tbuckley/cabot-search huggingface dataset:
Plasma ctDNA as a treatment response biomarker in metastatic cancers: evaluation by the RECIST working group
Authors: Alexander W. Wyatt, Saskia Litière, Francois-Clement Bidard, Luc Cabel, Lars Dyrskjøt, Chris A. Karlovich, Klaus Pantel, Joan Petrie, Reena Philip, Hillary S. Andrews, Paz J. Vellanki, Sofie H. Tolmeijer, Xenia Villalobos Alberu, Christian Alfano, Jan Bogaerts, Emiliano Calvo, Alice P. Chen, Rodrigo A. Toledo, Elisabeth G. E. de Vries, Lesley Seymour, Scott A. Laurie, Elena Garralda
Journal: Clinical Cancer Research (2024)

Abstract Early indicators of metastatic cancer response to therapy are important for evaluating new drugs and stopping ineffective treatment. The RECIST guidelines based on repeat cancer imaging are widely adopted in clinical trials, are used to identify active regimens that may change practice, and contribute to regulatory approvals. However, these criteria do not provide insight before 6 to 12 weeks of treatment and typically require that patients have measurable disease. Recent data suggest that measuring on-treatment changes in the amount or proportion of ctDNA in peripheral blood plasma may accurately identify responding and nonresponding cancers at earlier time points. Over the past year, the RECIST working group has evaluated current evidence for plasma ctDNA kinetics as a treatment response biomarker in metastatic cancers and early endpoint in clinical trials to identify areas of focus for future research and validation. Here, we outline the requirement for large standardized trial datasets, greater scrutiny of optimal ctDNA collection time points and assay thresholds, and consideration of regulatory body guidelines and patient opinions. In particular, clinically meaningful changes in plasma ctDNA abundance are likely to differ by cancer type and therapy class and must be assessed before ctDNA can be considered a potential pan-cancer response evaluation biomarker. Despite the need for additional data, minimally invasive on-treatment ctDNA measurements hold promise to build upon existing response assessments such as RECIST and offer opportunities for developing novel early endpoints for modern clinical trials.
Increasing power in screening trials by testing control-arm specimens: application to multicancer detection screening
Authors: Hormuzd A Katki, Philip C Prorok, Philip E Castle, Lori M Minasian, Paul F Pinsky
Journal: JNCI Journal of the National Cancer Institute (2024)

Cancer screening trials have required large sample sizes and long time-horizons to demonstrate cancer mortality reductions, the primary goal of cancer screening. We examine assumptions and potential power gains from exploiting information from testing control-arm specimens, which we call the "intended effect" (IE) analysis that we explain in detail herein. The IE analysis is particularly suited to tests that can be conducted on stored specimens in the control arm, such as stored blood for multicancer detection (MCD) tests.
Judy Lieberman: Stay curious and excited about science
Authors: Montserrat Cols
Journal: The Journal of Experimental Medicine (2024)

Judy Lieberman is a professor of pediatrics and adjunct professor of genetics at Harvard Medical School and an endowed chair in cellular and molecular medicine. Her lab studies cytotoxic T lymphocytes (CTL), key cells in the immune defense against viral infection and cancer, as well as molecular pathways activated by the granzymes, and how RNA interference (RNAi) regulates cell differentiation in health and disease states. We spoke to Judy about advice for early career researchers, how she first become interested in cytotoxic T lymphocytes, and key people who have provided mentorship across her career.
ICON 2023: International Scientific Tendinopathy Symposium Consensus – the core outcome set for Achilles tendinopathy (COS-AT) using a systematic review and a Delphi study of professional participants and patients
Authors: Robert-Jan de Vos, Karin Gravare Silbernagel, Peter Malliaras, Tjerk Sleeswijk Visser, Hakan Alfredson, Inge van den Akker-Scheek, Mathijs van Ark, Annelie Brorsson, Ruth Chimenti, Sean Docking, Pernilla Eliasson, Kenneth Farnqvist, Zubair Haleem, Shawn L Hanlon, Jean-Francois Kaux, Rebecca Samantha Kearney, Paul D Kirwan, Kornelia Kulig, Bhavesh Kumar, Trevor Lewis, Umile Giuseppe Longo, Tun Hing Lui, Nicola Maffulli, Adrian James Mallows, Lorenzo Masci, Dennis McGonagle, Dylan Morrissey, Myles Calder Murphy, Richard Newsham-West, Katarina Maria Nilsson-Helander, Richard Norris, Francesco Oliva, Seth O'Neill, Koen Peers, Ebonie Kendra Rio, Igor Sancho, Alex Scott, Kayla D Seymore, Sze-Ee Soh, Patrick Vallance, Jan A N Verhaar, Arco C van der Vlist, Adam Weir, Jennifer Ann Zellers, Bill Vicenzino
Journal: British Journal of Sports Medicine (2024)

To develop a core outcome set for Achilles tendinopathy (COS-AT) for use in clinical trials we performed a five-step process including (1) a systematic review of available outcome measurement instruments, (2) an online survey on truth and feasibility of the available measurement instruments, (3) an assessment of the methodological quality of the selected outcome measurement instruments, (4) an online survey on the outcome measurement instruments as COS and (5) a consensus in-person meeting. Both surveys were completed by healthcare professionals and patients. The Outcome Measures in Rheumatology guidelines with a 70% threshold for consensus were followed. We identified 233 different outcome measurement instruments from 307 included studies; 177 were mapped within the International Scientific Tendinopathy Symposium Consensus core domains. 31 participants (12 patients) completed the first online survey (response rate 94%). 22/177 (12%) outcome measurement instruments were deemed truthful and feasible and their measurement properties were evaluated. 29 participants (12 patients) completed the second online survey (response rate 88%) and three outcome measurement instruments were endorsed: the Victorian Institute of Sports Assessment-Achilles questionnaire, the single-leg heel rise test and evaluating pain after activity using a Visual Analogue Scale (VAS, 0–10). 12 participants (1 patient) attended the final consensus meeting, and 1 additional outcome measurement instrument was endorsed: evaluating pain during activity/loading using a VAS (0–10). It is recommended that the identified COS-AT will be used in future clinical trials evaluating the effectiveness of an intervention. This will facilitate comparing outcomes of intervention strategies, data pooling and further progression of knowledge about AT. As COS-AT is implemented, further evidence on measurement properties of included measures and new outcome measurement instruments should lead to its review and refinement.
Health Warnings on Instagram Advertisements for Synthetic Nicotine E-Cigarettes and Engagement
Authors: Jiaxi Wu, Briana M. Trifiro, Lynsie R. Ranker, Juan Manuel Origgi, Emelia J. Benjamin, Rose Marie Robertson, Aruni Bhatnagar, Andrew C. Stokes, Ziming Xuan, Derry Wijaya, Bryan Plummer, Jennifer Cornacchione Ross, Jessica L. Fetterman, Traci Hong
Journal: JAMA Network Open (2024)

Importance Synthetic nicotine is increasingly used in e-cigarette liquids along with flavors to appeal to youths. Regulatory loopholes have allowed tobacco manufacturers to use social media to target youths. Objective To analyze the extent to which synthetic nicotine e-cigarette brands have implemented US Food and Drug Administration (FDA) health warning requirements and to evaluate the association between health warnings and user engagement on Instagram. Design, Setting, and Participants In this cross-sectional study, posts from 25 brands were analyzed across a 14-month period (August 2021 to October 2022). A content analysis was paired with Warning Label Multi-Layer Image Identification, a computer vision algorithm designed to detect the presence of health warnings and whether the detected health warning complied with FDA guidelines by (1) appearing on the upper portion of the advertisement and (2) occupying at least 20% of the advertisement’s area. Data analysis was performed from March to June 2024. Exposure Synthetic nicotine e-cigarette advertisement on Instagram. Main Outcomes and Measures The outcome variables were user engagement (number of likes and comments). Negative binomial regression analyses were used to evaluate the association between the presence and characteristics of health warnings and user engagement. Results Of a total of 2071 posts, only 263 (13%) complied with both FDA health warning requirements. Among 924 posts with health warnings, 732 (79%) displayed warnings in the upper image portion, and 270 (29%) had a warning covering at least 20% of the pixel area. Posts with warnings received fewer comments than posts without warnings (mean [SD], 1.8 [2.5] vs 5.4 [11.7] comments; adjusted incident rate ratio [aIRR], 0.70; 95% CI, 0.57-0.86; P &amp;amp;lt; .001). For posts containing warnings, a larger percentage of the warning label’s pixel area was associated with fewer comments (aIRR, 0.96; 95% CI, 0.93-0.99; P = .003). Flavored posts with health warnings placed in the upper image portion received more likes than posts with warnings in the lower portion (mean [SD], 34.6 [35.2] vs 19.9 [19.2] likes; aIRR, 1.48; 95% CI, 1.07-2.06; P = .02). Conclusions and Relevance In this cross-sectional study of synthetic nicotine brand Instagram accounts, 87% of sampled posts did not adhere to FDA health warning requirements in tobacco promotions. Enforcement of FDA compliant health warnings on social media may reduce youth engagement with tobacco marketing.
Stimulant, Antidepressant, and Opioid Telehealth Prescription Trends Between 2019 and 2022
Authors: Ashwini Nagappan, Austin Miller, Sanjula Jain, Allison H. Oakes
Journal: JAMA Network Open (2024)

This cross-sectional study examines the rates of in-person and telehealth prescriptions for stimulants, antidepressants, and opioids before and during the COVID-19 pandemic.
Adolescents and Young Adults’ Sources of Contraceptive Information
Authors: Elizabeth Pleasants, Brooke Whitfield, Zoe H. Pleasure, Ci’erra Larsen, Dana Johnson, Riley J. Steiner, Laura D. Lindberg
Journal: JAMA Network Open (2024)

This cross-sectional study examines whether there is an association between adolescents and young adults’ preferred and actual sources of contraceptive information and reporting sufficient contraceptive information.
Kidney Health Monitoring in Neonatal Intensive Care Unit Graduates
Authors: Michelle C. Starr, Matthew W. Harer, Heidi J. Steflik, Stephen Gorga, Namasivayam Ambalavanan, Tara M. Beck, Paulomi M. Chaudhry, Jennifer L. Chmielewski, Marissa J. Defreitas, Dana Y. Fuhrman, Mina Hanna, Catherine Joseph, David M. Kwiatkowski, Catherine D. Krawczeski, Brianna M. Liberio, Shina Menon, Tahagod H. Mohamed, Jennifer A. Rumpel, Keia R. Sanderson, Meredith P. Schuh, Jeffrey L. Segar, Cara L. Slagle, Danielle E. Soranno, Kim T. Vuong, Jennifer R. Charlton, Katja M. Gist, David J. Askenazi, David T. Selewski, Carolyn L. Abitbol, Kaashif A. Ahmad, O.N. Ray Bignall, Paige E. Condit, Amanda B. Deford, Alex Feeney, Matthew C. Gillen, Ronnie Guillet, Jaya S. Isaac, Caroline V. Jackson, Jennifer G. Jetton, Marciana L. Laster, Kathryn J. Lowe, Morgan E. Marcuccilli, Kyle A. Merrill, Emily A. Niemyjski, Evelyn Obregon, Erin R. Rademacher, Evan A. Rajadhyaksha, Kimberly J. Reidy, Samantha R. Schwartz, Emily K. Scott, Kara C. Short, Christine N. Stoops, Namrata Todukar
Journal: JAMA Network Open (2024)

Importance Kidney disease is common in infants admitted to the neonatal intensive care unit (NICU). Despite the risk of chronic kidney disease (CKD) in infants discharged from the NICU, neither evidence- nor expert-based recommendations exist to guide clinical care after discharge. Objective To develop recommendations for risk stratification and kidney health monitoring among infants after discharge from the NICU. Evidence Review At the National Institute of Health–supported Consensus Workshop to Address Kidney Health in Neonatal Intensive Care Unit Graduates meeting conducted in February 2024, a panel of 51 neonatal nephrology experts focused on 3 at-risk groups: (1) preterm infants, (2) critically ill infants with acute kidney injury (AKI), and (3) infants with critical cardiac disease. Using established modified Delphi processes, workgroups derived consensus recommendations. Findings In this modified Delphi consensus statement, the panel developed 10 consensus recommendations, identified gaps in knowledge, and prioritized areas of future research. Principal suggestions include risk stratification at time of hospital discharge, family and clinician education and counseling for subsequent kidney health follow-up, and blood pressure assessment as part of outpatient care. Conclusions and Relevance Preterm infants, critically ill infants with AKI, and infants with critical cardiac disease are at increased risk of CKD. We recommend (1) risk assessment at the time of discharge, (2) clinician and family education, and (3) kidney health assessments based on the degree of risk. Future work should focus on improved risk stratification, identification of early kidney dysfunction, and development of interventions to improve long-term kidney health.
Systemic T-cell activation and interferon-γ activity in indeterminate severe hepatitis (iSH) are reminiscent of hemophagocytic lymphohistiocytosis (HLH): Implications for T-cell and interferon-γ directed therapies.
Authors: Thinh H Nguyen, Prakash Satwani, Deepak Kumar, Urvi Kapoor, Sakshi Malik, Chengyu Prince, Taylor Montminy, Kristi Smiley, Mercedes Martinez, Dana Goldner, Rebecca Marsh, Helen E Remotti, Ladan Fazlollahi, Heather B Rytting, Rene Romero, Shanmuganathan Chandrakasan
Journal: Journal of Allergy and Clinical Immunology (2024)
One-Year Weight Reduction With Semaglutide or Liraglutide in Clinical Practice
Authors: Hamlet Gasoyan, Elizabeth R. Pfoh, Rebecca Schulte, Phuc Le, W. Scott Butsch, Michael B. Rothberg
Journal: JAMA Network Open (2024)

Limited data are available on long-term weight loss achieved with semaglutide or liraglutide for type 2 diabetes (T2D) or obesity in clinical practice.
Alternating Magnetic Fields AMF) and Linezolid Reduce Staphylococcus aureus Biofilm in a Large Animal Implant Model
Authors: Isuru A Somawardana, Bibin Prasad, Walker Kay, Connor Hunt, Jacob Adams, Brooke Kawaguchi, Tyler B Smith, Nicholas Ashton, Varun Sadaphal, John Tepper, Marguerite Monogue, Josue I Ramirez, Olivia D Jones, John M Shelton, Bret M Evers, Rousselle Serge, Christine Pybus, Dustin Williams, Rajiv Chopra, David E Greenberg
Journal: Journal of Infection (2024)
Glycemic and Psychosocial Outcomes of Advanced Hybrid Closed Loop Therapy in Youth With High HbA1c: A Randomized Clinical Trial
Authors: Mary B. Abraham, Grant J. Smith, Julie Dart, Antony Clarke, Keely Bebbington, Janice M. Fairchild, Geoffrey R. Ambler, Fergus J. Cameron, Elizabeth A. Davis, Timothy W. Jones
Journal: Diabetes Care (2024)

OBJECTIVE To determine the efficacy of advanced hybrid closed loop (AHCL) therapy in a high-risk cohort of youth on continuous subcutaneous insulin infusion (CSII) ± continuous glucose monitoring (CGM) with suboptimal glycemia. RESEARCH DESIGN AND METHODS In a 6-month multicenter clinical trial, youth with type 1 diabetes with mean and most recent HbA1c &amp;gt; 8.5% (65 mmol/mol) were randomly assigned 1:1 to AHCL or treatment as usual (CSII ± CGM). The primary outcome was the 24-week between-group difference in HbA1c. Secondary outcomes included CGM metrics from masked CGM and psychological measures (youth-reported problem areas in diabetes [PAID], quality of life, anxiety, depression, and hypoglycemia fear) assessed using validated questionnaires. RESULTS A total of 42 participants were randomized (mean [SD] age 16.2 [2.5] years, HbA1c 9.8 [1.1]% or 84 [12] mmol/mol, PAID score 50.3 [19.8]). At study end, the mean (SD) HbA1c was 8.8 (1.1)% or 73 (12) mmol/mol with AHCL and 9.9 (1.2)% or 85 (13.1) mmol/mol with CSII ± CGM, with mean adjusted group difference of −0.77% (95% CI −1.45 to −0.09) or −8.4 mmol/mol (−15.8 to −1.0); P = 0.027. AHCL increased time in range 70–180 mg/dL (difference 19.1%; 95% CI 11.1 to 27.1), reduced time &amp;gt;180 mg/dL (difference −17.7%; 95% CI −26.6 to −8.8), with no increase in time spent &amp;lt;70 mg/dL (difference −0.8%; 95% CI −2.7 to 0.6). There was no evidence for difference in psychosocial outcomes between the two groups at study end. CONCLUSIONS AHCL should be encouraged in youth with suboptimal glycemia, as AHCL improves glycemia. However, psychological support remains vital, as technology alone may not be able to reduce the burden of diabetes care in this subgroup.
Emergency Department Utilization for Hypertensive Disorders of Pregnancy and Post Partum, 2006-2020
Authors: Courtney Townsel, LeAnn Louis, Chelsie Clark, Leah Mitchell Solomon, Charley Jiang, Martina Caldwell, Erica E. Marsh
Journal: JAMA Network Open (2024)

This cross-sectional study assesses emergency department (ED) admissions for hypertensive disorders of pregnancy and post partum between 2006 and 2020.
Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance
Authors: Adrienne G Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M Tolaney, Aleix Prat
Journal: Nature Reviews Clinical Oncology (2024)
Trastuzumab deruxtecan in HER2-positive advanced breast cancer with or without brain metastases: a phase 3b/4 trial
Authors: Nadia Harbeck, Eva Ciruelos, Guy Jerusalem, Volkmar Müller, Naoki Niikura, Giuseppe Viale, Rupert Bartsch, Christian Kurzeder, Michaela J Higgins, Roisin M Connolly, Sally Baron-Hay, María Gión, Valentina Guarneri, Giampaolo Bianchini, Hans Wildiers, Santiago Escrivá-de-Romaní, Manoj Prahladan, Helen Bridge, Nataliya Kuptsova-Clarkson, Nana Scotto, Sunil Verma, Nancy U Lin
Journal: Nature Medicine (2024)
Temporal Exploration of COPD Phenotypes: Insights from the COPDGene and SPIROMICS Cohorts
Authors: Alexander J. Bell, Sundaresh Ram, Wassim W. Labaki, Susan Murray, Ella A. Kazerooni, Stefanie Galban, Fernando J. Martinez, Charles R. Hatt, Jennifer M Wang, Vladimir Ivanov, Paul McGettigan, Edward Khokhlovich, Enrico Maiorino, Rahul Suryadevara, Adel Boueiz, Peter Castaldi, Evgeny M. Mirkes, Andrei Zinovyev, Alexander N. Gorban, Craig J Galban, MeiLan K. Han
Journal: American Journal of Respiratory and Critical Care Medicine (2024)

Chronic obstructive pulmonary disease (COPD) exhibits considerable progression heterogeneity. We hypothesized that elastic principal graph analysis (EPGA) would identify distinct clinical phenotypes and their longitudinal relationships.
Epigenome reprogramming through H3K27 and H3K4 trimethylation as a resistance mechanism to DNA methylation inhibition in BRAFV600E-mutated colorectal cancer.
Authors: Hey Min Lee, Ajay Kumar. Saw, Van K. Morris, Stefania Napolitano, Christopher Bristow, Sanjana Srinivasan, Michael Peoples, Alexey Sorokin, Preeti Kanikarla Marie, Jonathan Schulz, Anand K. Singh, Christopher Terranova, Oluwadara Coker, Abhinav Jain, Scott Kopetz, Kunal Rai
Journal: Clinical Cancer Research (2024)

Abstract Purpose: BRAFV600E-mutated colorectal cancer (CRC) exhibits a strong correlation with DNA hypermethylation suggesting this subgroup of tumors presents unique epigenomic phenotypes. Nonetheless, 5-azacitidine, which inhibits DNA methyltransferase activity, is not efficacious in BRAFV600E CRC in vivo. Experimental Design: We randomized and treated mice implanted with patient-derived tumor xenografts harboring BRAFV600E mutation with control, 5-azacitidine, vemurafenib (BRAF inhibitor), or the combination. Comprehensive epigenomic profiling was conducted on control and 5-azacitidine-treated tumor samples, including DNA methylation, histone modifications, chromatin accessibility, and gene expression. Combinations of epigenetic agents were explored in preclinical BRAFV600E CRC models. Results: A profound reduction of DNA methylation levels upon 5-azacitidine treatment was confirmed, however, transcriptional repression was not relieved. This study unbiasedly explored the adaptive engagement of other epigenomic modifications upon 5-azacitidine treatment. A loss of histone acetylation and a gain of histone methylations, including H3K27 and H3K4 trimethylation, were observed around these hypomethylated regions suggesting the involvement of polycomb repressive complex (PRC) activity around the genome with loss of DNA methylation, therefore maintaining the repression of key tumor suppressor genes. Combined inhibition of PRC activity through EZH2 inhibitor with 5-azacitidine treatment additively improved efficacies in BRAFV600E CRC cells. Conclusions: In conclusion, DNA hypomethylation by 5-azacitidine exhibits a close association with H3K27me3 and PRC activity in BRAFV600E CRC, and simultaneous blockade of DNMT and EZH2 holds promise as a potential therapeutic strategy for patients with BRAFV600E-mutated CRC.
Androgen Deprivation Therapy Drives a Distinct Immune Phenotype in Localized Prostate Cancer
Authors: Matthew C. Dallos, Aleksandar Z. Obradovic, Patrick McCann, Nivedita Chowdhury, Aditya Pratapa, David H. Aggen, Christopher Gaffney, Karen A. Autio, Renu K. Virk, Angelo M. De Marzo, Emmanuel S. Antonarakis, Howard I. Scher, Charles G. Drake, Dana E. Rathkopf
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Androgen deprivation therapy (ADT) remains the backbone of prostate cancer treatment. Beyond the suppression of testosterone and tumor cell growth, emerging evidence suggests that ADT also modulates the immune tumor microenvironment. However, a more precise understanding of the timing and intricacies of these immunologic shifts is needed. Experimental Design: In this study, we analyzed 49 primary prostate cancers, comparing those surgically removed either without treatment or following treatment with degarelix at 4, 7, and 14 days before surgery. Utilizing next-generation DNA and RNA sequencing and multiplexed immunofluorescence, we examined alterations in immune phenotypes in the presence or absence of ADT. Results: Our findings reveal that ADT rapidly transforms the typically bland prostate tumor microenvironment into an inflamed environment within days. Notably, we observed an increase in activated CD8 T cells along with an increase in suppressive regulatory T cells (Treg). We also found an expansion of the myeloid compartment, particularly proinflammatory M1-like tumor-associated macrophages. Intriguingly, discernable changes which have not previously been described also occurred in tumor cells, including upregulation of antigen presentation by MHC classes I and II and, unexpectedly, a decrease in the “do not eat me” signal CD47. Conclusions: These observations underscore the critical role of timing and disease context in order to optimize the therapeutic efficacy of immune modulators combined with androgen ablation, for which the presurgical neoadjuvant setting may be ideal. Our findings warrant future prospective validation, which is currently underway.