bluuebunny/crossref_metadata_2025_split huggingface dataset:
IL-33 stimulates the anticancer activities of eosinophils through extracellular vesicle-driven reprogramming of tumor cells
Authors: Gambardella Adriana Rosa , Antonucci Caterina , Zanetti Cristiana , Noto Francesco , Andreone Sara , Vacca Davide , Pellerito Valentina , Sicignano Chiara , Parrottino Giuseppe , Tirelli Valentina , Tinari Antonella , Falchi Mario , De Ninno Adele , Businaro Luca , Loffredo Stefania , Varricchi Gilda , Tripodo Claudio , Afferni Claudia , Parolini Isabella , Mattei Fabrizio , Schiavoni Giovanna 
Published: July 2024

AbstractImmune cell-derived extracellular vesicles (EV) affect tumor progression and hold promise for therapeutic applications. Eosinophils are major effectors in Th2-related pathologies recently implied in cancer. Here, we evaluated the anti-tumor activities of eosinophil-derived EV following activation with the alarmin IL-33. We demonstrate that IL-33-activated mouse and human eosinophils produce higher quantities of EV with respect to eosinophils stimulated with IL-5. Following incorporation of EV from IL-33-activated eosinophils (Eo33-EV), but not EV from IL-5-treated eosinophils (Eo5-EV), mouse and human tumor cells increased the expression of cyclin-dependent kinase inhibitor (CDKI)-related genes resulting in cell cycle arrest in G0/G1, reduced proliferation and inhibited tumor spheroid formation. Moreover, tumor cells incorporating Eo33-EV acquired an epithelial-like phenotype characterized by E-Cadherin up-regulation, N-Cadherin downregulation, reduced cell elongation and migratory extent in vitro, and impaired capacity to metastasize to lungs when injected in syngeneic mice. RNA sequencing revealed distinct mRNA signatures in Eo33-EV and Eo5-EV with increased presence of tumor suppressor genes and enrichment in pathways related to epithelial phenotypes and negative regulation of cellular processes in Eo33-EV compared to Eo5-EV. Our studies underscore novel IL-33-stimulated anticancer activities of eosinophils through EV-mediated reprogramming of tumor cells opening perspectives on the use of eosinophil-derived EV in cancer therapy.
Unveiling G-protein coupled receptors as potential targets for ovarian cancer nanomedicines: from RNA sequencing data analysis to in vitro validation
Authors: Khetan Riya , Eldi Preethi , Lokman Noor A. , Ricciardelli Carmela , Oehler Martin K. , Blencowe Anton , Garg Sanjay , Pillman Katherine , Albrecht Hugo 
Published: July 2024

AbstractGenetic heterogeneity in ovarian cancer indicates the need for personalised treatment approaches. Currently, very few G-protein coupled receptors (GPCRs) have been investigated for active targeting with nanomedicines such as antibody-conjugated drugs and drug-loaded nanoparticles, highlighting a neglected potential to develop personalised treatment. To address the genetic heterogeneity of ovarian cancer, a future personalised approach could include the identification of unique GPCRs expressed in cancer biopsies, matched with personalised GPCR-targeted nanomedicines, for the delivery of lethal drugs to tumour tissue before, during and after surgery. Here we report on the systematic analysis of public ribonucleic acid-sequencing (RNA-seq) gene expression data, which led to prioritisation of 13 GPCRs as candidates with frequent overexpression in ovarian cancer tissues. Subsequently, primary ovarian cancer cells derived from ascites and ovarian cancer cell lines were used to confirm frequent gene expression for the selected GPCRs. However, the expression levels showed high variability within our selection of samples, therefore, supporting and emphasising the need for the future development of case-to-case personalised targeting approaches.
Prevalence of delivery mode in an Italian nationwide cohort with celiac disease: a SIGENP multicenter retrospective study (the CD-deliver-IT)
Authors: Iorfida Donatella , Valitutti Francesco , Vestri Annarita , D’Adamo Grazia , Passaro Tiziana , Crocco Marco , Malerba Federica , Monzani Alice , Rabbone Ivana , Pensabene Licia , Giancotti Laura , Graziano Francesco , Citrano Michele , Ferretti Francesca , Trovato Chiara Maria , Pacenza Caterina , Iasevoli Mario , Banzato Claudia , Lubrano Riccardo , Montuori Monica ,   the “Food-induced disease” study group of SIGENP, Principessa Luigi , D’Angelo Elisa , Malamisura Basilio , Calvi Angela , Zampatti Noemi , Montafia Ilaria , Diamanti Antonella , Pisano Pasquale 
Published: July 2024

Abstract
Background
Studies have indicated an association between cesarean section (CS), especially elective CS, and an increased risk of celiac disease (CD), but the conclusions of other studies are contradictory. The primary aim of this study (CD-deliver-IT) was to evaluate the rate of CS in a large population of CD patients throughout Italy.

Methods
This national multicenter retrospective study was conducted between December 2020 and November 2021. The coordinating center was the Pediatric Gastroenterology and Liver Unit of Policlinico Umberto I, Sapienza, University of Rome, Lazio, Italy. Eleven other referral centers for CD have participated to the study. Each center has collected data on mode of delivery and perinatal period of all CD patients referring to the center in the last 40 years.

Results
Out of 3,259 CD patients recruited in different Italian regions, data on the mode of delivery were obtained from 3,234. One thousand nine hundred forty-one (1,941) patients (60%) were born vaginally and 1,293 (40%) by CS (8.3% emergency CS, 30.1% planned CS, 1.5% undefined CS). A statistically significant difference was found comparing median age at time of CD diagnosis of patients who were born by emergency CS (4 years, CI 95% 3.40–4.59), planned CS (7 years, CI 95% 6.02–7.97) and vaginal delivery (6 years, CI 95% 5.62–6.37) (log rank p < 0.0001).

Conclusions
This is the first Italian multicenter study aiming at evaluating the rate of CS in a large population of CD patients through Italy. The CS rate found in our CD patients is higher than rates reported in the general population over the last 40 years and emergency CS seems to be associated with an earlier onset of CD compared to vaginal delivery or elective CS in our large nationwide retrospective cohort. This suggests a potential role of the mode of delivery on the risk of developing CD and on its age of onset, but it is more likely that it works in concert with other perinatal factors. Further prospective studies on other perinatal factors potentially influencing gut microbiota are awaited in order to address heavy conflicting evidence reaming in this research field.
Effectiveness and cost-effectiveness of a 1-year dietary and physical activity intervention of childhood obesity—study protocol for a randomized controlled clinical trial
Authors: Martikainen A. , Eloranta AM , Schwab U. , Örmälä T. 
Published: July 2024

Abstract
Background
We investigate and try to find out the optimal duration and intensity for the treatment and content useful for clinical work. The aim of our study is to evaluate the effects of lifestyle intervention on the management of childhood overweight and to explore the factors that contribute to the outcome, as well as the costs for the health care system. The hypotheses of the study are that lifestyle intervention is efficient in reducing BMI-SDS and thus effective in preventing overweight from progressing to obesity, and it is also cost-effective.

Methods and analyses
We aim to recruit 80 children and they randomize either to an intervention group or a control group with standard care. The intervention group receives intensive, family-based diet, and physical activity counseling, delivered by a multidisciplinary team of a pediatrician, a nurse, and a clinical nutritionist. The control group does not receive any lifestyle intervention during the study. The inclusion criteria are age of 6–12 years, weight-for-height ≥  + 40% or ≥  + 30%, and increasing curve. All participants fill out the study questionnaires and plasma samples are taken at baseline and at 12 months. Outcome variables will be compared between intervention and control groups.

Discussion
If the effects of this lifestyle intervention are positive and it is also cost-effective, the implication of our study will be of great importance to the treatment of childhood obesity and to improve the health care system.

Trial registration
ClinicalTrials.gov NCT06126679. Registered on 25 October 2028 in Finland.
ORCID: 0009-0009-6659-5290.
The effect of prognostic nutritional index on diabetic patients with myocardial infarction
Authors: Peng Yanchun , Lin Aijie , Luo Baolin , Chen Liangwan , Lin Yanjuan 
Published: July 2024

Abstract
Background
The prognostic nutritional index (PNI), a simple and comprehensive predictor of nutritional and immunological health, is connected to cancer and cardiovascular disease. The effects of PNI on myocardial infarction (MI) in individuals with diabetes remain unclear. Thus, we aim to investigate the correlation of PNI with predictive outcomes in this specific population group to inform therapeutic decision-making.

Methods
This prospective observational study included 417 diabetic patients with MI who underwent coronary angiography intervention at Fujian Medical University Union Hospital from May 2017 to May 2020. We collected follow-up and prognostic data from these patients at 6, 12, 18, and 24 months post-procedure via outpatient visits or phone interviews. The main focus of the study was on major adverse cardiovascular events (MACE) in the two years after surgery. Based on the median PNI, patients were categorized into two groups: high PNI (H-PNI) and low PNI (L-PNI). Data were analyzed using IBM SPSS 25.0. Kalpan-Meier survival curves and Cox proportional hazards regression analysis were utilized to examine the associations between preoperative PNI and the prognosis of diabetic patients with MI.

Results
In the study, 417 participants were observed for two years. Of these patients, 159 (38.1%) had MACE. According to the Kaplan–Meier curves, patients in the L-PNI group had more MACE than those in the H-PNI group (log-rank p < 0.001) and had a heightened susceptibility to all categories of MACE. After adjusting for confounding variables, the corrected hazard ratio for developing unstable angina in the L-PNI group was 2.55 (95% CI 1.57–4.14, p < 0.001).

Conclusion
Low PNI levels are associated with MACE after coronary angiography intervention in diabetic patients with myocardial infarction. This highlights the prognostic value of PNI and broadens its potential use in larger populations.
Trial registration: Not applicable.
Sex-specific associations of kynurenic acid with neopterin in Alzheimer’s disease
Authors: Knapskog Anne-Brita , Edwin Trine Holt , Ueland Per Magne , Ulvik Arve , Fang Evandro Fei , Eldholm Rannveig Sakshaug , Halaas Nathalie Bodd , Giil Lasse M. , Saltvedt Ingvild , Watne Leiv Otto , Aksnes Mari 
Published: July 2024

Abstract
Background
Sex differences in neuroinflammation could contribute to women’s increased risk of Alzheimer’s disease (AD), providing rationale for exploring sex-specific AD biomarkers. In AD, dysregulation of the kynurenine pathway (KP) contributes to neuroinflammation and there is some evidence of sex differences in KP metabolism. However, the sex-specific associations between KP metabolism and biomarkers of AD and neuroinflammation need to be explored further.

Methods
Here we investigate sex differences in cerebrospinal fluid concentrations of seven KP metabolites and sex-specific associations with established AD biomarkers and neopterin, an indicator of neuroinflammation. This study included 311 patients with symptomatic AD and 105 age-matched cognitively unimpaired (CU) controls, followed for up to 5 years.

Results
We found sex differences in KP metabolites in the AD group, with higher levels of most metabolites in men, while there were no sex differences in the CU group. In line with this, more KP metabolites were significantly altered in AD men compared to CU men, and there was a trend in the same direction in AD women. Furthermore, we found sex-specific associations between kynurenic acid and the kynurenic acid/quinolinic acid ratio with neopterin, but no sex differences in the associations between KP metabolites and clinical progression.

Discussion
In our cohort, sex differences in KP metabolites were restricted to AD patients. Our results suggest that dysregulation of the KP due to increased inflammation could contribute to higher AD risk in women.
Scrub typhus with hemorrhagic stroke: a case report
Authors: Bhatta Om Prakash , Chand Sabita , Chand Hemant , Bhetwal Prashant , Awasthi Sachin , Acharya Aruna , Poudel Ram Chandra 
Published: July 2024

Abstract
Background
Scrub typhus, caused by Orientia tsutsugamushi, rarely leads to central nervous system involvement. Although intracerebral bleeding is rare due to endemicity and a significant proportion of underdiagnoses, it should be considered a noteworthy differential diagnosis in endemic regions in patients with relevant history and clinical findings.

Case presentation
We present the case of a 40-year-old Nepali woman who visited the emergency department with complaints of left-sided weakness for 6 hours and an acute febrile illness with an eschar for 7 days and was diagnosed with scrub typhus by immunoglobulin M enzyme-linked immunosorbent assay of the serum. Imaging revealed a right-sided frontotemporal hematoma, and further examination revealed pulmonary edema with multiple organ dysfunction syndrome. The patient was mechanically ventilated and was treated with antibiotics, steroids, vasopressors, and antipyretics. However, the hematoma was treated conservatively, with ongoing neurological recovery at the 6-month follow-up.

Conclusion
Although neurological complications and intracranial hemorrhage are uncommon, physicians must be cautious when making differential diagnoses and initiating appropriate therapies to avoid serious or fatal complications.
The impact of sex on gene expression in the brain of schizophrenic patients: a systematic review and meta-analysis of transcriptomic studies
Authors: Carceller Hector , Hidalgo Marta R. , Escartí María José , Nacher Juan , de la Iglesia-Vayá Maria , García-García Francisco 
Published: July 2024

Abstract
Background
Schizophrenia is a severe neuropsychiatric disorder characterized by altered perception, mood, and behavior that profoundly impacts patients and society despite its relatively low prevalence. Sex-based differences have been described in schizophrenia epidemiology, symptomatology and outcomes. Different studies explored the impact of schizophrenia in the brain transcriptome, however we lack a consensus transcriptomic profile that considers sex and differentiates specific cerebral regions.

Methods
We performed a systematic review on bulk RNA-sequencing studies of post-mortem brain samples. Then, we fulfilled differential expression analysis on each study and summarized their results with regions-specific meta-analyses (prefrontal cortex and hippocampus) and a global all-studies meta-analysis. Finally, we used the consensus transcriptomic profiles to functionally characterize the impact of schizophrenia in males and females by protein-protein interaction networks, enriched biological processes and dysregulated transcription factors.

Results
We discovered the sex-based dysregulation of 265 genes in the prefrontal cortex, 1.414 genes in the hippocampus and 66 genes in the all-studies meta-analyses. The functional characterization of these gene sets unveiled increased processes related to immune response functions in the prefrontal cortex in male and the hippocampus in female schizophrenia patients and the overexpression of genes related to neurotransmission and synapses in the prefrontal cortex of female schizophrenia patients. Considering a meta-analysis of all brain regions available, we encountered the relative overexpression of genes related to synaptic plasticity and transmission in females and the overexpression of genes involved in organizing genetic information and protein folding in male schizophrenia patients. The protein-protein interaction networks and transcription factors activity analyses supported these sex-based profiles.

Conclusions
Our results report multiple sex-based transcriptomic alterations in specific brain regions of schizophrenia patients, which provides new insight into the role of sex in schizophrenia. Moreover, we unveil a partial overlapping of inflammatory processes in the prefrontal cortex of males and the hippocampus of females.
The impact of mobile health interventions on service users’ health outcomes and the role of health professions: a systematic review of systematic reviews—protocol
Authors: Alkhuzaimi Fathiya , Rainey Deborah , Wilson Christine Brown , Bloomfield Jacqueline 
Published: July 2024

Abstract
Background
Mobile health tools have gained prominence in global health care in recent years. Mobile health (mHealth) interventions have demonstrated their impact on managing healthcare service users’ health. A pilot search revealed many systematic reviews on the effectiveness of mobile health tools on service users’ health outcomes. However, how the role of healthcare professionals in promoting the adoption of mobile health may lead to improved outcomes needs to be clarified. Therefore, this systematic review aims to synthesise existing systematic reviews that examine both the impact of mobile health interventions on service users’ outcomes and the role of healthcare professionals in facilitating the adoption of mobile health solutions.

Methods
Five electronic databases will be searched: EMBASE, CINHAL Plus, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews exploring the impact of mobile health interventions on service users’ outcomes and the role of healthcare professionals in facilitating the adoption of mobile health solutions. Systematic reviews published in English dated from January 2015 to June 2024 will be included. Screening and selection of the reviews against inclusion and exclusion criteria will be performed by three independent reviewers, as well as data extraction and quality assessment.

Discussion
Current systematic reviews in mHealth have primarily focused on assessing the effectiveness of mHealth interventions for managing a range of conditions. While these reviews provide valuable input into the outcomes for mHealth, more is needed to know about the impact of the involvement of health professions on service users’ outcomes when adopting mHealth. This systematic review of systematic reviews aims to bridge this critical gap in the literature by critically appraising and synthesising the evidence of mHealth interventions’ impact on service user outcomes and the level of involvement of health professionals.

Systematic review registration
PROSPERO CRD 42023414435.
Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder
Authors: Freet Christopher S. , Evans Brianna , Brick Timothy R. , Deneke Erin , Wasserman Emily J. , Ballard Sarah M. , Stankoski Dean M. , Kong Lan , Raja-Khan Nazia , Nyland Jennifer E. , Arnold Amy C. , Krishnamurthy Venkatesh Basappa , Fernandez-Mendoza Julio , Cleveland H. Harrington , Scioli Adam D. , Molchanow Amanda , Messner Amy E. , Ayaz Hasan , Grigson Patricia S. , Bunce Scott C. 
Published: July 2024

Abstract
Background
Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment.

Method
This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2–19), and following (Study Days 20–21) residential treatment.

Discussion
This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. Trial registration: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728.

Protocol Version
10 May 2023
Decoding single-cell molecular mechanisms in astrocyte-to-iN reprogramming via Ngn2- and Pax6-mediated direct lineage switching
Authors: Qin Rongxing , Zhang Yingdan , Yang Yue , Chen Jiafeng , Huang Lijuan , Xu Wei , Qin Qingchun , Liang Xiaojun , Lai Xinyu , Huang Xiaoying , Xie Minshan , Chen Li 
Published: July 2024

Abstract
Background
The limited regenerative capacity of damaged neurons in adult mammals severely restricts neural repair. Although stem cell transplantation is promising, its clinical application remains challenging. Direct reprogramming, which utilizes cell plasticity to regenerate neurons, is an emerging alternative approach.

Methods
We utilized primary postnatal cortical astrocytes for reprogramming induced neurons (iNs) through the viral-mediated overexpression of the transcription factors Ngn2 and Pax6 (NP). Fluorescence-activated cell sorting (FACS) was used to enrich successfully transfected cells, followed by single-cell RNA sequencing (scRNA-seq) using the 10 × Genomics platform for comprehensive transcriptomic analysis.

Results
The scRNA-seq revealed that NP overexpression led to the differentiation of astrocytes into iNs, with percentages of 36% and 39.3% on days 4 and 7 posttransduction, respectively. CytoTRACE predicted the developmental sequence, identifying astrocytes as the reprogramming starting point. Trajectory analysis depicted the dynamic changes in gene expression during the astrocyte-to-iN transition.

Conclusions
This study elucidates the molecular dynamics underlying astrocyte reprogramming into iNs, revealing key genes and pathways involved in this process. Our research contributes novel insights into the molecular mechanisms of NP-mediated reprogramming, suggesting avenues for optimizing the efficiency of the reprogramming process.