bluuebunny/crossref_metadata_2025_split huggingface dataset:
“It didn’t hurt me”: patients’ and providers’ perspectives on unsupervised take-home doses, drug diversion, and overdose risks in the provision of medication for opioid use disorder during COVID-19 in San Juan, Puerto Rico
Authors: Abadie Roberto , Fisher Celia B. 
Published: April 2024

Abstract
Background
During the COVID−19 pandemic, clinics offering medication for opioid use disorder (MOUD) needed to rapidly introduce unsupervised take−home dosing, while relapsing patients and patients unable to enter treatment faced increased risks of fentanyl−related overdose deaths and other drug−related harms. Based on a qualitative study of people who inject drugs (PWID) receiving MOUD treatment and MOUD staff in Puerto Rico, this paper documents the lived experiences of patients and providers during this period and the risk perceptions and management strategies to address substance misuse and drug diversion attributable to unsupervised take−home−dose delivery.

Methods
In−depth qualitative interviews were conducted with patients (N = 25) and staff (N = 25) in two clinics providing MOUD in San Juan, Puerto Rico, during 2022. Patients and staff were receiving or providing treatment during the pandemic, and patients reported injection drug use during the past thirty days.

Results
Patients were overwhelmingly male (84%), unmarried (72%), and unemployed (52%), with almost half (44%) injecting one to three times a day. Mean time in treatment was 7 years. Staff had a mean age of 46 years with more than half of the sample (63%) female. The majority of patients believed that unsupervised take−home dosing had no significant effect on their treatment adherence or engagement. In contrast, providers expressed concerns over the potential for drug diversion and possible increased risks of patient attrition, overdose episodes, and poor treatment outcomes.

Conclusion
This study underscores the importance of insider perspectives on harm−reduction changes in policy implemented during a health crisis. Of note is the finding that staff disagreed among themselves regarding the potential harms of diversion and changes in drug testing protocols. These different perspectives are important to address so that future pandemic policies are successfully designed and implemented. Our study also illuminates disagreement in risk assessments between patients and providers. This suggests that preparation for emergency treatment plans requires enhanced communication with patients to match treatments to the context of lived experience.
Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications
Authors: Qiao Xinyu , Yin Junhao , Zheng Zhihuan , Li Liangge , Feng Xiujing 
Published: April 2024

AbstractSepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS.
Comparing outcomes in patients with exsanguinating injuries: an Eastern Association for the Surgery of Trauma (EAST), multicenter, international trial evaluating prioritization of circulation over intubation (CAB over ABC)
Authors: Ferrada Paula , García Alberto , Duchesne Juan , Brenner Megan , Liu Chang , Ordóñez Carlos , Menegozzo Carlos , Salamea Juan Carlos , Feliciano David 
Published: April 2024

Abstract
Introduction
Hemorrhage is a major cause of preventable trauma deaths, and the ABC approach is widely used during the primary survey. We hypothesize that prioritizing circulation over intubation (CAB) can improve outcomes in patients with exsanguinating injuries.

Methods
A prospective observational study involving international trauma centers was conducted. Patients with systolic blood pressure below 90 who were intubated within 30 min of arrival were included. Prioritizing circulation (CAB) was defined as delaying intubation until blood products were started, and/or bleeding control was performed before securing the airway. Demographics, clinical data, and outcomes were recorded.

Results
The study included 278 eligible patients, with 61.5% falling within the “CAB” cohort and 38.5% in the “ABC” cohort. Demographic and disease characteristics, including age, sex, ISS, use of blood products, and other relevant factors, exhibited comparable distributions between the two cohorts. The CAB group had a higher proportion of penetrating injuries and more patients receiving intubation in the operating room. Notably, patients in the CAB group demonstrated higher GCS scores, lower SBP values before intubation but higher after intubation, and a significantly lower incidence of cardiac arrest and post-intubation hypotension. Key outcomes revealed significantly lower 24-hour mortality in the CAB group (11.1% vs. 69.2%), a lower rate of renal failure, and a higher rate of ARDS. Multivariable logistic regression models showed a 91% reduction in the odds of mortality within 24 h and an 89% reduction at 30 days for the CAB cohort compared to the ABC cohort. These findings suggest that prioritizing circulation before intubation is associated with improved outcomes in patients with exsanguinating injuries.

Conclusion
Post-intubation hypotension is observed to be correlated with worse outcomes. The consideration of prioritizing circulation over intubation in patients with exsanguinating injuries, allowing for resuscitation, or bleeding control, appears to be associated with potential improvements in survival. Emphasizing the importance of circulation and resuscitation is crucial, and this approach might offer benefits for various bleeding-related conditions.
METTL14-mediated N6-methyladenosine modification induces the ferroptosis of hypoxia/reoxygenation-induced cardiomyocytes
Authors: Zhao Chunyu , Li Jianing 
Published: April 2024

Abstract
Background
Hypoxia/reoxygenation (H/R) induces cardiomyocyte ferroptosis, a core remodeling event in myocardial ischemia/reperfusion injury. Methyltransferase-like 14 (METTL14) emerges as a writer of N6-methyladenosine (m6A) modification. This study was conducted to decipher the role of METTL14 in H/R-induced cardiomyocyte ferroptosis.

Methods
Mouse cardiomyocytes HL-1 were cultured and underwent H/R treatment. The degree of ferroptosis after H/R treatment was appraised by the cell counting kit-8 assay, assay kits (ROS/GSH/Fe2+), and Western blotting (GPX4/ACSL4). The intracellular expressions of METTL14, pri-miR-146a-5p, miR-146a-5p, or adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 1 (APPL1) were examined by real-time quantitative polymerase chain reaction or Western blotting, with m6A quantification analysis and RNA immunoprecipitation to determine the total m6A level and the expression of pri-miR-146a-5p bound to DiGeorge critical region 8 (DGCR8) and m6A-modified pri-miR-146a-5p. The binding of miR-146a-5p to APPL1 was testified by the dual-luciferase assay.

Results
H/R treatment induced cardiomyocyte ferroptosis (increased ROS, Fe2+, and ACSL4 and decreased GSH and GPX4) and upregulated METTL14 expression. METTL14 knockdown attenuated H/R-induced cardiomyocyte ferroptosis. METTL14 induced the recognition of pri-miR-146a-5p by DGCR8 by increasing m6A modification on pri-miR-146a-5p, which promoted the conversion of pri-miR-146a-5p into miR-146a-5p and further repressed APPL1 transcription. miR-146a-5p upregulation or APPL1 downregulation limited the inhibitory effect of METTL14 downregulation on H/R-induced cardiomyocyte ferroptosis.

Conclusion
METTL14 promoted miR-146a-5p expression through the recognition and processing of pri-miR-146a-5p by DGCR8, which repressed APPL1 transcription and triggered H/R-induced cardiomyocyte ferroptosis.
A retrospective analysis of mission reports in the national Swedish Police Registry on mountain rescue 2018–2022: here be snowmobiles
Authors: Westman Anton , Björnstig Johanna 
Published: April 2024

Abstract
Background
Increasing mountain activity and decreasing participant preparedness, as well as climate change, suggest needs to tailor mountain rescue. In Sweden, previous medical research of these services are lacking. The aim of the study is to describe Swedish mountain rescue missions as a basis for future studies, public education, resource allocation, and rescuer training.

Methods
Retrospective analysis of all mission reports in the national Swedish Police Registry on Mountain Rescue 2018–2022 (n = 1543). Outcome measures were frequencies and characteristics of missions, casualties, fatalities, traumatic injuries, medical conditions, and incident mechanisms.

Results
Jämtland county had the highest proportion of missions (38%), followed by Norrbotten county (36%). 2% of missions involved ≥ 4 casualties, and 44% involved ≥ 4 mountain rescuers. Helicopter use was recorded in 59% of missions. Non-Swedish citizens were rescued in 12% of missions. 37% of casualties were females. 14% of casualties were ≥ 66 or ≤ 12 years of age. Of a total 39 fatalities, cardiac event (n = 14) was the most frequent cause of death, followed by trauma (n = 10) and drowning (n = 8). There was one avalanche fatality. 8 fatalities were related to snowmobiling, and of the total 1543 missions, 309 (20%) were addressing snowmobiling incidents. Of non-fatal casualties, 431 involved a medical condition, of which 90 (21%) suffered hypothermia and 73 (17%) cardiovascular illness.

Conclusions
These baseline data suggest snowmobiling, cardiac events, drownings, multi-casualty incidents, and backcountry internal medicine merit future study and intervention.
Effects of risk factors on the development and mortality of early- and late-onset dementia: an 11-year longitudinal nationwide population-based cohort study in South Korea
Authors: Chun Min Young , Chae Wonjeong , Seo Sang Won , Jang Hyemin , Yun Jihwan , Na Duk L. , Kang Dongwoo , Lee Jungkuk , Hammers Dustin B. , Apostolova Liana G. , Jang Sung-In , Kim Hee Jin 
Published: April 2024

Abstract
Background
Early-onset dementia (EOD, onset age < 65) and late-onset dementia (LOD, onset age ≥ 65) exhibit distinct features. Understanding the risk factors for dementia development and mortality in EOD and LOD respectively is crucial for personalized care. While risk factors are known for LOD development and mortality, their impact on EOD remains unclear. We aimed to investigate how hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and osteoporosis influence the development and mortality of EOD and LOD, respectively.

Methods
Using the Korean National Health Insurance Service (NHIS) database, we collected 546,709 dementia-free individuals and followed up for 11 years. In the two study groups, the Younger group (< 65 years old) and the Older group (≥ 65 years old), we applied Cox proportional hazard models to assess risk factors for development of EOD and LOD, respectively. Then, we assessed risk factors for mortality among EOD and LOD.

Results
Diabetes mellitus and osteoporosis increased the risk of EOD and LOD development. Hypertension increased the risk of EOD, while atrial fibrillation increased the risk of LOD. Conversely, hyperlipidemia exhibited a protective effect against LOD development. Additionally, diabetes mellitus increased mortality in EOD and LOD. Hypertension and atrial fibrillation increased mortality in LOD, while hyperlipidemia decreased mortality in EOD and LOD.

Conclusions
Risk factors influencing dementia development and mortality differed in EOD and LOD. Targeted public health interventions addressing age-related risk factors may reduce dementia incidence and mortality.
Association of midlife body-weight variability and cycles with earlier dementia onset: a nationwide cohort study
Authors: Park Yujin , Kim Su Hwan , Ryu Jiwon , Yoon Hyung-Jin 
Published: April 2024

Abstract
Background
Given the rising awareness of health-related lifestyle modifications, the impact of changes in body weight (BW) on cognitive function and dementia generates significant concern. This study aimed to investigate the association between BW changes and dementia in a middle-aged Korean population.

Methods
A retrospective, population-based longitudinal study was conducted utilizing data from the National Health Insurance Service (NHIS) database. Participants aged 40 years or older in 2011 who underwent at least five health checkups between 2002 and 2011 were followed-up for dementia until 2020. A total of 3,635,988 dementia-free Korean aged < 65 at baseline were examined. We analyzed the association between BW variability independent of the mean (VIM) with BW cycle, defined as either an upward or a downward direction of BW, and the risk of incident dementia.

Results
The results showed an increased risk of dementia in the highest quartile of VIM quartile (hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.47–1.58) compared to the lowest quartile of VIM. Additionally, the results showed an even higher increased risk of dementia in the highest BW cycle (≥ 2 cycles of 10% BW = HR 2.00, 95% CI 1.74–1.29). Notably, the combined concept of VIM with BW cycle showed an even higher dementia risk (highest quartile of VIM with ≥ 2 cycles of 10% BW = HR 2.37, 95% CI 2.05–2.74) compared to the baseline group (lowest quartile of VIM with < 3% BW cycle).

Conclusions
The present study highlights the importance of considering BW changes with BW variability along with the BW cycle to assess dementia risk in detail, providing valuable insights for preventive strategies.
Matrix-assisted laser desorption/ionization mass spectrometry imaging for quorum sensing
Authors: Kuik Christel , van Hoogstraten Sanne W.G. , Arts Jacobus J.C. , Honing Maarten , Cillero-Pastor Berta 
Published: April 2024

AbstractQuorum sensing (QS) is a complex communication system in bacteria, directing their response to the environment. QS is also one of the main regulators of bacterial biofilms’ formation, maturation and dispersion. Matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) is a molecular imaging technique that allows the mapping of QS molecules in bacterial biofilms. Here, we highlight the latest advances in MALDI-MSI in recent years and how this technology can improve QS understanding at the molecular level.
Structural properties of immune complexes formed by viral antigens and specific antibodies shape the inflammatory response of macrophages
Authors: Lučiūnaitė Asta , Mašalaitė Kristina , Plikusiene Ieva , Maciulis Vincentas , Juciute Silvija , Norkienė Milda , Žvirblienė Aurelija 
Published: April 2024

AbstractData on the course of viral infections revealed severe inflammation as a consequence of antiviral immune response. Despite extensive research, there are insufficient data on the role of innate immune cells in promoting inflammation mediated by immune complexes (IC) of viral antigens and their specific antibodies. Recently, we demonstrated that antigens of human polyomaviruses (PyVs) induce an inflammatory response in macrophages. Here, we investigated macrophage activation by IC. We used primary murine macrophages as a cell model, virus-like particles (VLPs) of PyV capsid protein as antigens, and a collection of murine monoclonal antibodies (mAbs) of IgG1, IgG2a, IgG2b subclasses. The inflammatory response was investigated by analysing inflammatory chemokines and activation of NLRP3 inflammasome. We observed a diverse pattern of chemokine secretion in macrophages treated with different IC compared to VLPs alone. To link IC properties with cell activation status, we characterised the IC by advanced optical and acoustic techniques. Ellipsometry provided precise real-time kinetics of mAb-antigen interactions, while quartz crystal microbalance measurements showed changes in conformation and viscoelastic properties during IC formation. These results revealed differences in mAb-antigen interaction and mAb binding parameters of the investigated IC. We found that IC-mediated cell activation depends more on IC characteristics, including mAb affinity, than on mAb affinity for the activating Fc receptor. IC formed by the highest affinity mAb showed a significant enhancement of inflammasome activation. This may explain the hyperinflammation related to viral infection and vaccination. Our findings demonstrate that IC promote the viral antigen-induced inflammatory response depending on antibody properties.
“We’re sinking”: a qualitative interview-based study on stakeholder perceptions of structural and process limitations to the Canadian healthcare system
Authors: Parsons Leigh Jeanna , Moss Stephana Julia , Mizen Sara J. , Sriskandarajah Cynthia , FitzGerald Emily A. , Quinn Amity E. , Clement Fiona , Farkas Brenlea , Dodds Alexandra , Columbus Melanie , Stelfox Henry T. 
Published: April 2024

Abstract
Background
Despite longstanding efforts and calls for reform, Canada’s incremental approach to healthcare changes has left the country lagging behind other OECD nations. Reform to the Canadian healthcare system is essential to develop a higher performing system. This study sought to gain a deeper understanding of the views of Canadian stakeholders on structural and process deficiencies and strategies to improve the Canadian healthcare system substantially and meaningfully.

Methods
We conducted individual, ~ 45-minute, semi-structured virtual interviews from May 2022 to August 2022. Using existing contacts and snowball sampling, we targeted one man and one woman from five regions in Canada across four stakeholder groups: (1) public citizens; (2) healthcare leaders; (3) academics; and (4) political decision makers. Interviews centered on participants’ perceptions of the state of the current healthcare system, including areas where major improvements are required, and strategies to achieve suggested enhancements; Donabedian’s Model (i.e., structure, process, outcomes) was the guiding conceptual framework. Interviews were audio-recorded, transcribed verbatim, and de-identified, and inductive thematic analysis was performed independently and in duplicate according to published methods.

Results
The data from 31 interviews with 13 (41.9%) public citizens, 10 (32.3%) healthcare leaders, 4 (12.9%) academics, and 4 (12.9%) political decision makers resulted in three themes related to the structure of the healthcare system (1. system reactivity; 2. linkage with the Canadian identity; and 3. political and funding structures), three themes related to healthcare processes (1. staffing shortages; 2. inefficient care; and 3. inconsistent care), and three strategies to improve short- and long-term population health outcomes (1. delineating roles and revising incentives; 2. enhanced health literacy; 3. interdisciplinary and patient-centred care).

Conclusion
Canadians in our sample identified important structural and process limitations to the Canadian healthcare system. Meaningful reforms are needed and will require addressing the link between the Canadian identity and our healthcare system to facilitate effective development and implementation of strategies to improve population health outcomes.
Balancing the books: unveiling the direct impact of an integrated energy system model on industries, households and government revenues
Authors: George Jan Frederick , Marx Alexander , Held Anne , Winkler Jenny , Bekk Anke , Ragwitz Mario 
Published: April 2024

Abstract
Background
The transition towards a sustainable energy system is reshaping the demand for final energy, driven by the diffusion of new end-use technologies. This shift not only impacts consumers’ energy expenses, but also holds implications for the public budget. Building on data from a German energy transition scenario, we analyse the direct impact of energy costs on industries, low-income households, and changes in government revenues from the taxes and levies on final energy carriers. Our analysis considers the impact of current policies and explores a scenario introducing additional excise tax rates to offset potential revenue losses.

Results
We found that substantial carbon price increases could generate revenues that offset the losses from excise taxes on fossil fuels while enabling the financing of renewable support from the public budget by the end of this decade. Nevertheless, a decline in government revenues from taxes and levies is anticipated after 2030 until the middle of the century due to the declining use of fossil fuels. Maintaining current excise tax revenues during the transition could be achieved by introducing additional excise taxes on fossil fuels and electricity. Lastly, our analysis indicated a continuous decline in household energy expenditures until 2050, whereas energy-intensive industries face adverse impacts due to decarbonisation.

Conclusions
This research provides valuable insights into the fiscal implications of the energy transition, shedding light on different industrial sectors and households while considering the evolving impact on the public budget. Policymakers may need to consider systemic reforms or alternative financing mechanisms outside the energy system to balance the books.
Assessment of the antibacterial efficacy of silver nanoparticles-based Artemisia annua against methicillin-resistant Staphylococcus aureus-infected lung tissues in albino rats
Authors: Shaaban Mohamed T. , Abdel-Hamid Marwa Salah , Orabi Sahar H. , Korany Reda M. S. , Elbawab Rania Hamed 
Published: April 2024

AbstractThe production of alternative and effective medicines is crucial given that antibiotic resistance is currently a global health concern. Several biochemical identification tests were used to screen for Staphylococcus aureus isolates. Analysis of Artemisia annua extract was performed using a trace GC‒mass spectrometer, which revealed that the A. annua extract contains numerous compounds, such as artemisinins, palmitic acid and other vital essential compounds that have antioxidant and anti-inflammatory properties. The isolate st.8 was resistant to cefoxitin, oxacillin, and cephalosporins; furthermore, MALDI-TOF/MS Biotyper® identified it as methicillin-resistant S. aureus with confidence value 99.9% of mass spectrum compared with reference spectra. The synthesis of green silver nanoparticles based on A. annua as a reducing agent was confirmed via partial characterizations: (HR-TEM), (XRD), (SEM), (EDX) and (FTIR) analysis. The significant of antibacterial activity of the new green material (AgNPs) was achieved by determining the agar well diffusion assay. Furthermore, compared with those in the Staphylococcus-infected group, a significant decrease in hematological parameters was observed, with an increase in antioxidant biomarkers, a decrease in interstitial tissue thickening by inflammatory cells, and a weak positive immune reaction in a few cells (TNF-α and iNOS) in rats. Overall, this study is a promising step toward the development of new and effective strategies for combating MRSA infections.