bluuebunny/crossref_metadata_2025_split huggingface dataset:
A palliative care approach for adult non-cancer patients with life-limiting illnesses is cost-saving or cost-neutral: a systematic review of RCTs
Authors: Janke Katharina , Salifu Yakubu , Gavini Siva , Preston Nancy , Gadoud Amy 
Published: August 2024

Background
Patients living with life-limiting illnesses other than cancer constitute the majority of patients in need of palliative care globally, yet most previous systematic reviews of the cost impact of palliative care have not exclusively focused on this population. Reviews that tangentially looked at non-cancer patients found inconclusive evidence. Randomised controlled trials (RCTs) are the gold standard for treatment efficacy, while total health care costs offer a comprehensive measure of resource use. In the sole review of RCTs for non-cancer patients, palliative care reduced hospitalisations and emergency department visits but its effect on total health care costs was not assessed. The aim of this study is to review RCTs to determine the difference in costs between a palliative care approach and usual care in adult non-cancer patients with a life-limiting illness.

Methods
A systematic review using a narrative synthesis approach. The protocol was registered with PROSPERO prospectively (no. CRD42020191082). Eight databases were searched: Medline, CINAHL, EconLit, EMBASE, TRIP database, NHS Evidence, Cochrane Library, and Web of Science from inception to January 2023. Inclusion criteria were: English or German; randomised controlled trials (RCTs); adult non-cancer patients (> 18 years); palliative care provision; a comparator group of standard or usual care. Quality of studies was assessed using Drummond’s checklist for assessing economic evaluations.

Results
Seven RCTs were included and examined the following diseases: neurological (3), heart failure (2), AIDS (1) and mixed (1). The majority (6/7) were home-based interventions. All studies were either cost-saving (3/7) or cost-neutral (4/7); and four had improved outcomes for patients or carers and three no change in outcomes.

Conclusions
In a non-cancer population, this is the first systematic review of RCTs that has demonstrated a palliative care approach is cost-saving or at least cost-neutral. Cost savings are achieved without worsening outcomes for patients and carers. These findings lend support to calls to increase palliative care provision globally.
Consider CUX1 variants in children with a variation of sex development: a case report and review of the literature
Authors: Tan Lynn , Young Shelley G. , Sinclair Andrew H. , Hunter Matthew F. , Ayers Katie L. 
Published: August 2024

Abstract
Background
The Cut Homeobox 1 (CUX1) gene has been implicated in a number of developmental processes and has recently emerged as an important cause of developmental delay and impaired intellectual development. Individuals with variants in CUX1 have been described with a variety of co-morbidities including variations in sex development (VSD) although these features have not been closely documented.

Case presentation
The proband is a 14-year-old male who presented with congenital complex hypospadias, neurodevelopmental differences, and subtle dysmorphism. A family history of neurodevelopmental differences and VSD was noted. Microarray testing and whole exome sequencing found the 46,XY proband had a large heterozygous in-frame deletion of exons 4–10 of the CUX1 gene.

Conclusions
Our review of the literature has revealed that variants in CUX1 are associated with a range of VSD and suggest this gene should be considered in cases where a VSD is noted at birth, especially if there is a familial history of VSD and/or neurodevelopmental differences. Further work is required to fully investigate the role and regulation of CUX1 in sex development.
CircUBA2 promotes the cancer stem cell-like properties of gastric cancer through upregulating STC1 via sponging miR-144-5p
Authors: Wang Jia-Bin , Lin Tong-Xing , Fan Deng-Hui , Gao You-Xin , Chen Yu-Jing , Wu Yu-Kai , Xu Kai-Xiang , Qiu Qing-zhu , Li Ping , Xie Jian-Wei , Lin Jian-Xian , Chen Qi-Yue , Cao Long-Long , Huang Chang-Ming , Zheng Chao-Hui 
Published: August 2024

Abstract
Background
Cancer stem cells (CSCs) are critical factors that limit the effectiveness of gastric cancer (GC) therapy. Circular RNAs (circRNAs) are confirmed as important regulators of many cancers. However, their role in regulating CSC-like properties of GC remains largely unknown. Our study aimed to investigate the role of circUBA2 in CSC maintenance and the underlying mechanisms.

Methods
We identified circUBA2 as an upregulated gene using circRNA microarray analysis. qRT-PCR was used to examine the circUBA2 levels in normal and GC tissues. In vitro and in vivo functional assays were performed to validate the role of circUBA2 in proliferation, migration, metastasis and CSC-like properties of GC cell. The relationship between circUBA2, miR-144-5p and STC1 was characterised using bioinformatics analysis, a dual fluorescence reporter system, FISH, and RIP assays.

Results
CircUBA2 expression was significantly increased in GC tissues, and patients with GC with high circUBA2 expression had a poor prognosis. CircUBA2 enhances CSC-like properties of GC, thereby promoting cell proliferation, migration, and metastasis. Mechanistically, circUBA2 promoted GC malignancy and CSC-like properties by acting as a sponge for miR-144-5p to upregulate STC1 expression and further activate the IL-6/JAK2/STAT3 signaling pathway. More importantly, the ability of circUBA2 to enhance CSC-like properties was inhibited by tocilizumab, a humanised Interleukin-6 receptor (IL-6R) antibody. Thus, circUBA2 knockdown and tocilizumab synergistically inhibited CSC-like properties.

Conclusions
Our study demonstrated the critical role of circUBA2 in regulating CSC-like properties in GC. CircUBA2 may be a promising prognostic biomarker for GC.

Graphical Abstract
Restrictive migration policies and their impact on HIV prevention, care and treatment services
Authors: Ekerin Olabode , Shomuyiwa Deborah Oluwaseun , Lucero-Prisno Don Eliseo , Agboola Oluwafemi Oluwaseun , Damilola Ayelawa Samuel , Onoja Silvia Ojonoka , Chikwendu Chisom Favour , Manirambona Emery 
Published: August 2024

AbstractMigration policies have a significant impact on population health, particularly for individuals living with human immunodeficiency virus (HIV). These policies not only determine who is allowed to enter a country but also influence which immigrants can access services provided by the government. Some countries continue to impose restrictions on HIV-positive individuals, justifying these measures as necessary to protect public health and mitigate healthcare and economic concerns. However, these restrictions lack a valid public health rationale. Due to social, economic and political constraints, restrictive migration laws hinder access to HIV prevention, care and treatment services for immigrants living with HIV. Immigrants face numerous challenges in accessing medication, adhering to treatment regimens and benefitting from HIV preventive efforts. This situation increases the risk of HIV infection and adverse health outcomes due to limited access to preventive programmes, social stigma and engagement in risky behaviours. Additionally, these restrictive migration rules negatively affect immigrants’ mental health. To improve the health of both immigrants and host communities, inclusive and evidence-based migration policies that address healthcare through public health and human rights lenses are required.
Ameliorative effects of mesenchymal stromal cells on senescence associated phenotypes in naturally aged rats
Authors: Wang Lu , Deng Zihui , Li Yun , Wu Yiqi , Yao Renqi , Cao Yuan , Wang Min , Zhou Feihu , Zhu Hanyu , Kang Hongjun 
Published: August 2024

Abstract
Background
Aging is a multifaceted process that affects all organ systems. With the increasing trend of population aging, aging-related diseases have resulted in significant medical challenges and socioeconomic burdens. Mesenchymal stromal cells (MSCs), due to their antioxidative stress, immunoregulatory, and tissue repair capabilities, hold promise as a potential anti-aging intervention.

Methods
In this study, we transplanted MSCs into naturally aged rats at 24 months, and subsequently examined levels of aging-related factors such as β-galactosidase, superoxide dismutase, p16, p21 and malondialdehyde in multiple organs. Additionally, we assessed various aging-related phenotypes in these aged rats, including immune senescence, lipid deposition, myocardial fibrosis, and tissue damage. We also conducted a 16 S ribosomal ribonucleic acid (rRNA) analysis to study the composition of gut microbiota.

Results
The results indicated that MSCs significantly reduced the levels of aging-associated and oxidative stress-related factors in multiple organs such as the heart, liver, and lungs of naturally aging rats. Furthermore, they mitigated chronic tissue damage and inflammation caused by aging, reduced levels of liver lipid deposition and myocardial fibrosis, alleviated aging-associated immunodeficiency and immune cell apoptosis, and positively influenced the gut microbiota composition towards a more youthful state. This research underscores the diverse anti-aging effects of MSCs, including oxidative stress reduction, tissue repair, metabolic regulation, and improvement of immune functions, shedding light on the underlying anti-aging mechanisms associated with MSCs.

Conclusions
The study confirms that MSCs hold great promise as a potential anti-aging approach, offering the possibility of extending lifespan and improving the quality of life in the elderly population.
Inflammatory breast cancer microenvironment repertoire based on DNA methylation data deconvolution reveals actionable targets to enhance the treatment efficacy
Authors: Calanca Naiade , Faldoni Flavia Lima Costa , Souza Cristiano Pádua , Souza Jeferson Santos , de Souza Alves Bianca Elen , Soares Milena Botelho Pereira , Wong Deysi Viviana Tenazoa , Lima-Junior Roberto César Pereira , Marchi Fabio Albuquerque , Rainho Claudia Aparecida , Rogatto Silvia Regina 
Published: August 2024

Abstract
Background
Although the clinical signs of inflammatory breast cancer (IBC) resemble acute inflammation, the role played by infiltrating immune and stromal cells in this aggressive disease is uncharted. The tumor microenvironment (TME) presents molecular alterations, such as epimutations, prior to morphological abnormalities. These changes affect the distribution and the intricate communication between the TME components related to cancer prognosis and therapy response. Herein, we explored the global DNA methylation profile of IBC and surrounding tissues to estimate the microenvironment cellular composition and identify epigenetically dysregulated markers.

Methods
We used the HiTIMED algorithm to deconvolve the bulk DNA methylation data of 24 IBC and six surrounding non-tumoral tissues (SNT) (GSE238092) and determine their cellular composition. The prognostic relevance of cell types infiltrating IBC and their relationship with clinicopathological variables were investigated. CD34 (endothelial cell marker) and CD68 (macrophage marker) immunofluorescence staining was evaluated in an independent set of 17 IBC and 16 non-IBC samples.

Results
We found lower infiltration of endothelial, stromal, memory B, dendritic, and natural killer cells in IBC than in SNT samples. Higher endothelial cell (EC) and stromal cell content were related to better overall survival. EC proportions positively correlated with memory B and memory CD8+ T infiltration in IBC. Immune and EC markers exhibited distinct DNA methylation profiles between IBC and SNT samples, revealing hypermethylated regions mapped to six genes (CD40, CD34, EMCN, HLA-G, PDPN, and TEK). We identified significantly higher CD34 and CD68 protein expression in IBC compared to non-IBC.

Conclusions
Our findings underscored cell subsets that distinguished patients with better survival and dysregulated markers potentially actionable through combinations of immunotherapy and epigenetic drugs.
Prevalence and determinants of orthopedic surgical site infections in rural northern Ghana: a retrospective cohort study
Authors: Salia Solomon Mohammed , Amesiya Robert , Adedia David , Bilson Halilu , Limeng Cletus Werebay 
Published: August 2024

Abstract
Background
The annual incidence of orthopedic surgeries has been steadily rising globally. The rise in orthopedic surgeries is associated with increased surgical site infection, which is linked with high mortality, extended hospital stays, and decreased quality of patient life. There is a dearth of knowledge on the magnitude and risk factors of orthopedic surgical site infections in Ghana.

Objective
To investigate the prevalence and determinants of orthopedic surgical site infections in St. Theresa’s Hospital, Nandom.

Method
A retrospective cohort design among 1032 patients who underwent orthopedic surgeries between January 2014 and December 2018. Admission and patient record books constituted the data sources. The data were initially extracted into a Microsoft Excel spreadsheet, cleaned, and exported to SPSS version 27 and R for coding and analysis.

Results
The prevalence of orthopedic surgical site infection was 9.3%. The determinants of orthopedic surgical site infections were: male sex (OR = 2.33, 95%CI 1.04, 5.51) p = 0.04; self-employed (OR = 3.25, 95%CI 1.2, 10.29) p = 0.030; unemployed/retired (OR = 4.61, 95%CI 1.35, 17.72) p = 0.019; duration of admission (OR = 1.03, 95%CI 1.01, 1.05) p = 0.002; number of days on postoperative medications (OR = 1.21, 95%CI 1, 1.46) p = 0.045; white blood cell count (OR = 1.04, 95%CI 0.98, 1.08) p = 0.050; and revised surgery (OR = 9.89, 95%CI 5.32, 18.79) p = 0.001.

Conclusion
This study's prevalence of orthopedic surgical site infection was 9.3%. Surgical site infections are the most surveyed and common types of healthcare-associated infections that occur in low and middle-income countries. Several factors may contribute to these infections. Standardized guidelines are needed to consolidate the prevention of these infections globally.
Regulatory role of lncH19 in RAC1 alternative splicing: implication for RAC1B expression in colorectal cancer
Authors: Cordaro Aurora , Barreca Maria Magdalena , Zichittella Chiara , Loria Marco , Anello Denise , Arena Goffredo , Sciaraffa Nicolina , Coronnello Claudia , Pizzolanti Giuseppe , Alessandro Riccardo , Conigliaro Alice 
Published: August 2024

AbstractAberrant alternative splicing events play a critical role in cancer biology, contributing to tumor invasion, metastasis, epithelial-mesenchymal transition, and drug resistance. Recent studies have shown that alternative splicing is a key feature for transcriptomic variations in colorectal cancer, which ranks third among malignant tumors worldwide in both incidence and mortality. Long non-coding RNAs can modulate this process by acting as trans-regulatory agents, recruiting splicing factors, or driving them to specific targeted genes. LncH19 is a lncRNA dis-regulated in several tumor types and, in colorectal cancer, it plays a critical role in tumor onset, progression, and metastasis. In this paper, we found, that in colorectal cancer cells, the long non-coding RNA H19 can bind immature RNAs and splicing factors as hnRNPM and RBFOX2. Through bioinformatic analysis, we identified 57 transcripts associated with lncH19 and containing binding sites for both splicing factors, hnRNPM, and RBFOX2. Among these transcripts, we identified the mRNA of the GTPase-RAC1, whose alternatively spliced isoform, RAC1B, has been ascribed several roles in the malignant transformation. We confirmed, in vitro, the binding of the splicing factors to both the transcripts RAC1 and lncH19. Loss and gain of expression experiments in two colorectal cancer cell lines (SW620 and HCT116) demonstrated that lncH19 is required for RAC1B expression and, through RAC1B, it induces c-Myc and Cyclin-D increase. In vivo, investigation from biopsies of colorectal cancer patients showed higher levels of all the explored genes (lncH19, RAC1B, c-Myc and Cyclin-D) concerning the healthy counterpart, thus supporting our in vitro model. In addition, we identified a positive correlation between lncH19 and RAC1B in colorectal cancer patients. Finally, we demonstrated that lncH19, as a shuttle, drives the splicing factors RBFOX2 and hnRNPM to RAC1 allowing exon retention and RAC1B expression. The data shown in this paper represent the first evidence of a new mechanism of action by which lncH19 carries out its functions as an oncogene by prompting colorectal cancer through the modulation of alternative splicing.
Phenotyping COVID-19 respiratory failure in spontaneously breathing patients with AI on lung CT-scan
Authors: Rezoagli Emanuele , Xin Yi , Signori Davide , Sun Wenli , Gerard Sarah , Delucchi Kevin L. , Magliocca Aurora , Vitale Giovanni , Giacomini Matteo , Mussoni Linda , Montomoli Jonathan , Subert Matteo , Ponti Alessandra , Spadaro Savino , Poli Giancarla , Casola Francesco , Herrmann Jacob , Foti Giuseppe , Calfee Carolyn S. , Laffey John , Bellani Giacomo , Cereda Maurizio ,   for the CT-COVID19 Multicenter Study Group, Lorini Ferdinando Luca , Bonaffini Pietro , Cazzaniga Matteo , Ottaviani Irene , Tavola Mario , Borgo Asia , Ferraris Livio , Serra Filippo , Gatti Stefano , Ippolito Davide , Tamagnini Beatrice , Gatti Marino , Arlotti Massimo , Gamberini Emiliano , Cavagna Enrico , Galbiati Giuseppe , De Ponti Davide 
Published: August 2024

Abstract
Background
Automated analysis of lung computed tomography (CT) scans may help characterize subphenotypes of acute respiratory illness. We integrated lung CT features measured via deep learning with clinical and laboratory data in spontaneously breathing subjects to enhance the identification of COVID-19 subphenotypes.

Methods
This is a multicenter observational cohort study in spontaneously breathing patients with COVID-19 respiratory failure exposed to early lung CT within 7 days of admission. We explored lung CT images using deep learning approaches to quantitative and qualitative analyses; latent class analysis (LCA) by using clinical, laboratory and lung CT variables; regional differences between subphenotypes following 3D spatial trajectories.

Results
Complete datasets were available in 559 patients. LCA identified two subphenotypes (subphenotype 1 and 2). As compared with subphenotype 2 (n = 403), subphenotype 1 patients (n = 156) were older, had higher inflammatory biomarkers, and were more hypoxemic. Lungs in subphenotype 1 had a higher density gravitational gradient with a greater proportion of consolidated lungs as compared with subphenotype 2. In contrast, subphenotype 2 had a higher density submantellar–hilar gradient with a greater proportion of ground glass opacities as compared with subphenotype 1. Subphenotype 1 showed higher prevalence of comorbidities associated with endothelial dysfunction and higher 90-day mortality than subphenotype 2, even after adjustment for clinically meaningful variables.

Conclusions
Integrating lung-CT data in a LCA allowed us to identify two subphenotypes of COVID-19, with different clinical trajectories. These exploratory findings suggest a role of automated imaging characterization guided by machine learning in subphenotyping patients with respiratory failure.
Trial registration: ClinicalTrials.gov Identifier: NCT04395482. Registration date: 19/05/2020.
Fetal endocrine axes mRNA expression levels are related to sex and intrauterine position
Authors: Yael Ariel , Fishman Ruth , Matas Devorah , Doniger Tirza , Vortman Yoni , Koren Lee 
Published: August 2024

Abstract
Background
The hypothalamic–pituitary–adrenal (HPA) and -gonadal (HPG) axes are two major pathways that connect the neural and endocrine systems in vertebrates. Factors such as prenatal stress and maternal exposure to exogenous steroids have been shown to affect these pathways during fetal development. Another less studied factor is the transfer of hormones across fetuses in multifetal pregnancies. This form of transfer has been shown to influence the morphology, anatomy, physiology, and behavior of the offspring in litter-bearing mammals, an influence termed the intrauterine position (IUP) effect. In this study, we sought to delineate how the IUP effects HPA and HPG brain receptors, peptides, and enzymes (hereafter components) in utero and how these influences may differ between males and females.

Methods
We utilized the unconventional model of culled free-ranging nutria (Myocastor coypus), with its large natural variation. We collected brain tissues from nutria fetuses and quantified the expression of key HPA and HPG components in three brain regions: prefrontal cortex, hypothalamus, and striatum.

Results
We found an interaction between sex and IUP in the mineralocorticoid receptor (MR), gonadotropin-releasing hormone receptor (GNRHR), androgen receptor (AR), and estrogen receptor alpha (ESR1). IUP was significant in both gonadotropin-releasing hormone (GnRH) and its receptor GNRHR, but in different ways. In the hypothalamus, fetuses adjacent to same-sex neighbors had higher expression of GnRH than fetuses neighboring the opposite sex. Conversely, in the cortex, GNRHR exhibited the inverse pattern, and fetuses that were neighboring the opposite sex had higher expression levels than those neighboring the same sex. Regardless of IUP, in most components that showed significant sex differences, female fetuses had higher mRNA expression levels than male fetuses. We also found that HPA and HPG components were highly related in the early stages of gestation, and that there was an interaction between sex and developmental stage. In the early stages of pregnancy, female component expression levels were more correlated than males’, but in the last trimester of pregnancy, male components were more related to each other than female’s.

Conclusions
This study suggests that there are sexually different mechanisms to regulate the HPA and HPG axes during fetal development. Higher mRNA expression levels of endocrine axes components may be a mechanism to help females cope with prolonged androgen exposure over a long gestational period. Additionally, these findings suggest different coordination requirements of male and female endocrine axes during stages of fetal development.
A modelling approach for quantifying volcanic sulphur dioxide concentrations at flight altitudes and the potential hazard to aircraft occupants
Authors: Kristiansen N. I. , Witham C. S. , Beckett F. M. 
Published: August 2024

AbstractVolcanic eruptions can emit large quantities of sulphur dioxide (SO2) into the atmosphere, which can be harmful to people and the environment. Aircraft encounters with a volcanic SO2 cloud could represent a health hazard to crew and passengers onboard. In this study we have assessed concentration levels of volcanic SO2 in the atmosphere following eight historic eruptions and use four-dimensional dispersion model simulation data to calculate when and where the World Health Organisation (WHO) health protection guideline for SO2 of 500 μgm-3 over 10 minutes is exceeded. The time and area of exceedance varies and depends on the eruption characteristics: the amount, duration and height of the SO2 release. The WHO-based guideline value is exceeded for all historic eruptions considered. In several cases, the area delineated by the WHO-based guideline, here called the SO2 hazard area, can be considerably larger than the volcanic ash hazard area for the same eruption. SO2 hazard areas also often extend over a longer period of time compared to the equivalent ash advisories. For example, following the 2019 eruption of Raikoke, the SO2 hazard area reached up to 1.7 million km2 and the WHO-based guideline value was exceeded for about two weeks, while volcanic ash was considered hazardous to aviation for about five days. These results will help the aviation industry to better understand the potential risks to their passengers and crew from volcanic SO2, and aid in defining concentration thresholds for any potential volcanic SO2 forecasts for aviation.