bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increasing access to screening for blood-borne viruses and sexually transmissible infections for Aboriginal and Torres Strait Islander Australians: evaluation of the Deadly Liver Mob program’s ‘cascade of care’ across nine sites in New South Wales, Australia
Authors: Cama Elena , Beadman Kim , Beadman Mitch , Smith Kerri-Anne , Christian Jade , Jackson Aunty Clair , Tyson Beverley , Anderson Clayton , Smyth Larissa , Heslop Jennifer , Gahan Gary , Tawil Victor , Sheaves Felicity , Maher Louise , Page Julie , Tilley Donna , Ryan Ann , Grant Kim , Donovan Basil , Stevens Annabelle , Slattery Trevor , Pearce Kate , John-Leader Franklin , Walden Andrew , Lenton Jo , Crowley Margaret , Treloar Carla 
Published: September 2023

Abstract
Background
Aboriginal and Torres Strait Islander Australians are disproportionately impacted by blood-borne viruses (BBVs) and sexually transmissible infections (STIs). Stigma remains one of the key barriers to testing and treatment for BBVs and STIs, particularly among Aboriginal and Torres Strait Islander people. The Deadly Liver Mob (DLM) is a peer-delivered incentivised health promotion program by and for Aboriginal and Torres Strait Islander Australians. The program aims to increase access to BBV and STI education, screening, treatment, and vaccination for Aboriginal and Torres Strait Islander Australians in recognition of the systemic barriers for First Nations people to primary care, including BBV- and STI-related stigma, and institutional racism. This paper presents routinely collected data across nine sites on the ‘cascade of care’ progression of Aboriginal and Torres Strait Islander clients through the DLM program: hepatitis C education, screening, returning for results, and recruitment of peers.

Methods
Routinely collected data were collated from each of the DLM sites, including date of attendance, basic demographic characteristics, eligibility for the program, recruitment of others, and engagement in the cascade of care.

Results
Between 2013 and 2020, a total of 1787 Aboriginal and Torres Strait Islander clients were educated as part of DLM, of which 74% went on to be screened and 42% (or 57% of those screened) returned to receive their results. The total monetary investment of the cascade of care progression was approximately $56,220. Data highlight the positive impacts of the DLM program for engagement in screening, highlighting the need for culturally sensitive, and safe programs led by and for Aboriginal and Torres Strait Islander people. However, the data also indicate the points at which clients ‘fall off’ the cascade, underscoring the need to address any remaining barriers to care.

Conclusions
The DLM program shows promise in acting as a ‘one stop shop’ in addressing the needs of Aboriginal and Torres Strait Islander people in relation to BBVs and STIs. Future implementation could focus on addressing any potential barriers to participation in the program, such as co-location of services and transportation.
Efficacy of sequential TACE on primary hepatocellular carcinoma with microvascular invasion after radical resection: a systematic review and meta-analysis
Authors: Mo Anwei , Lin Biquan , Chen Denglin 
Published: September 2023

Abstract
Objectives
The purpose of this study is to examine the impact of sequential transcatheter arterial chemoembolization (TACE) on the prognosis of patients with hepatocellular carcinoma (HCC) and microvascular invasion (MVI) following radical resection.

Methods
Five databases were searched for studies on the efficacy of TACE after radical hepatectomy resection (HR) for treating HCC with MVI. Depending on the heterogeneity between included studies, the relative risk (RR) and 95% confidence interval (CI) were computed using a random or fixed effect model.

Results
Thirteen articles were included in this study. There were 1378 cases in the HR-TACE group (cases undergoing TACE after HR) and 1636 cases in the HR group (cases only undergoing HR). The recurrence-free survival (RFS) at 1 year, 2 years, 3 years, and 5 years after radical HCC resection was statistically significantly greater in the HR-TACE group than in the HR group. The HR-TACE group exhibited statistically significant advantages at 1-year, 2-year, 3-year, and 5-year overall survival (OS) after radical HCC resection when compared with the HR group.

Conclusion
Postoperative sequential TACE treatment can improve the RFS and OS rates at 1 year, 2 years, 3 years, and 5 years following radical HR in patients with HCC and MVI. These findings will guide clinicians in selecting appropriate cases for adjuvant TACE treatment during clinical diagnosis and treatment to maximize patient benefit.

Trial registration
PROSPERO CRD42023449238.
Genome-wide differential expression profiling of long non-coding RNAs in FOXA2 knockout iPSC-derived pancreatic cells
Authors: Elsayed Ahmed K. , Alajez Nehad M. , Abdelalim Essam M. 
Published: September 2023

Abstract
Background
Our recent studies have demonstrated the crucial involvement of FOXA2 in the development of human pancreas. Reduction of FOXA2 expression during the differentiation of induced pluripotent stem cells (iPSCs) into pancreatic islets has been found to reduce α-and β-cell masses. However, the extent to which such changes are linked to alterations in the expression profile of long non-coding RNAs (lncRNAs) remains unraveled.

Methods
Here, we employed our recently established FOXA2-deficient iPSCs (FOXA2−/− iPSCs) to investigate changes in lncRNA profiles and their correlation with dysregulated mRNAs during the pancreatic progenitor (PP) and pancreatic islet stages. Furthermore, we constructed co-expression networks linking significantly downregulated lncRNAs with differentially expressed pancreatic mRNAs.

Results
Our results showed that 442 lncRNAs were downregulated, and 114 lncRNAs were upregulated in PPs lacking FOXA2 compared to controls. Similarly, 177 lncRNAs were downregulated, and 59 lncRNAs were upregulated in islet cells lacking FOXA2 compared to controls. At both stages, we observed a strong correlation between lncRNAs and several crucial pancreatic genes and TFs during pancreatic differentiation. Correlation analysis revealed 12 DE-lncRNAs that strongly correlated with key downregulated pancreatic genes in both PPs and islet cell stages. Selected DE-lncRNAs were validated using RT-qPCR.

Conclusions
Our data indicate that the observed defects in pancreatic islet development due to the FOXA2 loss is associated with significant alterations in the expression profile of lncRNAs. Therefore, our findings provide novel insights into the role of lncRNA and mRNA networks in regulating pancreatic islet development, which warrants further investigations.
Ligand-based adoptive T cell targeting CA125 in ovarian cancer
Authors: Zhao Haihong , Wu Lina , Dai Jiemin , Sun Ke , Zi Zhenguo , Guan Junhua , Zhang Liwen 
Published: September 2023

Abstract
Background
Ovarian cancer (OC) is a highly aggressive gynecological malignancy prevalent worldwide. Most OC cases are typically diagnosed at advanced stages, which has led to a 5-year overall survival rate of less than 35% following conventional treatment. Furthermore, immune checkpoint inhibitor therapy has shown limited efficacy in the treatment of patients with OC, and CAR-T therapy has also demonstrated modest results owing to inadequate T cell infiltration. Therefore, novel strategies must be developed to enhance T cell persistence and trafficking within the OC tumor microenvironment.

Methods
In this study, we developed a novel adoptive T-cell therapy for ovarian cancer based on a chimeric antigen receptor structure. We used a ligand-receptor binding motif to enhance the therapeutic effect of targeting CA125. Since mesothelin can naturally bind to CA125 with high affinity, we concatenated the core-binding fragment of mesothelin with the 4-1BB and CD3ζ signal fragments to assemble a novel CA125-targeting chimeric receptor (CR). The CAR structure targeting CA125 derived from the 4H11 antibody was also constructed. CR- and CAR-encoding RNA were electroporated into T cells to evaluate their antitumor activity both in vitro and in vivo.

Results
While CR-T or CAR-T cells exhibited moderate activity against two ovarian cancer cell lines, T cells co-expressing CR and CAR exhibited a superior killing effect compared to T cells expressing either CR or CAR alone. Furthermore, upon interaction with ovarian tumors, the ability of CR and CAR T cells to release activation markers and functional cytokines increased significantly. Similarly, CR and CAR co-expressing T cells persistently controlled the growth of transplanted ovarian cancer tumors in NSG mice and significantly prolonged the overall survival of tumor-challenged mice. Transcriptome sequencing revealed that the survival and cytotoxicity of T cells co-expressing CR and CAR were significantly altered compared with those of T cells expressing either CR or CAR.

Conclusion
Our findings demonstrate that CA125 targeting CR and CAR can synergistically kill ovarian cancer cells, indicating that CA125 targeting by the two binding motifs simultaneously in tumors may improve the therapeutic outcomes of ovarian cancer treatment.
Survey of adolescents’ needs and parents’ views on sexual health in juvenile idiopathic arthritis
Authors: Savel Carine , Chausset Aurélie , Berland Pauline , Guiguet-Auclair Candy , Cabane Laura , Fautrel Bruno , Gaudin Philippe , Guillot Pascale , Hayem Gilles , Lafarge Delphine , Merlin Etienne , Pezière Nadine , Sordet Christelle , Trope Sonia , Tournadre Anne , Malochet Sandrine , Cohen Jean-David 
Published: September 2023

Abstract
Background
Although the advent of new therapeutics for juvenile idiopathic arthritis (JIA) patients has considerably lessened the impact of the disease and reduced its sequelae, the outcomes of JIA remain important in their lives. Disease repercussions and side effects of treatments may affect sexual health and cause psychological distress. This aim of the study was to determine the expectations of adolescent JIA patients and the perceptions of their parents regarding knowledge and communication with healthcare providers (HCPs) in the field of sexual health (SH).

Methods
In France, from September 2021 to April 2022, a survey was conducted, using anonymous self-administered questionnaires, among JIA patients (adults (aged 18–45 years) to provide insights from their recollection of their adolescence) and their parents in nine rheumatology centers and three patient associations.

Results
The responses to the 76 patient questionnaires and 43 parent questionnaires that were collected were analyzed. Half of the patients thought JIA impacted their romantic relationships, but the results were less clear-cut for their sexual activity; and 58.7% of the patients said they would be comfortable discussing the subject with HCPs, but only 26.3% had done so, mainly regarding biomedical issues. The patients and their parents thought that ideally, the topic should be addressed in an individual patient education session at the hospital (51.3% and 34.9%, respectively), in a regular consultation (47.4% and 53.5%), or in a dedicated consultation requested by the adolescent without the adolescent’s parents being informed (38.2% and 20.9%). Most of the respondents thought HCPs should be proactive in SH (77.6% of the patients and 69.8% of their parents). More patients than parents said the following digital information tools must be used: videos (29.0% vs. 9.3%, p = 0.0127) and smartphone applications (25.0% vs. 9.3%, p = 0.0372).

Conclusion
HCPs should consider addressing the unmet need for SH discussions during their patient encounters. To meet this need, we propose concrete actions in line with the wishes of patients and parents.

Clinical trial registration number
NCT04791189.
Support for a radiation of free-living flatworms in the African Great Lakes region and the description of five new Macrostomum species
Authors: Brand Jeremias N. 
Published: September 2023

Abstract
Background
The African Great Lakes have long been recognized as an excellent location to study speciation. Most famously, cichlid fishes have radiated in Lake Tanganyika and subsequently spread into Lake Malawi and Lake Victoria, where they again radiated. Other taxa have diversified in these lakes, such as catfish, ostracods, gastropods, and Monegenean gill parasites of cichlids. However, these radiations have received less attention, and the process leading to their speciation in this unique region remains to be further explored. Here I present evidence that suggests a radiation of Macrostomum flatworms has occurred in the African Great Lakes region, offering a good opportunity for such investigations.

Results
Recent field work has revealed a monophyletic clade of 16 Macrostomum flatworms that have, to date, only been collected from Lake Tanganyika. Additionally, a species collected from Lake Malawi was found nested within this clade. Molecular phylogenetic analysis, largely based on transcriptome data, suggests that this clade underwent rapid speciation, possibly due to a large habitat diversity in the lake. I also observed significant differences in the sperm morphology of these flatworms compared to those of species found outside Lake Tanganyika and Lake Malawi. These included the elongation of an anterior structure, a reduction in the size of the lateral sperm bristles, and changes in relative proportions. I propose functional hypotheses for these changes in sperm design, and formally describe Macrostomum gracilistylum sp. nov from Lake Malawi and its sister species Macrostomum crassum sp. nov., Macrostomum pellitum sp. nov., Macrostomum longispermatum sp. nov., and Macrostomum schareri sp. nov., from Lake Tanganyika.

Conclusions
The available evidence is consistent with the hypothesis that Macrostomum flatworms have radiated in Lake Tanganyika and subsequently spread to Lake Malawi. However, whether this represents a bona fide adaptive radiation still needs to be determined. Therefore, the African Great Lakes are promising targets for further research into flatworm diversity and speciation.
Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy
Authors: Cai Letong , Li Yuchen , Tan Jiaxiong , Xu Ling , Li Yangqiu 
Published: September 2023

AbstractIn one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) constitute the second wave of immunotherapy targets that show great promise for use in the treatment of solid tumors and leukemia. To promote the research and clinical application of ICBs directed at these targets, we summarize their discovery, immunotherapy mechanism, preclinical efficiency, and clinical trial results in this review.
SEC23A confers ER stress resistance in gastric cancer by forming the ER stress-SEC23A-autophagy negative feedback loop
Authors: Cheng Quan , Liu Kanghui , Xiao Jian , Shen Kuan , Wang Yuanhang , Zhou Xinyi , Wang Jiawei , Xu Zekuan , Yang Li 
Published: September 2023

Abstract
Background
Sec23 homolog A (SEC23A), a core component of coat protein complex II (COPII), has been reported to be involved in several cancers. However, the role of SEC23A in gastric cancer remains unclear.

Methods
The expression of SEC23A in gastric cancer was analyzed by using qRT-PCR, western blotting and IHC staining. The role of SEC23A in ER stress resistance was explored by functional experiments in vitro and vivo. The occupation of STAT3 on the SEC23A promoter region was verified by luciferase reporter plasmids and CHIP assay. The interaction between SEC23A and ANXA2 was identified by Co-IP and mass spectrometry analysis.

Results
We demonstrated that SEC23A was upregulated in gastric cancer and predicted poor prognosis in patients with gastric cancer. Mechanistically, SEC23A was transcriptional upregulated by ER stress-induced pY705-STAT3. Highly expressed SEC23A promoted autophagy by regulating the cellular localization of ANXA2. The SEC23A-ANXA2-autophay axis, in turn, protected gastric cancer cells from ER stress-induced apoptosis. Furthermore, we identified SEC23A attenuated 5-FU therapeutic effectiveness in gastric cancer cells through autophagy-mediated ER stress relief.

Conclusion
We reveal an ER stress-SEC23A-autophagy negative feedback loop that enhances the ability of gastric cancer cells to resist the adverse survival environments. These results identify SEC23A as a promising molecular target for potential therapeutic intervention and prognostic prediction in patients with gastric cancer.
Prospective, multicenter validation of the deep learning-based cardiac arrest risk management system for predicting in-hospital cardiac arrest or unplanned intensive care unit transfer in patients admitted to general wards
Authors: Cho Kyung-Jae , Kim Jung Soo , Lee Dong Hyun , Lee Sang‑Min , Song Myung Jin , Lim Sung Yoon , Cho Young-Jae , Jo You Hwan , Shin Yunseob , Lee Yeon Joo 
Published: September 2023

Abstract
Background
Retrospective studies have demonstrated that the deep learning-based cardiac arrest risk management system (DeepCARS™) is superior to the conventional methods in predicting in-hospital cardiac arrest (IHCA). This prospective study aimed to investigate the predictive accuracy of the DeepCARS™ for IHCA or unplanned intensive care unit transfer (UIT) among general ward patients, compared with that of conventional methods in real-world practice.

Methods
This prospective, multicenter cohort study was conducted at four teaching hospitals in South Korea. All adult patients admitted to general wards during the 3-month study period were included. The primary outcome was predictive accuracy for the occurrence of IHCA or UIT within 24 h of the alarm being triggered. Area under the receiver operating characteristic curve (AUROC) values were used to compare the DeepCARS™ with the modified early warning score (MEWS), national early warning Score (NEWS), and single-parameter track-and-trigger systems.

Results
Among 55,083 patients, the incidence rates of IHCA and UIT were 0.90 and 6.44 per 1,000 admissions, respectively. In terms of the composite outcome, the AUROC for the DeepCARS™ was superior to those for the MEWS and NEWS (0.869 vs. 0.756/0.767). At the same sensitivity level of the cutoff values, the mean alarm counts per day per 1,000 beds were significantly reduced for the DeepCARS™, and the rate of appropriate alarms was higher when using the DeepCARS™ than when using conventional systems.

Conclusion
The DeepCARS™ predicts IHCA and UIT more accurately and efficiently than conventional methods. Thus, the DeepCARS™ may be an effective screening tool for detecting clinical deterioration in real-world clinical practice.
Trial registration This study was registered at ClinicalTrials.gov (NCT04951973) on June 30, 2021.
Newly diagnosed Crohn’s disease, and hepatocellular and renal cell carcinoma in a bariatric surgery patient—dealing with the complexity of obesity-associated diseases: a case report and review of the literature
Authors: Seidemann Lena , Dietrich Arne 
Published: September 2023

Abstract
Background
Bariatric surgery candidates commonly suffer from conditions that constitute the metabolic syndrome. But they also have a higher risk for autoimmune and malignant diseases. Obesity-associated comorbidities aside from the metabolic syndrome are often given insufficient attention in the clinical routine, including preoperative work-ups for bariatric surgery.

Case presentation
We retrospectively report the case of a 65 years old Caucasian patient who was diagnosed with Crohn’s disease prior to, a hepatocellular carcinoma during, and a renal cell carcinoma post bariatric surgery. The relevance of these diseases for decision making in bariatric procedures and current recommendations for preoperative bariatric work-ups are discussed. In our case, the diagnosis of Crohn’s disease led to the performance of a sleeve gastrectomy instead of a Roux-en-Y gastric bypass and a previously unknown hepatocellular carcinoma was simultaneously removed by hepatic wedge resection.

Conclusions
Preoperative endoscopy and imaging techniques can be valuable since surprising pre- and intraoperative findings can force the bariatric surgeon to change the initially planned operative strategy. But the diagnostic accuracy of abdominal ultrasound may be limited in bariatric surgery patients. With the expansion of bariatric surgery, the complexity of bariatric surgery patients is also likely to increase. However, with the appropriate awareness and strategies, bariatric surgery can be safely executed and even contribute to the treatment of severe comorbidities that exceed the metabolic spectrum.
Impact of brain segmentation methods on regional metabolism quantification in 18F-FDG PET/MR analysis
Authors: Shan Yi , Yan Shao-zhen , Wang Zhe , Cui Bi-xiao , Yang Hong-wei , Yuan Jian-min , Yin Ya-yan , Shi Feng , Lu Jie 
Published: September 2023

Abstract
Background
Accurate analysis of quantitative PET data plays a crucial role in studying small, specific brain structures. The integration of PET and MRI through an integrated PET/MR system presents an opportunity to leverage the benefits of precisely aligned structural MRI and molecular PET images in both spatial and temporal dimensions. However, in many clinical workflows, PET studies are often performed without the aid of individually matched structural MRI scans, primarily for the sake of convenience in the data collection and brain segmentation possesses. Currently, two commonly employed segmentation strategies for brain PET analysis are distinguished: methods with or without MRI registration and methods employing either atlas-based or individual-based algorithms. Moreover, the development of artificial intelligence (AI)-assisted methods for predicting brain segmentation holds promise but requires further validation of their efficiency and accuracy for clinical applications. This study aims to compare and evaluate the correlations, consistencies, and differences among the above-mentioned brain segmentation strategies in quantification of brain metabolism in 18F-FDG PET/MR analysis.

Results
Strong correlations were observed among all methods (r = 0.932 to 0.999, P < 0.001). The variances attributable to subject and brain region were higher than those caused by segmentation methods (P < 0.001). However, intraclass correlation coefficient (ICC)s between methods with or without MRI registration ranged from 0.924 to 0.975, while ICCs between methods with atlas- or individual-based algorithms ranged from 0.741 to 0.879. Brain regions exhibiting significant standardized uptake values (SUV) differences due to segmentation methods were the basal ganglia nuclei (maximum to 11.50 ± 4.67%), and various cerebral cortexes in temporal and occipital regions (maximum to 18.03 ± 5.52%). The AI-based method demonstrated high correlation (r = 0.998 and 0.999, P < 0.001) and ICC (0.998 and 0.997) with FreeSurfer, substantially reducing the time from 8.13 h to 57 s on per subject.

Conclusions
Different segmentation methods may have impact on the calculation of brain metabolism in basal ganglia nuclei and specific cerebral cortexes. The AI-based approach offers improved efficiency and is recommended for its enhanced performance.