tbuckley/cabot-search huggingface dataset:
The not so innocent bystander: an unusual cause of progressive breathlessness
Authors: Max Lyon, Alastair Whiteway, Michael Darby, Nidhi Bhatt, Shaney L Barratt
Journal: Thorax (2021)

This case report discusses a 76-year-old man who presented with symptomatic diffuse alveolar-septal and tracheobronchial amyloidosis with a low-grade monoclonal gammopathy. This patient had a combination of both symptomatic diffuse alveolar-septal interstitial disease and tracheobronchial amyloidosis, features that contradict the widely accepted presentations seen in this disease. First, tracheobronchial amyloidosis has been documented as localised disease without systemic involvement. Second, diffuse alveolar-septal interstitial disease is rarely identified with clinical symptoms unless there is significant cardiac involvement. This case highlights a number learning points in the diagnosis and management of systemic amyloid light chain amyloidosis;(1) There is a need for a high index of suspicion for diagnosis due to the potential subtlety of a plasma cell clone underlying AL amyloidosis, requiring serum-free light chain assays to increase sensitivity; (2) Haematological response and recovery of organ dysfunction are not a linear relationship due to the slower reversal of amyloid deposition; therefore, ongoing monitoring is required to identify those in need of repeated therapy. However, haematological response is a marker of overall survival and (3) Multisystem assessment and multidisciplinary collaboration are critical in optimising the care of patients with systemic AL amyloidosis.
Trends in Within-Class Changes in US Average Wholesale Prices for Brand-Name Medications for Common Conditions From 2015 to 2020
Authors: Patrick Liu, Sanket S. Dhruva, Nilay D. Shah, Joseph S. Ross
Journal: JAMA Network Open (2021)

a A generic form of prasugrel was introduced in August 2017; this value represents the Kendall τb coefficient between Brilinta
Correspondence on ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’
Authors: Young Ho Lee
Journal: Annals of the Rheumatic Diseases (2021)

The paper by Akiyama et al 1 on the prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases was an interesting read. This systematic review and meta-analysis indicates that glucocorticoid usage increases the risk of developing COVID-19, while monotherapy with biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs, particularly antitumour necrosis factor (TNF) monotherapy, has been associated with a decreased risk of developing severe COVID-19 and related mortality.1 However, certain methodological issues in this meta-analysis study need to be addressed. First, the efficacy and safety of glucocorticoid usage in patients with …
Second-line tyrosine kinase inhibitors (TKIs) versus immunotherapy (IO) for advanced hepatocellular carcinoma (HCC): Real-world efficacy and safety analysis in patients with varying liver dysfunction.
Authors: Jeffrey Xia, Jonathan Gelfond, Sukeshi Patel Arora
Journal: Journal of Clinical Oncology (2021)

271 Background: Within the last 4 years, the FDA approved five drugs as second-line therapies for advanced HCC. At our cancer center, the majority of our patients are Hispanic with varying liver dysfunction, and this real world population is not represented in registration trials of TKIs and IOs. Therefore, we analyzed survival and toxicities among second-line therapies for HCC at our Hispanic-majority NCI-designated cancer center. Methods: Retrospective analysis of patients with advanced HCC diagnosed at Mays Cancer Center from 1/2015-3/2019 who received second-line therapies, including IO (i.e. nivolumab), TKIs (i.e. cabozantinib, regorafenib), or hospice/best supportive care (BSC). Progression-free survival (PFS) was determined using Kaplan-Meier method, and hazard ratios estimated with Cox proportional hazards model. AEs according to Common Terminology Criteria for AEs v5.0 were analyzed with Fisher’s exact test. Results: Of the patients receiving first-line therapy, the median age was 60 years (n=65), and patients were 75% (n=49) Hispanics. 58 (89%) patients went onto receive second-line therapy. Child-Pugh (CP) score: A 17%, B 55%, C 28%. Median PFS was 3.1 months with TKI (n=6), 3.3 months with IO (n=27), and 1.3 months with BSC (n=25) (Table). There was improved survival with IO when compared to BSC (HR=3.26; 95% CI: 1.58-6.72; p=0.00136). There was no significant difference when comparing IO to TKI (HR=0.94; 95% CI: 0.31-2.86; p=0.92), but a trend to improved PFS with TKI when compared to BSC (HR=3.08; 95% CI: 0.96-9.84; p=0.06). TKI group had significantly more rash (p=0.01) and hand-foot syndrome (HFS) (p&lt;0.001) compared to IO and BSC. All other AEs demonstrated no significant difference between groups (Table). Conclusions: In our Hispanic-majority cohort, patients with varying liver dysfunction, including CP B &amp; C cirrhosis, were more likely to receive IO or BSC. Both second-line treatment groups (IO or TKI) had increased mPFS compared to BSC. Both IO and TKI groups were tolerable compared to BSC, with expected toxicity per class of drug. More prospective studies comparing second-line agents should be done in patients with varying liver dysfunction to understand survival, tolerability, and quality of life. [Table: see text]
Modeling and targeting of erythroleukemia by hematopoietic genome editing
Authors: Ilaria Iacobucci, Chunxu Qu, Elena Varotto, Laura J. Janke, Xu Yang, Aman Seth, Anang Shelat, Jake D. Friske, Reiji Fukano, Jiyang Yu, Burgess B. Freeman, James A. Kennedy, Adam S. Sperling, Rena Zheng, Yingzhe Wang, Harini Jogiraju, Kirsten M. Dickerson, Debbie Payne-Turner, Sarah M. Morris, Emily S. Hollis, Nina Ghosn, Georgia E. Haggard, R. Coleman Lindsley, Benjamin L. Ebert, Charles G. Mullighan
Journal: Blood (2021)
The Need for an Improved Evidence Base to Inform the Health Care Decision-making Process
Authors: Qing Xia, Julie Campbell, Andrew J. Palmer
Journal: JAMA Surgery (2021)

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 Surgery 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 Surgery journal
Basophil activation test: Mechanisms and considerations for use in clinical trials and clinical practice
Authors: Alexandra F. Santos, Oral Alpan, Hans‐Jürgen Hoffmann
Journal: Allergy (2021)

The basophil activation test (BAT) is a functional assay that measures the degree of degranulation following stimulation with allergen or controls by flow cytometry. It correlates directly with histamine release. From the dose-response curve resulting from BAT in allergic patients, basophil reactivity (%CD63+ basophils) and basophil sensitivity (EC50 or similar) are the main outcomes of the test. BAT takes into account all characteristics of IgE and allergen and thus can be more specific than sensitization tests in the diagnosis of allergic disease. BAT reduces the need for in vivo procedures, such as intradermal tests and allergen challenges, which can cause allergic reactions of unpredictable severity. As it closely reflects the patients' phenotype in most cases, it may be used to support the diagnosis of food, venom and drug allergies and chronic urticaria, to monitor the natural resolution of food allergies and to predict and monitor clinical the response to immunomodulatory treatments, such as allergen-specific immunotherapy and biologicals. Clinical application of BAT requires analytical validation, clinical validation, standardization of procedures and quality assurance to ensure reproducibility and reliability of results. Currently, efforts are ongoing to establish a platform that could be used by laboratories in Europe and in the USA for quality assurance and certification.
SP0037 What has been achieved and what can be expected in rheumatology?
Authors: W Ollier
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Major advances have already been made in Rheumatology, many of which have translated into improved clinical care and management. These have largely centred around: Descriptive studies. These have resulted in: a better classification/diagnosis and thus treatment of rheumatic conditions a clearer understanding of the natural history of diseases epidemiologically defined disease parameters (e.g. prevalence, incidence, geographical distribution, age at onset, gender ratios) Imaging and definition of relevant laboratory tests higher resolution imaging of hard and soft tissues for appreciating both early disease processes and disease progression/severity. Laboratory investigations, as useful aids for diagnosis (autoantibody profiles, rheumatoid factor) and disease activity (e.g. CRP) Treatments and interventions The development of effective and lasting joint replacement prostheses The introduction of better treatments (e.g. Cox2 inhibitors) and biological based therapies to antagonise inflammatory cytokines and processes (e.g. TNF-alpha antagonists) What can be expected in the future for rheumatology remains speculation but exciting prospects are likely for clinical medicine in the post human genome sequencing era. A primary objective will be the identification of the genetic and environmental components to disease aetiopathogenesis. These should lead to: a better understanding of disease processes and classification resulting in more appropriate treatments. The identification of novel targets for pharmaceutical intervention. An ability to predict disease risk and disease outcome, permiting early screening and a more rapid or aggressive treatment plan. The characterisation of gene-environment interactions, resulting in health education and changes in life style or in possible proplylactic intervention. The identification of the pharmacogenetic basis for response to drugs and why there is variation in efficacy or adverse drug reactions. This should lead to personalised medicine. New developments in molecular biology and cell biology are also likely to impinge on rheumatology in the areas of: Tissue Engineering Gene therapy Stem cell transplation
Chlamydia pneumoniae and aortic valve stenosis: a comparative study with non-calcified valves
Authors: Marilia H. Santos, Humberto Pierri, Maria L. Higuchi, Sueli Palomino, Nadia V. Sambiase, Lea M. Demarchi, Jose A. Ramires, Mauricio Wajngarten
Journal: Journal of the American College of Cardiology (2002)
Abstract 10250: Oxidized-phospholipid Mediated Ischemia-reperfusion Injury and Its Mitigation by IL-10
Authors: Ashim K Bagchi, Arun Surendran, Akshi Malik, Amir Ravandi, Davinder S Jassal, Pawan K Singal
Journal: Circulation (2019)

Introduction: Oxidized phospholipids (OxPLs) promote inflammation as well as low density lipoprotein (LDL) uptake in a variety of physiological and pathological states. The cytokine interleukin-10 ...
Polygenic risk scores in the clinic: new perspectives needed on familiar ethical issues
Authors: Anna C. F. Lewis, Robert C. Green
Journal: Genome Medicine (2021)

Abstract Clinical use of polygenic risk scores (PRS) will look very different to the more familiar monogenic testing. Here we argue that despite these differences, most of the ethical, legal, and social issues (ELSI) raised in the monogenic setting, such as the relevance of results to family members, the approach to secondary and incidental findings, and the role of expert mediators, continue to be relevant in the polygenic context, albeit in modified form. In addition, PRS will reanimate other old debates. Their use has been proposed both in the practice of clinical medicine and of public health, two contexts with differing norms. In each of these domains, it is unclear what endpoints clinical use of PRS should aim to maximize and under what constraints. Reducing health disparities is a key value for public health, but clinical use of PRS could exacerbate race-based health disparities owing to differences in predictive power across ancestry groups. Finally, PRS will force a reckoning with pre-existing questions concerning biomarkers, namely the relevance of self-reported race, ethnicity and ancestry, and the relationship of risk factors to disease diagnoses. In this Opinion, we argue that despite the parallels to the monogenic setting, new work is urgently needed to gather data, consider normative implications, and develop best practices around this emerging branch of genomics.
Exposure of Adult Female Mice to Low Doses of di(2-ethylhexyl) Phthalate Alone or in an Environmental Phthalate Mixture: Evaluation of Reproductive Behavior and Underlying Neural Mechanisms
Authors: Nolwenn Adam, Linda Brusamonti, Sakina Mhaouty-Kodja
Journal: Environmental Health Perspectives (2021)

We have previously shown that adult male mice exposure to low doses of an ubiquitous endocrine disruptor, di(2-ethylhexyl) phthalate (DEHP), alters courtship behavior.The effects of adult exposure to low doses of DEHP alone or in an environmental phthalate mixture on estrous cyclicity, reproductive behavior, and underlying neural structures were analyzed in female mice.Two-month-old C57BL/6J females were exposed orally for 6 wk to DEHP alone (0, 5 or 50μg/kg/d) or to DEHP (5μg/kg/d) in a phthalate mixture. Estrous cyclicity was analyzed in intact mice, and behavior [lordosis, olfactory preference, partner preference, ability to stimulate male ultrasonic vocalizations (USVs)] was measured in ovariectomized mice primed with estradiol and progesterone. Immunohistochemical studies were conducted in the neural structures involved in behavior for estrogen receptor (ER) α and progesterone receptor (PR).Exposure to DEHP alone or in mixture lengthened the estrous cycle duration, with a shorter proestrus and longer estrus and metestrus stages. Under normalized hormonal levels, females exposed to DEHP alone or in mixture exhibited altered olfactory preference. A lower lordosis behavior and ability to attract and stimulate male emission of courtship USVs was observed, probably due to modifications of pheromonal emission in exposed females. The behavioral alterations were associated with a lower number of PR-expressing neurons, without changes in ERα, in the neural circuitry underlying sexual behavior. The majority of effects observed was comparable between the two DEHP doses and were driven by DEHP in the mixture.Exposure to environmental doses of DEHP alone or in mixture altered several components of female sexual behavior in mice, probably through selective disruption of neural PR signaling. Together with the previously reported vulnerability of male mice, this finding suggests a major impact of exposure to phthalates on sexual reproduction, including in other species with similar neural regulatory processes. https://doi.org/10.1289/EHP7662.
AB0006 HYPOMETHYLATION OF THE PROMOTER REGION OF TLR4 GENE AT A SYSTEMIC LEVEL IN PATIENTS WITH RHEUMATOID ARTHRITIS AND PERIODONTITIS
Authors: S. Chatterjee, D. Bhattacharjee, S. Misra, A. Rao, A. Chattopadhyay, A. Ghosh
Journal: Annals of the Rheumatic Diseases (2020)

Background: Periodontitis (PD) has long been linked with Rheumatoid arthritis (RA) [1]. Epigenetic modifications are being recently explored to explain such associations, DNA methylation being one such important mechanism. Objectives: To study the effect chronic generalized periodontitis on systemic methylation of TLR4 genes in comparison to only RA and RA with PD patients. Methods: Twenty-three RA patients, among which 11 patients had chronic generalized PD, 20 patients with only PD and 15 healthy individuals recruited. DNA was isolated from PBMCs of the participants blood, then were first bisulphite converted and then methylation specific PCR were performed using primers for methylated and um-methylated promoters of TLR4. The DNA amplifications were checked in horizontal gel electrophoresis. The methylation signatures were verified by DNA sequencing (Sanger) of the amplified products. Results: The anti-CCP, DAS-CRP and HAQ DI were higher in patients with both RA and PD (220±40, 5.7±0.2, 1.5±0.1 respectively, p&lt;0.05). Control samples had shown amplification bands for methylated primers of TLR4 but not for un-methylated primers of TLR4. However, only RA, only PD and RA with PD samples, had shown amplification for un-methylated primers and not for methylated primers. These results together with DNA sequencing indicated that 4 CpG sites in the promoter ofTLR4 genes were hypo-methylated in the PBMCs of patients whereas those remain methylated in healthy individuals. Conclusion: The observations indicated that though PD is a localised disease of the gingiva there is a systemic involvement of TLR mediated pathways in them which is similar to those in RA. However, further validation in larger cohort and down-stream signalling molecules needs to be studied. References: [1]Ceccarelli F, Saccucci M, Di Carlo G, Lucchetti R, Pilloni A, Pranno N, Luzzi V, Valesini G, Polimeni A. Periodontitis and rheumatoid arthritis: the same inflammatory mediators?. Mediators of inflammation. 2019;2019. Disclosure of Interests: None declared
Heterogeneity and Clonal Evolution of Acquired PARP Inhibitor Resistance in <i>TP53-</i> and <i>BRCA1</i>-Deficient Cells
Authors: Anniina Färkkilä, Alfredo Rodríguez, Jaana Oikkonen, Doga C. Gulhan, Huy Nguyen, Julieta Domínguez, Sandra Ramos, Caitlin E. Mills, Fernando Pérez-Villatoro, Jean-Bernard Lazaro, Jia Zhou, Connor S. Clairmont, Lisa A. Moreau, Peter J. Park, Peter K. Sorger, Sampsa Hautaniemi, Sara Frias, Alan D. D'Andrea
Journal: Cancer Research (2021)

Abstract Homologous recombination (HR)-deficient cancers are sensitive to poly-ADP ribose polymerase inhibitors (PARPi), which have shown clinical efficacy in the treatment of high-grade serous cancers (HGSC). However, the majority of patients will relapse, and acquired PARPi resistance is emerging as a pressing clinical problem. Here we generated seven single-cell clones with acquired PARPi resistance derived from a PARPi-sensitive TP53−/− and BRCA1−/− epithelial cell line generated using CRISPR/Cas9. These clones showed diverse resistance mechanisms, and some clones presented with multiple mechanisms of resistance at the same time. Genomic analysis of the clones revealed unique transcriptional and mutational profiles and increased genomic instability in comparison with a PARPi-sensitive cell line. Clonal evolutionary analyses suggested that acquired PARPi resistance arose via clonal selection from an intrinsically unstable and heterogenous cell population in the sensitive cell line, which contained preexisting drug-tolerant cells. Similarly, clonal and spatial heterogeneity in tumor biopsies from a clinical patient with BRCA1-mutant HGSC with acquired PARPi resistance was observed. In an imaging-based drug screening, the clones showed heterogenous responses to targeted therapeutic agents, indicating that not all PARPi-resistant clones can be targeted with just one therapy. Furthermore, PARPi-resistant clones showed mechanism-dependent vulnerabilities to the selected agents, demonstrating that a deeper understanding on the mechanisms of resistance could lead to improved targeting and biomarkers for HGSC with acquired PARPi resistance. Significance: This study shows that BRCA1-deficient cells can give rise to multiple genomically and functionally heterogenous PARPi-resistant clones, which are associated with various vulnerabilities that can be targeted in a mechanism-specific manner.
Emerging insights on the role of V‐ATPase in human diseases: Therapeutic challenges and opportunities
Authors: Cátia Santos‐Pereira, Lígia R. Rodrigues, Manuela Côrte‐Real
Journal: Medicinal Research Reviews (2021)

Abstract The control of the intracellular pH is vital for the survival of all organisms. Membrane transporters, both at the plasma and intracellular membranes, are key players in maintaining a finely tuned pH balance between intra‐ and extracellular spaces, and therefore in cellular homeostasis. V‐ATPase is a housekeeping ATP‐driven proton pump highly conserved among prokaryotes and eukaryotes. This proton pump, which exhibits a complex multisubunit structure based on cell type‐specific isoforms, is essential for pH regulation and for a multitude of ubiquitous and specialized functions. Thus, it is not surprising that V‐ATPase aberrant overexpression, mislocalization, and mutations in V‐ATPase subunit‐encoding genes have been associated with several human diseases. However, the ubiquitous expression of this transporter and the high toxicity driven by its off‐target inhibition, renders V‐ATPase‐directed therapies very challenging and increases the need for selective strategies. Here we review emerging evidence linking V‐ATPase and both inherited and acquired human diseases, explore the therapeutic challenges and opportunities envisaged from recent data, and advance future research avenues. We highlight the importance of V‐ATPases with unique subunit isoform molecular signatures and disease‐associated isoforms to design selective V‐ATPase‐directed therapies. We also discuss the rational design of drug development pipelines and cutting‐edge methodological approaches toward V‐ATPase‐centered drug discovery. Diseases like cancer, osteoporosis, and even fungal infections can benefit from V‐ATPase‐directed therapies.
ACCF/AHA 2007 Clinical Competence Statement on Vascular Imaging With Computed Tomography and Magnetic Resonance
Authors: Christopher M. Kramer, Matthew J. Budoff, Zahi A. Fayad, Victor A. Ferrari, Corey Goldman, John R. Lesser, Edward T. Martin, Sanjay Rajagopalan, John P. Reilly, George P. Rodgers, Lawrence Wechsler, Mark A. Creager, David R. Holmes, Geno Merli, L. Kristin Newby, Ileana Piña, George P. Rodgers, Howard H. Weitz
Journal: Journal of the American College of Cardiology (2007)
Germline variants drive myelodysplastic syndrome in young adults
Authors: Simone Feurstein, Jane E. Churpek, Tom Walsh, Sioban Keel, Marja Hakkarainen, Thomas Schroeder, Ulrich Germing, Stefanie Geyh, Michael Heuser, Felicitas Thol, Christian Pohlkamp, Torsten Haferlach, Juehua Gao, Carolyn Owen, Gudrun Goehring, Brigitte Schlegelberger, Divij Verma, Daniela S. Krause, Guimin Gao, Tara Cronin, Suleyman Gulsuner, Ming Lee, Colin C. Pritchard, Hari Prasanna Subramanian, Daniela del Gaudio, Zejuan Li, Soma Das, Outi Kilpivaara, Ulla Wartiovaara-Kautto, Eunice S. Wang, Elizabeth A. Griffiths, Konstanze Döhner, Hartmut Döhner, Mary-Claire King, Lucy A. Godley
Journal: Leukemia (2021)