tbuckley/cabot-search huggingface dataset:
Recurrent Human Papillomavirus–Related Head and Neck Cancer Undergoes Metabolic Reprogramming and Is Driven by Oxidative Phosphorylation
Authors: Avani Vyas, R. Alex Harbison, Daniel L. Faden, Mark Kubik, Drake Palmer, Qing Zhang, Hatice U. Osmanbeyoglu, Kirill Kiselyov, Eduardo Méndez, Umamaheswar Duvvuri
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Human papillomavirus (HPV) infection drives the development of some head and neck squamous cell carcinomas (HNSCC). This disease is rapidly increasing in incidence worldwide. Although these tumors are sensitive to treatment, approximately 10% of patients fail therapy. However, the mechanisms that underlie treatment failure remain unclear. Experimental Design: We performed RNA sequencing (RNA-seq) on tissues from matched primary- (pHNSCC) and metachronous-recurrent cancers (rHNSCC) to identify transcriptional differences to gain mechanistic insight into the evolutionary adaptations of metachronous-recurrent tumors. We used HPV-related HNSCC cells lines to investigate the effect of (i) NRF2 overexpression on growth in vitro and in vivo, (ii) oxidative phosphorylation (OXPHOS) inhibition using IACS-010759 on NRF2-dependent cells, and (iii) combination of cisplatin and OXPHOS inhibition. Results: The OXPHOS pathway is enriched in recurrent HPV-associated HNSCC and may contribute to treatment failure. NRF2-enriched HNSCC samples from The Cancer Genome Atlas (TCGA) with enrichment in OXPHOS, fatty-acid metabolism, Myc, Mtor, reactive oxygen species (ROS), and glycolytic signaling networks exhibited worse survival. HPV-positive HNSCC cells demonstrated sensitivity to the OXPHOS inhibitor, in a NRF2-dependent manner. Further, using murine xenograft models, we identified NRF2 as a driver of tumor growth. Mechanistically, NRF2 drives ROS and mitochondrial respiration, and NRF2 is a critical regulator of redox homeostasis that can be crippled by disruption of OXPHOS. NRF2 also mediated cisplatin sensitivity in endogenously overexpressing primary HPV-related HNSCC cells. Conclusions: These results unveil a paradigm-shifting translational target harnessing NRF2-mediated metabolic reprogramming in HPV-related HNSCC.
In patients hospitalized for COPD exacerbation, a PE diagnostic strategy + usual care did not improve outcomes
Authors: Roza Chaireti
Journal: Annals of Internal Medicine (2022)

Source Citation Jiménez D, Agustí A, Tabernero E, et al. Effect of a pulmonary embolism diagnostic strategy on clinical outcomes in patients hospitalized for COPD exacerbation: a randomized clinical trial. JAMA. 2021;326:1277-85. 34609451
Venetoclax-ponatinib for T315I/compound-mutated Ph+ acute lymphoblastic leukemia
Authors: Huafeng Wang, Chang Yang, Ting Shi, Yi Zhang, Jiejing Qian, Yungui Wang, Yongxian Hu, Liping Mao, Xiujin Ye, Fang Liu, Zhenfang Xi, Lihong Shou, Caiyun Fu, Hua Naranmandura, Jie Jin, Hong-Hu Zhu
Journal: Blood Cancer Journal (2022)
Identification and Treatment of Neonatal Seizures During Therapeutic Hypothermia and Rewarming—Reply
Authors: Lina F. Chalak
Journal: JAMA Neurology (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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 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 Neurology journal
Autoantibodies targeting neuronal proteins as biomarkers for neurodegenerative diseases
Authors: Gabriela Kocurova, Jan Ricny, Saak V. Ovsepian
Journal: Theranostics (2022)

Neurodegenerative diseases (NDDs) are associated with the accumulation of a range of misfolded proteins across the central nervous system and related autoimmune responses, including the generation of antibodies and the activation of immune cells. Both innate and adaptive immunity become mobilized, leading to cellular and humoral effects. The role of humoral immunity in disease onset and progression remains to be elucidated with rising evidence suggestive of positive (protection, repair) and negative (injury, toxicity) outcomes. In this study, we review advances in research of neuron-targeting autoantibodies in the most prevalent NDDs. We discuss their biological origin, molecular diversity and changes in the course of diseases, consider their relevance to the initiation and progression of pathology as well as diagnostic and prognostic significance. It is suggested that the emerging autoimmune aspects of NDDs not only could facilitate the early detection but also might help to elucidate previously unknown facets of pathobiology with relevance to the development of precision medicine.
Initiation and completion of treatment for latent tuberculosis infection in migrants globally: a systematic review and meta-analysis
Authors: Kieran Rustage, Jessica Lobe, Sally E Hayward, Kristina L Kristensen, Ioana Margineanu, Ymkje Stienstra, Delia Goletti, Dominik Zenner, Teymur Noori, Manish Pareek, Christina Greenaway, Jon S Friedland, Laura B Nellums, Sally Hargreaves
Journal: The Lancet Infectious Diseases (2021)
Abstract EP12: Uric Acid Predicts Recovery Of Left Ventricular Function And Adverse Events In Heart Failure With Reduced Ejection Fraction: Potential Mechanistic Insight From Network Analyses
Authors: Xiqiang Wang, Xiude Fan, Qihui Wu, Junkui Wang, Jiansong Fang
Journal: Circulation (2022)

Background and Aims: Heart failure with reduced ejection fraction (HFrEF) still carries a high risk for a sustained decrease in left ventricular ejection fraction (LVEF) even with the optimal medical therapy. Currently, there is no effective tool to stratify these patients according to their recovery potential. We tested the hypothesis that uric acid (UA) could predict recovery of LVEF and prognosis of HFrEF patients and attempted to explore mechanistic relationship between hyperuricemia and HFrEF. Methods: HFrEF patients with hyperuricemia were selected from the National Inpatient Sample (NIS) 2016-2018 database and our Xianyang prospective cohort study. Demographics, cardiac risk factors, and cardiovascular events were identified. Network-based analysis was utilized to examine the relationship between recovery of LVEF and hyperuricemia, and we further elucidated the underlying mechanisms for the impact of hyperuricemia on HFrEF. Results: After adjusting confounding factors by propensity score matching, hyperuricemia was a determinant of HFrEF [OR 1.247 (1.172-1.328); P &lt;0.001] of NIS dataset. In Xianyang prospective cohort study, hyperuricemia is a significant and independent risk factor for all-cause death (adjusted HR 2.387, 95% CI 1.141-4.993; P =0.021), heart failure readmission (adjusted HR 1.848, 95% CI 1.048-3.259; P =0.034), and composite events (adjusted HR 1.706, 95% CI 1.001-2.906; P =0.049) in HFrEF patients. UA value at baseline was negatively correlated to LVEF of follow-ups (r=-0.19; P =0.046). Cutoff UA value of 312.5 μmmol/L at baseline can work as a predictor of LVEF recovery during follow-up, with the sensitivity of 66.7%, the specificity of 35.1%, and the accuracy of 0.668 (95% CI, 0.561-0.775; P =0.006). Moreover, gene overlap analysis and network proximity analysis demonstrated a strong correlation between HFrEF and Hyperuricemia. Conclusion: Lower baseline UA value predicted the LVEF recovery and less long-term adverse events in HFrEF patients. Our results provide new insights into underlying mechanistic relationship between hyperuricemia and HFrEF.
Clinical Effectiveness of Elexacaftor/Tezacaftor/Ivacaftor in People with Cystic Fibrosis: A Clinical Trial
Authors: David P. Nichols, Alex C. Paynter, Sonya L. Heltshe, Scott H. Donaldson, Carla A. Frederick, Steven D. Freedman, Daniel Gelfond, Lucas R. Hoffman, Andrea Kelly, Michael R. Narkewicz, Jessica E. Pittman, Felix Ratjen, Margaret Rosenfeld, Scott D. Sagel, Sarah Jane Schwarzenberg, Pradeep K. Singh, George M. Solomon, Michael S. Stalvey, John P. Clancy, Shannon Kirby, Jill M. Van Dalfsen, Margaret H. Kloster, Steven M. Rowe
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The cystic fibrosis (CF) modulator drug, elexacaftor/tezacaftor/ivacaftor (ETI), proved highly effective in controlled clinical trials for individuals with at least one F508del allele, which occurs in at least 85% of people with CF.
Abstract P159: The Optimal Method To Predict Hemoglobin A1c From Flash Glucose Monitor Data
Authors: Soichi Takeishi
Journal: Circulation (2022)

In situations where it is difficult for patients to visit hospitals, such as the coronavirus disease pandemic, it is important to more detailly predict hemoglobin A1C (HbA1c) from flash glucose monitor (FGM) data. CGM data over 14 days can be obtained from a FGM sensor; therefore, there are many options for extracting the duration from which glucose levels are derived. Thus, the extracted durations were closely studied to determine which mean glucose levels can predict HbA1c more accurately. Seventy-three outpatients with type 2 diabetes mellitus underwent HbA1c testing, wore a FGM (FreeStyle Libre Pro), and did not change diabetic treatments, on a hospital visit. FGM data over 24 h х 13 days (from 00:00 on day 2 to 24:00 on day 14 [FGM attachment: day 1]) were analyzed. The mean glucose levels were calculated corresponding to the following durations: 1 day: day 2 ~ day 14 (n=13), 2 days: days 2-3 ~ days 13-14 (n=12) … 12 days: days 2-13 ~ days 3-14 (n=2), 13 days: days 2-14 (n=1) [total 91 durations] (extracted mean glucose levels). Data were analyzed in all patients (n=73), in patients with hypoglycemia in the 13 days (Hypo) group (n=40), and in patients without hypoglycemia in the 13 days (Nonhypo) group (n=33). In all patients, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.76-0.86, p&lt;0.001). HbA1c was the most significantly correlated to the mean glucose levels over 13 days (days 2-14). “Correlation coefficients between HbA1c and extracted mean glucose levels” (“r, HbA1c, EMGL”) were also correlated to number of extracted days for the extracted mean glucose levels (r=0.80, p&lt;0.001 [n=91]). In the Hypo group, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.55-0.73, p&lt;0.001). The mean glucose levels over 13 days (days 2-14) were the most significantly correlated to HbA1c. “r, HbA1c, EMGL” correlated to the number of extracted days for the extracted mean glucose levels (r=0.68, p&lt;0.001; Fig. 2). In the Nonhypo group, HbA1c was correlated to all 91 extracted mean glucose levels (r=0.73-0.87, p&lt;0.001). The mean glucose levels over 12 days (days 2-13) were the most significantly correlated to HbA1c. “r, HbA1c, EMGL” correlated to the number of extracted days for the extracted mean glucose levels (r=0.61, p&lt;0.001). The results of the present study are consistent with that of a previous study reporting that the minimum duration needed to estimate time in range over 90 days is 14 days. In the prediction of HbA1c using data from one FGM sensor, prolonged measurement can make the glucose management indicator more accurate. Especially for patients with hypoglycemia, the importance of prolonged measurement may be applicable.
Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial
Authors: Jean-Marc Naccache, Stéphane Jouneau, Morgane Didier, Raphaël Borie, Marine Cachanado, Arnaud Bourdin, Martine Reynaud-Gaubert, Philippe Bonniaud, Dominique Israël-Biet, Grégoire Prévot, Sandrine Hirschi, François Lebargy, Sylvain Marchand-Adam, Nathalie Bautin, Julie Traclet, Emmanuel Gomez, Sylvie Leroy, Frédéric Gagnadoux, Frédéric Rivière, Emmanuel Bergot, Anne Gondouin, Elodie Blanchard, Antoine Parrot, François-Xavier Blanc, Alexandre Chabrol, Stéphane Dominique, Aude Gibelin, Abdellatif Tazi, Laurence Berard, Pierre Yves Brillet, Marie-Pierre Debray, Alexandra Rousseau, Mallorie Kerjouan, Olivia Freynet, Marie-Christine Dombret, Anne-Sophie Gamez, Ana Nieves, Guillaume Beltramo, Jean Pastré, Aurélie Le Borgne-Krams, Tristan Dégot, Claire Launois, Laurent Plantier, Lidwine Wémeau-Stervinou, Jacques Cadranel, Cécile Chenivesse, Dominique Valeyre, Bruno Crestani, Vincent Cottin, Tabassome Simon, Hilario Nunes
Journal: The Lancet Respiratory Medicine (2021)
Longitudinal respiratory subphenotypes in patients with COVID-19-related acute respiratory distress syndrome: results from three observational cohorts
Authors: Lieuwe D J Bos, Michael Sjoding, Pratik Sinha, Sivasubramanium V Bhavani, Patrick G Lyons, Alice F Bewley, Michela Botta, Anissa M Tsonas, Ary Serpa Neto, Marcus J Schultz, Robert P Dickson, Frederique Paulus, J.P. van Akkeren, A.G. Algera, C.K. Algoe, R.B. van Amstel, A. Artigas, O.L. Baur, P. van de Berg, A.E. van den Berg, D.C.J.J. Bergmans, D.I. van den Bersselaar, F.A. Bertens, A.J.G.H. Bindels, M.M. de Boer, S. den Boer, L.S. Boers, M. Bogerd, L.D.J. Bos, M. Botta, J.S. Breel, H. de Bruin, S. de Bruin, C.L. Bruna, L.A. Buiteman-Kruizinga, O. Cremer, R.M. Determann, W. Dieperink, D.A. Dongelmans, H.S. Franke, M.S. Galek-Aldridge, M.J. de Graaff, L.A. Hagens, J.J. Haringman, S.T. van der Heide, P.L.J. van der Heiden, N.F.L. Heijnen, S.J.P. Hiel, L.L. Hoeijmakers, L. Hol, M.W. Hollmann, M.E. Hoogendoorn, J. Horn, R. van der Horst, E.L.K. Ie, D. Ivanov, N.P. Juffermans, E. Kho, E.S. de Klerk, A.W.M.M. Koopman-van Gemert, M. Koopmans, S. Kucukcelebi, M.A. Kuiper, D.W. de Lange, I. Martin-Loeches, G. Mazzinari, D.M.P. van Meenen, L. Morales-Quinteros, N. van Mourik, S.G. Nijbroek, M. Onrust, E.A.N. Oostdijk, F. Paulus, C.J. Pennartz, J. Pillay, L. Pisani, I.M. Purmer, T.C.D. Rettig, J.P. Roozeman, M.T.U. Schuijt, M.J. Schultz, A. Serpa Neto, M.E. Sleeswijk, M.R. Smit, P.E. Spronk, W. Stilma, A.C. Strang, A.M. Tsonas, P.R. Tuinman, C.M.A. Valk, F.L. Veen-Schra, L.I. Veldhuis, P. van Velzen, W.H. van der Ven, A.P.J. Vlaar, P. van Vliet, P.H.J. van der Voort, L. van Welie, H.J.F.T. Wesselink, H.H. van der Wier-Lubbers, B. van Wijk, T. Winters, W.Y. Wong, A.R.H. van Zanten
Journal: The Lancet Respiratory Medicine (2021)
Reduced Glomerular Filtration in Diabetes Is Attributable to Loss of Density and Increased Resistance of Glomerular Endothelial Cell Fenestrations
Authors: Natalie C. Finch, Sarah S. Fawaz, Chris R. Neal, Matthew J. Butler, Vivian K. Lee, Andrew J. Salmon, Abigail C. Lay, Megan Stevens, Lusyan Dayalan, Hamid Band, Harry H. Mellor, Steven J. Harper, David T. Shima, Gavin I. Welsh, Rebecca R. Foster, Simon C. Satchell
Journal: Journal of the American Society of Nephrology (2022)

Glomerular endothelial cell (GEnC) fenestrations are recognized as an essential component of the glomerular filtration barrier, yet little is known about how they are regulated and their role in disease.
Risk of Upstaging Due to Oncofertility Treatment Mimicking Pelvic Lymphoma on 18F-FDG PET/CT
Authors: Jan-Henning Schierz, Farzana Ali, Anke McLeod
Journal: Clinical Nuclear Medicine (2021)

Abstract A 23-year-old woman with primary mediastinal large B-cell lymphoma was referred to 18 F-FDG PET/CT for staging. Besides the large mediastinal FDG-avid tumor, another FDG-avid lesion with an SUV higher than expected in corpus luteum cysts was found in the pelvis, raising suspicion for tumor. However, gynecologic ultrasound and review of patient chart revealed history of oncofertility treatment with GNRH analog. This prior treatment was responsible for the intense 18 F-FDG uptake within the left ovary, way above the SUV levels commonly associated with menstrual cycle. In this case, the disease was downgraded to stage II, resulting in a less aggressive treatment.
68Ga-FAPI-04 PET/CT Imaging for Fibrous Dysplasia of the Bone
Authors: Yingwei Wang, Junhao Wu, Lin Liu, DengSai Peng, Yue Chen
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-labeled quinoline-based fibroblast activation protein inhibitors ( 68 Ga-FAPIs) are promising agents for tumor imaging. However, some nonneoplastic lesions can also cause increased FAPI uptake. We report a case of a patient with polyostotic fibrous dysplasia who showed widespread and intense metabolic activity on 68 Ga-FAPI PET/CT. Physicians should be aware that fibrous dysplasia can also cause elevated FAPI activity.
FDG PET/CT in Cryptogenic Multifocal Ulcerating Stenosing Enteropathy
Authors: Jian Zhang, Zhi Li, Ling Zhang, Aisheng Dong, Yuzhao Zhu
Journal: Clinical Nuclear Medicine (2021)

Abstract Cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) is a rare and exclusive small intestine disease, characterized by repeated anemia or obstruction resulting from multiple shallow ulcers with strictures in the small intestine. We present a case of CMUSE showing multiple foci of activity in the small bowel on FDG PET/CT. This case indicates that CMUSE should be included in the differential diagnosis of multifocal FDG activity in the small bowel along with lymphoma, carcinoma, tuberculosis, Crohn disease, Behçet disease, and drug-induced enteropathy.
Nanopore adaptive sampling: a tool for enrichment of low abundance species in metagenomic samples
Authors: Samuel Martin, Darren Heavens, Yuxuan Lan, Samuel Horsfield, Matthew D. Clark, Richard M. Leggett
Journal: Genome biology (2022)

Adaptive sampling is a method of software-controlled enrichment unique to nanopore sequencing platforms. To test its potential for enrichment of rarer species within metagenomic samples, we create a synthetic mock community and construct sequencing libraries with a range of mean read lengths. Enrichment is up to 13.87-fold for the least abundant species in the longest read length library; factoring in reduced yields from rejecting molecules the calculated efficiency raises this to 4.93-fold. Finally, we introduce a mathematical model of enrichment based on molecule length and relative abundance, whose predictions correlate strongly with mock and complex real-world microbial communities.
Abstract 11762: The Proximity of the Stomach to the Inferior Wall of the Heart: Implications for Non-Invasive Radio-Ablation of Ventricular Tachycardia
Authors: Bryan Wu, Sai Vanam, Todd Atwood, Andrew Bruggeman, Kevin Moore, Elliot McVeigh, Frederick Han, Jonathan C Hsu, Kurt S Hoffmayer, Farshad Raissi, Ulrika Birgersdotter-green, JENNIFER KARUNAMUNI, Paul Stark, Gregory K Feld, Arno Mundt, David Krummen, Gordon Ho
Journal: Circulation (2021)

Introduction: Stereotactic ablative radiotherapy is a promising therapy for ventricular tachycardia (VT), but the formation of gastro-pericardial fistula is a serious complication associated with this procedure. The proximity of the stomach to the heart has not been well characterized. Hypothesis: We hypothesized that the stomach is located in close proximity (&lt;1cm) to the inferior cardiac wall. Methods: Patients who underwent 4D cardiac computed tomography (4DCT) prior to a catheter ablation procedure for atrial or ventricular arrhythmias at 2 medical centers were studied retrospectively. 4DCT was acquired using cardiac-gated Siemens Force or GE Revolution scanners. The closest distance from the stomach or esophagus to the left ventricular (LV) myocardium was measured during both end systole and diastole (Fig 1) using imaging analysis software (Horos Project, Annapolis, MD). Clinical predictors of close proximity were assessed using Student’s t-test, Chi-squared and Pearson’s linear regression. Results: In 42 patients (age 65±11.4 years, VT/PVC ablation in 21/42 patients, 50%), the mean gastric proximity was 7.5±4.2mm during end-systole and 6.1±3.6mm during end-diastole (p=0.12). Smaller gastric proximity was significantly associated with increasing LV diameter (y=-1.376*x +12.55; p=0.03) or a history of coronary artery disease (4.8±2.2mm vs 8.3±4.4mm, p=0.02). The closest proximity of the stomach was found most frequently in the mid-segment (compared to the basal or apical segments of the inferior wall, p&lt;0.0001). Conclusions: In patients with arrhythmias, the stomach is located within a mean of 6mm to the mid-inferior wall of the LV, with closer proximity in patients with dilated hearts. Careful avoidance of the stomach is critical during radio-ablative therapy of VT to avoid complications, particularly in patients with mid-inferior wall targets and dilated hearts. Studies are ongoing to study motion management strategies to improve precision.
Highlights of the NCCN Oncology Research Program
Authors: Sarbajit Mukherjee, Sarah Chatley
Journal: Journal of the National Comprehensive Cancer Network (2022)

This is an open-label, multicenter, phase II study of trifluridine/tipiracil (FTD/TPI) administered with oxaliplatin before chemoradiation in patients with adenocarcinoma of the esophagus or gastroesophageal junction (GEJ).Patients meeting inclusion criteria will receive 3 cycles of FTD/TPI (35 mg/m 2 twice daily) and oxaliplatin (85 mg/m 2 ) before undergoing concurrent chemoradiation (standard-of-care radiation dose of 5,040 cGy will be used at all participating study sites) with carboplatin (area under the curve, 2) and paclitaxel (50 mg/m 2 ) for 6 weeks, followed by surgery.FTD/TPI will be self-administered (in tablet form) twice daily by study participants and documented in the provided drug diary.In this study, circulating tumor DNA (ctDNA) levels will be collected at 5 different time points: at diagnosis, after completion of induction chemotherapy, after completion of chemoradiation, after surgery, and at the time of disease recurrence, if this occurs.The aim is to correlate the ctDNA level with disease recurrence and metabolic response on PET/CT.Accrual is expected to take 24 months (N545) with an additional 12 months of follow-up on study.After completion of 1 year of on-study follow-up, patients will be followed (monitored for survival status) as per standard of care: year 1 through year 2, every 3 to 6 months, every 6 to 12 months for 3 to 5 years, and then annually until disease progression or death, whichever occurs first.Estimated time frame for analysis of the primary endpoint is approximately 3 years after study commencement.