bluuebunny/crossref_metadata_2025_split huggingface dataset:
Responses of B-type natriuretic peptide (BNP), mature BNP and proBNP to sacubitril/valsartan differs between responders and non-responders
Authors: Nishikimi Toshio , Nakagawa Yasuaki , Miyamoto Shoichi , Kanamori Takahiko , Inazumi Hideaki , Yanagisawa Hiromu , Moriuchi Kenji , Kinoshita Hideaki , Tamamura Yusuke , Takahama Hiroyuki , Minamino Naoto , Ono Koh 
Published: February 2025

BackgroundEarlier studies showed that measured changes in plasma B-type natriuretic peptide (BNP) levels are inconsistent after sacubitril/valsartan administration. The reason remains unknown but may reflect the fact that BNP immunoreactivity measured with commercial BNP assays (BNPcom) includes both mature BNP and proBNP, and neprilysin degrades only mature BNP. In addition, the responsiveness to sacubitril/valsartan varies among patients with heart failure. We investigated the mechanism underlying the inconsistency of BNP measurements after sacubitril/valsartan.MethodsWe measured plasma mature BNP, proBNP and total BNP (mature BNP+proBNP) levels with our immunochemiluminescent assay as well as NT-proBNP, A-type natriuretic peptide (ANP) and BNPcom with conventional assays in 54 patients with heart failure, before (baseline) and after 2, 4, 8 and 12 weeks of sacubitril/valsartan administration. Responders were defined as having NT-proBNP levels at <70% of baseline after 12 weeks.ResultsAmong all patients, total BNP and BNPcom did not change with sacubitril/valsartan treatment, whereas NT-proBNP and proBNP decreased, mature BNP modestly increased and ANP greatly increased. Responders (n=31) exhibited smaller %changes in all natriuretic peptide levels than non-responders (n=23; all p<0.01). Receiver operating characteristic curves analysis to assess the ability of the %change in each natriuretic peptide at 4 weeks to detect responders showed that the area under the curve was about 0.80 for each peptide. There were good correlations between plasma natriuretic peptides levels at baseline and throughout the sacubitril/valsartan administration.ConclusionThese results suggest that the magnitude and direction of change in each BNP form depends on its substrate specificity for neprilysin, that differences in plasma levels of each BNP form between responders and non-responders appear early and persist and that BNPcom levels at 4 weeks can be applicable to prediction of the responders. Notably, our findings show that the idea that BNPcom cannot be used as a marker of heart failure after sacubitril/valsartan should be reconsidered.
Comprehensive risk assessment for pulmonary manifestations in systemic lupus erythematosus: a large-scale Korean population-based longitudinal study
Authors: Kim Bo-Guen , Kim Jiyeong , Eun Yeonghee , Park Dong Won , Kim Sang-Heon , Lee Hyun 
Published: February 2025

ObjectivesPulmonary involvement is common in systemic lupus erythematosus (SLE), but the relative risk of pulmonary manifestations in SLE versus non-SLE subjects remains unclear. This study aimed to evaluate the risk of pulmonary manifestations in SLE subjects compared with matched controls.MethodsUsing data from the Korean National Health Insurance Service (2009–2017), we identified 6074 individuals aged ≥20 years with newly diagnosed SLE and 60 740 matched controls by age and sex (1:10 ratio) who did not have prior pulmonary manifestations.ResultsOver a mean follow-up of 9.3±2.7 years, the incidence of pulmonary manifestations was 15.2 per 1000 person-years in the SLE cohort and 4.5 per 1000 person-years in the matched cohort. The SLE cohort had a significantly higher risk of pulmonary manifestations (adjusted HR (aHR) 3.26; 95% CI 2.99 to 3.56). The highest risk was observed for pulmonary hypertension (aHR 14.66; 95% CI 9.43 to 22.80), followed by interstitial lung disease (aHR 9.58; 95% CI 7.99 to 11.49), pleural disorders (aHR 3.29; 95% CI 2.84 to 3.81), pulmonary embolism (aHR 2.66; 95% CI 2.06 to 3.43), tuberculosis (aHR 2.35; 95% CI 1.88 to 2.93), acute respiratory distress syndrome and haemorrhage (aHR 1.85; 95% CI 1.51 to 2.25) and lung cancer (aHR 1.41; 95% CI 1.02 to 1.95).ConclusionsSubjects with SLE have an approximately 3.3-fold higher risk of pulmonary manifestations compared with matched controls. Notably, the risks of pulmonary hypertension and interstitial lung disease are particularly elevated.
Public health and clinical response to an mpox outbreak in Slovenia: case study, 2022–2023
Authors: Češljarac Danilo , Brečko Kristina , Štrumbelj Martin , Likar Sabrina , Kokošar Ulčar Barbara , Zalaznik Mateja , Kejžar Nataša , Rus Katarina Resman , Korva Miša , Avšič Županc Tatjana , Grilc Eva , Murnik Rauh Andreja , Mastnak Maja , Becner Anja , Marovt Maruška , Lenart Mitja , Matičič Mojca 
Published: February 2025

ObjectivesThe emergence of mpox outbreaks in non-endemic areas, characterised by human-to-human transmission and unique clinical presentations, poses challenges in containment efforts. This study aimed to analyse the 2022 outbreak in Slovenia and characterise the country’s response to the outbreak.MethodsA retrospective, observational study analysed all confirmed mpox cases in Slovenia between 1 January 2022 and 31 December 2023 and specific public health measures and responses in the country to contain the mpox outbreak. Data were collected from clinical facilities, public health institutions and civil society organisations and analysed accordingly.ResultsOf 149 suspected cases tested, 49 were confirmed, all cisgender men, predominantly men who have sex with men (93%), exhibiting skin lesions, with 20% being HIV infected and 62% reporting recently having sex abroad. Hospitalisation was required in 14%, no specific treatment was needed, and no fatalities occurred. After the rapid spread of mpox from May to mid-July 2022, only occasional cases were detected afterwards until the outbreak’s termination in early September. Slovenia’s containment strategy started immediately after the first case detection, involving rapid diagnostics and active case search, centralised case management and targeted public health measures. The LGBTIQ+ (Lesbian, Gay, Bisexual, Trans, Intersex, Queer and other sexual identities) community civil society organisation Legebitra played a critical role by launching awareness campaigns and promoting easily accessible vaccination. Despite its late start in September 2022, by the end of 2023, the vaccination campaign achieved coverage of 309 individuals.ConclusionsSlovenia’s response to the 2022 mpox outbreak highlights prompt multisectoral collaboration, community engagement and timely public health interventions. Rapid diagnostics, centralised case management and targeted outreach likely contributed to containment. While vaccination had limited impact during the outbreak, its importance for long-term prevention cannot be overstated. As the global threat of mpox persists, continuous surveillance, cross-border cooperation and proactive vaccination strategies are recommended activities to address future challenges.
Trends in Premature Ejaculation Research From 2004 to 2023: A Bibliometric Analysis
Authors: Ma Dongyue , Wang Hao , Colonnello Elena , Sansone Andrea , Wang Chunlin , Zhang Hui , Wang Anmin , Chang Hongyuan , Yang Jiutian , Guo Jun , Wang Fu 
Published: February 2025

Background: Premature ejaculation (PE) is a largely prevalent sexual complaint that can lead to distress in couple relationships and can significantly reduce patients’ quality of life. Despite the considerable progress in PE research in the last decades, there is still a lack of visual and summarized literature for comprehensive understanding.Objective: This study aims to identify collaboration patterns among different authors, countries, and institutions in PE research and explore the hotspots and prospects in the field.Methods: On January 22, 2024, we conducted a search of all relevant literature in the Web of Science Core Collection (WoSCC) database from January 1, 2004, to December 31, 2023, and supplemented the search with PubMed database for author publication volumes. Visual analyses of authors and keywords were performed using the bibliometrix R package, CiteSpace, and VOSviewer software.Results: In the field of PE, 5457 authors contributed to 1760 articles published across 442 journals. The number of publications gradually increased from 2004 to 2023, with a relatively stable trend in the past 5 years. The Journal of Sexual Medicine (340 papers) had the highest number of publications, and positive collaboration was observed among countries and institutions. Several core author groups emerged, including Jannini EA (60 WoSCC/67 PubMed papers), Waldinger MD (59 WoSCC/90 PubMed papers), and Rowland DL (51 WoSCC/68 PubMed papers), contributing significantly to the literature. The United States was the major contributor, with 384 papers. Keyword cluster analysis revealed that research focuses on PE diagnosis, pharmaceutical treatment (e.g., selective serotonin reuptake inhibitors [SSRIs] and antidepressants), etiology (e.g., serotonin [5‐HT], NOS, and vas deferens), and relationships with prostate, thyroid, anxiety, depression, and other risk factors.Conclusion: Based on the knowledge map, this study provides an intuitive representation of the recent 20 years of PE research, offering a preliminary analysis of major research teams and exploring research hotspots, frontiers, and trends. This analysis aims to guide researchers and serve as a reference for future research on PE.
The Impact of Place of Residence on Antiretroviral Therapy Adherence: A Systematic Review and Meta‐Analysis
Authors: Badru Oluwaseun Abdulganiyu , Edeh Joy Chioma , Okonkwo Rita Ifeyinwa , Bain Luchuo Engelbert , Adeagbo Oluwafemi Atanda 
Published: February 2025

Objective: There is evidence of geographical variation in HIV coverage and antiretroviral therapy (ART) adherence, and studies have investigated how the place of residence of people living with HIV (PLWH) influences ART adherence. Where people reside influences their access to health care. Studies on the influence of place of residence on ART adherence among PLWH in Nigeria have been reported in the literature. However, no review has synthesized these findings. Against this backdrop, this review seeks to determine whether adherence to ART differs by place of residence in Nigeria.Methods: In May 2024, we searched four databases (CINAHL Plus, PubMed, Scopus, and Web of Science). Only empirical studies with a test of association between place of residence (i.e., urban and rural) and adherence to ART were included. We performed a fixed‐effect meta‐analysis with the meta package on R Studio Version 4.2.0.Results: We included six of the 91 articles across the four databases. Most studies (n = 5) were conducted in the Southern region. The assessment of place of residence and adherence varies across the studies. We found that PLWH who reside in urban areas were 20% more likely to adhere to ART compared to those who live in rural areas (odds ratio: 1.20; 95% confidence interval: 1.01–1.43). Similarly, PLWH in the South‐South region of Nigeria and reside in the urban areas were 1.27 (95% CI: 1.01–1.58) more likely to adhere to ART than those living in the rural areas. This observation was insignificantly true for the South‐East region.Conclusion: PLWH who reside in urban areas may better adhere to ART than their counterparts living in rural areas. Non‐governmental organizations and government agencies working with PLWH should prioritize those living in rural areas because they are more likely to face greater barriers to adherence.
Extreme Nipple‐Sparing Mastectomy: Feasibility of Nipple Preservation and Immediate Reconstruction in Breasts Weighing Over 600 Grams in a Cohort of 43 Patients
Authors: Purohit Vaishali , Dwyer Jasmine , Moreira Andrea , Li Jenna , Fernando Emil , Gomez Janette , Saldanha Jennifer , Julian Thomas , Coopey Suzanne 
Published: February 2025

Background: Limited data exist on complication rates in nipple‐sparing mastectomy (NSM) in patients with large‐volume breasts. Our aim was to evaluate the early complication rates of NSM with immediate reconstruction in a consecutive cohort of patients with large‐volume breasts.Methods: After IRB approval, patients treated with prophylactic or therapeutic NSM and immediate reconstruction from January 2020 to June 2022 at our health network were identified. Patients with breast weights > 600 g (the extreme NSM group) were compared to patients with breast weights of 600 g or less (the average‐volume NSM group).Results: A total of 184 patients underwent NSM with immediate reconstruction. Forty‐three of 184 (23.37%) NSM patients had breast weights > 600 g. Of these, 30 patients had bilateral NSM, for a total of 73 breasts with volumes over 600 g, ranging from 603 to 1658 g. There were significantly more total complications in the extreme NSM compared to average‐volume NSM groups (41.86% vs. 21.99%, p = 0.009852). When broken down into major and minor complications, the extreme NSM group had significantly more major complications than the average‐volume NSM group (27.91% vs. 12.86%, p = 0.01072), but no difference in minor complications (13.95% vs. 9.29%, p = 0.2205). Overall, one (2.33%) patient in the extreme NSM group had a reconstruction failure, compared to three (2.14%) in the average‐volume NSM group. Only two of 43 (4.65%) patients in the extreme NSM group lost their nipples due to total or partial nipple necrosis.Conclusions: NSM with immediate reconstruction was successful in the majority of patients with large‐volume breasts. The rate of nipple loss was acceptably low. Women with breast volumes larger than 600 g who are motivated to save their nipples at the time of mastectomy could be offered NSM.
Abstract A015: GPNMB CAR T cells target both Glioblastoma and its immunosuppressive niche to relieve immune evasion
Authors: Singh Sheila K , Savage Neil , Zemp Franz J , Shaikh Vaseem , Grewal Shan , Mikolajewicz Nicholas , Najem Hinda , Venugopal Chitra , Kislinger Thomas , Heimberger Amy , Mahoney Douglas , Moffat Jason 
Published: February 2025

Abstract
Glioblastoma (GBM) remains a formidable challenge in neuro-oncology, characterized by heterogeneity and aggressive tumor growth. The identification of novel biomarkers and therapeutic targets is crucial for advancing promising therapies. This study profiled patient-derived tumor samples utilizing single-cell RNA sequencing and proteomics platforms to uncover the upregulation of glycoprotein non-metastatic melanoma protein B (GPNMB) in tumor cells, particularly in post-treatment recurrent tumor cells, as well as in tumor-associated macrophages (TAMs), which constitute a major population of immune cells in treatment-refractory recurrent GBM. By exploring its expression patterns against normal tissue specimens and utilizing a series of patient-derived xenograft and humanized mouse models, we explored GPNMB as a target for Chimeric Antigen Receptor T cells (CAR-Ts) as a monotherapy and in rationally designed combination treatment regimens. We also demonstrated the utility of the GPNMB CAR-T cell in eliminating TAMs, a major contributor to immunosuppression in solid tumors. Our study reveals the development of GPNMB-targeting therapies as part of a promising and effective combinatorial treatment strategy for GBM.
Citation Format: Sheila K Singh, Neil Savage, Franz J Zemp, Vaseem Shaikh, Shan Grewal, Nicholas Mikolajewicz, Hinda Najem, Chitra Venugopal, Thomas Kislinger, Amy Heimberger, Douglas Mahoney, Jason Moffat. GPNMB CAR T cells target both Glioblastoma and its immunosuppressive niche to relieve immune evasion [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A015.
Abstract A023: VEGF-neutralization by armored CAR-T cells remodel the tumor microenvironment and enhance antitumor efficacy against solid tumors
Authors: Gao Torahito A , Clubb Justin D , Shih Ryan M , Singh Tanya , Dibernardo Gabriella , Shafer Amanda , Bouren Amber , Ceja Melanie A , Ong Sophie , Brown Christine , Okada Hideho , Memarzadeh Sanaz , Wu Han-Chung , Chen Yvonne Y 
Published: February 2025

Abstract
Adoptive cell therapy using T cells engineered to express chimeric antigen receptors (CARs) has only shown limited responses against solid tumors, and improved CAR-T cell designs are needed to achieve more potent and durable responses. One of the major factors limiting CAR-T cell activity within solid tumors is the highly immunosuppressive solid tumor microenvironment (TME) which promotes immune-cell dysfunction and tumor immune escape. Specifically, vascular endothelial growth factor A (VEGF-A) presents as a physical barrier through its pro-angiogenic properties and contribution to excessive tumor vascularization, giving rise to abnormal and dysfunctional vessels with impaired perfusion thus leading to intra-tumoral hypoxia. Furthermore, VEGF-A serves as a chemical barrier by suppressing T-cell activation and cytotoxicity, upregulating immune checkpoints on T cells, inhibiting dendritic cell maturation, and recruiting immunosuppressive cells. Here, we present a strategy to enhance CAR-T cell efficacy and reprogram the TME by engineering CAR-T cells to secrete a novel VEGF-A–neutralizing single-chain variable fragment (scFv). We demonstrate that scFv-secreting CAR-T cells (CAR-αVEGF T cells) achieve superior anti-tumor efficacy against models of ovarian cancer and brain cancer compared to conventional CAR-T cells that do not secret anti–VEGF-A scFvs. Notably, the enhanced efficacy exhibited by CAR-αVEGF T cells is not replicated by combining conventional CAR-T cells with anti-VEGF antibody therapy. Mechanistically, treatment with CAR-αVEGF T cells reduces or reverses multiple adverse effects associated with on-target CAR-T cell therapy, including intra-tumoral infiltration of myeloid cells, exaggerated vasculature abnormalities, and hypoxia. Treatment with CAR-αVEGF T cells also results in an enrichment of immune-stimulatory and anti-tumor signatures among intra-tumoral immune cells. These findings indicate that blocking of intra-tumoral VEGF by αVEGF-scFv armored CAR-T cells enable favorable remodeling of the immunosuppressive TME, resulting in more potent CAR-T cell therapies.
Citation Format: Torahito A Gao, Justin D Clubb, Ryan M Shih, Tanya Singh, Gabriella Dibernardo, Amanda Shafer, Amber Bouren, Melanie A Ceja, Sophie Ong, Christine Brown, Hideho Okada, Sanaz Memarzadeh, Han-Chung Wu, Yvonne Y Chen. VEGF-neutralization by armored CAR-T cells remodel the tumor microenvironment and enhance antitumor efficacy against solid tumors [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A023.
Abstract A029: Overcoming heterogeneous glioblastoma with armored CAR-T cell therapy. Authors: Clubb, J. D., Shih, R., Gao, T., Shafer, A, Vajragiri, S., Talluri, S., Bouren, A., Brown, C. E., Okada, H., Nathanson, D., Chen, Y
Authors: Clubb Justin D , Shih Ryan , Gao Torahito , Shafer Amanda , Vajragiri Shreya , Talluri Sohan , Bouren Amber , Brown Christine E , Okada Hideho , Nathanson David , Chen Yvonne 
Published: February 2025

Abstract
Glioblastoma is the most common primary central nervous system malignancy and has a median overall survival of only 8 months after diagnosis [1]. In recent years, chimeric-antigen receptor (CAR)-T cell therapy has shown unprecedented efficacy against advanced B-cell malignancies. However, the application of CAR-T cell therapy to solid tumors, including GBM, has been largely unsuccessful [2]. In glioblastoma, two key challenges curtail CAR-T cell efficacy: tumor heterogeneity, and an immunosuppressive tumor microenvironment [2]. To address solid-tumor challenges, one approach is to equip CAR-T cells with one or more immunomodulatory proteins, a term commonly referred to as “armoring” the CAR-T cells. In this work, we have engineered CAR-T cells to secrete combinations of armor proteins, such that the CAR-T cells can not only directly attack tumor cells, but also remodel the tumor milieu to inhibit immunosuppression and engage endogenous immunity as a powerful complementary force. Through an in vivo screen of potentially synergistic armor combinations, we have found that CAR-T cells engineered to secrete both IL-12 and the decoy-resistant form of IL-18 (CAR-12.DR18 T cells) are remarkably efficacious against syngeneic, orthotopic, antigen-heterogenous glioblastoma tumors. However, this combination of potent cytokines also results in transient but significant toxicity. Upon interrogating various toxicity reduction strategies, we found that pooling CAR-12.DR18 T cells with CAR-T cells that secrete a novel anti-VEGF scFv ameliorates toxicity while maintaining robust efficacy. References 1. Q. T. Ostrom et al., CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2016-2020. Neuro Oncol 25, iv1-iv99 (2023). 2. R. C. Sterner, R. M. Sterner, CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J 11, 69 (2021).
Citation Format: Justin D Clubb, Ryan Shih, Torahito Gao, Amanda Shafer, Shreya Vajragiri, Sohan Talluri, Amber Bouren, Christine E Brown, Hideho Okada, David Nathanson, Yvonne Chen. Overcoming heterogeneous glioblastoma with armored CAR-T cell therapy. Authors: Clubb, J. D., Shih, R., Gao, T., Shafer, A, Vajragiri, S., Talluri, S., Bouren, A., Brown, C. E., Okada, H., Nathanson, D., Chen, Y [abstract]. In: Proceedings of the AACR IO Conference: Discovery and Innovation in Cancer Immunology: Revolutionizing Treatment through Immunotherapy; 2025 Feb 23-26; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Immunol Res 2025;13(2 Suppl):Abstract nr A029.