bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex-specific differences in myocardial glucose metabolic rate in non-diabetic, pre-diabetic and type 2 diabetic subjects
Authors: Succurro Elena , Vizza Patrizia , Cicone Francesco , Cassano Velia , Massimino Mattia , Giofrè Federica , Fiorentino Teresa Vanessa , Perticone Maria , Sciacqua Angela , Guzzi Pietro Hiram , Veltri Pierangelo , Andreozzi Francesco , Cascini Giuseppe Lucio , Sesti Giorgio 
Published: April 2024

Abstract
Background
Evidence has shown that women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than men with T2DM. Subjects with either T2DM or prediabetes exhibit myocardial insulin resistance, but it is still unsettled whether sex-related differences in myocardial insulin resistance occur in diabetic and prediabetic subjects.

Methods
We aimed to evaluate sex-related differences in myocardial glucose metabolic rate (MRGlu), assessed using dynamic PET with 18F-FDG combined with euglycemic-hyperinsulinemic clamp, in subjects with normal glucose tolerance (NGT; n = 20), prediabetes (n = 11), and T2DM (n = 26).

Results
Women with prediabetes or T2DM exhibited greater relative differences in myocardial MRGlu than men with prediabetes or T2DM when compared with their NGT counterparts. As compared with women with NGT, those with prediabetes exhibited an age-adjusted 35% lower myocardial MRGlu value (P = 0.04) and women with T2DM a 74% lower value (P = 0.006), respectively. Conversely, as compared with men with NGT, men with T2DM exhibited a 40% lower myocardial MRGlu value (P = 0.004), while no significant difference was observed between men with NGT and prediabetes. The statistical test for interaction between sex and glucose tolerance on myocardial MRGlu (P < 0.0001) was significant suggesting a sex-specific association.

Conclusions
Our data suggest that deterioration of glucose homeostasis in women is associated with a greater impairment in myocardial glucose metabolism as compared with men. The sex-specific myocardial insulin resistance could be an important factor responsible for the greater effect of T2DM on the excess risk of cardiovascular disease in women than in men.
Identifying and characterizing high-risk populations in pilot malaria elimination districts in Madagascar: a mixed-methods study
Authors: Gebreegziabher Elisabeth , Raoliarison Andry , Ramananjato Andrinirina , Fanomezana Andriamamonjy , Rafaliarisoa Martin , Ralisata Sandy , Razafindrakoto Jocelyn , Smith Jennifer L. , Ahmed Jehan , Smith Gueye Cara 
Published: April 2024

AbstractBackgroundIn Madagascar, the districts of Antsirabe II, Faratsiho and Antsiranana I have relatively low malaria incidence rates and have been selected by the National Malaria Control Programme for pilot elimination strategies. The districts have residual transmission despite increasing coverage and quality of malaria services. This study sought to identify priority subpopulations at highest risk for malaria and collect information on intervention preferences and methods that will inform subnational tailoring of malaria service delivery.MethodsThis mixed methods study employed (i) a quantitative malaria risk factor assessment in Antsirabe II and Faratsiho comprising a test-negative frequency matched case–control study and a qualitative risk factor assessment in Antsiranana I; and (ii) a qualitative formative assessment in all three districts. For the case–control study, a mixed effects logistic regression was used with age, sex and district included as fixed effects and health facility included as a random effect. The qualitative risk factor assessment used semi-structured interview guides and key informant interviews. For the qualitative formative assessment in the three districts, a summary report was generated following semi-structured interviews and focus group discussions with high-risk populations (HRPs) and stakeholders.ResultsIn Antsirabe II and Faratsiho districts, rice agriculture workers, outdoor/manual workers, particularly miners, and those with jobs that required travel or overnight stays, especially itinerant vendors, had higher odds of malaria infection compared to other (non-rice) agricultural workers. In Antsiranana I, respondents identified non-rice farmers, mobile vendors, and students as HRPs. Risk factors among these groups included overnight stays and travel patterns combined with a lack of malaria prevention tools. HRPs reported treatment cost and distance to the health facility as barriers to care and expressed interest in presumptive treatment and involvement of gatekeepers or people who have influence over intervention access or participation.ConclusionsThe study results illustrate the value of in-depth assessments of risk behaviours, access to services and prevention tools, surveillance and prevention strategies, and the involvement of gatekeepers in shaping subnational tailoring to reach previously unreached populations and address residual transmission in elimination settings.
Blood brain barrier permeability and astrocyte-derived extracellular vesicles in children with juvenile idiopathic arthritis: a cross-sectional study
Authors: Berntson Lillemor , Elfving Andreas , Samuelsson Alice Gabrielsson , Öman Anders , Mobarrez Fariborz 
Published: April 2024

Abstract
Background
Juvenile idiopathic arthritis (JIA) is the most prevalent rheumatic disease in children, and the inflammatory process is widely studied, primarily characterized by its impact on joint health. Emerging evidence suggests that JIA may also affect the central nervous system (CNS). This study investigates the potential CNS involvement in JIA by analyzing the presence of astrocyte-derived extracellular vesicles (EVs) and the S100B protein in plasma, both of which are indicative of astrocyte activity and blood-brain barrier (BBB) integrity.

Methods
EDTA plasma from 90 children diagnosed with JIA and 10 healthy controls, matched by age and gender, was analyzed for extracellular vesicles by flow cytometric measurement. Astrocyte-derived EVs were identified using flow cytometry with markers for aquaporin 4 (AQP-4) and glial fibrillary acidic protein (GFAP). Levels of the S100B protein were measured using a commercial ELISA. Disease activity was assessed using the Juvenile Arthritis Disease Activity Score (JADAS27, 0–57), and pain levels were measured using a visual analogue scale (VAS, 0–10 cm).

Results
Our analyses revealed a significantly higher concentration of astrocyte-derived EVs in the plasma of children with JIA compared with healthy controls. Furthermore, children with JADAS27 scores of 1 or higher exhibited notably higher levels of these EVs. The S100B protein was detectable exclusively in the JIA group.

Conclusion
The elevated levels of astrocyte-derived EVs and the presence of S100B in children with JIA provide evidence of BBB disruption and CNS involvement, particularly in those with higher disease activity. These findings underscore the importance of considering CNS health in the comprehensive management of JIA. Further research is required to elucidate the mechanisms behind CNS engagement in JIA and to develop treatments that address both joint and CNS manifestations of the disease.
Lessons we learned during the past four challenging years in the COVID-19 era: pharmacotherapy, long COVID complications, and vaccine development
Authors: Ghasemiyeh Parisa , Mohammadi-Samani Soliman 
Published: April 2024

AbstractAbout four years have passed since the detection of the first cases of COVID-19 in China. During this lethal pandemic, millions of people have lost their lives around the world. Since the first waves of COVID-19 infection, various pharmacotherapeutic agents have been examined in the management of COVID-19. Despite all these efforts in pharmacotherapy, drug repurposing, and design and development of new drugs, multiple organ involvement and various complications occurred during COVID-19. Some of these complications became chronic and long-lasting which led to the “long COVID” syndrome appearance. Therefore, the best way to eradicate this pandemic is prophylaxis through mass vaccination. In this regard, various vaccine platforms including inactivated vaccines, nucleic acid-based vaccines (mRNA and DNA vaccines), adenovirus-vectored vaccines, and protein-based subunit vaccines have been designed and developed to prevent or reduce COVID-19 infection, hospitalization, and mortality rates. In this focused review, at first, the most commonly reported clinical presentations of COVID-19 during these four years have been summarized. In addition, different therapeutic regimens and their latest status in COVID-19 management have been listed. Furthermore, the “long COVID” and related signs, symptoms, and complications have been mentioned. At the end, the effectiveness of available COVID-19 vaccines with different platforms against early SARS-CoV-2 variants and currently circulating variants of interest (VOI) and the necessity of booster vaccine shots have been summarized and discussed in more detail.
Exploring the perspectives and practices of humanitarian actors towards the Participation Revolution in humanitarian digital health responses: a qualitative study
Authors: Benson Jennifer , Lakeberg Meret , Brand Tilman 
Published: April 2024

Abstract
Background
As crises escalate worldwide, there is an increasing demand for innovative solutions to enhance humanitarian outcomes. Within this landscape, digital health tools have emerged as promising solutions to tackle certain health challenges. The integration of digital health tools within the international humanitarian system provides an opportunity to reflect upon the system’s paternalistic tendencies, driven largely by Global North organisations, that perpetuate existing inequities in the Global South, where the majority of crises occur. The Participation Revolution, a fundamental pillar of the Localisation Agenda, seeks to address these inequities by advocating for greater participation from crisis-affected people in response efforts. Despite being widely accepted as a best practice; a gap remains between the rhetoric and practice of participation in humanitarian response efforts. This study explores the extent and nature of participatory action within contemporary humanitarian digital health projects, highlighting participatory barriers and tensions and offering potential solutions to bridge the participation gap to enhance transformative change in humanitarian response efforts.

Methods
Sixteen qualitative interviews were conducted with humanitarian health practitioners and experts to retrospectively explored participatory practices within their digital health projects. The interviews were structured and analysed according to the Localisation Performance Measurement Framework’s participation indicators and thematically, following the Framework Method. The study was guided by the COREQ checklist for quality reporting.

Results
Varied participatory formats, including focus groups and interviews, demonstrated modest progress towards participation indicators. However, the extent of influence and power held by crisis-affected people during participation remained limited in terms of breadth and depth. Participatory barriers emerged under four key themes: project processes, health evidence, technology infrastructure and the crisis context. Lessons for leveraging participatory digital health humanitarian interventions were conducting thorough pre-project assessments and maintaining engagement with crisis-affected populations throughout and after humanitarian action.

Conclusion
The emerging barriers were instrumental in shaping the limited participatory reality and have implications: Failing to engage crisis-affected people risks perpetuating inequalities and causing harm. To advance the Participation Revolution for humanitarian digital health response efforts, the major participatory barriers should be addressed to improve humanitarian efficiency and digital health efficacy and uphold the rights of crisis-affected people.
How can a behavioral economics lens contribute to implementation science?
Authors: Hodson Nathan , Powell Byron J. , Nilsen Per , Beidas Rinad S. 
Published: April 2024

Abstract
Background
Implementation science in health is an interdisciplinary field with an emphasis on supporting behavior change required when clinicians and other actors implement evidence-based practices within organizational constraints. Behavioral economics has emerged in parallel and works towards developing realistic models of how humans behave and categorizes a wide range of features of choices that can influence behavior. We argue that implementation science can be enhanced by the incorporation of approaches from behavioral economics.
Main body
First, we provide a general overview of implementation science and ways in which implementation science has been limited to date. Second, we review principles of behavioral economics and describe how concepts from BE have been successfully applied to healthcare including nudges deployed in the electronic health record. For example, de-implementation of low-value prescribing has been supported by changing the default in the electronic health record. We then describe what a behavioral economics lens offers to existing implementation science theories, models and frameworks, including rich and realistic models of human behavior, additional research methods such as pre-mortems and behavioral design, and low-cost and scalable implementation strategies. We argue that insights from behavioral economics can guide the design of implementation strategies and the interpretation of implementation studies. Key objections to incorporating behavioral economics are addressed, including concerns about sustainment and at what level the strategies work.

Conclusion
Scholars should consider augmenting implementation science theories, models, and frameworks with relevant insights from behavioral economics. By drawing on these additional insights, implementation scientists have the potential to boost efforts to expand the provision and availability of high quality care.
Metabolite identification of salvianolic acid A in rat using post collision-induced dissociation energy-resolved mass spectrometry
Authors: Li Han , Zhang Ke , Chen Wei , Zhou Yuxuan , Li Jun , Zhao Yunfang , Song Yuelin 
Published: April 2024

Abstract
Background
As one of the most famous natural products, salvianolic acid A (SAA) is undergoing clinical trials for the treatments of angina pectoris and coronary heart disorders. However, the in vivo metabolites of SAA have only been tentatively identified, leading to a barrier for precise therapeutical drug monitoring.

Methods
Ultra-high performance liquid chromatography coupled with quadrupole time of flight tandem mass spectrometry (UPLC–Qtof-MS/MS) was firstly employed to acquire high-resolution MS1 and MS2 spectra for all metabolites. Through paying special attention onto the features of ester bond dissociation, metabolism sites were restricted at certain regions. To further determine the metabolism site, such as the monomethylated products (M23, M25, and M26), post collision-induced dissociation energy-resolved mass spectrometry (post-CID ER-MS) was proposed through programming progressive exciting energies to the second collision chamber of hybrid triple quadrupole-linear ion trap mass spectrometry (Qtrap-MS) device.

Results
After SAA oral administration, 29 metabolites (M1–M29), including five, thirteen, and sixteen ones in rat plasma, urine, and feces, respectively, were detected in rats. The metabolism route was initially determined by applying well-defined mass fragmentation pathways to those HR-m/z values of precursor and fragment ions. Metabolism site was limited to SAF- or DSS-unit based on the fragmentation patterns of ester functional group. Through matching the dissociation trajectories of concerned 1st-generation fragment ions with expected decomposition product anions using post-CID ER-MS strategy, M23 and M25 were unequivocally assigned as 3'-methyl-SAA and 3''-methyl-SAA, and M26 was identified as 2-methyl-SAA or 3-methyl-SAA. Hydrolysis, methylation, glucuronidation, sulfation, and oxidation were the primary metabolism channels being responsible for the metabolites' generation.

Conclusion
Together, the metabolism regions and sites of SAA metabolites were sequentially identified based on the ester bond dissociation features and post-CID ER-MS strategy. Importantly, the present study provided a promising way to elevate the structural identification confidence of natural products and metabolites.

Graphical abstract
Integration of metabolomics and transcriptomics reveals the therapeutic mechanism underlying Chelidonium majus L. in the treatment of allergic asthma
Authors: Wang Renguang , Sui Xintong , Dong Xin , Hu Liming , Li Zhimeng , Yu Hang , Li Cuicui , Ji Guoxin , Wang Shumin 
Published: April 2024

Abstract
Background
Chelidonium majus is a well-known traditional Chinese medicine, and has been reported of the effect in relieving cough and asthma. However, the mechanism of action is still unknown.

Methods
Asthmatic SD rats were first sensitized and established through ovalbumin (OVA) motivation. Subsequently, Hematoxylin and eosin (H&E) staining, Masson’s trichrome (Masson) staining, Periodic acid-Schiff (PAS) staining and inflammatory cytokines assay of interleukin (IL)-4, IL-6, IL-17 were implemented to evaluate the protective effects of Chelidonium majus on asthma. Then, the effects of Chelidonium majus and their molecular mechanisms of action on asthma were detected based on the integration of transcriptomics and metabolomics analyses.

Results
After administration with Chelidonium majus, the histological injuries of inflammation, collagen deposition and mucus secretion in lungs were attenuated and the serum inflammatory cytokines perturbations were also converted. Furthermore, integrated analysis revealed that after Chelidonium majus treatment, 7 different expression genes (DEGs) (Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9) and 9 metabolic biomarkers (ADP, Xanthosine, Hypoxanthine, Inosine, prostaglandin E2 (PGE2), prostaglandin F2a (PGF2a), phosphatidylserine, Creatine and LysoPC (10:0)) were discovered to be connected with the enrichment metabolic pathways, including Purine metabolism, Arachidonic acid metabolism, Arginine and proline metabolism and Glycerophospholipid metabolism. The obtained metabolic biomarkers and DEGs were mainly related to energy metabolism and inflammation, and may be potential therapeutic targets.

Conclusion
Chelidonium majus relieved OVA-induced asthma in rats by regulating the Alox15, P4ha1, Pla2g16, Pde3a, Nme1, Entpd8 and Adcy9 genes expression to restore the disorders in energy metabolism and inflammation.
Adjustment of positive end-expiratory pressure to body mass index during mechanical ventilation in general anesthesia: BodyVent, a randomized controlled trial
Authors: Selpien Helene , Eimer Christine , Thunecke David , Penon Jann , Schädler Dirk , Lautenschläger Ingmar , Ohnesorge Henning , Becher Tobias 
Published: April 2024

Abstract
Background
In patients requiring general anesthesia, lung-protective ventilation can prevent postoperative pulmonary complications, which are associated with higher morbidity, mortality, and prolonged hospital stay. Application of positive end-expiratory pressure (PEEP) is one component of lung-protective ventilation. The correct strategy for setting adequate PEEP, however, remains controversial. PEEP settings that lead to a lower pressure difference between end-inspiratory plateau pressure and end-expiratory pressure (“driving pressure,” ΔP) may reduce the risk of postoperative pulmonary complications. Preliminary data suggests that the PEEP required to prevent both end-inspiratory overdistension and end-expiratory alveolar collapse, thereby reducing ΔP, correlates positively with the body mass index (BMI) of patients, with PEEP values corresponding to approximately 1/3 of patient’s respective BMI. Thus, we hypothesize that adjusting PEEP according to patient BMI reduces ΔP and may result in less postoperative pulmonary complications.

Methods
Patients undergoing general anesthesia and endotracheal intubation with volume-controlled ventilation with a tidal volume of 7 ml per kg predicted body weight will be randomized and assigned to either an intervention group with PEEP adjusted according to BMI or a control group with a standardized PEEP of 5 mbar. Pre- and postoperatively, lung ultrasound will be performed to determine the lung aeration score, and hemodynamic and respiratory vital signs will be recorded for subsequent evaluation. The primary outcome is the difference in ΔP as a surrogate parameter for lung-protective ventilation. Secondary outcomes include change in lung aeration score, intraoperative occurrence of hemodynamic and respiratory events, oxygen requirements and postoperative pulmonary complications.

Discussion
The study results will show whether an intraoperative ventilation strategy with PEEP adjustment based on BMI has the potential of reducing the risk for postoperative pulmonary complications as an easy-to-implement intervention that does not require lengthy ventilator maneuvers nor additional equipment.

Trial registration
German Clinical Trials Register (DRKS), DRKS00031336. Registered 21st February 2023.

Trial status
The study protocol was approved by the ethics committee of the Christian-Albrechts-Universität Kiel, Germany, on 1st February 2023. Recruitment began in March 2023 and is expected to end in September 2023.
Conservative versus liberal oxygen therapy for intensive care unit patients: meta-analysis of randomized controlled trials
Authors: Li Xin-yu , Dai Bing , Hou Hai-jia , Zhao Hong-wen , Wang Wei , Kang Jian , Tan Wei 
Published: April 2024

Abstract
Background
It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients.

Methods
We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events.

Results
In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days.

Conclusions
COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.