tbuckley/cabot-search huggingface dataset:
Implications of the initial <i>braidwood v. Becerra</i> ruling for colorectal cancer outcomes: a modeling study
Authors: Rosita Van Den Puttelaar, Kewei Sylvia Shi, Robert Smith, Jingxuan Zhao, Margaret Katana Ogongo, Matthias Harlass, Anne I Hahn, Ann G Zauber, K Robin Yabroff, Iris Lansdorp-Vogelaar
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract The Affordable Care Act (ACA) eliminated patient cost-sharing for USPSTF recommended services. However, if the US Court of Appeals for the Fifth Circuit fully upheld a US District Court ruling in Braidwood Management v. Becerra, 666 F. Supp. 3d 613 (N.D. Tex 2023), cost-sharing for USPSTF recommendations made after ACA passage would have been reinstated for over 150 million people. The case could still reinstate cost-sharing for colorectal cancer (CRC) screening for ages 45-49 years and for polyp removal during (diagnostic) colonoscopy across all ages. Using the MISCAN-Colon model, we simulated the potential impact on CRC outcomes, assuming early-onset CRC trends, and lower screening participation. An 8-percentage-points decline in screening participation could increase CRC incidence by 5.1%, and CRC mortality by 9.1%, with slightly lower costs due to increased cost-sharing. Larger decreases in screening participation can result in higher costs from increased incidence and delayed diagnoses.
The impact of increasing temperatures due to climate change on infectious diseases
Authors: Olga Anikeeva, Alana Hansen, Blesson Varghese, Matthew Borg, Ying Zhang, Jianjun Xiang, Peng Bi
Journal: BMJ (2024)

Abstract Global temperatures will continue to rise due to climate change, with high temperature periods expected to increase in intensity, frequency, and duration. Infectious diseases, including vector-borne diseases such as dengue fever and malaria, waterborne diseases such as cholera, and foodborne diseases such as salmonellosis are influenced by temperature and other climatic variables, thus contributing to higher disease burden and associated healthcare costs, particularly in socioeconomically disadvantaged regions. Targeted efforts and investments are therefore needed to support low and middle income countries to prepare for and respond to the increasing infectious disease threats posed by rising temperatures. This can be facilitated by the development and refinement of robust disease and entomological surveillance and early warning systems with integration of climatic information that promote enhanced understanding of the geographic distribution of disease risk. To enhance healthcare workforce capacity and capability to respond to these public health threats, medical curricula and continuing professional education programmes for healthcare providers must include evidence based components on the impacts of climate change on infectious diseases.
Esophageal Inflammatory Pseudotumor on Al18F-FAPI-74 and 18F-FDG PET/CT
Authors: Xin Cheng, Guozhu Hou, Rong Zheng, Yong Li, Xuejuan Wang
Journal: Clinical Nuclear Medicine (2024)

Abstract A 25-year-old woman experiencing dysphagia for 2 years underwent 18 F-FDG and Al 18 F-FAPI-74 PET/CT. The scans showed local thickening of the cervical and upper thoracic esophageal wall with several calcifications, accompanied by increased and heterogeneous FDG uptake and more intense FAPI activity. Histopathological analysis following thoracoscopic esophagectomy confirmed the diagnosis of esophageal inflammatory pseudotumor.
“Cancer Integrin” αvβ6 Imaging With 68Ga-Trivehexin PET/CT in Assessment of Ovarian Carcinoma
Authors: Parneet Singh, Kanhaiyalal Agrawal, Ralph Emerson, Abhinav Baranwal, P Sai Sradha Patro, Girish Kumar Parida
Journal: Clinical Nuclear Medicine (2024)

Abstract Peritoneal cancer index is an integral parameter for preoperative assessment of peritoneal disease. Current imaging modalities including 18 F-FDG PET/CT, though superior to CT, underestimate the disease extent, mainly due to its high physiological background activity. Novel “cancer integrin” targeting imaging with 68 Ga-trivehexin demonstrates limited physiological activity in the abdomen with superior target-to-background ratio than 18 F-FDG PET/CT. Thus, we describe the first case demonstrating potential utility of novel “cancer integrin” αvβ6 imaging agent 68 Ga-trivehexin for assessment of disease burden in advanced epithelial ovarian cancer.
Tumor Lysis Syndrome Following PSMA Radioligand Therapy
Authors: Pegah Sahafi, Michael Saeed, Mohammad Hadi Samadi, Kamran Aryana, Emran Askari
Journal: Clinical Nuclear Medicine (2024)

Tumor lysis syndrome (TLS) is a rare complication following treatment in prostate cancer patients. We present a 65-year-old man with history of castration-resistant prostate cancer who developed TLS following 2 sessions of 177 Lu-PSMA therapy. The patient presented with bulky axillary and mediastinal lymphadenopathies, an unusual site for prostate cancer metastasis. Although his PSA levels declined following treatment, he reported excessive weakness leading to immobility. Laboratory correlation showed markedly increased lactate dehydrogenase, from 413 to 543,000 U/L, suggesting the occurrence of TLS. Although being considered a relatively safe treatment, 177 Lu-PSMA can sometime lead to life-threatening events, which is reviewed here.
Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma
Authors: Surbhi Sidana, Krina K. Patel, Lauren C Peres, Radhika Bansal, Mehmet Hakan Kocoglu, Leyla Shune, Shebli Atrash, Kinaya Smith, Shonali Midha, Christopher J Ferreri, Binod Dhakal, Danai Dima, Patrick Costello, Charlotte Wagner, Ran Reshef, Hitomi Hosoya, Lekha Mikkilineni, Djordje Atanackovic, Saurabh Chhabra, Ricardo D Parrondo, Omar Nadeem, Hashim Mann, Nilesh Kalariya, Vanna Hovanky, Gabriel DeAvila, Ciara L Freeman, Frederick L Locke, Melissa Alsina, Sandy Wong, Megan M Herr, Myo Htut, Joseph P. McGuirk, Douglas W Sborov, Jack Khouri, Thomas Martin, Murali Janakiram, Yi Lin, Doris K Hansen
Journal: Blood (2024)
Online Medication Abortion Direct-to-Patient Fulfillment Before and After the <i>Dobbs v Jackson</i> Decision
Authors: Caila Brander, Jessica Nouhavandi, Terri-Ann Thompson
Journal: JAMA Network Open (2024)

Online pharmacies have emerged as stakeholders in abortion care since the US Food and Drug Administration (FDA) relaxed in-person dispensing requirements in 2020. The role of online pharmacies in dispensing abortion medications following the Dobbs v Jackson Women's Health Organization decision on June 24, 2022, is understudied.
Disparities in Screening for Substance Use Among Injured Adolescents
Authors: Jordan M. Rook, Ryan G. Spurrier, Christopher J. Russell, Cathy E. Shin, Steven L. Lee, Catherine J. Juillard, Lorraine I. Kelley-Quon
Journal: JAMA Network Open (2024)

This cohort study compares rates of biochemical substance use screening among injured adolescents by sociodemographic characteristics including sex, race, ethnicity, and insurance status.
Cost-Effectiveness of 9-Valent HPV Vaccination for Patients Treated for High-Grade Cervical Intraepithelial Neoplasia in the UK
Authors: Alhaji Cherif, Olga Ovcinnikova, Cody Palmer, Kayla Engelbrecht, Miriam Reuschenbach, Vincent Daniels
Journal: JAMA Network Open (2024)

Patients who have been treated for high-grade cervical intraepithelial neoplasia (CIN grade ≥2) are at a high risk for subsequent CIN and other cancers and diseases related to human papillomavirus (HPV). HPV vaccination can reduce the risk of subsequent disease in patients surgically treated for grade 2 or greater CIN; however, there is no formal recommendation for prophylactic HPV vaccination in this high-risk population, and the cost-effectiveness is unknown.
Real-world efficacy and safety of inetetamab-based therapy in patients with HER2-positive metastatic breast cancer with prior trastuzumab exposure: A multi-center retrospective study.
Authors: Yangyang Duan, Tao Sun, Zhanhong Chen, Quchang Ouyang, Kai Li, Min Yan, Zheng Lv, Zhaohui Li, Li Man, Xu Luo, Yuyang Dong, Mingxi Jing, Yan Wang, Xiangyu Guo, Junnan Xu, Xiaorui Li
Journal: Journal of Clinical Oncology (2024)

e13007 Background: Inetetamab is a novel recombinant humanized anti-HER2 monoclonal antibody (mAb). There was still no direct data with large sample sizes to evaluate the efficacy of inetetamab-based therapy in HER2-positive metastatic breast cancer patients who had previously received trastuzumab treatment. This study aimed to observe the larger-scale real-world efficacy and safety of inetetamab, analyze the characteristics of the benefit population and explore more excellent treatment choices. Methods: A multicenter retrospective real-world study which collected the clinicopathological data of HER2-positive metastatic breast cancer patients treated with inetetamab in multicenters in China. The progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) of patients who received inetetamab therapy were estimated. Adverse events (AEs) were classified based on the Common Toxicity Criteria established by the National Cancer Institute. Results: A total of 500 patients were included in the final analysis according to the established inclusion criteria. The median PFS was 7 months in the overall cohort. The median number of treatment lines administered was three. The ORR was 28.6%, and the DCR was 89.2%. Meanwhile, patients who received a combination treatment of inetetamab, tyrosine kinase inhibitors (TKIs) and chemotherapy achieved the most prolonged PFS of 9.0 months and the higher ORR of 29.3%. The most common treatment-related AEs were neutropenia (36.4%) and leukopenia (31.4%), which were generally well-tolerated. Conclusions: Inetetamab demonstrated promising efficacy and safety in HER2-positive metastatic breast cancer patients who had prior exposure to trastuzumab, particularly in combination with TKIs and chemotherapy. Further research and comparative analysis should be necessary for therapeutic benefits.
Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity
Authors: Rachael K. Ross, Shodai Inose, Matisyahu Shulman, Edward V. Nunes, Lauren C. Zalla, A. Kathleen Burlew, Kara E. Rudolph
Journal: JAMA Network Open (2024)

Importance Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. Objective To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. Design, Setting, and Participants This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. Exposure Combined race and ethnicity as self-classified by the patient at trial enrollment. Main Outcomes and Measures The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥ 16 mg and methadone ≥ 60 mg) were compared across race and ethnicity groups. Results A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI −4.6 to −0.5) mg lower and methadone doses 16.7 (95% CI, −30.7 to −2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥ 16 mg; methadone ≥ 60 mg) was 16.9 (95% CI, −31.9 to −1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. Conclusions and Relevance In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.
Infective Endocarditis Among Women Who Inject Drugs
Authors: Janica A. Adams, Cara Spence, Esfandiar Shojaei, Priyadarshini Thandrasisla, Anmol Gupta, Yun-Hee Choi, Stuart Skinner, Michael Silverman
Journal: JAMA Network Open (2024)

In the US and Canada, women comprise approximately one-third of people who inject drugs (PWID); however, clinical characteristics and outcomes of injection drug use complications in women are poorly described.
Characterizing Prehospital Wall Fall Injuries at the US-Mexico Border
Authors: Alexander Tenorio, Arielle Schecter, David Y. Greenblatt, Janine Young, Linda L. Hill, Jay J. Doucet, Michael Levy
Journal: JAMA Network Open (2024)

This cross-sectional study examines treatment received for falls from a section of the US-Mexico border wall with a focus on emergency medical services activation and type of treatment.
Content Evaluation of Pruritus, Skin Pain, and Sleep Disturbance Patient-Reported Outcome Measures in Adolescents and Adults With Moderate-to-Severe Atopic Dermatitis: Qualitative Interviews
Authors: Andrew Blauvelt, Jennifer Reckleff, Yang Zhao, Marci Clark, Katherine Kosa, Nimanee Harris, Ehsanollah Esfandiari, Susan Martin, Diane Whalley, Guttman-Yassky Emma
Journal: British Journal of Dermatology (2024)

Pruritus, skin pain, and sleep disturbance are a significant burden to individuals with moderate-to-severe atopic dermatitis (AD) and negatively impact quality of life. Fit-for-purpose patient-reported outcome measures (PROMs) that assess AD-related pruritus, skin pain, and sleep disturbance are important for evaluating the effectiveness of new AD treatments.
Substance Use Emergency Department Visits Among Youths With Chronic Conditions During COVID-19
Authors: Faith Summersett Williams, Isabella Zaniletti, Abbey R. Masonbrink, Robert Garofalo, Maria Rahmandar, Niranjan S. Karnik, Geri Donenberg, Lisa Kuhns
Journal: JAMA Network Open (2024)

Pediatric emergency department (ED) visits for substance use (SU) increased during COVID-19. Better understanding of trends associated with SU ED visits among youths with a chronic medical condition (CMC) is needed to target SU screening, prevention, and intervention efforts in this population.
Long-term outcome of a multicenter prospective study on efficacy and safety of high-dose Stereotactic Body Radiation Therapy ≥ 48 hour-interfraction interval for ≤ 5 cm hepatocellular carcinoma
Authors: Jin-Kyu Kang, Mi-Sook Kim, Won Il Jang, Chul Ju Han, Jin Kim, Su Cheol Park, Young-Joo Shin, Chul Won Choi, Wan Jeon, Tosol Yu, Ah Ram Chang, Hae Jin Park, Younghee Park, Eun Seog Kim, Sunmi Jo, Woo Chul Kim, Hun Jung Kim, Sun Hyun Bae, Eunji Kim
Journal: Liver Cancer (2024)

Introduction: The goal of this study was to evaluate the efficacy and safety of high-dose stereotactic body radiation therapy (SBRT) with an extended (48 h or more) interfraction interval for hepatocellular carcinoma (HCC) ≤5 cm in size after incomplete response to transarterial chemoembolization (TACE). Methods: This multicenter prospective study included 54 patients with inoperable HCC of ≤5 cm size between July 2012 and June 2015. A total SBRT dose of 60 Gy in 3 fractions was administered within 14 days with ≥48-h interfraction interval to patients who showed an incomplete response after 1–5 sessions of TACE. Treatment responses were defined according to the modified Response Evaluation Criteria for Solid Tumors. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Results: Forty-eight patients were evaluated with a median follow-up period of 66 months (range, 2–126 months). The median tumor size was 2.0 cm (range, 1.0–4.5 cm), and most patients (87.5%) had a single lesion. The 1-, 2-, and 5-year local control (LC) rates were 100%, 94.8%, and 90.7%, respectively. The 1-, 2-, and 5-year progression-free survival (PFS) rates were 63.4%, 56.9%, and 24.9%, respectively. The 1-, 2-, and 5-year overall survival (OS) rates were 95.6%, 90.9%, and 76.5%, respectively. None of the patients experienced grade 3+ gastrointestinal toxicity, while 1 patient developed non-classic radiation-induced liver disease 2 months after SBRT. Conclusion: High-dose SBRT with a ≥48-h interfraction interval after incomplete response to TACE is effective for HCC ≤5 cm in size as evidenced by the high rates of LC and OS and acceptable treatment-related toxicity.
Maintenance of X chromosome inactivation after T cell activation requires NF-κB signaling
Authors: Katherine S. Forsyth, Natalie E. Toothacre, Nikhil Jiwrajka, Amanda M. Driscoll, Lindsey A. Shallberg, Charlotte Cunningham-Rundles, Sara Barmettler, Jocelyn Farmer, James Verbsky, John Routes, Daniel P. Beiting, Neil Romberg, Michael J. May, Montserrat C. Anguera
Journal: Science Immunology (2024)

X chromosome inactivation (XCI) balances X-linked gene dosage between sexes. Unstimulated T cells lack cytological enrichment of X-inactive specific transcript (Xist) RNA and heterochromatic modifications on the inactive X chromosome (Xi), which are involved in maintenance of XCI, and these modifications return to the Xi after stimulation. Here, we examined allele-specific gene expression and epigenomic profiles of the Xi in T cells. We found that the Xi in unstimulated T cells is largely dosage compensated and enriched with the repressive H3K27me3 modification but not the H2AK119-ubiquitin (Ub) mark. Upon T cell stimulation mediated by both CD3 and CD28, the Xi accumulated H2AK119-Ub at gene regions of previous H3K27me3 enrichment. T cell receptor (TCR) engagement, specifically NF-κB signaling downstream of the TCR, was required for Xist RNA localization to the Xi. Disruption of NF-κB signaling in mouse and human T cells using genetic deletion, chemical inhibitors, and patients with immunodeficiencies prevented Xist/XIST RNA accumulation at the Xi and altered X-linked gene expression. Our findings reveal a previously undescribed connection between NF-κB signaling pathways, which affects XCI maintenance in T cells in females.
Proximity-dependent labeling identifies dendritic cells that drive the tumor-specific CD4 <sup>+</sup> T cell response
Authors: Aleksey Chudnovskiy, Tiago B. R. Castro, Sandra Nakandakari-Higa, Ang Cui, Chia-Hao Lin, Moshe Sade-Feldman, Brooke K. Phillips, Juhee Pae, Luka Mesin, Juliana Bortolatto, Lawrence D. Schweitzer, Giulia Pasqual, Li-Fan Lu, Nir Hacohen, Gabriel D. Victora
Journal: Science Immunology (2024)

Dendritic cells (DCs) are uniquely capable of transporting tumor antigens to tumor-draining lymph nodes (tdLNs) and interact with effector T cells in the tumor microenvironment (TME) itself, mediating both natural antitumor immunity and the response to checkpoint blockade immunotherapy. Using LIPSTIC (Labeling Immune Partnerships by SorTagging Intercellular Contacts)–based single-cell transcriptomics, we identified individual DCs capable of presenting antigen to CD4 + T cells in both the tdLN and TME. Our findings revealed that DCs with similar hyperactivated transcriptional phenotypes interact with helper T cells both in tumors and in the tdLN and that checkpoint blockade drugs enhance these interactions. These findings show that a relatively small fraction of DCs is responsible for most of the antigen presentation in the tdLN and TME to both CD4 + and CD8 + tumor–specific T cells and that classical checkpoint blockade enhances CD40-driven DC activation at both sites.
Oncogenic KRAS drives immunosuppression of colorectal cancer by impairing DDX60-mediated dsRNA accumulation and viral mimicry
Authors: Yi Zhou, Yaxin Zhang, Mingzhou Li, Tian Ming, Chao Zhang, Chengmei Huang, Jiexi Li, Fengtian Li, Huali Li, Enen Zhao, Feng Shu, Lingtao Liu, Xingyan Pan, Yijun Gao, Lin Tian, Libing Song, Huilin Huang, Wenting Liao
Journal: Science Immunology (2024)

The interferon (IFN) response is vital for the effectiveness of immune checkpoint inhibition (ICI) therapy. Our previous research showed that KRAS (Kirsten rat sarcoma viral) mutation impairs the IFN response in colorectal cancer (CRC), with an unclear mechanism. Here, we demonstrate that KRAS accelerates double-stranded RNA (dsRNA) degradation, impairing dsRNA sensing and IFN response by down-regulating DExD/H-box helicase 6 (DDX60). DDX60 was identified as a KRAS target here and could bind to dsRNAs to protect against RNA-induced silencing complex (RISC)-mediated degradation. Overexpressing DDX60 induced dsRNA accumulation, reactivated IFN signaling, and increased CRC sensitivity to ICI therapy. Mechanistically, KRAS engaged the AKT (also known as protein kinase B)-GSK3β (glycogen synthase kinase-3 beta) pathway to suppress STAT3 phosphorylation, thereby inhibiting STAT3-driven DDX60 transcription. Our findings reveal a role for KRAS in dsRNA homeostasis, suggesting potential strategies to convert "cold" tumors to "hot" and to overcome ICI resistance in CRC with KRAS mutations.
Effect of occlusion site on the effectiveness and safety of endovascular thrombectomy for large ischemic cores: A cohort study
Authors: Shihai Yang, Lele Wu, Xiaolei Shi, Changwei Guo, Chengsong Yue, Shitao Fan, Jie Yang, Jiaxing Song, Dongsheng Ye, Xu Xu, Zhouzhou Peng, Linyu Li, Jiandi Huang, Chang Liu, Jiacheng Huang, Nizhen Yu, Yan Tian, Jinfu Ma, Dahong Yang, Weilin Kong, Zhixi Wang, Wenzhe Sun, Qingwu Yang, Boyu Chen, Wenjie Zi
Journal: International Journal of Surgery (2024)

Background: Recent clinical trials have shown that patients with large ischemic cores have better outcomes with endovascular thrombectomy (EVT) compared with standard medical treatment (SMT) alone.We aim to assess whether the relationship between EVT and improvements in clinical outcomes varies depending on the location of the occlusive sites. Methods: This study is a subgroup analysis conducted within a prospective, nationwide, multi-center registry. The cohort included patients with acute large vessel occlusion in the anterior circulation and an Alberta Stroke Program Early Computed Tomography Score of 0 to 5 within 24 hours from last known well. We utilized the adjusted common odds ratio for a shift toward better outcome on the modified Rankin Scale after EVT compared with SMT alone as the primary outcome. Safety outcomes included symptomatic intracranial hemorrhage (sICH). Results: A total of 745 patients with large ischemic cores were included: 272(36.5%) with internal carotid artery occlusion, 392(52.6%) with M1 segment of the middle cerebral artery occlusion, and 81(11.0%) with M2 segment of the middle cerebral artery occlusion. The adjusted common odds ratios were as follows: 1.98 (95% CI, 1.01-3.89) for ICA occlusions, 2.09 (95% CI, 1.35-3.23) for M1 occlusions, and 1.13 (95% CI, 0.43-2.94) for M2 occlusions. There was no significant treatment-by-occlusion site interaction observed ( P =0.69). However, the incidence of sICH was significantly greater in all groups receiving EVT than in those receiving SMT alone. Additionally, we observed that the secondary outcomes and subgroup analyses were generally consistent with the main outcomes. Conclusions: In this study, we found that patients with internal carotid artery and M1 occlusion demonstrated a better outcome with EVT, while the benefit for patients with M2 occlusion remains uncertain.