bluuebunny/crossref_metadata_2025_split huggingface dataset:
The sexual and gender minority (LGBTQ+) medical trainee: the journey through medical education
Authors: Danckers Mauricio , Nusynowitz Jake , Jamneshan Lily , Shalmiyev Richard , Diaz Raiko , Radix Asa E. 
Published: January 2024

AbstractIn this literature overview, we share with the reader challenges faced by LGBTQ + individuals pursuing medical education, from undergraduate to postgraduate training. The LGBTQ + acronym has evolved to encompass the diverse spectrum of sexual orientation and gender identities. Recently, the term “Sexual and Gender Minority” (SGM) has emerged as an umbrella term to provide consistency in research advancing SGM health. The unique obstacles LGBTQ + trainees encounter are highlighted throughout this article, including external factors influencing career decisions, a lack of LGBTQ + healthcare curricula, discriminatory social interactions, limited mentorship opportunities, and a higher mental health burden. These challenges have the capacity to affect educational experiences, personal well-being, and professional growth. Additionally, we examine the impact of inclusive institutional climates on LGBTQ + trainees’ selection of medical schools and residency programs, as they may prioritize inclusiveness and diversity when making their choice. In postgraduate training, LGBTQ + trainees continue to face challenges, exemplified by disparities in placement rates and discriminatory experiences based on sexual orientation and gender identity. We describe the gap in current research and its long-term impact of these challenges on career paths. Hostile environments persist in certain specialties, and the lack of LGBTQ + mentorship and support can hinder academic pursuits. We shed light on the unique and pervasive challenges faced by LGBTQ + trainees throughout their medical education journey, while emphasizing the need for inclusive policies, support systems, and research to address these challenges. With increasing research and studies, we hope to create a medical workforce and community that better represents the diverse communities it serves.
People living with HIV’s perspectives of acceptability of fee for home delivery of ART: a qualitative study
Authors: Ntinga Xolani , Musiello Franco , Pita Thembelihle , Mabaso Nomagugu , Celum Connie , Szpiro Adam , van Rooyen Heidi , Barnabas Ruanne , van Heerden Alastair 
Published: January 2024

Abstract
Introduction
Significant progress has been made in the HIV response in South Africa; however, gaps remain in ensuring engagement in care to support life-long medication adherence and viral suppression. The National Department of Health (NDoH) has introduced community-based and clinic-based HIV differentiated service delivery (DSD) models to tackle suboptimal adherence and retention in care. Nevertheless, differentiated care models require adaptation to better serve clients who struggle with adherence. There is limited research on the acceptability of fee for home delivery of ART in resource-constrained settings. The current study investigates the acceptability of fee for home delivery of ART among people living with HIV in South Africa.

Methods
Two mixed-gender focus group discussions (FGDs) took place between June and November 2019, consisting of 10 participants in each group. A purposive sampling strategy was employed to identify and select 10 people living with HIV who were ART-eligible but not in care, and 10 people living with HIV who were currently taking ART and in care. Participants were grouped according to their treatment status. A coding framework, informed by a priori categories and derived from topics in the interview guide, was developed and utilized to facilitate analysis.

Results
Participants expressed enthusiasm for having ART home-delivered, as it would save the time spent waiting in long queues at the clinic. However, some participants raised concerns about potential payment difficulties due to high unemployment rates in the community. Some participants believed this would be acceptable, as patients already incur costs for travel and food when visiting the clinic. Participants in both FGDs expressed strong concerns about home delivery of their ART based on fear of accidental disclosure, especially for those who have not disclosed to their immediate families and partners.

Conclusion
Our study suggests that charging a fee for home delivery is an acceptable and innovative approach to supporting PLHIV in maintaining adherence to their medication and remaining in care.
Postabortion care service availability, readiness, and access in Burkina Faso: results from linked female-facility cross-sectional data
Authors: Onadja Yentéma , Compaoré Rachidatou , Yugbaré Danielle Belemsaga , Thomas Haley L. , Guiella Georges , Lougué Siaka , Ouedraogo Henri Gautier , Bazie Fiacre , Kouanda Seni , Moreau Caroline , Bell Suzanne O. 
Published: January 2024

Abstract
Background
Little is known about postabortion care (PAC) services in Burkina Faso, despite PAC’s importance as an essential and life-saving component of emergency obstetric care. This study aims to evaluate PAC service availability, readiness, and accessibility in Burkina Faso.

Methods
Data for this study come from the Performance Monitoring for Action (PMA) Burkina Faso project and the Harmonized Health Facility Assessment (HHFA) conducted by the Institut de Recherche en Sciences de la Santé and the Ministry of Health. PMA data from a representative sample of women aged 15–49 (n = 6,385) were linked via GPS coordinates to HHFA facility data (n = 2,757), which included all public and private health facilities in Burkina Faso. We assessed readiness to provide basic and comprehensive PAC using the signal functions framework. We then calculated distance to facilities and examined percent within 5 kms of a facility with any PAC, basic PAC, and comprehensive PAC overall and by women’s background characteristics.

Results
PAC services were available in 46.4% of health facilities nationwide; only 38.3% and 35.0% of eligible facilities had all basic and comprehensive PAC signal functions, respectively. Removal of retained products of conception was the most common missing signal function for both basic and comprehensive PAC, followed by provision of any contraception (basic) or any LARC (comprehensive). Nearly 85% of women lived within 5 km of a facility providing any PAC services, while 50.5% and 17.4% lived within 5 km of a facility providing all basic PAC and all comprehensive PAC signal functions, respectively. Women with more education, greater wealth, and those living in urban areas had greater odds of living within 5 km of a facility with offering PAC, basic PAC, or comprehensive PAC.

Conclusions
Results indicate a need for increased PAC availability and readiness, prioritizing basic PAC services at the primary level—the main source of care for many women—which would reduce structural disparities in access. The current deficiencies in PAC signal a need for broader strengthening of the primary healthcare services in Burkina Faso to reduce the burden of unsafe abortion-related morbidity and mortality while improving maternal health outcomes more broadly.
Use of chitin:DNA ratio to assess growth form in fungal cells
Authors: Kovács-Simon Andrea , Fones Helen N. 
Published: January 2024

Abstract
Background
Dimorphism, the ability to switch between a ‘yeast-like’ and a hyphal growth form, is an important feature of certain fungi, including important plant and human pathogens. The switch to hyphal growth is often associated with virulence, pathogenicity, biofilm formation and stress resistance. Thus, the ability to accurately and efficiently measure fungal growth form is key to research into these fungi, especially for discovery of potential drug targets. To date, fungal growth form has been assessed microscopically, a process that is both labour intensive and costly.

Results
Here, we unite quantification of the chitin in fungal cell walls and the DNA in nuclei to produce a methodology that allows fungal cell shape to be estimated by calculation of the ratio between cell wall quantity and number of nuclei present in a sample of fungus or infected host tissue. Using the wheat pathogen Zymoseptoria tritici as a test case, with confirmation in the distantly related Fusarium oxysporum, we demonstrate a close, linear relationship between the chitin:DNA ratio and the average polarity index (length/width) of fungal cells. We show the utility of the method for estimating growth form in infected wheat leaves, differentiating between the timing of germination in two different Z. tritici isolates using this ratio. We also show that the method is robust to the occurrence of thick-walled chlamydospores, which show a chitin:DNA ratio that is distinct from either ‘yeast-like’ blastospores or hyphae.

Conclusions
The chitin:DNA ratio provides a simple methodology for determining fungal growth form in bulk tissue samples, reducing the need for labour-intensive microscopic studies requiring specific staining or GFP-tags to visualise the fungus within host tissues. It is applicable to a range of dimorphic fungi under various experimental conditions.
Multiomics characterization of pyroptosis in the tumor microenvironment and therapeutic relevance in metastatic melanoma
Authors: Chen Wenqiong , He Yi , Zhou Guowei , Chen Xiang , Ye Youqiong , Zhang Guanxiong , Liu Hong 
Published: January 2024

AbstractBackgroundPyroptosis, mediated by gasdermins with the release of multiple inflammatory cytokines, has emerged as playing an important role in targeted therapy and immunotherapy due to its effectiveness at inhibiting tumor growth. Melanoma is one of the most commonly used models for immunotherapy development, though an inadequate immune response can occur. Moreover, the development of pyroptosis-related therapy and combinations with other therapeutic strategies is limited due to insufficient understanding of the role of pyroptosis in the context of different tumor immune microenvironments (TMEs).MethodsHere, we present a computational model (pyroptosis-related gene score, PScore) to assess the pyroptosis status. We applied PScore to 1388 melanoma samples in our in-house cohort and eight other publicly available independent cohorts and then calculated its prognostic power of and potential as a predictive marker of immunotherapy efficacy. Furthermore, we performed association analysis for PScore and the characteristics of the TME by using bulk, single-cell, and spatial transcriptomics and assessed the association of PScore with mutation status, which contributes to targeted therapy.ResultsPyroptosis-related genes (PRGs) showed distinct expression patterns and prognostic predictive ability in melanoma. Most PRGs were associated with better survival in metastatic melanoma. Our PScore model based on genes associated with prognosis exhibits robust performance in survival prediction in multiple metastatic melanoma cohorts. We also found PScore to be associated withBRAFmutation and correlate positively with multiple molecular signatures, such as KRAS signaling and the IFN gamma response pathway. Based on our data, melanoma with an immune-enriched TME had a higher PScore than melanoma with an immune-depleted or fibrotic TME. Additionally, monocytes had the highest PScore and malignant cells and fibroblasts the lowest PScore based on single-cell and spatial transcriptome analyses. Finally, a higher PScore was associated with better therapeutic efficacy of immune checkpoint blockade, suggesting the potential of pyroptosis to serve as a marker of immunotherapy response.ConclusionsCollectively, our findings indicate that pyroptosis is a prognostic factor and is associated with the immune response in metastatic melanoma, as based on multiomics data. Our results provide a theoretical basis for drug combination and reveal potential immunotherapy response markers.
Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke
Authors: Gao Xin , Zhao Xinyi , Li Jiacheng , Liu Chang , Li Wenqiang , Zhao Junjie , Li Zhixi , Wang Nan , Wang Fang , Dong Jiawei , Yan Xiuwei , Zhang Jiheng , Hu Xueyan , Jin Jiaqi , Mang Ge , Ma Ruishuang , Hu Shaoshan 
Published: January 2024

Abstract
Aims
Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process.

Methods
As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients’ blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs.

Results
A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients’ neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model.

Conclusions
NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS.
Systematic assessment of chemokine ligand bias at the human chemokine receptor CXCR2 indicates G protein bias over β-arrestin recruitment and receptor internalization
Authors: Boon Katrijn , Vanalken Nathan , Szpakowska Martyna , Chevigné Andy , Schols Dominique , Van Loy Tom 
Published: January 2024

Abstract
Background
The human CXC chemokine receptor 2 (CXCR2) is a G protein-coupled receptor (GPCR) interacting with multiple chemokines (i.e., CXC chemokine ligands CXCL1-3 and CXCL5-8). It is involved in inflammatory diseases as well as cancer. Consequently, much effort is put into the identification of CXCR2 targeting drugs. Fundamental research regarding CXCR2 signaling is mainly focused on CXCL8 (IL-8), which is the first and best described high-affinity ligand for CXCR2. Much less is known about CXCR2 activation induced by other chemokines and it remains to be determined to what extent potential ligand bias exists within this signaling system. This insight might be important to unlock new opportunities in therapeutic targeting of CXCR2.

Methods
Ligand binding was determined in a competition binding assay using labeled CXCL8. Activation of the ELR + chemokine-induced CXCR2 signaling pathways, including G protein activation, β-arrestin1/2 recruitment, and receptor internalization, were quantified using NanoBRET-based techniques. Ligand bias within and between these pathways was subsequently investigated by ligand bias calculations, with CXCL8 as the reference CXCR2 ligand. Statistical significance was tested through a one-way ANOVA followed by Dunnett’s multiple comparisons test.

Results
All chemokines (CXCL1-3 and CXCL5-8) were able to displace CXCL8 from CXCR2 with high affinity and activated the same panel of G protein subtypes (Gαi1, Gαi2, Gαi3, GαoA, GαoB, and Gα15) without any statistically significant ligand bias towards any one type of G protein. Compared to CXCL8, all other chemokines were less potent in β-arrestin1 and -2 recruitment and receptor internalization while equivalently activating G proteins, indicating a G protein activation bias for CXCL1,-2,-3,-5,-6 and CXCL7. Lastly, with CXCL8 used as reference ligand, CXCL2 and CXCL6 showed ligand bias towards β-arrestin1/2 recruitment compared to receptor internalization.

Conclusion
This study presents an in-depth analysis of signaling bias upon CXCR2 stimulation by its chemokine ligands. Using CXCL8 as a reference ligand for bias index calculations, no ligand bias was observed between chemokines with respect to activation of separate G proteins subtypes or recruitment of β-arrestin1/2 subtypes, respectively. However, compared to β-arrestin recruitment and receptor internalization, CXCL1-3 and CXCL5-7 were biased towards G protein activation when CXCL8 was used as reference ligand.
Transient immune activation without loss of intraepidermal innervation and associated Schwann cells in patients with complex regional pain syndrome
Authors: Hartmannsberger Beate , Scriba Sabrina , Guidolin Carolina , Becker Juliane , Mehling Katharina , Doppler Kathrin , Sommer Claudia , Rittner Heike L. 
Published: January 2024

Abstract
Background
Complex regional pain syndrome (CRPS) develops after injury and is characterized by disproportionate pain, oedema, and functional loss. CRPS has clinical signs of neuropathy as well as neurogenic inflammation. Here, we asked whether skin biopsies could be used to differentiate the contribution of these two systems to ultimately guide therapy. To this end, the cutaneous sensory system including nerve fibres and the recently described nociceptive Schwann cells as well as the cutaneous immune system were analysed.

Methods
We systematically deep-phenotyped CRPS patients and immunolabelled glabrous skin biopsies from the affected ipsilateral and non-affected contralateral finger of 19 acute (< 12 months) and 6 chronic (> 12 months after trauma) CRPS patients as well as 25 sex- and age-matched healthy controls (HC). Murine foot pads harvested one week after sham or chronic constriction injury were immunolabelled to assess intraepidermal Schwann cells.

Results
Intraepidermal Schwann cells were detected in human skin of the finger—but their density was much lower compared to mice. Acute and chronic CRPS patients suffered from moderate to severe CRPS symptoms and corresponding pain. Most patients had CRPS type I in the warm category. Their cutaneous neuroglial complex was completely unaffected despite sensory plus signs, e.g. allodynia and hyperalgesia. Cutaneous innate sentinel immune cells, e.g. mast cells and Langerhans cells, infiltrated or proliferated ipsilaterally independently of each other—but only in acute CRPS. No additional adaptive immune cells, e.g. T cells and plasma cells, infiltrated the skin.

Conclusions
Diagnostic skin punch biopsies could be used to diagnose individual pathophysiology in a very heterogenous disease like acute CRPS to guide tailored treatment in the future. Since numbers of inflammatory cells and pain did not necessarily correlate, more in-depth analysis of individual patients is necessary.
Splenic monocytes drive pathogenic subretinal inflammation in age-related macular degeneration
Authors: Roubeix Christophe , Nous Caroline , Augustin Sébastien , Ronning Kaitryn E. , Mathis Thibaud , Blond Frédéric , Lagouge-Roussey Pauline , Crespo-Garcia Sergio , Sullivan Patrick M. , Gautier Emmanuel L. , Reichhart Nadine , Sahel José-Alain , Burns Marie E. , Paques Michel , Sørensen Torben Lykke , Strauss Olaf , Guillonneau Xavier , Delarasse Cécile , Sennlaub Florian 
Published: January 2024

AbstractAge-related macular degeneration (AMD) is invariably associated with the chronic accumulation of activated mononuclear phagocytes in the subretinal space. The mononuclear phagocytes are composed of microglial cells but also of monocyte-derived cells, which promote photoreceptor degeneration and choroidal neovascularization. Infiltrating blood monocytes can originate directly from bone marrow, but also from a splenic reservoir, where bone marrow monocytes develop into angiotensin II receptor (ATR1)+ splenic monocytes. The involvement of splenic monocytes in neurodegenerative diseases such as AMD is not well understood. Using acute inflammatory and well-phenotyped AMD models, we demonstrate that angiotensin II mobilizes ATR1+ splenic monocytes, which we show are defined by a transcriptional signature using single-cell RNA sequencing and differ functionally from bone marrow monocytes. Splenic monocytes participate in the chorio-retinal infiltration and their inhibition by ATR1 antagonist and splenectomy reduces the subretinal mononuclear phagocyte accumulation and pathological choroidal neovascularization formation. In aged AMD-risk ApoE2-expressing mice, a chronic AMD model, ATR1 antagonist and splenectomy also inhibit the chronic retinal inflammation and associated cone degeneration that characterizes these mice. Our observation of elevated levels of plasma angiotensin II in AMD patients, suggests that similar events take place in clinical disease and argue for the therapeutic potential of ATR1 antagonists to inhibit splenic monocytes for the treatment of blinding AMD.
Conducting co-creation for public health in low and middle-income countries: a systematic review and key informant perspectives on implementation barriers and facilitators
Authors: Longworth Giuliana Raffaella , Erikowa-Orighoye Oritseweyinmi , Anieto Ebuka Miracle , Agnello Danielle Marie , Zapata-Restrepo Jorge Raul , Masquillier Caroline , Giné-Garriga Maria 
Published: January 2024

Abstract
Background
There has been an increase in the use of co-creation for public health because of its claimed potential to increase an intervention’s impact, spark change and co-create knowledge. Still, little is reported on its use in low-and-middle-income countries (LMICs). This study offers a comprehensive overview of co-creation used in public-health-related interventions, including the interventions’ characteristics, and reported implementation barriers and facilitators.

Methods
We conducted a systematic review within the Scopus and PubMed databases, a Google Scholar search, and a manual search in two grey literature databases related to participatory research. We further conducted eight interviews with first authors, randomly selected from included studies, to validate and enrich the systematic review findings.

Results
Through our review, we identified a total of twenty-two studies conducted in twenty-four LMIC countries. Majority of the interventions were designed directly within the LMIC setting. Aside from one, all studies were published between 2019 and 2023. Most studies adopted a co-creation approach, while some reported on the use of co-production, co-design, and co-development, combined either with community-based participatory research, participatory action research or citizen science. Among the most reported implementation barriers, we found the challenge of understanding and accounting for systemic conditions, such as the individual’s socioeconomic status and concerns related to funding constraints and length of the process. Several studies described the importance of creating a safe space, relying on local resources, and involving existing stakeholders in the process from the development stage throughout, including future and potential implementors. High relevance was also given to the performance of a contextual and/or needs assessment and careful tailoring of strategies and methods.

Conclusion
This study provides a systematic overview of previously conducted studies and of reported implementation barriers and facilitators. It identifies implementation barriers such as the setting’s systemic conditions, the socioeconomic status and funding constrains along with facilitators such as the involvement of local stakeholders and future implementors throughout, the tailoring of the process to the population of interest and participants and contextual assessment. By incorporating review and interview findings, the study aims to provide practical insights and recommendations for guiding future research and policy.