tbuckley/cabot-search huggingface dataset:
High risk stigmata and treatment strategy for acute lower gastrointestinal bleeding: a nationwide study in Japan
Authors: Tomonori Aoki, Naoyoshi Nagata, Eiji Sadashima, Katsumasa Kobayashi, Atsushi Yamauchi, Atsuo Yamada, Jun Omori, Takashi Ikeya, Taiki Aoyama, Naoyuki Tominaga, Yoshinori Sato, Takaaki Kishino, Naoki Ishii, Tsunaki Sawada, Masaki Murata, Akinari Takao, Kazuhiro Mizukami, Ken Kinjo, Shunji Fujimori, Takahiro Uotani, Minoru Fujita, Hiroki Sato, Yoku Hayakawa, Mitsuhiro Fujishiro, Mitsuru Kaise
Journal: Endoscopy (2024)

Background The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy. Methods We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment. Results 30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49–0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29–0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41–0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding. Conclusions A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.
Female reproductive histories and the risk of chronic obstructive pulmonary disease
Authors: Chen Liang, Hsin-Fang Chung, Annette Dobson, Sven Sandin, Elisabete Weiderpass, Gita D Mishra
Journal: Thorax (2024)

Background Female reproductive factors may influence the development of chronic obstructive pulmonary disease (COPD) through the female hormonal environment, but studies on this topic are limited. This study aimed to assess whether age at menarche, number of children, infertility, miscarriage, stillbirth and age at natural menopause were associated with the risk of COPD. Methods Women from three cohorts with data on reproductive factors, COPD and covariates were included. Cause specific Cox regression models were adjusted for birth year, race, educational level, body mass index and pack years of smoking, stratified by asthma, and incorporating interaction between birth year and time. Between cohort differences and within cohort correlations were taken into account. Results Overall, 2 83 070 women were included and 10 737 (3.8%) developed COPD after a median follow-up of 11 (IQR 10–12) years. Analyses revealed a U shaped association between age at menarche and COPD (≤11 vs 13: HR 1.17, 95% CI 1.11 to 1.23; ≥16 vs 13: HR 1.24, 95% CI 1.21 to 1.27). Women with three or more children (3 vs 2: HR 1.14, 95% CI 1.12 to 1.17; ≥4 vs 2: HR 1.34, 95% CI 1.28 to 1.40), multiple miscarriages (2 vs 0: HR 1.28, 95% CI 1.24 to 1.32; ≥3 vs 0: HR 1.36, 95% CI 1.30 to 1.43) or stillbirth (1 vs 0: HR 1.38, 95% CI 1.25 to 1.53; ≥2 vs 0: HR 1.67, 95% CI 1.32 to 2.10) were at a higher risk of COPD. Among postmenopausal women, earlier age at natural menopause was associated with an increased risk of COPD (&lt;40 vs 50–51: HR 1.69, 95% CI 1.63 to 1.75; 40–44 vs 50–51: HR 1.42, 95% CI 1.38 to 1.47). Conclusions Multiple female reproductive factors, including age at menarche, number of children, miscarriage, stillbirth, and age at natural menopause were associated with the risk of COPD.
Mno<i><sub>x</sub></i> Nanoenzyme Armed CAR‐NK Cells Enhance Solid Tumor Immunotherapy by Alleviating the Immunosuppressive Microenvironment
Authors: Jiazhi Duan, Songbo Zhao, Yuyao Duan, Dawei Sun, Gaorui Zhang, Dexin Yu, Yalin Lou, Huimin Liu, Shanshan Yang, Xiaohong Liang, Chunhong Ma, Hong Liu, Jichuan Qiu, Lifen Gao, Yuanhua Sang
Journal: Advanced Healthcare Materials (2024)

Abstract Adoptively transferred cells usually suffer from exhaustion, limited expansion, and poor infiltration, partially attributing to the complicated immunosuppressive microenvironment of solid tumors. Therefore, it is necessary to explore more effective strategies to improve the poor tumor microenvironment (TME) to efficaciously deliver and support extrinsic effector cells in vivo. Herein, an intelligent biodegradable hollow manganese dioxide nanoparticle (MnO X ) that possesses peroxidase activity to catalyze excess H 2 O 2 in the TME to produce oxygen and relieve the hypoxia of solid tumors is developed. MnO X nanoenzymes modified with CD56 antibody could specifically bind CAR‐NK (chimeric antigen receptor modified natural killer) cells. It is demonstrated that CAR‐NK cells incorporated with MnO X nanoenzymes effectively infiltrate into tumor tissues with an improved TME, which results in superior antitumor activity in solid tumor‐bearing mice. The antibody connection between MnO X nanoenzymes and CAR‐NK endows the lowest efficient dosage of MnO X . This study features a smart synergistic immunotherapy approach for solid tumors using MnO X nanoenzyme‐armed CAR‐NK cells, which would provide a valuable tool for immunocyte therapy in solid tumors.
Nanozyme‐based Clusterphene for Enhanced Electrically Catalytic Cancer Therapy
Authors: Zhengya Yue, Jialun Li, Minglu Tang, Tiedong Sun, Chunxia Chen, Zhiguang Wu
Journal: Advanced Healthcare Materials (2024)

Abstract Nanozyme mediated catalytic therapy is an attractive strategy for cancer therapy. However, the nanozymes are tended to assemble into 3D architectures, resulting in poor catalytic efficiency for therapy. This study designs the assembly of nanozymes and natural enzymes into the layered structures featuring hexagonal pores as nanozyme clusterphene and investigates their catalytic therapy with the assistance of electric field. The nanozyme‐based clusterphene consists of polyoxometalate (POM) and natural glucose oxidase (GOx), named POMG‐based clusterphene, which facilitate multi‐enzyme activities including peroxidase (POD), catalase (CAT), and glutathione oxidase (GPx). The highly ordered layers with hexagonal pores of POMG units significantly improve the peroxidase‐like (POD‐like) activity of the nanozyme and thus the sustained production of reactive oxygen species (ROS). At the same time, GOx can increase endogenous H 2 O 2 and produce gluconic acid while consuming glucose, the nutrient of tumor cell growth. The results indicate that the POD‐like activity of POMG‐based clusterphene increase approximately sevenfold under electrical stimulation compared with Nd‐substituted keggin type POM cluster (NdPW 11 ). The experiments both in vitro and in vivo show that the proposed POMG‐based clusterphene mediated cascade catalytic therapy is capable of efficient tumor inhibiting and preventing tumor proliferation in tumor‐bearing mice model, promising as an excellent candidate for catalytic therapy.
DNA Methylation Profiling Enables Accurate Classification of Nonductal Primary Pancreatic Neoplasms
Authors: Anna Vera D Verschuur, Wenzel M Hackeng, Florine Westerbeke, Jamal K Benhamida, Olca Basturk, Pier Selenica, G Mihaela Raicu, I Quintus Molenaar, Hjalmar C van Santvoort, Lois A Daamen, David S Klimstra, Shinichi Yachida, Claudio Luchini, Aatur D Singhi, Christoph Geisenberger, Lodewijk A A Brosens
Journal: Clinical Gastroenterology and Hepatology (2024)

Background & AimsCytologic and histopathologic diagnosis of non-ductal pancreatic neoplasms can be challenging in daily clinical practice, whereas it is crucial for therapy and prognosis. The cancer methylome is successfully used as a diagnostic tool in other cancer entities. Here, we investigate if methylation profiling can improve the diagnostic work-up of pancreatic neoplasms.MethodsDNA methylation data were obtained for 301 primary tumors spanning 6 primary pancreatic neoplasms and 20 normal pancreas controls. Neural Network, Random Forest, and extreme gradient boosting machine learning models were trained to distinguish between tumor types. Methylation data of 29 nonpancreatic neoplasms (n = 3708) were used to develop an algorithm capable of detecting neoplasms of non-pancreatic origin.ResultsAfter benchmarking 3 state-of-the-art machine learning models, the random forest model emerged as the best classifier with 96.9% accuracy. All classifications received a probability score reflecting the confidence of the prediction. Increasing the score threshold improved the random forest classifier performance up to 100% with 87% of samples with scores surpassing the cutoff. Using a logistic regression model, detection of nonpancreatic neoplasms achieved an area under the curve of >0.99. Analysis of biopsy specimens showed concordant classification with their paired resection sample.ConclusionsPancreatic neoplasms can be classified with high accuracy based on DNA methylation signatures. Additionally, non-pancreatic neoplasms are identified with near perfect precision. In summary, methylation profiling can serve as a valuable adjunct in the diagnosis of pancreatic neoplasms with minimal risk for misdiagnosis, even in the pre-operative setting.Graphical abstract
Early prediction of endocrine responsiveness in ER+/HER2-negative metastatic breast cancer (MBC): pilot study with 18F-fluoroestradiol (18F-FES) CT/PET
Authors: A. Gennari, E. Brain, A. De Censi, O. Nanni, R. Wuerstlein, A. Frassoldati, J. Cortes, V. Rossi, M. Palleschi, J.L. Alberini, F. Matteucci, A. Piccardo, G. Sacchetti, H. Ilhan, F. D’Avanzo, B. Ruffilli, S. Nardin, M. Monti, M. Puntoni, V. Fontana, L. Boni, N. Harbeck, Bianca Malagutti, Bassam Dib, Carmen Branni, Mauro D’Amico, Nicoletta Provinciali, Davide Corradengo, Francesco Fiz, Massimiliano Iacozzi, Andrea Rocca, Tom Degenhardt, Patrick Vavasseur
Journal: Annals of Oncology (2024)
Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC
Authors: H.A. Yu, C. Baik, D.-W. Kim, M.L. Johnson, H. Hayashi, M. Nishio, J.C.-H. Yang, W.-C. Su, K.A. Gold, M. Koczywas, E.F. Smit, C.E. Steuer, E. Felip, H. Murakami, S.-W. Kim, X. Su, S. Sato, P.-D. Fan, M. Fujimura, Y. Tanaka, P. Patel, D.W. Sternberg, D. Sellami, P.A. Jänne
Journal: Annals of Oncology (2024)

Background HER3 is broadly expressed in NSCLC and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase 1 study of HER3-DXd in patients with advanced NSCLC. Patients with EGFR-mutated NSCLC that progressed after EGFR TKI and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. Patients and Methods Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. Results In the safety population (N=102), median treatment duration was 5.5 (range, 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (per RECIST v1.1) was 41.0% (95% CI, 30.0%-52.7%), median progression-free survival was 6.4 (95% CI, 4.4-10.8) months, and median OS was 16.2 (95% CI, 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. Conclusion In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.
Treatment patterns and outcomes in metastatic castration-resistant prostate cancer patients with and without somatic or germline alterations in homologous recombination repair genes
Authors: D. Olmos, D. Lorente, D. Alameda, C. Cattrini, N. Romero-Laorden, R. Lozano, P.P. Lopez-Casas, A. Jambrina, C. Capone, A.M. Vanden Broecke, M. Trevisan, S. Van Sanden, A. Jürgens, B. Herrera-Imbroda, E. Castro
Journal: Annals of Oncology (2024)

BackgroundAlthough germline BRCA mutations have been associated with adverse outcomes in prostate cancer (PC), understanding of the association between somatic/germline alterations in homologous recombination repair (HRR) genes and treatment outcomes in metastatic castration-resistant PC (mCRPC) is limited.The aim of this study was to investigate the prevalence and outcomes associated with somatic/germline HRR alterations, particularly BRCA1/2, in patients initiating first-line (1L) mCRPC treatment with androgen receptor signalling inhibitors (ARSi) or taxanes.Patients and methodsData from 729 mCRPC patients were pooled for CAPTURE from four multicentre observational studies. Eligibility required 1L treatment with ARSi or taxanes, adequate tumour samples and biomarker panel results.Patients underwent paired normal and tumour DNA analyses by next-generation sequencing using a custom gene panel including ATM, BRCA1, BRCA2, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2, RAD51B and RAD54L. Patients were divided in subgroups based on somatic/germline alteration(s): with BRCA1/2 mutations (BRCA); with HRR mutations except BRCA1/2 (HRR non-BRCA), and without HRR alterations (non-HRR). Patients without BRCA1/2 mutations were classified as non-BRCA. Radiographic progression-free survival (rPFS), progression-free survival 2 (PFS2) and overall survival (OS) were assessed.ResultsOf 729 patients, 96 (13.2%), 127 (17.4%) and 506 (69.4%) were in the BRCA, HRR non-BRCA and non-HRR subgroups, respectively.BRCA patients performed significantly worse for all outcomes than non-HRR or non-BRCA patients (P<0.05), while PFS2 and OS were significantly shorter for BRCA than HRR non-BRCA patients (P<0.05). HRR non-BRCA patients also had significantly worse rPFS, PFS2 and OS than non-HRR patients. Exploratory analyses suggested that for BRCA patients, there were not significant differences in outcomes associated with 1L treatment choice (ARSi or taxanes) or with the somatic/germline origin of the alterations.ConclusionsWorse outcomes were observed for mCRPC patients in the BRCA subgroup compared with non-BRCA subgroups, either HRR non-BRCA or non-HRR. Despite its heterogeneity, the HRR non-BRCA subgroup presented worse outcomes than the non-HRR subgroup. Screening early for HRR mutations, especially BRCA1/2, is crucial in improving mCRPC patient prognosis.
Early-life nasal microbiota dynamics relate to longitudinal respiratory phenotypes in urban children
Authors: Kathryn E. McCauley, Juliana Durack, Kole V. Lynch, Douglas W. Fadrosh, Kei E. Fujimura, Faith Vundla, Mustafa Özçam, Petra LeBeau, Agustin Caltroni, Preston Burns, Hoang T. Tran, Leonard B. Bacharier, Meyer Kattan, George T. O’Connor, Robert A. Wood, Alkis Togias, Homer A. Boushey, Daniel J. Jackson, James E. Gern, Susan V. Lynch
Journal: Journal of Allergy and Clinical Immunology (2024)
Serum Ammonia Levels Do Not Correlate With Overt Hepatic Encephalopathy Severity in Hospitalized Patients With Cirrhosis
Authors: Jasmohan S. Bajaj, Nikolaos T. Pyrsopoulos, Robert S. Rahimi, Zeev Heimanson, Christopher Allen, Don C. Rockey
Journal: Clinical Gastroenterology and Hepatology (2024)

Although ammonia is involved in the pathophysiology of hepatic encephalopathy (HE), the use of ammonia levels in clinical practice is problematic.
Event-free survival by residual cancer burden with pembrolizumab in early-stage TNBC: exploratory analysis from KEYNOTE-522
Authors: L. Pusztai, C. Denkert, J. O’Shaughnessy, J. Cortes, R. Dent, H. McArthur, S. Kümmel, J. Bergh, Y.H. Park, R. Hui, N. Harbeck, M. Takahashi, M. Untch, P.A. Fasching, F. Cardoso, Y. Zhu, W. Pan, K. Tryfonidis, P. Schmid
Journal: Annals of Oncology (2024)
Robot-assisted Single Photon Emission Computed Tomography: Integrating Nuclear Medicine in Robotic Urologic Surgery
Authors: Samaneh Azargoshasb, Anne-Claire Berrens, Leon J. Slof, Michiel Sinaasappel, Pim J. van Leeuwen, Henk G. van der Poel, Matthias N. van Oosterom, Fijs W.B. van Leeuwen
Journal: European Urology (2024)
Reply to Borivoj Golijanin, Anthony Mega, and Dragan Golijanin’s Letter to the Editor re: Ivo I. de Vos, Sebastiaan Remmers, Renée Hogenhout, Monique J. Roobol, ERSPC Rotterdam Study Group. Prostate Cancer Mortality Among Elderly Men After Discontinuing Organised Screening: Long-term Results from the European Randomized Study of Screening for Prostate Cancer Rotterdam. Eur Urol 2024;85:74–81
Authors: Ivo I. de Vos, Sebastiaan Remmers, Monique J. Roobol
Journal: European Urology (2024)
Assessment of Visual Function with Cotoretigene Toliparvovec in X-Linked Retinitis Pigmentosa in the Randomized XIRIUS Phase 2/3 Study
Authors: Byron L. Lam, Mark E. Pennesi, Christine N. Kay, Sushil Panda, James A. Gow, Guolin Zhao, Robert E. MacLaren, Robert MacLaren, Tomas Aleman, David Birch, Assad Jalil, Andrew Lotery, Byron Lam, Mark Pennesi, Christine N. Kay, Imram H. Yusuf, Jasmina Cehajic Kapetanovic, Jasleen K. Jolly, Amandeep S. Josan, Laura J. Taylor, Kanmin Xue, Anika Nanda, Thomas Buckley, Anna Paola Salvetti, Suresh Thulasidharan, Miguel Kurc, Samir Khandhadia, Karla Orsine Murta Dias, Abeir Baltmr, Nakul Mandal, Georgios Tsokolas, Tsveta Ivanova, Muhannd EL-Faouri, Sherif Shaarawy, Graeme Black, Janet L. Davis, Ninel Z. Gregori, Carlos E. Mendoza-Santiesteban, Andreas K. Lauer, Paul Yang, Steven Bailey, Rand Spencer, Gary E. Fish, Robert Wang, Deborah Chong, Ashkan Abbey, Rajiv Anand, Albert A. MaGuire, Robert L. Roseman, Kaushik M. Hazariwala, Brandon Parrott
Journal: Ophthalmology (2024)
Progress is impossible without change: understanding the evolving nomenclature of steatotic liver disease and its effect on hepatology practice
Authors: Paul N Brennan, Oliver D Tavabie, Wenhao Li, Thomas Marjot, Lynsey Corless, Jonathan A Fallowfield, Helen Jarvis, Dina Mansour, Stuart McPherson, William Rosenberg, Karen Rockell, Jeremy Tomlinson, Andrew Yeoman, Emmanuel A Tsochatzis, John F Dillon, William Alazawi, Kushala W M Abeysekera
Journal: The Lancet. Gastroenterology & hepatology (2024)
Effect of robotic versus open pancreaticoduodenectomy on postoperative length of hospital stay and complications for pancreatic head or periampullary tumours: a multicentre, open-label randomised controlled trial
Authors: Qu Liu, Mengyang Li, Yuanxing Gao, Tao Jiang, Bing Han, Guodong Zhao, Chao Lin, Wan Yee Lau, Zhiming Zhao, Rong Liu
Journal: The Lancet. Gastroenterology & hepatology (2024)
First exploration of the on-treatment changes in tumor and organ uptake of a radiolabeled anti PD-L1 antibody during chemoradiotherapy in patients with non-small cell lung cancer using whole body PET
Authors: Johanna E E Pouw, Sayed M S Hashemi, Marc C Huisman, Jessica E Wijngaarden, Maarten Slebe, Daniela E Oprea-Lager, Gerben J C Zwezerijnen, Danielle Vugts, Ezgi B Ulas, Tanja D de Gruijl, Teodora Radonic, Suresh Senan, C Willemien Menke-van der Houven van Oordt, Idris Bahce
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background In patients with locally advanced unresectable non-small cell lung cancer (NSCLC), durvalumab, an anti-programmed cell death ligand-1 (PD-L1) antibody, has shown improved overall survival when used as consolidation therapy following concurrent chemoradiotherapy (CRT). However, it is unclear whether CRT itself upregulates PD-L1 expression. Therefore, this study aimed to explore the changes in the uptake of the anti PD-L1 antibody [ 89 Zr]Zr-durvalumab in tumors and healthy organs during CRT in patients with NSCLC. Methods Patients with NSCLC scheduled to undergo CRT were scanned 7±1 days after administration of 37±1 MBq [ 89 Zr]Zr-durvalumab at baseline, 1-week on-treatment and 1 week after finishing 6 weeks of CRT. First, [ 89 Zr]Zr-durvalumab uptake was visually assessed in a low dose cohort with a mass dose of 2 mg durvalumab (0.13% of therapeutic dose) and subsequently, quantification was done in a high dose cohort with a mass dose of 22.5 mg durvalumab (1.5% of therapeutic dose). Tracer pharmacokinetics between injections were compared using venous blood samples drawn in the 22.5 mg cohort. Visual assessment included suspected lesion detectability. Positron emission tomography (PET) uptake in tumoral and healthy tissues was quantified using tumor to plasma ratio (TPR) and organ to plasma ratio, respectively. Results In the 2 mg dose cohort, 88% of the 17 identified tumor lesions were positive at baseline, compared with 69% (9/13) for the 22.5 mg cohort. Although the absolute plasma concentrations between patients varied, the intrapatient variability was low. The ten quantitatively assessed lesions in the 22.5 mg cohort had a median TPR at baseline of 1.3 (IQR 0.7–1.5), on-treatment of 1.0 (IQR 0.7–1.4) and at the end of treatment of 0.7 (IQR 0.6–0.7). On-treatment, an increased uptake in bone marrow was seen in three out of five patients together with a decreased uptake in the spleen in four out of five patients. Conclusions This study successfully imaged patients with NSCLC with [ 89 Zr]Zr-durvalumab PET before and during CRT. Our data did not show any increase in [ 89 Zr]Zr-durvalumab uptake in the tumor 1-week on-treatment and at the end of treatment. The changes observed in bone marrow and spleen may be due to an CRT-induced effect on immune cells. Trial registration number EudraCT number: 2019-004284-51