bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between multiorgan immune-related adverse events and clinical outcomes in patients with extensive-stage small cell lung cancer (ES-SCLC) treated with chemo-immunotherapy.
Authors: Monaca Federico , Gomez-Randulfe Rodriguez Martin Igor , Vita Emanuele , Cosmai Antonia , Polidori Sara , Stefani Alessio , Horn Guido , Mastrantoni Luca , Vitale Antonio , Russo Jacopo , Occhipinti Denis , Scala Alessandro , Troisi Paola , D'Argento Ettore , Di Salvatore Mariantonietta , Tortora Giampaolo , Califano Raffaele , Bria Emilio 
Published: June 2024

e20129 Background: The addition of immune checkpoint inhibitors (ICIs) to platinum-based chemotherapy (CT-IO) has changed the first-line (1L) treatment landscape of extensive-stage small-cell lung cancer (ES-SCLC). Although ICIs improve survival, they can trigger immune related adverse events (irAEs). Notably, a correlation between irAEs and improved survival (OS) has been observed in several solid tumours including NSCLC. The impact of multiorgan irAEs in ES-SCLC treated with 1L CT-IO remains less clear. Methods: We retrospectively reviewed pts with ES-SCLC who received 1L CT-IO from November 2019 to September 2023 across 2 European centres. Demographic and clinical data were collected and analysed. We evaluated the correlation between irAEs (single and multiorgan) and OS. Results: A total of 217 pts were included. Median follow-up in censored pts was 13.2 m. Overall response rate was 75.1%, median PFS was 6.2 months (m) (95% CI, 5.8 - 6.7), and median OS 10.9 m (95% CI, 9.3 - 12.4). Single-organ any grade irAEs were reported in 58 pts (26.7%), while multi-organ irAEs occurred in 18 pts (8.3%). Clinicopathological characteristics stratified by irAEs are shown in the table. The most commonly affected organs were skin (n=25, 11.5%) and the digestive system (n=15, 6.9%). Treatment discontinuation rate due to irAEs was 11.1% (n=26). Median PFS in pts with multiorgan vs single vs no irAEs was 16.7m, 9.0m and 5.5m, respectively. Median OS was not reached, 17.9m and 8.2m, respectively. The multivariate analysis including irAEs as a time-varying covariate confirmed the association between irAEs and improved PFS (HR 0.38; 95% CI, 0.28 - 0.50, p<0.001) and OS (HR 0.37; 95% CI, 0.27-0.52, p<0.001). Conclusions: Our cohort shows that the incidence of irAEs in this setting is similar to previous real-world studies and that multiorgan irAEs were significantly associated with longer PFS and OS. Further research is needed to characterize the profile of irAEs associated with improved outcomes and to understand the role of concurrent therapeutic interventions. [Table: see text]
In-depth Microbiological Characterization of Urine From Subjects With Type 2 Diabetes
Authors: Calvigioni Marco , Biancalana Edoardo , Mazzantini Diletta , Celandroni Francesco , Rossi Chiara , Mengozzi Alessandro , Ghelardi Emilia , Solini Anna 
Published: June 2024

Abstract

Context
Lower urinary tract symptoms (LUTS) are common in type 2 diabetes (T2D), affecting quality of life and potentially leading to medication discontinuation. Among various factors contributing to LUTS, recent observations suggest a critical role of the urinary microbiota. Research on urinary dysbiosis in T2D remains underexplored.

Objective
We conducted a pilot study to investigate differences in the urinary microbiota between patients with T2D and healthy individuals and its potential indirect association with LUTS risk.

Methods
This case–control study included 50 patients with T2D and no LUTS, and 25 healthy controls. Microbial DNAs were extracted from urinary sediments and bacterial populations quantified by real-time quantitative polymerase chain reaction (PCR) and qualitatively investigated by 16S rRNA gene sequencing. Validation experiments with digital PCR were also performed.

Results
In patients with T2D a higher total bacterial load and an increased abundance of Bacillota were found. After stratification by gender, these results were observed only in women. However, no significant quantitative differences were observed at the genus level. Alpha diversity analysis showed no significant differences between T2D and control groups, or by gender. At the species level, a substantial qualitative and often gender-dependent shift was present in individuals with T2D.

Conclusion
The urinary microbiome of subjects with T2D was found to be different from that of healthy controls. Specifically, patients with T2D displayed higher total bacterial load and Bacillota levels, as well as qualitative changes in bacterial species. These changes suggested a dysbiotic condition of the urinary microbiota of subjects with T2D, with some gender-related differences. Although causality cannot be inferred, these findings highlight the impact of T2D on the urinary microbiota and its potential relevance in developing LUTS and, from a broader perspective, metabolic abnormalities.
Protein Arginine Methyltransferase CARM1 in Human Breast Cancer
Authors: Bacabac Megan , Liu Peng , Xu Wei 
Published: June 2024

Abstract
Coactivator-associated arginine methyltransferase 1 (CARM1) is a protein arginine methyltransferase that deposits asymmetrical dimethylation marks on both histone and nonhistone substrates. The regulatory role of CARM1 in transcription was first identified in estrogen receptor positive (ER+) breast cancer. Since then, the mechanism of CARM1 in activating ER-target genes has been further interrogated. CARM1 is expressed at the highest level in ER negative (ER–) breast cancer and higher expression correlates with poor prognosis, suggesting an oncogenic role of CARM1. Indeed, in ER– breast cancer, CARM1 can promote proliferation and metastasis at least partly through methylation of proteins and activation of oncogenes. In this review, we summarize the mechanisms of transcriptional activation by CARM1 in breast cancer. The methyltransferase activity of CARM1 is important for many of its functions; here, we also highlight the nonenzymatic roles of CARM1. We also cover the biological processes regulated by CARM1 that are often deregulated in cancer and the ways to harness CARM1 in cancer treatment.
Neural crest development and disorders: from patient to model system and back again – the NEUcrest conference
Authors: Antonaci Marco , Kerr Amy , Lawrence Merin , Lorenzini Francesca , Narwade Nitin , Paka Chloé , Wulf Anna Magdalena 
Published: June 2024

ABSTRACT
The neural crest (NC) is an embryonic multipotent and transitory population of cells that appears during late gastrulation/early neurulation in the developing embryos of vertebrate organisms. Often called “the fourth germ layer”, the NC is characterised by incredible mobility, which allows the NC cells to migrate throughout the whole embryo, giving rise to an astonishing number of different derivatives in the adult organism, such as craniofacial skeleton, adrenal gland, enteric nervous system and melanocytes. Because of these properties, neurocristopathies (NCPs), which is the term used to classify genetic diseases associated with NC developmental defects, are often syndromic and, taken all together, are the most common type of genetic disease. The NEUcrest consortium is an EU funded innovative training network (ITN) that aims to study the NC and NCPs. In March 2024, the early stage researchers (ESRs) in the NEUcrest consortium organised an in-person conference for well-established and early career researchers to discuss new advances in the NC and NCPs field, starting from the induction of the NC, and then moving on to migration and differentiation processes they undergo. The conference focused heavily on NCPs associated with each of these steps. The conference also included events, such as a round table to discuss the future of the NC research, plus a talk by a person living with an NCP. This 3-day conference aimed to bring together the past, present and future of this field to try and unravel the mysteries of this unique cell population.
Predicting Survival in Mucinous Adenocarcinoma of the Appendix: Demographics, Disease Presentation, and Treatment Methodology
Authors: McClelland Paul H. , Gregory Stephanie N. , Nah Shirley K. , Hernandez Jonathan M. , Davis Jeremy L. , Blakely Andrew M. 
Published: June 2024

Abstract
Background
Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses.

Methods
Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005–2019). Primary, secondary, and tertiary outcomes were disease-specific survival (DSS), overall survival (OS), and average annual percent change (AAPC) in incidence.

Results
Among 4,258 included patients, MACA was most frequently diagnosed at 50 to 69 years (52.0%), with female preponderance (55.9%). MACA incidence AAPC was 3.8 (95% confidence interval [CI] 1.9–5.9). For patients with exclusive, first-diagnosis MACA included in survival analysis (3,222 patients), median DSS and OS were 118 and 88 months, respectively. In DSS-based multivariable analysis, worse prognosis was associated with non-Hispanic Black background (HR 1.36, 95% CI 1.02–1.82; p = 0.036), high grade (grade 3 HR 3.10, 95% CI 2.44–3.92; p < 0.001), lymphatic spread (HR 2.73, 95% CI 2.26–3.30; p < 0.001), and distant metastasis (HR 5.84, 95% CI 3.86–8.83; p < 0.001). In subcohort analysis of patients with rationale for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC, 2,387 patients), CRS-HIPEC was associated with survival benefit compared with surgery alone but only for moderate-grade tumors (median DSS/OS 138/138 vs. 116/87 months; p < 0.001).

Conclusions
Mucinous adenocarcinoma of the appendix incidence is increasing in the United States. Survival rates are affected by both demographics and classical risk factors, and CRS-HIPEC-associated survival benefit predominantly occurs in moderate-grade tumors. Further exploration of biologic and clinicopathologic features may enhance risk stratification for this disease.
PROGRAMA INSTITUCIONAL DE BOLSA DE INICIAÇÃO À DOCÊNCIA (PIBID) NO CONTEXTO DA PANDEMIA DO COVID- 19:
Authors: Miranda Cardoso Coutinho Taís , Sena Santos Matheus , Leite Rodrigues Tainara , Oliveira Ramos Evódio Maurício 
Published: June 2024

O presente trabalho trata-se de um relato de experiência escrito por bolsistas do Programa Institucional de Bolsa de Iniciação à docência (PIBID), do curso de Educação Física- Licencitura da Universidade Estadual de Feira de Santana (UEFS), e tem como objetivo expor experiências vivenciadas no programa durante o período de outubro de 2020 junto a uma escola pública estadual de Feira de Santana, na Bahia no contexto da pandemia do COVID-19. A vivência de uma sala de aula real através do PIBID
proporciona um suporte significativo para a formação dos graduandos e enriquece a formação de novas práticas e metodologias didáticas a fim de superar os desafios do ser professor na atualidade. Porém, devido a pandemia, o ensino remoto é apresentado pelo governo como a melhor possibilidade de continuação das aulas nas escolas estaduais. O trabalho foi articulado em tópicos, abordamos sobre as experiências significativas do PIBID junto ao ensino remoto e as dificuldades do ensino remoto no contexto escolar no período da pandemia. Durante este estudo, narramos experiências positivas e as dificuldades enfrentadas no programa no contexto escolar, como a possibilidade de nos aproximarmos do nosso campo de atuação e a exposição de problemáticas relacionadas a questões financeiras, como por exemplo a deficiência de ferramentas tecnológicas entre os alunos que dificultam a participação nas aulas on-line.
Bioinformatics analyses and experimental validation of ferroptosis-related genes in bronchopulmonary dysplasia pathogenesis
Authors: Luo Yifan , Zhang Zongli , Xi Shibing , Li Tao 
Published: June 2024

Objective
We aimed to study the involvement of ferroptosis in the pathogenesis of bronchopulmonary dysplasia (BPD) by conducting bioinformatics analyses and identifying and validating the associated ferroptosis-related genes to explore new directions for treating BPD.

Methods
The dataset GSE32472 on BPD was downloaded from the public genome database. Using R language, differentially expressed genes (DEGs) between the BPD and normal group were screened. In the present study, we adopted weighted gene correlation network analysis (WGCNA) for identifying BPD-related gene modules and ferroptosis-related genes were extracted from FerrDb. Their results were intersected to obtain the hub genes. After that, to explore the hub gene-related signaling pathways, the hub genes were exposed to gene ontology enrichment analysis. With the purpose of verifying the mRNA expression of the hub genes, a single-gene gene set enrichment analysis and quantitative reverse transcription polymerase chain reaction were conducted. Immune cell infiltration in BPD was analyzed using the CIBERSORT inverse fold product algorithm.

Results
A total of 606 DEGs were screened. WGCNA provided the BPD-related gene module darkgreen4. The intersection of DEGs, intramodular genes, and ferroptosis-related genes revealed six ferroptosis-associated hub genes (ACSL1, GALNT14, WIPI1, MAPK14, PROK2, and CREB5). Receiver operating characteristic curve analysis demonstrated that the hub genes screened for BPD were of good diagnostic significance. According to the results of immune infiltration analysis, the proportions of CD8, CD4 naive, and memory resting T cells and M2 macrophage were elevated in the normal group, and the proportions of M0 macrophage, resting mast cell, and neutrophils were increased in the BPD group.

Conclusions
A total of six ferroptosis-associated hub genes in BPD were identified in this study, and they may be potential new therapeutic targets for BPD.
Dual- or single rinse? The tubular sealer penetration of endodontic chelating agents
Authors: Ozel Beliz , Ayhan Tuba , Kaptan Figen , Sahin Fikrettin , Karapınar-Kazandağ Meriç 
Published: June 2024

Introduction
In this study, we aimed to compare the effectiveness of various chelating agents, ethilenediaminetetraacetic acid (EDTA), citric acid (CA), and etidronic acid (HEDP) mixed in two different forms, in removing the smear layer and promoting the penetration of an endodontic sealer into the dentinal tubules of extracted single-rooted teeth.

Methods
The study used 75 teeth divided into five groups: 17% EDTA, 10% CA, 9% HEDP + NaOCl, 9% HEDP + distilled water (DW), and a control (DW) group. Scanning electron microscopy was used to assess smear layer removal and confocal laser microscopy was used to evaluate tubular sealer penetration at different depths from the apical tip.

Results
Sealer penetration was highest with 17% EDTA and 10% CA as compared with the other agents (p<0.001). At the cervical third, the sealer penetration for EDTA, HEDP + NaOCl, and HEDP + DW groups were significantly different than those in DW (p = 0.020). For the middle third, EDTA, CA, and HEDP + NaOCl groups were significantly higher than those of the DW group (p<0.001). Cervical-level values were significantly higher than apical-level values for HEDP + NaOCl, HEDP + DW, and DW (p<0.001). Smear layer removal was lower with 9% HEDP + DW than with 17% EDTA and 10% CA at all depths (p<0.001). A significancy in smear layer removal was observed between 10% CA and control (p = 0.015) in middle depth.

Conclusion
Within the limitations of this study, highest values were seen in EDTA and CA in terms of sealer penetration and smear layer removal. In the light of these findings, the use of strong chelating agents highlights better clinical efficiency than dual-rinse or single HEDP irrigation.
Association of hospital volume and operative approach with clinical and financial outcomes of elective esophagectomy in the United States
Authors: Mallick Saad , Chervu Nikhil L. , Balian Jeffrey , Charland Nicole , Valenzuela Alberto R. , Sakowitz Sara , Benharash Peyman 
Published: June 2024

Introduction
Literature regarding the impact of esophagectomy approach on hospitalizations costs and short-term outcomes is limited. Moreover, few have examined how institutional MIS experience affects costs. We thus examined utilization trends, costs, and short-term outcomes of open and minimally invasive (MIS) esophagectomy as well as assessing the relationship between institutional MIS volume and hospitalization costs.

Methods
All adults undergoing elective esophagectomy were identified from the 2016–2020 Nationwide Readmissions Database. Multiple regression models were used to assess approach with costs, in-hospital mortality, and major complications. Additionally, annual hospital MIS esophagectomy volume was modeled as a restricted cubic spline against costs. Institutions performing > 16 cases/year corresponding with the inflection point were categorized as high-volume hospitals (HVH). We subsequently examined the association of HVH status with costs, in-hospital mortality, and major complications in patients undergoing minimally invasive esophagectomy.

Results
Of an estimated 29,116 patients meeting inclusion, 10,876 (37.4%) underwent MIS esophagectomy. MIS approaches were associated with $10,600 in increased incremental costs (95% CI 8,800–12,500), but lower odds of in-hospital mortality (AOR 0.76; 95% CI 0.61–0.96) or major complications (AOR 0.68; 95% CI 0.60, 0.77). Moreover, HVH status was associated with decreased adjusted costs, as well as lower odds of postoperative complications for patients undergoing MIS operations.

Conclusion
In this nationwide study, MIS esophagectomy was associated with increased hospitalization costs, but improved short-term outcomes. In MIS operations, cost differences were mitigated by volume, as HVH status was linked with decreased costs in the setting of decreased odds of complications. Centralization of care to HVH centers should be considered as MIS approaches are increasingly utilized.
DNA alterations in ovarian adult granulosa cell tumours: A scoping review protocol
Authors: Karstensen Sven , Kaiser Karsten , Moos Caroline , Poulsen Tim Svenstrup , Jochumsen Kirsten , Høgdall Claus , Lauszus Finn , Høgdall Estrid 
Published: June 2024

Background
Identifying and describing molecular alterations in tumors has become common with the development of high-throughput sequencing. However, DNA sequencing in rare tumors, such as ovarian adult granulosa cell tumor (aGCT), often lacks statistical power due to the limited number of cases in each study. Questions regarding personalized treatment or prognostic biomarkers for recurrence or other malignancies therefore still need to be elucidated. This scoping review protocol aims to systematically map the current evidence and identify knowledge gaps regarding DNA alterations, actionable variations and prognostic biomarkers in aGCT.

Methods
This scoping review will be conducted based on Arksey and O’Malley’s methodological framework and later modifications by JBI Evidence Synthesis. The protocol complies with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews. All original publications describing molecular alterations of aGCT will be included. The search will be performed in May 2024 in the following databases: MEDLINE (Ovid), Embase (Ovid), Web of Science Core Collection and Google Scholar (100-top ranked).

Discussion
This scoping review will identify knowledge and gaps in the current understanding of the molecular landscape of aGCT, clinical trials on actionable variations and priorities for future research. As aGCT are rare, a possible limitation will be the small sample sizes and heterogenic study settings.

Scoping review registration
The review protocol is registered at Open Science Framework under https://doi.org/10.17605/OSF.IO/PX4MF.
A feasibility randomised waitlist-controlled trial of a personalised multi-level language treatment for people with aphasia: The remote LUNA study
Authors: Dipper Lucy , Devane Niamh , Barnard Rachel , Botting Nicola , Boyle Mary , Cockayne Lin , Hersh Deborah , Magdalani Carla , Marshall Jane , Swinburn Kate , Cruice Madeline 
Published: June 2024

Background
Stroke survivors with aphasia want to improve their everyday talking (discourse). In current UK practice, 90% of speech and language therapists believe discourse assessment and treatment is part of their role but are hampered by barriers in resources, time and expertise. There is a clinical need for well-articulated discourse assessment and treatments. LUNA is a multi-level treatment targeting words, sentences and discourse macrostructure in personal stories that addresses this clinical need.

Objectives
This study aimed to assess the feasibility and acceptability of LUNA trial procedures in a randomised waitlist-controlled trial; and to evaluate preliminary efficacy.

Methods
This paper reports a phase II, waitlist-controlled, proof-of-concept feasibility trial. Participants with chronic aphasia (n = 28) were recruited from the community and randomised to an Immediate (n = 14) or Delayed (n = 14) group. LUNA treatment was delivered twice weekly for 10 weeks via the videoconferencing technology, Zoom. Feasibility was assessed in terms of participant recruitment and retention, adherence, missing data, and treatment fidelity. Preliminary treatment efficacy was assessed in terms of between group differences in outcome measures relating to discourse, language, and psychosocial state.

Results
The remote LUNA trial was feasible: 85% of those eligible consented to the trial; trial retention was 86%; 87% of treatment sessions were delivered as scheduled, and 79% of participants completed 80%+ of the treatment programme; data was missing only for participants who withdrew; treatment fidelity was high at 92% adherence; and only one clinical outcome measure demonstrated ceiling effects. ANCOVA analysis of the clinical outcome measures revealed group differences with medium and large effect sizes, indicating, improvements in the production of words, sentences, discourse macrostructure, overall language functioning (WAB-R), and psychosocial state (VAMS) following LUNA treatment. For most outcomes measured, similar treatment benefits were suggested in a secondary, non-parametric analysis.

Conclusions
Large-scale evaluation of the clinical efficacy and cost-effectiveness of LUNA is warranted and supported by these findings.

Trial registration
Clinical trials registration: NCT05847023 (clinical trials.gov).