tbuckley/cabot-search huggingface dataset:
Self-Management in Long-Term Prostate Cancer Survivors: A Randomized, Controlled Trial
Authors: Ted A. Skolarus, Tabitha Metreger, Daniela Wittmann, Soohyun Hwang, Hyungjin Myra Kim, Robert L. Grubb, Jeffrey R. Gingrich, Hui Zhu, John D. Piette, Sarah T. Hawley
Journal: Journal of Clinical Oncology (2019)

PURPOSE This randomized clinical trial compared a personally tailored, automated telephone symptom management intervention to improve self-management among long-term survivors of prostate cancer with usual care enhanced with a nontailored newsletter about symptom management. We hypothesized that intervention-group participants would have more confident symptom self-management and reduced symptom burden. METHODS A total of 556 prostate cancer survivors who, more than 1 year after treatment, were experiencing symptom burden were recruited from April 2015 to February 2017 across four Veterans Affairs sites. Participants were randomly assigned to intervention (n = 278) or usual care (n = 278) groups. We compared differences in the primary (symptom burden according to Expanded Prostate Cancer Index Composite-26 [EPIC], confidence in self-management) and secondary outcomes between groups using intent-to-treat analyses. We compared domain-specific changes in symptom burden from baseline to 5 and 12 months among the intervention group according to the primary symptom focus area (urinary, bowel, sexual, general) of participants. RESULTS Most of the prostate cancer survivors in this study were married (54.3%), were white (69.2%), were retired (62.4%), and underwent radiation therapy (56.7% v 46.2% who underwent surgery), and the mean age was 67 years. There were no baseline differences in urinary, bowel, sexual, or hormonal domain EPIC scores across groups. We observed higher EPIC scores in the intervention arm in all domain areas at 5 months, though differences were not statistically significant. No differences were found in secondary outcomes; however, coping appraisal was higher (2.8 v 2.6; P = .02) in intervention-arm patients at 5 months. In subgroup analyses, intervention participants reported improvement from baseline at 5 and 12 months in their symptom focus area domains. CONCLUSION This intervention was well received among veterans who were long-term survivors of prostate cancer. Although overall outcome differences were not observed across groups, the intervention tailored to symptom area of choice may hold promise to improve associated burden.
From the American College of Chest Physicians: Guidelines on Conflict-of-Interest Management
Authors: Kevin O’Neil, Lisa Moores, Frank Detterback
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Regenerative pharmacology for COPD: breathing new life into old lungs
Authors: John-Poul Ng-Blichfeldt, Reinoud Gosens, Charlotte Dean, Mark Griffiths, Matthew Hind
Journal: Thorax (2019)

Chronic obstructive pulmonary disease (COPD) is a major global health concern with few effective treatments. Widespread destruction of alveolar tissue contributes to impaired gas exchange in severe COPD, and recent radiological evidence suggests that destruction of small airways is a major contributor to increased peripheral airway resistance in disease. This important finding might in part explain the failure of conventional anti-inflammatory treatments to restore lung function even in patients with mild disease. There is a clear need for alternative pharmacological strategies for patients with COPD/emphysema. Proposed regenerative strategies such as cell therapy and tissue engineering are hampered by poor availability of exogenous stem cells, discouraging trial results, and risks and cost associated with surgery. An alternative therapeutic approach is augmentation of lung regeneration and/or repair by biologically active factors, which have potential to be employed on a large scale. In favour of this strategy, the healthy adult lung is known to possess a remarkable endogenous regenerative capacity. Numerous preclinical studies have shown induction of regeneration in animal models of COPD/emphysema. Here, we argue that given the widespread and irreversible nature of COPD, serious consideration of regenerative pharmacology is necessary. However, for this approach to be feasible, a better understanding of the cell-specific molecular control of regeneration, the regenerative potential of the human lung and regenerative competencies of patients with COPD are required.
Correction to: Revefenacin: First Global Approval
Authors: Young-A Heo
Journal: Drugs (2019)

The article Revefenacin: First Global Approval, written by Young-A Heo, was originally published Online First without open access. After publication in volume 79, issue 1, pages 85–91, Mylan Inc. (Canonsburg, Pennsylvania, USA) and Theravance Biopharma US, Inc. (South San Francisco, California, USA) requested that the article be Open Choice to make the article an open access publication. Post-publication open access was funded by Mylan Inc. (Canonsburg, Pennsylvania, USA) and Theravance Biopharma US, Inc. (South San Francisco, California, USA). The article is forthwith distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License ( http://creativecommons.org/licenses/by-nc/4.0/ ), which permits any noncommercial use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.
Mucus accumulation in the lungs precedes structural changes and infection in children with cystic fibrosis
Authors: Charles R. Esther, Marianne S. Muhlebach, Camille Ehre, David B. Hill, Matthew C. Wolfgang, Mehmet Kesimer, Kathryn A. Ramsey, Matthew R. Markovetz, Ian C. Garbarine, M. Gregory Forest, Ian Seim, Bryan Zorn, Cameron B. Morrison, Martial F. Delion, William R. Thelin, Diane Villalon, Juan R. Sabater, Lidija Turkovic, Sarath Ranganathan, Stephen M. Stick, Richard C. Boucher
Journal: Science Translational Medicine (2019)

Although destructive airway disease is evident in young children with cystic fibrosis (CF), little is known about the nature of the early CF lung environment triggering the disease. To elucidate early CF pulmonary pathophysiology, we performed mucus, inflammation, metabolomic, and microbiome analyses on bronchoalveolar lavage fluid (BALF) from 46 preschool children with CF enrolled in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) program and 16 non-CF disease controls. Total airway mucins were elevated in CF compared to non-CF BALF irrespective of infection, and higher densities of mucus flakes containing mucin 5B and mucin 5AC were observed in samples from CF patients. Total mucins and mucus flakes correlated with inflammation, hypoxia, and oxidative stress. Many CF BALFs appeared sterile by culture and molecular analyses, whereas other samples exhibiting bacterial taxa associated with the oral cavity. Children without computed tomography-defined structural lung disease exhibited elevated BALF mucus flakes and neutrophils, but little/no bacterial infection. Although CF mucus flakes appeared "permanent" because they did not dissolve in dilute BALF matrix, they could be solubilized by a previously unidentified reducing agent (P2062), but not N-acetylcysteine or deoxyribonuclease. These findings indicate that early CF lung disease is characterized by an increased mucus burden and inflammatory markers without infection or structural lung disease and suggest that mucolytic and anti-inflammatory agents should be explored as preventive therapy.
Function and clinical relevance of RHAMM isoforms in pancreatic tumor progression
Authors: Soyoung Choi, Dunrui Wang, Xiang Chen, Laura H. Tang, Akanksha Verma, Zhengming Chen, Bu Jung Kim, Leigh Selesner, Kenneth Robzyk, George Zhang, Sharon Pang, Teng Han, Chang S. Chan, Thomas J. Fahey, Olivier Elemento, Yi-Chieh Nancy Du
Journal: Molecular Cancer (2019)

The receptor for hyaluronic acid-mediated motility (RHAMM) is upregulated in various cancers. We previously screened genes upregulated in human hepatocellular carcinomas for their metastatic function in a mouse model of pancreatic neuroendocrine tumor (PNET) and identified that human RHAMMB promoted liver metastasis. It was unknown whether RHAMMB is upregulated in pancreatic cancer or contributes to its progression. In this study, we found that RHAMM protein was frequently upregulated in human PNETs. We investigated alternative splicing isoforms, RHAMMA and RHAMMB, by RNA-Seq analysis of primary PNETs and liver metastases. RHAMMB, but not RHAMMA, was significantly upregulated in liver metastases. RHAMMB was crucial for in vivo metastatic capacity of mouse and human PNETs. RHAMMA, carrying an extra 15-amino acid-stretch, did not promote metastasis in spontaneous and experimental metastasis mouse models. Moreover, RHAMMB was substantially higher than RHAMMA in pancreatic ductal adenocarcinoma (PDAC). RHAMMB, but not RHAMMA, correlated with both higher EGFR expression and poorer survival of PDAC patients. Knockdown of EGFR abolished RHAMMB-driven PNET metastasis. Altogether, our findings suggest a clinically relevant function of RHAMMB, but not RHAMMA, in promoting PNET metastasis in part through EGFR signaling. RHAMMB can thus serve as a prognostic factor for pancreatic cancer.
Clinical and Genome-wide Analysis of Cisplatin-induced Tinnitus Implicates Novel Ototoxic Mechanisms
Authors: Omar El Charif, Brandon Mapes, Matthew R. Trendowski, Heather E. Wheeler, Claudia Wing, Paul C. Dinh, Robert D. Frisina, Darren R. Feldman, Robert J. Hamilton, David J. Vaughn, Chunkit Fung, Christian Kollmannsberger, Taisei Mushiroda, Michiaki Kubo, Eric R. Gamazon, Nancy J. Cox, Robert Huddart, Shirin Ardeshir-Rouhani-Fard, Patrick Monahan, Sophie D. Fossa, Lawrence H. Einhorn, Lois B. Travis, M. Eileen Dolan
Journal: Clinical Cancer Research (2019)

Cisplatin, a commonly used chemotherapeutic, results in tinnitus, the phantom perception of sound. Our purpose was to identify the clinical and genetic determinants of tinnitus among testicular cancer survivors (TCS) following cisplatin-based chemotherapy.TCS (n = 762) were dichotomized to cases (moderate/severe tinnitus; n = 154) and controls (none; n = 608). Logistic regression was used to evaluate associations with comorbidities and SNP dosages in genome-wide association study (GWAS) following quality control and imputation (covariates: age, noise exposure, cisplatin dose, genetic principal components). Pathway over-representation tests and functional studies in mouse auditory cells were performed.Cisplatin-induced tinnitus (CisIT) significantly associated with age at diagnosis (P = 0.007) and cumulative cisplatin dose (P = 0.007). CisIT prevalence was not significantly greater in 400 mg/m2-treated TCS compared with 300 (P = 0.41), but doses >400 mg/m2 (median 580, range 402-828) increased risk by 2.61-fold (P < 0.0001). CisIT cases had worse hearing at each frequency (0.25-12 kHz, P < 0.0001), and reported more vertigo (OR = 6.47; P < 0.0001) and problems hearing in a crowd (OR = 8.22; P < 0.0001) than controls. Cases reported poorer health (P < 0.0001) and greater psychotropic medication use (OR = 2.4; P = 0.003). GWAS suggested a variant near OTOS (rs7606353, P = 2 × 10-6) and OTOS eQTLs were significantly enriched independently of that SNP (P = 0.018). OTOS overexpression in HEI-OC1, a mouse auditory cell line, resulted in resistance to cisplatin-induced cytotoxicity. Pathway analysis implicated potassium ion transport (q = 0.007).CisIT associated with several neuro-otological symptoms, increased use of psychotropic medication, and poorer health. OTOS, expressed in the cochlear lateral wall, was implicated as protective. Future studies should investigate otoprotective targets in supporting cochlear cells.
The Impact of a Physical Activity Intervention Can be Accurately Assessed By Smart Watches in Patients Completing Autologous Stem Cell Transplantation for Lymphoma or Multiple Myeloma: Results of a Feasibility Study
Authors: Andrew Ip, Michael C Churnetski, Oscar Calzada, Andres Chang, Yuan Liu, Nassoma Bumpers, Deborah Leeson, Ernestine Mahar, Iraj Hesaroieh, Maria Crain, Ajay K Nooka, Jean L. Koff, Craig C Hofmeister, Vikas A. Gupta, Pamela Allen, Mary Jo Lechowicz, Jonathan L Kaufman, Kristie A. Blum, Sagar Lonial, Amelia Langston, Edmund K. Waller, Christopher R Flowers, Jonathon B. Cohen
Journal: Blood (2018)
Metagenomic analysis of colorectal cancer datasets identifies cross-cohort microbial diagnostic signatures and a link with choline degradation
Authors: Andrew Maltez Thomas, Paolo Manghi, Francesco Asnicar, Edoardo Pasolli, Federica Armanini, Moreno Zolfo, Francesco Beghini, Serena Manara, Nicolai Karcher, Chiara Pozzi, Sara Gandini, Davide Serrano, Sonia Tarallo, Antonio Francavilla, Gaetano Gallo, Mario Trompetto, Giulio Ferrero, Sayaka Mizutani, Hirotsugu Shiroma, Satoshi Shiba, Tatsuhiro Shibata, Shinichi Yachida, Takuji Yamada, Jakob Wirbel, Petra Schrotz-King, Cornelia M. Ulrich, Hermann Brenner, Manimozhiyan Arumugam, Peer Bork, Georg Zeller, Francesca Cordero, Emmanuel Dias-Neto, João Carlos Setubal, Adrian Tett, Barbara Pardini, Maria Rescigno, Levi Waldron, Alessio Naccarati, Nicola Segata
Journal: Nature Medicine (2019)
Endothelial Cells Regulate Physiological Cardiomyocyte Growth via VEGFR2-Mediated Paracrine Signaling
Authors: Riikka Kivelä, Karthik Amudhala Hemanthakumar, Katri Vaparanta, Marius Robciuc, Yasuhiro Izumiya, Hiroyasu Kidoya, Nobuyuki Takakura, Xuyang Peng, Douglas B. Sawyer, Klaus Elenius, Kenneth Walsh, Kari Alitalo
Journal: Circulation (2019)

Heart failure, which is a major global health problem, is often preceded by pathological cardiac hypertrophy. The expansion of the cardiac vasculature, to maintain adequate supply of oxygen and nutrients, is a key determinant of whether the heart grows in a physiological compensated manner or a pathological decompensated manner. Bidirectional endothelial cell (EC)-cardiomyocyte (CMC) cross talk via cardiokine and angiocrine signaling plays an essential role in the regulation of cardiac growth and homeostasis. Currently, the mechanisms involved in the EC-CMC interaction are not fully understood, and very little is known about the EC-derived signals involved. Understanding how an excess of angiogenesis induces cardiac hypertrophy and how ECs regulate CMC homeostasis could provide novel therapeutic targets for heart failure.Genetic mouse models were used to delete vascular endothelial growth factor (VEGF) receptors, adeno-associated viral vectors to transduce the myocardium, and pharmacological inhibitors to block VEGF and ErbB signaling in vivo. Cell culture experiments were used for mechanistic studies, and quantitative polymerase chain reaction, microarrays, ELISA, and immunohistochemistry were used to analyze the cardiac phenotypes.Both EC deletion of VEGF receptor (VEGFR)-1 and adeno-associated viral vector-mediated delivery of the VEGFR1-specific ligands VEGF-B or placental growth factor into the myocardium increased the coronary vasculature and induced CMC hypertrophy in adult mice. The resulting cardiac hypertrophy was physiological, as indicated by preserved cardiac function and exercise capacity and lack of pathological gene activation. These changes were mediated by increased VEGF signaling via endothelial VEGFR2, because the effects of VEGF-B and placental growth factor on both angiogenesis and CMC growth were fully inhibited by treatment with antibodies blocking VEGFR2 or by endothelial deletion of VEGFR2. To identify activated pathways downstream of VEGFR2, whole-genome transcriptomics and secretome analyses were performed, and the Notch and ErbB pathways were shown to be involved in transducing signals for EC-CMC cross talk in response to angiogenesis. Pharmacological or genetic blocking of ErbB signaling also inhibited part of the VEGF-B-induced effects in the heart.This study reveals that cross talk between the EC VEGFR2 and CMC ErbB signaling pathways coordinates CMC hypertrophy with angiogenesis, contributing to physiological cardiac growth.
EMTALA—A Noble Policy That Needs Improvement
Authors: Mitchell H. Katz, Eric K. Wei
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
AdenoLibrary approach for vector construction and selection of targeted adenoviruses employing novel fiber-fibritin chimeric fibers
Authors: Sam C. Noureddini, Alexander Krendelshchikov, Vera Simonenko, Joanne T. Douglas, David T. Curiel, Nikolay Korokhov
Journal: Cancer Research (2005)

1332  Adenovirus serotype 5 (Ad5) has been widely used as a viral vector for cancer gene therapy applications. However, the paucity of the Ad5 primary receptor (coxsackie and adenovirus receptor, CAR) on target cancer cells of interest has rendered many tissues refractory to Ad-mediated transduction. Additionally, this endogenous tropism may potentially lead to undesired transduction of tissues expressing CAR. In view of this, strategies have been proposed to modify Ad5 to achieve targeted gene delivery by ablating native tropism while redirecting Ad to target cell markers of interest. Such strategies involve modification of the trimeric capsid fiber protein, whose C-terminal knob domain has been shown to dictate the native tropism associated with Ad5. While approaches employing genetic fusion of simple targeting ligands to the fiber have shown promise in retargeting, in many cases, the incorporated ligands tend to lose specificity and/or affect virion integrity. As an alternative, several so-called knob-less fiber platforms have been utilized. These modifications are based on the concept of replacing the native fiber with an alternative protein capable of providing the trimerization functions that the knob usually confers. Such a strategy would accrue the additional benefit of an expanded repertoire of incorporable ligands, based on removal of the structural constraints imposed by the fiber knob. Previously, our group has utilized the bacteriophage T4 fibritin protein for fiber replacement, with subsequent display of complex targeting ligands providing for expanded tropism. However, vectors employing these knob-less fiber platforms often exhibit poor capsid incorporation of the alternate fibers in comparison to that of wild-type Ad5 fiber, which consequently leads to limited gene transfer efficacy and difficulty in vector propagation. In view of these obstacles, we have hypothesized that direct analysis of modified adenoviruses during their rescue/propagation is the only straightforward approach that guarantees the selection of functional, targeted vectors with optimized structural integrity and targeting efficiency. Herein, we describe a new schema for Ad vector construction, which allows for the selection of vectors with the optimal modified capsid configuration at the level of viral rescue. Based on our first generation fiber-fibritin molecule, several new fibers employing variant amounts of fibritin and Ad5 fiber shaft were analyzed via this library selection schema. Our selected variant, composed of the entire Ad5 fiber shaft connected to 12th coiled-coil segment of fibritin, is capable of efficient fiber incorporation, ligand display, and CAR-independent transduction. Furthermore, we have concluded that various targeting ligands require individual optimization, which may be accomplished by utilizing this adenoviral library approach.
In the Eye of the Storm: Immune‐mediated Toxicities Associated With CAR‐T Cell Therapy
Authors: Jorge Garcia Borrega, Philipp Gödel, Maria Adele Rüger, Özgür A. Onur, Alexander Shimabukuro‐Vornhagen, Matthias Kochanek, Boris Böll
Journal: HemaSphere (2019)

The success of chimeric antigen receptor (CAR)-T cell therapy with impressive response rates in hematologic malignancies but also promising data in solid tumors came along with the cognition of unexpected, potentially life-threatening immune-mediated toxicities, namely the cytokine release syndrome (CRS) and neurotoxicity recently referred to as "immune effector cell-associated neurotoxicity syndrome" (ICANS). These toxicities require urgent diagnostic and therapeutic interventions and targeted modulation of key cytokine pathways represents the mainstay of CRS treatment. However, as the underlying mechanisms of ICANS are not well understood, treatment options remain limited and further investigation is warranted. Importantly, after the recent market approval of 2 CAR-T cell constructs, the application of CAR-T cells will expand to nonacademic centers with limited experience in the management of CAR-T cell-associated toxicities. Here, we review the current evidence of CRS and ICANS pathophysiology, diagnostics, and treatment.