tbuckley/cabot-search huggingface dataset:
Correction: St. Jude Survivorship Portal: Sharing and Analyzing Large Clinical and Genomic Datasets from Pediatric Cancer Survivors
Authors: Gavriel Y. Matt, Edgar Sioson, Kyla Shelton, Jian Wang, Congyu Lu, Airen Zaldivar Peraza, Karishma Gangwani, Robin Paul, Colleen Reilly, Aleksandar Acić, Qi Liu, Stephanie R. Sandor, Clay McLeod, Jaimin Patel, Fan Wang, Cindy Im, Zhaoming Wang, Yadav Sapkota, Carmen L. Wilson, Nickhill Bhakta, Kirsten K. Ness, Gregory T. Armstrong, Melissa M. Hudson, Leslie L. Robison, Jinghui Zhang, Yutaka Yasui, Xin Zhou
Journal: Cancer Discovery (2024)
Tumor-Associated Microglia Secrete Extracellular ATP to Support Glioblastoma Progression
Authors: Caren Yu-Ju Wu, Yiyun Chen, Ya-Jui Lin, Kuo-Chen Wei, Kwang-Yu Chang, Li-Ying Feng, Ko-Ting Chen, Gordon Li, Alexander Liang Ren, Ryan Takeo Nitta, Janet Yuling Wu, Kwang Bog Cho, Ayush Pant, John Choi, Crystal L. Mackall, Lily H. Kim, An-Chih Wu, Jian-Ying Chuang, Chiung-Yin Huang, Christopher M. Jackson, Pin-Yuan Chen, Michael Lim
Journal: Cancer Research (2024)

Abstract Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis and high recurrence rates. The complex immune microenvironment of GBM is highly infiltrated by tumor-associated microglia and macrophages (TAM). TAMs are known to be heterogeneous in their functional and metabolic states and can transmit either protumoral or antitumoral signals to glioma cells. Here, we performed bulk RNA sequencing and single-cell RNA sequencing on samples from patients with GBM, which revealed increased ATP synthase expression and oxidative phosphorylation activity in TAMs located in the tumor core relative to the tumor periphery. Both in vitro and in vivo models displayed similar trends of augmented TAM mitochondrial activity, along with elevated mitochondrial fission, glucose uptake, mitochondrial membrane potential, and extracellular ATP (eATP) production by TAMs in the presence of GBM cells. Tumor-secreted factors, including GM-CSF, induced the increase in TAM eATP production. Elevated eATP in the GBM microenvironment promoted glioma growth and invasion by activating the P2X purinoceptor 7 (P2X7R) on glioma cells. Inhibition of the eATP–P2X7R axis attenuated tumor cell viability in vitro and reduced tumor size and prolonged survival in glioma-bearing mouse models. Overall, this study revealed elevated TAM-derived eATP in GBM and provided the basis for targeting the eATP–P2X7R signaling axis as a therapeutic strategy in GBM. Significance: Glioblastoma-mediated metabolic reprogramming in tumor-associated microglia increases ATP secretion that supports cancer cell proliferation and invasion by activating P2X7R, which can be inhibited to attenuate tumor growth.
Editor’s Note: BRAF Status in Personalizing Treatment Approaches for Pediatric Gliomas
Authors: Aleksandra Olow, Sabine Mueller, Xiaodong Yang, Rintaro Hashizume, Justin Meyerowitz, William Weiss, Adam C. Resnick, Angela J. Waanders, Lukas J.A. Stalpers, Mitchel S. Berger, Nalin Gupta, C. David James, Claudia K. Petritsch, Daphne A. Haas-Kogan
Journal: Clinical Cancer Research (2024)
Editor’s Note: Deciphering the Mechanisms of Tumorigenesis in Human Pancreatic Ductal Epithelial Cells
Authors: Zhe Chang, Zhongkui Li, Xiaoyang Wang, Ya’an Kang, Yuhui Yuan, Jiangong Niu, Huamin Wang, Deyali Chatterjee, Jason B. Fleming, Min Li, James L. Abbruzzese, Paul J. Chiao
Journal: Clinical Cancer Research (2024)
Layered Double Hydroxides for Radium‐223 Targeted Alpha Therapy with Elicitation of the Immune Response
Authors: Mengdie Yang, Jianguo Li, Zongtai Han, Xiaohui Luan, Xiaoyi Zhang, Jie Gao, Shanshan Qin, Fei Yu
Journal: Advanced Healthcare Materials (2024)

Abstract Targeted Alpha therapy (TAT) has promising application prospects in tumor therapy. It is very appealing to design alpha‐emitting radiopharmaceuticals that can modulate the immune microenvironment to overcome the limitations of immunotherapy. Herein, Mg/Al layered double hydroxide nanomaterials (LDH) are utilized to load the alpha‐emitting nuclide Radium‐223 ( 223 Ra), achieving precise delivery of 223 Ra to the tumor microenvironment. Dual‐modal imaging is employed to dynamically monitor the in vivo distribution of 223 Ra‐LDH, ensuring its prolonged retention at the tumor site. In vitro experimentsshowed that ionizing radiation from alpha‐emitting nuclides effectively reduced glutathione (GSH) and produced large amounts of reactive oxygen species (ROS), which damaged mitochondria and released free calcium (Ca 2+ ), thereby aggravating tumor cell death. Additionally, DNA double‐strand breaks induced by alpha‐emitting radiation triggered the STING signaling pathway, which in turn effectively induced immunogenic cell death (ICD) and promoted immune cell maturation and activation. The synergistic effect with immunotherapy triggered a powerful systemic antitumor immune response. Overall, this study develops a novel TAT therapeutic strategy with sufficient antitumor immunity.
In HF with secondary MR at high surgical risk, TEER was noninferior to surgery for CV events and reduced safety events at 1 y
Authors: Sukhpreet Kaur, Steven Borzak
Journal: Annals of Internal Medicine (2024)

Transcatheter repair versus mitral-valve surgery for secondary mitral regurgitation. N Engl J Med. 2024;391:1787-1798. 39216093.
In HF with functional MR, TEER with MitraClip improved HF hospitalization or CV death and health status
Authors: Sukhpreet Kaur, Steven Borzak
Journal: Annals of Internal Medicine (2024)

Transcatheter valve repair in heart failure with moderate to severe mitral regurgitation. N Engl J Med. 2024;391:1799-1809. 39216092.
The Past, Present, and Future of Restrictive Covenants in Medicine in the United States
Authors: Anand Prasad, Rishi Goswamy, Roger Bresnahan
Journal: Annals of Internal Medicine (2024)

Restrictive covenants (RCs) are clauses placed into employment agreements across various industries, and they are frequently used in health care-specifically within physician contracts. Given the most recent guidance and rule determined by the Federal Trade Commission in April 2024, the relevancy of RCs in health care has come under even more scrutiny in the latter half of 2024. This review will focus on the history of RC law and review the value of these clauses from the perspectives of the employer, practicing physician, and patient. We also provide the stakeholder responses to both the ban and the subsequent blockage of enforcement by a Texas federal court in August of 2024.
After COVID-19 diagnosis, risk for incident type 2 diabetes was elevated for up to 2 y
Authors: Stephanos Vassilopoulos, Eleftherios Mylonakis
Journal: Annals of Internal Medicine (2024)

Taylor K, Eastwood S, Walker V, et al. Incidence of diabetes after SARS-CoV-2 infection in England and the implications of COVID-19 vaccination: a retrospective cohort study of 16 million people. Lancet Diabetes Endocrinol. 2024;12:558-568. 39054034.
Self-experience of a negative event alters responses to others in similar states through prefrontal cortex CRF mechanisms
Authors: Federica Maltese, Giada Pacinelli, Anna Monai, Fabrizio Bernardi, Ana Marta Capaz, Marco Niello, Roman Walle, Noelia de Leon, Francesca Managò, Felix Leroy, Francesco Papaleo
Journal: Nature Neuroscience (2024)
Virtual Reality-based Infrared Pupillometry (VIP) for long COVID
Authors: Chen Hui Tang, Yi Fei Yang, Ken Chun Fung Poon, Hanson Yiu Man Wong, Kenneth Ka Hei Lai, Cheng Kun Li, Joey Wing Yan Chan, Yun Kwok Wing, Qi Dou, Clement Chee Yung Tham, Chi Pui Pang, Kelvin Kam Lung Chong
Journal: Ophthalmology (2024)
Ruxolitinib Treatment Ameliorates Clinical, Immunological, and Transcriptomic Aberrations in Patients with STAT3 Gain-of-Function Disease
Authors: Feyza Bayram Catak, Mehmet Cihangir Catak, Royala Babayeva, John Toubia, Nicholas I. Warnock, Fatih Celmeli, Demet Hafizoglu, Nalan Yakici, Basak Kayaoglu, Naz Surucu, Ezgi Yalcin Gungoren, Salim Can, Melek Yorgun Altunbas, Ibrahim Serhat Karakus, Ayca Kiykim, Fazil Orhan, Sevgi Bilgic Eltan, Elif Karakoc-Aydiner, Ahmet Ozen, Baran Erman, Mayda Gursel, Chung Hoow Kok, Gökhan Cildir, Safa Baris
Journal: Journal of Allergy and Clinical Immunology (2024)
Correction: Efficacy and safety in a 4-year follow-up of the ELEVATE-TN study comparing acalabrutinib with or without obinutuzumab versus obinutuzumab plus chlorambucil in treatment-naïve chronic lymphocytic leukemia
Authors: Jeff P. Sharman, Miklos Egyed, Wojciech Jurczak, Alan Skarbnik, John M. Pagel, Ian W. Flinn, Manali Kamdar, Talha Munir, Renata Walewska, Gillian Corbett, Laura Maria Fogliatto, Yair Herishanu, Versha Banerji, Steven Coutre, George Follows, Patricia Walker, Karin Karlsson, Paolo Ghia, Ann Janssens, Florence Cymbalista, Jennifer A. Woyach, Emmanuelle Ferrant, William G. Wierda, Veerendra Munugalavadla, Ting Yu, Min Hui Wang, John C. Byrd
Journal: Leukemia (2024)
Genetic and environmental risks for clonal hematopoiesis and cancer
Authors: Stephanie Franco, Lucy A. Godley
Journal: The Journal of Experimental Medicine (2024)

Somatic variants accumulate in all organs with age, with a positive selection of clonal populations that provide a fitness advantage during times of heightened cellular stress leading to clonal expansion. Easily measured within the hematopoietic compartment, clonal hematopoiesis (CH) is now recognized as a common process in which hematopoietic clones with somatic variants associated with hematopoietic neoplasms exist within the blood or bone marrow of individuals without evidence of malignancy. Most cases of CH involve a limited number of genes, most commonly DNMT3A, TET2, and ASXL1. CH confers risk for solid and hematopoietic malignancies as well as cardiovascular and numerous inflammatory diseases and offers opportunities for cancer prevention. Here, we explore the genetic and environmental factors that predispose individuals to CH with unique variant signatures and discuss how CH drives cancer progression with the goals of improving individual cancer risk stratification, identifying key intervention opportunities, and understanding how CH impacts therapeutic strategies and outcomes.
Bridging the gap between tumor and disease: Innovating cancer and glioma models
Authors: Stefano M. Cirigliano, Howard A. Fine
Journal: The Journal of Experimental Medicine (2024)

Recent advances in cancer biology and therapeutics have underscored the importance of preclinical models in understanding and treating cancer. Nevertheless, current models often fail to capture the complexity and patient-specific nature of human tumors, particularly gliomas. This review examines the strengths and weaknesses of such models, highlighting the need for a new generation of models. Emphasizing the critical role of the tumor microenvironment, tumor, and patient heterogeneity, we propose integrating our advanced understanding of glioma biology with innovative bioengineering and AI technologies to create more clinically relevant, patient-specific models. These innovations are essential for improving therapeutic development and patient outcomes.
Multitracer PET/CT Findings in a Case of Behavioral Variant Frontotemporal Dementia With Parkinsonism
Authors: Shuai Chen, Chang Fu, Jing-Yu Shao, Jun-Ling Xu, Jie-Wen Zhang
Journal: Clinical Nuclear Medicine (2024)

Abstracts We report the clinical and multimodal PET/CT manifestations in a patient with behavioral variant frontotemporal dementia and parkinsonism. The 18 F-FDG PET scan revealed hypometabolism in the left supratentorial cortex. The 18 F-fluorodopa PET scan demonstrated decreased uptake in the bilateral striatum, most prominent in the head of caudate nucleus. The 18 F-florbetapir PET scan indicated an absence of β-amyloid deposition, whereas the 18 F-flortaucipir PET scan showed uptake in the left hemisphere neocortex. The clinical presentation and asymmetric neuroimaging features supported the underlying frontotemporal lobar degeneration-tau pathology.
Foreign Body Perforating the Descending Colon Incidentally Detected on 18F-FDG PET/CT
Authors: Paulo Schiavom Duarte, George Barberio Coura-Filho, Marcelo Tatit Sapienza, Hongming Zhuang, Carlos Alberto Buchpiguel
Journal: Clinical Nuclear Medicine (2024)

Abstract A 78-year-old woman was diagnosed having unresectable tongue cancer 6 months ago, for which she received radiation therapy. She was on enteral nutrition for more than 2 months due to dysphagia and underwent an 18 F-FDG PET/CT for restaging. The images showed uptake in a left cervical node. In addition, there was a focal uptake in the descending colon corresponding to a foreign body in its anterior wall, which was removed by colonoscopy.
FDG PET/CT in Papillary Intralymphatic Angioendothelioma of the Spleen
Authors: Benzheng Jiao, Hongxia Liu, Xiaobo Ma, Aisheng Dong, Hongguang Zhao
Journal: Clinical Nuclear Medicine (2024)

Abstract Splenic papillary intralymphatic angioendothelioma is extremely rare. We describe FDG PET/CT and MRI findings of splenic papillary intralymphatic angioendothelioma in a young adult. The splenic tumor showed hypodensity and increased FDG uptake with SUV max of 4 on PET/CT, heterogeneous signal intensity with internal hypointense stellate scars on T2-weighted image, and progressive centripetal enhancement on dynamic contrast-enhanced T1-weighted images. This case indicates that papillary intralymphatic angioendothelioma should be included in the differential diagnosis of FDG-avid splenic lesions.
Frontline treatment of adults with newly diagnosed B-cell acute lymphoblastic leukaemia
Authors: Ibrahim Aldoss, Gail J Roboz, Renato Bassan, Nicolas Boissel, Daniel J DeAngelo, Shaun Fleming, Nicola Gökbuget, Aaron C Logan, Selina M Luger, Tobias Menne, Jae Park, Andre C Schuh, Bijal Shah, Elias Jabbour
Journal: The Lancet Haematology (2024)
Underwater endoscopic submucosal dissection with nasal intubation using a small-bore tracheal tube for an early epiglottic lesion
Authors: Hui Wang, Jingjing Yao, Yang Liu, Feifei Zhang, Yuehong Qiu, Wen Jiao, Jindong Fu
Journal: Endoscopy (2024)

A 60-year-old man was diagnosed during gastroscopy with an early neoplastic lesion on the lingual surface of the epiglottis. He had a history of long-term alcohol consumption. The lesion, measuring approximately 1.5 × 2.0 cm, was identified as a superficial, flat (0-IIb) area with a clear boundary, exhibiting a reddish hue under white light ([Fig. 1] a) and appearing brown under narrow-band imaging (NBI) ([Fig. 1] b). Following biopsy, histopathological examination confirmed high grade intraepithelial neoplasia (HGIN), and computed tomography (CT) scans showed no evidence of metastasis.
Mucosal inverted closure of a post-gastric endoscopic submucosal dissection defect using grasping forceps with good rotatability and sharp claws
Authors: Kaho Nakatani, Noriko Nishiyama, Kazuhiro Kozuka, Yukiko Koyama, Takanori Matsui, Tatsuo Yachida, Hideki Kobara
Journal: Endoscopy (2024)

Although post-gastric endoscopic submucosal dissection (ESD) bleeding is reduced by defect closure [1] [2] [3], there is no convenient and secure mucosal inverted closure method that enables early wound healing through sustained closure. We previously reported on post-ESD closure using jumbo grasping forceps (FG-47L-1; Olympus, Tokyo, Japan) [4]; however, one problem was the poor maneuverability of the grasping forceps. Subsequently, we used EndoGrip grasping forceps (EndoGrip, AG-5039-2323; AGS MedTech, Tokyo, Japan) ([Fig. 1]), which allows closure while inverting the mucosa. EndoGrip has two advantages: 1) small, sharp teeth at the tip and sharp claws in the arms that enable secure fold-and-drag maneuvers; and 2) good rotatability that provides easy maneuverability. We introduce a novel closure technique using EndoGrip forceps and endoclips.
Endoscopic transcecal resection of a low grade appendiceal mucinous neoplasm
Authors: Xiwei Ding, Shanshan Shen, Lei Wang
Journal: Endoscopy (2024)

Appendiceal mucinous neoplasms are rare tumors for which clinical management is challenging. Endoscopic transcecal appendectomy has been shown to be effective for the treatment of appendiceal orifice lesions [1] [2] [3]. Herein, we report the application of this technique to successfully remove an appendiceal mucinous neoplasm without adverse events.
A self-made wire snare used in combination with a long transparent cap to remove a giant phytobezoar
Authors: Lizhi Yi, Huarong Qiu, Ke Liu, Yanhong Ge, Zhengyu Cheng
Journal: Endoscopy (2024)

A 76-year-old man with a 3-year history of consumption of persimmons was admitted to our hospital because of a 6-month history of abdominal distension. We performed esophagogastroduodenoscopy and revealed a giant phytobezoar (about 4 × 6 cm) in his stomach ([Fig. 1] a). Because of its large size, the phytobezoar could not be trapped using the maximal diameter snare that was available (3 cm in diameter). A self-made wire snare was therefore created using a zebra guidewire, and a long transparent cap, with an edge that protrudes approximately 12 mm beyond the tip of the gastroscope, was installed onto the gastroscope ([Video 1]). At the second attempt, the phytobezoar was successfully trapped with the self-made wire snare and was then slowly pulled to the edge of the long transparent cap ([Fig. 1] b). Next, we continued pulling on the snare to cold-cut the phytobezoar with the assistance of the cap ([Fig. 1] c). The procedure was repeated until the phytobezoar had been cut into several small pieces, all of which were then successfully removed ([Fig. 2]). The patient did not feel any discomfort postoperatively and was discharged the following day.
Hemospray as first-line treatment option for malignant gastrointestinal bleeding: A cost-utility analysis in the United Kingdom
Authors: Dawn Andrew Cooper, Benjamin Norton, Neil D Hawkes, Srisha Hebbar, Andrea Telese, John Morris, Rehan Haidry, Alan Barkun
Journal: Endoscopy (2024)

Aims: For managing malignant upper gastrointestinal bleeding (MUGIB), randomised control trial data have shown the haemostatic powder; Hemospray (TC-325), results in greater immediate haemostasis and lower 30-day rebleeding rates than standard endoscopic therapy (SET). We sought to determine if using TC-325 as a first-line option for patients with MUGIB would be cost-effective compared with SET in the United Kingdom. Methods: A decision tree was developed among patients with MUGIB, assessing initial therapy with TC-325 or SET over a 30-day time horizon. Patients with failed initial haemostasis, or a rebleed within 30 days, underwent further endoscopic treatment, escalation to either transcatheter arterial embolisation or surgery, or radiotherapy. Overall, 30-day mortality was applied. Costs, in Great British Pounds, were based on the United Kingdom National Health Services costs for 2023/2024. Results are reported as incremental differences in cost, quality-adjusted life years, and net monetary benefit. Deterministic and probabilistic sensitivity analyses and scenario analyses were performed. Results: The cost of treating MUGIB patients with TC-325 was £245.88 lower than SET, with an incremental increase of 0.001 Quality Adjusted Life Years (QALYs). TC-325 remained cost-saving for sensitivity and scenario analyses. Probabilistic sensitivity analysis revealed TC-325 as more effective and cost-saving in 82.0% of simulations (range 68.8-97.8%). Conclusions: Initial treatment of MUGIB with TC-325 compared to SET is more effective (higher primary haemostasis and lower 30-day rebleeding) and cost-saving due to requiring fewer interventions, readmissions, and length of stay. Additional studies are needed to address model uncertainties in the follow-up management of these complex patients.
Clinical and patient-reported outcomes after oncoplastic versus conventional breast conserving surgery—a longitudinal, multicenter cohort study
Authors: Claudia A Bargon, Dieuwke R Mink Van Der Molen, Danny A Young-Afat, Marilot C T Batenburg, Iris E Van Dam, Inge O Baas, Miranda F Ernst, Wiesje Maarse, Maartje F Sier, Ernst J P Schoenmaeckers, Josephina P J Burgmans, Rhodé M Bijlsma, Sabine Siesling, Hinne A Rakhorst, Marc Am Mureau, Femke Van Der Leij, Annemiek Doeksen, Helena M Verkooijen
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Oncoplastic breast conserving surgery (OP-BCS) is becoming increasingly popular to avoid mastectomy or optimize cosmetic outcomes of breast conserving surgery (BCS). Few studies have compared clinical outcomes and patient-reported outcomes (PROs) of OP-BCS to conventional BCS (C-BCS). This study aims to compare clinical outcomes and short and long-term PROs after OP-BCS and C-BCS in a large prospective breast cancer cohort. Methods Women in the prospective, multicenter UMBRELLA-breast cancer cohort who underwent OP-BCS or C-BCS were included. Clinical outcomes and PROs (measured by EORTC QLQ-C30/BR23) up to 24 months postoperatively were evaluated. Mixed-model analysis was performed to assess differences in PROs over time between groups. Results 1628 (84.9%) patients received C-BCS and 290 (15.1%) OP-BCS. After C-BCS and OP-BCS, free resection margins were obtained in 84.2% (n = 1370) and 86.2% (n = 250), respectively, reoperation for re-exision of margins &amp;lt;3 months occurred in 5.3% (n = 86) and 4.8% (n = 14), median time interval from surgery until adjuvant systemic therapy was 66 and 63 days, and 36 and 41 days until radiotherapy. Shortly postoperative, OP-BCS was associated with statistically significant lower mean scores for physical functioning (83.6 vs 87.2) and body image (82.8 vs 89.4) and more pain (19.8 vs 26.5) and breast symptoms (22.7 vs 30.3) than C-BCS. Body image scores remained significantly less favorable after OP-BSC than C-BCS up to 24 months postoperatively (87.8 vs 92.2). Conclusions Oncoplastic surgery safely enables BCS, but may lead to less favorable long-term body image compared to C-BCS. These findings are important for patient education and shared decision-making.
Increased Occurrence of Malignancy Before and after Chemoradiation for Anal Squamous Cell Carcinoma: A Multi-Institutional Analysis
Authors: Ritesh Kumar, Chris L Hallemeier, Daniel T Chang, Shou-En Lu, Lara Hathout, Vasilis C Hristidis, Krishnan R Jethwa, J Richelcyn M Baclay, Veeraswamy Manne, Zakaria Chakrani, Michael G Haddock, Diego Augusto Santos Toesca, Erqi Liu Pollom, Abraham J Wu, Harigopal Sandhyavenu, Paul B Romesser, Salma K Jabbour
Journal: JNCI Journal of the National Cancer Institute (2024)

Abstract Background Anal squamous cell carcinoma (ASCC) is a rare cancer with increased occurrence of multiple cancers before and after the ASCC diagnosis. However, there is limited data on this aspect. This multi-institutional analysis aimed to define the occurrence of malignancies before and after ASCC, time trends, impact on survival, and identify prognostic factors. Material and Methods Initial primary malignancy (IPM) was defined as a malignancy occurring before the ASCC. Second primary malignancy (SPM) was defined as a distinct primary cancer that developed after ASCC diagnosis. Retrospective multi-institutional chart review was done. Progression free survival (PFS), overall survival (OS) and prognostic factors were evaluated. Results 647 patients with ASCC treated with curative intent were analyzed. Median age was 61.23 years with 72% as females. 150 patients (23.3%) had multiple malignancies with IPM in 16% and SPM in 8%. Patients without prior cancer had better 5-year PFS (81.2% vs 67.2%, p = .011) and OS (81% vs 69%, p = .008) compared to those with prior cancer. SPMs had a significant adverse impact on PFS (HR 4.22) and OS (HR 3.56). Females had better 5-year PFS (82% vs 70%, p = .016) as compared to males. The median time interval for developing ASCC (as SPM) after IPM was 9.32 years. Conclusions ASCC patients have increased risk of multiple malignancies. Patients with prior cancer have inferior outcomes. SPM is a poor prognostic factor in patients without any prior cancer. SPM can develop years after treatment of primary ASCC.