tbuckley/cabot-search huggingface dataset:
Methodological challenges in the development of endpoints for myelofibrosis clinical trials
Authors: Giovanni Barosi, Ayalew Tefferi, Naseema Gangat, Natasha Szuber, Alessandro Rambaldi, Olatoyosi Odenike, Nicolaus Kröger, Nico Gagelmann, Moshe Talpaz, Hagop Kantarjian, Robert Peter Gale
Journal: The Lancet Haematology (2024)
Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer
Authors: Hui Yang, Jinghui Cheng, Hao Zhuang, Hongchuang Xu, Yinuo Wang, Tingting Zhang, Yinmo Yang, Honggang Qian, Yinying Lu, Feng Han, Lihua Cao, Nanmu Yang, Rong Liu, Xing Yang, Jiangong Zhang, Jianmin Wu, Ning Zhang
Journal: Cancer Cell (2024)

Inter- and intra-tumor heterogeneity is a major hurdle in primary liver cancer (PLC) precision therapy. Here, we establish a PLC biobank, consisting of 399 tumor organoids derived from 144 patients, which recapitulates histopathology and genomic landscape of parental tumors, and is reliable for drug sensitivity screening, as evidenced by both in vivo models and patient response. Integrative analysis dissects PLC heterogeneity, regarding genomic/transcriptomic characteristics and sensitivity to seven clinically relevant drugs, as well as clinical associations. Pharmacogenomic analysis identifies and validates multi-gene expression signatures predicting drug response for better patient stratification. Furthermore, we reveal c-Jun as a major mediator of lenvatinib resistance through JNK and β-catenin signaling. A compound (PKUF-01) comprising moieties of lenvatinib and veratramine (c-Jun inhibitor) is synthesized and screened, exhibiting a marked synergistic effect. Together, our study characterizes the landscape of PLC heterogeneity, develops predictive biomarker panels, and identifies a lenvatinib-resistant mechanism for combination therapy.
Housing assistance among patients with cancer: SEER-Medicare US Department of Housing and Urban Development data linkage
Authors: Craig Evan Pollack, Veronica Garrison, Taylor Johnson, Amanda L Blackford, Bob Banks, William Howe, K Robin Yabroff, Lindsey Enewold
Journal: JNCI Journal of the National Cancer Institute (2024)

Lack of stable, affordable housing is an important social determinant of health. Federal housing assistance may buffer against housing vulnerabilities among low-income households, but research examining the association of housing assistance and cancer care has been limited. We introduce a new linkage of Surveillance, Epidemiology, and End Results (SEER) program-Medicare and US Department of Housing and Urban Development (HUD) administrative data.
Evaluating colonoscopy quality by performing provider type
Authors: Emily Berry, Jeff Hostetter, Joseph Bachtold, Sarah Zamarripa, Keith E Argenbright
Journal: JNCI Journal of the National Cancer Institute (2024)

Colorectal cancer is the third most diagnosed cancer and the second leading cause of cancer death in the United States. Colonoscopy is an essential tool for screening, used as a primary approach and follow-up to an abnormal stool-based colorectal cancer screening result. Colonoscopy quality is often measured with 4 key indicators: bowel preparation, cecal intubation, mean withdrawal time, and adenoma detection. Colonoscopies are most often performed by gastroenterologists (GI), however, in rural and medically underserved areas, non-GI providers often perform colonoscopies. This study aims to evaluate the quality and safety of screening colonoscopies performed by non-GI practitioner, comparing their outcomes with those of GI providers.
Long-Term Effect of Salt Substitution for Cardiovascular Outcomes
Authors: Hannah Greenwood, Katelyn Barnes, Justin Clark, Lauren Ball, Loai Albarqouni
Journal: Annals of Internal Medicine (2024)

Salt substitution is a simple yet increasingly promising strategy to improve cardiovascular outcomes. To evaluate the long-term effects of salt substitution on cardiovascular outcomes. PubMed, EMBASE, Cochrane CENTRAL, and CINAHL searched from inception to 23 August 2023. Trial registries, citation analysis, and hand-search were also done. Randomized controlled trials (RCTs) comparing provision of or advice to use a salt substitute with no intervention or use of regular salt among adults for 6 months or longer in total study duration. Two authors independently screened articles, extracted data, and assessed risk of bias. Primary outcomes include mortality, major cardiovascular events (MACE), and adverse events at 6 months or greater. Secondary and post hoc outcomes include blood pressure, cause-specific mortality, and urinary excretion at 6 months or greater. Random-effects meta-analyses were done and certainty of effect estimates were assessed using GRADE (Grading of Recommendations Assessment, Development and Evaluation). Of the 16 included RCTs, 8 reported on primary outcomes. Most (n = 7 of 8) were done in China or Taiwan, 3 were done in residential facilities, and 7 included populations of older age (average 62 years) and/or with higher-than-average cardiovascular risk. In this population, salt substitute may reduce risk for all-cause mortality (6 RCTs; 27 710 participants; rate ratio [RR], 0.88 [95% CI, 0.82 to 0.93]; low certainty) and cardiovascular mortality (4 RCTs; 25 050 participants; RR, 0.83 [CI, 0.73 to 0.95]; low certainty). Salt substitute may result in a slight reduction in MACE (3 RCTs; 23 215 participants; RR, 0.85 [CI, 0.71 to 1.00]; very low certainty), with very low-certainty evidence of serious adverse events (6 RCTs; 27 995 participants; risk ratio, 1.04 [CI, 0.87 to 1.25]). The evidence base is dominated by a single, large RCT. Most RCTs were from China or Taiwan and involved participants with higher-than-average cardiovascular risk; therefore, generalizability to other populations is very limited. Salt substitution may reduce all-cause or cardiovascular mortality, but the evidence for reducing cardiovascular events and for not increasing serious adverse events is uncertain, particularly for a Western population. The certainty of evidence is higher among populations at higher cardiovascular risk and/or following a Chinese diet. National Health and Medical Research Council. (PROSPERO: CRD42022327566).
Renal Intercalated Cell Differentiation and Acid–Base Regulation
Authors: Carsten A. Wagner
Journal: Journal of the American Society of Nephrology (2024)

Department of Physiology, University of Zurich, Zürich, Switzerland Correspondence: Dr. Carsten A. Wagner, email: [email protected] See related article, "Foxp1 is Required for Renal Intercalated Cell Differentiation and Acid–Base Regulation," on pages 532–547.
Screening for Colorectal Cancer
Authors: Swati G. Patel, Jason A. Dominitz
Journal: Annals of Internal Medicine (2024)

Colorectal cancer (CRC) is the second leading cause of cancer death. Screening has been proven to reduce both cancer incidence and cancer-related mortality. Various screening tests are available, each with their own advantages and disadvantages and varying levels of evidence to support their use. Clinicians should offer CRC screening to average-risk persons aged 50 to 75 years; starting screening at age 45 years remains controversial. Screening may be beneficial in select persons aged 76 to 85 years, based on their overall health and screening history. Offering a choice of screening tests or sequentially offering an alternate test for those who do not complete screening can significantly increase participation.
Trends in U.S. Medical Cannabis Registrations, Authorizing Clinicians, and Reasons for Use From 2020 to 2022
Authors: Kevin F. Boehnke, Rachel Sinclair, Felicia Gordon, Avinash Hosanagar, Douglas R. Roehler, Tristin Smith, Brooke Hoots
Journal: Annals of Internal Medicine (2024)

As medical cannabis availability increases, up-to-date trends in medical cannabis licensure can inform clinical policy and care. To describe current trends in medical cannabis licensure in the United States. Ecological study with repeated measures. Publicly available state registry data from 2020 to 2022. People with medical cannabis licenses and clinicians authorizing cannabis licenses in the United States. Total patient volume and prevalence per 10 000 persons in the total population, symptoms or conditions qualifying patients for licensure (that is, patient-reported qualifying conditions), and number of authorizing clinicians. In 2022, of 39 jurisdictions allowing medical cannabis use, 34 reported patient numbers, 19 reported patient-reported qualifying conditions, and 29 reported authorizing clinician numbers. Enrolled patients increased 33.3% from 2020 (3 099 096) to 2022 (4 132 098), with a corresponding 23.0% increase in the population prevalence of patients (175.0 per 10 000 in 2020 to 215.2 per 10 000 in 2022). However, 13 of 15 jurisdictions with nonmedical adult-use laws had decreased enrollment from 2020 to 2022. The proportion of patient-reported qualifying conditions with substantial or conclusive evidence of therapeutic value decreased from 70.4% (2020) to 53.8% (2022). Chronic pain was the most common patient-reported qualifying condition in 2022 (48.4%), followed by anxiety (14.2%) and posttraumatic stress disorder (13.0%). In 2022, the United States had 29 500 authorizing clinicians (7.7 per 1000 patients), 53.5% of whom were physicians. The most common specialties reported were internal or family medicine (63.4%), physical medicine and rehabilitation (9.1%), and anesthesia or pain (7.9%). Missing data (for example, from California), descriptive analysis, lack of information on individual use patterns, and changing evidence base. Enrollment in medical cannabis programs increased overall but generally decreased in jurisdictions with nonmedical adult-use laws. Use for conditions or symptoms without a strong evidence basis continues to increase. Given these trends, more research is needed to better understand the risks and benefits of medical cannabis. National Institute on Drug Abuse of the National Institutes of Health.
Consent for High–Kidney Donor Profile Index Kidneys
Authors: Peter Stock, Charles Gerard Rickert
Journal: Journal of the American Society of Nephrology (2024)

Division of Transplant Surgery, Department of Surgery, University of California San Francisco, San Francisco, California Correspondence: Dr. Peter Stock, email: [email protected] See related article, "Quantifying the Effect of Consent for High–Kidney Donor Profile Index Deceased Donor Transplants in the United States," on pages 630–641.
Kidney Endothelial Cell Biology in Health and Disease
Authors: Sargis Sedrakyan
Journal: Journal of the American Society of Nephrology (2024)

GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics in Urology, Division of Urology, Saban Research Institute, Children's Hospital Los Angeles (CHLA), Los Angeles, California, and Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, California Correspondence: Dr. Sargis Sedrakyan, email: [email protected] See related articles, "Single-Cell RNA Sequencing Identifies Response of Renal Lymphatic Endothelial Cells to Acute Kidney Injury," and "Integrated Single-Cell Transcriptomic Atlas of Human Kidney Endothelial Cells," on pages 549–565 and 578–593, respectively.
Progressive Resistance Training or Neuromuscular Exercise for Hip Osteoarthritis
Authors: Troels Kjeldsen, Søren T. Skou, Ulrik Dalgas, Lisa U. Tønning, Kim G. Ingwersen, Sara Birch, Pætur M. Holm, Thomas Frydendal, Mette Garval, Claus Varnum, Bo M. Bibby, Inger Mechlenburg
Journal: Annals of Internal Medicine (2024)

Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). However, randomized controlled trials providing evidence for the optimal exercise type are lacking.
How Would You Manage HIV Pre-exposure Prophylaxis in This Patient With Medical Comorbidities?
Authors: Howard Libman, Douglas Krakower, Jessica L. Taylor, Risa B. Burns
Journal: Annals of Internal Medicine (2024)

Despite advances in treatment, HIV infection remains an important cause of morbidity and mortality, with more than 30 000 new cases diagnosed in the United States each year. There are several interventions traditionally used to prevent HIV transmission, but these vary in effectiveness and there are challenges to their implementation. In 2014, the Centers for Disease Control and Prevention published initial guidance on the use of antiretroviral pre-exposure prophylaxis (PrEP) to prevent transmission of HIV infection in persons at risk based on multiple studies that showed it to be highly efficacious in various populations. It was updated in 2021 to reflect new drug options. The U.S. Preventive Services Task Force also recently updated its recommendations for PrEP, which strongly support its use in persons at risk. Despite its well-established effectiveness, the implementation of PrEP in clinical practice has been variable, especially among populations underserved by the medical system and marginalized by society. Fewer than one third of persons in the United States who are eligible for PrEP currently receive it. Here, 2 physicians experienced in HIV PrEP debate how best to identify patients who might benefit from PrEP, how to decide what regimen to use, and how to monitor therapy.
Equity in Preemptive Kidney Transplantation
Authors: Robert W. Steiner
Journal: Journal of the American Society of Nephrology (2024)

UCSD Center for Transplantation and Division of Nephrology, University of California at San Diego School of Medicine, San Diego, California Correspondence: Dr. Robert W. Steiner, email [email protected] See related article, "Allocation and Utilization Patterns of Deceased Donor Kidneys for Preemptive Transplantation in the United States," on pages 642–645.
Indicated Stress Prevention Addressing Adolescents with High Stress Levels Based on Principles of Acceptance and Commitment Therapy: A Randomized Controlled Trial
Authors: Franziska Binder, Julian Koenig, Franz Resch, Michael Kaess
Journal: Psychotherapy and Psychosomatics (2024)

Stress affects many adolescents and is associated with physical and mental health symptoms that can have a negative impact on normative development. However, there are very few evidence-based, specific treatment approaches. The aim of the study was to investigate an eight-session group intervention using components of Acceptance and Commitment Therapy (ACT) enriched with elements of CBT (psychoeducation, problem solving) and art therapy, compared to a waitlist control (WLC) group, regarding its efficacy in reducing stress and associated symptoms.
Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma
Authors: Emma Kroeze, Ingram Iaccarino, Michelle M Kleisman, Mayukh Mondal, Thomas Beder, Mouhamad Khouja, Marc P Höppner, Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Monika Brüggemann, Claudia D. Baldus, Gunnar Cario, Reno S. Bladergroen, Nathalie Garnier, Andishe Attarbaschi, Jaime Verdu-Amorós, Rosemary Sutton, Elizabeth A. Macintyre, Kenneth Scholten, Laura Arias Padilla, Birgit Burkhardt, Auke Beishuizen, Monique L den Boer, Roland P. Kuiper, Jan L.C. Loeffen, Judith M Boer, Wolfram Klapper
Journal: Blood (2024)
pH‐Triggered Transformable Peptide Nanocarriers Extend Drug Retention for Breast Cancer Combination Therapy
Authors: Xiaomeng Yuan, Xiaoying Liu, Hongjie Li, Shan Peng, Haiqin Huang, Zhe Yu, Limei Chen, Xinlu Liu, Jingkun Bai
Journal: Advanced Healthcare Materials (2024)

Increasing the penetration and accumulation of antitumor drugs at the tumor site are crucial in chemotherapy. Smaller drug-loaded nanoparticles (NPs) typically exhibit increased tumor penetration and more effective permeation through the nuclear membrane, whereas larger drug-loaded NPs show extended retention at the tumor site. In addition, cancer stem cells (CSCs) have unlimited proliferative potential and are crucial for the onset, progression, and metastasis of cancer. Therefore, a drug-loaded amphiphilic peptide, DDP- and ATRA-loaded Pep1 (DA/Pep1), is designed that self-assembles into spherical NPs upon the encapsulation of cis-diamminedichloroplatinum (DDP) and all-trans retinoic acid (ATRA). In an acidic environment, DA/Pep1 transforms into aggregates containing sheet-like structures, which significantly increases drug accumulation at the tumor site, thereby increasing antitumor effects and inhibiting metastasis. Moreover, although DDP treatment can increase the number of CSCs present, ATRA can induce the differentiation of CSCs in breast cancer to increase the therapeutic effect of DDP. In conclusion, this peptide nanodelivery system that transforms in response to the acidic tumor microenvironment is an extremely promising nanoplatform that suggests a new idea for the combined treatment of tumors.
Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure
Authors: Adriana Marton, Seyed Ehsan Saffari, Manfred Rauh, Ruo-Ning Sun, Armin M. Nagel, Peter Linz, Tzy Tiing Lim, Kaoru Takase-Minegishi, Anastacia Pajarillaga, Sharon Saw, Norihiko Morisawa, Wan Keat Yam, Shintaro Minegishi, John J. Totman, Serena Teo, Louis L.Y. Teo, Choon Ta Ng, Kento Kitada, Johannes Wild, Jean-Paul Kovalik, Friedrich C. Luft, Peter J. Greasley, Calvin W.L. Chin, David K.L. Sim, Jens Titze
Journal: Journal of the American College of Cardiology (2024)

Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor–naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51–4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98–3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77–12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: −9.1 mL/kg/d [95% CI: −14 to −4.12; P < 0.001]; late: −11.0 mL/kg/d [95% CI: −15.94 to −6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28–229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: −1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: −3.83 to 5.62]; P = 0.70). Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).
Variation in Health Status With Invasive vs Conservative Management of Chronic Coronary Disease
Authors: Suzanne V. Arnold, Philip G. Jones, David J. Maron, David J. Cohen, Daniel B. Mark, Harmony R. Reynolds, Sripal Bangalore, Jiyan Chen, Jonathan D. Newman, Robert A. Harrington, Gregg W. Stone, Judith S. Hochman, John A. Spertus
Journal: Journal of the American College of Cardiology (2024)
Effectiveness of Clopidogrel vs Alternative P2Y12 Inhibitors Based on the ABCD-GENE Score
Authors: Cameron D. Thomas, Francesco Franchi, Joseph S. Rossi, Ellen C. Keeley, R. David Anderson, Amber L. Beitelshees, Julio D. Duarte, Luis Ortega-Paz, Yan Gong, Richard A. Kerensky, Natasha Kulick, Caitrin W. McDonough, Anh B. Nguyen, Yehua Wang, Marshall Winget, William E. Yang, Julie A. Johnson, Almut G. Winterstein, George A. Stouffer, Dominick J. Angiolillo, Craig R. Lee, Larisa H. Cavallari
Journal: Journal of the American College of Cardiology (2024)
Role of Physiology in the Management of Nonculprit Lesions in Acute Coronary Syndrome
Authors: Vijay Kunadian
Journal: New England Journal of Medicine (2024)

Current international clinical practice guidelines recommend complete revascularization for patients with ST-segment elevation myocardial infarction (STEMI) with multivessel coronary artery disease1 on the basis of evidence from randomized, controlled trials.2 The COMPLETE trial (Complete versus Culprit-Only Revascularization Strategies to Treat Multivessel Disease after Early PCI for STEMI), which included 4041 patients with STEMI, showed a 26% lower risk of death from cardiovascular causes or myocardial infarction and a greater improvement in angina scores after 3 years of follow-up among patients who had been assigned to undergo complete revascularization of angiographically significant nonculprit lesions than among patients who had had no . . .
Efficacy and Safety of Adagrasib plus Cetuximab in Patients with <i>KRAS</i>G12C-Mutated Metastatic Colorectal Cancer
Authors: Rona Yaeger, Nataliya V. Uboha, Meredith S. Pelster, Tanios S. Bekaii-Saab, Minal Barve, Joel Saltzman, Joshua K. Sabari, Julio A. Peguero, Andrew Scott Paulson, Pasi A. Jänne, Marcia Cruz-Correa, Kenna Anderes, Karen Velastegui, Xiaohong Yan, Hirak Der-Torossian, Samuel J. Klempner, Scott E. Kopetz
Journal: Cancer Discovery (2024)

Adagrasib, an irreversible, selective KRASG12C inhibitor, may be an effective treatment in KRASG12C-mutated colorectal cancer, particularly when combined with an anti-EGFR antibody. In this analysis of the KRYSTAL-1 trial, patients with previously treated KRASG12C-mutated unresectable or metastatic colorectal cancer received adagrasib (600 mg twice daily) plus cetuximab. The primary endpoint was objective response rate (ORR) by blinded independent central review. Ninety-four patients received adagrasib plus cetuximab. With a median follow-up of 11.9 months, ORR was 34.0%, disease control rate was 85.1%, and median duration of response was 5.8 months (95% confidence interval [CI], 4.2-7.6). Median progression-free survival was 6.9 months (95% CI, 5.7-7.4) and median overall survival was 15.9 months (95% CI, 11.8-18.8). Treatment-related adverse events (TRAEs) occurred in all patients; grade 3-4 in 27.7% and no grade 5. No TRAEs led to adagrasib discontinuation. Exploratory analyses suggest circulating tumor DNA may identify features of response and acquired resistance.