tbuckley/cabot-search huggingface dataset:
Healthcare costs related to respiratory syncytial virus in paediatric intensive care units in the Netherlands: a nationwide prospective observational study (the BRICK study)
Authors: Emily W.E.M. Phijffer, Joanne G. Wildenbeest, Carole N.M. Brouwer, Matthijs de Hoog, Martin C.J. Kneyber, Sofie Maebe, Anneliese Nusmeier, Maaike A. Riedijk, Roelie M. Wösten-van Asperen, Job B.M. van Woensel, Louis J. Bont, Geert W.J. Frederix
Journal: The Lancet Regional Health - Europe (2024)

BackgroundThe implementation of the approved respiratory syncytial virus (RSV) preventive interventions in immunisation programmes is advancing rapidly. Insight into healthcare costs of RSV-related paediatric intensive care unit (PICU) admissions is lacking, but of great importance to evaluate the impact of implementation. Therefore, this study aimed to determine the total annual RSV-related paediatric intensive care healthcare costs in the Netherlands.MethodsA nationwide prospective, observational, multicenter study was performed from September 2021 until June 2023. The total annual RSV-related healthcare costs on PICUs in the Netherlands were calculated using RSV-related costs (subgroup I) and consequential costs (subgroup II and III). Subgroup I comprised all PICU admitted infants ≤12 months of age with laboratory-confirmed RSV infection. Subgroup II and III consisted of postponed elective PICU admissions and refused acute PICU admissions due to RSV-related lack of PICU capacity.FindingsA total of 424 infants with RSV-related PICU admission were included. Median age at PICU admission was 46 days (IQR 25–89). The median length of PICU admission was 5 days (IQR 3–8). The total RSV-related PICU costs are € 3,826,386 in 2021–2022, and € 3,183,888 in 2022–2023. Potential costs averted by RSV preventive interventions is € 1.9 to € 2.6 million depending on season, and the duration of protection.InterpretationRSV-related PICU admissions cost €3.1 to €3.8 million in the Netherlands during one season. The introduction of new RSV preventive interventions into the Dutch immunisation programme will generate significant cost-savings on PICUs and decreases the admission burden of PICUs.FundingNone.
Safety and Efficacy of Epithelium-Off Corneal Collagen Cross-Linking for the Treatment of Corneal Ectasia
Authors: Maria S Cortina, Mark A Greiner, Anthony N Kuo, Jennifer Y Li, Darby D Miller, Roni M Shtein, Peter B Veldman, Jia Yin, Stephen J Kim, Joanne F Shen
Journal: Ophthalmology (2024)
Resolving intra-repeat variation in medically relevant VNTRs from short-read sequencing data using the cardiovascular risk gene LPA as a model
Authors: Silvia Di Maio, Peter Zöscher, Hansi Weissensteiner, Lukas Forer, Johanna F. Schachtl-Riess, Stephan Amstler, Gertraud Streiter, Cathrin Pfurtscheller, Bernhard Paulweber, Florian Kronenberg, Stefan Coassin, Sebastian Schönherr
Journal: Genome biology (2024)

Abstract Background Variable number tandem repeats (VNTRs) are highly polymorphic DNA regions harboring many potentially disease-causing variants. However, VNTRs often appear unresolved (“dark”) in variation databases due to their repetitive nature. One particularly complex and medically relevant VNTR is the KIV-2 VNTR located in the cardiovascular disease gene LPA which encompasses up to 70% of the coding sequence. Results Using the highly complex LPA gene as a model, we develop a computational approach to resolve intra-repeat variation in VNTRs from largely available short-read sequencing data. We apply the approach to six protein-coding VNTRs in 2504 samples from the 1000 Genomes Project and developed an optimized method for the LPA KIV-2 VNTR that discriminates the confounding KIV-2 subtypes upfront. This results in an F1-score improvement of up to 2.1-fold compared to previously published strategies. Finally, we analyze the LPA VNTR in &gt; 199,000 UK Biobank samples, detecting &gt; 700 KIV-2 mutations. This approach successfully reveals new strong Lp(a)-lowering effects for KIV-2 variants, with protective effect against coronary artery disease, and also validated previous findings based on tagging SNPs. Conclusions Our approach paves the way for reliable variant detection in VNTRs at scale and we show that it is transferable to other dark regions, which will help unlock medical information hidden in VNTRs.
To what extent can wildfires in the Mediterranean influence pollen abundance?
Authors: Irene Camacho, Elsa Caeiro, Roberto Camacho, Agnieszka Grinn‐Gofroń, Agnieszka Strzelczak, Manuel Branco Ferreira, Pedro Carreiro‐Martins
Journal: Allergy (2024)

The data that support the findings of this study are available from the corresponding author upon reasonable request. Appendix S1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice
Authors: Matthew O. Burgess, Piotr Janas, Karla Berry, Hannah Mayr, Matthias Mack, Stephen J. Jenkins, Calum C. Bain, Henry J. McSorley, Jurgen Schwarze
Journal: Allergy (2024)

Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model.
Recent progress of ferroptosis in cancers and drug discovery
Authors: Xiang Wang, Xinxin Ren, Xu Lin, Qi Li, Yingqiong Zhang, Jun Deng, Binxin Chen, Guoqing Ru, Ying Luo, Nengming Lin
Journal: Asian Journal of Pharmaceutical Sciences (2024)

Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation. In addition, a series of small-molecule compounds have been developed, including erastin, RSL3, and FIN56, which can be used as ferroptosis inducers. The combination of ferroptosis inducers with anticancer drugs can produce a significant synergistic effect in cancer treatment, and patients treated with these combinations exhibit a better prognosis than patients receiving traditional therapy. Therefore, a thorough understanding of the roles of ferroptosis in cancer is of great significance for the treatment of cancer. This review mainly elaborates the molecular biological characteristics and mechanism of ferroptosis, summarizes the function of ferroptosis in cancer development and treatment,illustrates the application of ferroptosis in patient's prognosis prediction and drug discovery, and discusses the prospects of targeting ferroptosis.
Choroid plexus CCL2‒CCR2 signaling orchestrates macrophage recruitment and cerebrospinal fluid hypersecretion in hydrocephalus
Authors: Qiguang Wang, Fei Liu, Yue Li, Huan Zhang, Xin Qi, Ke Wu, Yi Zhang, Shenglan You, Wenke Liu, Xuhui Hui, Hanmei Li, Lei Zhu, Huile Gao, Jian Cheng
Journal: Acta Pharmaceutica Sinica B (2024)

The choroid plexus (ChP) serves as the principal origin of cerebrospinal fluid (CSF). CSF hypersecretion due to ChP inflammation has emerged as an important pathogenesis of hydrocephalus recently. Nevertheless, the precise mechanisms of ChP inflammation and the ensuing CSF hypersecretion in hydrocephalus remain ill-defined. In the present study, we elucidate the critical role of macrophages in the pathogenesis of ChP inflammation. Specifically, we identify the chemokine CCL2, released by ChP epithelial cells, recruits CCR2
Genome-wide pan-GPCR cell libraries accelerate drug discovery
Authors: Hanting Yang, Yongfu Wang, Wei Liu, Taiping He, Jiayu Liao, Zhongzhi Qian, Jinghao Zhao, Zhaotong Cong, Dan Sun, Zhixiang Liu, Can Wang, Lingping Zhu, Shilin Chen
Journal: Acta Pharmaceutica Sinica B (2024)

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors. Cell expression systems play crucial roles in the GPCR drug discovery field, including novel target identification, structural and functional characterization, potential ligand screening, signal pathway elucidation, and drug safety evaluation. Here, we discuss the principles, applications, and limitations of widely used cell expression systems in GPCR-targeted drug discovery, GPCR function investigation, signal pathway characterization, and pharmacological property studies. We also propose three strategies for constructing genome-wide pan-GPCR cell libraries, which will provide a powerful platform for GPCR ligand screening, and facilitate the study of GPCR mechanisms and drug safety evaluation, ultimately accelerating the process of GPCR-targeted drug discovery.
Letter to the Editor: Chronic hepatitis B baseline viral load and on-treatment liver cancer risk: A multinational cohort study of HBeAg-positive patients
Authors: Xingmei Liao, Rong Fan
Journal: Hepatology (2024)

To the editor, We read with great interest the article by Choi et al,1 which concluded that in a multinational cohort of HBeAg-positive adult patients without cirrhosis and with chronic hepatitis B (CHB), patients with the highest viral load who initiated treatment had the lowest long-term risk of HCC. Over the past 5 years, the authors have discovered a nonlinear parabolic pattern in the relationship between pretreatment HBV DNA and HCC risk. This significant discovery offers valuable insights for guiding the treatment of CHB; however, several crucial aspects require further clarification and thorough discussion. First, the study enrolled patients with a median age of 44 (IQR: 35–53) years. However, in most Asian countries, mother-to-child transmission is the main mode of HBV transmission. Hence, most patients with CHB have carried HBV and had a high-viral load since childhood.2 This study did not include these younger patients; thus, the applicability of the findings to this patient population remains unclear. Additionally, there is uncertainty regarding the optimal timing for initiating antiviral therapy for these younger patients. Therefore, stratified and subgroup analyses should be conducted to determine the optimal age group for patients with CHB with high-viral loads who benefit most from initiating antiviral treatment. Second, the authors confirmed the results were valid at different alanine aminotransferase levels. However, the previous guidelines and studies have consistently recommended that normal alanine aminotransferase cutoff value for patients with CHB should be set lower, with 30 IU/L for male and 19 IU/L for female.3 Are the current study results still applicable to patients with REAL normal alanine aminotransferase levels? This results maybe more attractive for clinicians. Third, HBV DNA rapidly decreases to undetectable after treatment, and its value as an assessment of on-treatment HCC risk is limited. Therefore, other virological markers, such as HBsAg, hepatitis B core-related antigen, and HBV RNA, may play more important role in evaluating on-treatment HCC risk.4,5 Hence, the effect of the above virological markers should be adjusted.
Expression of VISTA regulated via IFN-γ governs endogenous T-cell function and exhibits correlation with the efficacy of CD19 CAR-T cell treated B-malignant mice
Authors: Donghai Tang, Li Zhao, Fen Yan, Chunxiao Ren, Kailin Xu, Kai Zhao
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Despite continuous improvements in the new target and construction of chimeric antigen receptor (CAR)-T, relapse remains a significant challenge following CAR-T therapy. Tumor microenvironment (TME) strongly correlates with the efficacy of CAR-T therapy. V-domain Ig suppressor of T-cell activation (VISTA), which exerts a multifaceted and controversial role in regulating the TME, acts not only as a ligand on antigen-presenting cells but also functions as a receptor on T cells. However, the characteristics and underlying mechanisms governing endogenous T-cell activation by VISTA, which are pivotal for reshaping the TME, remain incompletely elucidated. Methods The immunocompetent B acute lymphoblastic leukemia (B-ALL), lymphoma, and melanoma murine models were employed to investigate the characteristics of endogenous T cells within the TME following CD19 and hCAIX CAR-T cell therapy, respectively. Furthermore, we examined the role of VISTA controlled by interferon (IFN)-γ signaling in regulating endogenous T-cell activation and functionality in B-ALL mice. Results We demonstrated that the administration of CD19 CAR-T or hCAIX CAR-T cell therapy elicited augmented immune responses of endogenous T cells within the TME of B-ALL, lymphoma, and melanoma mice, thereby substantiating the efficacy of CAR-T cell efficacy. However, in the TME lacking IFN-γ signaling, VISTA levels remained elevated, resulting in attenuated cytotoxicity of endogenous T cells and reduced B-ALL recipient survival. Mice treated with CD19 CAR-T cells exhibited increased proportions of endogenous memory T cells during prolonged remission, which possessed the tumor-responsive capabilities to protect against B-ALL re-challenge. Compared with wild-type (WT) CAR-T treated mice, the administration of IFN-γ −/− CAR-T to both WT and IFN-γ −/− recipients resulted in a reduction in the numbers of endogenous CD4 + and CD8 + effectors, while exhibiting increased populations of naïve-like CD4 + T and memory CD8 + T cells. VISTA expression consistently remained elevated in resting or memory CD4 + T cells, with distinct localization from programmed cell death protein-1 (PD-1) expressing T subsets. Blocking the VISTA signal enhanced dendritic cell-induced proliferation and cytokine production by syngeneic T cells. Conclusion Our findings confirm that endogenous T-cell activation and functionality are regulated by VISTA, which is associated with the therapeutic efficiency of CAR-T and provides a promising therapeutic strategy for relapse cases in CAR-T therapy.
Patients with ASPSCR1-TFE3 fusion achieve better response to ICI based combination therapy among TFE3-rearranged renal cell carcinoma
Authors: Junjie Zhao, Yanfeng Tang, Xu Hu, Xiaoxue Yin, Yuntian Chen, Junru Chen, Haoyang Liu, Haolin Liu, Jiayu Liang, Xingming Zhang, Jinge Zhao, Sha Zhu, Yuchao Ni, Zhipeng Wang, Jindong Dai, Zilin Wang, Yaowen Zhang, Jin Yao, Ni Chen, Pengfei Shen, Zhenhua H. Liu, Hao Zeng, Guangxi X. Sun
Journal: Molecular Cancer (2024)

TFE3-rearranged renal cell carcinoma (TFE3-rRCC) is a rare but highly heterogeneous renal cell carcinoma (RCC) entity, of which the clinical treatment landscape is largely undefined. This study aims to evaluate and compare the efficacy of different systemic treatments and further explore the molecular correlates.
Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
Authors: Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
Journal: Molecular Cancer (2024)

Abstract Tumor immune microenvironment (TIME) consists of intra-tumor immunological components and plays a significant role in tumor initiation, progression, metastasis, and response to therapy. Chimeric antigen receptor (CAR)-T cell immunotherapy has revolutionized the cancer treatment paradigm. Although CAR-T cell immunotherapy has emerged as a successful treatment for hematologic malignancies, it remains a conundrum for solid tumors. The heterogeneity of TIME is responsible for poor outcomes in CAR-T cell immunotherapy against solid tumors. The advancement of highly sophisticated technology enhances our exploration in TIME from a multi-omics perspective. In the era of machine learning, multi-omics studies could reveal the characteristics of TIME and its immune resistance mechanism. Therefore, the clinical efficacy of CAR-T cell immunotherapy in solid tumors could be further improved with strategies that target unfavorable conditions in TIME. Herein, this review seeks to investigate the factors influencing TIME formation and propose strategies for improving the effectiveness of CAR-T cell immunotherapy through a multi-omics perspective, with the ultimate goal of developing personalized therapeutic approaches.
Nanoliposomes as nonviral vectors in cancer gene therapy
Authors: Safiye Nur Yildiz, Maliheh Entezari, Mahshid Deldar Abad Paskeh, Sepideh Mirzaei, Alireza Kalbasi, Amirhossein Zabolian, Farid Hashemi, Kiavash Hushmandi, Mehrdad Hashemi, Mehdi Raei, Mohammad Ali Sheikh Beig Goharrizi, Amir Reza Aref, Ali Zarrabi, Jun Ren, Gorka Orive, Navid Rabiee, Yavuz Nuri Ertas
Journal: MedComm (2024)

Abstract Nonviral vectors, such as liposomes, offer potential for targeted gene delivery in cancer therapy. Liposomes, composed of phospholipid vesicles, have demonstrated efficacy as nanocarriers for genetic tools, addressing the limitations of off‐targeting and degradation commonly associated with traditional gene therapy approaches. Due to their biocompatibility, stability, and tunable physicochemical properties, they offer potential in overcoming the challenges associated with gene therapy, such as low transfection efficiency and poor stability in biological fluids. Despite these advancements, there remains a gap in understanding the optimal utilization of nanoliposomes for enhanced gene delivery in cancer treatment. This review delves into the present state of nanoliposomes as carriers for genetic tools in cancer therapy, sheds light on their potential to safeguard genetic payloads and facilitate cell internalization alongside the evolution of smart nanocarriers for targeted delivery. The challenges linked to their biocompatibility and the factors that restrict their effectiveness in gene delivery are also discussed along with exploring the potential of nanoliposomes in cancer gene therapy strategies by analyzing recent advancements and offering future directions.
Cardiac aging: from hallmarks to therapeutic opportunities
Authors: Margaret H Hastings, Qiulian Zhou, Chao Wu, Parisa Shabani, Shengyuan Huang, Xuejing Yu, Anand P Singh, J Sawalla Guseh, Haobo Li, Carolin Lerchenmüller, Anthony Rosenzweig
Journal: Cardiovascular Research (2024)

Abstract Cardiac ageing is an intricate and multifaceted process with considerable impact on public health, especially given the global demographic shift towards aged populations. This review discusses structural, cellular, and functional changes associated with cardiac ageing and heart failure with preserved ejection fraction (HFpEF). Key molecular mediators are considered within the framework of the established hallmarks of ageing, with particular attention to promising therapeutic candidates. We further delineate the differential impacts of ageing on cardiac structure and function in men and women, addressing hormonal and chromosomal influences. The protective and mitigating effects of exercise in cardiac ageing and HFpEF in particular are discussed, as an inspiration for the identification of pathways that mitigate biological ageing. We also emphasize how much remains to be learned and the importance of these efforts in enhancing the cardiac health of ageing populations worldwide.
Influence of body fat tissue on outcomes in patients undergoing hepatectomy or liver transplantation
Authors: Lilong Zhang, Zhijia Xia, Zhongyi Li, Jing Zhang, Kunpeng Wang, Weixing Wang
Journal: International Journal of Surgery (2024)

The purpose of this study is to investigate potential associations between body fat composition and postoperative outcomes in patients with hepatectomy or liver transplantation.
Recurrence of breast cancer after reconstruction with macro-textured silicone breast implants: A retrospective cohort study
Authors: Jonathan Spoor, Frederike Dieleman, Eveline M.A. Bleiker, Linetta B. Koppert, Marie-Jeanne T.F.D. Vrancken Peeters, Flora E. van Leeuwen, Marc A.M. Mureau
Journal: International Journal of Surgery (2024)

Background: Recently, old concerns linking silicone breast implants (SBIs) with breast cancer have resurfaced. These concerns apply specifically to the risk of breast cancer recurrence in patients who received breast reconstructions with macro-textured SBIs. In this study, the authors investigated the effect of breast reconstruction with macro-textured SBIs on long-term oncologic outcomes of breast cancer patients. Materials and methods: The authors conducted a retrospective cohort study in two large cancer centres in the Netherlands. Patients who had been treated for primary breast cancer between 1 January 2000 and 31 December 2015 were included. Data on treatment and oncologic outcomes were obtained from prospectively maintained institutional and nationwide registries. Patient files were reviewed manually to complement missing information. Missing data were accounted for by multiple imputations by chained equations (MICE). Reconstruction with a macro-textured SBI was analysed as a time-dependent variable. The main outcomes of interest were locoregional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS). Hazard ratios (HRs) were estimated using multivariable Cox proportional hazard models. Results: Of the 4695 women who were eligible for inclusion, 2393 had undergone mastectomy. Of these women, 1187 (25%) had received breast reconstruction with a macro-textured SBI. The mean follow-up time was 11.5 (SD, 5.0) years. Compared with women who had undergone a simple mastectomy or autologous breast reconstruction, women with an implant-based reconstruction did not differ significantly in LRRFS or DMFS after accounting for various confounding factors [HR 1.27 (95% CI 0.93–1.72) and HR 0.94 (95% CI 0.74–1.20), respectively]. Sensitivity analysis in complete cases of patients and various subgroup analyses yielded similar results. Conclusion: Reassuringly, in this multi-centre cohort study no difference was found in long-term oncologic outcomes between women who had received breast reconstruction with a macro-textured SBI and women who had undergone a simple mastectomy or autologous breast reconstruction.