tbuckley/cabot-search huggingface dataset:
ACE-Breast-02: A pivotal phase II/III trial of ARX788, a novel anti-HER2 antibody-drug conjugate (ADC), versus lapatinib plus capecitabine for HER2+ advanced breast cancer (ABC).
Authors: Xichun Hu, Leiping Wang, Jian Zhang, Qingyuan Zhang, Quchang Ouyang, Xiaojia Wang, Wei Li, Weimin Xie, Zhongsheng Tong, Faliang Xu, Wei Liu, Shushen Wang, Tao Sun
Journal: Journal of Clinical Oncology (2024)

1020 Background: ARX788 is a next-generation ADC of HER2 monoclonal antibody site-specifically conjugated with Amberstatin 269, a potent cytotoxic tubulin inhibitor. Here we report the interim result from this seamless phase II/III trial in patients who progressed on trastuzumab based therapy. Methods: This randomized study was conducted in HER2+ (FISH+ or IHC3+) ABC in 85 centers in China. Patients with unresectable or metastatic breast cancer pretreated with trastuzumab and taxane were randomized 1:1 to receive ARX788 (1.5mg/kg, IV, Q3W) or lapatinib plus capecitabine (LC, lapatinib 1250mg, QD; capecitabine 1000mg/m 2 BID, d1-14, Q3W), stratified by previous chemotherapy lines (0-1 vs. &gt;1) and visceral metastasis (yes vs. no). ARX788 was not pre-medicated with any prophylactic measures. Primary endpoint was progress-free survival (PFS) determined by Independent Review Committee (IRC). Results: As of Dec. 21, 2022, 221 patients were randomly assigned to ARX788 and 220 to LC, and 240 PFS events occurred. Efficacy results are listed in table 1. The median PFS was 11.33 months with ARX788 versus 8.25 months with LC as per IRC (HR 0.64, p=0.0006). Treatment-related adverse events (TRAEs) of any grade occurred in 98.6% (217/220) and 99.1% (213/215) of patients, respectively. TRAEs of grade 3-5 was similar in two groups (41.4% and 40.0%, respectively), commonest being blurred vision (12.3%), dry eye (9.1%), keratopathy (5.9%) and interstitial lung disease (5.9%) with ARX788 and hand-foot syndrome (18.1%), hypokalemia (5.1%), diarrhea (4.2%) with LC. 71 patients (32.3%) had interstitial lung disease with ARX788, primarily grade 1 or 2 (26.8%) with 3 (1.4%) possibly having drug-related deaths. 164 patients (74.5%) had ocular events related to ARX788, primarily grade 1 or 2 (55.5%) with no grade 4 or 5. Conclusions: ARX788 significantly prolonged PFS comparing to LC in patients with HER2+ ABC previously treated with trastuzumab and taxane. While ocular toxicity and interstitial lung disease were common and manageable, its hematological and GI toxicities under no prophylactic premedication compared favorably with already available ADCs. Clinical trial information: CTR20201708. [Table: see text]
Prediction Models for Individualized Treatment Effects of Oxygen Targets
Authors: Hengjia Tu, Yuzhuo Zhang, Zhixuan You
Journal: JAMA (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Contemporary Pediatric Heart Transplant Waitlist Mortality
Authors: Alyssa Power, Kurt R. Sweat, Alvin Roth, John C. Dykes, Beth Kaufman, Michael Ma, Sharon Chen, Seth A. Hollander, Elizabeth Profita, David N. Rosenthal, Lynsey Barkoff, Chiu-Yu Chen, Ryan R. Davies, Christopher S. Almond
Journal: Journal of the American College of Cardiology (2024)
Phase II study of neoadjuvant ipilimumab and nivolumab in combination with paclitaxel following anthracycline-based chemotherapy in patients with treatment resistant stage III triple negative breast cancer (TNBC): BCT1702—Survival results.
Authors: Sherene Loi, Prudence A. Francis, Nicholas Zdenkowski, Val Gebski, Stephen B. Fox, Michelle White, Belinda Emma Kiely, Rina Hui, Andrew David Redfern, Raewyn Calvert, Lauren Rennie, Heath Badger, Frances M. Boyle
Journal: Journal of Clinical Oncology (2024)

608 Background: We examined the efficacy and safety of neoadjuvant ipilimumab and nivolumab combined with paclitaxel following suboptimal response to anthracycline-based chemotherapy in patients with early-stage TNBC. Methods: This single arm phase 2 study enrolled 34 patients at 8 sites. Patients had stage 3 TNBC, after 4 cycles of anthracycline-based therapy, with ≥15mm of tumor remaining or ≥10mm of tumor with ≥1 positive lymph node. A suboptimal response at baseline was defined as &lt;50% reduction in tumor volume after anthracycline-based therapy. Patients received neoadjuvant ipilimumab 1mg/kg IV 6 weekly for 2 doses and nivolumab 240mg every 2 weeks for 6 doses, with weekly paclitaxel at 80mg/m 2 for 12 weeks, followed by surgery. Nivolumab (480mg 4-weekly) continued post operatively for a further 9 months. Primary endpoint was pathological complete response (pCR: ypT0/is, ypN0) in breast and axilla, with secondary endpoints pCR in the suboptimal responders, pCR in PD-L1 positive (≥1% by SP142) or TIL% high (≥30%), event-free (EFS) and overall survival (OS). Results: Between December 2018 and April 2020, 34 patients were enrolled, 33 were evaluable for the primary endpoint. Median age was 46.6yrs. At diagnosis, 97% patients were clinical stage III, 24/34 (70.5%) were clinically node positive, 9/31 (27%) were PD-L1 positive and 6/30 (20%) were TILs% high. At study entry (after anthracycline-based chemo), the median tumor size by ultrasound was 28mm (12-62). The pCR rate was 24.2% (95% CI, 11.09-42.26) in all evaluable, 44.4% [4/9] in PD-L1+ and 9.5% [2/21] in PD-L1- patients. In suboptimal responders, the pCR rate was 25% (95% CI,8.6-49.1) (3/16). At a median follow up of 36.6 months, 9 patients have died. The KM estimates for EFS and OS at 12 months were 96.8% and 93.7%, at 24 months were 84.4% and 84.4% and at 36 months 61.2% and 71.9%, respectively. Patients who achieved a pCR had numerically better EFS (HR 3.61 (0.47-28.2, p=0.2) and OS (HR 2.6 (0.33-21.08); p=0.34). Patients with PD-L1+ tumors vs PD-L1- had a 3-year EFS of 100% vs 52% (p=0.01) and 100% vs 67% OS (p=0.05). Results were similarly favorable for TIL high vs low. Conclusions: The addition of ipilimumab and nivolumab to neoadjuvant chemotherapy resulted in 100% survival for high-risk patients with PD-L1+ and/or TIL% high tumors. Combination CTLA4 and PD-1 targeting agents should be further investigated in Stage 3 TNBC patients. Translational research is ongoing. Clinical trial information: ACTRN12617000651381. [Table: see text]
Active-Duty Sailor Develops PFO-Associated Decompression Sickness
Authors: Tarin C. Phillips, W. Rainey Johnson, Nitin L. Rao, Caroline E. Murphy, Robert M. Gallagher, Sonya N. Waters
Journal: Journal of the American College of Cardiology (2024)

We report a case of an active-duty diver who developed severe decompression sickness with concomitant patent foramen ovale that was successfully closed contrary to standard guideline recommendations. This case should prompt evaluation of the role of cardiac screening in occupational divers, including tactical athletes, relative to recreational divers.
Redirecting B7-H3.CAR T cells to Chemokines Expressed in Osteosarcoma Enhances Homing and Antitumor Activity in Preclinical Models
Authors: Lindsay J. Talbot, Ashley Chabot, Aaron B. Ross, Alexandra Beckett, Phuong Nguyen, Andrew Fleming, Peter J. Chockley, Heather Shepphard, Jian Wang, Stephen Gottschalk, Christopher DeRenzo
Journal: Clinical Cancer Research (2024)

Abstract Purpose: Clinical efficacy of chimeric antigen receptor (CAR) T cells against pediatric osteosarcoma (OS) has been limited. One strategy to improve efficacy may be to drive chemokine-mediated homing of CAR T cells to tumors. We sought to determine the primary chemokines secreted by OS and evaluate the efficacy of B7-H3.CAR T cells expressing the cognate receptors. Experimental Design: We developed a pipeline to identify chemokines secreted by OS by correlating RNA-seq data with chemokine protein detected in media from fresh surgical specimens. We identified CXCR2 and CXCR6 as promising receptors for enhancing CAR T-cell homing against OS. We evaluated the homing kinetics and efficiency of CXCR2- and CXCR6.T cells and homing, cytokine production, and antitumor activity of CXCR2- and CXCR6.B7-H3.CAR T cells in vitro and in vivo. Results: T cells transgenically expressing CXCR2 or CXCR6 exhibited ligand-specific enhanced migration over T cells modified with nonfunctional control receptors. Differential homing kinetics were observed, with CXCR2.T-cell homing quickly and plateauing early, whereas CXCR6.T cells took longer to home but achieved a similar plateau. When expressed in B7-H3.CAR T cells, CXCR2- and CXCR6 modification conferred enhanced homing toward OS in vitro and in vivo. CXCR2- and CXCR6-B7-H3.CAR-treated mice experienced prolonged survival in a metastatic model compared with B7-H3.CAR T-cell-treated mice. Conclusions: Our patient-based pipeline identified targets for chemokine receptor modification of CAR T cells targeting OS. CXCR2 and CXCR6 expression enhanced the homing and anti-OS activity of B7-H3.CAR T cells. These findings support clinical evaluation of CXCR-modified CAR T cells to improve adoptive cell therapy for patients with OS.
scPriorGraph: constructing biosemantic cell–cell graphs with prior gene set selection for cell type identification from scRNA-seq data
Authors: Xiyue Cao, Yu-An Huang, Zhu-Hong You, Xuequn Shang, Lun Hu, Peng-Wei Hu, Zhi-An Huang
Journal: Genome biology (2024)

Cell type identification is an indispensable analytical step in single-cell data analyses. To address the high noise stemming from gene expression data, existing computational methods often overlook the biologically meaningful relationships between genes, opting to reduce all genes to a unified data space. We assume that such relationships can aid in characterizing cell type features and improving cell type recognition accuracy. To this end, we introduce scPriorGraph, a dual-channel graph neural network that integrates multi-level gene biosemantics. Experimental results demonstrate that scPriorGraph effectively aggregates feature values of similar cells using high-quality graphs, achieving state-of-the-art performance in cell type identification.
The Role of Social Workers in Hypertension Care for Black Adults
Authors: Shijie Guo, Zihan Cai
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Efficacy, safety, and predictive biomarkers of dalpiciclib combined with letrozole, pertuzumab and trastuzumab as neoadjuvant therapy in HR+/HER2+ breast cancer: A phase II study.
Authors: Xinrui Liang, Jing Wu, Ningning Zhang, Xiaohua Zeng
Journal: Journal of Clinical Oncology (2024)

e12621 Background: HR+/HER2+ breast cancer is a unique subtype of breast cancer. Between ER and HER2 crosstalk pathways may affect the sensitivity to both HER2-targeted and endocrine therapy in patients with HR+/HER2+ breast cancer. Current therapies for HER2-positive breast cancer have demonstrated limited efficacy in patients with HR+/HER2+ breast cancer. This Phase II trial aimed to assess the efficacy and safety of a neoadjuvant regimen combining trastuzumab, pertuzumab, dalpiciclib (a cyclin dependent kinase 4/6 inhibitor) and letrozole in patients with HR+/HER2+ breast cancer, alongside the exploration of efficacy biomarkers. Methods: Patients were administered six 28-day cycles of dalpiciclib (150 mg once daily on days 1-21) and letrozole (2.5 mg once daily), plus six 21-day cycles of trastuzumab (8 mg/kg loading dose followed by 6 mg/kg maintenance dose on day 1), pertuzumab (840mg loading dose followed by 420mg maintenance dose on day 1), prior to surgery. The primary endpoint was total pathological complete response (tpCR, ypT0/is, ypN0) rate. Secondary endpoints were objective response rate (ORR), breast pathological complete response (bpCR; ypT0/is) rate, change in Ki-67 level from baseline to one cycle of treatment and to surgery, and safety. For biomarkers analysis, next-generation sequencing was performed on pre-treatment tissue and circulating tumor DNA (ctDNA) at various time points before surgery. Results: A total of 14 patients who completed the neoadjuvant treatment and surgery between July 12, 2022 and August 12, 2023 were enrolled. A 50.0% (7 out of 14) tpCR and bpCR rate was observed, with an ORR of 92.9%. Significant reductions in Ki-67 levels were noted after both one ( P&lt;0.05) and six cycles of neoadjuvant therapy ( P&lt;0.05). Grade 4 neutropenia was reported in one case, with no fatalities. The most common grade 3 adverse events were neutropenia (10 [71.4%]) and leukopenia (8 [57.1%]). NGS identified frequent mutations in TP53 (84.6%), PIK3CA (53.8%), and ARID1A (30.8%). Cell cycle pathway gene alterations correlated with a higher pCR rate (80% vs 25%, P=0.103). Eight (61.5%) patients had positive ctDNA at baseline, and ctDNA positivity decreased significantly post-neoadjuvant treatment ( P&lt;0.05). Patients with positive ctDNA at baseline without clearance post-treatment exhibited a trend towards a lower pCR rate. Conclusions: This combination neoadjuvant regimen of dalpiciclib, letrozole, pertuzumab and trastuzumab demonstrated promising pathological responses and manageable safety in patients with HR+/HER2+ breast cancer. The predictive value of genetic alterations and ctDNA status for treatment efficacy warrants further investigation. Clinical trial information: ChiCTR2200062114.
Heightened Vigilance Needed When Patients Are Prescribed GLP-1 and GIP Agonists
Authors: Tyrone A. Johnson, Michael A. Incze, William K. Silverstein
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
MELODY: A prospective non-interventional multicenter cohort study to evaluate different imaging-guided methods for localization of malignant breast lesions (EUBREAST-4/iBRA-NET).
Authors: Maggie Banys-Paluchowski, Thorsten Kuehn, Yazan Masannat, Nina Ditsch, Neslihan Cabioglu, James Harvey, Lina Pankratjevaite, Dawid Murawa, Maria Luisa Gasparri, Guldeniz Karadeniz Cakmak, Michalis Kontos, Mah Muneer Khan, Aoife J Lowery, Lia Pamela Rebaza, Antonio J Esgueva, Achim Rody, Natalia Krawczyk, Steffi Hartmann, Bilge Aktas Sezen, Tove Filtenborg Tvedskov
Journal: Journal of Clinical Oncology (2024)

TPS623 Background: In the last decades, the proportion of breast cancer patients receiving breast-conserving surgery has increased, reaching 70-80% in developed countries. In case of non-palpable lesions, surgical excision requires some form of breast localization. While wire-guided localization has long been considered gold standard, it carries several limitations, including logistical difficulties, the potential for displacement and patient discomfort, and re-excision rates reaching 21%. Other techniques (radioactive seed or radio-occult lesion localization, intraoperative ultrasound, magnetic, radiofrequency, and radar localization) have been developed with the aim of overcoming these disadvantages. However, comparative data on the rates of successful lesion removal, negative margins, and re-operations are limited. In most studies, the patient perspective, addressing e.g. discomfort and pain, has not been evaluated. The aim of MELODY (Methods for Localization of Different Types of Breast Lesions) is to evaluate different imaging-guided localization methods with regard to oncological safety, patient-reported outcomes, and surgeon and radiologist satisfaction. Methods: The EUBREAST and the iBRA-NET have initiated the MELODY study to assess breast localization techniques and devices from several perspectives (NCT05559411, http://eubreast.org/melody ). MELODY is a prospective intergroup cohort study which enrolls female and male patients. planned for breast-conserving surgery with imaging-guided localization for invasive breast cancer or DCIS. Multiple or bilateral lesions and neoadjuvant chemotherapy are allowed. Primary outcomes are: 1) Intended target lesion and/or marker removal and 2) Negative resection margin rates. Secondary outcomes are, among others: rates of second surgery and secondary mastectomy, Resection Ratio (defined as actual resection volume divided by the calculated optimum specimen volume), duration of surgery, marker dislocation rates, rates of marker placement or localization failure, patient-reported outcomes, rates of “lost markers”, radiologist and surgeon satisfaction, and health economic evaluation of the different techniques. Target accrual: 7,416 patients. The study will be conducted in 30 countries. Clinical trial information: NCT05559411 .
Harming Health by Imposing In-Prison Co-Payments
Authors: Benjamin A. Howell, Judith Resnik, Emily A. Wang
Journal: JAMA Internal Medicine (2024)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2024 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
STdGCN: spatial transcriptomic cell-type deconvolution using graph convolutional networks
Authors: Yawei Li, Yuan Luo
Journal: Genome biology (2024)

Spatially resolved transcriptomics integrates high-throughput transcriptome measurements with preserved spatial cellular organization information. However, many technologies cannot reach single-cell resolution. We present STdGCN, a graph model leveraging single-cell RNA sequencing (scRNA-seq) as reference for cell-type deconvolution in spatial transcriptomic (ST) data. STdGCN incorporates expression profiles from scRNA-seq and spatial localization from ST data for deconvolution. Extensive benchmarking on multiple datasets demonstrates that STdGCN outperforms 17 state-of-the-art models. In a human breast cancer Visium dataset, STdGCN delineates stroma, lymphocytes, and cancer cells, aiding tumor microenvironment analysis. In human heart ST data, STdGCN identifies changes in endothelial-cardiomyocyte communications during tissue development.
An In Vitro Model of the Blood–Brain Barrier for the Investigation and Isolation of the Key Drivers of Barriergenesis
Authors: Christina Schofield, Stylianos Sarrigiannidis, Alejandro Moran‐Horowich, Emma Jackson, Aleixandre Rodrigo‐Navarro, Tom van Agtmael, Marco Cantini, Matthew J. Dalby, Manuel Salmeron‐Sanchez
Journal: Advanced Healthcare Materials (2024)

Abstract The blood–brain barrier (BBB) tightly regulates substance transport between the bloodstream and the brain. Models for the study of the physiological processes affecting the BBB, as well as predicting the permeability of therapeutic substances for neurological and neurovascular pathologies, are highly desirable. Existing models, such as Transwell utilizing‐models, do not mimic the extracellular environment of the BBB with their stiff, semipermeable, non‐biodegradable membranes. To help overcome this, we engineered electrospun membranes from poly L‐lactic acid in combination with a nanometric coating of poly(ethyl acrylate) (PEA) that drives fibrillogenesis of fibronectin, facilitating the synergistic presentation of both growth factors and integrin binding sites. Compared to commercial semi‐porous membranes, these membranes significantly improve the expression of BBB‐related proteins in brain endothelial cells. PEA‐coated membranes in combination with different growth factors and extracellular protein coatings reveal nerve growth factor (NGF) and fibroblast growth factor (FGF‐2) caused formation of better barriers in vitro. This BBB model offers a robust platform for studying key biochemical factors influencing barrier formation that marries the simplicity of the Transwell model with the highly tunable electrospun PEA‐fibronectin membranes. This enables the generation of high‐throughput drug permeability models without the need of complicated co‐culture conditions.