tbuckley/cabot-search huggingface dataset:
A phase II trial of anlotinib plus EGFR-TKIs in advanced non-small cell lung cancer with gradual, oligo, or potential progression after EGFR-TKIs treatment (CTONG-1803/ALTER-L001)
Authors: Hua-Jun Chen, Hai-Yan Tu, Yanping Hu, Yun Fan, Guowu Wu, Shundong Cang, Yi Yang, Nong Yang, Rui Ma, Gaowa Jin, Ximing Xu, Anwen Liu, Shubin Tang, Ying Cheng, Yan Yu, Chong-Rui Xu, Qing Zhou, Yi-Long Wu
Journal: Journal of Hematology & Oncology (2025)

The study is to evaluate the efficacy and safety of combined anlotinib and EGFR-tyrosine kinase inhibitors (TKIs) in patients with advanced non-small cell lung cancer (NSCLC) who had gradual, oligo, or potential progression after previous EGFR-TKIs treatment. We conducted an open-label, single-arm, multicenter, phase II trial in China. Eligible patients were 18-75 years old with histologically or cytologically confirmed NSCLC who were EGFR mutation positive and showed gradual, oligo, or potential progression after EGFR-TKIs. Anlotinib (12 mg/day) was administered orally for 2 weeks and then off 1 week in a 3-week cycle. EGFR-TKIs were continue used. The primary endpoint was progression-free survival (PFS). The secondary endpoints included 6- and 12-month PFS rate, objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. From July 2019 to December 2022, 120 patients were enrolled. The median PFS (mPFS) was 9.1 months (95% CI 6.8-11.7). The PFS rates at 6 and 12 months was 68.5% and 38.8% respectively. For 86 patients with first-line 1st /2nd generation EGFR-TKIs, the mPFS was 9.2 months (95% CI 6.7-12.6). For 32 patients with first-line 3rd generation EGFR-TKIs, the mPFS was 10.3 months (95% CI 6.1-13.3). Overall ORR and DCR were 6.7% (95% CI 2.9-12.7) and 87.5% (95% CI 80.2-92.8), respectively. 52.5% of patients had grade 3 or higher treatment-emergent adverse events (TEAEs). Anlotinib in combination with continuation of EGFR-TKIs prolonged the clinical benefit of EGFR-TKIs, demonstrating favorable survival outcomes and manageable toxicity in NSCLC treated with EGFR-TKIs and had specific progression modes, such as gradual progression. NCT04007835.
Lack of correlation between school reopening and trends in adult COVID-19 hospitalisations and death rates during the Delta and early Omicron periods: an ecological analysis of five countries
Authors: Darren Suryawijaya Ong, Matthew Harris, John D Hart, Fiona M Russell
Journal: Journal of Infection (2025)

Highlights•School closures were used during the COVID-19 pandemic to limit the transmission of infection.•We found that reopening schools in Australia, Canada, Denmark, Finland or the United Kingdom and jurisdictions did not alter the existing trajectory of COVID-19 hospitalisation and death rates during the Delta and early Omicron periods.•There were no consistent patterns in SARS-CoV-2 case, COVID-19 hospitalisation and death rates, irrespective of whether schools were open or changes to public health or social measures.•Understanding the role of schools in transmission is critical for pandemic planning and response and pre-approved pandemic research protocols are needed along with the documentation of the harms of school closures.AbstractObjectivesIn this ecological study, we describe SARS-CoV-2 case incidence for school age and adult populations, COVID-19 hospitalisation and death rates during Delta and the early Omicron periods, before and after schools reopened in five countries.MethodsData were extracted from government websites. Cases and COVID-19 hospitalisation and death incidence rates were calculated during the Delta and early Omicron periods in Australia, Canada, Denmark, Finland and the United Kingdom, for two weeks preceding and six weeks after schools reopened. We summarised stringency of public health measures (GRI), vaccination by age and testing rates.ResultsDuring Delta, cases increased in 2/7 sites after schools reopened, hospitalisations increased in 1/5 sites, while deaths decreased in one and increased then decreased in another. During Omicron, cases increased in 2/8 sites, hospitalisations increased in 1/6 sites and deaths increased in 1/4 sites. The hospitalisation and death rate trends that commenced before schools reopened continued on the same trajectory after schools reopened. Vaccination rates in ≥70-year-olds were 75-100% during Delta and 95-100% during Omicron. Wide variations in testing rates may explain differences in case incidence. GRI were higher during Delta with more variation than during Omicron.ConclusionsReopening schools did not change the existing trajectory of COVID-19 rates.
HER2 and HER3 expression during neoadjuvant treatment of HER2‐negative early breast cancer: potential for biomarker‐driven sequencing of T‐DXd and HER3‐DXd
Authors: Christian Fridolin Singer, Stephan Wenzel Jahn, Dominik Hlauschek, Ulrike Maria Heber, Charlotte Mang‐Manger, Daniel Egle, Marija Balic, Angelika Pichler, Georg Pfeiler, Stephanie Kacerovsky‐Strobl, Christoph Suppan, Magdalena Ritter, Edgar Petru, Richard Greil, Zsuzsanna Bago‐Horvath, Christine Deutschmann, Günther Georg Steger, Michael Seifert, Florian Fitzal, Rupert Bartsch, Anu Santhanagopal, Jana Machacek‐Link, Dalila Sellami, Magdalena Schwarz, Christian Fesl, Lidija Sölkner, Stephen Esker, Martin Filipits, Michael Gnant
Journal: Cancer Communications (2025)
Skin Tape Stripping Reveals Distinct Biomarker Profiles in Chronic Hand Eczema of Patients With and Without Comorbid Atopic Dermatitis
Authors: Jonathan Bar, Ester Del Duca, Eden David, Swaroop Bose, Gabriella Chefitz, Patrick M. Brunner, Robert Bissonnette, Emma Guttman‐Yassky
Journal: Allergy (2025)

ABSTRACT Introduction Chronic hand eczema (CHE) is a highly prevalent inflammatory skin condition which is often resistant to conventional treatments. Molecular insights of CHE remain limited. Tape stripping combined with high‐throughput RNA sequencing can now provide a better insight into CHE pathogenesis in a minimally invasive fashion. Methods We collected tape strip samples from lesional and non‐lesional skin of 66 patients with moderate‐to‐severe CHE, comprising 33 with and 33 without comorbid atopic dermatitis (AD), and performed bulk RNA sequencing. Results were compared to tape strips from palmar skin of age/race/sex‐matched healthy controls (HC). Differentially expressed genes (DEGs) (fold change/FCH &gt; 1.5 and false discovery rate/FDR &lt; 0.05) were calculated and correlated with clinical severity scores including hand eczema severity index (HECSI) and modified total lesion symptoms score (mTLSS). Results Tape strip isolates detected a common phenotype in CHE lesions regardless of AD status, including upregulated type‐1 ( IL12RB2 , IFNGR1 , IFNGR2 , MX1 ) and type‐2‐associated inflammatory mediators ( CCL22 , CCL24 , OX40/ TNFRSF4 , TSLPR/ CRLF2 , GATA3 ), paralleled by downregulated epidermal barrier markers (i.e., FLG or LORICRIN ). Non‐lesional skin demonstrated a similar, albeit milder, dysregulation pattern, with additional reduction in type‐17 pathways. Lesional skin of CHE patients without AD showed greater skewing towards type‐1 immunity ( IL15RA , CXCL9 ), while CHE from AD patients showed a more pronounced type‐2 inflammatory pattern ( IL13 , CCL17 ) and their gene expression biomarkers had greater and more significant correlations with clinical severity markers. Conclusion Tape stripping can capture detailed immune and skin barrier abnormalities in CHE and identify potential novel subtype‐specific treatment targets. Stronger correlations in patients with AD suggest a more homogenous disease phenotype than in CHE non‐AD patients. Trial Registration: NCT03728504
Resolving the source of branch length variation in the Y chromosome phylogeny
Authors: Yaniv Swiel, Janet Kelso, Stéphane Peyrégne
Journal: Genome biology (2025)

Abstract Background Genetic variation in the non-recombining part of the human Y chromosome has provided important insight into the paternal history of human populations. However, a significant and yet unexplained branch length variation of Y chromosome lineages has been observed, notably amongst those that are highly diverged from the human reference Y chromosome. Understanding the origin of this variation, which has previously been attributed to changes in generation time, mutation rate, or efficacy of selection, is important for accurately reconstructing human evolutionary and demographic history. Results Here, we analyze Y chromosomes from present-day and ancient modern humans, as well as Neandertals, and show that branch length variation amongst human Y chromosomes cannot solely be explained by differences in demographic or biological processes. Instead, reference bias results in mutations being missed on Y chromosomes that are highly diverged from the reference used for alignment. We show that masking fast-evolving, highly divergent regions of the human Y chromosome mitigates the effect of this bias and enables more accurate determination of branch lengths in the Y chromosome phylogeny. Conclusion We show that our approach allows us to estimate the age of ancient samples from Y chromosome sequence data and provide updated estimates for the time to the most recent common ancestor using the portion of the Y chromosome where the effect of reference bias is minimized.
Depletion of myeloid-derived suppressor cells sensitizes murine multiple myeloma to PD-1 checkpoint inhibitors
Authors: Wei Xiong, Liuling Xiao, Rui Duan, Qiang Wang, Miao Xian, Chuanchao Zhang, Pan Su, Yabo Li, Ling Zhong, Jianfei Qian, Chengyun Zheng, Qing Yi
Journal: Journal for ImmunoTherapy of Cancer (2025)

Cancer immunotherapy using immune checkpoint blockade (ICB) has revolutionized cancer treatment. However, patients with multiple myeloma (MM) rarely respond to ICB. Accumulating evidence indicates that the complicated tumor microenvironment (TME) significantly impacts the efficacy of ICB therapy. Therefore, investigating how TME components in MM influence ICB treatment is urgent.
Early treatment discontinuation in patients with deficient mismatch repair or microsatellite instability high metastatic colorectal cancer receiving immune checkpoint inhibitors
Authors: Julien Taieb, Margherita Ambrosini, Emily Alouani, Sara Lonardi, Frank A Sinicrope, Marie Decraecker, Alice Boileve, Emilie Hafliger, Thibault Mazard, Simon Pernot, Pauline Parent, Javier Ros, Michael J Overman, Priya Jayachandran, Vincenzo Nasca, Lisa Salvatore, Rosine Guimbaud, Chiara Cremolini, David Tougeron, Filippo Pietrantonio
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (ICIs) are recommended to treat patients with deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) metastatic colorectal cancer (mCRC). Pivotal trials have fixed a maximum ICI duration of 2 years, without a compelling rationale. A shorter treatment duration has the potential to improve patients' quality of life and reduce both toxicity and cost without compromising efficacy. Here we examine whether early treatment discontinuation (ETD) before 13 months in patients without progressive disease (PD) can lead to similar long-term disease control compared with a longer treatment duration (LTD). Methods To assess whether ETD is associated with similar outcomes compared with LTD, we assembled an international cohort of patients with dMMR/MSI-H mCRC treated with ICIs who stopped treatment for a reason other than PD within 395 days (ETD group) and compared them to those who continued for &gt;395 days (LTD group). Outcomes were adjusted for patient/tumor characteristics. Primary endpoint was progression-free survival (PFS) and secondary endpoints were objective response rate (ORR), overall survival (OS) and safety. Results Of 976 patients, 137 and 394 were allocated to the ETD and LTD groups, respectively. In the ETD group, treatment was discontinued due to toxicity (n=56), objective response (n=43), surgery (n=28), patient decision (n=2) or other reasons (n=8). Baseline characteristics were well balanced between the two groups: 22% in both groups received both anti-programmed death-(ligand) 1 (anti-PD-(L)1) + anti-cytotoxic T-lymphocyte antigen-4 (anti-CTLA-4); all others received anti-PD-(L)1 monotherapy. ORR to ICIs was 81% in both groups. Median duration of treatment was ~7 months in the ETD and ~24 months in the LTD group. After a median follow-up of 44 months (IQR: 30–67), similar PFS (HR: 0.92, 95% CI: 0.60 to 1.40, p=0.69) and OS (HR: 1.15, 95% CI: 0.66 to 1.99, p=0.62) from the start of ICIs were observed in ETD and LTD patients. In the ETD group, 28 (20%) patients had a PFS event and 9 restarted ICIs with a disease control rate of 66%. Conclusions In our international series of dMMR/MSI-H mCRC, ETD of ICIs in the absence of PD did not seem detrimental in terms of PFS and OS compared with continuing treatment beyond 1 year. Randomized clinical trials to compare short and long treatment duration are now warranted.
Effect of radiotherapy exposure on fruquintinib plus sintilimab treatment in refractory microsatellite stable metastatic colorectal cancer: a prospective observation study
Authors: Mingxia Cheng, Min Jin, Shengli Yang, Lei Zhao, Dandan Yu, Zhenyu Lin, Pindong Li, Chuying Huang, Junli Liu, Jing Wang, Jun Xue, Hong Ma, Jianli Hu, Kunyu Yang, Tao Zhang, Hongli Liu
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&amp;S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers. Methods In this prospective observational study, patients with mCRC receiving F&amp;S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment. Results A total of 55 patients were included, of which 25 were in the RTC and 30 in the NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% vs 36.7%, p=0.002), median PFS (6.2 vs 2.7 months, p&lt;0.001), and median OS (14.8 vs 5.9 months, p=0.019) were noted in patients with RTC than those with NRTC. The enrichment of Lactobacillus , Bifidobacterium , and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) in RTC significantly predicted better DCR and PFS, whereas guanosine and interleukin-10 predominated in patients with NRTC were negatively correlated with PFS and OS. Conclusions Patients with RT exposure benefited significantly from F&amp;S in the third-line or subsequent treatment for MSS-mCRC. Gut microbiota, metabolites, and cytokines may help predict F&amp;S outcomes for mCRC, which may be helpful in treatment decision-making. Trial registration number ClinicalTrials.gov identifier: NCT05635149 .
Spatial and single-cell transcriptomics reveal cellular heterogeneity and a novel cancer-promoting Treg cell subset in human clear-cell renal cell carcinoma
Authors: Xiyu Song, Yumeng Zhu, Wenwen Geng, Jianhua Jiao, Hongjiao Liu, Ruo Chen, Qian He, Lijuan Wang, Xiuxuan Sun, Weijun Qin, Jiejie Geng, Zhinan Chen
Journal: Journal for ImmunoTherapy of Cancer (2025)

Clear cell renal cell carcinoma (ccRCC) is the most common histologic type of RCC. However, the spatial and functional heterogeneity of immunosuppressive cells and the mechanisms by which their interactions promote immunosuppression in the ccRCC have not been thoroughly investigated. To further investigate the cellular and regional heterogeneity of ccRCC, we analyzed single-cell and spatial transcriptome RNA sequencing data from four patients, which were obtained from samples from multiple regions, including the tumor core, tumor-normal interface, and distal normal tissue. On the basis, the findings were investigated in vitro using tissue and blood samples from 15 patients with ccRCC and validated in the broader samples on tissue microarrays. In this study, we revealed previously unreported subsets of both stromal and immune cells, as well as mapped their spatial location at finer resolution. In addition, we validated the clusters of tumor cells after removing batch effects according to six characterized gene sets, including epithelial-mesenchymal transitionhigh clusters, metastatic clusters and proximal tubulehigh clusters. Importantly, we identified a special regulatory T (Treg) cell subpopulation that has the molecular characteristics of terminal effector Treg cells but expresses multiple cytokines, such as interleukin (IL)-1β and IL-18. This group of Treg cells has stronger immunosuppressive function and was associated with a worse prognosis in ccRCC cohorts. They were colocalized with MRC1 + FOLR2 + tumor-associated macrophages (TAMs) at the tumor-normal interface to form a positive feedback loop, maintaining a synergistic procarcinogenic effect. In addition, we traced the origin of IL-1β+ Treg cells and revealed that IL-18 can induce the expression of IL-1β in Treg cells via the ERK/NF-κB pathway. We demonstrated a novel cancer-promoting Treg cell subset and its interactions with MRC1 + FOLR2 +TAMs, which provides new insight into Treg cell heterogeneity and potential therapeutic targets for ccRCC.
Marsilea: an intuitive generalized paradigm for composable visualizations
Authors: Yimin Zheng, Zhihang Zheng, André F. Rendeiro, Edwin Cheung
Journal: Genome biology (2025)

Biological data visualization is challenged by the growing complexity of datasets. Traditional single-data plots or simple juxtapositions often fail to fully capture dataset intricacies and interrelations. To address this, we introduce "cross-layout," a novel visualization paradigm that integrates multiple plot types in a cross-like structure, with a central main plot surrounded by secondary plots for enhanced contextualization and interrelation insights. We also introduce "Marsilea," a Python-based implementation of cross-layout visualizations, available in both programmatic and web-based interfaces to support users of all experience levels. This paradigm and its implementation offer a customizable, intuitive approach to advance biological data visualization.
Umbrella review of social inequality in digital interventions targeting dietary and physical activity behaviors
Authors: Laura M. König, Max J. Western, Andrea H. Denton, Rebecca A. Krukowski
Journal: npj Digital Medicine (2025)

Digital interventions are increasingly utilized as a lever to promote population health, yet not everyone may equally benefit from them. This umbrella review pooled the insights from available systematic and scoping reviews regarding potential social inequalities in digital intervention uptake, engagement and effectiveness, focusing on the promotion of weight-related behaviors (diet, physical activity, sedentary behavior) and weight loss (maintenance) in adults. Six databases were searched from 1970 to October 2023. Forty-six reviews were included, of which most focused on physical activity and intervention effectiveness. Age and gender/ sex differences were most frequently studied. Most reviews found digital interventions to be effective irrespective of age, while men benefitted more from digital interventions than women. Other inequality indicators (e.g., income, education) were rarely studied, despite them being potential causes of a digital divide. A more systematic and thorough exploration of inequalities in digital health is required to promote health for all.
Gut microbes metabolize strawberry phytochemicals and mediate their beneficial effects on vascular inflammation
Authors: Chrissa Petersen, Adhini Kuppuswamy Satheesh Babu, Ceres Mattos Della Lucia, Henry A. Paz, Lisard Iglesias-Carres, Ying Zhong, Thunder Jalili, J David Symons, Kartik Shankar, Andrew P. Neilson, Umesh D. Wankhade, Pon Velayutham Anandh Babu
Journal: Gut Microbes (2025)

Evidence suggests that a healthy gut microbiome is essential for metabolizing dietary phytochemicals. However, the microbiome's role in metabolite production and the influence of gut dysbiosis on this process remain unclear. Further, studies on the relationship among gut microbes, metabolites, and biological activities of phytochemicals are limited. We addressed this knowledge gap using strawberry phytochemicals as a model. C57BL/6J mice were fed a standard diet [C]; strawberry-supplemented diet (~2 human servings) [CS]; strawberry-supplemented diet and treated with antibiotics (to deplete gut microbes) [CSA]; high-fat diet (HFD) [HF]; strawberry-supplemented HFD [HS]; and strawberry-supplemented HFD and treated with antibiotics [HSA] for 12 weeks. First, antibiotic treatment suppressed the production of selected metabolites (CSA vs. CS), and p-coumaric acid was identified as a strawberry-derived microbial metabolite. Second, HFD-induced dysbiosis negatively affected metabolite production (HS vs. HF), and hippuric acid was identified as a microbial metabolite in HFD conditions. Third, dietary strawberries improved HFD-induced vascular inflammation (HS vs. HF). However, antibiotic treatment reduced metabolite production and abolished the vascular effects of strawberries (HSA vs. HS), indicating the importance of gut microbes in mediating the vascular benefits of strawberries via metabolites. Fourth, strawberry supplementation decreased Coprobacillus that was positively associated with vascular inflammation, whereas it increased Lachnospiraceae that was negatively associated with vascular inflammation and positively associated with hippuric acid. Fifth, hippuric acid was negatively associated with vascular inflammation. Our study fills in some pieces of the giant puzzle regarding the influence of gut microbes on the biological activities of phytochemicals. HFD-induced gut dysbiosis negatively impacts metabolite production and a strong association exists among gut microbes, strawberry-derived microbial metabolites, and the vascular benefits of dietary strawberries. Further, our study provides significant proof of concept to warrant future research on the use of strawberries as a nutritional strategy to prevent vascular complications.
Fractional exhaled nitric oxide in a respiratory healthy general population through the lifespan
Authors: Christina Bal, Caspar Schiffers, Marie-Kathrin Breyer, Sylvia Hartl, Alvar Agusti, Ahmad Karimi, Wolfgang Pohl, Marco Idzko, Robab Breyer-Kohansal
Journal: Pulmonology (2025)

Introduction and Objectives The fractional exhaled fraction of nitric oxide (FeNO) is used in clinical practice for asthma diagnosis, phenotyping, and therapeutic management. Therefore, accurate thresholds are crucial. The normal FeNO values over lifespan in a respiratory healthy population and the factors related to them remain unclear.