bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploratory study of an anti-PD-L1/TGF-β antibody, TQB2858, in patients with refractory or recurrent osteosarcoma and alveolar soft part sarcoma: a report from Chinese sarcoma study group (TQB2858-Ib-02)
Authors: Xie Lu , Liang Xin , Xu Jie , Sun Xin , Liu Kuisheng , Sun Kunkun , Li Yuan , Tang Xiaodong , Li Xianan , Zhan Xing , Niu Xiaohui , Guo Wei 
Published: September 2023

Abstract
Background
Novel and effective immunotherapies are required for refractory or recurrent sarcomas. Transforming growth factor-beta (TGF-β) is a diverse regulatory and fibrogenic protein expressed in multiple sarcoma tumors that promotes epithelial-mesenchymal transition and excessive deposition of extracellular matrix. This study evaluated the efficacy and safety of the anti-PD-L1/TGF-β antibody TQB2858 in patients with refractory osteosarcoma and alveolar soft part sarcoma (ASPS).

Methods
This single-arm phase 1b exploratory study included patients with refractory osteosarcoma or ASPS who had previously undergone at least two lines of systemic therapy. Patients were administered 1200 mg of TQB2858 once every 3 weeks. The primary endpoint was objective response rate (ORR), with null and alternative hypotheses of ORR ≤5% and ≥20%, respectively. Exploratory biomarker analyses using immunohistochemistry (IHC) staining (for PD-L1 and TGF-β) were performed on pre-treatment tumor samples.

Results
Eleven eligible patients were included in this study. TQB2858 did not demonstrate evidence of efficacy as 0/5 osteosarcomas had any objective response, while 2/6 ASPS showed a partial response. The median progression-free survivals were 1.51 (1.38, Not Evaluable) and 2.86 (1.38, Not Evaluable) months for the osteosarcoma and ASPS groups, respectively. None of the administered cycles met the criteria for unacceptable toxicity. Other Grade 3 toxicities included abnormal liver function and elevation of γ-glutamyl transferase. IHC analysis revealed that functional enrichment in the TGF-β pathway or PD-L1 was not associated with treatment outcomes.

Conclusions
The combination of PD-L1 and TQB2858 did not significantly improve the ORR in patients with recurrent osteosarcoma. However, it improved immunogenic responses in ASPS, even after progression upon anti-PD-1/PD-L1 therapy, with an acceptable safety profile. IHC profiling with pathway enrichment analysis may not have any predictive value for survival outcomes.

Trial registration
Prospectively registered in the Ethical Review Committee of Peking University People’s Hospital. The trial registration number is 2021PHA105-001 and 2021PHA140-001 and the registration date was March 2, 2022.
ClinicalTrials.gov Identifier CTR20213001 and CTR20220390
Comparative analysis of clinical features of lower respiratory tract infection with respiratory syncytial virus and influenza virus in adults: a retrospective study
Authors: Tian Jiahua , Liu Congyue , Wang Xunling , Zhang Ling , Zhong Guoying , Huang Guichuan , Wang Hongping , Hu Hao , Gong Ling , Liu Daishun 
Published: September 2023

Abstract
Background
Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment.

Methods
Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups.

Results
In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05).

Conclusion
Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.
Assessing young adults' menopause knowledge to increase understanding of symptoms and help improve quality of life for women going through menopause; a student survey
Authors: Patel Vaishvi , Ross Sue , Sydora Beate C. 
Published: September 2023

Abstract
Background
Due to menopause being a largely invisible and under-discussed topic in wider society, women often deal with menopause-related complications on their own. Social support and awareness have been shown to reduce negative menopausal experiences; however, lack of menopause knowledge, particularly among younger people, may deter support for women suffering from menopause symptoms. This study aims to assess the level of knowledge young adults have on menopause to be able to create interventions that target knowledge gaps and increase understanding of women’s experiences and difficulties during their menopause transition.

Methods
We created an electronic questionnaire based on menopause literature and guidelines from Menopause Societies. It was pilot-tested on young people in the target group age (n = 14; 7 male and 7 female), menopause clinicians (n = 5), and women experiencing menopause (n = 4). The final survey included questions on participant demographics, general menopause knowledge, and options to support menopause management and was distributed through university student newsletters. Responses over a two week period were collected anonymously. Descriptive statistics were applied to characterize participants, define menopause knowledge, and identify gaps. Chi-squared statistics was used for group comparison, and open questions were analyzed using qualitative content analysis.

Results
Survey responses were collected from 828 students; the average age was 22.1 ± 5.1 and 83.6% were female. Participants belonged to all faculties and included students from a variety of family settings and living conditions. Knowledge questions revealed a good understanding of the basic menopause physiology for most respondents, but there were gaps in understanding of symptoms and symptom management. Female sex and personal connection to menopausal women had a positive effect on the degree of menopause knowledge. Both males and females reported increased knowledge confidence at the end of the survey.

Conclusion
Our survey provides evidence that young adults of both sexes have a general baseline knowledge of menopause and its symptoms and are open to learning strategies to help support menopausal women. Our findings will assist in developing targeted educational resources to increase social support and awareness, reduce stigma and improve the quality of life for menopausal women, and help prepare younger women for their future menopause journey.
A nomogram for predicting sepsis-associated delirium: a retrospective study in MIMIC III
Authors: Gu Qiong , Yang Shucong , Fei DanTing , Lu Yuting , Yu Huijie 
Published: September 2023

Abstract
Objective
To develop a nomogram for predicting the occurrence of sepsis-associated delirium (SAD).

Materials and methods
Data from a total of 642 patients were retrieved from the Medical Information Mart for Intensive Care (MIMIC III) database to build a prediction model. Multivariate logistic regression was performed to identify independent predictors and establish a nomogram to predict the occurrence of SAD. The performance of the nomogram was assessed in terms of discrimination and calibration by bootstrapping with 1000 resamples.

Results
Multivariate logistic regression identified 4 independent predictors for patients with SAD, including Sepsis-related Organ Failure Assessment(SOFA) (p = 0.004; OR: 1.131; 95% CI 1.040 to 1.231), mechanical ventilation (P < 0.001; OR: 3.710; 95% CI 2.452 to 5.676), phosphate (P = 0.047; OR: 1.165; 95% CI 1.003 to 1.358), and lactate (P = 0.023; OR: 1.135; 95% CI 1.021 to 1.270) within 24 h of intensive care unit (ICU) admission. The area under the curve (AUC) of the predictive model was 0.742 in the training set and 0.713 in the validation set. The Hosmer − Lemeshow test showed that the model was a good fit (p = 0.471). The calibration curve of the predictive model was close to the ideal curve in both the training and validation sets. The DCA curve also showed that the predictive nomogram was clinically useful.

Conclusion
We constructed a nomogram for the personalized prediction of delirium in sepsis patients, which had satisfactory performance and clinical utility and thus could help clinicians identify patients with SAD in a timely manner, perform early intervention, and improve their neurological outcomes.
Fluoride-activated photothermal system for promoting bacteria-infected wound healing
Authors: Du Yuanchun , Liu Zekai , Yang Qingxin , Zhen Deshuai , Liu Yu , Feng Guangfu 
Published: September 2023

AbstractAlthough photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F− + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.
Doing community-based research during dual public health emergencies (COVID and overdose)
Authors: Beck McGreevy Phoenix , Wood Shawn , Thomson Erica , Burmeister Charlene , Spence Heather , Pelletier Josh , Giesinger Willow , McDougall Jenny , McLeod Rebecca , Hutchison Abby , Lock Kurt , Norton Alexa , Barker Brittany , Urbanoski Karen , Slaunwhite Amanda , Nosyk Bohdan , Pauly Bernie 
Published: September 2023

AbstractMeaningful engagement and partnerships with people who use drugs are essential to conducting research that is relevant and impactful in supporting desired outcomes of drug consumption as well as reducing drug-related harms of overdose and COVID-19. Community-based participatory research is a key strategy for engaging communities in research that directly affects their lives. While there are growing descriptions of community-based participatory research with people who use drugs and identification of key principles for conducting research, there is a gap in relation to models and frameworks to guide research partnerships with people who use drugs. The purpose of this paper is to provide a framework for research partnerships between people who use drugs and academic researchers, collaboratively developed and implemented as part of an evaluation of a provincial prescribed safer supply initiative introduced during dual public health emergencies (overdose and COVID-19) in British Columbia, Canada. The framework shifts from having researchers choose among multiple models (advisory, partnership and employment) to incorporating multiple roles within an overall community-based participatory research approach. Advocacy by and for drug users was identified as a key role and reason for engaging in research. Overall, both academic researchers and Peer Research Associates benefited within this collaborative partnerships approach. Each offered their expertise, creating opportunities for omni-directional learning and enhancing the research. The shift from fixed models to flexible roles allows for a range of involvement that accommodates varying time, energy and resources. Facilitators of involvement include development of trust and partnering with networks of people who use drugs, equitable pay, a graduate-level research assistant dedicated to ongoing orientation and communication, technical supports as well as fluidity in roles and opportunities. Key challenges included working in geographically dispersed locations, maintaining contact and connection over the course of the project and ensuring ongoing sustainable but flexible employment.
Prevalence of unmet health care need in older adults in 83 countries: measuring progressing towards universal health coverage in the context of global population ageing
Authors: Kowal Paul , Corso Barbara , Anindya Kanya , Andrade Flavia C. D. , Giang Thanh Long , Guitierrez Maria Teresa Calzada , Pothisiri Wiraporn , Quashie Nekehia T. , Reina Herney Alonso Rengifo , Rosenberg Megumi , Towers Andy , Vicerra Paolo Miguel Manalang , Minicuci Nadia , Ng Nawi , Byles Julie 
Published: September 2023

AbstractCurrent measures for monitoring progress towards universal health coverage (UHC) do not adequately account for populations that do not have the same level of access to quality care services and/or financial protection to cover health expenses for when care is accessed. This gap in accounting for unmet health care needs may contribute to underutilization of needed services or widening inequalities. Asking people whether or not their needs for health care have been met, as part of a household survey, is a pragmatic way of capturing this information. This analysis examined responses to self-reported questions about unmet need asked as part of 17 health, social and economic surveys conducted between 2001 and 2019, representing 83 low-, middle- and high-income countries. Noting the large variation in questions and response categories, the results point to low levels (less than 2%) of unmet need reported in adults aged 60+ years in countries like Andorra, Qatar, Republic of Korea, Slovenia, Thailand and Viet Nam to rates of over 50% in Georgia, Haiti, Morocco, Rwanda, and Zimbabwe. While unique, these estimates are likely underestimates, and do not begin to address issues of poor quality of care as a barrier or contributing to unmet need in those who were able to access care. Monitoring progress towards UHC will need to incorporate estimates of unmet need if we are to reach universality and reduce health inequalities in older populations.
Arginine methylation of HSPA8 by PRMT9 inhibits ferroptosis to accelerate hepatitis B virus-associated hepatocellular carcinoma progression
Authors: Deng Wensheng , Ai Jiaoyu , Zhang Wanlin , Zhou Zhenyu , Li Muqi , Yan Likun , Zhang Lidong , Huang Zongjing , Wu Ziyi , Ai Junhua , Jiang Hai 
Published: September 2023

Abstract
Background
The hepatitis B virus X (HBx) protein is an established cause of hepatitis B virus (HBV)-induced hepatocellular carcinoma (HCC). Whether arginine methylation regulates ferroptosis involved in HBx-induced HCC progression has not been reported. This study aimed to explore whether HBx-regulated protein arginine methyltransferase 9 (PRMT9) mediates the involvement of ferroptosis in the development of HCC.

Methods and results
HBx inhibited ferroptosis through promoting PRMT9 expression in HCC cells. PRMT9 suppressed ferroptosis to accelerate HCC progression in vivo. PRMT9 targeted HSPA8 and enhanced arginine methylation of HSPA8 at R76 and R100 to regulate ferroptosis in HCC. HSPA8 overexpression altered the transcriptome profile of HepG2 cells, in particular, ferroptosis and immune-related pathways were significantly enriched by differentially expressed genes, including CD44. HSPA8 overexpression up-regulated CD44 expression and knockdown of CD44 significantly reversed the inhibition of ferroptosis caused by PRMT9 overexpression.

Conclusions
In conclusion, HBx/PRMT9/HSPA8/CD44 axis is a vital signal pathway regulating ferroptosis in HCC cells. This study provides new opportunities and targets for the treatment of HBV-induced HCC.

Graphical Abstract
Targeting FGFRs by pemigatinib induces G1 phase cell cycle arrest, cellular stress and upregulation of tumor suppressor microRNAs
Authors: Pace Angelica , Scirocchi Fabio , Napoletano Chiara , Zizzari Ilaria Grazia , Po Agnese , Megiorni Francesca , Asquino Angela , Pontecorvi Paola , Rahimi Hassan , Marchese Cinzia , Ferretti Elisabetta , Nuti Marianna , Rughetti Aurelia 
Published: September 2023

Abstract
Background
Fibroblast growth factor receptor (FGFR) gene family alterations are found in several cancers, indicating their importance as potential therapeutic targets. The FGFR-tyrosine kinase inhibitor (TKI) pemigatinib has been introduced in the treatment of advanced cholangiocarcinoma and more recently for relapsed or refractory myeloid/lymphoid neoplasms with FGFR2 and FGFR1 rearrangements, respectively. Several clinical trials are currently investigating the possible combination of pemigatinib with immunotherapy.
In this study, we analyzed the biological and molecular effects of pemigatinib on different cancer cell models (lung, bladder, and gastric), which are currently objective of clinical trial investigations.

Methods
NCI-H1581 lung, KATO III gastric and RT-112 bladder cancer cell lines were evaluated for FGFR expression by qRT-PCR and Western blot. Cell lines were treated with Pem and then characterized for cell proliferation, apoptosis, production of intracellular reactive oxygen species (ROS), and induction of senescence. The expression of microRNAs with tumor suppressor functions was analyzed by qRT-PCR, while modulation of the proteins coded by their target genes was evaluated by Western blot and mRNA. Descriptive statistics was used to analyze the various data and student’s t test to compare the analysis of two groups.

Results
Pemigatinib exposure triggered distinct signaling pathways and reduced the proliferative ability of all cancer cells, inducing G1 phase cell cycle arrest and strong intracellular stress resulting in ROS production, senescence and apoptosis. Pemigatinib treatment also caused the upregulation of microRNAs (miR-133b, miR-139, miR-186, miR-195) with tumor suppressor functions, along with the downregulation of validated protein targets with oncogenic roles (c-Myc, c-MET, CDK6, EGFR).

Conclusions
These results contribute to clarifying the biological effects and molecular mechanisms mediated by the anti-FGFR TKI pemigatinib in distinct tumor settings and support its exploitation for combined therapies.
Neural precursor cell delivery induces acute post-ischemic cerebroprotection, but fails to promote long-term stroke recovery in hyperlipidemic mice due to mechanisms that include pro-inflammatory responses associated with brain hemorrhages
Authors: Yin Dongpei , Wang Chen , Qi Yachao , Wang Ya-Chao , Hagemann Nina , Mohamud Yusuf Ayan , Dzyubenko Egor , Kaltwasser Britta , Tertel Tobias , Giebel Bernd , Gunzer Matthias , Popa-Wagner Aurel , Doeppner Thorsten R. , Hermann Dirk M. 
Published: September 2023

Abstract
Background
The intravenous delivery of adult neural precursor cells (NPC) has shown promising results in enabling cerebroprotection, brain tissue remodeling, and neurological recovery in young, healthy stroke mice. However, the translation of cell-based therapies to clinical settings has encountered challenges. It remained unclear if adult NPCs could induce brain tissue remodeling and recovery in mice with hyperlipidemia, a prevalent vascular risk factor in stroke patients.

Methods
Male mice on a normal (regular) diet or on cholesterol-rich Western diet were exposed to 30 min intraluminal middle cerebral artery occlusion (MCAO). Vehicle or 106 NPCs were intravenously administered immediately after reperfusion, at 3 day and 7 day post-MCAO. Neurological recovery was evaluated using the Clark score, Rotarod and tight rope tests over up to 56 days. Histochemistry and light sheet microscopy were used to examine ischemic injury and brain tissue remodeling. Immunological responses in peripheral blood and brain were analyzed through flow cytometry.

Results
NPC administration reduced infarct volume, blood–brain barrier permeability and the brain infiltration of neutrophils, monocytes, T cells and NK cells in the acute stroke phase in both normolipidemic and hyperlipidemic mice, but increased brain hemorrhage formation and neutrophil, monocyte and CD4+ and CD8+ T cell counts and activation in the blood of hyperlipidemic mice. While neurological deficits in hyperlipidemic mice were reduced by NPCs at 3 day post-MCAO, NPCs did not improve neurological deficits at later timepoints. Besides, NPCs did not influence microglia/macrophage abundance and activation (assessed by morphology analysis), astroglial scar formation, microvascular length or branching point density (evaluated using light sheet microscopy), long-term neuronal survival or brain atrophy in hyperlipidemic mice.

Conclusions
Intravenously administered NPCs did not have persistent effects on post-ischemic neurological recovery and brain remodeling in hyperlipidemic mice. These findings highlight the necessity of rigorous investigations in vascular risk factor models to fully assess the long-term restorative effects of cell-based therapies. Without comprehensive studies in such models, the clinical potential of cell-based therapies cannot be definitely determined.