tbuckley/cabot-search huggingface dataset:
Ten Americas: a systematic analysis of life expectancy disparities in the USA
Authors: Laura Dwyer-Lindgren, Mathew M Baumann, Zhuochen Li, Yekaterina O Kelly, Chris Schmidt, Chloe Searchinger, Wichada La Motte-Kerr, Thomas J Bollyky, Ali H Mokdad, Christopher Jl Murray
Journal: The Lancet (2024)

Nearly two decades ago, the Eight Americas study offered a novel lens for examining health inequities in the USA by partitioning the US population into eight groups based on geography, race, urbanicity, income per capita, and homicide rate. That study found gaps of 12·8 years for females and 15·4 years for males in life expectancy in 2001 across these eight groups. In this study, we aimed to update and expand the original Eight Americas study, examining trends in life expectancy from 2000 to 2021 for ten Americas (analogues to the original eight, plus two additional groups comprising the US Latino population), by year, sex, and age group.
Perioperative tislelizumab plus neoadjuvant chemotherapy for patients with resectable non-small-cell lung cancer (RATIONALE-315): an interim analysis of a randomised clinical trial
Authors: Dongsheng Yue, Wenxiang Wang, Hongxu Liu, Qixun Chen, Chun Chen, Lunxu Liu, Peng Zhang, Guofang Zhao, Fan Yang, Guang Han, Ying Cheng, Bentong Yu, Yue Yang, Haiquan Chen, Jie Jiang, Lijie Tan, Shidong Xu, Naiquan Mao, Jian Hu, Lanjun Zhang, Bin Yao, Shengfei Wang, Rui-Hua Wang, Wenjuan Zheng, Changli Wang
Journal: The Lancet Respiratory Medicine (2024)
Corrigendum to “Network meta-analysis examining efficacy of components of cognitive behavioural therapy for insomnia’ [Clinical Psychology Review 114 (2024) 102507].
Authors: Lisa Steinmetz, Laura Simon, Bernd Feige, Dieter Riemann, Anna F Johann, Johanna Ell, David D Ebert, Harald Baumeister, Fee Benz, Kai Spiegelhalder
Journal: Clinical Psychology Review (2024)
The co-receptor Neuropilin-1 enhances proliferation in inv(16) acute myeloid leukemia via VEGF signaling
Authors: Mahesh Hegde, Mohd H. Ahmad, Roger Mulet Lazaro, Mayumi Sugita, Rui Li, Kai Hu, Claudia Gebhard, Monica L. Guzman, John H. Bushweller, Lihua J. Zhu, Michael Brehm, Scot A. Wolfe, Ruud Delwel, Lucio H. Castilla
Journal: Leukemia (2024)
JNK1 inhibitors target distal B cell receptor signaling and overcome BTK-inhibitor resistance in CLL
Authors: Shifa Khaja Saleem, Sarah Decker, Sandra Kissel, Marcus Bauer, Dmitry Chernyakov, Daniela Bräuer-Hartmann, Konrad Aumann, Claudia Wickenhauser, Marco Herling, Oleksandra Skorobohatko, Nimitha Mathew, Cornelius Schmidt, Claudius Klein, Marie Follo, Christine Dierks
Journal: The Journal of Experimental Medicine (2024)

Inhibition of the proximal B cell receptor (BCR) signaling pathway by BTK inhibitors is highly effective in the treatment of CLL, but drug resistance or intolerance occurs. Here, we investigated c-Jun N-terminal protein kinase 1 (JNK1) as an alternative drug target in the distal BCR pathway. JNK1 was preferentially overexpressed and activated in poor prognostic CLL with unmutated IGHV. Proximal BCR inhibition (BTK, PI3K, or SYK inhibitors) or SYK knockdown efficiently dephosphorylated JNK1, identifying JNK1 as a critical BCR downstream kinase in CLL. JNK1 inhibition induced apoptosis in primary CLL cells, resulting in the downregulation of BCL2, MCL1, and c-JUN. JNK1 inhibition in patient-derived CLL xenografted mice and Eµ-TCL1-tg mice prevented CLL progression, reduced splenic infiltration, and restored T cell function and normal hematopoiesis. JNK1 inhibitors even remained effective in ibrutinib refractory CLL. In conclusion, our study revealed JNK1 as a promising drug target in CLL downstream of the BCR, overcoming ibrutinib resistance, blocking the protective microenvironment, and improving CLL-specific immunosuppressive mechanisms.
Systematic review to understand users perspectives on AI-enabled decision aids to inform shared decision making
Authors: Nehal Hassan, Robert Slight, Kweku Bimpong, David W. Bates, Daniel Weiand, Akke Vellinga, Graham Morgan, Sarah P. Slight
Journal: npj Digital Medicine (2024)

Abstract Artificial intelligence (AI)-enabled decision aids can contribute to the shared decision-making process between patients and clinicians through personalised recommendations. This systematic review aims to understand users’ perceptions on using AI-enabled decision aids to inform shared decision-making. Four databases were searched. The population, intervention, comparison, outcomes and study design tool was used to formulate eligibility criteria. Titles, abstracts and full texts were independently screened and PRISMA guidelines followed. A narrative synthesis was conducted. Twenty-six articles were included, with AI-enabled decision aids used for screening and prevention, prognosis, and treatment. Patients found the AI-enabled decision aids easy to understand and user-friendly, fostering a sense of ownership and promoting better adherence to recommended treatment. Clinicians expressed concerns about how up-to-date the information was and the potential for over- or under-treatment. Despite users’ positive perceptions, they also acknowledged certain challenges relating to the usage and risk of bias that would need to be addressed. Registration: PROSPERO database: (CRD42020220320)
Development of hyperdiploidy starts at an early age and takes a decade to complete
Authors: Mehmet K. Samur, Anil Aktas Samur, Parth Shah, Joseph Park, Mariateresa Fulciniti, Masood A Shammas, Jill Corre, Kenneth C. Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Nikhil C. Munshi
Journal: Blood (2024)
Serum free light chains in a racially diverse population including African Americans and populations from South Africa
Authors: Luca Bertamini, Jean-Baptiste Alberge, David J. Lee, Habib El-Khoury, Sungjae Kim, Grace Fleming, Ciara Murphy, Julia Colchie, Maya I. Davis, Jacqueline Perry, Elizabeth D. Lightbody, Sabine Allam, Lindokuhle N. Goqwana, Vinitha Philip, Natalie Smyth, Dhananjay Sakrikar, Mark Perkins, Stephen Harding, Derek Troske, Gad Getz, Elizabeth W. Karlson, Nikhil Munshi, Kenneth C. Anderson, Lorenzo Trippa, Catherine R. Marinac, Wenlong C. Chen, Maureen Joffe, Irene M. Ghobrial
Journal: Blood (2024)
Phenotype driven molecular genetic test recommendation for diagnosing pediatric rare disorders
Authors: Fangyi Chen, Priyanka Ahimaz, Quan M. Nguyen, Rachel Lewis, Wendy K. Chung, Casey N. Ta, Katherine M. Szigety, Sarah E. Sheppard, Ian M. Campbell, Kai Wang, Chunhua Weng, Cong Liu
Journal: npj Digital Medicine (2024)

Patients with rare diseases often experience prolonged diagnostic delays. Ordering appropriate genetic tests is crucial yet challenging, especially for general pediatricians without genetic expertise. Recent American College of Medical Genetics (ACMG) guidelines embrace early use of exome sequencing (ES) or genome sequencing (GS) for conditions like congenital anomalies or developmental delays while still recommend gene panels for patients exhibiting strong manifestations of a specific disease. Recognizing the difficulty in navigating these options, we developed a machine learning model trained on 1005 patient records from Columbia University Irving Medical Center to recommend appropriate genetic tests based on the phenotype information. The model achieved a remarkable performance with an AUROC of 0.823 and AUPRC of 0.918, aligning closely with decisions made by genetic specialists, and demonstrated strong generalizability (AUROC:0.77, AUPRC: 0.816) in an external cohort, indicating its potential value for general pediatricians to expedite rare disease diagnosis by enhancing genetic test ordering.
CD70 CAR T cells secreting an anti-CD33/anti-CD3 dual targeting antibody overcome antigen heterogeneity in AML
Authors: Harrison Silva, Grace Martin, Filippo Birocchi, Marc Wehrli, Michael C Kann, Valentina M Supper, Aiyana Parker, Charlotte E Graham, Alexandra Grace Bratt, Amanda A Bouffard, Hannah Donner, Giulia Escobar, Hana N Takei, Alexander Armstrong, Sadie Goncalves, Trisha R Berger, Bryan D. Choi, Marcela V Maus, Mark B Leick
Journal: Blood (2024)
Anaplerotic filling in heart failure: a review of mechanism and potential therapeutics
Authors: Karm A Alhasan, Melissa A King, Badal S B Pattar, Ian A Lewis, Gary D Lopaschuk, Steven C Greenway
Journal: Cardiovascular Research (2024)

Abstract Heart failure (HF) is a complex syndrome and a leading cause of mortality worldwide. While current medical treatment is based on known pathophysiology and is effective for many patients, the underlying cellular mechanisms are poorly understood. Energy deficiency is a characteristic of HF, marked by complex alterations in metabolism. Within the tricarboxylic acid cycle, anaplerosis emerges as an essential metabolic process responsible for replenishing lost intermediates, thereby playing a crucial role in sustaining energy metabolism and consequently cardiac function. Alterations in cardiac anaplerosis are commonly observed in HF, demonstrating potential for therapeutic intervention. This review discusses recent advances in understanding the anaplerotic adaptations that occur in HF. We also explore therapeutics that can directly modulate anaplerosis or are likely to confer cardioprotective effects through anaplerosis, which could potentially be implemented to rescue the failing heart.
Multi-omics Analysis Reveals Molecular Changes During Early Progression of Precancerous Lesions to Lung Adenocarcinoma in Never-Smokers
Authors: Yun-Ching Chen, Chia-Lang Hsu, Hui-Min Wang, Shang-Gin Wu, Yih-Leong Chang, Jin-Shing Chen, Yu-Ching Wu, Yen-Ting Lin, Ching-Yao Yang, Mong-Wei Lin, Jang-Ming Lee, Shuenn-Wen Kuo, Ke-Cheng Chen, Hsao-Hsun Hsu, Pei-Ming Huang, Yen-Lin Huang, Chong-Jen Yu, Mehdi Pirooznia, Bevan E. Huang, Rob Yang, Jin-Yuan Shih, Pan-Chyr Yang
Journal: Cancer Research (2024)

Abstract Lung cancer is the most common cause of cancer mortality globally, and the prevalence of lung adenocarcinoma (LUAD), the most common lung cancer subtype, has increased sharply in East Asia. Early diagnosis leads to better survival rates, but this requires an improved understanding of the molecular changes during early tumorigenesis, particularly in non-smokers. Here, we performed whole exome-sequencing and RNA-sequencing of samples from 94 East Asian patients with precancerous lesions (25 with atypical adenomatous hyperplasia [AAH]; 69 with adenocarcinoma in situ [AIS]) and 73 patients with early invasive lesions (minimally invasive adenocarcinoma [MIA]). Cellular analysis revealed that the activities of endothelial and stromal cells could be used to categorize tumors into molecular subtypes within pathologically defined types of lesions. The subtypes were linked with the radiologically defined type of lesions and corresponded to immune cell infiltration throughout the early progression of LUAD. Spatial transcriptomic analysis revealed the distribution of epithelial cells, endothelial cells, fibroblasts, and plasma cells within MIA samples. Characterization of the molecular lesion subtypes identified positively selected mutational patterns and suggested that angiogenesis in the late-stage AIS type potentially contributes to tissue invasion of the MIA type. This study offers a resource that may help to improve early diagnosis and patient prognosis, and the findings suggest possible approaches for early disease interception.
Cancer-Related Cognitive Impairment and the Potential of Dietary Interventions for the Prevention and Mitigation of Neurodegeneration
Authors: Sylvia L. Crowder, Lisa M. Gudenkauf, Aasha I. Hoogland, Hyo S. Han, Brent J. Small, Tiffany L. Carson, Nathan H. Parker, Margaret Booth-Jones, Heather S.L. Jim
Journal: Cancer Research (2024)

Abstract Approximately 35% of long-term cancer survivors experience ongoing cancer-related cognitive impairment (CRCI). Yet, few efficacious interventions exist to prevent or ameliorate CRCI. The underlying biological processes driving CRCI are complex and are reported to include changes in brain structure and function, increased oxidative stress and inflammation, and alterations in gut microbiome composition. Some of the mechanisms promoting CRCI have the potential to be modified through behavioral changes, such as dietary changes. Compelling evidence from randomized controlled trials and observational research supports the positive impacts of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet on cognition outside of the context of cancer, but studies investigating the MIND diet as an intervention for people who experience CRCI are lacking. This review examines the current state of the science for cognitive outcomes of dietary interventions in aging populations and discusses future opportunities to adapt these interventions to cancer populations.
PTBP1 Lactylation Promotes Glioma Stem Cell Maintenance through PFKFB4-Driven Glycolysis
Authors: Zijian Zhou, Xianyong Yin, Hao Sun, Jiaze Lu, Yuming Li, Yang Fan, Peiwen Lv, Min Han, Jing Wu, Shengjie Li, Zihao Liu, Hongbo Zhao, Haohan Sun, Hao Fan, Shan Wang, Tao Xin
Journal: Cancer Research (2024)

Longstanding evidence implicates glioma stem cells (GSCs) as the major driver for glioma propagation and recurrence. GSCs have a distinctive metabolic landscape characterized by elevated glycolysis. Lactate accumulation resulting from enhanced glycolytic activity can drive lysine lactylation to regulate protein functions, suggesting that elucidating the lactylation landscape in GSCs could provide insights into glioma biology. Herein, we demonstrated that global lactylation was significantly elevated in GSCs compared to differentiated glioma cells (DGCs). PTBP1, a central regulator of RNA processing, was hyperlactylated in GSCs, and SIRT1 induced PTBP1 delactylation. PTBP1-K436 lactylation supported glioma progression and GSC maintenance. Mechanistically, K436 lactylation inhibited PTBP1 proteasomal degradation by attenuating the interaction with TRIM21. Moreover, PTBP1 lactylation enhanced its RNA-binding capacity and facilitated PFKFB4 mRNA stabilization, which further increased glycolysis. Together, these findings uncovered a lactylation-mediated mechanism in GSCs driven by metabolic reprogramming that induces aberrant epigenetic modifications to further stimulate glycolysis, resulting in a vicious cycle to exacerbate tumorigenesis.
Midkine at the Crossroads of Aging and Cancer
Authors: Huiru Bai, Shang Cai
Journal: Cancer Research (2024)

Abstract Aging in mammals, including humans, is marked by a multitude of molecular, cellular, and systemic changes that increase the risk of various diseases, including cancer. While the link between aging and increased cancer incidence is well documented, the precise biological mechanisms driving tumor initiation remain less clear. In a recent issue of Cancer Cell, Yan and colleagues have identified Midkine, a heparin-binding growth factor, as an age-related biomarker mediating both ageing related phenotypes and cancer development. Further exploration of these molecular dynamics, alongside the development of targeted drugs, holds great promise for reducing aging-related cancer incidence.
A Rare Case of Eosinophilic Myocarditis Described With 18F-FDG PET/CT
Authors: Hugo Peslier, Gilles Metrard, Bianca-Angela Malmare, Matthieu Bailly
Journal: Clinical Nuclear Medicine (2024)

Late-stage eosinophilic myocarditis (or Löffler endocarditis) is known to occur in patients with hypereosinophilic syndrome and can cause restrictive cardiomyopathy. Eosinophilic myocarditis is an acute life-threatening inflammatory disease of the heart that can be associated with cancer. We report a case of a 70-year-old White woman, previously treated for diffuse large B-cell lymphoma in remission, admitted for acute dyspnea with a 1-year history of hypereosinophilia. 18F-FDG PET/CT revealed endocardial uptake consistent with MRI gadolinium enhancement, suggesting left ventricular wall inflammation.
The volume-outcome relation for pulmonary endarterectomy in chronic thrombo-embolic pulmonary hypertension
Authors: Samuel Heuts, Michal J. Kawczynski, Arthur Leus, Laurent Godinas, Catharina Belge, Vanessa van Empel, Bart Meyns, Jos G. Maessen, Marion Delcroix, Tom Verbelen
Journal: European Respiratory Journal (2024)

Background We conducted a volume-outcome (V-O) meta-analysis of PEA procedures for chronic thromboembolic pulmonary hypertension (CTEPH), to objectively determine the minimum required annual case load that can define a high-volume centre. Methods Three electronic databases were systematically queried until May 1st, 2024. Centres were divided in volume tertiles (Ts). The primary outcomes were early mortality and long-term survival. Restricted cubic splines were used to demonstrate the V-O relation, and the elbow-method was applied to define high-volume centres. Long-term survival was assessed using Cox-frailty models. Results Fifty-one centres (52 consecutive cohorts) were included and divided in tertiles (T1: &lt;6 cases/year, T2: 6–15 cases/year, T3: &gt;15 cases/year), comprising a total of 11 345 patients (mean age 52.3 years). Overall early mortality was 6.0% (T1: 11.6%, T2: 7.2%, T3: 5.2%, p&lt;0.001), for which a significant non-linear volume-outcome relation was observed (p=0.0437) with a statistically determined minimally required volume of 33 cases/year (95% confidence interval [CI] 29–35 cases), and a modelled volume of 40 cases/year corresponding to a 5.0% mortality rate. Nevertheless, early mortality still progressively declined in higher volume centres (from 6.7% to 5.4% to 2.9% in centres performing 16–50, 51–100, and &gt;100 procedures annually). In addition, a significant effect of volume was observed for long-term survival (adjusted hazard ratio per tertile 0.75, 95%CI 0.63–0.89, p=0.001). Conclusion There is a significant association between procedural volume and early mortality in PEA. An annual procedural volume of &gt;33–40 cases/year may define a high-volume centre, although higher volumes still lead to progressively lower mortality rates.
Eosinophils, mucus plugs, and clinical outcomes: Findings from two COPD cohorts
Authors: Alejandro A. Diaz, Scott Grumley, Andrew Yen, Sushilkumar Sonavane, Rim Elalami, Maya Abdalla, Kangjin Kim, Pietro Nardelli, Sharon Brouha, Padma P. Manapragada, Mostafa Abozeed, Muhammad Usman Aziz, Mohd Zahid, Hrudaya P. Nath, Wei Wang, James C. Ross, Carrie L. Pistenmaa, Raul San José Estépar, Michael H. Cho
Journal: European Respiratory Journal (2024)

<title>Extract</title> Type 2 inflammation (Th2i) —indicated by blood eosinophil counts— and airway-occluding mucus plugs (MPs) on computed tomography (CT) are frequent phenotypes in people with COPD. [1–4] Furthermore, the Th2i pathway involves type 2 helper T cells and epithelial-derived cytokines, such as interleukin (IL-) 33 and thymic stromal lymphopoietin (TSLP), that drive a cascade of events, including eosinophils mobilization and activation in the airways. [5] A persistent Th2i milieu leads to airway structural changes, such as mucus gland hypertrophy, ensuing mucus hypersecretion, and plug formation. [5, 6] Therefore, we tested the hypothesis that high blood eosinophils are associated with airway MPs. We also sought to determine the association of those phenotypes with functional and clinical measures of COPD.
Estimated Effectiveness of Influenza Vaccines in Preventing Secondary Infections in Households
Authors: Carlos G. Grijalva, Huong Q. Nguyen, Yuwei Zhu, Alexandra M. Mellis, Trey McGonigle, Jennifer K. Meece, Jessica E. Biddle, Natasha B. Halasa, Carrie Reed, Alicia M. Fry, Yang Yang, Edward A. Belongia, H. Keipp Talbot, Melissa A. Rolfes
Journal: JAMA Network Open (2024)

Importance Influenza vaccine effectiveness (VE) is commonly assessed against prevention of illness that requires medical attention. Few studies have evaluated VE against secondary influenza infections. Objective To determine the estimated effectiveness of influenza vaccines in preventing secondary infections after influenza was introduced into households. Design, Settings, and Participants During 3 consecutive influenza seasons (2017-2020), primary cases (the first household members with laboratory-confirmed influenza) and their household contacts in Tennessee and Wisconsin were enrolled into a prospective case-ascertained household transmission cohort study. Participants collected daily symptom diaries and nasal swabs for up to 7 days. Data were analyzed from September 2022 to February 2024. Exposures Vaccination history, self-reported and verified through review of medical and registry records. Main Outcomes and Measures Specimens were tested using reverse transcription-polymerase chain reaction to determine influenza infection. Longitudinal chain binomial models were used to estimate secondary infection risk and the effectiveness of influenza vaccines in preventing infection among household contacts overall and by virus type and subtype and/or lineage. Results The analysis included 699 primary cases and 1581 household contacts. The median (IQR) age of the primary cases was 13 (7-38) years, 381 (54.5%) were female, 60 (8.6%) were Hispanic, 46 (6.6%) were non-Hispanic Black, 553 (79.1%) were Non-Hispanic White, and 343 (49.1%) were vaccinated. Among household contacts, the median age was 31 (10-41) years, 833 (52.7%) were female, 116 (7.3%) were Hispanic, 78 (4.9%) were non-Hispanic Black, 1283 (81.2%) were non-Hispanic White, 792 (50.1%) were vaccinated, and 356 (22.5%) had laboratory-confirmed influenza during follow-up. The overall secondary infection risk of influenza among household contacts was 18.8% (95% CI, 15.9% to 22.0%). The risk was highest among children and was 20.3% (95% CI, 16.4% to 24.9%) for influenza A and 15.9% (95% CI, 11.8% to 21.0%) for influenza B. The overall estimated VE for preventing secondary infections among unvaccinated household contacts was 21.0% (95% CI, 1.4% to 36.7%) and varied by type; estimated VE against influenza A was 5.0% (95% CI, −22.3% to 26.3%) and 56.4% (95% CI, 30.1% to 72.8%) against influenza B. Conclusions and Relevance After influenza was introduced into households, the risk of secondary influenza among unvaccinated household contacts was approximately 15% to 20%, and highest among children. Estimated VE varied by influenza type, with demonstrated protection against influenza B virus infection.
More on Waterpipe Tobacco Smoking and Cancer Mortality Content
Authors: Ping-Hao Chiang, Chieh-Hsuan Tsai
Journal: JAMA Oncology (2024)

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A SEER Registry–Based Analysis of Pediatric Colorectal Adenocarcinomas
Authors: Sameh Hany Emile, Nir Horesh, Zoe Garoufalia, Rachel Gefen, Justin Dourado, Steven D. Wexner
Journal: JAMA Oncology (2024)

This cohort study analyzes the characteristics of colorectal cancer in pediatric patients using Surveillance, Epidemiology, and End Results (SEER) registry data.