tbuckley/cabot-search huggingface dataset:
Abstract IA04: New approaches to study cancer predisposition syndromes
Authors: Christian P. Kratz
Journal: Cancer Research (2020)

Abstract The diagnosis of a cancer predisposition syndrome (CPS) in a child diagnosed with cancer influences medical care; however, many open questions remain in the areas of counseling, psychosocial support, cancer prevention, surveillance, and therapy. To address such issues, a CPS-registry was launched: www.cancer-predisposition.org. The CPS-registry (1) provides detailed information for affected families and health care professionals, (2) collects biospecimens for translational research, (3) assembles both retrospective and annual prospective data on cancer diagnoses and surveillance measures in individuals with approximately 60 different CPS, (4) makes mutation data publicly available through accessible databases, (5) shares data internationally, (6) links data with trial groups and cancer registries, and (7) provides expert opinion for individual treatment decisions. Due to hidden clinical signs, CPS are often overlooked; however, various clinical tools have been developed to increase the percentage of families that are being offered counseling and testing. Moreover, CPS diagnosis is dramatically facilitated by the increasing use of agnostic next-generation sequencing in pediatric oncology, supporting the notion that 10% of children with cancer harbor mutations in cancer predisposition genes, often in the absence of clinical signs. CPS diagnosis yet remains a challenge prior to a first cancer diagnosis; however, a more systematic diagnostic approach is required to offer prevention and surveillance measures to these individuals. Strong family support organizations such as LFSA and FARF have dramatically improved collaborative research in the CPS field. In the future, clinical protocols for CPS individuals will pave the way for better prevention, surveillance, and cancer treatment strategies. Citation Format: Christian P. Kratz. New approaches to study cancer predisposition syndromes [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr IA04.
Quest for Ideal Composite Biomarkers for Response to Immunotherapies
Authors: Umang Swami, Roberto H. Nussenzveig, Neeraj Agarwal
Journal: Clinical Cancer Research (2020)

Abstract In the CheckMate 275 study, composite biomarkers appear to better predict response to immunotherapy over individual ones. Nevertheless, the path forward needs consensus guidelines for biomarker interpretation. Thereafter, prospective validation with real-time, serial biospecimen collection along with the development of composite biomarker models leads to the goal of personalized therapy. See related article by Galsky et al., p. 5120
THU0274 RENAL CHARACTERISTICS AND OUTCOME OF LUPUS NEPHRITIS ACCORDING TO ITS TIME OF ONSET
Authors: O. C. Kwon, J. H. Park, M. C. Park
Journal: Annals of the Rheumatic Diseases (2020)

Background: Lupus nephritis (LN) usually develops within 5 years of systemic lupus erythematosus (SLE) onset. It is unclear whether the course and outcome of LN differ between patients who initially had LN at SLE onset (initial-onset LN) and those who developed LN within 5 years after SLE onset (early-onset LN). Objectives: To compare clinical characteristics and renal outcomes between SLE patients with initial-onset LN and SLE patients with early-onset LN. Methods: SLE patients with biopsy-proven LN were retrospectively reviewed. The clinical parameters and renal outcomes were compared between initial-onset LN and early-onset LN groups. We used Cox regression analysis to estimate risk of worse renal outcome, according to the onset time of LN. Results: Of the total 136 LN patients, 92 (67.6%) and 44 (32.4%) patients were classified into the initial-onset and early-onset LN groups, respectively. The initial-onset LN group had higher prevalences of impaired renal function (34.8% vs. 11.4%, p=0.004) and microscopic hematuria (73.9% vs. 54.5%, p=0.024), and higher urine protein/creatinine ratio (4626.1 [2180.0–6788.3] vs. 2410.0 [1265.0–5168.5] mg/g, p=0.006) at LN diagnosis. Renal relapse (46.3% vs 25.7%, p=0.039) and progression to chronic kidney disease (CKD) or end-stage renal disease (ESRD) were more common (24.4% vs. 8.3%, p=0.042) in the initial-onset LN group. In the multivariable Cox regression analysis, initial-onset LN group had higher risk of renal relapse (adjusted hazard ratio [HR] 2.938, 95% confidence interval [95% CI] 1.344–6.426, p=0.007) and progression to CKD or ESRD (adjusted HR 4.642, 95% CI 1.107–19.458, p=0.036), compared with early-onset LN group. Conclusion: Patients with LN at SLE onset may have more severe renal presentations and worse renal outcome than those who develop LN within 5 years. References: Not applicable Table. Hazard ratios for renal relapse and progression to CKD/ESRD according to onset time of LN Univariable analysis Multivariable analysis a HR (95% CI) p HR (95% CI) p Renal relapse Early-onset LN 1.000 (reference) 1.000 (reference) Initial-onset LN 2.734 (1.315–5.686) 0.007 2.938 (1.344–6.426) 0.007 Progression to CKD/ESRD Early-onset LN 1.000 (reference) 1.000 (reference) Initial-onset LN 4.201 (1.249–14.132) 0.020 4.642 (1.107–19.458) 0.036 a Adjusted for age, ISN/RPS class, activity index, chronicity index, GFR, UPCR, hematuria and use of HCQ LN, lupus nephritis; CKD, chronic kidney disease; ESRD, end-stage renal disease; ISN/RPS, International Society of Nephrology/Renal Pathology Society (ISN/RPS); GFR, glomerular filtration rate; UPCR, urine protein/creatinine ratio; HCQ, hydroxychloroquine; HR, hazard ratio; CI, confidence interval Acknowledgments: None. Disclosure of Interests: None declared
Endothelin-1–Mediated Drug Resistance in <i>EGFR</i>-Mutant Non-Small Cell Lung Carcinoma
Authors: Inés Pulido, Stephen Ollosi, Salvador Aparisi, Jeffrey H. Becker, Alicia Aliena-Valero, Marta Benet, María L. Rodríguez, Adrián López, Eva Tamayo-Torres, Lourdes Chuliá-Peris, Juan Carlos García-Cañaveras, Margaret Soucheray, Annika V. Dalheim, Juan B. Salom, Wei Qiu, Simon Kaja, Javier Alcácer Fernández-Coronado, Sandra Alandes, Javier Alcácer, Fátima Al-Shahrour, Jeffrey A. Borgia, Oscar Juan, Michael I. Nishimura, Agustín Lahoz, Julián Carretero, Takeshi Shimamura
Journal: Cancer Research (2020)

Abstract Progression on therapy in non-small cell lung carcinoma (NSCLC) is often evaluated radiographically, however, image-based evaluation of said therapies may not distinguish disease progression due to intrinsic tumor drug resistance or inefficient tumor penetration of the drugs. Here we report that the inhibition of mutated EGFR promotes the secretion of a potent vasoconstrictor, endothelin-1 (EDN1), which continues to increase as the cells become resistant with a mesenchymal phenotype. As EDN1 and its receptor (EDNR) is linked to cancer progression, EDNR-antagonists have been evaluated in several clinical trials with disappointing results. These trials were based on a hypothesis that the EDN1-EDNR axis activates the MAPK-ERK signaling pathway that is vital to the cancer cell survival; the trials were not designed to evaluate the impact of tumor-derived EDN1 in modifying tumor microenvironment or contributing to drug resistance. Ectopic overexpression of EDN1 in cells with mutated EGFR resulted in poor drug delivery and retarded growth in vivo but not in vitro. Intratumoral injection of recombinant EDN significantly reduced blood flow and subsequent gefitinib accumulation in xenografted EGFR-mutant tumors. Furthermore, depletion of EDN1 or the use of endothelin receptor inhibitors bosentan and ambrisentan improved drug penetration into tumors and restored blood flow in tumor-associated vasculature. Correlatively, these results describe a simplistic endogenous yet previously unrealized resistance mechanism inherent to a subset of EGFR-mutant NSCLC to attenuate tyrosine kinase inhibitor delivery to the tumors by limiting drug-carrying blood flow and the drug concentration in tumors. Significance: EDNR antagonists can be repurposed to improve drug delivery in VEGFA–secreting tumors, which normally respond to TKI treatment by secreting EDN1, promoting vasoconstriction, and limiting blood and drug delivery.
Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice
Authors: Xin Xu, Chenyu Wang, Yingang Wu, Katie Houck, Tristan Hilton, Ashley Zhou, Xiaoping Wu, Cha Han, Mengchen Yang, Wei Yang, Fu-Dong Shi, Moritz Stolla, Miguel A. Cruz, Min Li, Jianning Zhang, Jing-fei Dong
Journal: Blood (2020)
Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis
Authors: Anabela S. Ramalho, Eva Fürstová, Annelotte M. Vonk, Marc Ferrante, Catherine Verfaillie, Lieven Dupont, Mieke Boon, Marijke Proesmans, Jeffrey M. Beekman, Ifat Sarouk, Carlos Vazquez Cordero, Francois Vermeulen, Kris De Boeck
Journal: European Respiratory Journal (2020)

Given the vast number of cystic fibrosis transmembrane conductance regulator (CFTR) mutations, biomarkers predicting benefit from CFTR modulator therapies are needed for subjects with cystic fibrosis (CF).To study CFTR function in organoids of subjects with common and rare CFTR mutations and evaluate correlations between CFTR function and clinical data.Intestinal organoids were grown from rectal biopsies in a cohort of 97 subjects with CF. Residual CFTR function was measured by quantifying organoid swelling induced by forskolin and response to modulators by quantifying organoid swelling induced by CFTR correctors, potentiator and their combination. Organoid data were correlated with clinical data from the literature.Across 28 genotypes, residual CFTR function correlated (r2=0.87) with sweat chloride values. When studying the same genotypes, CFTR function rescue by CFTR modulators in organoids correlated tightly with mean improvement in lung function (r2=0.90) and sweat chloride (r2=0.95) reported in clinical trials. We identified candidate genotypes for modulator therapy, such as E92K, Q237E, R334W and L159S. Based on organoid results, two subjects started modulator treatment: one homozygous for complex allele Q359K_T360K, and the second with mutation E60K. Both subjects had major clinical benefit.Measurements of residual CFTR function and rescue of function by CFTR modulators in intestinal organoids correlate closely with clinical data. Our results for reference genotypes concur with previous results. CFTR function measured in organoids can be used to guide precision medicine in patients with CF, positioning organoids as a potential in vitro model to bring treatment to patients carrying rare CFTR mutations.
Delivering Proangiogenic Factors from 3D‐Printed Polycaprolactone Scaffolds for Vascularized Bone Regeneration
Authors: Haoming Liu, Yingying Du, Gaojie Yang, Xixi Hu, Lin Wang, Bin Liu, Jianglin Wang, Shengmin Zhang
Journal: Advanced Healthcare Materials (2020)

Abstract Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Inadequacy of neovascularization may compromise the tissue ingrowth to the implanted scaffolds, and eventually results in failure for the repair. To tackle this issue and enhance self‐vascularized bone regeneration, herein a 3D biomimetic selective lasersintering (SLS) derived scaffold, with an angiogenic growth factor immobilized on its surface, that can be released in a controlled manner is proposed. To this end, a porous polycaprolactone/hydroxyapatite (PCL/HA) scaffold is prepared via the SLS technique, which is further modified with vascular endothelial growth factor (VEGF) by coprecipitation with apatite. The resultant scaffold (PCL/HA/VEGF) has an excellent cytocompatibility, and subcutaneous implantation experiment shows that the VEGF‐loaded scaffold significantly enhances the blood vessel formation compared with the VEGF‐free control. It is further demonstrated that the PCL/HA/VEGF scaffold is able to enhance the in vivo bone regeneration in a rat cranial defect model. Taken together, the current study provides not only a feasible and promising scaffold candidate to enhance the vascularized bone regeneration, but also a general strategy to overcome the inadequate vascularization issue for the repair of other tissue and organs.
Ofatumumab versus Teriflunomide in Multiple Sclerosis
Authors: Stephen Hauser, Amit Bar-Or, Jeffrey Cohen, Giancarlo Comi, Jorge Correale, Patricia Coyle, Anne Cross, Jerome de Seze, David Leppert, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Cecile Kerloeguen, Roman Willi, Bingbing Li, Algirdas Kakarieka, Davorka Tomic, Alexandra Goodyear, Ratnakar Pingili, Dieter Häring, Krishnan Ramanathan, Martin Merschhemke, Ludwig Kappos, Pierre M. Labauge
Journal: New England Journal of Medicine (2020)

Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.
The perpetual enigma of bronchoalveolar lavage fluid lymphocytosis in chronic hypersensitivity pneumonitis: is it of diagnostic value?
Authors: Francesco Bonella, Ulrich Costabel
Journal: European Respiratory Journal (2020)

What did ILD guidelines of the past two decades tell us? In the American Thoracic Society (ATS)/European Respiratory Society (ERS) statement on idiopathic pulmonary fibrosis (IPF) of 2000 [2], BAL was considered one of the requirements for the exclusion of other diseases in a patient with IPF who did not undergo surgical lung biopsy, and was included as one of the four major criteria for making a clinical diagnosis of IPF. BAL was also found to be useful in the diagnostic work-up of ILDs in the ATS/ERS international consensus classification of idiopathic interstitial pneumonias (IIPs) of 2002 [3]. In the first evidence-based international IPF guidelines of 2011, however, there was a weak negative recommendation against performing a BAL cellular analysis in the diagnostic evaluation of suspected IPF [4]. A marked increase in BAL lymphocyte percentage is of additional value in distinguishing cHP from other forms of fibrotic ILD <https://bit.ly/3ciR8zG>
Cabbage and fermented vegetables: From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID‐19
Authors: Jean Bousquet, Josep M. Anto, Wienczyslawa Czarlewski, Tari Haahtela, Susana C. Fonseca, Guido Iaccarino, Hubert Blain, Alain Vidal, Aziz Sheikh, Cezmi A. Akdis, Torsten Zuberbier
Journal: Allergy (2020)

Abstract Large differences in COVID‐19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS‐CoV‐2 binds to its receptor, the angiotensin‐converting enzyme 2 (ACE2). As a result of SARS‐CoV‐2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT 1 R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID‐19. The nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT 1 R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof‐of‐concept of dietary manipulations that may enhance Nrf2‐associated antioxidant effects, helpful in mitigating COVID‐19 severity.
Insights Into the Biology of Persistent Chemotherapy-Induced Alopecia via Genomic Approaches—An Avenue to Clinical Translation?
Authors: Fitnat Buket Basmanav, Markus M. Nöthen, Regina C. Betz
Journal: JAMA Dermatology (2020)

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 Dermatology 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 Dermatology journal
Comprehensive analyses of B-cell compartments across the human body reveal novel subsets and a gut-resident memory phenotype
Authors: Nadine M. Weisel, Florian J. Weisel, Donna L. Farber, Lisa A. Borghesi, Yufeng Shen, Wenji Ma, Eline T. Luning Prak, Mark J. Shlomchik
Journal: Blood (2020)
Zinc Microrocket Pills: Fabrication and Characterization toward Active Oral Delivery
Authors: Rodolfo Mundaca‐Uribe, Berta Esteban‐Fernández de Ávila, Maya Holay, Pooyath Lekshmy Venugopalan, Bryan Nguyen, Jiarong Zhou, Amal Abbas, Ronnie H. Fang, Liangfang Zhang, Joseph Wang
Journal: Advanced Healthcare Materials (2020)

Abstract Here the fabrication of a zinc (Zn) microrocket pill is reported, and its unique features toward active and enhanced oral delivery application are demonstrated. By loading Zn‐based tubular microrockets into an orally administrable pill formulation, the resulting Zn microrocket pill can rapidly dissolve in the stomach, releasing numerous encapsulated Zn microrockets that are instantaneously activated and then propel in the gastric fluid. The released Zn microrockets display efficient propulsion without being affected by the presence of the inactive excipient materials of the pill. An in vivo retention study performed in mice clearly shows that the active pill dissolution and powerful acid‐driven Zn microrocket propulsion greatly enhance the microrocket retention within the gastric tissue without causing toxic effects. By combining the active delivery feature of Zn microrockets with the oral administration of a pill, the Zn microrocket pill holds considerable potential for active oral delivery of various therapeutics for diverse medical applications.
AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer
Authors: Julia Varga, Adele Nicolas, Valentina Petrocelli, Marina Pesic, Abdelrahman Mahmoud, Birgitta E. Michels, Emre Etlioglu, Diego Yepes, Björn Häupl, Paul K. Ziegler, Katrin Bankov, Peter J. Wild, Stefan Wanninger, Hind Medyouf, Henner F. Farin, Sabine Tejpar, Thomas Oellerich, Jürgen Ruland, Christian W. Siebel, Florian R. Greten
Journal: The Journal of Experimental Medicine (2020)

Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.
A Comparison between 3 Staging Systems in Multiple Myeloma Using the Center for International Blood and Marrow Transplant Research (CIBMTR) Database
Authors: Emma Scott, Parameswaran Hari, Sathish Kumar, Raphael Fraser, Omar Davila, Yago Nieto, Tomer M Mark, Shaji K Kumar, Cristina J. Gasparetto, Anita D'Souza
Journal: Blood (2017)
Abstract 15751: Episodes of Asymptomatic Atrial Fibrillation Patients With Heart Failure and ICD/CRT-D Based on Analysis Intracardiac Electrocardiograms
Authors: Barbara Dominik, Zorawski Wojciech, Kowalik Ilona, Ciesielski Adam, Mitkowski Przemyslaw
Journal: Circulation (2019)

Introduction: Implantable cardioverter defibrillators have the opportunity to register various types of arrhythmia. Many models beyond the detection of life-threatening ventricular arrhythmias, can...
Induction of a Timed Metabolic Collapse to Overcome Cancer Chemoresistance
Authors: Nick van Gastel, Jessica B. Spinelli, Azeem Sharda, Amir Schajnovitz, Ninib Baryawno, Catherine Rhee, Toshihiko Oki, Eliane Grace, Heather J. Soled, Jelena Milosevic, David B. Sykes, Peggy P. Hsu, Matthew G. Vander Heiden, Charles Vidoudez, Sunia A. Trauger, Marcia C. Haigis, David T. Scadden
Journal: Cell Metabolism (2020)
Abstract 10096: Assessment of the Pulmonary Arterial Remodeling and the Risk Stratification Score During Short-term Follow-up in Prevalent Pulmonary Arterial Hypertension Patients
Authors: Enric Domingo, Juan C Grignola, Alvaro Calabuig, Santiago Pérez Hoyos, Manuel López Messeguer, Antonio Roman
Journal: Circulation (2019)

Introduction: A multidimensional risk strategy provides a useful method to estimate prognosis in pulmonary arterial hypertension (PAH) at time of diagnosis and in the follow-up (FU). Hypothesis: Th...