tbuckley/cabot-search huggingface dataset:
Paclitaxel, interferons and functional reprogramming of tumor-associated macrophages in optimized chemo-immunotherapy
Authors: Pawel Kalinski, Kathleen M Kokolus, Shipra Gandhi
Journal: Journal for ImmunoTherapy of Cancer (2025)

Immune checkpoint inhibition (ICI) targeting programmed cell death protein-1 (PD1) prevents the elimination of activated cytotoxic T lymphocytes (CTLs) by programmed death-ligand 1/2-expressing cancer and myeloid cells in the tumor microenvironment (TME). ICI has shown its effectiveness in many solid tumors, but it lacks activity against "cold" tumors which lack CTL infiltration, including most of the colon, prostate, lung and breast cancers. Metastatic triple-negative breast cancer (TNBC) responds to PD-1 blockade only in 5-20% cases. Chemotherapy has been shown to have a PD1-sensitizing effect in a fraction of patients with TNBC but the underlying mechanism and the reasoning behind its limitation to only a subset of patients are unknown. Recent data demonstrate the key roles played by paclitaxel-driven Toll-like receptor 4 (TLR4) signaling and the resulting activation of type-1 and type-2 interferon pathways in tumor-associated macrophages, resulting in local M2 to M1 transition and enhanced tumor antigen cross-presentation, in the paclitaxel-driven sensitization of "cold" tumors to ICI. These data and the known ability of the TLR4-activated MyD88-NFκB pathway to mobilize both antitumor and tumor-promoting events in the TME provide new tools to enhance the efficacy of chemo-immunotherapy for metastatic, and potentially early, TNBC and other taxane-sensitive cancers.
Interplay between sarcopenia, GDF-15, and the efficacy of nivolumab plus ipilimumab in patients with mismatch repair deficient metastatic colorectal cancer: final survival analysis of the phase II GERCOR NIPICOL study
Authors: Leonard Depotte, Paula Nay, Christophe Borg, Aurélia Meurisse, Julie Henriques, Jaafar Bennouna, Christelle De La Fouchardière, David Tougeron, Thibault Mazard, Benoist Chibaudel, Christophe Tournigand, Dewi Vernerey, Frédéric Pigneur, Thierry Andre, Romain Cohen
Journal: Journal for ImmunoTherapy of Cancer (2025)

Background Sarcopenia and growth differentiation factor 15 (GDF-15) are linked to poor cancer survival. In this exploratory analysis, we evaluated their interaction with nivolumab-ipilimumab efficacy in chemoresistant metastatic colorectal cancer (mCRC) harboring microsatellite instability and/or mismatch-repair deficiency (MSI/dMMR), based on the final survival analysis of the NIPICOL phase II trial. Patients and methods 57 patients with MSI/dMMR chemoresistant mCRC received nivolumab-ipilimumab for 3 months (3M), then, nivolumab alone for 9M. Skeletal muscle mass index (SMI) was evaluated by CT scan at baseline and 12M to assess sarcopenia. GDF-15 levels were assessed at baseline and 3M. Main endpoints were overall survival (OS) and immune Response Evaluation Criteria In Solid Tumors progression-free survival (iPFS). Results After excluding three patients not confirmed as MSI/dMMR by central review, the overall median follow-up was 60.4 months. The 3-year and 5 year iPFS rates were 72.0% and 65.3%, with OS rates of 77.5% and 73.3%, respectively. Among 49 patients with evaluable GDF-15, high-baseline GDF-15 was associated with poorer survival: 3-year iPFS rate of 56.3% for GDF-15≥2500 versus 81.7% for GDF-15&lt;2500 (PFS HR=2.45, 95% CI 0.91 to 6.55), 3-year OS rates of 61.4% versus 84.5% (OS HR=2.08, 95% CI 0.70 to 6.22). Of the 48 evaluable patients for SMI, 31 (65.0%) displayed sarcopenia at baseline. 11 out of 20 (55%) patients with baseline sarcopenia and assessed for SMI at 12M, reversed sarcopenia by 12M. They had higher baseline GDF-15 levels and greater GDF-15 decrease by 3M (delta mean change: −69.8% vs −40.3%) compared with patients who remained sarcopenic. Conclusion 1-year nivolumab-ipilimumab demonstrates consistent efficacy after 5-year follow-up in an MSI/dMMR chemoresistant mCRC population. GDF-15 confirms to be a promising biomarker for sarcopenia and survival. Trial registration number NCT03350126 .
Oncolytic VSV-IL-2 has enhanced anticancer vaccination adjuvant abilities
Authors: Victor Mullins-Dansereau, Marie-Lou Myre, Angelina Bardoul, Karen Geoffroy, Marco J Rallo Pita, Delphine Béland, Kim Leclerc Desaulniers, Dominic Guy Roy, Marie-Claude Bourgeois-Daigneault
Journal: Journal for ImmunoTherapy of Cancer (2025)

Heterologous oncolytic virus prime-boost vaccination is emerging as a promising cancer immunotherapy to establish potent antitumor immunity. With their natural ability to specifically destroy cancer cells, oncolytic viruses also allow for direct oncolysis and our team has previously demonstrated that they can be used as vaccination adjuvants when co-administered with antigenic peptides. As such, adjuvant oncolytic virus vaccines can easily be tailored to target any antigen, which is particularly important in the context of personalized vaccines against patient-specific mutations. Here, we tested if oncolytic viruses engineered to express the immune-stimulating transgene interleukin-2 have improved vaccination adjuvant potential. For this proof-of-concept study, we generated an oncolytic vesicular stomatitis virus (VSV) variant (MD51) that encodes the T-cell activator cytokine interleukin-2 and measured its vaccination adjuvant potential in a heterologous virus immune boosting approach, 1 week after immune priming compared with the parental virus (also MD51). Tumor-free and B16F10-Ova tumor-bearing mice were vaccinated against the Ova peptide using either virus as adjuvants. The immune response induced by each vaccination regimen was assessed by flow cytometry to characterize antigen-specific CD8 T cells over time. Treatment efficacy was also measured. Our data show that VSV-interleukin-2 is superior as a vaccine boosting adjuvant compared with the parental virus as it induces more antigen-specific CD8 T cells with enhanced effector functions that persist over time. VSV-interleukin-2 vaccination also improves tumor control and survival. Overall, we show that engineered oncolytic virus platforms, such as VSV-interleukin-2, have the potential to improve vaccination efficacy and treatment outcomes. Our findings deepen our understanding of the immune mechanisms underlying the use of oncolytic viruses as anticancer vaccination platforms and will allow for the development of a new generation of improved oncolytic virus vaccine adjuvants. NCT02285816.
Biolimus-Eluting Biomatrix Stent Versus a Dual-Therapy Sirolimus-Eluting Stent in PCI: SORT OUT XI Randomized Trial
Authors: Ashkan Eftekhari, Lisette Okkels Jensen, Karsten Veien, Bent Raungaard, Jeppe Grøndahl Rasmussen, Michael Mæng, Christian Juhl Terkelsen, Julia Ellert-Gregersen, Nicolaj Brejnholt Støttrup, Jens Flensted Lassen, Henrik Steen Hansen, Troels Thim, Rebekka Vibjerg Jensen, Roni Nielsen, Svend Eggert Jensen, Steen Dalby Kristensen, Mikkel Hougaard, Anders Junker, Martin Kirk Christensen, Jens Aarøe, Trine Frøslev, Lars Jakobsen, Evald Høj Christiansen
Journal: Journal of the American College of Cardiology (2025)
<scp>PET</scp>/<scp>CT</scp> in the Staging and Treatment Response Assessment of Patients With Extranodal Marginal Zone Lymphoma
Authors: Juan Pablo Alderuccio, Russ A. Kuker, Eduardo Edelman Saul, Michele D. Stanchina, Mark K. Polar, Jennifer Chapman, Wei Zhao, Rafael Hennemann Sassi, Craig H. Moskowitz, Isildinha M. Reis, Izidore S. Lossos
Journal: American Journal of Hematology (2025)

ABSTRACT 18 Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is the standard imaging modality in lymphoma. The 2014 Lugano classification considers extranodal marginal zone lymphoma (EMZL) a non‐FDG‐avid disease, recommending contrast‐enhanced CT. We reassessed the utility of PET/CT for staging workup and response assessment of EMZL. We reviewed staging and response PET/CT of 190 EMZL sites from 152 patients. Each location was counted independently for patients with &gt; 1 extranodal site. Although not standard, we considered FDG‐avid disease if SUVmax was ≥ 2, and calculated ratios between lymphoma SUVmax and mediastinal blood pool (BP index) and liver background (liver index). FDG avidity was detected in 151 (79.5%) out of 190 extranodal sites (in 117 [76.7%] out of 152 patients), with a median SUVmax of 4.5 (IQR 2.5–6.9, range 0–26.8). Locations showing FDG avidity in &gt; 90% of extranodal sites included salivary gland, bone, lung, soft tissue, ocular adnexa, and airways. Skin was commonly non‐FDG avid (93.8%). Among 22 patients with &gt; 1 extranodal location, there was concordant FDG avidity in all sites in 18 (81.8%) patients. Considering measurable extranodal disease size &gt; 0.5 cm, we observed significant Pearson correlation coefficients ( r ) between lymphoma size and SUVmax ( r = 0.20, p = 0.019, n = 142), BP index ( r = 0.34, p &lt; 0.001, n = 124), and liver index ( r = 0.36, p &lt; 0.001, n = 124). We also observed improved precision in response to treatment assessment in FDG‐avid EMZL tumors. This study demonstrates that EMZL is commonly an FDG‐avid disease, suggesting that PET/CT should be routinely used in the staging and response assessment workup of patients with EMZL.
Genetic and Phenotypic correlates of clinical outcomes with Venetoclax in Acute Myeloid Leukemia: The GEN-PHEN-VEN study
Authors: Curtis A. Lachowiez, Mael Heiblig, Gaspar Aspas Requena, Emmanuelle Tavernier-Tardy, Fangyan Dai, Amenech B. Ashango, Daniel T. Peters, Jacob Fang, Andy Kaempf, Nicola Long, Christopher A. Eide, Stephen E. Kurtz, Wei Xie, Anupriya Agarwal, Aishwarya Sahasrabudhe, Christine M. McMahon, Maria L. Amaya, Gabrielle Meyers, Arpita Gandhi, Jessica Leonard, Brandon Hayes-Lattin, Richard T. Maziarz, Elie Traer, Rachel J. Cook, Ronan Swords, Theodore P. Braun, Jennifer N. Saultz, Ashley M. Eckel, Michael R. Loken, Joshua F. Zeidner, Jeffrey W. Tyner, Daniel A. Pollyea
Journal: Blood Cancer Discovery (2025)

Abstract Resistance to venetoclax-based therapy in acute myeloid leukemia (AML) includes genetic (i.e., mutations in N/KRAS, FLT3-ITD, TP53) and phenotypic (i.e., monocytic differentiation) features. Whether monocytic differentiation contributes to clinical venetoclax resistance secondary to a genetic bias remains unknown. This multimodal, multicenter, international analysis inclusive of 678 patients comprehensively characterized the prognostic role of monocytic differentiation in AML patients treated with hypomethylating agents combined with venetoclax. AML genetics and monocytic differentiation (HR: 1.89, 95% CI: 1.35-2.66, p &amp;lt; 0.001) in NPM1 wild-type cases correlated with an increased risk of death. Clustering of centralized quantitative multiparameter flow cytometry data, evaluation of RNA sequencing-derived AML maturation stage, and single-cell proteogenomics linked driver mutations with AML phenotype and anti-apoptotic gene expression. This comprehensive analysis of AML genetics, phenotype, and anti-apoptotic protein expression highlights the complementary role these factors impart following venetoclax-based therapy.
An ancient regulatory variant of ACSF3 influences the coevolution of increased human height and basal metabolic rate via metabolic homeostasis
Authors: Yufeng Zhang, Jie Wang, Chuanyou Yi, Yue Su, Zi Yin, Shuxian Zhang, Li Jin, Mark Stoneking, Jian Yang, Ke Wang, He Huang, Jin Li, Shaohua Fan
Journal: Cell Genomics (2025)
Characterization of Patients with Lymph Node Only Metastatic Urothelial Carcinoma Treated with Nivolumab Plus Gemcitabine-Cisplatin Versus Gemcitabine-Cisplatin Alone from the CheckMate 901 Trial
Authors: Matthew D Galsky, Michiel S van der Heijden, Thomas Powles, Melanie Claps, Mauricio Burotto, Michael Schenker, Juan Pablo Sade, Aristotelis Bamias, Philippe Beuzeboc, Jens Bedke, Jan Oldenburg, Yüksel Ürün, Dingwei Ye, Begoña P Valderrama, Yoshihiko Tomita, Ruiyun Jiang, Jeiry Filian, Lily Wang, Maximiliano van Kooten Losio, Guru Sonpavde
Journal: European Urology (2025)
Recurrent event analyses in patients receiving maintenance dialysis and the effect of higher‐ versus lower‐dose chronic intravenous iron therapy: A report focusing on heart failure events from the <scp>PIVOTAL</scp> trial
Authors: Stefan D. Anker, Michele Robertson, John J.V. McMurray, Pardeep S. Jhund, Claire White, Chante Reid, Sunil Bhandari, Ken Farrington, Philip A. Kalra, Khawaja M. Talha, Patrick B. Mark, Charles R.V. Tomson, David C. Wheeler, Chris G. Winearls, Iain C. Macdougall, Ian Ford
Journal: European Journal of Heart Failure (2025)
Loss of PTSD Diagnosis in Response to Evidence-Based Treatments
Authors: Tiffany Milligan, Derek Smolenski, Jose Lara-Ruiz, Marija S. Kelber
Journal: JAMA Psychiatry (2025)

Importance In recent decades, evidence-based psychotherapies to treat posttraumatic stress disorder (PTSD) have been developed with robust evidence bases. However, efficacy observed in clinical trials is not always directly applicable to clinical practice. Objective To estimate the percentage of patients in both military and veteran (hereafter milvet) and nonmilvet populations that lose their PTSD diagnosis after treatment. Data Sources We used the PTSD Repository to identify studies with adults with a DSM-IV / DSM -5 PTSD diagnosis based on a validated assessment. The repository, maintained by the US National Center for PTSD, is continually updated with randomized clinical trials and includes studies published from January 1988 on. Study Selection For eligibility, PTSD had to be the primary treatment target, with psychotherapy applied as monotreatment. Eligible studies reported the number of participants who did not meet diagnostic criteria for PTSD posttreatment. When this review was initiated (October 2023), the repository contained 496 unique studies. Data analysis was completed from October 2023 to June 2024. Data Extraction and Synthesis The repository follows Preferred Reporting Items for Systematic Reviews and Meta-analyses ( PRISMA ) reporting guidelines and uses Cochrane Risk of Bias 2.0. We used mixed-effects logistic regression models to estimate diagnosis loss and incorporated milvet status and sex as covariates. Main Outcomes and Measures The primary outcome was the proportion of participants who no longer met criteria for a diagnosis of PTSD posttreatment as assessed by a validated instrument. Results We included 34 randomized clinical trials (N = 3208 participants). Point estimates of diagnosis loss across trauma-focused treatments for nonmilvet samples ranged from 65% to 86%. Milvet samples had lower proportions of diagnosis loss in studies of cognitive processing therapy and prolonged exposure compared to nonmilvet samples, ranging from 44% to 50%. There was substantial overlap between the covariates of milvet status and sex. An exploratory analysis identified eye movement desensitization and reprocessing as having the highest proportion of diagnosis loss, but there was substantial heterogeneity, and none of the studies were milvet-focused or conducted in the US. Also, 95% confidence intervals partially overlapped for all trauma-focused treatment estimates. Conclusions and Relevance This systematic review and meta-analysis contributes to the substantial literature on psychotherapeutic treatments for PTSD by meta-analyzing the probabilities of diagnosis loss for each psychotherapy. Diagnosis loss data are a relatively straightforward way to discuss potential benefits when initiating a therapy or when discussing potential barriers to progress in treatment.
Comparative Effectiveness of Long-Acting Lipoglycopeptides vs Standard-of-Care Antibiotics in Serious Bacterial Infections
Authors: David Goodman-Meza, Robert E. Weiss, Michelle L. Poimboeuf, Jeffrey Feng, Tara Vijayan, Marianne Martinello, Gail V. Matthews, Gregory J. Dore
Journal: JAMA Network Open (2025)

Importance Serious bacterial infections such as bacteremia, endocarditis, osteomyelitis, and septic arthritis typically require prolonged intravenous antibiotics. Long-acting lipoglycopeptides (laLGPs), such as dalbavancin and oritavancin, offer extended treatment intervals for gram-positive infections that may benefit populations with barriers to traditional treatment, including persons who use drugs (PWUD individuals). Objective To assess the effectiveness of laLGPs in managing serious bacterial infections in both PWUD and non-PWUD populations compared with standard-of-care (SOC) antibiotics. Design, Setting, and Participants This comparative effectiveness study using a target trial emulation framework included data extracted from the US Cerner Real World Data platform. Individuals hospitalized and discharged for serious bacterial infections between October 1, 2015, and October 1, 2022, were included in the analysis. Data were analyzed from July 7, 2023, to February 28, 2025. Intervention Receipt of an laLGP (dalbavancin or oritavancin) vs SOC antibiotics. Main Outcome and Measures The primary outcome measure was a composite of readmission, emergency department visit, and inpatient death or discharge to hospice within 90 days post discharge from the index admission. Analyses were stratified by PWUD and non-PWUD status. Clone censor weighting was used to emulate a per-protocol analysis. Hazard ratios (HR) of time to the composite event and 95% CIs were calculated using bootstrapping. Results Among 42 067 included individuals, median age was 61 (IQR, 47-73) years, 24 704 were male (58.7%), and 5047 (12.0%) were classified as PWUD. laLGPs were prescribed in 825 individuals (2.0%). There was no statistically significant difference in the composite outcome between the laLGP and SOC groups in both the PWUD (HR, 1.01; 95% CI, 0.88-1.13) and non-PWUD (HR, 0.93; 95% CI, 0.86-1.00) participants. Conclusions and Relevance In this study of laLGPs vs SOC, findings suggested that laLGPs were effective as step-down treatment of serious gram-positive bacterial infections, offering comparable outcomes to those of SOC antibiotics in PWUD and non-PWUD individuals. Clinicians may consider laLGPs as alternative step-down options to SOC antibiotics for the treatment of serious gram-positive bacterial infections.
Burden of Skin Cancer in Older Adults From 1990 to 2021 and Modelled Projection to 2050
Authors: Ruiyao Wang, Yangmei Chen, Xinyi Shao, Tingqiao Chen, Judan Zhong, Yi Ou, Jin Chen
Journal: JAMA Dermatology (2025)

Importance Skin cancer is a significant public health threat in the aging population, yet data on its burden and trends are limited. Objective To evaluate the global burden of skin cancer among adults 65 years or older from 1990 to 2021, and to project its change to 2050. Design, Setting, and Participants In this observational study, population-based registry data were extracted from the Global Burden of Diseases (GBD) Study 2021. The database covers 204 countries and territories, ensuring global applicability of the results. Data analysis was conducted from June 9, 2024, to February 18, 2025. Main Outcomes and Measures Age-standardized rates of prevalence, incidence, deaths, and disability-adjusted life-years (DALYs) were calculated per 100 000 population. Estimated rates of disease burden were calculated for 2050. Results A worldwide total of 153 993 melanoma, 1 463 424 squamous cell carcinoma (SCC), and 2 802 354 basal cell carcinoma (BCC) instances were estimated for 2021. SCC exhibited the highest age-standardized rate of prevalence (236.91 per 100 000 population; 95% uncertainty interval [UI], 188.23-303.82), deaths (6.16 per 100 000 population; 95% UI, 5.13-6.87), and DALYs (95.50 per 100 000 population; 95% UI, 81.65-106.39), whereas BCC displayed the highest incidence rate (371.97 per 100 000 population; 95% UI, 310.75-439.58). The disease burden was notably greater in male individuals than in female individuals. During the observation period, the global burden of skin cancer among older people demonstrated a general upward trend. Decomposition analysis indicated that population growth was the primary contributor to this increase. Health-inequality analysis revealed a disproportionately higher burden shouldered by countries with higher sociodemographic index (SDI) levels. Frontier analysis identified the countries with considerable potential to mitigate skin cancer. It was anticipated that only incidence and prevalence rates attributable to keratinocyte cancer (KC), along with DALYs rate related to BCC, would increase by 2050. Conclusions and Relevance The older population (particularly male individuals and those living in high-SDI countries) is facing a substantial growing burden of skin cancer. Despite the relative incompleteness of KC data and lack of race and ethnicity data, these results highlight the urgency for more effective prevention and management strategies targeting high-risk groups.
Pseudoxanthoma Elasticum–Like Phenotype With a Novel <i>MGP</i> Variant
Authors: Yun-Shiuan (Olivia) Hsu, Rai-Hseng Hsu, Jau-Yu Liau, Ni-Chung Lee, Yin-Hsiu Chien, Yi-Hua Liao
Journal: JAMA Dermatology (2025)

This case report describes a patient with pseudoxanthoma elasticum–like phenotype associated with a novel MGP gene variant.
Asymptomatic Yellow-Brown Plaques on the Great Toes
Authors: Jessica Zhao, Christine J. Ko, Kenneth Helmandollar
Journal: JAMA Dermatology (2025)

A man in his 30s presented with a 6-month history of asymptomatic yellow-brown plaques on the first digits of his feet that were unresponsive to urea cream and clobetasol treatment. What is your diagnosis?