bluuebunny/crossref_metadata_2025 huggingface dataset:
Multiprotein collagen/keratin hydrogel promoted myogenesis and angiogenesis of injured skeletal muscles in a mouse model
Authors: Namjoo Atieh Rezaei , Hassani Ayla , Amini Hassan , Nazaryabrbekoh Fateme , Saghati Sepideh , Saadatlou Mohammad Ali Ebrahimi , Khoshfetrat Ali Baradar , Khosrowshahi Nafiseh Didar , Rahbarghazi Reza
Published: April 2024

Volumetric loss is one of the challenging issues in muscle tissue structure that causes functio laesa. Tissue engineering of muscle tissue using suitable hydrogels is an alternative to restoring the physiological properties of the injured area. Here, myogenic properties of type I collagen (0.5%) and keratin (0.5%) were investigated in a mouse model of biceps femoris injury. Using FTIR, gelation time, and rheological analysis, the physicochemical properties of the collagen (Col)/Keratin scaffold were analyzed. Mouse C2C12 myoblast-laden Col/Keratin hydrogels were injected into the injury site and histological examination plus western blotting were performed to measure myogenic potential after 15 days. FTIR indicated an appropriate interaction between keratin and collagen. The blend of Col/Keratin delayed gelation time when compared to the collagen alone group. Rheological analysis revealed decreased stiffening in blended Col/Keratin hydrogel which is favorable for the extrudability of the hydrogel. Transplantation of C2C12 myoblast-laden Col/Keratin hydrogel to injured muscle tissues led to the formation of newly generated myofibers compared to cell-free hydrogel and collagen groups (p < 0.05). In the C2C12 myoblast-laden Col/Keratin group, a low number of CD31+ cells with minimum inflammatory cells was evident. Western blotting indicated the promotion of MyoD in mice that received cell-laden Col/Keratin hydrogel compared to the other groups (p < 0.05). Despite the increase of the myosin cell-laden Col/Keratin hydrogel group, no significant differences were obtained related to other groups (p > 0.05). The blend of Col/Keratin loaded with myoblasts provides a suitable myogenic platform for the alleviation of injured muscle tissue.
Why are medical students so motivated to learn ultrasound skills? A qualitative study
Authors: Pless Anina , Hari Roman , Harris Michael
Published: April 2024

Background

The introduction of ultrasound (US) courses into medical undergraduate courses is usually met with a particularly high level of student motivation. The reasons for this are unclear. The aim of this study was to investigate the factors that contribute to undergraduate medical students’ motivation to learn US skills. Understanding what motivates students to learn US will inform the efforts of faculty to foster students’ motivation to learn.

Methods

We carried out in-depth semi-structured one-to-one interviews with medical students participating in an optional US course at two Swiss universities. The interview guide consisted of 10 main questions. The content was informed by experts in the field of medical education and US, as well as by a literature review of motivation theories for learning, in particular by self-determination theory (SDT). SDT was used to guide the development of the interview guide and to reflect on the resulting themes in the discussion section. The interview guide was piloted with two medical students. The interviews lasted an average of 45 min and were audio recorded and transcribed. Thematic analysis was used to analyse the data.

Results

Fourteen undergraduate medical students in their preclinical (year 3) and clinical studies (years 4 and 5) elaborated on a wide range of reasons for their high motivation to learn US. They were motivated for US training because of the positive nimbus of the US modality, emphasising the advantages of visualisation. Students acknowledged the potential professional benefits of learning US and described it as a fun, exciting group activity.

Conclusions

The four themes we found in our analysis can all be related to the three universal needs described in SDT. The strong focus on the visual aspect and the positive nimbus of the modality goes beyond that and reflects the visuo-centric Zeitgeist, which claims the superiority of visual information over other data. Educators should be aware that motivation to learn is affected by the Zeitgeist and ensuing preconceptions, such as the perception of the positive nimbus surrounding a topic. Other key elements that can be implemented to motivate students are just-in-time feedback, enabling group experiences and creating awareness of the clinical relevance of learning content.
Impact of medical school experiences on the career choice of neurosurgery: a cross- sectional study from Pakistan
Authors: Shakir Muhammad , Irshad Hammad Atif , Ali Eisha Abid , Adil Amna , Altaf Ahmed , Enam Syed Ather
Published: April 2024

Background

Pakistan grapples with the issue of an inadequate neurosurgery workforce but the reasons for such a disparity remain uncertain. Previous studies have highlighted how various factors including medical school experiences have an impact on career choice, but no study has delved into the impact of medical school exposure among Pakistani medical students, especially for the field of neurosurgery. This study aims to evaluate the impact of neurosurgery exposure, mentorship, and interest groups on medical students' decision to pursue neurosurgery.

Methods

A national cross-sectional survey was conducted in Pakistan, collecting data from medical students, interns, and medical officers over a one-month period. Ethical approval was obtained from the Ethical Review Committee at Aga Khan University, Pakistan. The data was analyzed using SPSS version 26.

Results

Out of 2618 participants, 38.0% were male and 62.0% were female, with an average age of 21.82 years (± 2.65). Among them, only 358 (13.6%) were interested in pursuing neurosurgery as a career, while the remaining 2,260 (86.3%) were not. More females (58.9%) than males (41.1%) expressed interest in pursuing neurosurgery as their intended career. Most medical students interested in pursuing neurosurgery were in the early years of their medical school (1st Year: 19.6%, 2nd Year: 26.0%, 3rd Year: 20.9%). In our study, students from public sector institutions (52.2%) showed more interest in neurosurgery as a career choice compared to those from private sector institutions (44.1%). The main deterrents for choosing neurosurgery were intense training (42.2%), work-life balance (39.9%), limited residency slots (56.7%), medical knowledge (34.1%), and surgical skills (36.6%).

Conclusion

This study highlights the need for increased student engagement to inculcate the decision to pursue neurosurgery among medical students in Pakistan. A significant gap is highlighted, with the majority of interested students in early years. Public sector students show higher interest than their private sector counterparts. However, barriers like intense training, limited residency slots, and work-life balance concerns influence career choice. Targeted interventions like mentorship programs are crucial for fostering future neurosurgeons and advancing patient care and research. By addressing the identified disparities in experiences and promoting a supportive educational environment, it is possible to cultivate a future generation of skilled and dedicated neurosurgeons who can contribute to advancements in patient care and research in the field.
Six in ten female youths in low-income East African countries had problems in accessing health care: a multilevel analysis of recent demographic and health surveys from 2016–2021
Authors: Tiruneh Misganaw Guadie , Fenta Eneyew Talie , Endeshaw Destaw , Eshetu Habitu Birhan , Adal Ousman , Tareke Abiyu Abadi , Kebede Natnael , Delie Amare Mebrat , Bogale Eyob Ketema , Anagaw Tadele Fentabel
Published: April 2024

Background

Access to health care services is a basic human right, and an individual’s health and overall quality of life may suffer as a result of barriers to accessing health services. Access to comprehensive and quality health care is fundamental for promoting and maintaining health, preventing and treating diseases, and reducing premature deaths. However, only half of the African population has access to modern health services. Therefore, this study aimed to assess the health care access and associated factors among female youths in low-income East African countries.

Methods

This study used secondary data from 2016 to 2021 demographic and health surveys of 7 low-income East African countries. A total weighted sample of 51,064 youths was included. A multilevel binary logistic regression was employed to identify the associated factors of access to health care since the data has a hierarchical structure. Adjusted Odds Ratio (AOR) with a 95% confidence interval (CI) at a p-value less than 0.05 was used to measure the association of variables whereas Intra-class correlation coefficient (ICC), Median Odds Ratio (MOR), and proportional change in variance (PCV) were used to measure random effects.

Result

The overall magnitude of access to healthcare among female youths in low-income East African countries was 38.84% (95% CI: 38.41, 39.26). Youth’s educational level, rich wealth status, media exposure, and community level education were the positive while higher youth’s age and rural residence were the negative predictors of access to healthcare among female youths. Besides, living in different countries compared to Burundi was also an associated factor for accessing healthcare in low-income East African countries.

Conclusion

About six in ten female youths were not accessing health care in low-income East African countries. Therefore, to increase healthcare access, health managers and policymakers needed to develop strategies to improve the poor household wealth index, and redistribution of health services for rural residents. The decision-makers and program planners should also work on increasing access to education and media exposure for youths. Further research including health system and quality of service-related factors for accessing healthcare should also be considered by researchers.
Clinician and staff experiences with frustrated patients during an electronic health record transition: a qualitative case study
Authors: Ball Sherry L. , Kim Bo , Cutrona Sarah L. , Molloy-Paolillo Brianne K. , Ahlness Ellen , Moldestad Megan , Sayre George , Rinne Seppo T.
Published: April 2024

Background

Electronic health record (EHR) transitions are known to be highly disruptive, can drastically impact clinician and staff experiences, and may influence patients’ experiences using the electronic patient portal. Clinicians and staff can gain insights into patient experiences and be influenced by what they see and hear from patients. Through the lens of an emergency preparedness framework, we examined clinician and staff reactions to and perceptions of their patients’ experiences with the portal during an EHR transition at the Department of Veterans Affairs (VA).

Methods

This qualitative case study was situated within a larger multi-methods evaluation of the EHR transition. We conducted a total of 122 interviews with 30 clinicians and staff across disciplines at the initial VA EHR transition site before, immediately after, and up to 12 months after go-live (September 2020-November 2021). Interview transcripts were coded using a priori and emergent codes. The coded text segments relevant to patient experience and clinician interactions with patients were extracted and analyzed to identify themes. For each theme, recommendations were defined based on each stage of an emergency preparedness framework (mitigate, prepare, respond, recover).

Results

In post-go-live interviews participants expressed concerns about the reliability of communicating with their patients via secure messaging within the new EHR portal. Participants felt ill-equipped to field patients’ questions and frustrations navigating the new portal. Participants learned that patients experienced difficulties learning to use and accessing the portal; when unsuccessful, some had difficulties obtaining medication refills via the portal and used the call center as an alternative. However, long telephone wait times provoked patients to walk into the clinic for care, often frustrated and without an appointment. Patients needing increased in-person attention heightened participants’ daily workload and their concern for patients’ well-being. Recommendations for each theme fit within a stage of the emergency preparedness framework.

Conclusions

Application of an emergency preparedness framework to EHR transitions could help address the concerns raised by the participants, (1) mitigating disruptions by identifying at-risk patients before the transition, (2) preparing end-users by disseminating patient-centered informational resources, (3) responding by building capacity for disrupted services, and (4) recovering by monitoring integrity of the new portal function.
Ventricular bigeminy associated with myocardial ischemia in a dog with a colonic torsion: a case report
Authors: Burns Charlotte , Barletta Michele
Published: April 2024

Background

Ventricular bigeminy due to myocardial ischemia has been reported in humans as well as in canine patients with obstructive gastrointestinal diseases. This is the first case report of ventricular bigeminy in a dog with a colonic torsion that resolved after fluid resuscitation and restoration of myocardial perfusion.

Case presentation

An 11-year-old, male neutered mixed breed dog presented with a one day history of vomiting, tenesmus, and lethargy. Physical examination identified an irregular heart rhythm and intermittent pulse deficits. A ventricular arrhythmia represented by ventricular premature complexes (VPCs) organized in bigeminy, was appreciated on a 3-lead electrocardiogram (ECG) with a single lead (II) view. Abdominal radiographs confirmed a colonic torsion. Prior to anesthetic induction, ventricular bigeminy was non responsive to fentanyl or lidocaine. The patient was anesthetized and intravascular volume deficit was identified by dampened plethysmographic wave amplitude (plethysomographic variability), audible softening of the Doppler sound, and more pronounced pulse deficits. Fluid resuscitation was achieved with a combination of intravenous crystalloid and colloid fluid therapy comprising 7.2% hypertonic saline and 6% hetastarch. The patient’s cardiac rhythm converted to normal sinus after fluid resuscitation. The colonic torsion was surgically corrected. The patient recovered well from anesthesia and was ultimately discharged from the hospital 5 days later.

Conclusions

The present case report highlights that myocardial ischemia can lead to ventricular arrythmias, such as ventricular bigeminy. This is the first documented case of ventricular bigeminy in the canine patient with a colonic torsion. Assessment of patient volume status and appropriate fluid resuscitation along with continuous electrocardiogram (ECG) monitoring are vital to patient stability under general anesthesia.
Comprehensive characterization of immunogenic cell death in acute myeloid leukemia revealing the association with prognosis and tumor immune microenvironment
Authors: Chen Yongyu , Qiu Xue , Liu Rongrong
Published: April 2024

Background

This study aimed to explore the clinical significance of immunogenic cell death (ICD) in acute myeloid leukemia (AML) and its relationship with the tumor immune microenvironment characteristics. It also aimed to provide a potential perspective for bridging the pathogenesis of AML and immunological research, and to provide a theoretical basis for precise individualized treatment of AML patients.

Methods

Firstly, we identified two subtypes associated with ICD by consensus clustering and explored the biological enrichment pathways, somatic mutations, and tumor microenvironment landscape between the ICD subtypes. Additionally, we developed and validated a prognostic model associated with ICD-related genes. Finally, we conducted a preliminary exploration of the construction of disease regulatory networks and prediction of small molecule drugs based on five signature genes.

Results

Differentially expressed ICD-related genes can distinguish AML into subgroups with significant differences in clinical characteristics and survival prognosis. The relationship between the ICD- high subgroup and the immune microenvironment was tight, showing significant enrichment in immune-related pathways such as antibody production in the intestinal immune environment, allograft rejection, and Leishmaniasis infection. Additionally, the ICD- high subtype showed significant upregulation in a variety of immune cells such as B_cells, Macrophages_M2, Monocytes, and T_cells_CD4. We constructed a prognostic risk feature based on five signature genes (TNF, CXCR3, CD4, PIK3CA and CALR), and the time-dependent ROC curve confirmed the high accuracy in predicting the clinical outcomes.

Conclusion

There is a strong close relationship between the ICD- high subgroup and the immune microenvironment. Immunogenicity-related genes have the potential to be a prognostic biomarker for AML.
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

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

Background

In 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.

Methods

This 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.

Results

In 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.

Conclusions

The 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

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

About 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

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

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

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

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

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

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.
Impact of the COVID-19 era on preventative primary care for children 0–5 years old: a scoping review protocol
Authors: Qi Xin , Jordan Mackenzie , Mignacca Isabella , Bayoumi Imaan , Li Patricia
Published: April 2024

Background

The COVID-19 pandemic has resulted in widespread disruptions to primary healthcare delivery and shifts to virtual care. Reduced in-person paediatric primary care visit rates have been reported. However, the extent to which access to primary preventative care has been impacted remains unclear. The objective of this scoping review is to characterise the utilisation of preventative primary care and its association with child development for children ages 0–5 years old during the COVID-19 era. In addition, we will determine if specific groups of children are at greater risk for reduced access to care.

Methods

A systematic search will be conducted for studies published between March 11, 2020, and October 2023 in the following databases: MEDLINE (Ovid), Embase (Ovid), Cochrane Library (CENTRAL and CDSR), Web of Science, and CINAHL (EBSCOhost). This scoping review will follow the methodological framework developed by Arksey and O’Malley and updated by the Joanna Briggs Institute (JBI). Studies related to primary preventative care of children aged 0–5 years old conducted in English and in high-income countries will be screened. Studies published before March 11, 2020, in acute care and low–middle-income settings will be excluded. Results will be summarised for appointments attended, delayed, and missed. In addition, we will summarise findings on the impact of COVID-19 on child development. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) guidelines.

Discussion

Further investigation is required to better understand the relationship between attendance of preventative primary care for children and its effects on child development. The findings obtained from this review will offer essential context to guide policy-making and healthcare service planning for the period following the pandemic.
Agomirs upregulating carboxypeptidase E expression rescue hippocampal neurogenesis and memory deficits in Alzheimer’s disease
Authors: Jiang Dongfang , Liu Hongmei , Li Tingting , Zhao Song , Yang Keyan , Yao Fuwen , Zhou Bo , Feng Haiping , Wang Sijia , Shen Jiaqi , Tang Jinglan , Zhang Yu-Xin , Wang Yun , Guo Caixia , Tang Tie-Shan
Published: April 2024

Background

Adult neurogenesis occurs in the subventricular zone (SVZ) and the subgranular zone of the dentate gyrus in the hippocampus. The neuronal stem cells in these two neurogenic niches respond differently to various physiological and pathological stimuli. Recently, we have found that the decrement of carboxypeptidase E (CPE) with aging impairs the maturation of brain-derived neurotrophic factor (BDNF) and neurogenesis in the SVZ. However, it remains unknown whether these events occur in the hippocampus, and what the role of CPE is in the adult hippocampal neurogenesis in the context of Alzheimer’s disease (AD).

Methods

In vivo screening was performed to search for miRNA mimics capable of upregulating CPE expression and promoting neurogenesis in both neurogenic niches. Among these, two agomirs were further assessed for their effects on hippocampal neurogenesis in the context of AD. We also explored whether these two agomirs could ameliorate behavioral symptoms and AD pathology in mice, using direct intracerebroventricular injection or by non-invasive intranasal instillation.

Results

Restoration of CPE expression in the hippocampus improved BDNF maturation and boosted adult hippocampal neurogenesis. By screening the miRNA mimics targeting the 5’UTR region of Cpe gene, we developed two agomirs that were capable of upregulating CPE expression. The two agomirs significantly rescued adult neurogenesis and cognition, showing multiple beneficial effects against the AD-associated pathologies in APP/PS1 mice. Of note, noninvasive approach via intranasal delivery of these agomirs improved the behavioral and neurocognitive functions of APP/PS1 mice.

Conclusions

CPE may regulate adult hippocampal neurogenesis via the CPE–BDNF–TrkB signaling pathway. This study supports the prospect of developing miRNA agomirs targeting CPE as biopharmaceuticals to counteract aging- and disease-related neurological decline in human brains.
Estimating additional health and social costs in eating disorder care for young people during the COVID-19 pandemic: implications for surveillance and system transformation
Authors: Obeid Nicole , Coelho Jennifer S. , Booij Linda , Dimitropoulos Gina , Silva-Roy Patricia , Bartram Mary , Clement Fiona , de Oliveira Claire , Katzman Debra K.
Published: April 2024

Background

The impact of the COVID-19 pandemic on young people with eating disorders (EDs) and their families was profound, with surging rates of hospitalizations and referrals reported internationally. This paper provides an account of the additional health and social costs of ED care for young people living in Canada incurred during the COVID-19 pandemic, drawing attention to the available data to inform these estimates while noting gaps in data capacities to account for a full view of the ED system of care.

Methods

Three methodologies were used to capture costs: (1) provincial administrative data holdings available at the Canadian Institute of Health Information (CIHI) were used by Deloitte Access Economics to conduct analyses on costs related to hospitalizations, emergency room visits, outpatient visits with physicians and loss of well-being from being on a waitlist. These were examined across three fiscal years (April 1 to March 31, 2019–2022) to compare costs from one year before to two years after the onset of the pandemic, (2) data collected on support-based community ED organizations and, (3) costs identified by young people, caregivers and health care professionals.

Results

Estimates of additional health care costs and social costs arising from ED care waitlists were estimated to have increased by 21% across the two years after the onset of the pandemic and is likely to represent an underestimate of costs. Costs related to some standard ED care services (e.g. day treatment programs) and support-based community ED organizations that saw a 118% increase in services during this time, are some examples of costs not captured in the current cost estimate.

Conclusions

This paper provides a first account of the additional health and social ED care costs associated with the pandemic, which indicate at minimum, a 21% increase. The results invite discussion for more investments in ED services for young people in Canada, as it is unclear if needs are expected to remain elevated. We suggest a call for a national surveillance strategy to improve data holdings to aid in managing services and informing policy. A robust strategy could open the door for much-needed, data-informed, system transformation efforts that can improve ED care for youth, families and clinicians.