tbuckley/cabot-search huggingface dataset:
The Genetic Architecture of Congenital Diarrhea and Enteropathy
Authors: Zeenat Gaibee, Neil Warner, Katlynn Bugda Gwilt, Wenjuan Li, Rei Guan, Michael Yourshaw, Ryder Whittaker Hawkins, Christiane Zorbas, Jonathan St.-Germain, Mahdi Tabatabaie, Suli Mao, Vered Pinsk, Baruch Yerushalmi, Lee-kai Wang, Stanley F. Nelson, Laura Wozniak, Dror S. Shouval, Manar Matar, Amit Assa, Nathaniel Frost, Lissette Jimenez, Sari Acra, Thomas Walters, Stephen Mouat, Michael Li, Denis L.J. Lafontaine, Matthew Tyska, Brian Raught, Yaron Avitzur, Wayne I. Lencer, James R. Goldenring, Martín G. Martín, Jay R. Thiagarajah, Aleixo M. Muise
Journal: New England Journal of Medicine (2025)

Next-generation sequencing has enabled precision therapeutic approaches that have improved the lives of children with rare diseases. Congenital diarrhea and enteropathies (CODEs) are associated with high morbidity and mortality. Although treatment of these disorders is largely supportive, emerging targeted therapies based on genetic diagnoses include specific diets, pharmacologic treatments, and surgical interventions. We analyzed the exomes or genomes of infants with suspected monogenic congenital diarrheal disorders. Using cell and zebrafish models, we tested the effects of variants in newly implicated genes. In our case series of 129 infant probands with suspected monogenic congenital diarrheal disorders, we identified causal variants, including a new founder NEUROG3 variant, in 62 infants (48%). Using cell and zebrafish models, we also uncovered and functionally characterized three novel genes associated with CODEs: GRWD1, MYO1A, and MON1A. We have characterized the broad genetic architecture of CODE disorders in a large case series of patients and identified three novel genes associated with CODEs. (Funded by the National Institutes of Health and others.).
Association between Wealth and Mortality in the United States and Europe
Authors: Sara Machado, Ilias Kyriopoulos, E. John Orav, Irene Papanicolas
Journal: New England Journal of Medicine (2025)

Amid growing wealth disparity, we have little information on how health among older Americans compares with that among older Europeans across the distribution of wealth. We performed a longitudinal, retrospective cohort study involving adults 50 to 85 years of age who were included in the Health and Retirement Study and the Survey of Health, Ageing, and Retirement in Europe between 2010 and 2022. Wealth quartiles were defined according to age group and country, with quartile 1 comprising the poorest participants and quartile 4 the wealthiest. Mortality and Kaplan-Meier curves were estimated for each wealth quartile across the United States and 16 countries in northern and western, southern, and eastern Europe. We used Cox proportional-hazards models that included adjustment for baseline covariates (age group, sex, marital status [ever or never married], educational level [any or no college education], residence [rural or nonrural], current smoking status [smoking or nonsmoking], and absence or presence of a previously diagnosed long-term condition) to quantify the association between wealth quartile and all-cause mortality from 2010 through 2022 (the primary outcome). Among 73,838 adults (mean [±SD] age, 65±9.8 years), a total of 13,802 (18.7%) died during a median follow-up of 10 years. Across all participants, greater wealth was associated with lower mortality, with adjusted hazard ratios for death (quartile 2, 3, or 4 vs. quartile 1) of 0.80 (95% confidence interval [CI], 0.76 to 0.83), 0.68 (95% CI, 0.65 to 0.71), and 0.60 (95% CI, 0.57 to 0.63), respectively. The gap in survival between the top and bottom wealth quartiles was wider in the United States than in Europe. Survival among the participants in the top wealth quartiles in northern and western Europe and southern Europe appeared to be higher than that among the wealthiest Americans. Survival in the wealthiest U.S. quartile appeared to be similar to that in the poorest quartile in northern and western Europe. In cohort studies conducted in the United States and Europe, greater wealth was associated with lower mortality, and the association between wealth and mortality appeared to be more pronounced in the United States than in Europe.
Alteplase for Posterior Circulation Ischemic Stroke at 4.5 to 24 Hours
Authors: Shenqiang Yan, Ying Zhou, Maarten G. Lansberg, David S. Liebeskind, Changzheng Yuan, Han Yu, Fujian Chen, Hongfang Chen, Bing Zhang, Lingqun Mao, Xiaoling Zhang, Xiaona Wang, Xuting Zhang, Yi Chen, Huan Zhou, Wansi Zhong, Yaode He, Kun Chen, Jianbing Wang, Hui Chen, Yuhui Huang, Bruce C.V. Campbell, Min Lou
Journal: New England Journal of Medicine (2025)

The effects and risks of the use of intravenous thrombolysis between 4.5 and 24 hours after the onset of a posterior circulation ischemic stroke are not well studied. In a trial conducted in China, we randomly assigned patients with posterior circulation stroke, without extensive early hypodensity on computed tomography and with no planned thrombectomy, to receive alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg) or standard medical treatment 4.5 to 24 hours after the onset of symptoms. The primary outcome was functional independence (defined as a score of 0 to 2 on the modified Rankin scale; scores range from 0 to 6, with higher scores indicating greater disability) at 90 days. The key safety outcomes were symptomatic intracranial hemorrhage and death. A total of 234 patients were enrolled; 117 were assigned to the alteplase group and 117 to the standard-treatment group. The median score on the National Institutes of Health Stroke Scale was 3 (interquartile range, 2 to 6) (scores range from 0 to 42, with higher scores indicating greater neurologic deficit). A higher percentage of patients in the alteplase group than in the standard-treatment group had functional independence at 90 days (89.6% vs. 72.6%; adjusted risk ratio, 1.16; 95% confidence interval [CI], 1.03 to 1.30; P = 0.01). The incidence of symptomatic intracranial hemorrhage within 36 hours was 1.7% in the alteplase group and 0.9% in the standard-treatment group. At 90 days, 5.2% of the patients in the alteplase group and 8.5% of those in the standard-treatment group had died. Among Chinese patients with mainly mild posterior circulation stroke who did not receive thrombectomy, alteplase administered 4.5 to 24 hours after stroke onset resulted in a higher frequency of functional independence at 90 days than standard medical care. (Funded by the National Natural Science Foundation of China; EXPECTS ClinicalTrials.gov number, NCT05429476.).
Corrigendum to “The multifunctional human ocular melanocortin system” [Prog. Retin. Eye Res. 95 (2023) 1–23 101187]
Authors: Chieh-Lin Stanley Wu, Adrian V Cioanca, Maria C Gelmi, Li Wen, Nick Di Girolamo, Ling Zhu, Riccardo Natoli, R Max Conway, Constantinos Petsoglou, Martine J Jager, Peter J McCluskey, Michele C Madigan
Journal: Progress in Retinal and Eye Research (2025)
PP01.20 Predictive Utility of Circulating Tumor DNA in First- Line Osimertinib Therapy for EGFR-Mutant Metastatic Lung Adenocarcinoma
Authors: Rodrigo Paredes, Toshiro Goto, Shira Litchman, Jorge Gomez, Deborah Doroshow, Fred R. Hirsch, Rajwanth Veluswamy, Thomas Marron, Cardinale Smith, Nicholas Rohs, Christian Rolfo
Journal: Journal of Thoracic Oncology (2025)
PP01.09 Integrin-Linked Kinase Drives Drug-Tolerant Persister Cell Survival and EMT in Response to EGFR Inhibition in Lung Adenocarcinoma
Authors: Rocky Shi, Dylan A. Farnsworth, Christopher A. Febres-Aldana, Justine LM. Chow, Ravinder Sheena, Tejveer Atwal, Juan Luis Gomez Marti, Kiersten N. Thomas, Che-Min Lee, Shannon J. Awrey, Paul C. McDonald, Romel Somwar, Shoukat Dedhar, Marc Ladanyi, Kevin L. Bennewith, William W. Lockwood
Journal: Journal of Thoracic Oncology (2025)
PP01.13 Temporal Immune Evolution in a Murine EML4-ALK NSCLC Model: Genomic, Proteomic, and Drug Co-Culture Characterization
Authors: Marisa E. Aikins, Abdullah Saeed, Derek Nancarrow, Sydney Malawer, Tejas Thiyagarajan, Andrew Yu, Sofia E. Merajver, Kiran Lagisetty
Journal: Journal of Thoracic Oncology (2025)
PP01.17 Neutrophil to Lymphocyte Ratio (NLR) and Platelet to Lymphocyte Ratio (PLR) as Independent Prognostic Markers in EGFR- Tested Advanced Non-small Cell Lung Cancer
Authors: Kijjakom Thanasombunsukh, Sukrit Treewattanawong
Journal: Journal of Thoracic Oncology (2025)
PP01.22 Targeting GTP-Bound KRAS and mTOR in Lung Adenocarcinoma and Squamous Cell Carcinoma Harboring KRAS G12C
Authors: Masaoki Ito, Yoshihiro Miyata, Kenichi Suda, Yasuhiro Tsutani, Morihito Okada
Journal: Journal of Thoracic Oncology (2025)
PP01.02 Potentiating ERK Hyperactivation by Targeting the Proteostasis Network
Authors: Dylan A. Farnsworth, Lok In Josephine Ma, Elise Macdougall, Daniel Lu, Farhana Naznin, Rocky Shi, Katherine Sew, Asha Subramanian, Romel Somwar, Arun M. Unni, William W. Lockwood
Journal: Journal of Thoracic Oncology (2025)
Activating mutations in the MET kinase domain co-occur with other driver oncogenes and mediate resistance to targeted therapy in NSCLC
Authors: Seshiru Nakazawa, Federica Pecci, Biagio Ricciuti, Felix H Gottlieb, Francesco Facchinetti, Guilherme Harada, Monica F Chen, Matteo Repetto, Flavia Giacomini, Jie Jiang, Marie-Anaïs Locquet, Maisam Makarem, Joao V Alessi, Alessandro Di Federico, Mihaela Aldea, Edoardo Garbo, Malini M Gandhi, Arushi Saini, Danielle Haradon, Magda Bahcall, William W Feng, Jessica K Lee, Alexa B Schrock, Alexander Drilon, Mark M Awad, Pasi A Jänne
Journal: Journal of Thoracic Oncology (2025)
PP01.12 Extracellular Matrix Remodeling and Immune Evasion Drive Lung Adenocarcinoma Brain Metastasis
Authors: Manlu Liu, Albert Wang, Jared Brown, Darya Buehler, Saniya Khullar, Christina Kendziorski, Andrew M. Baschnagel, Gopal Iyer
Journal: Journal of Thoracic Oncology (2025)
PP01.08 Pilot Study to Evaluate the Potential of the Tumor-Educated Platelets (TEP) as the Tool to Detect Minimal Residual Disease and Drug Resistance
Authors: Shuta Ohara, Kenichi Suda, Kazuko Sakai, Junko Tanaka, Takamichi Muramatsu, Chihiro Uematsu, Yasuhiro Tsutani, Kazuto Nishio, Tetsuya Mitsudomi
Journal: Journal of Thoracic Oncology (2025)
PP01.10 Dual Targeting of RET and SRC to Treat RET-Positive Non-Small Cell Lung Cancer
Authors: Juhyeon Son, Lily L. Remsing Rix, Bin Fang, Eric A. Welsh, Alexander Drilon, John M. Koomen, Emiliano Cocco, Uwe Rix
Journal: Journal of Thoracic Oncology (2025)
PP01.01 Oncogenic Signaling is Rewired to Support Nucleotide Metabolism in Acquired Resistance to Targeted Therapies in NSCLC
Authors: Jaime L. Schneider, Yutong Dai, Ishita Dhiman, Jingpeng Chen, Shakchhi Joshi, Kiran Kurmi, Morgan Payne, Brandon Gassaway, Steven Gygi, Jessica J. Lin, Aaron Hata, Marcia Haigis
Journal: Journal of Thoracic Oncology (2025)
PP01.03 Characterization of Mutated KRAS Genotype and Clinical Outcomes in Patients With Advanced NSCLC Treated With Mecbotamab Vedotin, a CAB-AXL-ADC
Authors: Julia Rotow, Grace K. Dy, Edwin Yau, Elaine Shum, Mariam Alexander, Karen L. Reckamp, Roland Leung, Dariusz M. Kowalski, Jose Fuentes Pradera, Jon Zugazagoitia Fraile, Kyechin Chen, Kartik Aysola, D. Ross Camidge
Journal: Journal of Thoracic Oncology (2025)
OA05.01 Deep Mutational Scanning Reveals Novel EGFR Mutations Conferring Resistance to Osimertinib and BLU-945
Authors: Dylan Yueyang Wang, Michela Ranieri, Fiona Sherman, Jiehui Deng, Kwok-Kin Wong, Elaine Shum, John T. Poirier
Journal: Journal of Thoracic Oncology (2025)
OA07.01 KRAS Pharmacological Blockade Elicits Tumoral Homologous Recombination Deficiency Exploitable With PARP Inhibitors
Authors: Connor Welch, Gabriela Novoa, Alba Santos, Carlos Vasquez, Alejandra Lagos, Iker Feliu, Irati Macaya, Nerea Bakartxo, Rosario Prados-Carvajal, Alberto Sogari, Pablo Huertas, Alfonso Calvo, Elizabeth Guruceaga, Luis Paz-Ares, Alberto Bardelli, Mariangela Russo, Irene Ferrer, Silve Vicent
Journal: Journal of Thoracic Oncology (2025)
PP01.07 Alterations in Tumor Suppressor Genes are Associated With Aggressive Disease Phenotypes in EGFR-Mutant NSCLC
Authors: Paul Stockhammer, Kieran Sweeney, Stephen V. Liu, Balazs Halmos, Dipesh Uprety, Andrew Elliott, Ari VanderWalde, Katerina Politi, Sarah B. Goldberg, Michael Grant
Journal: Journal of Thoracic Oncology (2025)
OA03.01 Unveiling the Anti-Tumor Activity of Exarafenib in BRAF-Mutated NSCLC Through Genomic Analysis and Combined Preclinical, Clinical Outcomes
Authors: Tadashi Manabe, Tim Sen Wang, Paul Severson, Nichol Miller, Catherine Lee, Elifnur Yay Donderici, Nicole Zhang, Hannah C. Bergo, Yu-ting Chou, Daniel L. Kerr, Wei Wu, Kathryn B. Grandinetti, Liliana Soroceanu, Robert J. Pelham, Eric S. Martin, Eric A. Murphy, Vishesh Khanna, Joel W. Neal, Christopher T. Chen, Shumei Kato, Richard Williams, Trever G. Bivona
Journal: Journal of Thoracic Oncology (2025)
CAR T cell therapy for treatment of Acute Myeloid Leukemia, Advances and Outcomes.
Authors: Malak Khalifeh, Emily Hopewell, Huda Salman
Journal: Molecular Therapy (2025)

Despite recent U.S. FDA approval of multiple therapies for patients with acute myeloid leukemia (AML), clinical outcomes for those patients continue to remain poor. There are very few effective immunotherapeutic modalities such as allogeneic stem cell transplant, SCT, for AML, and this is, in part, due to a lack of known antigens which are unique to AML and not present on vital normal hematopoietic precursors. Additionally, AML is supported by a hostile marrow TME that has a notable role in dampening T cell effector function 1-4. MDSCs and Tregs play a pivotal role in AML microenvironment immune hostility towards endogenous T cells as well as adoptively transferred T cells (ACT). There are many clinical trials that are designed to test the feasibility and efficacy of ACT including Chimeric Antigen Receptor T cell therapies (CAR T cell) in AML, yet none is FDA approved for this fatal disease. In this review, we dissect these trials, their contribution to this therapeutic direction and their success.
PP01.16 Ixazomib Overcomes Platinum Resistance and Induces Autophagy-Mediated Cell Death in Lung Adenocarcinoma
Authors: Muthamil Iniyan Appadurai, Zahraa Wajih Alsafwani, Sanjib Chaudhary, Ashu Shah, Pranay Somavarapu, Sriman N. Dooshety, Ben S. Kubicek, Surinder K. Batra, Imayavaramban Lakshmanan, Apar Kishor Ganti
Journal: Journal of Thoracic Oncology (2025)
OA02.01 Selective Translation of PBK (PDZ-Binding Kinase) is a Novel Mechanism of Drug Tolerance to Targeted Therapies in EGFR-Mutant Lung Cancer
Authors: Camille Léonce, Anne-Laure Desage, Nour El-Houda Mourksi, Geneviève De Souza, Béatrice Vanbervliet, Camille Charrondière, Constance Nicq, Aurélie Swalduz, Gabriel Ichim, Jean-Jacques Diaz, Christine Lovly, Julien Mazières, Mayeul Tabutin, Maurice Pérol, Sylvie Lantuejoul, Olivier Calvayrac, Fabien Forest, Virginie Marcel, Pierre Saintigny, Sandra Ortiz- Cuaran
Journal: Journal of Thoracic Oncology (2025)
PP01.05 Targeting MUC16-Mediated KRASi Resistance in NSCLC
Authors: Ashu Shah, Shamema Salam, Sanjib Chaudhary, Iniyan A. Muthamil, Imayavaramban Lakshmanan, Surinder K. Batra, Apar K. Ganti
Journal: Journal of Thoracic Oncology (2025)
PP01.15 Transcriptional Changes Associated with Tolerance to EGFR Tyrosine Kinase Inhibitors in Mutant EGFR Lung Cancer PDX Models
Authors: Nhu-An Pham, Quan Li, Arundhathi Arivajiagane, Katrina Hueniken, Yoshiaki Inoue, Masashi Mikubo, Ming Li, Ming-Sound Tsao
Journal: Journal of Thoracic Oncology (2025)
PP01.14 Paired Sample Analyses of NSCLC After SCLC Transformation
Authors: Brinda Gupta, Kieran Sweeney, Andrew Elliott, Jennifer Marks, Ari Vanderwalde, Sonam Puri, Misty D. Shields, Jorge J. Nieva, Heloisa P. Soares, Patrick C. Ma, Balazs Halmos, Stephen V. Liu
Journal: Journal of Thoracic Oncology (2025)
Next-Generation Replication-Defective HSV Vectors for Delivery of Large DNA Payloads
Authors: Selene Ingusci, William F Goins, Justus B Cohen, Yoshitaka Miyagawa, David M Knipe, Joseph C Glorioso
Journal: Molecular Therapy (2025)

The application of gene therapy to the treatment of human disease with complex etiology and pathology will often require the delivery of large payloads exceeding 10-kbp in size. This is generally not possible with the most popular vectors such as adeno-associated viruses (AAV), lentiviruses (LV), retroviruses (RV) and many nonviral delivery systems. There is a high likelihood that the correction of many human gene defects such as those associated with neurodegenerative diseases and inflammatory processes, will require single large genes or complex genetic payloads that will often necessitate precise regulatory control of the specificity, timing and duration of corrective gene expression. The regulation of cellular gene products typically depends on genomic promoter systems and splicing-driven transcription variants, necessitating a delivery vector with substantial payload capacity. Replication-defective herpes simplex virus (rdHSV) mutants lack at least one essential viral gene product and are propagated in host cells that supply the missing gene product. This review explores next-generation rdHSV vectors, which do not express viral genes, offer high payload capacity, and can be engineered for safe, long-term transgene expression. These advanced vectors enable the correction of complex diseases affecting neurons and other tissues, paving the way for large or intricate gene replacement strategies.
AAV-Sparcl1 Promotes Hair Cell Regeneration by Increasing Supporting Cell Plasticity
Authors: Nianci Li, Fangzhi Tan, Liyan Zhang, Xiaoqiong Ding, Qiuhan Sun, Man Wang, Ziyu Zhang, Yicheng Lu, Yinyi Zhou, Xiaoyun Qian, Fanglei Ye, Jieyu Qi, Renjie Chai
Journal: Molecular Therapy (2025)
DNA lesions piece together impossible trees
Authors: Claudia Arnedo-Pac, Sarah J Aitken
Journal: Trends in Genetics (2025)

DNA lesions can persist through multiple cell cycles, resulting in mutational strand asymmetry, multiallelic variation, and somatic mosaicism. But for how long do these lesions persist? Recent work from Spencer Chapman et al. shows that they can last for months to years, even arising from endogenous exposures in utero.
The effect of China’s Integrated Medical and Social Care Policy on functional dependency and care deficits in older adults: a nationwide quasi-experimental study
Authors: Wenjian Zhou, Muqi Guo, Bo Hu, Yuling Jiang, Yao Yao
Journal: The Lancet Healthy Longevity (2025)

With population ageing, the development and implementation of pragmatic care strategies for older people with functional dependencies have become critical issues. In alliance with WHO's Integrated Care for Older People framework, China implemented the Integrated Medical and Social Care Policy (IMSCP) in several cities in 2016. This study aims to evaluate whether and to what extent the IMSCP has achieved its primary objectives of reducing functional dependency and addressing care needs in Chinese older adults aged 65 years and older. The IMSCP was initiated in 2016 in several pilot cities from various provinces. We did a quasi-experimental study with a difference-in-differences analysis by using the data collected in the 2014 and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey. Participants from pilot cities constituted the intervention group, whereas participants from non-pilot cities were assigned into the control group. Functional dependency was measured based on activities of daily living and instrumental activities of daily living. Care deficits were recorded for those who were functionally dependent, and for whom care needs were unmet. We used fixed-effects models to examine between-group differences in functional dependency and care deficits. 3080 individuals who participated in both the 2014 and 2018 surveys were included (mean age 81·7 years [SD 9·1] in 2014; 1621 [52·6%] were female and 1459 [47·4%] were male). Of these, 1146 (37·2%) were in the intervention group and 1934 (62·8%) were in the control group. Implementing the IMSCP was associated with a reduced risk of functional dependency (odds ratio [OR] 0·72 [95% CI 0·58-0·89], p=0·0024). Among those who were functionally dependent, the IMSCP was also associated with less care deficits (0·62 [0·41-0·95], p=0·029). We also examined the relatively long-term impact of the IMSCP with duration from 2014 to 2021; the influence of the IMSCP on mitigating functional dependency remained in male participants (OR 0·45 [95% CI 0·23-0·87], p=0·017) but not in female participants (0·85 [0·52-1·39], p=0·524); while its association with bridging care deficits remained among the total participants. Implementing integrated medical and social care policy could reduce the risk of both functional dependency in older adults and care deficits in those who need care. These findings support the continued and expanded implementation of the IMSCP to address the growing care needs of China's ageing population. National Natural Science Foundation of China, National Key Research and Development Project of China, and National Science and Technology Major Project of China.
New models for the development of and access to CAR T-cell therapies for children and adolescents with cancer: an ACCELERATE multistakeholder analysis
Authors: Andrew D J Pearson, Claudia Rossig, Crystal L Mackall, Nirali N Shah, André Baruchel, Sam Daems, John Anderson, Andrea Biondi, Nicholas Bird, Nicole Bodmer, Erica Brivio, Jochen Buechner, Friso G Calkoen, Todd Cooper, Teresa de Rojas, Elizabeth Fox, Rebecca Gardner, Sara Ghorashian, Delphine Heenen, Marianne Ifversen, Elad Jacoby, Manel Juan, Leona Knox, Krishna Komanduri, Jerome Larghero, Franco Locatelli, Donna Ludwinski, Robbie G Majzner, Joe McDonough, Veronique Minard-Colin, Karsten Nysom, Alberto Pappo, Julie R Park, Waseem Qasim, Concetta Quintarelli, Susana Rives, Rayne H Rouce, Nicole Scobie, Christian Seitz, Sarah K Tasian, Brenda Weigel, Susan Weiner, C Michel Zwaan, Gilles Vassal
Journal: The Lancet Oncology (2025)
First-line talazoparib plus enzalutamide versus placebo plus enzalutamide for metastatic castration-resistant prostate cancer: patient-reported outcomes from the randomised, double-blind, placebo-controlled, phase 3 TALAPRO-2 trial
Authors: Nobuaki Matsubara, Arun A Azad, Neeraj Agarwal, Fred Saad, Ugo De Giorgi, Jae Young Joung, Peter C C Fong, Robert J Jones, Stefanie Zschäbitz, Jan Oldenburg, Neal D Shore, Curtis Dunshee, Joan Carles, Andre P Fay, Paul Cislo, Jane Chang, Cynthia G Healy, Alexander Niyazov, Karim Fizazi
Journal: The Lancet Oncology (2025)