tbuckley/cabot-search huggingface dataset:
Patient and physician perceptions regarding treatment expectations and symptomatology in polycythemia vera: Insights from the Landmark 2.0 global health survey
Authors: Claire N. Harrison, David M. Ross, Laura Maria Fogliatto, Lynda Foltz, Lambert Busque, Zhijian Xiao, Florian H. Heidel, Michael Koehler, Giuseppe A. Palumbo, Massimo Breccia, Norio Komatsu, Keita Kirito, Blanca Xicoy Cirici, Joaquin Martinez‐Lopez, Alicia Rovo, Cheryl Petruk, Catalin Bobirca, Laura Mirams, Abigail McMillan, Gavin Harper, Jean‐Jacques Kiladjian
Journal: HemaSphere (2025)

Abstract Polycythemia vera (PV) is a myeloproliferative neoplasm associated with a high symptom and psychological burden, resulting in decreased quality of life (QoL). Patients with PV have an increased risk of cardiovascular (CV) complications, making regular monitoring crucial. The Landmark 2.0 survey was conducted worldwide among patients with PV and their treating physicians to identify any potential gaps in perceptions regarding PV management. Data were collected between April 2021 and April 2022 from physicians and patients across 11 countries. Overall, 133 physicians and 274 patients with PV participated in the survey. There were discrepancies between physicians and patients in reporting whether symptom assessments and basic CV assessments were conducted during routine visits (83% vs. 68% and 64% vs. 55%, respectively). Emotional assessments were not performed routinely (reported by 36% of physicians and 34% of patients). Patients attributed the highest impact on QoL to physical symptoms (67%); however, physicians were less likely to report highly prevalent symptoms such as bruising, difficulty sleeping, inactivity, and depression among the most common symptoms. While both physicians and patients aimed for symptom improvement, their treatment goals differed: physicians focused on managing hematocrit, preventing thrombotic events, and reducing spleen size, while patients focused on slowing down disease progression. Patient satisfaction with treatment was generally high but decreased in later therapy stages. Overall, these data underscore the disparity in patient–physician perceptions of PV management and treatment expectations, showing the gaps in communication and the need for greater patient education, as well as highlighting areas for potential improvement in clinical practice.
In the time of COVID-19: challenges, successes and lessons learned from studies in cancer patients
Authors: Philip C Mack, James M Crawford, Andres Chang, Anna Yin, Sabra L Klein, Patrick Shea, Fred R Hirsch, David Zidar, Viviana Simon, Charles Gleason, Russell McBride, Carlos Cordon-Cardo, Jennifer VanOudenhove, Stephanie Halene, F Eun-Hyung Lee, Nicholas Mantis, Lawrence H Kushi, Daniela Weiskopf, Akil Merchant, Karen L Reckamp, Jacek Skarbinski, Jane C Figueiredo
Journal: JNCI Journal of the National Cancer Institute (2025)

The COVID-19 pandemic created the urgent need to monitor risk of SARS-CoV-2 infection and mortality, and to evaluate immune responses to novel vaccines. A foremost concern was the unknown risks to patients with cancer, considering their overall health, immune status and interactions with cancer therapies. The U.S. National Cancer Institute, in partnership with the National Institute of Allergy and Infectious Diseases, established the SARS-CoV-2 Serological Sciences Network (SeroNet) as the nation's largest coordinated effort to identify and establish standardized serology tests to study immune responses against SARS-CoV-2. SeroNet-sponsored institutions established cohort studies in 2020 and 2021 across the nation to prospectively follow over 3,000 patients with solid and hematologic malignancies. Concerted efforts were launched to define common data elements for self-reported and clinicopathological data as well as standardized approaches for serological, cellular and molecular assays. However, the urgency of the situation, the pace of scientific evolution and the changing public health landscape presented unique challenges to this effort. Here, we discuss these challenges, including regulatory and institution-specific requirements, enrollment of participants, data and biospecimen collection and harmonization, and the need to adapt study designs to align with the ever-changing landscape. This information is critical to the continuance of research on SARS-CoV-2 and provides a roadmap for combatting the emergence of future pathogens with pandemic potential.
Tetraspanin CD37 regulates platelet hyperreactivity and thrombosis
Authors: Marcin A Sowa, Carmen Hannemann, Ivan Pinos Cabezas, Elissa Ferreira, Bharti Biwas, Min Dai, Emma M Corr, Macintosh G Cornwell, Kamelia Drenkova, Angela H Lee, Tanya Spruill, Harmony R Reynolds, Judith Hochman, Kelly V Ruggles, Robert A Campbell, Coen van Solingen, Mark D Wright, Kathryn J Moore, Jeffrey S Berger, Tessa J Barrett
Journal: Cardiovascular Research (2025)

To investigate how psychosocial stress contributes to accelerated thrombosis, focusing on platelet activation and hyperreactivity. The specific objective was to identify novel platelet regulators involved in stress-mediated thrombosis, with a particular emphasis on the tetraspanin CD37. To explore how stress contributes to platelet hyperreactivity, platelets were isolated from (1) mice that experienced chronic variable stress and stress-free controls (n=8/group) and (2) human subjects with self-reported high and no stress levels (n=18/group), followed by RNA-sequencing. By comparing mutually expressed transcripts, a subset of genes differentially expressed following psychosocial stress was identified in both human and mouse platelets. In both mice and humans, platelet CD37 positively associates with platelet aggregation responses that underlie thrombosis, with Cd37-/- platelets exhibiting impaired integrin αIIbβ3 signaling, characterized by reduced platelet fibrinogen spreading and decreased agonist-induced αIIbβ3 activation. Consistent with a role for CD37 in regulating platelet activation responses, chimeric mice that received Cd37-/- bone marrow experienced a significantly increased time to vessel occlusion in the carotid artery FeCl3 model compared to mice reconstituted with wild-type bone marrow. CD37 deficiency did not alter hemostasis, as platelet count, coagulation metrics, prothrombin time, and partial thromboplastin time did not differ in Cd37-/- mice relative to wild-type mice. Consistent with this, bleeding time did not differ between wild-type and Cd37-/- mice following tail tip transection. This study provides new insights into the platelet-associated mechanisms underlying stress-mediated thrombosis. Identifying CD37 as a novel regulator of platelet activation responses offers potential therapeutic targets for reducing the thrombotic risk associated with psychosocial stress. The findings also contribute to understanding how psychosocial stress accelerates thrombotic events and underscore the importance of platelet activation in this process.
Targeting PDGFRA-SHP2 Signaling Enhances Radiotherapy in IDH1-Mutant Glioma
Authors: Xiaozhou Yu, Xiao Song, Deanna Tiek, Runxin Wu, Maya Walker, Craig Horbinski, Bo Hu, Shi-Yuan Cheng
Journal: Neuro-Oncology (2025)

Abstract Background Isocitrate dehydrogenase mutant (IDH-mut) gliomas represent a distinct subtype of glioma, characterized by a relatively better prognosis compared to IDH wildtype (wt) glioblastoma (GBM). Despite this advantage, these tumors remain incurable due to the limited availability of effective treatments. Targeting SHP2, a non-receptor protein tyrosine phosphatase, is a promising therapeutic strategy for several types of human cancers. In this study, we aim to determine the efficacy of SHP inhibition in IDH-mut gliomas. Methods Bioinformatic and biological analyses revealed increased expression and activation of the PDGFRA-SHP2-ERK pathway in clinical IDH-mut gliomas and patient-derived IDH-mut glioma stem-like cells (GSCs). The effects of SHP2 inhibition, alone or with radiation therapy (RT), were assessed through assays including cell growth, sphere formation, cell differentiation markers, flow cytometry, immunoblotting, immunohistochemistry, and orthotopic brain tumor xenografts. Results PDGFRA expression was elevated in IDH-mut gliomas and GSCs, activating the SHP2-ERK pathway. SHP099, a SHP2 inhibitor, reduced GSC tumorigenicity in vitro and in vivo by disrupting SHP2-ERK signaling and promoting differentiation. SHP099 also enhanced cytotoxicity of RT, the standard treatment for IDH-mut glioma, in IDH-mut GSCs and orthotopic glioma models. Mechanistically, the PDGFRA-SHP2-ERK axis is activated in IDH-mut gliomas and RT further activates this pathway. Targeting SHP2 suppressed ERK signaling thereby enhancing the therapeutic effect of RT. Conclusion Combining SHP2 inhibition with RT is a promising therapeutic avenue for IDH-mut glioma by suppressing the activated SHP2-ERK axis.
SOX2 commands LIM homeobox transcription factors in choroid plexus development and tumorigenesis
Authors: Lukas J Faltings, Fengjuan Lin, Mariam Zahran, Heena Jalili, Anjali Siluveru, Mahek Chaudry, Leah M Wachsmuth, Navjot Guru, Melanie Schoof, Ping Cao, Yuan Huang, Noreen Mian, Sohyun Moon, Asmaa Zahran, Kristen Green, Siddhi Modi, Maheen Umer, James Q Virga, Ying-Tao Zhao, Ulrich Schüller, Qun Li, Haotian Zhao
Journal: Neuro-Oncology (2025)

Abstract Background Choroid plexus (CP) tumors are rare brain neoplasms that mainly affect the pediatric population. Unlike benign CP papilloma (CPP), CP carcinoma (CPC) is an aggressive cancer with a dismal survival rate. Despite chromosome-wide rearrangements, drivers of most CP tumors remain elusive except recurrent alterations in TP53. Studies of signaling dysregulation may bring biological understanding of these malignancies. Previous studies implicated NOTCH signaling in CP tumors; we developed mouse models of CP tumors driven by NOTCH activation and Trp53 loss, respectively. This work examined the role of the transcription factor SOX2 in CP development and tumorigenesis. Methods Multi-omics approaches were used to characterize cellular heterogeneity in NOTCH-driven CP tumors. SOX2 functions in the molecular signature of tumor cells were investigated. Results Single-cell transcriptomics and epigenetics methods identified diverse cell populations in tumors that resemble normal CP, such as epithelial and glial groups. Pseudo-time trajectory analysis indicated that NOTCH-driven CP tumor arises from bi-potential glial progenitors and retains a progenitor-like signature characterized by an enhanced SOX2 profile. SOX2 inactivation attenuated progenitor-like features and blunted tumor growth. Integrative omics studies revealed SOX2 binding to genes expressed in progenitors in the rhombic lip, including LIM homeobox transcription factors LMX1A and LMX1B. Consistently, SOX2 maintains progenitor identity through regulating their expression in CP tumors and during development, whereas LMX1A and LMX1B support SOX2 functions in tumor cell proliferation. Furthermore, spatial transcriptomics revealed aberrant SOX2 and LMX1A expression in human CP tumors. Conclusions SOX2-LMX1 signaling maintains progenitor identity in CP development and tumor formation.
Averted lung cancer deaths due to reductions in cigarette smoking in the United States, 1970–2022
Authors: Farhad Islami, Nigar Nargis, Qinran Liu, Priti Bandi, Rebecca L. Siegel, Parichoy Pal Choudhury, Neal D. Freedman, Kenneth E. Warner, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2025)

Lung cancer mortality rates in the United States have declined steeply in recent decades, largely because of substantial reductions in smoking prevalence, as approximately 85% of lung cancer deaths are attributable to cigarette smoking. In this study, the authors estimate the number of averted lung cancer deaths and corresponding person-years of life gained during 1970-2022 as a measure of progress in cancer prevention through tobacco control. By using the 1970-2022 National Center for Health Statistics mortality data (with national coverage), the authors calculated the expected number of deaths for each year, age, sex, race, and age group based on the expected lung cancer death rate multiplied by the population at risk in that group. The number of averted lung cancer deaths were calculated by subtracting the observed number of deaths from the expected number in each group. Person-years of life gained were estimated as a measure of avoided premature mortality based on the average additional years a person would have lived if they had not died from lung cancer. The authors estimated that 3,856,240 lung cancer deaths (2,246,610 in men, 1,609,630 in women) were averted, and 76,275,550 person-years of life (40,277,690 in men, 35,997,860 in women) were gained during 1970-2022, with an average of 19.8 person-years of life gained (17.9 in men, 22.4 in women) per averted death. The number of averted lung cancer deaths accounted for 51.4% of the estimated declines in overall cancer deaths and was substantially greater in men (60.1%) than in women (42.7%). By race, this proportion was 53.6% in the White population (62.8% in men, 44.6% in women) and 40.0% in the Black population (44.4% in men, 34.7% in women). The substantial estimated numbers of averted lung cancer deaths and person-years of life gained highlight the remarkable effect of progress against smoking on reducing premature mortality from lung cancer.
Differentiation of Tumor vs. Peritumoral Cortex in Gliomas by Intraoperative Electrocorticography
Authors: Belén Díaz-Fernández, David Henao-Herreno, Juan Nieto, Alesya Evstratova, Silvia Cases-Cunillera, Louise Deboeuf, Alexandre Roux, Edouard Dezamis, Marc Zanello, Bertrand Mathon, Carine Karachi, Alexandre Carpentier, Pascale Varlet, Johan Pallud, Laurent Capelle, Catalina Alvarado-Rojas, Michel Le Van Quyen, Gilles Huberfeld
Journal: Neuro-Oncology (2025)

Abstract Background Brain diffuse gliomas are highly epileptic and infiltrative tumors. Glioma surgery consists in the resection of the tumor core and the maximum of the peritumoral zone, infiltrated by tumor cells, guided by the intraoperative assessment of brain functionality and connectivity. However, its electrophysiological characteristics are poorly characterized. Methods We studied the characteristics of Electrocorticographic (ECoG) signals, in the context of glioma surgery in awake condition on 29 patients, using EEG activity sampled on the tumor itself versus on its borders and in healthy areas. We assessed the features of frequency bands and aperiodic components (offset and slope) of ECoG power spectra during awake glioma surgery, according to cortical tumoral vs peritumoral and healthy status. Results We found that tumor contacts present a decrease in activity for all the frequency bands except for delta activity, which was increased. Second, the peritumoral cortex was characterized by an increase in relative beta activity and slopes between 20-40 Hz. Low cortical tumor cell infiltration was directly correlated with a reduction in the production of physiological brain rhythms. Finally, an automatic classifier based on neural networks allowed the classification of the electrodes based on their power spectrum characteristics. Conclusions This intraoperative study shows that ECoG during glioma surgery in awake condition may characterize the peritumoral cortices, key for pathophysiology and therapy, and deepens our knowledge of the effects of tumor cells infiltration on nervous tissue activity. Its assessment during the surgical procedure should better delineation of the cortical areas to be removed.
Rescue Therapy in Malignant Atrophic Papulosis: A New Era of Promising Treatments Targeting Interferon and Complement Pathways
Authors: Yasmine El Maamar, Clément Pruvot, Meryem-Maud Farhat, Barbara Noiret, Constance Laroye, Alexandre Barbe, Lila Ghannem, Pierre Labalette, Delphine Staumont-Salle, David Launay, Éric Hachulla, Emmanuel Ledoult
Journal: British Journal of Dermatology (2025)

Targeting both interferon and complement pathways demonstrates significant efficacy to treat malignant atrophic papulosis, offering a potential groundbreaking therapeutic avenue for this rare and life-threatening disease.
Membrane‐Anchoring and Oxygen‐Generating Mediated Nanosonosensitizer for Optimizing Cancer Immunotherapy
Authors: Qing Zhao, Ye Han, Wushuang Gong, Zhiyue Cao, Haonan Chang, Shaofan Gong, Qunying Li, Mengmeng Li, Chao Ma, Liangcan He, Hang Zhou
Journal: Advanced Healthcare Materials (2025)

Despite its antitumor promise, sonodynamic therapy (SDT)'s efficacy in immune activation requires enhancement, primarily due to the hypoxic tumor microenvironment (TME) and insufficient targeting of sonosensitizers to specific subcellular regions. Herein, we developed macrophage membrane (MM)-intermingled membrane fusogenic liposomes (MFL) to optimize sonoimmunotherapy that encapsulate catalase (CAT) within the core and incorporate the sonosensitizer chlorin e6 (Ce6) in the outer shell (CAT@MM-MFL-Ce6). The MM confers immune evasion properties and promotes nanoparticles' targeted accumulation in tumor tissue. The membrane fusion effect enables Ce6 to anchor onto cancer cell membrane and facilitates the direct delivery of CAT into the cytoplasm, bypassing endosomal degradation. Upon ultrasound stimulation, generated reactive oxygen species directly damage the plasma membrane, initiating the Caspase 3/Gasdermin E-mediated pyroptosis pathway. Concurrently, the encapsulated CAT efficiently decompose H₂O₂ in the cytoplasm, thus enhancing local oxygen levels in hypoxic tumors. Contributed by these effects, the combination of nanosonosensitizer-augmented SDT and immune checkpoint agent successfully reverse the immunosuppressive TME, driving a potent immune response that inhibits primary tumor growth, distant metastasis, and lung metastases in an orthotopic triple-negative breast cancer model. This study demonstrates the potential of a novel SDT-based combinatorial approach to modulate immune-cold TMEs, advancing proof-of-concept tumor therapeutics.
A new comparative framework for estimating selection on synonymous substitutions
Authors: Hannah Verdonk, Alyssa Pivirotto, Vitor Pavinato, Jody Hey, Sergei LK Pond
Journal: Molecular Biology and Evolution (2025)

Selection on synonymous codon usage is a well-known and widespread phenomenon, yet existing models often do not account for it or its effect on synonymous substitution rates. In this article, we develop and expand the capabilities of Multiclass Synonymous Substitution (MSS) models, which account for such selection by partitioning synonymous substitutions into two or more classes and estimating a relative substitution rate for each class, while accounting for important confounders like mutation bias. We identify extensive heterogeneity among relative synonymous substitution rates in an empirical dataset of ∼12,000 gene alignments from twelve Drosophila species. We validate model performance using data simulated under a forward population genetic simulation, demonstrating that MSS models are robust to model misspecification. MSS rates are significantly correlated with other covariates of selection on codon usage (population-level polymorphism data and tRNA abundance data), suggesting that models can detect weak signatures of selection on codon usage. With the MSS model, we can now study selection on synonymous substitutions in diverse taxa, independent of any a priori assumptions about the forces driving that selection.
LocusMasterTE: integrating long-read RNA sequencing improves locus-specific quantification of transposable element expression
Authors: Sojung Lee, Jayne A. Barbour, Yee Man Tam, Haocheng Yang, Yuanhua Huang, Jason W. H. Wong
Journal: Genome biology (2025)

Abstract Transposable elements (TEs) can influence human diseases by disrupting genome integrity, yet their quantification has been challenging due to the repetitive nature of these sequences across the genome. We develop LocusMasterTE, a method that integrates long-read with short-read RNA-seq to increase the accuracy of TE expression quantification. By incorporating fractional transcript per million values from long-read sequencing data into an expectation–maximization algorithm, LocusMasterTE reassigns multi-mapped reads, enhancing accuracy in short-read-based TE quantification. We validate the method with simulated and human datasets. LocusMasterTE may give new insights into TE functions through precise quantification.
Regulatory and disruptive variants in the CLCN2 gene are associated with modified skin color pattern phenotypes in the corn snake
Authors: Sophie A. Montandon, Pierre Beaudier, Asier Ullate-Agote, Pierre-Yves Helleboid, Maya Kummrow, Sergi Roig-Puiggros, Denis Jabaudon, Leif Andersson, Michel C. Milinkovitch, Athanasia C. Tzika
Journal: Genome biology (2025)

Abstract Background Snakes exhibit a broad variety of adaptive colors and color patterns, generated by the spatial arrangement of chromatophores, but little is known of the mechanisms responsible for these spectacular traits. Here, we investigate a mono-locus trait with two recessive alleles, motley and stripe , that both cause pattern aberrations in the corn snake. Results We use mapping-by-sequencing to identify the genomic interval where the causal mutations reside. With our differential gene expression analyses, we find that CLCN2 (Chloride Voltage-Gated Channel 2), a gene within the genomic interval, is significantly downregulated in Motley embryonic skin. Furthermore, we identify the stripe allele as the insertion of an LTR-retrotransposon in CLCN2 , resulting in a disruptive mutation of the protein. We confirm the involvement of CLCN2 in color pattern formation by producing knock-out snakes that present a phenotype similar to Stripe. In humans and mice, disruption of CLCN2 results in leukoencephalopathy, as well as retinal and testes degeneration. Our single-cell transcriptomic analyses in snakes reveal that CLCN2 is indeed expressed in chromatophores during embryogenesis and in the adult brain, but the behavior and fertility of Motley and Stripe corn snakes are not impacted. Conclusions Our genomic, transcriptomic, and functional analyses identify a plasma membrane anion channel to be involved in color pattern development in snakes and show that an active LTR-retrotransposon might be a key driver of trait diversification in corn snakes.