bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility and Acceptability of a Prospective Syphilis Sexual Network Study for Sexual Minority Men
Authors: Ricks JaNelle M. , Spahnie Morgan , Endres-Dighe Stacy , Conroy Sara , Miller William C. , Turner Abigail N. 
Published: July 2024

Background
In preparation for a prospective syphilis network study of sexual minority men, we conducted a mixed-methods formative study with the following objectives: (a) assess acceptability of respondent-driven sampling, (b) assess acceptability of study procedures, (c) social network seed selection, and (d) pilot an ecological momentary assessment (EMA) study to assess social networking, sexual, and substance use behaviors.

Methods
We conducted in-depth interviews with 8 providers serving sexual minority men and 5 focus group discussions with 34 sexual minority men, prioritizing 4 target populations: (1) young Black sexual minority men, (2) on preexposure prophylaxis, (3) living with HIV, and (4) not engaged in care. The 4-week EMA pilot was conducted with 40 sexual minority men. Ecological momentary assessment survey responses were analyzed to evaluate how different compensation levels influenced response rates. Brief exit surveys were used to assess EMA app acceptability.

Results
Primary themes identified through qualitative data collection: (1) importance of developing trust and maintaining confidentiality during proposed recruitment activities, (2) importance of compensating participants appropriately for study activities, and (3) cultural considerations for increasing visibility and participation of young Black sexual minority men. All EMA participants reported being “completely comfortable” reporting sexual behavior through the app. Most (78%) preferred the app to in-person interviews. Several participants identified technical issues with the app, including not receiving push notifications and spontaneous closure.

Conclusions
This mixed-methods formative study allowed for adjustments to and tailoring of the planned network study, including recruitment protocols, compensation type and amount, and EMA survey wording and response items.
Usability Testing Via Simulation
Authors: Wing Robyn , Goldman Michael P. , Prieto Monica M. , Miller Kelsey A. , Baluyot Mariju , Tay Khoon-Yen , Bharath Anita , Patel Deepa , Greenwald Emily , Larsen Ethan P. , Polikoff Lee A. , Kerrey Benjamin T. , Nishisaki Akira , Nagler Joshua 
Published: July 2024

Objectives
To inform development of a preintubation checklist for pediatric emergency departments via multicenter usability testing of a prototype checklist.

Methods
This was a prospective, mixed methods study across 7 sites in the National Emergency Airway Registry for Pediatric Emergency Medicine (NEAR4PEM) collaborative. Pediatric emergency medicine attending physicians and senior fellows at each site were first oriented to a checklist prototype, including content previously identified using a modified Delphi approach. Each site used the checklist in 2 simulated cases: an “easy airway” and a “difficult airway” scenario. Facilitators recorded verbalization, completion, and timing of checklist items. After each simulation, participants completed an anonymous usability survey. Structured debriefings were used to gather additional feedback on checklist usability. Comments from the surveys and debriefing were qualitatively analyzed using a framework approach. Responses informed human factors-based optimization of the checklist.

Results
Fifty-five pediatric emergency medicine physicians/fellows (4–13 per site) participated. Participants found the prototype checklist to be helpful, easy to use, clear, and of appropriate length. During the simulations, 93% of checklist items were verbalized and more than 80% were completed. Median time to checklist completion was 6.2 minutes (interquartile range, 4.8–7.1) for the first scenario and 4.2 minutes (interquartile range, 2.7–5.8) for the second. Survey and debriefing data identified the following strengths: facilitating a shared mental model, cognitively offloading the team leader, and prompting contingency planning. Suggestions for checklist improvement included clarifying specific items, providing more detailed prompts, and allowing institution-specific customization. Integration of these data with human factors heuristic inspection resulted in a final checklist.

Conclusions
Simulation-based, human factors usability testing of the National Emergency Airway Registry for Pediatric Emergency Medicine Preintubation Checklist allowed optimization prior to clinical implementation. Next steps involve integration into real-world settings utilizing rigorous implementation science strategies, with concurrent evaluation of the impact on patient outcomes and safety.
Immune responses and severe dengue: what have we learned?
Authors: Malavige Gathsaurie Neelika , Ogg Graham S. 
Published: July 2024

Purpose of review
With the marked rise in dengue globally, developing well tolerated and effective vaccines and therapeutics is becoming more important. Here we discuss the recent developments in the understanding of immune mechanisms that lead to severe dengue and the learnings from the past, that can help us to find therapeutic targets, prognostic markers, and vaccines to prevent development of severe disease.

Recent findings
The extent and duration of viraemia often appears to be associated with clinical disease severity but with some variability. However, there also appear to be significant differences in the kinetics of viraemia and nonstructural protein 1 (NS1) antigenemia and pathogenicity between different serotypes and genotypes of the DENV. These differences may have significant implications for development of treatments and in inducing robust immunity through dengue vaccines. Although generally higher levels of neutralizing antibodies are thought to protect against infection and severe disease, there have been exceptions and the specificity, breadth and functionality of the antibody responses are likely to be important.

Summary
Although there have been many advances in our understanding of dengue pathogenesis, viral and host factors associated with occurrence of severe dengue, vascular leak and the immune correlates of protection remain poorly understood.
Elevated levels of KLF12 impair trophoblast syncytialization via GCM1 downregulation
Authors: Shi Qing-Qing , Wu Xing , Kang Nan-Nan , Zhou Ji-Dong , Zhen Xin , Li Ze-Wu , Yan Gui-Jun , Sun Hai-Xiang , Liu Jing-Yu , Liu Yang 
Published: July 2024

Objective:
Placental dysfunction is a major contributor to miscarriages in humans. We observed elevated expression of Kruppel-like factor 12 (KLF12) in placental villi of women who experienced miscarriage compared to that in women with healthy pregnancies. This study aimed to elucidate the role of KLF12 in maintaining a successful pregnancy.

Methods:
To investigate the role of KLF12 in placentation, we employed a model of forskolin-induced syncytialization in BeWo cells.

Results:
Our findings revealed that KLF12 expression is downregulated during normal syncytialization. Conversely, we observed that abnormally high KLF12 levels directly suppressed glial cells missing-1 (GCM1) expression. This suppression of GCM1 expression subsequently impaired BeWo cell syncytialization. Furthermore, we observed placental deformities in KLF12-overexpressing mouse fetuses.

Conclusion:
This study demonstrated that elevated levels of KLF12 disrupt trophoblast syncytialization by downregulating GCM1 expression. These findings suggest that KLF12 may be a novel candidate gene contributing to unexplained miscarriages.
Revolutionizing Liver Transplantation
Authors: Li Zhihao , Pfister Matthias , Huwyler Florian , Hoffmann Waldemar , Tibbitt Mark W. , Dutkowski Philipp , Clavien Pierre-Alain 
Published: July 2024

Objective:
To assess the impact of normothermic machine perfusion (NMP) on patients, medical teams, and costs by gathering global insights and exploring current limitations.

Background:
NMP for ex situ liver graft perfusion is gaining increasing attention for its capability to extend graft preservation. It has the potential to transform liver transplantation (LT) from an urgent to a purely elective procedure, which could revolutionize LT logistics, reduce burden on patients and health care providers, and decrease costs.

Methods:
A 31-item survey was sent to international transplant directors to gather their NMP experiences and vision. In addition, we performed a systematic review on cost-analysis in LT and assessed studies on cost-benefit in converting urgent-to-elective procedures. We compared the costs of available NMPs and conducted a sensitivity analysis of NMP’s cost benefits.

Results:
Of 120 transplant programs contacted, 64 (53%) responded, spanning North America (31%), Europe (42%), Asia (22%), and South America (5%). Of the total, 60% had adopted NMP, with larger centers (>100 transplants/year) in North America and Europe more likely to use it. The main NMP systems were OrganOx-metra (39%), XVIVO (36%), and TransMedics-OCS (15%). Despite NMP adoption, 41% of centers still perform >50% of LTs at nights/weekends. Centers recognized NMP’s benefits, including improved work satisfaction and patient outcomes, but faced challenges like high costs and machine complexity. 16% would invest $100,000 to 500’000, 33% would invest $50,000 to 100’000, 38% would invest $10,000 to 50’000, and 14% would invest <$10,000 in NMP. These results were strengthened by a cost analysis for NMP in emergency-to-elective LT transition. Accordingly, while liver perfusions with disposables up to $10,000 resulted in overall positive net balances, this effect was lost when disposables’ cost amounted to >$40,000/organ.

Conclusions:
The adoption of NMP is hindered by high costs and operational complexity. Making LT elective through NMP could reduce costs and improve outcomes, but overcoming barriers requires national reimbursements and simplified, automated NMP systems for multiday preservation.
Identification of potential SARS-CoV-2 genetic markers resulting from host domestication
Authors: Wiśniewski Janusz , Chen Heng-Chang 
Published: July 2024

AbstractWe developed ak-mer-based pipeline, namely the Pathogen Origin Recognition Tool using EnrichedK-mers (PORT-EK) to identify genomic regions enriched in the respective hosts after the comparison of metagenomes of isolates between two host species. Using it we identified thousands ofk-mers enriched in US white-tailed deer and betacoronaviruses in bat reservoirs while comparing them with human isolates. We demonstrated different coverage landscapes ofk-mers enriched in deer and bats and unraveled 148 mutations in enrichedk-mers yielded from the comparison of viral metagenomes between bat and human isolates. We observed that the third position within a genetic codon is prone to mutations, resulting in a high frequency of synonymous mutations of amino acids harboring the same physicochemical properties as unaltered amino acids. Finally, we classified and predicted the likelihood of host species based on the enrichedk-mer counts. Altogether, PORT-EK showcased its feasibility for identifying enriched viral genomic regions, illuminating the different intrinsic tropisms of coronavirus after host domestication.TeaserA measure of enriched viral genomic correlates resulting from host domestication as a potential predictor of zoonotic risk.
Analysis of Factors Determining Success in FFPE Based NGS Panel Testing For Lung & Ovarian Cancer
Authors: Bhattacharya P. , Bishop P. , Gokhale D. , Rowlston S. , Eggington B. , Burghel G. J. , Schlecht H. 
Published: July 2024

AbstractThe identification of oncogenic variants in both lung and ovarian cancer is central to personalised treatment. NGS approaches using formalin-fixed paraffin-embedded (FFPE) tissue samples are routinely implemented for variant detection, but optimisation of pre-analytic factors is critical for success. We performed a large multi-cohort retrospective audit assessing pre-analytic factors related to Qiagen in house custom designed NGS panel testing for lung (n=801 from 23 referring hospitals) and ovarian (n=882 from 85 referring hospitals) FFPE cancer samples, sequenced at the NHS Northwest Genomic Laboratory Hub (NWGLH). A further detailed analysis of a cohort of lung samples (n=461) submitted from a single high-volume referral centre was also undertaken. Overall NGS cohort success ranged from 74-85% with large variation amongst referring laboratories. Multivariate logistic regression analysis revealed DNA yield and quality to be significant predictors of NGS success (p<0.001) alongside sample type for lung (p=0.035) and use of macrodissection for ovarian (p=0.025). Univariate analysis revealed specific poor lung performance within biopsy samples and associated with number and length of core biopsy samples. Furthermore, excessive fixation time for lung cytology and ovarian samples was associated with NGS failure (p<0.05), with only 49.5% of lung endoscopic bronchial ultrasound (EBUS) cytology samples meeting existing local guidelines for fixation time <24 hours, with 2/3 of prolonged fixation samples being received in the lab the following day. Variation in key identified pre-analytic factors amongst referring centres and variable adherence to best practice guidelines is likely to be responsible for the wide variation in NGS success. Improved collaboration between NHS genomic hubs and referring pathology laboratories through the establishment of a regional interactive collaborative network, facilitating guideline sharing and assessing adherence to pre-analytic optimisation of sample collection and processing for genomic testing, is crucial to improve future NGS genomic cancer testing.
PREDICTORS OF VIRAL REBOUND AMONG ADOLESCENTS AT AN URBAN CLINIC IN KAMPALA USING REPEATED EVENTS SURVIVAL ANALYSIS
Authors: Kirabira Anthony , Bukenya Justine , Ssenkusu John , Ssekamatte Noah K , Tumwesigye Nazarius M , Kiwanuka Noah 
Published: July 2024

ABSTRACTBackgroundA suppressed HIV viral load below 1000 copies/ml is mark of HIV treatment success because it is associated with reduced risk of transmission of HIV. However, following viral suppression, some people experience viral rebound which may occur multiple times. We used repeated events survival analysis to assess the predictors of viral rebound among adolescents (aged 10-19 years) at an urban clinic in Kampala, Uganda.MethodsThe study was a retrospective cohort design conducted at Baylor-Uganda, an HIV care facility. The Lognormal model was used to estimate time from viral suppression to viral rebound (in months) and to determine factors associated with time to first viral rebound. The Prentice, Williams, and Peterson (PWP) model was used to determine the factors associated with repetitive viral rebound.ResultsData from 219 participants were included in the study; 160 (73.06%) were female, and 117 (53.42%) were aged 15-19 years. The overall proportion of viral rebound was 31.5% (31.51/100); 23.29% (23.29/100) experienced one rebound whereas 8.22% (8.22/100) had multiple rebounds. The probability of viral rebound did not reach 50%, so the median time from viral suppression to viral rebound could not be estimated. The 25thpercentile survival time to first viral rebound was 34.1 months. The incidence rate of first viral rebound was 84.7 (95%CI, 66.9 - 107.2) per 10,000-person months of observation. The predictors of first viral rebound included; duration on ART (adjusted Time Ratio (TR), 1.04; 95%CI, 1.04-1.05; p<0.001), having psychosocial issues (adjusted TR, 0.67; 95%CI, 0.58-0.77; p<0.001), baseline viral load of <1000 (adjusted TR, 0.85; 95%CI, 0.72-0.99; p=0.008) and protease inhibitors (PI) based ART regimens (adjusted TR, 0.67; 95%CI, 0.49-0.92; p=0.012). The predictors of multiple rebounds included duration on ART (adjusted Hazard Ratio (HR), 0.86, 95%CI, 0.84-0.89; p<0.001), having psychosocial issues (adjusted HR, 11.04, 95%CI, 6.09-20.0; p<0.001), WHO clinical stage II (adjusted HR, 2.28, 95%CI, 1.22-4.25; p=0.002), and WHO clinical stage III (adjusted HR, 2.17, 95%CI, 1.14-4.14; p=0.005)ConclusionIn an urban HIV care facility in Kampala, we found an overall proportion of viral rebound among the adolescents of 31.5%. Occurrence of multiple viral rebounds was associated with duration on ART, psychosocial issues, and WHO clinical staging. Therefore, there is need to incorporate screening of adolescents for psychosocial challenges into the routine programming of HIV care and treatment so as identify and appropriately support those affected in time.
Financial Feasibility Study and policy recommendations of Incremental Modified Drugs Development by the Domestic Pharmaceutical Industry
Authors: Laichapis Manthana , Sakulbumrungsil Rungpetch , Udomaksorn Khunjira , Kessomboon Nusaraporn , Nerapusee Osot , Hongthong Charkkrit , Poonpolsub Sitanun 
Published: July 2024

AbstractThe Thai pharmaceutical industry aims to strengthen its drug system in accordance with the National Strategic Master Plan, emphasizing sustainable development, particularly in biologics and herbal products, to achieve self-reliance. Current efforts are mainly focused on generic drug production, but there’s a significant need for Research and Development (R&D) in Innovative Medicines (IMDs). This study explores the financial feasibility of locally developing an IMDs dosage form. To assess this feasibility, a mixed-methods approach was used, incorporating a literature review, surveys, and interviews. This process involved selecting types of IMDs, constructing financial models, determining cost structures, and conducting a thorough feasibility analysis. The results indicated that a sustained-release dosage form was the most viable option. The analysis took into account total development costs, payback periods, growth rates, and the revenue required to recoup investments. It was found that IMD development is associated with higher costs and longer durations compared to new generic drugs.The study identified several challenges, such as the high cost of clinical studies, extended development times, market feasibility, and drug selection difficulties. Policy recommendations were made to address these challenges, including incentives for clinical studies and fostering industry expertise through collaborative efforts and supportive government policies.In conclusion, the financial feasibility of developing IMDs requires strategic policies and collaboration to overcome these challenges and ensure sustainability. The findings of this study are intended to aid stakeholders in making informed R&D investment decisions.
Unraveling the Web of Life: Incomplete lineage sorting and hybridization as primary mechanisms over polyploidization in the evolutionary dynamics of pear species
Authors: Jin Ze-Tao , Lin Xiao-Hua , Ma Dai-Kun , Hodel Richard G.J. , Ren Chen , Zhao Liang , Duan Lei , Xu Chao , Wu Jun , Liu Bin-Bin 
Published: July 2024

AbstractIn contrast to the traditional Tree of Life (ToL) paradigm, the Web of Life (WoL) model provides a more nuanced and precise depiction of organismal phylogeny, particularly considering the prevalent incongruence observed among gene/species trees. The lack of a generalized pipeline for teasing apart potential evolutionary mechanisms—such as Incomplete Lineage Sorting (ILS), hybridization, introgression, polyploidization, and Whole-Genome Duplication—poses significant challenges to the delineation of the WoL. The pear genusPyrus, characterized by extensive hybridization events, serves as an excellent model for investigating the WoL. This study introduces a novel Step-by-Step Exclusion (SSE) approach to deciphering the complexities inherent in the WoL. Our findings indicate: 1) ILS, rather than polyploidization, is identified as the primary driver behind the origin ofPyrusfrom the arid regions of the Himalayas-Central Asia; 2) the two subgenera ofPyrushave independent evolutionary trajectories, facilitated by the geographical barriers that arose via the uplift of the Tibetan Plateau and increased aridity in Central Asia; 3) ILS and hybridization have facilitated the diversification of Oriental pears, while hybridization alone has driven the reticulate evolution of Occidental pears; 4) the establishment of the Silk Road during the Han Dynasty acted as a conduit for genetic exchange between Occidental and Oriental pears. The novel SSE approach provides a universally applicable framework for investigating evolutionary mechanisms defining the WoL paradigm.
Brown Adipose Tissue undergoes pathological perturbations and shapes C2C12 myoblast homeostasis in the SOD1-G93A mouse model of Amyotrophic Lateral Sclerosis
Authors: Rosina Marco , Scaricamazza Silvia , Riggio Flaminia , Fenili Gianmarco , Giannessi Flavia , Matteocci Alessandro , Nesci Valentina , Salvatori Illari , Angelini Daniela F. , Aquilano Katia , Chiurchiù Valerio , Barbato Daniele Lettieri , Mercuri Nicola Biagio , Valle Cristiana , Ferri Alberto 
Published: July 2024

AbstractAmyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the selective loss of motor neurons. While the contribution of peripheral organs remains incompletely understood, recent evidence suggests that brown adipose tissue (BAT) and its secreted extracellular vesicles (EVs) could play a role in diseased context as ALS. In this study, we employed a multi-omics approach, including RNA sequencing (GEO identifier GSE273052) and proteomics (ProteomeXchange identifier PXD054147), to investigate the alterations in BAT and its EVs in the SOD1-G93A mouse model of ALS. Our results revealed significant changes in the proteomic and transcriptomic profiles of BAT from SOD1-G93A mice, highlighting ALS-related features such as mitochondrial dysfunction and impaired differentiation capacity. Specifically, primary brown adipocytes (PBAs) from SOD1-G93A mice exhibited differentiation impairment, respiratory defects, and alterations in mitochondrial dynamics. Furthermore, the BAT-derived EVs from SOD1-G93A mice displayed distinct changes in size distribution and cargo content, which negatively impacted the differentiation and homeostasis of C2C12 murine myoblasts, as well as induced atrophy in C2C12-derived myotubes. These findings suggest that BAT undergoes pathological perturbations in ALS, contributing to skeletal muscle degeneration through the secretion of dysfunctional EVs. This study provides novel insights into the role of BAT in ALS pathogenesis and highlights potential therapeutic targets for mitigating muscle wasting in ALS patients.