tbuckley/cabot-search huggingface dataset:
A Novel Role for DNA-PK in Metabolism by Regulating Glycolysis in Castration-Resistant Prostate Cancer
Authors: Emanuela Dylgjeri, Vishal Kothari, Ayesha A. Shafi, Galina Semenova, Peter T. Gallagher, Yi F. Guan, Angel Pang, Jonathan F. Goodwin, Swati Irani, Jennifer J. McCann, Amy C. Mandigo, Saswati Chand, Christopher M. McNair, Irina Vasilevskaya, Matthew J. Schiewer, Costas D. Lallas, Peter A. McCue, Leonard G. Gomella, Erin L. Seifert, Jason S. Carroll, Lisa M. Butler, Jeff Holst, William K. Kelly, Karen E. Knudsen
Journal: Clinical Cancer Research (2022)

Abstract Purpose: DNA-dependent protein kinase catalytic subunit (DNA-PKcs, herein referred as DNA-PK) is a multifunctional kinase of high cancer relevance. DNA-PK is deregulated in multiple tumor types, including prostate cancer, and is associated with poor outcomes. DNA-PK was previously nominated as a therapeutic target and DNA-PK inhibitors are currently undergoing clinical investigation. Although DNA-PK is well studied in DNA repair and transcriptional regulation, much remains to be understood about the way by which DNA-PK drives aggressive disease phenotypes. Experimental Design: Here, unbiased proteomic and metabolomic approaches in clinically relevant tumor models uncovered a novel role of DNA-PK in metabolic regulation of cancer progression. DNA-PK regulation of metabolism was interrogated using pharmacologic and genetic perturbation using in vitro cell models, in vivo xenografts, and ex vivo in patient-derived explants (PDE). Results: Key findings reveal: (i) the first-in-field DNA-PK protein interactome; (ii) numerous DNA-PK novel partners involved in glycolysis; (iii) DNA-PK interacts with, phosphorylates (in vitro), and increases the enzymatic activity of glycolytic enzymes ALDOA and PKM2; (iv) DNA-PK drives synthesis of glucose-derived pyruvate and lactate; (v) DNA-PK regulates glycolysis in vitro, in vivo, and ex vivo; and (vi) combination of DNA-PK inhibitor with glycolytic inhibitor 2-deoxyglucose leads to additive anti-proliferative effects in aggressive disease. Conclusions: Findings herein unveil novel DNA-PK partners, substrates, and function in prostate cancer. DNA-PK impacts glycolysis through direct interaction with glycolytic enzymes and modulation of enzymatic activity. These events support energy production that may contribute to generation and/or maintenance of DNA-PK–mediated aggressive disease phenotypes.
Screening for Atrial Fibrillation
Authors: Karina W. Davidson, Michael J. Barry, Carol M. Mangione, Michael Cabana, Aaron B. Caughey, Esa M. Davis, Katrina E. Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, James Stevermer, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2022)

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF increases with age, from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, with a higher prevalence in men than in women. It is uncertain whether the prevalence of AF differs by race and ethnicity. Atrial fibrillation is a major risk factor for ischemic stroke and is associated with a substantial increase in the risk of stroke. Approximately 20% of patients who have a stroke associated with AF are first diagnosed with AF at the time of the stroke or shortly thereafter. To update its 2018 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the benefits and harms of screening for AF in older adults, the accuracy of screening tests, the effectiveness of screening tests to detect previously undiagnosed AF compared with usual care, and the benefits and harms of anticoagulant therapy for the treatment of screen-detected AF in older adults. Adults 50 years or older without a diagnosis or symptoms of AF and without a history of transient ischemic attack or stroke. The USPSTF concludes that evidence is lacking, and the balance of benefits and harms of screening for AF in asymptomatic adults cannot be determined. The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AF. (I statement).
Which infertile men with normal semen analysis deserve a second semen analysis in the real-life setting?
Authors: L. Boeri, P. Capogrosso, E. Pozzi, L. Candela, F. Belladelli, W. Cazzaniga, G. Fallara, D. Cignoli, N. Schifano, E. Ventimiglia, G. Colandrea, M. Alfano, C. Abbate, F. Montorsi, A. Salonia
Journal: European Urology (2021)
Contents
Authors: Masanori Iwanishi, Ken Ebihara, Toru Kusakabe, Wen Chen, Jun Ito, Hiroaki Masuzaki, Kiminori Hosoda, Kazuwa Nakao, Ako Fukami, Hisashi Adachi, Sho-Ichi Yamagishi, Takanori Matsui, Shin-Ichiro Ueda, Kazuo Nakamura, Mika Enomoto, Maki Otsuka, Shun-Ichi Kumagae, Yasuki Nanjo, Eita Kumagai, Eishi Esaki, Kyoko Murayama, Yuji Hirai, Tsutomu Imaizumi, Yanfeng Chen, Ying Li, Yanwen Wang, Ying Wen, Changhao Sun, Elena Philippou, Candace Bovill-Taylor, Chakravarthi Rajkumar, Maria Vampa, Eleana Ntatsaki, Audrey Brynes, Mary Hickson, Gary Frost, Hilary Tulk, Lindsay Robinson, Robert Henkin, I Velicu, Marcello Mancini, Anna Prinster, Giovanni Annuzzi, Raffaele Liuzzi, Rosalba Giacco, Carmela Medagli, Matteo Cremone, Gennaro Clemente, Simone Maurea, Gabriele Riccardi, Angela Rivellese, Marco Salvatore, Sang-Yeon Suh, Sung-Eun Choi, Hong-Yup Ahn, Hye-Min Yang, Yu-Il Kim, Nak-Jin Sung, Yeong Yoon, Hye Park, Kyung Yun, Soon Kim, Brahmesh Sivaprakasapillai, Indika Edirisinghe, Jody Randolph, Francene Steinberg, Tissa Kappagoda, Abbass Ghanbari-Niaki, Hossein Abednazari, Morteza Tayebi, Alireza Hossaini-Kakhak, Robert Kraemer, Ingrid Mostad, Kristian Bjerve, Samar Basu, Pauline Sutton, Keith Frayn, Valdemar Grill
Journal: Metabolism (2009)
Immunomodulatory effects and mechanisms of distraction osteogenesis
Authors: Shude Yang, Ning Wang, Yutong Ma, Shuaichen Guo, Shu Guo, Hongchen Sun
Journal: International Journal of Oral Science (2022)

Abstract Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
CDC Establishes Global Networks to Combat Antimicrobial Resistance
Authors: Bridget M. Kuehn
Journal: JAMA (2022)

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 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 Terms of Use | Privacy Policy | Accessibility Statement 2023 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
Development of a novel combined nomogram model integrating deep learning-pathomics, radiomics and immunoscore to predict postoperative outcome of colorectal cancer lung metastasis patients
Authors: Renjie Wang, Weixing Dai, Jing Gong, Mingzhu Huang, Tingdan Hu, Hang Li, Kailin Lin, Cong Tan, Hong Hu, Tong Tong, Guoxiang Cai
Journal: Journal of Hematology & Oncology (2022)

Abstract Limited previous studies focused on the death and progression risk stratification of colorectal cancer (CRC) lung metastasis patients. The aim of this study is to construct a nomogram model combing machine learning-pathomics, radiomics features, Immunoscore and clinical factors to predict the postoperative outcome of CRC patients with lung metastasis. In this study, a total of 103 CRC patients having metastases limited to lung and undergoing radical lung resection were identified. Patch-level convolutional neural network training in weakly supervised manner was used to perform whole slides histopathological images survival analysis. Synthetic minority oversampling technique and support vector machine classifier were used to identify radiomics features and build predictive signature. The Immunoscore for each patient was calculated from the density of CD3+ and CD8+ cells at the invasive margin and the center of metastatic tumor which were assessed on consecutive sections of automated digital pathology. Finally, pathomics and radiomics signatures were successfully developed to predict the overall survival (OS) and disease free survival (DFS) of patients. The predicted pathomics and radiomics scores are negatively correlated with Immunoscore and they are three independent prognostic factors for OS and DFS prediction. The combined nomogram showed outstanding performance in predicting OS (AUC = 0.860) and DFS (AUC = 0.875). The calibration curve and decision curve analysis demonstrated the considerable clinical usefulness of the combined nomogram. Taken together, the developed nomogram model consisting of machine learning-pathomics signature, radiomics signature, Immunoscore and clinical features could be reliable in predicting postoperative OS and DFS of colorectal lung metastasis patients.
Prostatic artery embolization: Results from a large multi-institutional Italian series
Authors: S. Secco, A. Olivero, P.M. Brambillasca, F. Barbosa, A.L. Pastore, A. Fuschi, A. Carbone, M. Gacci, P. Spatafora, S. Pieri, P. Dell’Oglio, S. Tappero, C. Trombetta, E. D’Andrea, F. Pozzi Mucelli, M. Rizzo, S. Serni, A. Liaci, A. Galfano, A.G. Rampoldi, A.M. Bocciardi
Journal: European Urology (2021)
Data Plotted Incorrectly in Figure 2
Journal: JAMA (2022)

David M. Kent, MD, MS; Jeffrey L. Saver, MD; Scott E. Kasner, MD; Jason Nelson, MS; John D. Carroll, MD; Gilles Chatellier, MD; Geneviève Derumeaux, MD; Anthony J. Furlan, MD; Howard C. Herrmann, MD; Peter Jüni, MD; Jong S. Kim, MD; Benjamin Koethe, MS; Pil Hyung Lee, MD; Benedicte Lefebvre, MD; Heinrich P. Mattle, MD; Bernhard Meier, MD; Mark Reisman, MD; Richard W. Smalling, MD, PhD; Lars Soendergaard, MD; Jae-Kwan Song, MD; Jean-Louis Mas, MD; David E. Thaler, MD, PhD
Optimizing the number of systematic cores during an MRI target biopsy: Preliminary results from the prospective, single center SCOT Trial (NCT 04183699)
Authors: A. Stabile, F. Pellegrino, F. Barletta, G. Sorce, S. Scuderi, E. Mazzone, V. Cucchiara, C.A. Bravi, L. Nocera, G. Rosiello, G. Cirulli, D. Cannoletta, L. D’Ambrosio, M. Picozzi, N. Fossati, G. Gandaglia, G. Brembilla, A. Esposito, F. De Cobelli, F. Montorsi, A. Briganti
Journal: European Urology (2021)
Clinical Outcomes Among Patients With 1-Year Survival Following Intensive Care Unit Treatment for COVID-19
Authors: Hidde Heesakkers, Johannes G. van der Hoeven, Stijn Corsten, Inge Janssen, Esther Ewalds, Koen S. Simons, Brigitte Westerhof, Thijs C. D. Rettig, Crétien Jacobs, Susanne van Santen, Arjen J. C. Slooter, Margaretha C. E. van der Woude, Mark van den Boogaard, Marieke Zegers
Journal: JAMA (2022)

<h3>Importance</h3> One-year outcomes in patients who have had COVID-19 and who received treatment in the intensive care unit (ICU) are unknown. <h3>Objective</h3> To assess the occurrence of physical, mental, and cognitive symptoms among patients with COVID-19 at 1 year after ICU treatment. <h3>Design, Setting, and Participants</h3> An exploratory prospective multicenter cohort study conducted in ICUs of 11 Dutch hospitals. Patients (N = 452) with COVID-19, aged 16 years and older, and alive after hospital discharge following admission to 1 of the 11 ICUs during the first COVID-19 surge (March 1, 2020, until July 1, 2020) were eligible for inclusion. Patients were followed up for 1 year, and the date of final follow-up was June 16, 2021. <h3>Exposures</h3> Patients with COVID-19 who received ICU treatment and survived 1 year after ICU admission. <h3>Main Outcomes and Measures</h3> The main outcomes were self-reported occurrence of physical symptoms (frailty [Clinical Frailty Scale score ≥5], fatigue [Checklist Individual Strength—fatigue subscale score ≥27], physical problems), mental symptoms (anxiety [Hospital Anxiety and Depression {HADS} subscale score ≥8], depression [HADS subscale score ≥8], posttraumatic stress disorder [mean Impact of Event Scale score ≥1.75]), and cognitive symptoms (Cognitive Failure Questionnaire—14 score ≥43) 1 year after ICU treatment and measured with validated questionnaires. <h3>Results</h3> Of the 452 eligible patients, 301 (66.8%) patients could be included, and 246 (81.5%) patients (mean [SD] age, 61.2 [9.3] years; 176 men [71.5%]; median ICU stay, 18 days [IQR, 11 to 32]) completed the 1-year follow-up questionnaires. At 1 year after ICU treatment for COVID-19, physical symptoms were reported by 182 of 245 patients (74.3% [95% CI, 68.3% to 79.6%]), mental symptoms were reported by 64 of 244 patients (26.2% [95% CI, 20.8% to 32.2%]), and cognitive symptoms were reported by 39 of 241 patients (16.2% [95% CI, 11.8% to 21.5%]). The most frequently reported new physical problems were weakened condition (95/244 patients [38.9%]), joint stiffness (64/243 patients [26.3%]) joint pain (62/243 patients [25.5%]), muscle weakness (60/242 patients [24.8%]) and myalgia (52/244 patients [21.3%]). <h3>Conclusions and Relevance</h3> In this exploratory study of patients in 11 Dutch hospitals who survived 1 year following ICU treatment for COVID-19, physical, mental, or cognitive symptoms were frequently reported.
Commentary
Authors: Linda Y. Zhang, Mouen A. Khashab
Journal: Endoscopy (2021)

The spectrum of malignant gastrointestinal tract obstruction is broad. Gastric outlet obstruction is now effectively managed by traditional enteral stenting or more recently by endoscopic ultrasound (EUS)-guided gastroenterostomy. However, malignant distal small-bowel obstruction often requires surgical intervention. Here, the authors describe a patient with a preterminal ileum obstruction that was successfully treated with an EUS-guided coloenterostomy. The challenges in this scenario are threefold. First, the distal location of the stricture necessitates echoendoscope passage transanally, or alternatively via a colostomy as in this case. Second, the most distal small-bowel loop needs to be identified from multiple surrounding dilated loops. Importantly, while contrast and methylene blue is usually used to mark the target organ, here it marks the proximal small bowel which is intentionally avoided in preference of more distal loops. Finally, the small bowel is a mobile structure of relatively small diameter. Nevertheless, the authors expertly bypass these issues, thereby providing a valuable alternative for palliation of malignant distal small-bowel obstruction that avoids the morbidities of surgery. Although a venting gastrostomy and parenteral nutrition would have been a valid alternative, it would probably have constituted significant impairment to the patient’s quality of life.
Preoperative PSMA PET/CT as a predictor of biochemical persistence and early biochemical recurrence
Authors: D.J.H. Baas, M.G.M. Schilham, J.M.S. De Baaij, H.J.E.J. Vrijhof, R.J. Hoekstra, J.P.M. Sedelaar, R. Hermsen, D.M. Somford, J.P.A. Van Basten
Journal: European Urology (2021)
Outcomes of lymph node dissection in nephroureterectomy in treatment of upper tract urothelial carcinoma: Analysis of the robuust registry
Authors: K. Hakimi, R. Autorino, M. Meagher, S. Soliman, J. Yuan, R. Stein, K. Badani, R. Mehrazin, D. Eun, M. Gonzalgo, V. Margulis, R. Li, R. Uzzo, J. Porter, C. Sundaram, F. Abdollah, A. Mottrie, A. Minervini, M. Ferro, K. Rha, I. Derweesh
Journal: European Urology (2021)
PD-L1 CAR effector cells induce self-amplifying cytotoxic effects against target cells
Authors: Malgorzata Bajor, Agnieszka Graczyk-Jarzynka, Katsiaryna Marhelava, Anna Burdzinska, Angelika Muchowicz, Agnieszka Goral, Andriy Zhylko, Karolina Soroczynska, Kuba Retecki, Marta Krawczyk, Marta Klopotowska, Zofia Pilch, Leszek Paczek, Karl-Johan Malmberg, Sébastien Wälchli, Magdalena Winiarska, Radoslaw Zagozdzon
Journal: Journal for ImmunoTherapy of Cancer (2022)

Immune checkpoint inhibitors and chimeric antigen receptor (CAR)-based therapies have transformed cancer treatment. Recently, combining these approaches into a strategy of PD-L1-targeted CAR has been proposed to target PD-L1high tumors. Our study provides new information on the efficacy of such an approach against PD-L1low targets.New atezolizumab-based PD-L1-targeted CAR was generated and introduced into T, NK, or NK-92 cells. Breast cancer MDA-MB-231 and MCF-7 cell lines or non-malignant cells (HEK293T, HMEC, MCF-10A, or BM-MSC) were used as targets to assess the reactivity or cytotoxic activity of the PD-L1-CAR-bearing immune effector cells. Stimulation with IFNγ or with supernatants from activated CAR T cells were used to induce upregulation of PD-L1 molecule expression on the target cells. HER2-CAR T cells were used for combination with PD-L1-CAR T cells against MCF-7 cells.PD-L1-CAR effector cells responded vigorously with degranulation and cytokine production to PD-L1high MDA-MB-231 cells, but not to PD-L1low MCF-7 cells. However, in long-term killing assays, both MDA-MB-231 and MCF-7 cells were eliminated by the PD-L1-CAR cells, although with a delay in the case of PD-L1low MCF-7 cells. Notably, the coculture of MCF-7 cells with activated PD-L1-CAR cells led to bystander induction of PD-L1 expression on MCF-7 cells and to the unique self-amplifying effect of the PD-L1-CAR cells. Accordingly, PD-L1-CAR T cells were active not only against MDA-MD-231 and MCF-7-PD-L1 but also against MCF-7-pLVX cells in tumor xenograft models. Importantly, we have also observed potent cytotoxic effects of PD-L1-CAR cells against non-malignant MCF-10A, HMEC, and BM-MSC cells, but not against HEK293T cells that initially did not express PD-L1 and were unresponsive to the stimulation . Finally, we have observed that HER-2-CAR T cells stimulate PD-L1 expression on MCF-7 cells and therefore accelerate the functionality of PD-L1-CAR T cells when used in combination.In summary, our studies show that CAR-effector cells trigger the expression of PD-L1 on target cells, which in case of PD-L1-CAR results in the unique self-amplification phenomenon. This self-amplifying effect could be responsible for the enhanced cytotoxicity of PD-L1-CAR T cells against both malignant and non-malignant cells and implies extensive caution in introducing PD-L1-CAR strategy into clinical studies.
Immunogenicity of BNT162b2 vaccine against the Alpha and Delta variants in immunocompromised patients with systemic inflammatory diseases
Authors: Jerome Hadjadj, Delphine Planas, Amani Ouedrani, Solene Buffier, Laure Delage, Yann Nguyen, Timothée Bruel, Marie-Claude Stolzenberg, Isabelle Staropoli, Natalia Ermak, Laure Macraigne, Caroline Morbieu, Soledad Henriquez, David Veyer, Hélène Péré, Marion Casadevall, Luc Mouthon, Frederic Rieux-Laucat, Lucienne Chatenoud, Olivier Schwartz, Benjamin Terrier
Journal: Annals of the Rheumatic Diseases (2022)

The emergence of strains of SARS-CoV-2 exhibiting increase viral fitness and immune escape potential, such as the Delta variant (B.1.617.2), raises concerns in immunocompromised patients. We aimed to evaluate seroconversion, cross-neutralisation and T-cell responses induced by BNT162b2 in immunocompromised patients with systemic inflammatory diseases.Prospective monocentric study including patients with systemic inflammatory diseases and healthcare immunocompetent workers as controls. Primary endpoints were anti-spike antibodies levels and cross-neutralisation of Alpha and Delta variants after BNT162b2 vaccine. Secondary endpoints were T-cell responses, breakthrough infections and safety.Sixty-four cases and 21 controls not previously infected with SARS-CoV-2 were analysed. Kinetics of anti-spike IgG after BNT162b2 vaccine showed lower and delayed induction in cases, more pronounced with rituximab. Administration of two doses of BNT162b2 generated a neutralising response against Alpha and Delta in 100% of controls, while sera from only one of rituximab-treated patients neutralised Alpha (5%) and none Delta. Other therapeutic regimens induced a partial neutralising activity against Alpha, even lower against Delta. All controls and cases except those treated with methotrexate mounted a SARS-CoV-2 specific T-cell response. Methotrexate abrogated T-cell responses after one dose and dramatically impaired T-cell responses after two doses of BNT162b2. Third dose of vaccine improved immunogenicity in patients with low responses.Rituximab and methotrexate differentially impact the immunogenicity of BNT162b2, by impairing B-cell and T-cell responses, respectively. Delta fully escapes the humoral response of individuals treated with rituximab. These findings support efforts to improve BNT162b2 immunogenicity in immunocompromised individuals (ClinicalTrials.gov number, NCT04870411).
Dupilumab‐associated head and neck dermatitis is associated with elevated pretreatment serum <i>Malassezia</i> ‐specific <scp>IgE</scp> : a multicentre, prospective cohort study
Authors: Emily Kozera, Thomas Stewart, Kyra Gill, Mae Anne De La Vega, John W. Frew
Journal: British Journal of Dermatology (2022)

Dupilumab associated head and neck dermatitis is incompletely understood. This prospective multicentre prospective study identified baseline Malassezia-specific IgE as associated with the development of Dupilumab associated head and neck dermatitis.
DNA methylation urine biomarkers test (EpiCheck® assay) in the diagnosis of upper tract urothelial carcinoma: Results from a single-center prospective study
Authors: A. Gallioli, M. Fontana, R. Boissier, A. Territo, P. Diana, A. Piana, C. Martinez, A. Sanchez-Puy, J.D. Subiela, F. Sanguedolce, J.M. Gaya Sopena, J. Palou, A. Breda
Journal: European Urology (2021)