bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ewing Sarcoma Single-cell Transcriptome Analysis Reveals Functionally Impaired Antigen-presenting Cells
Authors: Visser Lindy L. , Bleijs Margit , Margaritis Thanasis , van de Wetering Marc , Holstege Frank C. P. , Clevers Hans 
Published: October 2023

Abstract

Novel therapeutic strategies are urgently needed for patients with high-risk Ewing sarcoma and for the reduction of severe side effects for all patients. Immunotherapy may fill this need, but its successful application has been hampered by a lack of knowledge on the composition and function of the Ewing sarcoma immune microenvironment. Here, we explore the immune microenvironment of Ewing sarcoma, by single-cell RNA sequencing of 18 Ewing sarcoma primary tissue samples. Ewing sarcoma is infiltrated by natural killer, T, and B cells, dendritic cells, and immunosuppressive macrophages. Ewing sarcoma–associated T cells show various degrees of dysfunction. The antigen-presenting cells found in Ewing sarcoma lack costimulatory gene expression, implying functional impairment. Interaction analysis reveals a clear role for Ewing sarcoma tumor cells in turning the Ewing sarcoma immune microenvironment into an immunosuppressive niche. These results provide novel insights into the functional state of immune cells in the Ewing sarcoma tumor microenvironment and suggest mechanisms by which Ewing sarcoma tumor cells interact with, and shape, the immune microenvironment.

Significance:
This study is the first presenting a detailed analysis of the Ewing sarcoma microenvironment using single-cell RNA sequencing. We provide novel insight into the functional state of immune cells and suggests mechanisms by which Ewing tumor cells interact with, and shape, their immune microenvironment. These insights provide help in understanding the failures and successes of immunotherapy in Ewing sarcoma and may guide novel targeted (immuno) therapeutic approaches.
Widening the Prostacyclin Paradigm: Tissue Fibroblasts Are a Critical Site of Production and Antithrombotic Protection
Authors: Vinokurova Maria , Lopes-Pires Maria Elisa , Cypaite Neringa , Shala Fisnik , Armstrong Paul C. , Ahmetaj-Shala Blerina , Elghazouli Youssef , Nüsing Rolf , Liu Bin , Zhou Yingbi , Hao Chuan-ming , Herschman Harvey R. , Mitchell Jane A. , Kirkby Nicholas S. 
Published: October 2023

BACKGROUND:
Prostacyclin is a fundamental signaling pathway traditionally associated with the cardiovascular system and protection against thrombosis but which also has regulatory functions in fibrosis, proliferation, and immunity. Prevailing dogma states that prostacyclin is principally derived from vascular endothelium, although it is known that other cells can also synthesize it. However, the role of nonendothelial sources in prostacyclin production has not been systematically evaluated resulting in an underappreciation of their importance relative to better characterized endothelial sources.

METHODS:

To address this, we have used novel endothelial cell–specific and fibroblast-specific COX (cyclo-oxygenase) and prostacyclin synthase knockout mice and cells freshly isolated from mouse and human lung tissue. We have assessed prostacyclin release by immunoassay and thrombosis in vivo using an FeCl
3
-induced carotid artery injury model.

RESULTS:
We found that in arteries, endothelial cells are the main source of prostacyclin but that in the lung, and other tissues, prostacyclin production occurs largely independently of endothelial and vascular smooth muscle cells. Instead, in mouse and human lung, prostacyclin production was strongly associated with fibroblasts. By comparison, microvascular endothelial cells from the lung showed weak prostacyclin synthetic capacity compared with those isolated from large arteries. Prostacyclin derived from fibroblasts and other nonendothelial sources was seen to contribute to antithrombotic protection.

CONCLUSIONS:
These observations define a new paradigm in prostacyclin biology in which fibroblast/nonendothelial-derived prostacyclin works in parallel with endothelium-derived prostanoids to control thrombotic risk and potentially a broad range of other biology. Although generation of prostacyclin by fibroblasts has been shown previously, the scale and systemic activity was unappreciated. As such, this represents a basic change in our understanding and may provide new insight into how diseases of the lung result in cardiovascular risk.
The Application of the Good Faith Principle in the 2018 Commercial Lien Law: Toward a Better Performance
Authors: Alshahrani Shaya Abdullah 
Published: October 2023

Abstract
The Saudi legislator requires the creditor to meet the requirements of the Good Faith Principle in commercial lien contracts to obtain legal protection against the debtor. Since this principle was originally a moral obligation, there are questions about applying it in the legal context. To identify potential obstacles and address them, this paper critically evaluates current applications of the Good Faith Principle in the context of the 2018 Commercial Lien Law (2018 CLL). The assessment is made by considering the impact of such a principle on the interests of both contracting parties. Thus, this paper proposes practical solutions to improve the current regulatory framework of good faith within the 2018 CLL to achieve adequate protection for the creditor in a manner that does not harm the debtor’s interests.
Economic evaluations of alcohol pharmacotherapy: Systematic review of economic evaluations of pharmacotherapy for the treatment of alcohol use disorder
Authors: Higginbotham Benjamin , Perez Joahna Kevin , Louie Eva , Haber Paul S , Lubman Dan , Arunogiri Shalini , Chatterton Mary Lou , Morley Kirsten C 
Published: October 2023

Objective:Alcohol use disorders confer a significant burden of disease and economic cost worldwide. However, the utilisation of pharmacotherapies to manage alcohol use disorder is poor. We aimed to conduct a systematic review of economic evaluation studies of alcohol use disorder pharmacotherapies.Methods:A search was conducted in Embase, Medline, CINAHL, PsychINFO and EconLit (August 2019, updated September 2022). Full economic evaluations using pharmacotherapy to treat alcohol use disorders were included. Included studies were stratified by medication and summarised descriptively. The Consensus on Health Economic Criteria list was used to assess the methodological quality.Results:A total of 1139 studies were retrieved, of which 15 met the inclusion criteria. All studies were conducted in high-income countries. Four studies analysed nalmefene, four studies assessed acamprosate, three for naltrexone and four for stand-alone and/or combinations of naltrexone and acamprosate. There were 21 interventions synthesised from 15 studies as some studies evaluated multiple interventions and comparators. More than half of the included studies (73%) reported pharmacotherapy as dominant (less costly and more effective than comparators). From healthcare payer perspectives, five studies found that pharmacotherapy added to psychosocial support was dominant or cost-effective, accruing additional benefits at a higher cost but under accepted willingness to pay thresholds. Three analyses from a societal perspective found pharmacotherapy added to psychosocial support was a dominant or cost-effective strategy. Quality scores ranged from 63% to 95%.Conclusion:Pharmacotherapy added to psychosocial support was cost-effective from both healthcare and societal perspectives, emphasising an increased role for pharmacotherapy to reduce the burden of alcohol use disorders.
ADC histogram parameters differentiating atypical from transitional meningiomas: correlation with Ki-67 proliferation index
Authors: Han Tao , Liu Xianwang , Jing Mengyuan , Zhang Yuting , Zhang Bin , Deng Liangna , Zhou Junlin 
Published: October 2023

Background Preoperative differentiation of atypical meningioma (AtM) from transitional meningioma (TrM) is critical to clinical treatment. Purpose To investigate the role of apparent diffusion coefficient (ADC) histogram analysis in differentiating AtM from TrM and its correlation with the Ki-67 proliferation index (PI). Methods Clinical, imaging, and pathological data of 78 AtM and 80 TrM were retrospectively collected. Regions of interest (ROIs) were delineated on axial ADC images using MaZda software and histogram parameters (mean, variance, skewness, kurtosis, 1st percentile [ADCp1], 10th percentile [ADCp10], 50th percentile [ADCp50], 90th percentile [ADCp90], and 99th percentile [ADCp99]) were generated. The Mann–Whitney U test was used to compare the differences in histogram parameters between the two groups; receiver operating characteristic (ROC) curves were used to assess diagnostic efficacy in differentiating AtM from TrM preoperatively. The correlation between histogram parameters and Ki-67 PI was analyzed. Results All histogram parameters of AtM were lower than those of TrM, and the variance, skewness, kurtosis, ADCp90, and ADCp99 were significantly different ( P < 0.05). Combined ADC histogram parameters (variance, skewness, kurtosis, ADCp90, and ADCp99) achieved the best diagnostic performance for distinguishing AtM from TrM. Area under the curve (AUC), sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.800%, 76.25%, 67.95%, 70.15%, 70.93%, and 73.61%, respectively. All histogram parameters were negatively correlated with Ki-67 PI (r = −0.012 to −0.293). Conclusion ADC histogram analysis is a potential tool for non-invasive differentiation of AtM from TrM preoperatively, and ADC histogram parameters were negatively correlated with the Ki-67 PI.
Choice of product quality in supply chain of live-streaming e-commerce under different power structures
Authors: Zhang Zhijian , Chen Zhenwu , Wan Miyu , Qiu Shuai 
Published: October 2023

Product quality has become an important factor affecting consumer demand and the sustainable and stable development of the live-streaming e-commerce supply chain. In this article, two types of Stackelberg game of manufacturer-led or streamer-led and centralized decision game models are constructed to explore the impact of streamer commission proportion and different power structures on product quality decision-making of live-streaming e-commerce supply chain. The results show that (1) product quality decreases with the increase of streamer commission proportion under streamer’s dominant power structure and manufacturer’s dominant power structure, and product quality is not affected by streamer commission proportion under a centralized decision-making mode; (2) the product quality under the three power structures increases with the increase of quality sensitivity coefficient and decreases with the increase of quality-improvement cost coefficient; (3) comparatively speaking, the live-streaming under centralized decision-making mode has lower price and higher product quality, while the power structure dominated by manufacturers is unfavorable to the improvement of product quality. JEL Classification: C72, D21
Association of Changes in Hip and Knee Kinematics During a Single-Leg Squat With Changes in Patient-Reported Outcomes at 6 Months and 1 Year After Hip Arthroscopy
Authors: Swindell Hasani , Wichman Daniel M. , Guidetti Martina , Chahla Jorge , Nho Shane J. , Malloy Philip 
Published: October 2023

Background: Previous studies have demonstrated alterations in squat kinematics in patients with femoroacetabular impingement syndrome (FAIS). Little is known about the effects of arthroscopic hip surgery on biomechanics during a single-leg squat (SLS) in these patients. Purpose/Hypothesis: The purpose of this study was to determine if (1) lower extremity dynamic range of motion (ROM) during an SLS task improves after hip arthroscopy for FAIS and (2) correlations exist between changes in patient-reported outcomes (PROs) and changes in lower extremity dynamic ROM during an SLS after hip arthroscopy for FAIS. It was hypothesized that dynamic hip ROM would improve after hip arthroscopy and that hip dynamic ROM would be associated with changes in PRO scores at both 6 months and 1 year. Study Design: Descriptive laboratory study. Methods: Patients with FAIS performed 3 SLSs that were analyzed using a 20-camera motion capture system. Dynamic ROMs were calculated in 3 planes for the hip, knee, ankle, and pelvic segments. Squat depth was calculated as the change in vertical center of mass during the squat cycle. PROs including the Hip Outcome Score–Activities of Daily Living (HOS-ADL), Hip Outcome Score–Sports (HOS–Sports), International Hip Outcome Tool–12, and visual analog scale for pain scores were collected preoperatively and at the time of postoperative testing. Paired-samples t tests were used to compare kinematic variables pre- and postoperatively. Correlations were used to compare changes in PROs with changes in kinematics. All statistical analysis was performed using SPSS Version 26. Results: Fifteen patients were tested preoperatively and at a mean of 9 months postoperatively. All PRO measures improved postoperatively at 6 months and 1 year. Squat depth and sagittal plane hip and knee dynamic ROMs were significantly improved postoperatively. Positive correlations existed between changes in (1) hip ROM with the 6-month HOS-ADL score ( r = 0.665) and (2) knee ROM with the 6 month ( r = 0.590) and 1-year ( r = 0.565) HOS–Sports scores. Conclusion: Dynamic sagittal plane hip and knee ROMs improve after hip arthroscopy for FAIS. These improvements demonstrate strong correlations with improvements in some but not all postoperative PROs. Clinical Relevance: The current study sought to better understand the role of dynamic movement in the diagnosis and treatment of FAIS. These findings indicate that dynamic ROM and squat depth can, similarly to PROs, serve as biomarkers for patient function both before and after hip arthroscopic surgery.
METTL3-mediated m6A modification of lncRNA SNHG3 accelerates gastric cancer progression by modulating miR-186-5p/cyclinD2 axis
Authors: Ji Guo , Wang Xiu , Xi Hao 
Published: October 2023

Objectives METTL3 as an m6A methyltransferase acts in diverse malignancies including gastric cancer (GC). We aimed to reveal the underlying mechanisms by which METTL3 contributes to gastric carcinogenesis. Methods The association of METTL3 and SNHG3 with GC was analyzed by qRT-PCR, Western blot, and TCGA cohort. The functional experiments were implemented to uncover the role of METTL3 in GC. m6A dot blot and MeRIP were used to determine METTL3-mediated m6A modification of lncRNA SNHG3. The effect of METTL3 on SNHG3-mediated miR-186-5p/cyclinD2 axis was evaluated by luciferase gene report, RT-qPCR, and Western blot assays. Results We found that METTL3 was remarkably elevated in GC tissues and correlated with poor survival in patients with GC. Silencing of METTL3 impaired GC cell growth and invasion, whereas restored METTL3 expression promoted these effects. Mechanistically, reduced expression of METTL3 decreased SNHG3 m6A level and caused a decrease in SNHG3 expression, which could further act as a sponge of miR-186-5p to upregulate cyclinD2. Overexpression of SNHG3 attenuated METTL3 knockdown-induced anti-proliferating and miR-186-5p upregulation and cyclinD2 downregulation. Conclusion We find that METTL3-mediated m6A modification of lncRNA SNHG3 accelerates GC progression by modulating miR-186-5p/cyclinD2 axis.
Investigating the Anti-inflammatory Effects of Rutin in Carbon Tetrachloride-induced Hepatotoxicity: Role of TLR4/MyD88/NFκB Signaling Pathway Modulation
Authors: He Qianyu , Hao Hu , Zhao Keke 
Published: October 2023

Objectives Rutin protects and stabilizes hepatocytes and is used to treat hepatitis, liver cirrhosis, and other diseases. However, there is little evidence to suggest that Rutin is associated with CCl4-induced hepatotoxicity. In this study, we investigated the effects of Rutin on CCl4-induced liver inflammation and discussed in vivo and in vitro mechanisms. Materials and Methods CCl4 was used to induce liver inflammation, and Rutin was used for intervention in mice. Then the body weight, liver weight, and liver inflammation of all mice were measured. Western blotting and RT-PCR were used to assess TLR4/MyD88/NFκB inflammation signaling pathways and inflammatory gene expression. Finally, TLR4 was activated in primary hepatocytes to verify the above signal pathways. Findings CCl4 mice developed liver function damage and liver inflammation. Further investigations showed that the inhibitory effects of Si on inflammation were mediated by TLR4/MyD88/NFκB inflammation signaling pathways inhibition. Primary hepatocyte studies also confirmed the participation of these signaling pathways and proteins. Significance Rutin improved CCl4-induced liver inflammation. Such mechanisms may be related to TLR4/MyD88/NFκB inflammation signaling pathways.
Implementation of Risk-Stratified Breast Cancer Prevention With a Polygenic Risk Score Test in Clinical Practice
Authors: Padrik Peeter , Puustusmaa Mikk , Tõnisson Neeme , Kolk Berit , Saar Regina , Padrik Anna , Tasa Tõnis 
Published: October 2023

Background: Breast cancer (BC) screening with mammography reduces mortality but considers currently only age as a risk factor. Personalized risk-based screening has been proposed as a more efficient alternative. For that, risk prediction tools are necessary. Genome-wide association studies have identified numerous genetic variants (single-nucleotide polymorphisms [SNPs]) associated with BC. The effects of SNPs are combined into a polygenic risk score (PRS) as a risk prediction tool. Objectives: We aimed to develop a clinical-grade PRS test suitable for BC risk-stratified screening with clinical recommendations and implementation in clinical practice. Design and methods: In the first phase of our study, we gathered previously published PRS models for predicting BC risk from the literature and validated them using the Estonian Biobank and UK Biobank data sets. We selected the best performing model based on prevalent data and independently validated it in both incident data sets. We then conducted absolute risk simulations, developed risk-based recommendations, and implemented the PRS test in clinical practice. In the second phase, we carried out a retrospective analysis of the PRS test’s performance results in clinical practice. Results: The best performing PRS included 2803 SNPs. The C-index of the Cox regression model associating BC status with PRS was 0.656 (SE = 0.05) with a hazard ratio of 1.66. The PRS can stratify individuals with more than a 3-fold risk increase. A total of 2637 BC PRS tests have been performed for women between the ages 30 and 83. Results in clinical use overlap well with expected PRS performance with 5.7% of women with more than 2-fold and 1.4% with more than 3-fold higher risk than the population average. Conclusion: The PRS test separates different BC risk levels and is feasible to implement in clinical practice.
Affordances of code-switching in Polish–Australian families: An exploration of language ideologies, practices and management
Authors: Romanowski Piotr 
Published: October 2023

Aims and objectives: As there remains a paucity of research into the use of communication strategies in Polish transnational communities, this paper seeks to delineate the code-switching practices of Polish-speaking families residing in Australia. The tripartite framework of Family Language Policy has been applied for the analysis of affordances of code-switching patterns. Methodology: Based on the data collected through the online questionnaire supplemented with in-depth interviews and observations, a qualitative analysis has been conducted to obtain the sociolinguistic picture of the code-switching practices. Data and analysis: The interviews and discussions during the observations were recorded, transcribed verbatim and coded according to the Grounded Theory Approach. The recurrent themes were noted. The existing patterns were conceptualised through the process of constant comparison. Findings and conclusions: The conducted study draws our attention to the fact that Polish speakers in Australia differ from speakers of other heritage languages. Language management efforts through a great exposure to Polish translates to HL proficiency, maintenance and the degree of bilingualism, as well as the rate of code-switching. All joint family and extracurricular activities organised by Saturday schools and cultural centres augment the HL retention despite the constant attempts to code-switch among the young family members. Originality: This paper delves into how Polish is maintained as a HL among Polish-speaking immigrants to Australia and their offspring. It explores one of the well-established yet understudied communities that makes up multicultural Australia. It unfolds an account of the dynamics of code-switching, illustrating how its affordances are utilised to foster communication.
Racial and Ethnic Disparities in Hip Fracture Surgery: A Systematic Review and Meta-Analysis
Authors: Rudisill Samuel S. , Hornung Alexander L. , Varady Nathan H. , Pean Christian A. , Lane Joseph M. , Amen Troy B. 
Published: October 2023

Background: Hip fractures are common injuries that result in substantial loss of quality of life to elderly patients. To date, no meta-analyses have been performed to consolidate findings related to racial and ethnic disparities in hip fracture care. Purpose: We sought to examine associations between racial or ethnic identity and several metrics of hip fracture care. Methods: For a systematic review and meta-analysis, we searched PubMed, Scopus, CINAHL, and SPORTDiscus databases in December 2021 for articles examining racial and ethnic disparities in hip fracture surgery among White, Black, Hispanic, Asian, Pacific Islander (PI), and American Indian/Alaska Native (AIAN) patients. Twenty-three studies reported time to surgery (TTS), complications, mortality, length of stay (LOS), discharge disposition, readmissions, or reoperations. Meta-analyses were conducted for outcomes for which there were at least 3 comparable studies with requisite data available. Results: Compared with White patients, Black patients experienced greater rates of TTS longer than 2 days, 30-day complication, 90-day readmission, 1-year reoperation, and longer LOS, though odds of 30-day mortality were reduced. Hispanic patients had higher 90-day complication rates and longer LOS but lower risk of mortality and nonhome discharge than other racial and ethnic groups. Time to surgery of longer than 2 days was more common among Asian patients, though mortality, nonhome discharge, and readmission rates were lower. There were higher mortality rates in White patients compared with Hispanic patients at all timepoints and compared with Black patients until 1 year following surgery, when rates were higher among Black patients. Conclusions: This systematic review and meta-analysis found evidence of disparities in hip fracture surgery, with minority patients facing greater rates of surgical delay and perioperative complications. Even though the studies may not have been uniform in defining race or ethnicity or in accounting for the effects of systemic racism, these findings suggest that concerted efforts are needed to understand these gaps and promote equity in hip fracture care.