tbuckley/cabot-search huggingface dataset:
1-Food versus 4-Food Elimination Diet for Pediatric Eosinophilic Esophagitis: A Multi-site Randomized Trial
Authors: Kara L. Kliewer, J. Pablo Abonia, Seema S. Aceves, Dan Atkins, Peter A. Bonis, Kelley E. Capocelli, Mirna Chehade, Margaret H. Collins, Evan S. Dellon, Lin Fei, Glenn T. Furuta, Sandeep K. Gupta, Amir Kagalwalla, John Leung, Sabina Mir, Vincent A. Mukkada, Robbie Pesek, Chen Rosenberg, Tetsuo Shoda, Jonathan M. Spergel, Qin Sun, Joshua B. Wechsler, Guang-Yu Yang, Marc E. Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2024)
Randomized phase 2 dose comparison LITESPARK-013 study of belzutifan in patients with advanced clear cell renal cell carcinoma
Authors: N. Agarwal, J. Brugarolas, P. Ghatalia, S. George, J.B. Haanen, H. Gurney, R. Ravilla, A. Van der Veldt, B. Beuselinck, I. Pokataev, B.B.M. Suelmann, M.H. Tuthill, D. Vaena, F. Zagouri, J. Wu, R.F. Perini, Y. Liu, J. Merchan, M.B. Atkins
Journal: Annals of Oncology (2024)
cIMPACT-NOW update 8: Clarifications on molecular risk parameters and recommendations for WHO grading of meningiomas
Authors: Felix Sahm, Kenneth D Aldape, Priscilla K Brastianos, Daniel J Brat, Sonika Dahiya, Andreas von Deimling, Caterina Giannini, Mark R Gilbert, David N Louis, David R Raleigh, Guido Reifenberger, Sandro Santagata, Chitra Sarkar, Gelareh Zadeh, Pieter Wesseling, Arie Perry
Journal: Neuro-Oncology (2024)

Meningiomas are the most frequent primary intracranial tumors. Hence, they constitute a major share of diagnostic specimens in neuropathology practice. The 2021 WHO Classification of Central Nervous System Tumors ("CNS5") has introduced the first molecular grading parameters for meningioma with oncogenic variants in the TERT promoter and homozygous deletion of CDKN2A/B as markers for CNS WHO grade 3. However, after the publication of the new classification volume, clarifications were requested, not only on novel but also on long-standing questions in meningioma grading that were beyond the scope of the WHO "blue book." In addition, more recent research into possible new molecular grading parameters could not yet be implemented in the 2021 classification but constitutes a compelling body of literature. Hence, the consortium to inform molecular and practical approaches to CNS tumor taxonomy-not official WHO (cIMPACT-NOW) Steering Committee convened a working group to provide such clarification and assess the evidence of possible novel molecular criteria. As a result, this cIMPACT-NOW update provides guidance for more standardized morphological evaluation and interpretation, most prominently pertaining to brain invasion, identifies scenarios in which advanced molecular testing is recommended, proposes to assign CNS WHO grade 2 for cases with CNS WHO grade 1 morphology but chromosomal arm 1p deletion in combination with 22q deletion and/or NF2 oncogenic variants, and discusses areas in which the current evidence is not yet sufficient to result in new recommendations.
Programmed death receptor (PD-)1/PD-ligand (L)1 in urological cancers : the “all-around warrior” in immunotherapy
Authors: Qiang Liu, Yujing Guan, Shenglong Li
Journal: Molecular Cancer (2024)

Programmed death receptor-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1) are essential molecules that are key in modulating immune responses. PD-L1 is constitutively expressed on various immune cells, epithelial cells, and cancer cells, where it functions as a co-stimulatory molecule capable of impairing T-cell mediated immune responses. Upon binding to PD-1 on activated T-cells, the PD-1/PD-L1 interaction triggers signaling pathways that can induce T-cell apoptosis or anergy, thereby facilitating the immune escape of tumors. In urological cancers, including bladder cancer (BCa), renal cell carcinoma (RCC), and prostate cancer (PCa), the upregulation of PD-L1 has been demonstrated. It is linked to poor prognosis and enhanced tumor immune evasion. Recent studies have highlighted the significant role of the PD-1/PD-L1 axis in the immune escape mechanisms of urological cancers. The interaction between PD-L1 and PD-1 on T-cells further contributes to immunosuppression by inhibiting T-cell activation and proliferation. Clinical applications of PD-1/PD-L1 checkpoint inhibitors have shown promising efficacy in treating advanced urological cancers, significantly improving patient outcomes. However, resistance to these therapies, either intrinsic or acquired, remains a significant challenge. This review aims to provide a comprehensive overview of the role of the PD-1/PD-L1 signaling pathway in urological cancers. We summarize the regulatory mechanism underlying PD-1 and PD-L1 expression and activity, including genetic, epigenetic, post-transcriptional, and post-translational modifications. Additionally, we discuss current clinical research on PD-1/PD-L1 inhibitors, their therapeutic potential, and the challenges associated with resistance. Understanding these mechanisms is crucial for developing new strategies to overcome therapeutic limitations and enhance the efficacy of cancer immunotherapy.
Integrating injury prevention into the planetary health agenda: a vital opportunity
Authors: Jagnoor Jagnoor, Kent Buse
Journal: BMJ (2024)

The injury prevention community has much to gain from more systematically considering how it might integrate its agenda into the climate and health agendas. To do so, it will need to find and exploit existing entry points, argue <b>Jagnoor Jagnoor</b> and <b>Kent Buse</b>
Clinical Implications of Basic Research: Exploring the Transformative Potential of Spatial 'Omics in Uro-oncology
Authors: Sandy Figiel, Anthony Bates, David A. Braun, Renu Eapen, Markus Eckstein, Brandon J. Manley, Matthew I. Milowsky, Tom J. Mitchell, Richard J. Bryant, John P. Sfakianos, Alastair D. Lamb
Journal: European Urology (2024)

New spatial molecular technologies are poised to transform our understanding and treatment of urological cancers. By mapping the spatial molecular architecture of tumours, these platforms uncover the complex heterogeneity within and around individual malignancies, offering novel insights into disease development, progression, diagnosis, and treatment. They enable tracking of clonal phylogenetics in situ and immune-cell interactions in the tumour microenvironment. A whole transcriptome/genome/proteome-level spatial analysis is hypothesis generating, particularly in the areas of risk stratification and precision medicine. Current challenges include reagent costs, harmonisation of protocols, and computational demands. Nonetheless, the evolving landscape of the technology and evolving machine learning applications have the potential to overcome these barriers, pushing towards a future of personalised cancer therapy, leveraging detailed spatial cellular and molecular data. Tumours are complex and contain many different components. Although we have been able to observe some of these differences visually under the microscope, until recently, we have not been able to observe the genetic changes that underpin cancer development. Scientists are now able to explore molecular/genetic differences using approaches such as "spatial transcriptomics" and "spatial proteomics", which allow them to see genetic and cellular variation across a region of normal and cancerous tissue without destroying the tissue architecture. Currently, these technologies are limited by high associated costs, and a need for powerful and complex computational analysis workflows. Future advancements and results through these new technologies may assist patients and their doctors as they make decisions about treating their cancer.
Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial
Authors: Matthew C Choy, Christopher F D Li Wai Suen, Danny Con, Kristy Boyd, Raquel Pena, Kathryn Burrell, Ourania Rosella, David Proud, Richard Brouwer, Alexandra Gorelik, Danny Liew, William R Connell, Emily K Wright, Kirstin M Taylor, Aviv Pudipeddi, Michelle Sawers, Britt Christensen, Watson Ng, Jakob Begun, Graham Radford-Smith, Mayur Garg, Neal Martin, Daniel R van Langenberg, Nik S Ding, Lauren Beswick, Rupert W Leong, Miles P Sparrow, Peter De Cruz
Journal: The Lancet. Gastroenterology & hepatology (2024)
Combinations of immunomodulatory agents for prevention of uveitis relapse in patients with severe Behçet's disease already on corticosteroid therapy: a randomised, open-label, head-to-head trial
Authors: Zhenyu Zhong, Dan Deng, Yu Gao, Qingqing Bu, Lingyu Dai, Xiaojie Feng, Chong Tang, Xiang Luo, Yao Wang, Chunjiang Zhou, Guannan Su, Peizeng Yang
Journal: The Lancet Rheumatology (2024)
Effect of timing of casirivimab and imdevimab administration relative to mRNA-1273 COVID-19 vaccination on vaccine-induced SARS-CoV-2 neutralising antibody responses: a prospective, open-label, phase 2, randomised controlled trial
Authors: Flonza Isa, Ana M Gonzalez Ortiz, Jonathan Meyer, Jennifer D Hamilton, Benjamin A Olenchock, Taylor Brackin, Samit Ganguly, Eduardo Forleo-Neto, Lori Faria, Ingeborg Heirman, Mary Marovich, Julia Hutter, Laura Polakowski, Susan C Irvin, Mazhar Thakur, Andrea T Hooper, Alina Baum, Christopher D Petro, Faisal A Fakih, M Juliana McElrath, Stephen C De Rosa, Kristen W Cohen, LaTonya D Williams, Caleb A Hellman, Ahmad J Odeh, Aloki H Patel, Georgia D Tomaras, Gregory P Geba, Christos A Kyratsous, Bret Musser, George D Yancopoulos, Gary A Herman
Journal: The Lancet Infectious Diseases (2024)
Liver-targeting chimeras as a potential modality for the treatment of liver diseases
Authors: Chuanjie Chen, Yongzhang Pan, Xiaoyu Yang, Huiqin Li, Xinhui Cai, Shengyuan He, Qiong Wang, Yiwen Yang, Runzi Zheng, Huiwen Li, Shengjie Yuan, Xin Dong, Priyadarshani Nadeeshika Samarawickrama, Meiting Zi, Yonghan He, Xuan Zhang
Journal: Journal of Controlled Release (2024)
Dynamic peripheral T-cell analysis identifies on-treatment prognostic biomarkers of atezolizumab plus bevacizumab in hepatocellular carcinoma
Authors: Ji Won Han, Min Woo Kang, Soon Kyu Lee, Hyun Yang, Ji Hoon Kim, Jae-Sung Yoo, Hee Sun Cho, Eun Ji Jang, Deok Hwa Seo, Jung Hyun Kwon, Soon Woo Nam, Si Hyun Bae, Jeong Won Jang, Jong Young Choi, Seung Kew Yoon, Pil Soo Sung
Journal: Liver Cancer (2024)

Introduction: Variability in response to atezolizumab plus bevacizumab (AB) treatment of hepatocellular carcinoma (HCC) underscores the critical need for the development of effective biomarkers. We sought to identify peripheral blood biomarkers reflecting response to AB treatment. Methods: We analyzed dynamic changes in peripheral blood mononuclear cells from a prospective, multicenter cohort of 65 patients with HCC, using flow cytometry to evaluate the T-cell population before and 3 weeks after the first AB treatment. Results: We found a unique response of the CD8+ T cells in terms of both frequency and phenotype, in contrast to CD4+ T cells and regulatory T cells. Notably, CD8+ T cells showed significant changes in expression of Ki-67 and T-cell immunoreceptors with Ig and ITIM domains (TIGIT). These distinct responses were observed particularly in the programmed cell death receptor-1 (PD-1)+ subpopulation of CD8+ T cells. Interestingly, the baseline differentiation status of PD-1+CD8+ T cells, particularly the central memory T-cell subset, correlated positively with greater proliferation (higher Ki-67 expression) of PD-1+CD8+ T cells after treatment. Moreover, effector memory cells expressing CD45RA correlated negatively with the increase in TIGIT+/PD-1+CD8+ T cells. The increase in TIGIT+/CD8+ T cells was associated with the development of immune-related adverse events, whereas increase in Ki-67+/PD-1+CD8+ T cells was associated with the better objective response rate. Importantly, dynamic shifts of Ki-67+/PD-1+CD8+ T cells and TIGIT+/CD8+ T cells significantly predicted progression-free survival and overall survival, as confirmed by multivariate analysis. Conclusion: These findings highlight the potential of dynamic changes in CD8+ T cells as an on-treatment prognostic biomarker. Our study underscores the value of peripheral blood profiling as a noninvasive and practical method for predicting the clinical outcomes of AB treatment in patients with HCC.
Comparative Performance of Common Fecal Immunochemical Tests
Authors: Barcey T. Levy, Yinghui Xu, Jeanette M. Daly, Richard M. Hoffman, Jeffrey D. Dawson, Navkiran K. Shokar, Marc J. Zuckerman, Jennifer Molokwu, Daniel S. Reuland, Seth D. Crockett
Journal: Annals of Internal Medicine (2024)

Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited.
Comparing Cardiovascular Risk Classification of U.S. Adults According to Pooled Cohort Equations and PREVENT Equations: Cross-Sectional Analysis of the National Health and Nutrition Examination Survey
Authors: Abdul Mannan Khan Minhas, Salim S. Virani, Erin D. Michos, Vijay Nambi, Roger S. Blumenthal, Alexander C. Razavi, Layla Abushamat, Christie M. Ballantyne, Dmitry Abramov
Journal: Annals of Internal Medicine (2024)
Long-Term Effects of Individualized Acupuncture for Chronic Neck Pain
Authors: Ling Zhao, Mingsheng Sun, Zihan Yin, Jin Cui, Ruihui Wang, Laixi Ji, Guoyan Geng, Jiao Chen, Dingjun Cai, Qi Liu, Hui Zheng, Fanrong Liang
Journal: Annals of Internal Medicine (2024)

Long-term effects of individualized acupuncture in persons with chronic neck pain (CNP) remain unknown.
In persons smoking after 6 wk of varenicline or combined NRT, increasing dose or switching combined NRT to varenicline increased cessation
Authors: Lenard I. Lesser
Journal: Annals of Internal Medicine (2024)

Source CitationCinciripini PM, Green CE, Shete S, et al. Smoking cessation after initial treatment failure with varenicline or nicotine replacement: a randomized clinical trial. JAMA. 2024;331:1722-1731. https://pubmed.ncbi.nlm.nih.gov/38696203/AbstractClinical Impact RatingsGIM/FP/GP: Public Health:
Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort
Authors: Diana L. Miglioretti, Linn Abraham, Brian L. Sprague, Christoph I. Lee, Michael C.S. Bissell, Thao-Quyen H. Ho, Erin J.A. Bowles, Louise M. Henderson, Rebecca A. Hubbard, Anna N.A. Tosteson, Karla Kerlikowske
Journal: Annals of Internal Medicine (2024)

False-positive results on screening mammography may affect women's willingness to return for future screening.
In sepsis, continuous and intermittent infusion of β-lactam antibiotics did not differ for mortality at 90 d
Authors: Morgan K. Walker, Jeffrey R. Strich
Journal: Annals of Internal Medicine (2024)

Source CitationDulhunty JM, Brett SJ, De Waele JJ, et al; BLING III Study Investigators. Continuous vs intermittent β-lactam antibiotic infusions in critically ill patients with sepsis: the BLING III randomized clinical trial. JAMA. 12 June 2024. [Epub ahead of print.] https://pubmed.ncbi.nlm.nih.gov/38864155/AbstractClinical Impact RatingsGIM/FP/GP: Infectious Disease: Critical Care:
In early Parkinson disease, daily subcutaneous lixisenatide reduced motor disability progression at 12 mo
Authors: Joseph H. Friedman
Journal: Annals of Internal Medicine (2024)

Meissner WG, Remy P, Giordana C, et al; LIXIPARK Study Group. Trial of lixisenatide in early Parkinson's disease. N Engl J Med. 2024;390:1176-1185. 38598572.
Vaccine-based immunotherapy and related preclinical models for glioma
Authors: Binghao Zhao, Longping Yao, Maryam Hatami, Wenbin Ma, Thomas Skutella
Journal: Trends in Molecular Medicine (2024)

Due to conflicting interests, Binghao Zhao requested to remove his authorship from the review article. All remaining authors and the editor of Trends in Molecular Medicine have agreed to this correction. This change does not affect the conclusions presented in the article. The authors apologize for any inconvenience this may cause.
Mavacamten in Obstructive Hypertrophic Cardiomyopathy Patients Referred for Septal Reduction
Authors: Milind Y. Desai, Anjali Owens, Kathy Wolski, Jeffrey B. Geske, Sara Saberi, Andrew Wang, Mark Sherrid, Paul C. Cremer, Neal K. Lakdawala, Albree Tower-Rader, David Fermin, Srihari S. Naidu, Nicholas G. Smedira, Hartzell Schaff, Ellen McErlean, Christina Sewell, Yue Zhong, Kathleen W. Wyrwich, Kathy L. Lampl, Amy J. Sehnert, Steven E. Nissen, John A. Spertus
Journal: Journal of the American College of Cardiology (2024)
Association of Postnatal Opioid Exposure and 2-Year Neurodevelopmental Outcomes in Infants Undergoing Cardiac Surgery
Authors: Michael L. O’Byrne, Keith Baxelbaum, Vicky Tam, Heather Griffis, Maryjane L. Pennington, Alyssa Hagerty, Maryam Y. Naim, Susan C. Nicolson, Amanda J. Shillingford, Tori N. Sutherland, Lyla E. Hampton, Nebiat G. Gebregiorgis, Thuyvi Nguyen, Elizabeth Ramos, Joseph W. Rossano
Journal: Journal of the American College of Cardiology (2024)
Prediction of Cumulative Exposure to Atherogenic Lipids During Early Adulthood
Authors: John T. Wilkins, Hongyan Ning, Norrina B. Allen, Alexander Zheutlin, Nilay S. Shah, Matthew J. Feinstein, Amanda M. Perak, Sadiya S. Khan, Ankeet S. Bhatt, Ravi Shah, Venkatesh Murthy, Allan Sniderman, Donald M. Lloyd-Jones
Journal: Journal of the American College of Cardiology (2024)
Triglyceride Levels, Alirocumab Treatment, and Cardiovascular Outcomes After an Acute Coronary Syndrome
Authors: Doron Zahger, Gregory G. Schwartz, Weiming Du, Michael Szarek, Deepak L. Bhatt, Vera A. Bittner, Andrzej J. Budaj, Rafael Diaz, Shaun G. Goodman, J. Wouter Jukema, Robert G. Kiss, Robert A. Harrington, Patrick M. Moriarty, Michel Scemama, Garen Manvelian, Robert Pordy, Harvey D. White, Andreas M. Zeiher, Sergio Fazio, Gregory P. Geba, Ph Gabriel Steg
Journal: Journal of the American College of Cardiology (2024)

It is unknown whether clinical benefit of proprotein convertase subtilisin/kexin type 9 inhibitors is associated with baseline or on-treatment triglyceride concentrations. This study sought to examine relations between triglyceride levels and the effect of alirocumab vs placebo on cardiovascular outcomes using prespecified and post hoc analyses of the ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial. Patients with recent acute coronary syndrome (ACS) (n = 18,924) and elevated atherogenic lipoproteins despite optimized statin therapy were randomized to alirocumab 75 to 150 mg or matching placebo every 2 weeks subcutaneously. Major adverse cardiovascular events (MACE) were examined in relation to continuous or dichotomous triglyceride concentrations. Median baseline triglyceride concentration was 129 mg/dL. In both treatment groups, a 10-mg/dL higher baseline concentration was associated with an adjusted MACE HR of 1.008 (95% CI: 1.003-1.013; P < 0.005). Baseline triglycerides ≥150 vs <150 mg/dL were associated with a HR of 1.184 (95% CI: 1.080-1.297; P < 0.005). Versus placebo, alirocumab reduced low-density lipoprotein cholesterol from baseline (average, 54.7%) and reduced MACE (HR: 0.85; 95% CI: 0.78-0.93). At month 4, triglyceride levels were reduced from baseline by median 17.7 mg/dL (P < 0.001) and 0.9 mg/dL (P = NS) with alirocumab and placebo, respectively. A 10-mg/dL decline from baseline in triglycerides was associated with lower subsequent risk of MACE with placebo (HR: 0.988; 95% CI: 0.982-0.995; P < 0.005) but not with alirocumab (HR: 0.999; 95% CI: 0.987-1.010; P = 0.82). Among patients with recent ACS on optimized statin therapy, baseline triglycerides was associated with cardiovascular risk. However, the reduction in triglycerides with alirocumab did not contribute to its clinical benefit. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)
Mosaic chromosomal alterations in hematopoietic cells and clinical outcomes in patients with multiple myeloma
Authors: Simon Husby, Morten Tulstrup, Mads Harsløf, Christian Nielsen, Eva Haastrup, Lene Hyldahl Ebbesen, Mette Klarskov Andersen, Maroulio Pertesi, Christian Brieghel, Carsten U. Niemann, Björn Nilsson, Agoston Gyula Szabo, Niels Frost Andersen, Niels Abildgaard, Annette Vangsted, Kirsten Grønbæk
Journal: Leukemia (2024)

Abstract Mosaic chromosomal alterations (mCAs) in hematopoietic cells increase mortality and risk of hematological cancers and infections. We investigated the landscape of mCAs and their clinical consequences in 976 patients with multiple myeloma undergoing high-dose chemotherapy and autologous stem cell support (ASCT) with median 6.4 years of follow-up. mCAs were detected in the stem cell harvest product of 158 patients (16.2%). Autosomal aberrations were found in 60 patients (6.1%) and affected all chromosomes. Loss of chromosome X was found in 51 females (12.7%) and loss of chromosome Y in 55 males (9.6%). Overall survival and progression were similar between carriers of autosomal mCAs and non-carriers. In contrast, female patients with loss of the X chromosome had longer overall survival (age-adjusted[a.a.] HR 0.54, 95% CI 0.32–0.93, p = 0.02), lower risk of progression (a.a. HR 0.55, 95% CI 0.35–0.87; p = 0.01), and better post-transplant response (higher degree of complete response (CR) or very good partial response (VGPR)). The reason for this substantial effect is unknown. Additionally, myeloma clones in the stem cell product was confirmed by mCA analysis in the few patients with multiple mCAs ( n = 12 patients). Multiple mCAs conferred inferior overall survival (a.a. HR 2.0, 95% CI 1.02–3.84; p = 0.04) and higher risk of myeloma progression (a.a. HR 3.36, 95% CI 1.67–6.81; p &lt; 0.001), which is presumed to be driven by suspected myeloma contaminants.
Potential for Misapplication of a Uniform vs Sex-Specific High-Sensitivity Cardiac Troponin Threshold
Authors: Amy G. Huebschmann, Nanette K. Wenger, C. Noel Bairey Merz, Allan S. Jaffe, Larry A. Allen, Stacy A. Trent, Judith G. Regensteiner
Journal: Journal of the American College of Cardiology (2024)
A Comprehensive Analysis of Metastatic Disease following Surgery for Clinically Localized Cutaneous Melanoma
Authors: Christina S Boutros, Hanna Kakish, Omkar S Pawar, Alexander W Loftus, John B Ammori, Jeremy Bordeaux, Ankit Mangla, Iris Sheng, Gary Schwartz, Luke D Rothermel, Richard S Hoehn
Journal: JNCI Journal of the National Cancer Institute (2024)

The NCCN considers "baseline staging" (whole body CT or PET scan +/- brain MRI) for all asymptomatic melanoma patients with a positive sentinel lymph node biopsy. The true yield of these workups is unknown.