bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Authors: Bhandari Rajan , Yang Heetaek , Kosarek Noelle N , Smith Avi E , Garlick Jonathan A , Hinchcliff Monique , Whitfield Michael L , Pioli Patricia A 
Published: August 2022

Abstract

Objectives
Prior work demonstrates that co-cultured macrophages and fibroblasts from patients with SSc engage in reciprocal activation. However, the mechanism by which these cell types communicate and contribute to fibrosis and inflammation in SSc is unknown.

Methods
Fibroblasts were isolated from skin biopsies obtained from 7 SSc patients or 6 healthy age and gender-matched control subjects following written informed consent. Human donor-derived macrophages were cultured with exosomes isolated from control or SSc fibroblasts for an additional 48 h. Macrophages were immunophenotyped using flow cytometry, qRT-PCR and multiplex. For mutual activation studies, exosome-activated macrophages were co-cultured with SSc or healthy fibroblasts using Transwells.

Results
Macrophages activated with dermal fibroblast-derived exosomes from SSc patients upregulated surface expression of CD163, CD206, MHC Class II and CD16 and secreted increased levels of IL-6, IL-10, IL-12p40 and TNF compared with macrophages incubated with healthy control fibroblasts (n = 7, P &lt; 0.05). Exosome-stimulated macrophages and SSc fibroblasts engaged in reciprocal activation, as production of collagen and fibronectin was significantly increased in SSc fibroblasts receiving signals from SSc exosome-stimulated macrophages (n = 7, P &lt; 0.05).

Conclusion
In this work, we demonstrate for the first time that human SSc dermal fibroblasts mediate macrophage activation through exosomes. Our findings suggest that macrophages and fibroblasts engage in cross-talk in SSc skin, resulting in mutual activation, inflammation, and extracellular matrix (ECM) deposition. Collectively, these studies implicate macrophages and fibroblasts as cooperative mediators of fibrosis in SSc and suggest therapeutic targeting of both cell types may provide maximal benefit in ameliorating disease in SSc patients.
First-Episode Psychosis Patients Who Deteriorated in the Premorbid Period Do Not Have Higher Polygenic Risk Scores Than Others: A Cluster Analysis of EU-GEI Data
Authors: Ferraro Laura , Quattrone Diego , La Barbera Daniele , La Cascia Caterina , Morgan Craig , Kirkbride James B , Cardno Alastair G , Sham Pak , Tripoli Giada , Sideli Lucia , Seminerio Fabio , Sartorio Crocettarachele , Szoke Andrei , Tarricone Ilaria , Bernardo Miquel , Rodriguez Victoria , Stilo Simona A , Gayer-Anderson Charlotte , de Haan Lieuwe , Velthorst Eva , Jongsma Hannah , Bart Rutten B P , Richards Alexander , Arango Celso , Menezez Paulo Rossi , Lasalvia Antonio , Tosato Sarah , Tortelli Andrea , Del Ben Cristina Marta , Selten Jean-Paul , Jones Peter B , van Os Jim ,   The WP2 EU-GEI Group, Di Forti Marta , Vassos Evangelos , Murray Robin M 
Published: August 2022

Abstract
Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean_IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ_PRS than controls [F(4,1319) = 20.4, P &lt; .001]. Among the clusters, the deteriorating group had lower SCZ_PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use.
Services, Jobs, and Economic Development in Africa
Authors: Baccini Leonardo , Fiorini Matteo , Hoekman Bernard , Sanfilippo Marco 
Published: August 2022

Abstract
This article presents data and analyzes the structure of employment in 13 African economies at the administrative unit level, with a focus on the role of services. We provide two novel pieces of evidence. First, we present a descriptive snapshot of changes in the composition of employment over time and across geographies. This reveals evidence of structural transformation toward services and service-related occupations at subnational level and provides a fine-grained overview of who works in services and where and how this has changed over time. Second, we provide correlations between services and economic development, using per capita nightlight luminosity as a proxy. We document (1) a strong positive association between high skills services and economic development; (2) substantial heterogeneity across industries within services; and (3) a mediating role of market conditions and technology in the relation between services and economic development. Overall, our work highlights an important role of services activities for employment, skills, and economic development in Africa.
Ambroxol, a mucolytic agent, boostsHO‐1, suppressesNF‐κB, and decreases the susceptibility of the inflamed rat colon to apoptosis: A new treatment option for treating ulcerative colitis
Authors: Cavalu Simona , Sharaf Hossam , Saber Sameh , Youssef Mahmoud E. , Abdelhamid Amir Mohamed , Mourad Ahmed A. E. , Ibrahim Samar , Allam Shady , Elgharabawy Rehab Mohamed , El‐Ahwany Eman , Amin Noha A. , Shata Ahmed , Eldegla Mai , Atef Marina , Aboraya Maii , Mohamed Mayar , Anz Niera , Elmotelb Dina Abd , Gabr Fayrouz , Elzablawy Dalia , Hamada Menna , Yehia Amr , Osama Dalia , Mohammed Osama A. 
Published: August 2022

AbstractUlcerative colitis (UC) is a chronic inflammatory bowel disease of unknown etiology that increases the risk of developing colorectal cancer and imposes a lifelong healthcare burden on millions of patients worldwide. Current treatment strategies are associated with significant risks and have been shown to be fairly effective. Hence, discovering new therapies that have better efficacy and safety profiles than currently exploited therapeutic strategies is challenging. It has been well delineated that NF‐κB/Nrf2 crosstalk is a chief player in the interplay between oxidative stress and inflammation. Ambroxol hydrochloride, a mucolytic agent, has shown antioxidant and anti‐inflammatory activity in humans and animals and has not yet been examined for the management of UC. Therefore, our approach was to investigate whether ambroxol could be effective to combat UC using the common acetic acid rat model. Interestingly, a high dose of oral ambroxol (200 mg/kg/day) reasonably improved the microscopic and macroscopic features of the injured colon. This was linked to low disease activity and a reduction in the colonic weight/length ratio. In the context of that, ambroxol boosted Nrf2 activity and upregulated HO‐1 and catalase to augment the antioxidant defense against oxidative damage. Besides, ambroxol inactivated NF‐κB signaling and its consequent target pro‐inflammatory mediators, IL‐6 and TNF‐α. In contrast, IL‐10 is upregulated. Consistent with these results, myeloperoxidase activity is suppressed. Moreover, ambroxol decreased the susceptibility of the injured colon to apoptosis. To conclude, our findings highlight the potential application of ambroxol to modify the progression of UC by its anti‐inflammatory, antioxidant, and antiapoptotic properties.
Transforming Clinical Education During a Global Pandemic: Building New Approaches to Clinical Education
Authors: Rembish Melissa , Snyder Marianne , Sarage Dawn , Spadafora Nancy , Alexander Ivy M. 
Published: August 2022

Abstract
The sudden and severe impact of COVID-19 on nursing education brought about many challenges and opportunities. The Community of Inquiry model and Online Collaborative Learning theory provided a guiding framework for preparing faculty to develop curriculum and deliver online/virtual synchronous clinical and laboratory experiences for junior and senior nursing students, overcome identified challenges, and evaluate the experiences. The swift change to virtual clinical education required careful reflection about how we teach, evaluate learning, and move forward with precision while establishing new best practices.
Facilitating Residents’ Understanding of Electronic Health Record Report Card Data Using Faculty Feedback and Coaching
Authors: Sebok-Syer Stefanie S. , Shaw Jennifer M. , Sedran Robert , Shepherd Lisa , McConnell Allison , Dukelow Adam M. , Syer Mark D. , Lingard Lorelei 
Published: August 2022

Purpose
Feedback continues to present a challenge for competency-based medical education. Clear, consistent, and credible feedback is vital to supporting one’s ongoing development, yet it can be difficult to gather clinical performance data about residents. This study sought to determine whether providing residents with electronic health record (EHR)-based report cards, as well as an opportunity to discuss these data with faculty trained using the R2C2 model, can help residents understand and interpret their clinical performance metrics.

Method
Using action research methodology, the author team collected EHR data from July 2017 to February 2020, for all residents (n = 21) in one 5-year Emergency Medicine program and created personalized report cards for each resident. During October 6–17, 2020, 8 out of 17 eligible residents agreed to have their feedback conversations recorded and participate in a subsequent interview with a nonphysician member of the research team. Data were analyzed using thematic analysis, and the authors used inductive analysis to identify themes in the data.

Results
In analyzing both the feedback conversations as well as the individual interviews with faculty and residents, the authors identified 2 main themes: (1) Reactions and responses to receiving personalized EHR data and (2) The value of EHR data for assessment and feedback purposes. All participants believed that EHR data metrics are useful for prompting self-reflection, and many pointed to their utility in providing suggestions for actionable changes in their clinical practice. For faculty, having a tool through which underperforming residents can be shown “objective” data about their clinical performance helps underscore the need for improvement, particularly when residents are resistant.

Conclusions
The EHR is a valuable source of educational data, and this study demonstrates one of the many thoughtful ways it can be used for assessment and feedback purposes.
Optimizing Clinical Reasoning Assessments With Analytic and Holistic Ratings: Examining the Validity, Reliability, and Cost of a Simplified Patient Note Scoring Procedure
Authors: Cheung Jeffrey J.H. , Park Yoon Soo , Aufderheide Kassidee , Holden Jaime , Yudkowsky Rachel 
Published: August 2022

Purpose
Post-standardized patient (SP) encounter patient notes used to assess students’ clinical reasoning represent a significant time burden for faculty who traditionally score them. To reduce this burden, the authors previously reported a complex faculty-developed scoring method to assess patient notes rated by nonclinicians. The current study explored whether a simplified scoring procedure for nonclinician raters could further optimize patient note assessments by reducing time, cost, and creating additional opportunities for formative feedback.

Method
Ten nonclinician raters scored patient notes of 141 students across 5 SP cases by identifying case-specific patient note checklist items. The authors identified the bottom quintile of students using the proportion of correct items identified in the note (percent-scores) and case-specific faculty-generated scoring formulas (formula-scores). Five faculty raters scored a subset of notes from low, borderline, and high-performing students (n = 30 students) using a global rating scale. The authors performed analyses to gather validity evidence for percent-scores (i.e., relationship to other variables), investigate its reliability (i.e., generalizability study), and evaluate its costs (i.e., faculty time).

Results
Nonclinician percent- and formula-scores were highly correlated (r = .88) and identified similar lists of low-performing students. Both methods demonstrated good agreement for pass-fail determinations with each other (Kappa = .68) and with faculty global ratings (Kappapercent =.61; Kappaformula =.66). The G-coefficient of percent-scores was .52, with 38% of variability attributed to checklist items nested in cases. Using percent-scores saved an estimated $746 per SP case (including 6 hours of faculty time) in development costs over formula-scores.

Conclusions
Nonclinician percent-scores reliably identified low-performing students without the need for complex faculty-developed scoring formulas. Combining nonclinician analytic and faculty holistic ratings can reduce the time and cost of patient note scoring and afford faculty more time to coach at-risk students and provide targeted assessment input for high-stakes summative exams.
Racial/Ethnic Disparities in Clerkship Grading: Perspectives of Students and Teachers
Authors: Hanson Janice L. , Pérez Maria , Mason Hyacinth R.C. , Aagaard Eva M. , Jeffe Donna B. , Teherani Arianne , Colson Eve R. 
Published: August 2022

Purpose
Racial/ethnic disparities exist in clinical clerkship grading, yet little is known about medical student and faculty perspectives on why these disparities occur. This study explored what happens during clerkships that might explain grading disparities.

Method
Medical students and clerkship teachers at 3 U.S. medical schools completed a demographic survey and semistructured interview. The constant comparative method was used to analyze transcripts by inductively developing codes; grouping codes in categories; and refining codes, descriptions, and group assignments to identify themes. Interpretations of and relationships among themes were iteratively discussed to develop a grounded theory.

Results
Fifty-nine participants (29 medical students, 30 teachers [28 clinical faculty, 2 residents]) were interviewed in 2020. The Social Milieu of Medical Education (relationships, fit, opportunities, and judgments in the clinical-learning setting) was the organizing theme, influenced by 5 additional themes: Societal Influence (experiences in society), Students’ Characteristics and Background (personal characteristics and experiences outside medical school), Assessment Processes (collection of student performance data and how data inform grades), Learning Environment (resources available and messaging within the clinical setting), and Students’ Interactions and Reactions (interactions with and reactions to peers and teachers). The grounded theory highlights complex, multilayered aspects of how the social milieu of medical education is shaped by and shapes students’ experiences, relationships, and clerkship assessments and promotes clerkship-grading disparities.

Conclusions
Mitigating clerkship-grading disparities will require intervening on interrelated, contextual factors to provide equitable opportunities for students from diverse backgrounds and with varying styles of engagement in clinical-learning settings, along with attending to modifying assessment processes.
Medial Head of the Gastrocnemius Tenotomy Through a Posteromedial Approach Significantly Improves Surgical Accessibility of the Tibial Plateau
Authors: Cardon Jeffrey J. , DeKeyser Graham J. , Peterson Andrew C. , Higgins Thomas F. , Lenz Amy L. , Haller Justin M. 
Published: August 2022

Objectives:
Compare accessible area of the posterior tibial plateau through a modified posteromedial (PM) approach before and after tenotomy of the medial head gastrocnemius. We report the outcomes of 8 patients who underwent gastrocnemius tenotomy during PM approach.

Methods:
A modified PM approach was performed on 10 cadaveric legs, and the surgically accessible area was outlined. Next, a medial head gastrocnemius mid substance tenotomy was completed, and the accessible area was again outlined. Tibia specimens were imaged in a micro-CT scanner to measure accessible surface area and linear distance along the joint line. In addition, 8 patients who underwent tenotomy for tibial plateau fracture had outcomes recorded.

Results:
The modified PM approach with tenotomy provided significantly more access to the posterior plateau than without tenotomy. The modified PM approach before tenotomy allowed access to 1774 mm2 (SD = 274) of the posterior plateau surface and 2350 mm2 (SD = 421, P < 0.0001) with tenotomy. A linear distance of 38 mm (SD = 7) and 57 mm (SD = 7, P < 0.00001) was achieved before and after tenotomy, respectively. In the clinical series, the average knee arc of motion was 116 degrees (95–135).

Conclusions:
The modified PM approach with medial head gastrocnemius tenotomy significantly improves surgical access to the posterior plateau. Patients who received tenotomy have acceptable functional outcomes. This cadaveric study provides an alternative approach for treatment of posterolateral tibial plateau fractures which may mitigate damage to neurovascular structures.
Novel Neurocognitive Profile in a Minority of Boys with 47,XXY (Klinefelter Syndrome)
Authors: Samango-Sprouse Carole A. , Hamzik Mary P. , Khaksari Kosar , Brooks Michaela R. , Sadeghin Teresa , Gropman Andrea L. 
Published: August 2022

ABSTRACT:

Introduction:
47,XXY, also known as Klinefelter syndrome, is the most commonly occurring sex chromosomal variation (1:660). The neurocognitive profile of boys with 47,XXY, in addition to verbal abilities, language skills, and general intelligence, has been explored in this study.

Methods:
Fifty-five participants with 47,XXY were segregated into groups according to their performance on the Wechsler Intelligence Scale for Children (WISC): (1) those with a higher performance intelligence quotient (PIQ) in comparison with their verbal IQ (VIQ) and (2) those with a higher VIQ compared with their PIQ. Two-tailed independent t tests were completed to analyze group differences.

Results:
Our study results demonstrate novel findings that one-third of subjects have higher verbal capabilities than perceptual skills. Those participants who showed the typical presentation of 47,XXY with increased PIQ in comparison with their VIQ excelled on perceptual and visual spatial subtests on the WISC and on nonverbal IQ on the Leiter International Performance Scale-III. In addition, it was found that expressive and receptive vocabulary skills were commensurate in both groups, which has not been reported previously.

Discussion:
To the best of our knowledge, this is the first study to identify an alternative profile of 47,XXY with increased verbal capabilities in comparison with perceptual skills. In addition, previous research has found that boys with 47,XXY often show increased receptive vocabulary skills in comparison with their expressive vocabulary skills early in life. Therefore, our findings of commensurate expressive and receptive vocabulary skills suggest that age may be an impactful factor in vocabulary development. Further research is necessary to determine individualized treatment options for these patients, focusing on the specific cognitive profile they present.
Potent Periorbital Fractionated CO2 Laser Resurfacing
Authors: Watson Alison H. , Van Brummen Alexandra , Somogyi Marie B. , Homer Natalie , Nakra Tanuj 
Published: August 2022

BACKGROUND
The aged face results from a culmination of skin changes, gravitational descent, and volume loss. Surgical interventions in the periorbital region are beneficial for addressing these 3 factors. Despite this, studies describing CO2 laser safety settings are lacking.

OBJECTIVE
There is no present consensus on ideal periorbital CO2 laser; therefore, this study evaluates the safety of periorbital laser resurfacing as an adjunct to lower blepharoplasty using robust settings.

MATERIALS AND METHODS
A retrospective review was performed of all patients who underwent bilateral lower blepharoplasty with adjunctive periorbital (upper and lower eyelid) fractionated CO2 laser resurfacing from 2013 to 2018 performed by a single oculoplastic surgeon.

RESULTS
Fifty-nine patients were included. Six patients experienced side effects including postinflammatory hyperpigmentation, (3/59, 5.1%), prolonged superficial excoriations (1/59, 1.7%), prolonged hyperemia (1/59, 1.7%), and lower eyelid retraction requiring lower eyelid recession (1/59, 1.7%). None of the patients developed postoperative infection. All patient expressed satisfaction at their final postoperative visit.

CONCLUSION
CO2 laser resurfacing, even with robust settings, is a safe and effective adjunct to lower blepharoplasty.
Stabilizing Cardiac Ryanodine Receptor With Dantrolene Treatment Prevents Binge Alcohol–Enhanced Atrial Fibrillation in Rats
Authors: Greco Lisa V. , Migirov Allan , Ojamaa Kaie , Li Ying , Huang Yuan , Kobayashi Satoru , Udo-Bellner Lars , Stout Randy , Cohen Todd J. , Zhang Youhua 
Published: August 2022

Abstract:
Binge drinking is a risk factor for cardiac arrhythmias, known as the holiday heart syndrome. Atrial fibrillation (AF) is the most frequently diagnosed arrhythmia in this condition. Recent reports indicated that cardiac ryanodine receptor (RyR2) dysfunction and Ca2+ leak contribute to alcohol-enhanced AF. In this study, we investigated whether stabilizing RyR2 with dantrolene treatment can prevent alcohol-enhanced AF in rats. A binge drinking rat model was established with alcohol (2g/kg, IP) delivered once every other day for 4 times. The study consisted of following 3 groups: control group (n = 9), binge alcohol group (n = 10), and binge alcohol + dantrolene (A+D) group (dantrolene, 10 mg/kg, IP before each alcohol injection, n = 9). Echocardiography, left ventricular hemodynamics, in vivo atrial electrophysiology and AF inducibility test, RyR2 phosphorylation level, and blood norepinephrine level were studied 24 hours after the last injection. Ca2+ leak in isolated atrial myocytes from control and binge alcohol rats was examined. Binge alcohol significantly increased AF inducibility (1/9 in control vs. 8/9 in binge alcohol group, P < 0.05) and AF duration. Dantrolene treatment significantly reduced both AF inducibility (2/9 in dantrolene group, P < 0.05) and AF duration. Binge alcohol significantly increased Ca2+ leak in isolated atrial myocytes, which was reduced by dantrolene treatment. Blood norepinephrine,7 RyR2 phosphorylation level, cardiac echocardiography, and left ventricular hemodynamics were not significantly affected 24 hours after binge drinking. In conclusion, stabilizing RyR2 with dantrolene treatment significantly attenuated binge drinking–enhanced AF, suggesting that therapeutic strategies stabilizing RyR2 could be a preventive measure to blunt binge drinking–enhanced AF arrhythmogenesis.