bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased secretion of adipocyte-derived extracellular vesicles is associated with adipose tissue inflammation and the mobilization of excess lipid in human obesity
Authors: Matilainen Johanna , Berg Viivi , Vaittinen Maija , Impola Ulla , Mustonen Anne-Mari , Männistö Ville , Malinen Marjo , Luukkonen Veera , Rosso Natalia , Turunen Tanja , Käkelä Pirjo , Palmisano Silvia , Arasu Uma Thanigai , Sihvo Sanna P. , Aaltonen Niina , Härkönen Kai , Caddeo Andrea , Kaminska Dorota , Pajukanta Päivi , Kaikkonen Minna U. , Tiribelli Claudio , Käkelä Reijo , Laitinen Saara , Pihlajamäki Jussi , Nieminen Petteri , Rilla Kirsi 
Published: July 2024

Abstract
Background
Obesity is a worldwide epidemic characterized by adipose tissue (AT) inflammation. AT is also a source of extracellular vesicles (EVs) that have recently been implicated in disorders related to metabolic syndrome. However, our understanding of mechanistic aspect of obesity’s impact on EV secretion from human AT remains limited.

Methods
We investigated EVs from human Simpson Golabi Behmel Syndrome (SGBS) adipocytes, and from AT as well as plasma of subjects undergoing bariatric surgery. SGBS cells were treated with TNFα, palmitic acid, and eicosapentaenoic acid. Various analyses, including nanoparticle tracking analysis, electron microscopy, high-resolution confocal microscopy, and gas chromatography–mass spectrometry, were utilized to study EVs. Plasma EVs were analyzed with imaging flow cytometry.

Results
EVs from mature SGBS cells differed significantly in size and quantity compared to preadipocytes, disagreeing with previous findings in mouse adipocytes and indicating that adipogenesis promotes EV secretion in human adipocytes. Inflammatory stimuli also induced EV secretion, and altered EV fatty acid (FA) profiles more than those of cells, suggesting the role of EVs as rapid responders to metabolic shifts. Visceral AT (VAT) exhibited higher EV secretion compared to subcutaneous AT (SAT), with VAT EV counts positively correlating with plasma triacylglycerol (TAG) levels. Notably, the plasma EVs of subjects with obesity contained a higher number of adiponectin-positive EVs than those of lean subjects, further demonstrating higher AT EV secretion in obesity. Moreover, plasma EV counts of people with obesity positively correlated with body mass index and TNF expression in SAT, connecting increased EV secretion with AT expansion and inflammation. Finally, EVs from SGBS adipocytes and AT contained TAGs, and EV secretion increased despite signs of less active lipolytic pathways, indicating that AT EVs could be involved in the mobilization of excess lipids into circulation.

Conclusions
We are the first to provide detailed FA profiles of human AT EVs. We report that AT EV secretion increases in human obesity, implicating their role in TAG transport and association with adverse metabolic parameters, thereby emphasizing their role in metabolic disorders. These findings promote our understanding of the roles that EVs play in human AT biology and metabolic disorders.
Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19
Authors: Liu Fengjiao , Yang Huqin , Yang Tingyu , Zhang Zhijin , Guan Lujia , Gao Leyi , Ma Haomiao , Zhang Haifan , Song Nan , Tong Zhaohui , Li Jieqiong 
Published: July 2024

AbstractThe persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1–3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients.
Impact of therapeutic inhibition of oncogenic cell signaling tyrosine kinase on cell metabolism: in vivo-detectable metabolic biomarkers of inhibition
Authors: Nath Kavindra , Gupta Pradeep K. , Basappa Johnvesly , Wang Shengchun , Sen Neil , Lobello Cosimo , Tomar Jyoti S. , Shestov Alexander A. , Orlovskiy Stepan , Arias-Mendoza Fernando , Rauert-Wunderlich Hilka , Nelson David S. , Glickson Jerry D. , Wasik Mariusz A. 
Published: July 2024

Abstract
Background
Inhibition of kinases is the ever-expanding therapeutic approach to various types of cancer. Typically, assessment of the treatment response is accomplished by standard, volumetric imaging procedures, performed weeks to months after the onset of treatment, given the predominantly cytostatic nature of the kinase inhibitors, at least when used as single agents. Therefore, there is a great clinical need to develop new monitoring approaches to detect the response to kinase inhibition much more promptly. Noninvasive 1H magnetic resonance spectroscopy (MRS) can measure in vitro and in vivo concentration of key metabolites which may potentially serve as biomarkers of response to kinase inhibition.

Methods
We employed mantle cell lymphoma (MCL) cell lines demonstrating markedly diverse sensitivity of inhibition of Bruton’s tyrosine kinase (BTK) regarding their growth and studied in-depth effects of the inhibition on various aspects of cell metabolism including metabolite synthesis using metabolomics, glucose and oxidative metabolism by Seahorse XF technology, and concentration of index metabolites lactate, alanine, total choline and taurine by 1H MRS.

Results
Effective BTK inhibition profoundly suppressed key cell metabolic pathways, foremost pyrimidine and purine synthesis, the citrate (TCA) cycle, glycolysis, and pyruvate and glutamine/alanine metabolism. It also inhibited glycolysis and amino acid-related oxidative metabolism. Finally, it profoundly and quickly decreased concentration of lactate (a product of mainly glycolysis) and alanine (an indicator of amino acid metabolism) and, less universally total choline both in vitro and in vivo, in the MCL xenotransplant model. The decrease correlated directly with the degree of inhibition of lymphoma cell expansion and tumor growth.

Conclusions
Our results indicate that BTK inhibition exerts a broad and profound suppressive effect on cell metabolism and that the affected index metabolites such as lactate, alanine may serve as early, sensitive, and reliable biomarkers of inhibition in lymphoma patients detectable by noninvasive MRS-based imaging method. This kind of imaging-based detection may also be applicable to other kinase inhibitors, as well as diverse lymphoid and non-lymphoid malignancies.
Designing a Midwife-Led Birth Center Program Based on the MAP-IT Model: A Sequential Explanatory Mixed-Methods Study
Authors: Bakhshi Mohaddeseh , Mollazadeh Sanaz , Khadivzadeh Talat , Moghri Javad , Saki Azadeh , Firoozi Mahboobeh 
Published: July 2024

Abstract
Background
In recent decades, medical supervision of the labor and delivery process has expanded beyond its boundaries to the extent that in many settings, childbirth has become a medical event. This situation has influenced midwifery care. One of the significant barriers to midwives providing care to pregnant women is the medicalization of childbirth. So far, the policies and programs of the Ministry of Health to reduce medical interventions and cesarean section rates have not been successful. Therefore, the current study aims to be conducted with the purpose of “Designing a Midwife-Led Birth Center Program Based on the MAP-IT Model”.

Methods/design
The current study is a mixed-methods sequential explanatory design by using the MAP-IT model includes 5 steps: Mobilize, Assess, Plan, Implement, and Track, providing a framework for planning and evaluating public health interventions in a community. It will be implemented in three stages: The first phase of the research will be a cross-sectional descriptive study to determine the attitudes and preferences towards establishing a midwifery-led birthing center focusing on midwives and women of childbearing age by using two researcher-made questionnaires to assess the participants’ attitudes and preferences toward establishing a midwifery-led birthing center. Subsequently, extreme cases will be selected based on the participants’ average attitude scores toward establishing a midwifery-led birthing center in the quantitative section. In the second stage of the study, qualitative in-depth interviews will be conducted with the identified extreme cases from the first quantitative phase and other stakeholders (the first and second steps of the MAP-IT model, namely identifying and forming a stakeholder coalition, and assessing community resources and real needs). In this stage, the conventional qualitative content analysis approach will be used. Subsequently, based on the quantitative and qualitative data obtained up to this stage, a midwifery-led birthing center program based on the third step of the MAP-IT model, namely Plan, will be developed and validated using the Delphi method.

Discussion
This is the first study that uses a mixed-method approach for designing a midwife-led maternity care program based on the MAP-IT model. This study will fill the research gap in the field of improving midwife-led maternity care and designing a program based on the needs of a large group of pregnant mothers. We hope this program facilitates improved eligibility of midwifery to continue care to manage and improve their health easily and affordably.

Ethical code
IR.MUMS.NURSE.REC. 1403. 014.
The effect of matrine and glycyrrhizic acid on porcine reproductive and respiratory syndrome virus in Vitro and in vivo
Authors: Zhang Zhilong , Wu Wenyi , Li Qiannan , Du Fangfang , Wang Xuebing , Yang Mingfan , Zhang Hongying 
Published: July 2024

AbstractPorcine reproductive and respiratory syndrome (PRRS) is endemic worldwide, seriously affecting the development of the pig industry, but vaccines have limited protective effects against PRRSV transmission. The aim of this study was to identify potential anti-PRRSV drugs. We examined the cytotoxicity of seven compounds formulated based on the mass ratio of glycyrrhizic acid to matrine and calculated their inhibition rates against PRRSV in vitro. The results showed that the seven compounds all had direct killing and therapeutic effects on PRRSV, and the compounds inhibited PRRSV replication in a time- and dose-dependent manner. The compound with the strongest anti-PRRSV effect was selected for subsequent in vivo experiments. Pigs were divided into a control group and a medication group for the in vivo evaluation. The results showed that pigs treated with the 4:1 compound had 100% morbidity after PRRSV challenge, and the mortality rate reached 75% on the 8th day of the virus challenge. These results suggest that this compound has no practical anti-PRRSV effect in vivo and can actually accelerate the death of infected pigs. Next, we further analyzed the pigs that exhibited semiprotective effects following vaccination with the compound to determine whether the compound can synergize with the vaccine in vivo. The results indicated that pigs treated with the compound had higher mortality rates and more severe clinical reactions after PRRSV infection (p < 0.05). The levels of proinflammatory cytokines (IL-6, IL-8, IL-1β, IFN-γ, and TNF-α) were significantly greater in the compound-treated pigs than in the positive control-treated pigs (p < 0.05), and there was no synergistic enhancement with the live attenuated PRRSV vaccine (p < 0.05). The compound enhanced the inflammatory response, prompted the body to produce excessive levels of inflammatory cytokines and caused body damage, preventing a therapeutic effect. In conclusion, the present study revealed that the in vitro effectiveness of these agents does not indicate that they are effective in vivo or useful for developing anti-PRRSV drugs. Our findings also showed that, to identify effective anti-PRRSV drugs, comprehensive drug screening is needed, for compounds with solid anti-inflammatory effects both in vitro and in vivo. Our study may aid in the development of new anti-PRRSV drugs.
Predictors of the sustainability for an evidence-based eating disorder prevention program delivered by college peer educators
Authors: Bearman Sarah Kate , Rohde Paul , Pauling Sydney , Gau Jeff M. , Shaw Heather , Stice Eric 
Published: July 2024

Abstract
Background
Despite ongoing efforts to introduce evidence-based interventions (EBIs) into mental health care settings, little research has focused on the sustainability of EBIs in these settings. College campuses are a natural place to intervene with young adults who are at high risk for mental health disorders, including eating disorders. The current study tested the effect of three levels of implementation support on the sustainability of an evidence-based group eating disorder prevention program, the Body Project, delivered by peer educators. We also tested whether intervention, contextual, or implementation process factors predicted sustainability.

Methods
We recruited 63 colleges with peer educator programs and randomly assigned them to (a) receive a 2-day Train-the-Trainer (TTT) training in which peer educators were trained to implement the Body Project and supervisors were taught how to train future peer educators (TTT), (b) TTT training plus a technical assistance (TA) workshop (TTT + TA), or (c) TTT plus the TA workshop and quality assurance (QA) consultations over 1-year (TTT + TA + QA). We tested whether implementation support strategies, perceived characteristics of the intervention and attitudes towards evidence-based interventions at baseline and the proportion of completed implementation activities during the implementation year predicted three school-level dichotomous sustainability outcomes (offering Body Project groups, training peer educators, training supervisors) over the subsequent two-year sustainability period using logistic regression models.

Results
Implementation support strategies did not significantly predict any sustainability outcomes, although a trend suggested that colleges randomized to the TTT + TA + QA strategy were more likely to train new supervisors (OR = 5.46, 95% CI [0.89–33.38]). Colleges that completed a greater proportion of implementation activities were more likely to offer Body Project groups (OR = 1.53, 95% CI [1.19–1.98]) and train new peer educators during the sustainability phase (OR = 1.39, 95% CI [1.10–1.74]). Perceived positive characteristics of the Body Project predicted training new peer educators (OR = 18.42, 95% CI [1.48–299.66]), which may be critical for sustainability in routine settings with high provider turnover.

Conclusions
Helping schools complete more implementation activities and increasing the perceived positive characteristics of a prevention program may result in greater sustainment of prevention program implementation.

Trial Registration
This study was preregistered on 12/07/17 with ClinicalTrials.gov, ID NCT03409809, https://clinicaltrials.gov/ct2/show/NCT03409809.
Durvalumab supplementation for non-small-cell lung cancer: a meta-analysis study
Authors: Wang Chengchen , Fu Hongyi , Wang Feng 
Published: July 2024

Abstract
Background
Durvalumab supplementation may have some potential in improving the efficacy in patients with non-small-cell lung cancer (NSCLC), and this meta-analysis aims to explore the impact of durvalumab supplementation on efficacy for NSCLC.

Methods
PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases were systematically searched, and we included randomized controlled trials (RCTs) assessing the effect of durvalumab supplementation on efficacy in patients with NSCLC. Overall survival and progression-free survival were included for this meta-analysis.

Results
Four RCTs were finally included in the meta-analysis. Overall, compared with control group for NSCLC, durvalumab supplementation showed significantly improved survival rate (odd ratio [OR] = 1.64; 95% confidence interval [CI] = 1.31 to 2.06; P < 0.0001), overall survival ( hazard ratio [HR] = 0.73; 95% CI = 0.61 to 0.87; P = 0.0003), progression-free survival rate (OR = 2.31; 95% CI = 1.78 to 3.01; P < 0.00001) and progression-free survival (HR = 0.71; 95% CI = 0.54 to 0.95; P = 0.02), and had the capability to reduce the incidence of grade ≥ 3 adverse events (OR = 0.26; 95% CI = 0.16 to 0.42; P < 0.00001).

Conclusions
Durvalumab supplementation is effective to improve the efficacy for NSCLC.
Measuring health related quality of life (HRQoL) in Lysosomal Storage Disorders (LSDs): a rapid scoping review of available tools and domains
Authors: McDool Emily , Powell Philip , Carlton Jill 
Published: July 2024

AbstractBackgroundLysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders, consisting of over 70 diseases that are characterised by lysosomal dysfunction. Due to their varied and progressive symptoms, LSDs have a continual impact on patients’ health-related quality of life (HRQoL). Several recently published studies have provided insight into the HRQoL of individuals with LSDs. However, it is challenging to meaningfully synthesise this evidence, since studies often focus upon a particular type of LSD and / or utilise different self-report questionnaires or patient-reported outcome measures (PROMs) to assess HRQoL.AimsThe aim of this study was to review the published literature in LSDs, to identify the PROMs which have been used to assess HRQoL and generate a conceptual map of HRQoL domains measured in individuals diagnosed with LSDs.MethodsThree electronic databases were searched in March 2022. Primary studies of any design which utilised multi-item PROMs to assess at least one aspect of HRQoL in individuals with LSDs since 2017 were identified. Data were extracted to assess both the characteristics of each study and of the PROMs utilised within each study. The extraction of HRQoL domains and synthesis were informed by an a priori framework, inductively modified to reflect data emerging from the identified literature. Selection and extraction was undertaken independently by two reviewers; discrepancies were ratified by a third reviewer.ResultsSixty nine studies were identified which were published 2017-2022, with a combined total of 52 PROMs (71 variants) used to assess HRQoL in individuals with LSDs. The final extracted HRQoL framework included 7 domains (Activities; Physical sensations; Autonomy; Cognition; Feelings and emotions; Self-identity; Relationships), characterised by 37 sub-domains.ConclusionsThis review highlights the breadth and variety of HRQoL domains assessed in individuals with LSDs, across three broad domains of physical, psychological and social functioning. The resultant framework and mapped PROMs will aid researchers and clinicians in the selection of PROMs to assess aspects of HRQoL in people living with LSDs, based on their conceptual coverage.
Harnessing health information technology to promote equitable care for patients with limited English proficiency and complex care needs
Authors: Strechen Inna , Wilson Patrick , Eltalhi Targ , Piche Kimberly , Tschida-Reuter Dan , Howard Diane , Sutor Bruce , Tiong Ing , Herasevich Svetlana , Pickering Brian , Barwise Amelia 
Published: July 2024

Abstract
Background
Patients with language barriers encounter healthcare disparities, which may be alleviated by leveraging interpreter skills to reduce cultural, language, and literacy barriers through improved bidirectional communication. Evidence supports the use of in-person interpreters, especially for interactions involving patients with complex care needs. Unfortunately, due to interpreter shortages and clinician underuse of interpreters, patients with language barriers frequently do not get the language services they need or are entitled to. Health information technologies (HIT), including artificial intelligence (AI), have the potential to streamline processes, prompt clinicians to utilize in-person interpreters, and support prioritization.

Methods
From May 1, 2023, to June 21, 2024, a single-center stepped wedge cluster randomized trial will be conducted within 35 units of Saint Marys Hospital & Methodist Hospital at Mayo Clinic in Rochester, Minnesota. The units include medical, surgical, trauma, and mixed ICUs and hospital floors that admit acute medical and surgical care patients as well as the emergency department (ED). The transitions between study phases will be initiated at 60-day intervals resulting in a 12-month study period. Units in the control group will receive standard care and rely on clinician initiative to request interpreter services. In the intervention group, the study team will generate a daily list of adult inpatients with language barriers, order the list based on their complexity scores (from highest to lowest), and share it with interpreter services, who will send a secure chat message to the bedside nurse. This engagement will be triggered by a predictive machine-learning algorithm based on a palliative care score, supplemented by other predictors of complexity including length of stay and level of care as well as procedures, events, and clinical notes.

Discussion
This pragmatic clinical trial approach will integrate a predictive machine-learning algorithm into a workflow process and evaluate the effectiveness of the intervention. We will compare the use of in-person interpreters and time to first interpreter use between the control and intervention groups.

Trial registration
NCT05860777. May 16, 2023.