bluuebunny/crossref_metadata_2025_split huggingface dataset:
FTY720 ameliorates experimental MPO-ANCA-associated vasculitis by regulating fatty acid oxidation via the neutrophil PPARα–CPT1a pathway
Authors: Wang Rui-Xue , Wang Luo-Yi , Han Xiang-Yu , Chen Su-Fang , Sun Xiao-Jing , Li Zhi-Ying , Little Mark A , Zhao Ming-Hui , Chen Min 
Published: June 2024

Abstract

Objectives
Increasing studies demonstrated the importance of C5a and anti-neutrophil cytoplasmic antibody (ANCA)-induced neutrophil activation in the pathogenesis of ANCA-associated vasculitis (AAV). Sphingosine-1-phosphate (S1P) acts as a downstream effector molecule of C5a and enhances neutrophil activation induced by C5a and ANCA. The current study investigated the role of a S1P receptor modulator, FTY720, in experimental autoimmune vasculitis (EAV) and explored the immunometabolism-related mechanisms of FTY720 in modulating ANCA-induced neutrophil activation.

Methods
The effects of FTY720 in EAV were evaluated by quantifying haematuria, proteinuria, crescent formation, tubulointerstitial injury and pulmonary haemorrhage. RNA sequencing of renal cortex and gene enrichment analysis were performed. The proteins of key identified pathways were analysed in neutrophils isolated from peripheral blood of patients with active AAV and normal controls. We assessed the effects of FTY720 on ANCA-induced neutrophil respiratory burst and neutrophil extracellular traps formation (NETosis).

Results
FTY720 treatment significantly attenuated renal injury and pulmonary haemorrhage in EAV. RNA sequencing analyses of renal cortex demonstrated enhanced fatty acid oxidation (FAO) and peroxisome proliferator-activated receptor (PPAR) signalling in FTY720-treated rats. Compared with normal controls, patients with active AAV showed decreased FAO in neutrophils. FTY720-treated differentiated HL-60 cells showed increased expression of carnitine palmitoyltransferase 1a (CPT1a) and PPARα. Blocking or knockdown of CPT1a or PPARα in isolated human neutrophils and HL-60 cells reversed the inhibitory effects of FTY720 on ANCA-induced neutrophil respiratory burst and NETosis.

Conclusion
FTY720 attenuated renal injury in EAV through upregulating FAO via the PPARα–CPT1a pathway in neutrophils, offering potential immunometabolic targets in AAV treatment.
IEnglish Language
Authors: Schönefeld Doris , Kostadinova Viktorija , Dreschler Gea , Rivas Tamara Bouso , Benczes Réka , Zhong Ai , Scott Maggie , Anderwald Lieselotte , Ahlers Wiebke , Vida-Mannl Manuela , Al-Thubaiti Kholoud A , Cogo Alessia , Ting Shawnea Sum Pok , Parise Ida , Da Silva Juliana Souza , Reber Elisabeth , Adam Naomi , Stradling Fransina 
Published: June 2024

Abstract
This chapter has fourteen sections: 1. General; 2. History of English Linguistics; 3. Phonetics and Phonology will resume next year; 4. Morphology; 5. Syntax; 6. Semantics; 7. Lexicography, Lexicology, and Lexical Semantics; 8. Onomastics; 9. Dialectology and Sociolinguistics; 10. New Englishes and Creolistics; 11. Second Language Acquisition; 12. English as a Lingua Franca; 13. Pragmatics and Discourse Analysis; 14. Stylistics. Section 1 is by Doris Schönefeld; section 2 is by Viktorija Kostadinova; sections 4 and 5 are by Gea Dreschler and Tamara Bouso Rivas; section 6 is by Réka Benczes; section 7 is by Ai Zhong; section 8 is by Maggie Scott; section 9 is by Lieselotte Anderwald; section 10 is by Manuela Vida-Mannl and Wiebke Ahlers; section 11 is by Kholoud A. Al-Thubaiti; section 12 is by Alessia Cogo, Shawnea Sum Pok Ting, Ida Parise, and Juliana Souza Da Silva; section 13 is by Elisabeth Reber; section 14 is by Naomi Adam and Fransina Stradling.
Leadership Experiences and Perceptions of Mid-Career to Senior Clinician-Scientists: A Qualitative Exploration
Authors: Greene Amanda K. , Szczygiel Lauren A. , Thomas J. Denard , Jones Rochelle D. , Cutter Christina M. , Feldman Eva L. , Kerr Eve A. , Paradis Kelly C. , Settles Isis H. , Singer Kanakadurga , Spector Nancy D. , Stewart Abigail J. , Telem Dana , Ubel Peter A. , Jagsi Reshma 
Published: June 2024

Abstract

Purpose
This study aimed to elucidate the experiences and perceptions of mid-career to senior clinician-scientists in academic medicine regarding pursuing, attaining, or rejecting leadership roles as well as their conceptualization of the influence of leadership in their broader career trajectories.

Method
The authors conducted a qualitative analysis of in-depth, semistructured interviews conducted in 2022 with a diverse sample of clinician-scientists who received new National Institutes of Health K08 or K23 Career Development Awards between 2006 and 2009. A total of 859 of the 915 survey respondents (94%) were eligible to be recruited for the qualitative study. Qualitative analysis was informed by thematic analysis and used a social constructionist approach to understanding participants’ conceptualizations of their experiences. Interview transcripts were coded using an iterative, inductive coding process. Themes were generated by reviewing coded data and identifying common patterns in participant narratives, affording particular attention to participants’ discussion of the effect of race and/or gender on their leadership experiences.

Results
Sixty clinician-scientists participated in individual interviews. Five themes were generated surrounding participants’ conceptualizations of their leadership experiences. Themes were (1) feeling unprepared for leadership roles, (2) reluctance and lack of intention in attaining leadership positions, (3) influence of networks on leadership access and decision-making, (4) impact-related benefits and downsides of leadership, and (5) confining ideas of who leaders are.

Conclusions
The study highlighted the need for formal leadership training in academic medicine and the importance of mentorship and sponsorship in attaining and succeeding in leadership positions. Individuals from communities underrepresented in leadership positions faced additional challenges internalizing a leadership identity. Efforts to encourage current leaders to engage in intentional succession planning and development of faculty toward leadership roles, including expansion of institutional leadership development programs, are needed to promote equitable distribution of leadership opportunities.
Using Community Engagement to Move Upstream to Address Social Determinants of Health
Authors: Jones Ross , Bilello Lori , Knight Ann-Marie , Livingood William C. , Whitner Chardaé , Webb Fern 
Published: June 2024

Abstract
Given its role as a safety net institution, the University of Florida Health (UF Health) Jacksonville has responded to the community’s needs through partnerships with the community for decades. Such academic-community partnerships have a broad emphasis on population health and primary care that expands the model of care to include community engagement, which allows such partnerships to promote health and well-being and reduce health inequalities by addressing social determinants of health (SDOH).
This report describes the UF Health Jacksonville and University of Florida College of Medicine—Jacksonville’s creation of the Urban Health Alliance (UHA) in June 2019 due to continued poor health outcomes and inequities within the community. The mission of the UHA is to improve community health using community-focused, self-sustainable strategies and solutions to impact SDOH (i.e., more upstream interventions). Using the tenets of the collective impact model, the UHA acts as a backbone organization to achieve these objectives by empowering community partners to affect changes in policy, systems, and other structures necessary for the optimal health of the community. The UHA’s work is divided across 4 pillars: services, research, education, and policy. These pillars reflect the traditional missions of academic medical centers—clinical care, research, and education—and the need to address structural changes to improve community health—namely, policy. By addressing the issues that most impact the patients and community of UF Health Jacksonville, the UHA can serve as an example of how an academic medical center can use the traditional missions to improve the community’s health and move toward health equity.
New tools for learning airway management
Authors: Onrubia Xavier , Martínez Estefanía , Charco Pedro , Baldó Joana , Reviriego Laura , Greif Robert 
Published: June 2024

INTRODUCTION
Game-based learning, also called edutainment, has been promoted as an alternative to the unidirectional, passive teaching of traditional medical education. Solving enigmas and problems through creativity and critical thinking, which is encapsulated in ‘escape rooms’, has been adapted to teach medicine as a way to enhance the mental models of proceeding.
We considered an educational escape room as an activity to promote teaching and training in airway management, integrating knowledge, technical and nontechnical skills and collaborative teamwork during crisis situations.

METHODS
No published experience on this topic was found. Therefore, we created an educational escape room focused on airway management.
We describe the steps undertaken from the design and development of the escape room process (as part of the curriculum of an international airway course) to the results of a survey completed by the participants at the end of the escape room process.

RESULTS
Satisfaction with the experience was rated at least 8 points (0 to 10 numerical rating scale) by 80% of the 147 course participants. Two thirds also rated the experience as at least 8 points (0 to 10 Likert scale) as being helpful in improving behaviour in real cases, and enhance organisational teamwork skills.

CONCLUSION
The airway escape room was feasible for training in airway management. Participants rated it as valuable to gain team competencies. The experience encourages further development and its possible use in other clinical settings.
TcPO2 changes are more pronounced than SpO2 changes during simulated altitude changes in a hypobaric oxygen chamber: a nonrandomized controlled trial
Authors: Li Yang , Chen Liang , Fu Ziyu , Wang Zhiwei , Sun Shijun , Luan Xiaorong , Ma Dedong , Hu Tianliang 
Published: June 2024

Abstract

Background
Hypoxia is a significant risk factor of hypertension. However, no studies have used transcutaneous tissue partial pressure of oxygen (TcPO2) and partial pressure of carbon dioxide (TcPCO2) monitors to measure the respective partial pressures in healthy individuals. Oxygen saturation (SpO2) is often used for traditional monitoring of vital signs. This study investigated the changes in TcPO2 and SpO2 values during rapid changes in altitude. The trial was registered at ClinicalTrials.gov (registration no. NCT06076057).

Methods
Healthy adult volunteers were instructed to sit vertically in a hypobaric oxygen chamber, which ascended from 0 m to 2500 m at a uniform speed within 10 min. The Danish Radiometer TCM4 was used to measure TcPO2 and TcPCO2 with the ventral side of the upper arm as the measurement site. The Shenzhen Kerokan P0D-1 W pulse oximeter was used to measure heart rate and SpO2, with values recorded once every 500 m.

Results
Altogether, 49 healthy volunteers were recruited between March 2023 and August 2023. With increasing altitude, TcPO2 and SpO2 decreased significantly (P < 0.01). During the ascent from 0 m, TcPO2 began to change statistically at 500 m (P < 0.05), whereas SpO2 began to change statistically at 1000 m (P < 0.05). At the same altitude, the difference in TcPO2 was greater than the difference in SpO2. At 1000 m, there were statistically significant changes in TcPO2 and SpO2 (P < 0.001). At altitudes >500 m, statistical significance was identified between TcPO2 in both sexes (P < 0.05). Statistical significance in TcPCO2 and heart rate was observed at the different elevations (P < 0.05).

Conclusion
In acutely changing low-pressure hypoxic environments, TcPO2 changed more dramatically than SpO2.
Metformin-Induced Proprotein Convertase Subtilisin/Kexin Type 9 Inhibition Further Decreases Low-Density Lipoprotein Cholesterol Following Statin Treatment in Patients With Coronary Artery Disease and Without Diabetes
Authors: Hu Die , Qin Donglu , Kuang Jie , Yang Yang , Weng Shuwei , Chen Jin , Wu Sha , Wang Shuai , Mao Ling , Peng Daoquang , Yu Bilian 
Published: June 2024

Abstract:
In vitro investigations have established metformin's capacity to downregulate proprotein convertase subtilisin/kexin type 9 (PCSK9) expression, suggesting a potential beneficial effect on atherogenic lipoprotein particles when combined with metformin therapy. Our objective was to assess whether metformin could mitigate statin-induced adverse effects on PCSK9, thereby improving lipid profiles in patients with coronary artery disease (CAD) but without diabetes. Employing an open-label, placebo-controlled, randomized trial, we randomized patients with CAD but without diabetes into CLA (cholesterol-lowering agents alone: atorvastatin ± ezetimibe, n = 38) and Met + CLA groups (metformin plus CLA, n = 33) in a 1:1 ratio. The primary end point was the therapeutic impact of 1-month metformin combination treatment on low-density lipoprotein cholesterol (LDL-C) and PCSK9 levels. Baseline LDL-C and PCSK9 levels were 76.18 mg·dL−1 and 80.54 ng·mL−1, respectively. After 1 month, metformin significantly reduced LDL-C (−20.81%, P < 0.001), enabling 72% of patients to attain guideline-recommended LDL-C goals. Noteworthy reductions in PCSK9 levels (−15.03%, P < 0.001) were observed. Moreover, Met + CLA markedly reduced LDL particle number more than CLA alone (−10.65% vs. 1.45%, P = 0.009), primarily due to diminished small-dense LDL particle count. Mechanistically, our study demonstrated metformin's inhibition of statin-induced PCSK9 expression in human hepatocellular cells. In summary, a 1-month metformin combination regimen reduced LDL-C levels in patients with CAD but without diabetes by inhibiting PCSK9 expression.

Trial registration:
Chinese Clinical Trial Registry identifier: ChiCTR1900026925 (26/10/2019).
The Expanded Forehead Flap for Resurfacing of Multi-unit Congenital Nevi of the Face
Authors: Wu Meagan , Pontell Matthew E. , Massenburg Benjamin B. , Ng Jinggang J. , Romeo Dominic J. , Swanson Jordan W. , Taylor Jesse A. , Bartlett Scott P. 
Published: June 2024

Summary:
The forehead flap is a timeless and robust reconstructive option for complex facial defects. In accordance with aesthetic subunit principles, it has traditionally been used to resurface defects affecting a single cervicofacial region, most commonly the nose or periorbital unit. In this article, we present three cases of congenital nevi treated with expanded forehead flap reconstruction of the nasal, periorbital, and cheek units in early childhood. This series demonstrates an approach that, while violating facial units, limits total scar burden and optimizes aesthetic and functional results. With precise staging and execution, this reconstructive technique allows for a single flap to resurface multi-unit defects in the pediatric population with excellent long-term results.
An Alternative Technique For Intraocular Lens Removal: Bimanual Cleavage In The Vitreous Chamber
Authors: Carlà Matteo Mario , Mateo Carlos 
Published: June 2024

Purpose:
To present a new technique for lens explantation, involving intraocular lens (IOL) cleavage in the vitreous chamber using two forceps and successive removal from the anterior chamber.

Methods:
Retrospective monocentric analysis of 10 eyes affected by IOL subluxation/luxation who underwent IOL explantation and 23-G vitrectomy. After separating the capsular bag rests from the IOL using the vitrectomy probe, serrated forceps were used to grab the IOL, while microscissors performed an “initiation” cut at the midpoint of the lens plate. A second pair of serrated forceps grabbed the IOL plate on the other side. Then, the two forceps were slowly pulled one apart from the other, exerting a separative force perpendicular to the initiation cut and causing the IOL to cleave in two pieces. In case of asymmetric cleavage, a second cleavage was performed. The pieces of the IOL were then moved to the anterior chamber and removed through a clear corneal incision.

Results:
Intraoperative mean IOL removal time was 14.1 ± 6.5 minutes. The IOLs (seven 1-piece and three three-pieces IOLs) were successfully explanted with this technique in all patients. Overall, four cases underwent exclusive IOL explantation, and the eyes were left aphakic. Postoperatively, best corrected visual acuity improved in all patients at 1-week follow-up, and no intraoperative or postoperative adverse events were reported. Cornea was completely clear in every case since postoperative Day 1.

Conclusion:
Bimanual cleavage technique for IOL removal ensured safer IOL handling in the larger vitreous chamber and minimized the procedures to be performed in the anterior chamber.
PREVALENCE OF DIDANOSINE-RELATED RETINAL TOXICITY AT AN URBAN ACADEMIC CENTER AS DIAGNOSED WITH ULTRA-WIDEFIELD IMAGING
Authors: Kim Joshua Seokju , Shah Jaffer , Papakostas Thanos , Mahrous M. Abdallah , D'Amico Donald J. , Kiss Szilard , Kovacs Kyle D. 
Published: June 2024

Purpose:
Antiretroviral therapy has revolutionized HIV treatment with didanosine (DDI) as a pioneering drug. However, DDI has been associated with retinal toxicity, characterized by peripheral chorioretinal degeneration with macular sparing. Despite its clinical recognition, the prevalence and risk factors for didanosine-induced retinopathy are not well described.

Methods:
This retrospective case series analyzed 127 DDI-treated patients at Weill Cornell Medicine Department of Ophthalmology. Inclusion criteria included at least 6 months of DDI use and available ultra-widefield imaging. Patients were categorized as affected or unaffected based on retinal imaging assessed by two reviewers. The affected group was further divided into “probable” or “possible” retinopathy. Patient demographics, DDI usage characteristics, and imaging findings were analyzed with statistical comparisons drawn between affected and unaffected cohorts.

Results:
Of the 127 patients, 9 (7%) showed signs of didanosine-induced retinal toxicity. On average, the affected group was older compared with the unaffected group (65.1 vs. 56.5 years, P = 0.025), with lower BMI (23.2 vs. 27.4, P = 0.04), and older at the start of the treatment (51.6 vs. 40.8 years, P = 0.026). Mild phenotypes with peripheral pigmentary changes were also identified using ultra-widefield imaging.

Conclusion:
This pioneering academic study highlighted a notable prevalence of DDI-induced retinal toxicity. Statistical analysis demonstrated age, BMI, and age at treatment initiation as potential risk factors. Ultra-widefield autofluorescence emerged as a valuable tool in detecting and delineating findings. Follow-up studies are needed to determine the necessity of regular screening for individuals on or with a history of didanosine use.
Trends in analgesia prescribing in primary care in Ireland and England between 2014 and 2022 - a repeated cross-sectional study
Authors: Mattsson Molly , Flood Michelle , MacKenna Brian , Wallace Emma , Boland Fiona , Kirke Ciara , Walsh Mary E , Fahey Tom , Moriarty Frank 
Published: June 2024

AbstractBackgroundPain is a major public health issue, and a common reason people seek medical care. Pharmacological treatments depend on the type of pain and carry different risks and benefits. The aim of this study was to examine trends in analgesic prescribing in Ireland and England between 2014 and 2022.MethodsMonthly data on medicines prescribed and dispensed in primary care were used. For Ireland, data on the means-tested General Medical Services (GMS) scheme were used, covering approximately 32% of the population. For England, data from the NHS Digital platform for all general practices were used. Outcomes were the volume of prescribed analgesic use, including rates of dispensings, costs, and standard doses (including oral morphine equivalents (OMEs) for opioids) per 1,000 population, summarised per year for each drug class/drug.ResultsIn Ireland, the rate of analgesia dispensings increased between 2014 and 2022 for most drugs. Opioid dispensings increased from 979 to 1,220 per 1,000 population, while paracetamol increased from 1,295 to 1,824. Systemic NSAIDs decreased from 781 to 734. In England, most analgesia dispensing rates decreased, with opioids decreasing from 721 to 585 per 1,000 population, paracetamol from 734 to 484, and systemic NSAIDs from 259 to 167.DiscussionSubstantially different dispensing patterns were found in Ireland and England, with higher increasing overall rates in Ireland and lower decreasing rates in England, potentially driven by the older age and lower socioeconomic status of GMS patients in Ireland. Further research to understand drivers for this higher volume of use is required.
Beyond Exploratory Data: Using Cluster Detection Tests to Pinpoint Malaria Hotspots in Nigeria
Authors: Oyamakin S. O. , Mayowa Owolabi 
Published: June 2024

AbstractMalaria is not communicable, but it can deteriorate and even kill a person within a day if treatment is not taken. Plasmodium falciparum is the malaria parasite that is most prevalent and deadly in Africa. This study attempts to identify malaria hotspots and potentially high-risk areas in Oyo state, Nigeria. Data on malaria cases from 2013 to 2016 were provided by the Department of Research, Planning, and Statistics (DPRS) of the Oyo State Ministry of Health. Spatial autocorrelation testing, spatiotemporal analysis, and descriptive statistics were performed using SatScan V9.11 and ArcGIS V10.8. The four-year malaria incidence study was conducted in Oyo West LGA and is geographically focused. Four clusters were found using spatial analysis, with the majority of the clusters located in the Oyo South region. Spatial-temporal research revealed three noteworthy groups. The cluster that happened between January 2013 and December 2014 is located in the Oyo South and Oyo Central region. High-high malaria clusters were identified by spatial autocorrelation analysis, particularly in Oyo Central; the yearly clustered pattern of malaria incidence was not coincidental. In order to better achieve effective disease surveillance, this study suggests employing more cluster detection tests (or CDTs) rather than just exploratory data analysis prior to the implementation of health treatments and regulations.
Determinants of de novo mutations in extended pedigrees of 43 dog breeds
Authors: Zhang Shao-Jie , Ma Jilong , Riera Meritxell , Besenbacher Søren , Niskanen Julia , Salokorpi Noora , Hundi Sruthi , Hytönen Marjo K , Zhou Tong , Li Gui-Mei , Ostrander Elaine A. , Schierup Mikkel Heide , Lohi Hannes , Wang Guo-Dong 
Published: June 2024

AbstractIntensive breeding of dogs has had dramatic effects on genetic variants underlying phenotypes. To investigate whether this also affected mutation rates, we deep-sequenced pedigrees from 43 different dog breeds representing 404 trios. We find that the mutation rate is remarkably stable across breeds and is predominantly influenced by variation in parental ages. The effect of paternal age per year on mutation rates is approximately 1.5 times greater in dogs than humans, suggesting that the elevated yearly mutation rate in dogs is only partially attributed to earlier reproduction. While there is no significant effect of breeds on the overall mutation rate, larger breeds accumulate proportionally more mutations earlier in development than small breeds. Interestingly, we find a 2.6 times greater mutation rate in CG Islands (CGIs) compared to the remaining genome in dogs, unlike humans, where there is no difference. Our estimated rate of mutation by recombination in dogs is more than 10 times larger than estimates in humans. We ascribe these to the fact that canids have lost PRDM9-directed recombination and draw away recombination from CGIs. In conclusion, our study sheds light on stability of mutation processes and disparities in mutation accumulation rates reflecting the influence of differences in growth patterns among breeds, and the impact of PRDM9 gene loss on the de novo mutations of canids.