrics that might better reflect its cardioprotective functions. HDL is made up of different types of particles that vary in size, protein and lipid composition, and function. This review focuses on recent findings on the specific roles of HDL subpopulations defined by size in CVD.

Recent findings
Small HDL particles are more effective than larger particles at promoting cellular cholesterol efflux because apolipoprotein A-I on their surface better engages ABCA1 (ATP binding cassette subfamily A member 1). In contrast, large HDL particles bind more effectively to scavenger receptor class B type 1 on endothelial cells, which helps prevent LDL from moving into the artery wall. The specific role of medium-sized HDL particles, the most abundant subpopulation, is still unclear.

Summary
HDL is made up of subpopulations of different sizes of particles, with selective functional roles for small and large HDLs. The function of HDL may depend more on the size and composition of its subpopulations than on HDL-C levels. Further research is required to understand how these different HDL subpopulations influence the development of CVD.
Analysis of factors influencing the surgical treatment outcomes of spinal injuries in polytrauma patients
Authors: Sun Xiangyao , Huang Jiang , Wang Weiliang , Gan Limeng , Cao Li , Liu Yuqi , Sun Siyuan , Wang Juyong , Lu Shibao 
Published: October 2024

Background:
This study aims to analyze the diagnosis and treatment conditions of polytrauma patients with spinal injuries, to clarify the site of the first surgical intervention, the timing of the surgery, and factors influencing prognosis.

Methods:
This study collected and analyzed data on polytrauma patients with spinal injuries who were treated from January 2017 to January 2023. Data collected primarily included basic patient information, treatment strategy-related information, clinical scoring systems, imaging parameters, and prognosis. The impacts of relevant variables on postoperative survival outcomes were analyzed.

Results:
This study included 60 patients. There was no significant change in the number of patients rated ASIA grade E after 90 days of admission, while there was a significant increase in those rated grade D (P<0.001). Among the groups, patients operated on within less than 12 h had the highest number of ASIA grade A, while those operated on after more than 48 h had the highest number of ASIA grade E (P=0.003). The survival rate of patients who underwent their first spinal surgery between 12 and 48 h was significantly better than those operated earlier than 12 h or later than 48 h (P=0.047). Patients who experienced hemorrhagic shock postsurgery had the lowest survival rate (P<0.001). Only age (P=0.004) and the number of surgeries outside the spine (P=0.033), as covariates, were significantly correlated with patient mortality (R2=0.519).

Conclusions:
Performing spinal surgery too early or too late can adversely affect patient outcomes; the appropriate timing of surgery should be chosen based on the specific characteristics of the patient. In polytrauma patients under emergency conditions, the use of combined surgical treatments should be minimized to prevent the occurrence of a ‘second hit’. Patients who experience hemorrhagic shock have the worst postsurgical survival; targeted treatment should be administered upon hospital admission.
MELAS Presenting as Bilateral Symmetric Occipital and Temporal Cortices Lesions
Authors: Liu Qing , Wang Zhaoxia , Shi Jing , Wang Wenxia , Wen Chao , Zhu Yanping , Chen Xuan , Xing Xiaolian , Su Yangli 
Published: October 2024

Introduction:
Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS) is one of the most common maternally inherited mitochondrial diseases. The stroke-like episode affecting the cortical cortex is the hallmark of MELAS; however, it rarely presents as simultaneously bilateral symmetric cortices lesions.

Case Report:
We reported a case of MELAS in a 46-year-old female patient with bilateral symmetric occipital and internal temporal cortices involvements on brain magnetic resonance imaging (MRI). A literature review of MELAS patients and a retrospective analysis were performed. She had a family history of diabetes. Although she denied a history of diabetes, elevated blood glucose was noted after admission, and diabetes was diagnosed. Laboratory examination revealed elevated lactate acid and creatine kinase levels in blood. Cranial computed tomography (CT) image demonstrated basal ganglia calcification, as well as subtle decreased attenuation in bilateral symmetric occipital and internal temporal cortices. Brain magnetic resonance imaging (MRI) demonstrated symmetric gyriform hyperintensity in bilateral occipital lobes and internal temporal lobes in both grey and white matter on fluid-attenuated inversion recovery (FLAIR) images with restricted diffusion on diffusion weighted images (DWI). A genetic test revealed a point mutation in the mtDNA(3243A > G) by blood examination. Literature review showed that there were 231 eligible patients with MELAS identified from 212 published papers. Symmetric cortical involvements were seen in 15 (6.5%) patients on brain MRI.

Conclusions:
MELAS should be considered as a potential diagnosis in the patients with bilateral symmetric stroke-like cortices lesions.
SS18-SSX Expression and Clinicopathologic Profiles in a Contemporary Cohort of Primary Paratesticular Synovial Sarcoma
Authors: Lobo Anandi , Mishra Sourav K. , Acosta Andres M. , Kaushal Seema , Akgul Mahmut , Williamson Sean R. , Sangoi Ankur R. , Aron Manju , Kandukuri Shivani R. , Shinde Sayali , Sharma Shivani , Jain Ekta , Dhillon Jasreman , Deshwal Akansha , Peddinti Kamal , Jaiswal Sunil , Das Sthiti , Kapoor Rahul , Biswas Ghanashyam , Pradhan Manas R. , Osunkoya Adeboye O. , Pradhan Dinesh , Chakrabarti Indranil , Jha Shilpy , Parwani Anil V. , Shah Rajal B. , Amin Mahul B. , Cheng Liang , Mohanty Sambit K. 
Published: October 2024

Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30 y). The tumor size ranged from 4​​​​​​ to 15 cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10 mo). Four patients died of metastatic disease (range: 5 to 16 mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.
Sex differences in tuberculosis infection and disease among people with HIV
Authors: Chaisson Lelia H. , Durovni Betina , Umar Nasir , Cohn Silvia , Moulton Lawrence H. , Scully Eileen , Cavalcante Solange , Golub Jonathan E. , Chaisson Richard E. , Saraceni Valeria 
Published: October 2024

Objectives:
Worldwide, adult men experience an excess burden of tuberculosis (TB) disease compared with women, but few studies have examined sex differences in TB among people with HIV. In this study, we aimed to investigate sex differences in TB infection and disease among people with HIV in Rio de Janeiro, Brazil.

Design:
Analysis of data from a randomized controlled trial and retrospective cohort study.

Methods:
We analyzed data from two studies conducted between 2005 and 2017. The THRio Study (2005–2012) evaluated increasing tuberculin skin testing (TST) and TB preventive therapy (TPT), and Universal ART in Rio study (UnivART; 2010–2017) was a virtual cohort study of people with HIV and TB with data from four national electronic registries.

Results:
Among 4606 people with HIV in THRio, 2992 (65.0%) had a TST placed and read, of whom 312 of 1865 (17%) males and 203 of 1127 (18%) females (P = 0.37) had prevalent TB infection. TB disease incidence was higher among males compared with females overall [IRR 1.33, 95% confidence interval (95% CI) 1.04–1.69], among males compared with females who did not receive TPT [incidence rate ratios (IRR) 1.30, 95% CI 1.01–1.67], and among males compared with females on ART (IRR 1.64, 95% CI 1.17–2.29). Among 54 957 people with HIV in UnivART, TB disease incidence rates were higher among males than females overall (IRR 1.28, 95% CI 1.18–1.39), among males compared with females on ART (IRR 1.58, 95% CI 1.40–1.77), and among males compared with females not on ART (IRR 1.11, 95% CI 0.99–1.25).

Conclusion:
In this medium TB and HIV burden setting, TB disease incidence was higher among males than females with HIV, despite similar prevalence of TB infection.
Biomarkers of microbial translocation and generalized inflammation are associated with frailty among people with HIV
Authors: Ruderman Stephanie A. , Hunt Peter W. , Beck-Engeser Gabriele , Ambayec Gabrielle , Willig Amanda L. , Saag Michael S. , Napravnik Sonia , Cachay Edward , Bamford Laura , Landay Alan , Drumright Lydia N. , Mixson L. Sarah , Whitney Bridget M. , Nance Robin M. , Kitahata Mari M. , Crane Heidi M. , Delaney Joseph A.C. , Hahn Andrew W. 
Published: October 2024

Background:
Frailty occurs at higher rates and younger ages among people with HIV (PWH) compared with the general population and is often attributed to chronic inflammation and subsequent immune exhaustion. We assessed how inflammatory biomarkers are associated with frailty among PWH.

Methods:
The Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems (CNICS) cohort is comprised of adult PWH in care at 10 sites, and harmonizes demographic, clinical, and patient-reported outcomes (PRO) data. A panel of 13 inflammatory biomarkers was collected from a subset of virally suppressed PWH once per person between 2010 and 2018. Frailty was measured with a validated PRO phenotype, scored 0–4, from biomarker collection date through July 2022. With adjusted linear mixed models, we estimated longitudinal associations between standard deviation-scaled log2-transformed biomarkers and frailty score.

Results:
Among 273 PWH, most were men (91%), average age at baseline was 45, 42% were non-Hispanic White whereas 35% were non-Hispanic Black, and average follow-up time was 5.5 years. Several biomarkers were associated with higher frailty, including those linked to microbial translocation (sCD14, LBP, KT ratio) and systemic inflammation (CRP, IL-6, suPAR, sTNFR1, sTNFR2). Higher IL-6 was associated with a 0.25-point higher frailty score [95% confidence interval (CI) 0.12–0.39]. Higher sTNFR1 [0.35 (0.13–0.56)], sCD14 [0.21 (0.11–0.31)], and suPAR [0.24 (0.11–0.36)] levels were also associated with higher frailty scores over follow-up.

Conclusion:
Higher levels of biomarkers linked to microbial translocation and systemic inflammation are associated with higher average frailty scores over time in a cohort of virally suppressed PWH, highlighting these pathways as potential interventional targets for mitigating frailty in PWH.
FLUID OVERLOAD MODIFIES HEMODYNAMIC IMPACT OF CONTINUOUS RENAL REPLACEMENT THERAPY: EVIDENCE OF A COVERT CARDIORENAL SYNDROME?
Authors: Thadani Sameer , Lang Anna , Silos Christin , Price Jack , Gelbart Ben , Typpo Katri , Horvat Christopher , Fuhrman Dana Y. , Neumayr Tara , Arikan Ayse Akcan 
Published: October 2024

ABSTRACT

Background: Fluid overload (FO) in critically ill children correlates with higher morbidity and mortality rates. Continuous renal replacement therapy (CRRT) is commonly employed to manage FO. In adults, both FO and CRRT adversely affect myocardial function. It remains unclear if children experience similar cardiovascular effects. Methods: Observational single-center study on children (<18 years) receiving CRRT at Texas Children’s Hospital from 11/2019 to 3/2021. Excluded were those with end-stage renal disease, pacemakers, extracorporeal membrane oxygenation, ventricular assist devices, apheresis, or without an arterial line. Electrocardiometry (ICON Osypka Medical GmbH, Berlin, Germany) which is noninvasive and utilizes bioimpedance, was applied to obtain hemodynamic data over the first 48 h of CRRT. Our aim was to identify how FO >15% affects hemodynamics in children receiving CRRT. Results: Seventeen children, median age 43 months (interquartile range [IQR] 12–124), were included. The median FO at CRRT initiation was 14.4% (2.4%–25.6%), with 9 (53%) patients having FO >15%. Differences were noted in systemic vascular resistance index (1,277 [IQR 1088–1,666] vs. 1,030 [IQR 868–1,181] dynes/s/cm5/m2, P < 0.01), and cardiac index (3.90 [IQR 3.23–4.75] vs. 5.68 [IQR 4.65–6.32] L/min/m2, P < 0.01), with no differences in heart rate or mean arterial pressure between children with and without FO. Conclusion: FO affects the hemodynamic profile of children on CRRT, with those having FO >15% showing higher systemic vascular resistance index and lower cardiac index, despite heart rate and mean arterial pressure remaining unchanged. Our study illustrates the feasibility and utility of electrocardiometry in these patients, suggesting future research employ this technology to further explore the hemodynamic effects of dialysis in children.
ZBTB16 DRIVES VASCULAR CALCIFICATION THROUGH ACCELERATING VSMCS OSTEOBLASTIC TRANSITION IN CHRONIC KIDNEY DISEASE VIA WNT/Β-CATENIN PATHWAY
Authors: Shen Yan , Huang Huaxing , Shen Lianglan , Yao Wubin , Wang Rong , Kang Meizi , Huang Jiashan , Xie Yan , Yang Hongli 
Published: October 2024

ABSTRACT
Chronic kidney disease (CKD)-related vascular calcification (VC) is a common degenerative phenomenon of the vessel wall and its pathological basis is the phenotypic transformation of vascular smooth muscle cells (VSMCs). Zinc finger and BR-C (Broad-Complex), ttk (tramtrack), and bab (bric à brac) (BTB) domain containing 16 (ZBTB16) have been reported to be expressed in the aortic tissues in a rat model of VC. This work is conducted to reveal the functions of ZBTB16 on VC in CKD and to probe its involved reaction mechanisms. In vivo CKD rat models were established by adenine and VSMC calcification were stimulated with high phosphate (Pi) in vitro. Renal function indexes were estimated with relevant assay kits. Renal tissues were histologically examined with hematoxylin and eosin staining. Alizarin red and von kossa staining were used to measure arterial calcification. Reverse transcription-quantitative PCR and western blot were used to detect ZBTB16 expression. Western blot, immunohistochemistry, and immunofluorescence staining were used to detect osteogenic markers and smooth muscle cell markers. Western blot was used to measure the expressions of proteins implicated in Wnt/β-catenin pathway. In the blood samples of CKD patients with VC, aortic tissues of CKD rats, and Pi-treated VSMCs, ZBTB16 expression was significantly increased. ZBTB16 knockdown reduced renal dysfunction, calcium deposition and inhibited VSMCs osteoblast differentiation both in vitro and in vivo. Moreover, silencing with ZBTB16 inactivated Wingless-related integration site (Wnt)/β-catenin pathway. LiCl (Wnt/β-catenin agonist) reversed the protective effects of ZBTB16 knockdown on the calcification and osteoblastic transformation in vitro. Together, ZBTB16 silencing may downregulate Wnt/β-catenin pathway to protect against CKD-associated VC via repressing the osteoblastic transformation of VSMCs.