tbuckley/cabot-search huggingface dataset:
Activating soluble guanylyl cyclase attenuates ischemic kidney damage
Authors: Falk-Bach Lichtenberger, Minze Xu, Cem Erdoğan, Lingyan Fei, Ilka Mathar, Lisa Dietz, Peter Sandner, Erdmann Seeliger, Sengül Boral, Julia Sophie Bonk, Tobias Sieckmann, Pontus B Persson, Andreas Patzak, Kathleen Cantow, Pratik H Khedkar
Journal: Kidney International (2024)
Responsive Plasmonic Hybrid Nanorods Enables Metabolism Reprogramming via Cuproptosis-Photothermal Combined Cancer Therapy
Authors: Qian Xie, Tao Sun, Liang Zhang, Mingfu Gong, Wansu Zhang, Xu Liu, Yue Zhao, Miaomiao Wang, Xiaofeng Yang, Zhipeng Zhang, Gang Liu, Chunyu Zhou, Dong Zhang
Journal: Biomaterials (2024)
The New Perspective of Alzheimer's Disease Research: Mechanism and Therapeutic Strategy of Neuronal Senescence
Authors: Qianqian Niu, Danjie Li, Jiayin Zhang, Zhengji Piao, Bo Xu, Yuting Xi, Nik Nur Syazni Nik Mohamed Kamal, Vuanghao Lim, Peng Li, Yaling Yin
Journal: Ageing Research Reviews (2024)
Interpretable machine learning model for digital lung cancer prescreening in Chinese populations with missing data
Authors: Shuaijie Zhang, Qing Wang, Xifeng Hu, Botao Zhang, Shuangshuang Sun, Ying Yuan, Xiaofeng Jia, Yuanyuan Yu, Fuzhong Xue
Journal: npj Digital Medicine (2024)

We developed an interpretable model, BOUND (Bayesian netwOrk for large-scale lUng caNcer Digital prescreening), using a comprehensive EHR dataset from the China to improve lung cancer detection rates. BOUND employs Bayesian network uncertainty inference, allowing it to predict lung cancer risk even with missing data and identify high-risk factors. Developed using data from 905,194 individuals, BOUND achieved an AUC of 0.866 in internal validation, with time- and geography-based external validations yielding AUCs of 0.848 and 0.841, respectively. In datasets with 10%–70% missing data, AUC ranged from 0.827 – 0.746. The model demonstrates strong calibration, clinical utility, and robust performance in both balanced and imbalanced datasets. A risk scorecard was also created, improving detection rates up to 6.8 times, available free online ( https://drzhang1.aiself.net/ ). BOUND enables non-radiative, cost-effective lung cancer prescreening, excels with missing data, and addresses treatment inequities in resource-limited primary healthcare settings.
Considerations in the search for epistasis
Authors: Marleen Balvert, Johnathan Cooper-Knock, Julian Stamp, Ross P. Byrne, Soufiane Mourragui, Juami van Gils, Stefania Benonisdottir, Johannes Schlüter, Kevin Kenna, Sanne Abeln, Alfredo Iacoangeli, Joséphine T. Daub, Brian L. Browning, Gizem Taş, Jiajing Hu, Yan Wang, Elham Alhathli, Calum Harvey, Luna Pianesi, Sara C. Schulte, Jorge González-Domínguez, Erik Garrisson, Ammar Al-Chalabi, Jorge Avila Cartes, Jasmijn Baaijens, Joanna von Berg, Davide Bolognini, Paola Bonizzoni, Andrea Guarracino, Mehmet Koyuturk, Magda Markowska, Raghuram Dandinasivara, Jasper van Bemmelen, Sebastian Vorbrugg, Sai Zhang, Bogdan Pasanuic, Michael P. Snyder, Alexander Schönhuth, Letitia M. F. Sng, Natalie A. Twine
Journal: Genome biology (2024)

Epistasis refers to changes in the effect on phenotype of a unit of genetic information, such as a single nucleotide polymorphism or a gene, dependent on the context of other genetic units. Such interactions are both biologically plausible and good candidates to explain observations which are not fully explained by an additive heritability model. However, the search for epistasis has so far largely failed to recover this missing heritability. We identify key challenges and propose that future works need to leverage idealized systems, known biology and even previously identified epistatic interactions, in order to guide the search for new interactions.
CRISPR targeting of mmu-miR-21a through a single adeno-associated virus vector prolongs survival of glioblastoma-bearing mice
Authors: Lisa Nieland, Anne B Vrijmoet, Isabelle W Jetten, David Rufino-Ramos, Alexandra J E M de Reus, Koen Breyne, Benjamin P Kleinstiver, Casey A Maguire, Marike L D Broekman, Xandra O Breakefield, Erik R Abels
Journal: Molecular Therapy (2024)
Extension of the PRISMA 2020 statement for living systematic reviews (PRISMA-LSR): checklist and explanation
Authors: Elie A Akl, Joanne Khabsa, Claire Iannizzi, Vanessa Piechotta, Lara A Kahale, James M Barker, Joanne E McKenzie, Matthew J Page, Nicole Skoetz
Journal: BMJ (2024)

Publications of living systematic reviews (LSRs) are increasing rapidly. Guidance facilitating transparent, complete, and accurate reporting of LSRs is needed. This paper reports the development of an extension of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 statement for LSRs (PRISMA-LSR). The PRISMA-LSR extension includes the PRISMA-LSR checklist, the PRISMA-LSR flow diagram, reporting recommendations for the LSR status, and an explanation and elaboration document. This extension has been developed as an "add-on" to the PRISMA 2020 statement, meaning it should be used in addition to the PRISMA 2020 statement. The PRISMA-LSR extension is expected to benefit authors, editors, peer reviewers, and users of LSRs through transparent, complete, and accurate reporting of LSRs.
Longitudinal Results From the Nationwide Just ASK Initiative to Promote Routine Smoking Assessment in American College of Surgeons–Accredited Cancer Programs
Authors: Jessica L. Burris, Jamie S. Ostroff, Eileen M. Reilly, Graham W. Warren, Rachel C. Shelton, Timothy W. Mullett, Rob Adsit, Lisa Allison, Daniel Boffa, Jessica Burris, Asa Carter, Audrey Darville, Michael Fiore, Ellen Hahn, James Harris, Laurie Kirstein, Danielle McCarthy, Timothy Mullett, Heidi Nelson, Jamie Ostroff, Eileen Reilly, Erin Reuter, Sarah Shafir, Rachel Shelton, Elisa Tong, Graham Warren
Journal: Journal of Clinical Oncology (2024)

PURPOSE Persistent smoking after cancer diagnosis causes adverse outcomes while smoking cessation can improve survival. Thus, integration of smoking assessment and cessation assistance into routine cancer care is critical. Aiming for incremental practice change that could be sustained and built upon through future quality improvement (QI) projects, the American College of Surgeons initiated Just ASK in 2022 to increase implementation of smoking assessment among its accredited Cancer Programs. This manuscript describes outcomes from Just ASK. METHODS Seven hundred sixty-two programs enrolled in this cohort study, followed Plan Do Study Act methodology, and used local QI teams to facilitate practice change. The primary outcome was the ask rate (ie, patients asked/patients seen). Programs completed three surveys across the 1-year study (89.8% retention), answering questions about their program plus organizational readiness, implementation barriers, implementation strategies, and clinical practices related to assessing smoking among patients newly diagnosed with cancer. Data analysis involved descriptive statistics and analysis of change over time (eg, McNemar chi-squares). RESULTS Programs (53.1% community-based) tended to report moderate organizational readiness, multiple implementation barriers, and adoption of 4.63 ± 1.49 of eight possible implementation strategies (eg, training staff/providers). Programs reported frequency of assessing smoking status, documenting it in the electronic health record, advising patients who smoke to quit, and documenting advice and treatment increased over time (all P &lt; .001). The ask rate increased from baseline to mid to final survey ( P &lt; .01; 87.79% v 88.65% v 91.92%, respectively). CONCLUSION Just ASK is the latest, and by far the largest, endeavor to improve assessment of cancer patients' smoking status. Participants reported significant advances within a short time span and study results underscore the potential for national accreditation organizations to transform oncology practice.
Development of ALL-Hematotox (ALL-HT): Predicting post CAR T-cell hematotoxicity in B-cell acute lymphoblastic leukemia
Authors: Monica S Nair, Sara K Silbert, Kai Rejeski, Karilynn A Wilson, Adam Joseph Lamble, Yannis K. Valtis, Bonnie Yates, Alexa Morales Arana, Roni Shouval, Kevin J. Curran, Rebecca A Gardner, Haneen Shalabi, Colleen Annesley, Jae H. Park, Marion Subklewe, Nirali N Shah
Journal: Blood (2024)

Immune effector cell-associated hematotoxicity (ICAHT) is a major B-cell targeted chimeric antigen receptor (CAR) T-cell related toxicity. While ICAHT incidence and severity is documented in large B-cell lymphoma (LBCL), mantle cell lymphoma (MCL), and multiple myeloma (MM), ICAHT has not been described in B-cell acute lymphoblastic leukemia (B-ALL). Similarly, the CAR-HEMATOTOX (CAR-HT) model, designed to predict severe prolonged neutropenia (&amp;gt;14 days of ANC &amp;lt;500/µl), has been validated in LBCL, MCL, and MM, but not in B-ALL. As B-ALL bone marrow (BM) infiltration can impact cytopenias, we sought to describe ICAHT and assess CAR-HT for predicting hematotoxicity in B-ALL. In a cohort of 156 children and young adults with relapsed/refractory B-ALL, the median duration of severe neutropenia (ANC &amp;lt;500/µl) was 13 days (95% CI 10-16), with 83 (53%) experiencing grade &amp;gt;3 ICAHT. Applying CAR-HT, nearly 90% were classified as high-risk, demonstrating limited discriminative power and prompting further development. Using the association identified between BM disease burden and post-infusion neutropenia (r=0.64, p&amp;lt;0.0001), we developed the ALL-Hematotox (ALL-HT) score which substitutes BM disease burden for ferritin in CAR-HT. The ALL-HT score associated with severe prolonged neutropenia (area under the curve=0.84, p&amp;lt;0.0001), and appropriately discriminated high-risk patients (47%) who had more cumulative days of neutropenia (26 vs 4 days, p&amp;lt;0.0001), fewer rates of complete response (88% vs 98%, p=0.03), and shorter median overall survival (9.8 vs 24 months, logrank p=0.0002). ALL-HT was also validated in two independent cohorts. The ALL-HT score refines a widely accepted predictive model of post-infusion hematotoxicity, applicable in B-ALL.
Analysis of shared variants between cancer biospecimens
Authors: Michael B. Foote, James Robert. White, Walid K. Chatila, Guillem Argilés, Steve Lu, Benoit Rousseau, Oliver Artz, Paul Johannet, Henry Walch, Mitesh Patel, Michelle F. Lamendola-Essel, David Casadevall, Somer Abdelfattah, Shrey Patel, Rona Yaeger, Andrea Cercek, Clara Montagut, Michael Berger, Nikolaus Schultz, Luis A. Diaz
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Mutational data from multiple solid and liquid biospecimens of a single patient is often integrated to track cancer evolution. However, there is no accepted framework to resolve if individual samples from the same individual share variants due to common identity versus coincidence. Experimental Design: Utilizing 8,000 patient tumors from The Cancer Genome Atlas (TCGA) across 33 cancer types, we estimated background rates of co-occurrence rates of mutations between discrete pairs of samples across cancers and by cancer type. We developed a mutational profile similarity score (MPS) that uses a large background database to produce confidence estimates that two tumors share a unique, related molecular profile. The MPS algorithm was applied to randomly paired tumor profiles, including patients who underwent repeat solid tumor biopsies sequenced with MSK-IMPACT (n=53,113). We also evaluated the MPS in sample pairs from single patients with multiple cancers (n=2,012), as well as patients with plasma and solid-tumor variant profiles (n=884 patients). Results: In unrelated tumors, nucleotide-specific variants are shared in 1.3% (cancer-type agnostic) and in 10-13% (cancer-type specific) of cases. The mutational profile similarity (MPS) method contextualized shared variants to specify whether patients had a single cancer versus multiple distinct cancers. When multiple tumors were compared from the same patient, and an initial clinicopathologic diagnosis was discordant with molecular findings, the MPS anticipated future diagnosis changes in 28% of examined cases. Conclusions: Use of a novel shared variant framework can provide information to clarify the molecular relationship between compared biospecimens with minimal required input.
A Phase II Study of Fulvestrant plus Abemaciclib in Hormone Receptor-Positive Advanced or Recurrent Endometrial Cancer
Authors: Angela K. Green, Qin Zhou, Alexia Iasonos, William A. Zammarrelli, Britta Weigelt, Lora H. Ellenson, Rashmi Chhetri-Long, Pooja Shah, Jade Loh, Vania Hom, Pier Selenica, Joseph Erinjeri, Iva Petkovska, Sarat Chandarlapaty, Seth Cohen, Rachel Grisham, Jason Konner, Maria M. Rubinstein, William Tew, Tiffany Troso-Sandoval, Carol Aghajanian, Vicky Makker
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Inhibition of the cyclin D-cyclin dependent kinase (CDK)4/6-INK4-retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to endocrine monotherapy in advanced endometrial cancer (EC) are suboptimal, perhaps due to genomic alterations that promote estrogen receptor (ER)-independent cyclin D1-CDK4/6 activation. We hypothesized that addition of abemaciclib, a CDK4/6 kinase inhibitor, to antiestrogen therapy with fulvestrant will be an effective therapeutic strategy in patients with advanced or recurrent EC. Methods: In this phase II study, patients with advanced or recurrent EC received 150 mg of abemaciclib orally twice daily with 500 mg of fulvestrant intramuscularly monthly with a 2-week loading dose. Eligibility included ER or progesterone receptor expression ³1% by immunohistochemistry, measurable disease, £2 prior lines of chemotherapy, and £1 prior line of hormonal therapy. The primary endpoint was objective response rate (ORR) by RECIST v1.1. Results: Twenty-seven patients initiated therapy and 25 were evaluable for efficacy. Eleven patients achieved partial response; 10 responses (91%) were in copy number-low/no specific molecular profile tumors, 1 (9%) was in a microsatellite instability-high tumor, and no responses were observed in copy number-high/TP53abnormal tumors. The ORR was 44% (90% CI, 27.0%-62.1%). Median duration of response was 15.6 months. Median progression-free survival was 9.0 months (90% CI: 1.8-20.4). The most common grade ³3 treatment-related adverse events were neutropenia (26%) and anemia (19%); no new safety signals were identified. Conclusions: The combination of abemaciclib and fulvestrant has promising activity with durable responses in advanced or recurrent EC; a randomized trial is planned.
Quantitative and Morphology-Based Deep Convolutional Neural Network Approaches for Osteosarcoma Survival Prediction in the Neoadjuvant and Metastatic Setting.
Authors: Nicolas Coudray, Michael A. Occidental, Jose G. Mantilla, Adalberto Claudio Quiros, Ke Yuan, Jan Balko, Aristotelis Tsirigos, George Jour
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Necrosis quantification in the neoadjuvant setting using pathology slide review is the most important validated prognostic marker in conventional osteosarcoma. Herein, we explored three deep learning strategies on histology samples to predict outcome for OSA in the neoadjuvant setting. Experimental Design: Our study relies on a training cohort from New York University (New York, NY) and an external cohort from Charles university (Prague, Czechia). We trained and validated the performance of a supervised approach that integrates neural network predictions of necrosis/tumor content, and compared predicted overall survival (OS) using Kaplan-Meier curves. Furthermore, we explored morphology-based supervised and self-supervised approaches to determine whether intrinsic histomorphological features could serve as a potential marker for OS in the setting of neoadjuvant. Results: Excellent correlation between the trained network and the pathologists was obtained for the quantification of necrosis content (R2=0.899, r=0.949, p &amp;lt; 0.0001). OS prediction cutoffs were consistent between pathologists and the neural network (22% and 30% of necrosis, respectively). Morphology-based supervised approach predicted OS with p-value=0.0028, HR=2.43 [1.10-5.38]. The self-supervised approach corroborated the findings with clusters enriched in necrosis, fibroblastic stroma, and osteoblastic morphology associating with better OS (lg2HR; -2.366; -1.164; -1.175; 95% CI=[-2.996; -0.514]). Viable/partially viable tumor and fat necrosis were associated with worse OS (lg2HR;1.287;0.822;0.828; 95% CI=[0.38-1.974]). Conclusions: Neural networks can be used to automatically estimate the necrosis to tumor ratio, a quantitative metric predictive of survival. Furthermore, we identified alternate histomorphological biomarkers specific to the necrotic and tumor regions themselves which can be used as predictors.
A Phase II Basket Trial of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) SWOG S1609: Vulvar Cancers
Authors: Young Kwang Chae, Lucy Corthell, Sandip Pravin. Patel, Robert Edwards, Jennifer M. Scalici, Hye Sung Kim, Liam IL-Young Chung, Megan Othus, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock
Journal: Clinical Cancer Research (2024)

Abstract Background: Dual PD-1/CTLA-4 inhibition shows promise in various malignancies. The SWOG S1609 DART trial presents initial results of ipilimumab/nivolumab in vulvar cancers. Methods: DART is a prospective/open-label/multicenter (1,016 US sites)/multi-cohort phase II clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint was objective response rate [ORR, confirmed complete and partial responses (CR and PR, respectively)] per RECISTv1.1; progression-free survival (PFS), overall survival (OS), clinical benefit rate [CBR; overall response plus stable disease (SD) ≥6 months], and toxicity are secondary endpoints. Results: Sixteen evaluable patients (median age, 55.5 years; 0-6 prior therapies; no prior immunotherapy) were analyzed, all of whom had squamous cell carcinoma histology. ORR was 18.8% (3/16), CBR was 25% (4/16), and CBR plus unconfirmed PR rate was 31% (5/16); PFS was 34.1, 16.7. 15.5, 7.2 and 7.0 months for these five patients. The median PFS and OS were 2.2 and 7.6 months. The most common adverse events were diarrhea, fatigue, pruritus, anorexia, and nausea (25%, n=4 each). Grade 3-4 adverse events occurred in 25% of patients (n=4). There was 1 grade 1-2 adverse event (6.7%) that led to discontinuation, and 1 (6.7%) grade 5 death adverse event. Conclusion: Ipilimumab plus nivolumab in vulvar cancers resulted in an objective response in three out of 16 patients, all of whom had durable responses lasting over one year. Notably, two additional patients experienced durable SD and unconfirmed PR. Correlative studies to determine response and resistance markers are ongoing.
Preclinical efficacy of CDK7 inhibitor-based combinations against myeloproliferative neoplasms transformed to AML
Authors: Warren Fiskus, Christopher P Mill, Prithviraj Bose, Lucia Masarova, Naveen Pemmaraju, Andrew Dunbar, Christine Birdwell, John A Davis, Kaberi Das, Hanxi Hou, Taghi Manshouri, Antrix Jain, Anna Malovannaya, Kevin Philip, Noor Alhamadani, Alicia Matthews, Katie Lin, Lauren Flores, Sanam Loghavi, Courtney D. DiNardo, Xiaoping Su, Raajit K. Rampal, Kapil N Bhalla
Journal: Blood (2024)
Bivalent CD47 Immunotoxin for Targeted Therapy of T-Cell Acute Lymphoblastic Leukemia
Authors: Jihong Ma, Zhaohui Wang, Danielle Mintzlaff, Huiping Zhang, Rashmi Ramakrishna, Eduardo Davila, Matthew T. Witkowski, M Scott Lucia, Marc S. Schwartz, Elizabeth A. Pomfret, David W. Mathes, Zhirui Wang
Journal: Blood (2024)
Nanobody-based Naturally Selected CD7-Targeted CAR-T Therapy for Acute Myeloid Leukemia
Authors: Peihua Lu, Xian Zhang, Junfang Yang, Jingjing Li, Liyuan Qiu, Meiwei Gong, Hui Wang, Jiaqi Chen, Hongxing Liu, Min Xiong, Ying Liu, Lin Wang
Journal: Blood (2024)
Hormone Receptor Positive HER2-negative/MammaPrint High-2 Breast Cancers Closely Resemble Triple Negative Breast Cancers
Authors: Alejandro Rios-Hoyo, Kaitlyn Xiong, Jiawei Dai, Christina Yau, Michal Marczyk, Rolando Garcia-Milian, Denise M. Wolf, Laura A. Huppert, Rita Nanda, Gillian L. Hirst, Erin F. Cobain, Laura J. van 't Veer, Laura J. Esserman, Lajos Pusztai
Journal: Clinical Cancer Research (2024)

Abstract Purpose: The MammaPrint prognostic assay categorizes breast cancers into high- and low-risk subgroups, and the high-risk group can be further subdivided into high 1 (MP-H1), and very high-risk high-2 (MP/H-2). The aim of this analysis was to assess clinical and molecular differences between the hormone receptor positive/HER2-negative (HR+) MP-H1, -H2, and triple negative (TN) MP-H1 and -H2 cancers. Experimental design: Pre-treatment gene expression data from 742 HER2 negative breast cancers enrolled in the I-SPY2 neoadjuvant trial was used. Prognostic risk categories were assigned using the MammaPrint assay. Transcriptional similarities across the 4 receptor and prognostic groups were assessed using principal component analyses and by identifying differentially expressed genes. We also examined pathologic complete response (pCR) rates and event-free survivals (EFS) by risk group. Results: Principal component analysis showed that HR+/MP-H2 tumors clustered with TN/MP-H2 cancers. Only 125 genes showed differential expression between the HR+/MP-H2 and TN/MP-H2 cancers while 1,465 genes were differentially expressed between HR+/MP-H2 and -H1. Gene set analysis revealed similarly high expression of cell cycle, DNA repair, and immune-infiltration related pathways in HR+/MP-H2 and TN/MP-H2 cancers. HR+/MP-H2 cancers also showed low estrogen receptor (ER)-related gene expression. pCR rates were similarly high in TN/MP-H2 and HR+/MP-H2 cancers (42% vs 30.5%, p=0.11), and MP-H2 cancers with residual cancer had similarly poor EFS regardless of ER status. Conclusions: In conclusion, HR+/MP-H2 cancers closely resemble TN breast cancers in transcriptional and clinical features and benefit from similar treatment strategies.
Coronary Artery Calcium Scores After Prophylactic Premenopausal Bilateral Salpingo-Oophorectomy
Authors: Maarten J Beekman, Lara Terra, Bernadette A M Heemskerk-Gerritsen, Carlijn M van der Aalst, Jeanine E Roeters van Lennep, Marc van Beurden, Helena C van Doorn, Joanne A de Hullu, Eleonora B L van Dorst, Constantijne H Mom, Marian J E Mourits, Brigitte F M Slangen, Annemarieke Bartels-Rutten, Ricardo P J Budde, Miranda M Snoeren, Tim Leiner, Pim A de Jong, Rozemarijn Vliegenthart, R Nils Planken, Casper Mihl, Marleen Vonder, Matthijs Oudkerk, Katja N Gaarenstroom, Jan Willem C Gratama, Klaartje van Engelen, Lizet E van der Kolk, J Margriet Collée, Marijke R Wevers, Margreet G E M Ausems, Lieke P V Berger, Encarna B Gomez Garcia, Christi J van Asperen, Maartje J Hooning, Harry J de Koning, Angela H E M Maas, Flora E van Leeuwen
Journal: JACC CardioOncology (2024)