tbuckley/cabot-search huggingface dataset:
Lifetime occupational exposures and chronic obstructive pulmonary disease risk in the UK Biobank cohort
Authors: Sara De Matteis, Debbie Jarvis, Lucy Darnton, Dario Consonni, Hans Kromhout, Sally Hutchings, Steven S Sadhra, David Fishwick, Roel Vermeulen, Lesley Rushton, Paul Cullinan
Journal: Thorax (2022)

Background and aim Occupational exposures are important, preventable causes of COPD. We previously found an increased risk of COPD among six occupations by analysing lifetime job histories and lung function data in the population-based UK Biobank cohort. We aimed to build on these findings and elucidate the underlying potential causal agents to focus preventive strategies. Methods We applied the ALOHA+job exposure matrix (JEM) based on the International Standard Classification of Occupations V.1988 codes, where exposure to 12 selected agents was rated as 0 (no exposure), 1 (low) or 2 (high). COPD was spirometrically defined as FEV 1 /FVC less than the lower limit of normal. We calculated semiquantitative cumulative exposure estimates for each agent by multiplying the duration of exposure and squared intensity. Prevalence ratio (PR) and 95% CI for COPD were estimated using robust Poisson regression adjusted for centre, sex, age, smoking and coexposure to JEM agents. Only associations confirmed among never-smokers and never-asthmatics were considered reliable. Results Out of 116 375 participants with complete job histories, 94 514 had acceptable/repeatable spirometry and smoking data and were included in the analysis. Pesticide exposure showed increased risk of COPD for ever exposure (PR=1.13, 95% CI 1.01 to 1.28) and high cumulative exposure (PR=1.32, 95% CI 1.12 to 1.56), with positive exposure–response trends (p trend=0.004), which were confirmed among never-smokers (p trend=0.005) and never-asthmatics (p trend=0.001). Conclusion In a large population-based study, occupational exposure to pesticides was associated with risk of COPD. Focused preventive strategies for workers exposed to pesticides can prevent the associated COPD burden.
Restrictive Cardiomyopathy
Authors: J R Benotti, W Grossman
Journal: Annual Review of Medicine (1984)

CD40 is a cell-surface member of the TNF (tumor necrosis factor) receptor superfamily. Upon activation, CD40 can license dendritic cells to promote antitumor T cell activation and re-educate macrophages to destroy tumor stroma. Numerous agonist CD40 ...Read More
ATR Inhibitor AZD6738 (Ceralasertib) Exerts Antitumor Activity as a Monotherapy and in Combination with Chemotherapy and the PARP Inhibitor Olaparib
Authors: Zena Wilson, Rajesh Odedra, Yann Wallez, Paul W.G. Wijnhoven, Adina M. Hughes, Joe Gerrard, Gemma N. Jones, Hannah Bargh-Dawson, Elaine Brown, Lucy A. Young, Mark J. O'Connor, Alan Lau
Journal: Cancer Research (2022)

Abstract AZD6738 (ceralasertib) is a potent and selective orally bioavailable inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase. ATR is activated in response to stalled DNA replication forks to promote G2–M cell-cycle checkpoints and fork restart. Here, we found AZD6738 modulated CHK1 phosphorylation and induced ATM-dependent signaling (pRAD50) and the DNA damage marker γH2AX. AZD6738 inhibited break-induced replication and homologous recombination repair. In vitro sensitivity to AZD6738 was elevated in, but not exclusive to, cells with defects in the ATM pathway or that harbor putative drivers of replication stress such as CCNE1 amplification. This translated to in vivo antitumor activity, with tumor control requiring continuous dosing and free plasma exposures, which correlated with induction of pCHK1, pRAD50, and γH2AX. AZD6738 showed combinatorial efficacy with agents associated with replication fork stalling and collapse such as carboplatin and irinotecan and the PARP inhibitor olaparib. These combinations required optimization of dose and schedules in vivo and showed superior antitumor activity at lower doses compared with that required for monotherapy. Tumor regressions required at least 2 days of daily dosing of AZD6738 concurrent with carboplatin, while twice daily dosing was required following irinotecan. In a BRCA2-mutant patient-derived triple-negative breast cancer (TNBC) xenograft model, complete tumor regression was achieved with 3 to5 days of daily AZD6738 per week concurrent with olaparib. Increasing olaparib dosage or AZD6738 dosing to twice daily allowed complete tumor regression even in a BRCA wild-type TNBC xenograft model. These preclinical data provide rationale for clinical evaluation of AZD6738 as a monotherapy or combinatorial agent. Significance: This detailed preclinical investigation, including pharmacokinetics/pharmacodynamics and dose–schedule optimizations, of AZD6738/ceralasertib alone and in combination with chemotherapy or PARP inhibitors can inform ongoing clinical efforts to treat cancer with ATR inhibitors.
Leads from the MMWR. Tubal sterilization-related deaths in US, 1977-1981
Journal: JAMA (1983)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Overlooking the importance of immunoassays – Authors' reply
Authors: Lieselotte Cnops, Johan van Griensven, Anna N Honko, Daniel G Bausch, Armand Sprecher, Charles E Hill, Robert Colebunders, Joshua C Johnson, Anthony Griffiths, Gustavo F Palacios, Colleen S Kraft, Gary Kobinger, Angela Hewlett, David A Norwood, Pardis Sabeti, Peter B Jahrling, Pierre Formenty, Jens H Kuhn, Kevin K Ariën
Journal: The Lancet Infectious Diseases (2016)
Outcomes of surgery in patients 90 years of age and older
Authors: M. P. Hosking
Journal: JAMA (1989)

During the 11-year period 1975 through 1985, seven hundred ninety-five patients 90 years of age and older underwent operative procedures at the Mayo Clinic, Rochester, Minn. Overall serious morbidity within 48 hours after surgery was 9.4%, and the mortality was 1.6%. The 30-day, 1-year, and 5-year mortality rates were 8.4%, 31.4%, and 78.8%, respectively. Short-term morbidity and both short- and long-term mortality were highly associated with the American Society of Anesthesiologists physical status classification of the patient. Emergency procedures carried a significantly higher risk for morbidity and mortality within the 48-hour period and, to a lesser extent, for long-term mortality. Overall, poorer patient survival was associated with higher American Society of Anesthesiologists class; male sex; preoperative renal, liver, and central nervous system impairment; and surgery on the mouth, nose, or pharynx. When compared with age-, sex-, and calendar Year-matched peers from the general population, there was a modest decrease in patient survival at 1 year that reversed by 2 years, with observed survival at 5 years comparable to the rate expected. (<i>JAMA</i>. 1989;261:1909-1915)
FIONA1 is an RNA N6-methyladenosine methyltransferase affecting Arabidopsis photomorphogenesis and flowering
Authors: Chunling Wang, Junbo Yang, Peizhe Song, Wei Zhang, Qiang Lu, Qiong Yu, Guifang Jia
Journal: Genome biology (2022)

Abstract Background N 6 -methyladenosine (m 6 A) mRNA modification is essential for mammalian and plant viability. The U6 m 6 A methyltransferases in other species regulate S-adenosylmethionine (SAM) homeostasis through installing m 6 A in pre-mRNAs of SAM synthetases. However, U6 m 6 A methyltransferase has not been characterized in Arabidopsis and little is known about its role in regulating photomorphogenesis and flowering. Results Here we characterize that FIONA1 is an Arabidopsis U6 m 6 A methyltransferase that installs m 6 A in U6 snRNA and a small subset of poly(A) + RNA. Disruption of FIONA1 leads to phytochrome signaling-dependent hypocotyl elongation and photoperiod-independent early flowering. Distinct from mammalian METTL16 and worm METT-10, FIONA1 neither installs m 6 A in the mRNAs of Arabidopsis SAM synthetases nor affects their transcript expression levels under normal or high SAM conditions. We confirm that FIONA1 can methylate plant mRNA m 6 A motifs in vitro and in vivo. We further show that FIONA1 installs m 6 A in several phenotypic related transcripts, thereby affecting downstream mRNA stability and regulating phytochrome signaling and floral transition. Conclusion FIONA1 is functional as a U6 m 6 A methyltransferase in Arabidopsis, distinct from mammalian METTL16 and worm METT-10. Our results demonstrate that FIONA1-mediated m 6 A post-transcriptional regulation is an autonomous regulator for flowering and phytochrome signaling-dependent photomorphogenesis.
TCT CONNECT-260 A Prospective Randomized Multicenter Study to Assess the Safety and Effectiveness of the Orsiro Sirolimus-Eluting Stent in the Treatment of Subjects With up to 2 De Novo Coronary Artery Lesions—BIOFLOW IV: 5-Year Clinical Results
Authors: Bernhard Witzenbichler, Ton Slagboom, Ralph Toelg, Michael Haude, Monica Masotti, Rafael Ruiz-Salmerón, Adam Witkowski, Ron Waksman, Shigeru Saito
Journal: Journal of the American College of Cardiology (2020)
Recurrent pulmonary embolism. A sign of multiple myeloma
Authors: L. E. Monta
Journal: JAMA (1975)

HEMORRHAGE resulting from hyperviscosity and coagulation defects is a recognized manifestation of myelomatosis.<sup>1,2</sup>Thromboembolism as a complication of this disease is, however, much less frequently recognized. Even more uncommon is myelomatosis presenting as deep vein thrombosis or pulmonary embolism. This is the case report of a patient with recurrent thromboembolic phenomena of unknown cause, until the diagnosis was established six months later. <h3>Report of a Case</h3> A 60-year-old woman was referred to West Virginia University Medical Center in July 1973 for evaluation of recurrent pulmonary emboli. She had been well until September 1972, when shortness of breath and midline chest pain with hemoptysis suddenly developed. The patient was admitted to her local hospital, where a diagnosis of embolism in the left lung was made and anticoagulant therapy begun. Information gleaned from hospital records of September 1972 indicated increased serum globulin at that time; however, this abnormality was not investigated.
Endoscopic ultrasound-guided jejunojejunal anastomosis as salvage therapy for a complex gastric outlet obstruction
Authors: Enrique Pérez-Cuadrado-Robles, Guillaume Perrod, Alexandre Lansier, Juliette Palle, Antoine Mariani, Christophe Cellier, Gabriel Rahmi
Journal: Endoscopy (2022)

Lumen-apposing metal stents are gaining ground in the treatment of gastric outlet obstruction (GOO) caused by malignant duodenal stenosis [1]. This technique is also opening up new alternatives as a rescue therapy for patients presenting with benign GOO and a previous history of gastric surgery or endoscopic procedures [2].
Radiotracer stereochemistry affects substrate affinity and kinetics for improved imaging of system x<sub>C</sub><sup>-</sup> in tumors
Authors: Hannah E. Greenwood, Richard Edwards, Norman Koglin, Mathias Berndt, Friedrich Baark, Jana Kim, George Firth, Eman Khalil, Andre Mueller, Timothy H. Witney
Journal: Theranostics (2022)

Amino acid utilization is perturbed in cancer cells, which rewire their metabolism to support cell survival and proliferation.This metabolic reprogramming can be exploited for diagnostic purposes through positron emission tomography imaging of fluorine-18 labeled amino acids.Despite its promise, little is known regarding transporter-recognition of non-natural amino acid stereoisomers or their utility for cancer imaging.We report here the synthesis and in vivo characterization of a radiolabeled amino acid (R)-4-(3-18 F-fluoropropyl)-ʟ-glutamate ([ 18 F]FRPG) and compared its tumor imaging properties to the 4S-isomer, [ 18 F]FSPG.Methods: [ 18 F]FRPG and [ 18 F]FSPG uptake was assessed in H460 lung cancer cells, with efflux measured 30 min after removal of exogenous activity.Specificity of [ 18 F]FRPG for system xC -was further examined following transporter inhibition and blocking studies with system xC -substrates.[ 18 F]FRPG and [ 18 F]FSPG pharmacokinetics was next quantified in mice bearing subcutaneous A549, H460, VCAP and PC3 tumors, with mice bearing A549 tumors imaged by PET/CT.To better-understand differential tumor retention, radiometabolite analysis was performed on tissue and blood samples after imaging.Next, [ 18 F]FRPG and [ 18 F]FSPG retention in lipopolysaccharide-treated lungs were compared to an orthotopic H460 lung cancer model.Finally, the sensitivity of [ 18 F]FRPG to manipulation of the redox environment was examined in cell and in vivo models.Results: [ 18 F]FRPG was specifically transported across the plasma membrane by the cystine/glutamate antiporter system xC -and retained at high levels in multiple tumor models.Conversely, [ 18 F]FRPG was rapidly extracted from the blood and cleared from tissues with low system xC -expression.Due to its favorable imaging properties, tumor-to-blood ratios ≥10 were achieved with [ 18 F]FRPG, which were either equal to or greater than [ 18 F]FSPG.In addition, [ 18 F]FRPG retention in orthotopic lung tumors with high system xC -expression was 2.5-fold higher than inflamed tissue, allowing for clear tumor visualization.In vivo, [ 18 F]FRPG and [ 18 F]FSPG were metabolized to a single species, with [ 18 F]FRPG showing a higher percentage of parent radiotracer in tumors compared to [ 18 F]FSPG.[ 18 F]FRPG was sensitive to redox manipulations and tumor retention was reduced following treatment with liposomal doxorubicin in mice bearing ovarian tumors.Conclusions: Given the fast clearance and low background retention of [ 18 F]FRPG throughout the body, this radiotracer holds promise for the imaging of system xC -activity and treatment response monitoring in tumors of the thorax, abdomen, and head and neck.[ 18 F]FRPG PET imaging provides a sensitive noninvasive measure of system xC -and excellent properties for cancer imaging.
Update: Expanded Availability of Thimerosal Preservative-Free Hepatitis B Vaccine
Journal: JAMA (2000)

Thimerosal, a mercury-based compound, is no longer used as a preservative in any of the pediatric hepatitis B vaccines licensed in the United States. On March 28, 2000, SmithKline Beecham Biologicals (Rixensart, Belgium) received approval from the Food and Drug Administration of a supplement to its hepatitis B license to include the manufacture of single-antigen, preservative-free hepatitis B vaccine (Engerix-B, pediatric/adolescent); distribution of this product has begun. A single-antigen, preservative-free hepatitis B vaccine (Recombivax HB, pediatric) from Merck Vaccine Division (West Point, Pennsylvania) had earlier received similar approval (1). A preservative-free Haemophilus influenzae type b (Hib)/hepatitis B combination vaccine (Comvax) from Merck Vaccine Division also is available. An adequate supply of preservative-free hepatitis B vaccine is available for all infant and childhood vaccinations. Thimerosal preservative-containing hepatitis B vaccines may continue to be used for vaccination of adolescents and adults as recommended (2).
The emergence of COVID-19 associated mucormycosis: a review of cases from 18 countries
Authors: Martin Hoenigl, Danila Seidel, Agostinho Carvalho, Shivaprakash M Rudramurthy, Amir Arastehfar, Jean-Pierre Gangneux, Nosheen Nasir, Alexandro Bonifaz, Javier Araiza, Nikolai Klimko, Alexandra Serris, Katrien Lagrou, Jacques F Meis, Oliver A Cornely, John R Perfect, P Lewis White, Arunaloke Chakrabarti
Journal: The Lancet Microbe (2022)
Practical Applications of Heredity.
Journal: JAMA (1931)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Arthritis Awareness Month — May 2019
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Arthritis Awareness Month, led by the Arthritis Foundation (https://www.arthritis.org), is observed each May to bring attention to arthritis and its impact. Arthritis affects an estimated 54.4 million U.S. adults, or approximately one in four (1); and of these adults with arthritis, approximately 27% have severe joint pain (2). Arthritis also is linked to higher rates of physical inactivity (1).
THE NEW ORLEANS SESSION
Journal: JAMA (1903)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
<i>ATMIN</i> Is a Tumor Suppressor Gene in Lung Adenocarcinoma
Authors: Hanna Foster, E. Josue Ruiz, Christopher Moore, Gordon W. H. Stamp, Emma L. Nye, Ningning Li, Yihang Pan, Yulong He, Julian Downward, Axel Behrens
Journal: Cancer Research (2019)

Tumor cells proliferate rapidly and thus are frequently subjected to replication stress and the risk of incomplete duplication of the genome. Fragile sites are replicated late, making them more vulnerable to damage when DNA replication fails to complete. Therefore, genomic alterations at fragile sites are commonly observed in tumors. FRA16D is one of the most common fragile sites in lung cancer, however, the nature of the tumor suppressor genes affected by FRA16D alterations has been controversial. Here, we show that the
Comorbidity and Disability in Medicare Beneficiaries Newly Diagnosed with Non-Advanced Systemic Mastocytosis (Non-AdvSM)
Authors: Allison Petrilla, Erin Sullivan, Maria Roche, Jenna Cohen, Chelsea Norregaard, Uyen Nguyen, Chris Sloan, Alison Silverstein, Anne Murunga, Jill Schinkel
Journal: Journal of Allergy and Clinical Immunology (2022)
Tumor Imaging With 68Ga-DOTA-FAPI-04 PET/CT
Authors: Tevfik Fikret Çermik, Nurhan Ergül, Burçak Yılmaz, Güldem Mercanoğlu
Journal: Clinical Nuclear Medicine (2022)

Cancer-associated fibroblasts, which are densely found in tumor tissue, express high levels of fibroblast activation protein (FAP), and FAP inhibitors (FAPIs) labeled with radionuclides can be used in the diagnosis and treatment of cancer. In this study, the role of 68Ga-DOTA-FAPI-04 PET/CT in imaging of primary, metastatic, and recurrent cancers was investigated.A total of 42 patients (16 females, 26 males; mean age, 58.5 years; range, 31-84 years) with 22 different types of malignant diseases were included in the study. 68Ga-DOTA-FAPI-04 PET/CT imaging was performed 1 to 7 days after 18F-FDG PET/CT. Pathological uptake levels in primary tumoral lesions, lymph nodes, skeletal system, liver, peritoneal surfaces, and other body parts were compared between 2 PET/CTs. In addition, physiological uptake levels of 18F-FDG and 68Ga-FAPI were defined measuring the liver, thoracic aorta, gluteal muscle activities, and uterus activity in female patients.Of the 42 patients in the study group, 33 patients were included for staging, 8 patients for restaging, and 1 patient for evaluation of treatment response. 68Ga-DOTA-FAPI-04 PET/CT showed intense uptake in 94.2% of primary tumoral lesions. In patients with multiple myeloma, 18F-FDG uptake in the bone marrow was significantly higher than 68Ga-FAPI uptake, whereas in gastric signet ring cell tumors, 68Ga-FAPI uptake was found to be significantly higher than 18F-FDG uptake. It was observed that 68Ga-DOTA-FAPI-04 PET/CT detected bone, liver, and peritoneum metastases with higher sensitivity and accuracy compared 18F-FDG PET/CT.The preliminary findings of this study showed that 68Ga-DOTA-FAPI-04 PET/CT can contribute to the diagnostic process in solid tumors. Especially in malignancies with mild uptake on 18F-FDG PET/CT, it stands out in diagnosis, staging, and restaging. It is also predicted that FAPI molecules can be used for radionuclide therapy in patients with metastatic disease and unresponsive to other treatments showing intense uptake on 68Ga-DOTA-FAPI-04 PET/CT.
Longitudinal Association of Parent and Child Patient Reported Outcomes in Eosinophilic Esophagitis in a Multicenter Cohort
Authors: Seema Aceves, Lisa Martin, Xue Znang, Mirna Chehade, Margaret Collins, Evan Dellon, Nirmala Gonsalves, Sandeep Gupta, Ikuo Hirano, Girish Hiremath, David Katzka, Paneez Khoury, John Leung, Robbie Pesek, Kathryn Peterson, Jonathan Spergel, Joshua Wechsler, Nicole Arva, Guang-Yu Yang, Glenn Furuta, Marc Rothenberg
Journal: Journal of Allergy and Clinical Immunology (2022)