tbuckley/cabot-search huggingface dataset:
Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer
Authors: Maha Hussain, Joaquin Mateo, Karim Fizazi, Fred Saad, Neal Shore, Shahneen Sandhu, Kim N. Chi, Oliver Sartor, Neeraj Agarwal, David Olmos, Antoine Thiery-Vuillemin, Przemyslaw Twardowski, Guilhem Roubaud, Mustafa Özgüroğlu, Jinyu Kang, Joseph Burgents, Christopher Gresty, Claire Corcoran, Carrie A. Adelman, Johann de Bono
Journal: New England Journal of Medicine (2020)

We previously reported that olaparib led to significantly longer imaging-based progression-free survival than the physician's choice of enzalutamide or abiraterone among men with metastatic castration-resistant prostate cancer who had qualifying alterations in homologous recombination repair genes and whose disease had progressed during previous treatment with a next-generation hormonal agent. The results of the final analysis of overall survival have not yet been reported. In an open-label, phase 3 trial, we randomly assigned patients in a 2:1 ratio to receive olaparib (256 patients) or the physician's choice of enzalutamide or abiraterone plus prednisone as the control therapy (131 patients). Cohort A included 245 patients with at least one alteration in BRCA1, BRCA2, or ATM, and cohort B included 142 patients with at least one alteration in any of the other 12 prespecified genes. Crossover to olaparib was allowed after imaging-based disease progression for patients who met certain criteria. Overall survival in cohort A, a key secondary end point, was analyzed with the use of an alpha-controlled, stratified log-rank test at a data maturity of approximately 60%. The primary and other key secondary end points were reported previously. The median duration of overall survival in cohort A was 19.1 months with olaparib and 14.7 months with control therapy (hazard ratio for death, 0.69; 95% confidence interval [CI], 0.50 to 0.97; P = 0.02). In cohort B, the median duration of overall survival was 14.1 months with olaparib and 11.5 months with control therapy. In the overall population (cohorts A and B), the corresponding durations were 17.3 months and 14.0 months. Overall, 86 of 131 patients (66%) in the control group crossed over to receive olaparib (56 of 83 patients [67%] in cohort A). A sensitivity analysis that adjusted for crossover to olaparib showed hazard ratios for death of 0.42 (95% CI, 0.19 to 0.91) in cohort A, 0.83 (95% CI, 0.11 to 5.98) in cohort B, and 0.55 (95% CI, 0.29 to 1.06) in the overall population. Among men with metastatic castration-resistant prostate cancer who had tumors with at least one alteration in BRCA1, BRCA2, or ATM and whose disease had progressed during previous treatment with a next-generation hormonal agent, those who were initially assigned to receive olaparib had a significantly longer duration of overall survival than those who were assigned to receive enzalutamide or abiraterone plus prednisone as the control therapy, despite substantial crossover from control therapy to olaparib. (Funded by AstraZeneca and Merck Sharp and Dohme; PROfound ClinicalTrials.gov number, NCT02987543.).
Elevated plasma sTIM-3 levels in patients with severe COVID-19
Authors: Thor Ueland, Lars Heggelund, Andreas Lind, Aleksander R. Holten, Kristian Tonby, Annika E. Michelsen, Synne Jenum, Marthe J. Jørgensen, Andreas Barratt-Due, Linda G. Skeie, Ingvild Nordøy, Mai Sasaki Aanensen Fraz, Else Quist-Paulsen E, Søren E. Pischke, Simreen K. Johal, Liv Hesstvedt, Mette Bogen, Børre Fevang, Bente Halvorsen, Fredrik Müller, Gry Kloumann Bekken, Tom E. Mollnes, Susanne Dudman, Pål Aukrust, Anne M. Dyrhol-Riise, Jan C. Holter
Journal: Journal of Allergy and Clinical Immunology (2020)
Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery
Authors: Piotr Dobrowolski, Andrzej Januszewicz, Anna Klisiewicz, Maria Gosk-Przybyłek, Mariola Pęczkowska, Marek Kabat, Aleksandra Kwapiszewska, Ewa Warchoł-Celińska, Urszula Ambroziak, Adrian Doroszko, Sadegh Toutounchi, Zbigniew Gałązka, Tomasz Bednarczuk, Barbara Górnicka, Magdalena Januszewicz, Piotr Hoffman, Jacques W.M. Lenders, Graeme Eisenhofer, Aleksander Prejbisz
Journal: JACC. Cardiovascular imaging (2020)
Covid-19 communication: planning ahead to help inpatients when key contacts can’t be present
Authors: Joanne Wilson, Jane Hawdon, Sarah Lally, Danielle Wilde
Journal: BMJ (2020)

We thank Gray and Back for their article on communication and covid-19.1 Conversations in our trust have increased and been complicated by the use of personal protective equipment. This particularly affects professionals and patients who are deaf2 but also affects those with other sensory impairments, dementia, or learning disabilities.

Visiting has been restricted in UK hospitals,3 with a move towards telephone and video consultations.4 This is complex work, especially when phoning patients or families who …
Covid-19: Minorities account for 78% of US deaths in under 21s, says CDC
Authors: Owen Dyer
Journal: BMJ (2020)

The first US government review of covid-19 deaths in people aged under 21 1 has found that, of 121 such fatalities reported to the Centers for Disease Control and Prevention (CDC) before 31 July, 94 (78%) involved people belonging to minority groups.1
Mineralized Hydrogels Induce Bone Regeneration in Critical Size Cranial Defects
Authors: Xinchen Wu, Tengfei Zhang, Brianna Hoff, Sanika Suvarnapathaki, Darlin Lantigua, Colleen McCarthy, Bin Wu, Gulden Camci‐Unal
Journal: Advanced Healthcare Materials (2020)

Abstract Sequential mineralization enables the integration of minerals within the 3D structure of hydrogels. Hydrolyzed collagen‐based hydrogels are sequentially mineralized over 10 cycles. One cycle is defined as an incubation period in calcium chloride dihydrate followed by incubation in sodium phosphate dibasic dihydrate. Separate cycles are completed at 30‐minute and 24‐hour intervals. For the gels mineralized for 30 min and 24 h, the compressive moduli increases from 4.25 to 87.57 kPa and from 4.25 to 125.47 kPa, respectively, as the cycle number increases from 0 to 10. As indicated by X‐ray diffraction (XRD) and Fourier transform infrared analysis (FTIR) analyses, the minerals in the scaffolds are mainly hydroxyapatite. In vitro experiments, which measure mechanical properties, porous structure, mineral content, and gene expression are performed to evaluate the physical properties and osteoinductivity of the scaffolds. Real time‐quantitative polymerase chain reaction (RT‐qPCR) demonstrates 4–10 fold increase in the expression of BMP‐7 and osteocalcin. The in vivo subcutaneous implantation demonstrates that the scaffolds are biocompatible and 90% biodegradable. The critical size cranial defects in vivo exhibit nearly complete bone regeneration. Cycle 10 hydrogels mineralized for 24 h have a volume of 59.86 mm 3 and a density of 1946.45 HU. These results demonstrate the suitability of sequentially mineralized hydrogel scaffolds for bone repair and regeneration.
The Great Technological Divide
Authors: George Gubernikoff
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
A placebo-controlled randomised trial of budesonide for PBC following an insufficient response to UDCA
Authors: Gideon M. Hirschfield, Ulrich Beuers, Limas Kupcinskas, Peter Ott, Annika Bergquist, Martti Färkkilä, Michael P. Manns, Albert Parés, Ulrich Spengler, Michael Stiess, Roland Greinwald, Markus Pröls, Dominique Wendum, Uta Drebber, Raoul Poupon
Journal: Journal of Hepatology (2020)

In patients with primary biliary cholangitis (PBC), the efficacy of budesonide, a synthetic corticosteroid displaying high first-pass metabolism, is unresolved. In a placebo-controlled, double-blind trial, we evaluated the added-value of budesonide in those with PBC and ongoing risk of progressive disease despite ursodeoxycholic acid (UDCA) treatment.We evaluated 62 patients with PBC who had histologically confirmed hepatic inflammatory activity, according to the Ishak score, and an alkaline phosphatase (ALP) >1.5× upper limit of normal (ULN), after at least 6 months of UDCA therapy. Participants were randomly assigned 2:1 to receive budesonide (9 mg/day) or placebo once daily, for 36 months, with UDCA treatment (12-16 mg/kg body weight/day) maintained. Primary efficacy was defined as improvement of liver histology with respect to inflammation and no progression of fibrosis. Secondary outcomes included changes in biochemical markers of liver injury.Recruitment challenges resulted in a study that was underpowered for the primary efficacy analysis. Comparing patients with paired biopsies only (n = 43), the primary histologic endpoint was not met (p >0.05). The proportion of patients with ALP <1.67×ULN, a ≥15% decrease in ALP and normal bilirubin was higher in the budesonide group than in the placebo group at 12, 24, and 36 months (p <0.05, each). In contrast to placebo, budesonide reduced mean ALP and 35% of budesonide-treated patients achieved normalisation of ALP (placebo 9%; p = 0.023). Serious adverse events occurred in 10 patients receiving budesonide and 7 patients receiving placebo.Budesonide add-on therapy was not associated with improved liver histology in patients with PBC and insufficient response to UDCA; however, improvements in biochemical markers of disease activity were demonstrated in secondary analyses.Around one-third of patients with primary biliary cholangitis (PBC) needs additional medical therapy alongside ursodeoxycholic acid (UDCA) treatment. In this clinical trial, the addition of the corticosteroid budesonide did not improve liver histology; there were however relevant improvements in liver blood tests. CLINICALTRIALS.NCT00746486.
Only Hyperuricemia with Crystalluria, but not Asymptomatic Hyperuricemia, Drives Progression of Chronic Kidney Disease
Authors: Markus Sellmayr, Moritz Roman Hernandez Petzsche, Qiuyue Ma, Nils Krüger, Helen Liapis, Andreas Brink, Barbara Lenz, Maria Lucia Angelotti, Viviane Gnemmi, Christoph Kuppe, Hyojin Kim, Eric Moniqué Johannes Bindels, Ferenc Tajti, Julio Saez-Rodriguez, Maciej Lech, Rafael Kramann, Paola Romagnani, Hans-Joachim Anders, Stefanie Steiger
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement The role of asymptomatic hyperuricemia in the progression of CKD has been unclear due to lack of animal models with clinically relevant uric acid (UA) levels. A new mouse model reveals that persistent asymptomatic hyperuricemia (approximately 15 mg/dl) does not cause CKD, nor accelerate progression, unless UA crystallizes in acidic tubular fluid. Crystallization initially causes tubular injury, inflammation, and interstitial fibrosis, and subsequently granulomatous interstitial nephritis with perilesional proinflammatory M1-like macrophage infiltrates. Modulating the M1-like macrophage phenotype, but not JAK/STAT inhibition, attenuates granulomatous nephritis. Background The roles of asymptomatic hyperuricemia or uric acid (UA) crystals in CKD progression are unknown. Hypotheses to explain links between UA deposition and progression of CKD include that ( 1 ) asymptomatic hyperuricemia does not promote CKD progression unless UA crystallizes in the kidney; ( 2 ) UA crystal granulomas may form due to pre-existing CKD; and ( 3 ) proinflammatory granuloma-related M1-like macrophages may drive UA crystal-induced CKD progression. Methods MALDI-FTICR mass spectrometry, immunohistochemistry, 3D confocal microscopy, and flow cytometry were used to characterize a novel mouse model of hyperuricemia and chronic UA crystal nephropathy with granulomatous nephritis. Interventional studies probed the role of crystal-induced inflammation and macrophages in the pathology of progressive CKD. Results Asymptomatic hyperuricemia alone did not cause CKD or drive the progression of aristolochic acid I-induced CKD. Only hyperuricemia with UA crystalluria due to urinary acidification caused tubular obstruction, inflammation, and interstitial fibrosis. UA crystal granulomas surrounded by proinflammatory M1-like macrophages developed late in this process of chronic UA crystal nephropathy and contributed to the progression of pre-existing CKD. Suppressing M1-like macrophages with adenosine attenuated granulomatous nephritis and the progressive decline in GFR. In contrast, inhibiting the JAK/STAT inflammatory pathway with tofacitinib was not renoprotective. Conclusions Asymptomatic hyperuricemia does not affect CKD progression unless UA crystallizes in the kidney. UA crystal granulomas develop late in chronic UA crystal nephropathy and contribute to CKD progression because UA crystals trigger M1-like macrophage-related interstitial inflammation and fibrosis. Targeting proinflammatory macrophages, but not JAK/STAT signaling, can attenuate granulomatous interstitial nephritis.
HGF/c-met expression signature defines a subset of human hepatocellular carcinomas with poor prognosis and an aggressive phenotype
Authors: Pal Kaposi-Novak, Ju-Seog Lee, Luis Gomez-Quiroz, Cedric Coulouarn, Valentina M. Factor, Snorri S. Thorgeirsson
Journal: Cancer Research (2006)

3386  Identification of specific gene expression signatures characteristic of oncogenic pathways is an important step towards molecular classification of human malignancies. Aberrant activation of the c-met signaling pathway is frequently associated with tumor progression and metastasis. Recently we defined the c-met dependent gene expression signature using global gene expression profiling of wild-type and c-met deficient primary mouse hepatocytes. Newly identified transcriptional targets of the c-met pathway included genes involved in the regulation of oxidative stress responses as well as cell motility, cytoskeletal organization, and angiogenesis. To assess the importance of a c-met regulated gene expression signature, we applied a comparative functional genomic approach on 242 human hepatocellular carcinomas (HCC) and 7 metastatic liver lesions. Hierarchical cluster analysis of the combined human HCC and mouse hepatocyte expression profiles with conserved orthologous c-met target genes revealed that a subset of human HCC and all the liver metastasis shared the c-met regulated expression signature with the HGF treated murine hepatocytes. Moreover, the presence of the c-met signature showed significant correlation (p
Enhanced Sonodynamic Therapy: An Ultrasound‐Excitable Aggregation‐Induced Emission Dye for Enhanced Sonodynamic Therapy of Tumors (Adv. Healthcare Mater. 17/2020)
Authors: Weiwei Zeng, Yan Xu, Weitao Yang, Kai Liu, Kexin Bian, Bingbo Zhang
Journal: Advanced Healthcare Materials (2020)
Frequency of and risk factors for reversion of QuantiFERON test in healthcare workers in an intermediate-tuberculosis-burden country
Authors: Ja Young Kim, Jiwon Jung, Kyung Jin Jung, Min Jee Hong, Sun Hee Kwak, Eun Ok Kim, Sang-Oh Lee, Sang-Ho Choi, Yang Soo Kim, Jun Hee Woo, Kyung-Wook Jo, Tae Sun Shim, Sung-Han Kim
Journal: Clinical Microbiology and Infection (2020)
The sodium/proton exchanger NHA2 regulates blood pressure through a WNK4-NCC dependent pathway in the kidney
Authors: Manuel A. Anderegg, Giuseppe Albano, Daniela Hanke, Christine Deisl, Dominik E. Uehlinger, Simone Brandt, Rajesh Bhardwaj, Matthias A. Hediger, Daniel G. Fuster
Journal: Kidney International (2020)
Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs
Authors: Agathe Jouet, Cyril Gaudin, Nelly Badalato, Caroline Allix-Béguec, Stéphanie Duthoy, Alice Ferré, Maren Diels, Yannick Laurent, Sandy Contreras, Silke Feuerriegel, Stefan Niemann, Emmanuel André, Michel K. Kaswa, Elisa Tagliani, Andrea Cabibbe, Vanessa Mathys, Daniela Cirillo, Bouke C. de Jong, Leen Rigouts, Philip Supply
Journal: European Respiratory Journal (2020)

Conventional molecular tests for detecting Mycobacterium tuberculosis complex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture. Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum. With MTBC DNA tests, the limit of detection was 100–1000 genome copies for fixed resistance mutations. Deeplex Myc-TB captured in silico 97.1–99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 isolates, the assay predicted 92.2% of 2369 first- and second-line phenotypes, with a sensitivity of 95.3% and a specificity of 95.0% (95.4% and 97.1%, respectively, when excluding ethionamide). 83 out of 102 (81.4%) residual discrepancies with phenotypic results involved pyrazinamide, ethambutol and ethionamide, and low-level rifampicin or isoniazid resistance mutations, all notoriously prone to phenotypic testing variability. Only two out of 96 (2.1%) resistance phenotypes undetected by Deeplex Myc-TB had known resistance-associated mutations by WGS analysis outside Deeplex Myc-TB targets. Phenotype predictions from Deeplex Myc-TB analysis directly on 109 sputa from a Djibouti survey matched those of MTBSeq/PhyResSE/Mykrobe, fed with WGS data from subsequent cultures, with a sensitivity of 93.5/98.5/93.1% and a specificity of 98.5/97.2/95.3%, respectively. Most residual discordances involved gene deletions/indels and 3–12% heteroresistant calls undetected by WGS analysis or natural pyrazinamide resistance of globally rare “ Mycobacterium canettii ” strains then unreported by Deeplex Myc-TB. On 1494 arduous sputa from a Democratic Republic of the Congo survey, 14 902 out of 19 422 (76.7%) possible susceptible or resistance phenotypes could be predicted culture-free. Deeplex Myc-TB may enable fast, tailored tuberculosis treatment.
FDG PET/CT Findings of Extrarenal Wilms Tumor Originating From the Spinal Cord
Authors: Nuh Filizoglu, Kevser Oksuzoglu, Suheyla Bozkurt, Salih Ozguven, Tanju Yusuf Erdil
Journal: Clinical Nuclear Medicine (2020)

Extrarenal Wilms tumor (ERWT) is an extremely rare neoplasm of childhood. It occurs predominantly in retroperitoneum and pelvic or inguinal region without involvement of the kidneys. Although the importance of FDG PET/CT in Wilms tumor is well known, its use in ERWT is limited. Herein, we present FDG PET/CT findings of a 3-year-old girl with a lumbar mass, which was later diagnosed with ERWT.
Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients
Authors: Carl A. Pierce, Paula Preston-Hurlburt, Yile Dai, Clare Burn Aschner, Natalia Cheshenko, Benjamin Galen, Scott J. Garforth, Natalia G. Herrera, Rohit K. Jangra, Nicholas C. Morano, Erika Orner, Sharlene Sy, Kartik Chandran, James Dziura, Steven C. Almo, Aaron Ring, Marla J. Keller, Kevan C. Herold, Betsy C. Herold
Journal: Science Translational Medicine (2020)

Children and youth infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have milder disease than do adults, and even among those with the recently described multisystem inflammatory syndrome, mortality is rare. The reasons for the differences in clinical manifestations are unknown but suggest that age-dependent factors may modulate the antiviral immune response. We compared cytokine, humoral, and cellular immune responses in pediatric (children and youth, age <24 years) (n = 65) and adult (n = 60) patients with coronavirus disease 2019 (COVID-19) at a metropolitan hospital system in New York City. The pediatric patients had a shorter length of stay, decreased requirement for mechanical ventilation, and lower mortality compared to adults. The serum concentrations of interleukin-17A (IL-17A) and interferon-γ (IFN-γ), but not tumor necrosis factor-α (TNF-α) or IL-6, were inversely related to age. Adults mounted a more robust T cell response to the viral spike protein compared to pediatric patients as evidenced by increased expression of CD25+ on CD4+ T cells and the frequency of IFN-γ+ CD4+ T cells. Moreover, serum neutralizing antibody titers and antibody-dependent cellular phagocytosis were higher in adults compared to pediatric patients with COVID-19. The neutralizing antibody titer correlated positively with age and negatively with IL-17A and IFN-γ serum concentrations. There were no differences in anti-spike protein antibody titers to other human coronaviruses. Together, these findings demonstrate that the poor outcome in hospitalized adults with COVID-19 compared to children may not be attributable to a failure to generate adaptive immune responses.
The evolution of Kraepelin's nosological principles
Authors: Stephan Heckers, Kenneth S. Kendler
Journal: World Psychiatry (2020)

Emil Kraepelin developed a new psychiatric nosology in the eight editions of his textbook. Previous papers have explored his construction of particular diagnoses, including dementia praecox and manic‐depressive insanity. Here we are providing a close reading of his introductory textbook chapter, that presents his general principles of nosology. We identify three phases: 1) editions 1‐4, in which he describes nosological principles in search of data; 2) editions 5‐7, in which he declares the mature version of his nosological principles and develops new disease categories; 3) edition 8, in which he qualifies his nosological claims and allows for greater differentiation of psychiatric disorders. We propose that Kraepelin's nosology is grounded in three principles. First, psychiatry, like other sciences, deals with natural phenomena. Second, mental states cannot be reduced to neural states, but science will progress and will, ultimately, reveal how nature creates abnormal mental states and behavior. Third, there is a hierarchy of validators of psychiatric diagnoses, with the careful study of clinical features (signs, symptoms and course) being more important than neuropathologic and etiological studies. These three principles emerged over the course of the eight editions of Kraepelin's textbook and were informed by his own research and by available scientific methods. His scientific views are still relevant today: they have generated and, at the same time, constrained our current psychiatric nosology.