tbuckley/cabot-search huggingface dataset:
Incidental Detection of Lung Adenocarcinoma Presenting as an Anterior Mediastinal Mass on 18F-Fluciclovine PET/CT in a Patient With Primary Prostate Cancer
Authors: Olayinka A. Abiodun-Ojo, Akinyemi A. Akintayo, Gabriel L. Sica, Mehrdad Alemozaffar, David M. Schuster
Journal: Clinical Nuclear Medicine (2020)

Abstract 18 F-fluciclovine is a PET radiotracer approved for detection of recurrent prostate cancer, with utility in other malignancies being investigated. We present the case of a 71-year-old man with high-risk primary prostate cancer (Gleason score 9, prostate-specific antigen 34 ng/mL) and newly diagnosed lung adenocarcinoma. As part of a clinical trial (NCT03081884), preoperative 18 F-fluciclovine PET/CT showed localized abnormal uptake in the prostate gland with extracapsular extension. Additionally, an incidental anterior mediastinal mass measuring 2.2 × 1.8 cm demonstrated abnormal radiotracer uptake. Biopsy of the mediastinal mass confirmed invasive lung adenocarcinoma with solid and acinar patterns and high programmed death 1 ligand expression.
Can telerheumatology improve rheumatic and musculoskeletal disease service delivery in sub-Saharan Africa?
Authors: Akpabio Akpabio, Richard Oluyinka Akintayo, Utibe Effiong
Journal: Annals of the Rheumatic Diseases (2020)

We note with great interest the paper by Costa et al ,1 who submits that telemedicine has emerged as a key tool for managing psoriatic arthritis (PsA) among patients in Italy during the COVID-19 pandemic. The WHO has emphasised that universal health coverage cannot be achieved without the support of e-health of which telemedicine is a subset.2 In sub-Saharan Africa, there is a dearth of rheumatologists. Rheumatology services are mostly centred in urban tertiary academic hospitals despite the greater rheumatic and musculoskeletal disease (RMD) burden in rural communities.3 In an attempt to link technology and healthcare in the region, innovative tools for electronic data capture and clinical decision support have been developed with varying degrees of success.4 5

Telemedicine (also used interchangeably with telehealth) can be defined as the use of medical information that is exchanged from one site to another through electronic communication to improve a patient’s health.6 It has wide use in radiology, dermatology and psychiatry. Its usage in specialties like rheumatology (telerheumatology) appears to be increasing. Different telemedicine services exist. These include teleconsultation (synchronous or asynchronous), remote patient monitoring, as well as tele-education (online continuing medical education). Key advantages include convenience, …
Nuclear localization of Akt in gallbladder carcinoma from BK5.erbB2 mice
Authors: Mohammad Rumi, Lynnsie Ruffino, John DiGiovanni, Kaoru Kiguchi
Journal: Cancer Research (2007)

106  Gallbladder carcinomas carry poor prognosis and difficulties with treatment, often due to late stage diagnosis, highly malignant nature, and limited knowledge regarding the pathogenesis. Overexpression of erbB2 in gallbladder epithelial cells in BK5.erbB2 transgenic mice leads to development of adenocarcinoma in 90% of the homozygous transgenic mice. This transgenic mouse model provided a useful tool for investigating the mechanism of erbB2 induced development of gallbladder carcinoma. We detected that erbB2 overexpression in transgenic gallbladder epithelial cells was associated with a high level of EGFR and both erbB2 and EGFR were constitutively activated. We further analyzed the downstream of erbB2/EGFR signaling in gallbladder epithelial cells from BK5.erbB2 mice to investigate the mechanism of carcinogenesis. Immunohistochemical analysis revealed that activated Akt was predominantly nuclear in gallbladder epithelial cells from the transgenic mice, but not in nontransgenic mice. Western blot analysis of proteins extracted from nuclear and cytosolic fractions of gallbladder epithelial cells also showed the nuclear localization of activated Akt. In addition, when the EGFR/erbB2 signaling was stimulated by EGF in primary gallbladder epithelial cell culture from BK5.erbB2 mice, a prolonged nuclear localization of activated Akt was observed compared to that of nontransgenic mice. Although activated Erk1/2 was mainly localized to the cytoplasm of gallbladder epithelial cells from transgenic mice, it was also detected in the nucleus. But in nontransgenic mice, no activated Erk1/2 could be detected in the nucleus of gallbladder epithelial cells. We speculate that nuclear localization of Akt and Erk1/2 mediated by constitutively activated erbB2 and EGFR signaling may play important roles during development of gallbladder carcinoma in BK5.erbB2 mice.
A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome
Authors: Zimu Deng, Zhenlu Chong, Christopher S. Law, Kojiro Mukai, Frances O. Ho, Tereza Martinu, Bradley J. Backes, Walter L. Eckalbar, Tomohiko Taguchi, Anthony K. Shum
Journal: The Journal of Experimental Medicine (2020)

Pathogenic COPA variants cause a Mendelian syndrome of immune dysregulation with elevated type I interferon signaling. COPA is a subunit of coat protein complex I (COPI) that mediates Golgi to ER transport. Missense mutations of the COPA WD40 domain impair binding and sorting of proteins targeted for ER retrieval, but how this causes disease remains unknown. Given the importance of COPA in Golgi–ER transport, we speculated that type I interferon signaling in COPA syndrome involves missorting of STING. We show that a defect in COPI transport causes ligand-independent activation of STING. Furthermore, SURF4 is an adapter molecule that facilitates COPA-mediated retrieval of STING at the Golgi. Activated STING stimulates type I interferon–driven inflammation in CopaE241K/+ mice that is rescued in STING-deficient animals. Our results demonstrate that COPA maintains immune homeostasis by regulating STING transport at the Golgi. In addition, activated STING contributes to immune dysregulation in COPA syndrome and may be a new molecular target in treating the disease.
Projected impact of a reduction in sugar-sweetened beverage consumption on diabetes and cardiovascular disease in Argentina: A modeling study
Authors: M. Victoria Salgado, Joanne Penko, Alicia Fernandez, Jonatan Konfino, Pamela G. Coxson, Kirsten Bibbins-Domingo, Raul Mejia
Journal: PLoS Medicine (2020)

Background Sugar-sweetened beverage (SSB) consumption is associated with obesity, diabetes, and hypertension. Argentina is one of the major consumers of SSBs per capita worldwide. Determining the impact of SSB reduction on health will inform policy debates. Methods and findings We used the Cardiovascular Disease Policy Model-Argentina (CVD Policy Model-Argentina), a local adaptation of a well-established computer simulation model that projects cardiovascular and mortality events for the population 35–94 years old, to estimate the impact of reducing SSB consumption on diabetes incidence, cardiovascular events, and mortality in Argentina during the period 2015–2024, using local demographic and consumption data. Given uncertainty regarding the exact amount of SSBs consumed by different age groups, we modeled 2 estimates of baseline consumption (low and high) under 2 different scenarios: a 10% and a 20% decrease in SSB consumption. We also included a range of caloric compensation in the model (0%, 39%, and 100%). We used Monte Carlo simulations to generate 95% uncertainty intervals (UIs) around our primary outcome measures for each intervention scenario. Over the 2015–2024 period, a 10% reduction in SSBs with a caloric compensation of 39% is projected to reduce incident diabetes cases by 13,300 (95% UI 10,800–15,600 [low SSB consumption estimate]) to 27,700 cases (95% UI 22,400–32,400 [high SSB consumption estimate]), i.e., 1.7% and 3.6% fewer cases, respectively, compared to a scenario of no change in SSB consumption. It would also reduce myocardial infarctions by 2,500 (95% UI 2,200–2,800) to 5,100 (95% UI 4,500–5,700) events and all-cause deaths by 2,700 (95% UI 2,200–3,200) to 5,600 (95% UI 4,600–6,600) for "low" and "high" estimates of SSB intake, respectively. A 20% reduction in SSB consumption with 39% caloric compensation is projected to result in 26,200 (95% UI 21,200–30,600) to 53,800 (95% UI 43,900–62,700) fewer cases of diabetes, 4,800 (95% UI 4,200–5,300) to 10,000 (95% UI 8,800–11,200) fewer myocardial infarctions, and 5,200 (95% UI 4,300–6,200) to 11,000 (95% UI 9,100–13,100) fewer deaths. The largest reductions in diabetes and cardiovascular events were observed in the youngest age group modeled (35–44 years) for both men and women; additionally, more events could be avoided in men compared to women in all age groups. The main limitations of our study are the limited availability of SSB consumption data in Argentina and the fact that we were only able to model the possible benefits of the interventions for the population older than 34 years. Conclusions Our study finds that, even under conservative assumptions, a relatively small reduction in SSB consumption could lead to a substantial decrease in diabetes incidence, cardiovascular events, and mortality in Argentina.
Drug Prices, Rebates, and Discounts—Reply
Authors: Inmaculada Hernandez, Walid F. Gellad
Journal: JAMA (2020)

In Reply In our study, we estimated changes in list prices, net prices, and discounts for branded drugs from 2007 to 2018.1 We found that discounts offset 62% of increases in list prices, and that after discounts, net prices still increased by 60% from 2007 to 2018, or 4.5% per year.
Mood Homeostasis Before and During the Coronavirus Disease 2019 (COVID-19) Lockdown Among Students in the Netherlands
Authors: Maxime Taquet, Jordi Quoidbach, Eiko I. Fried, Guy M. Goodwin
Journal: JAMA Psychiatry (2020)

Mood Homeostasis Before and During the Coronavirus Disease 2019 (COVID-19) Lockdown Among Students in the NetherlandsThe impact of lockdowns implemented in response to coronavirus disease 2019 (COVID-19) on mental health has raised concerns. 1,2Understanding the mechanisms underlying this impact to mitigate it is a research priority. 3We hypothesized that one mechanism involves impaired mood homeostasis (ie, failure to stabilize mood via mood-modifying activities).
AB1038 INFLAMMATORY ORBITAL DISEASES: THE EXPERIENCE OF A TERTIARY RHEUMATOLOGY CENTRE
Authors: M. S. Aksun, T. K. Sahin, E. C. Bolek, L. Kiliç, E. G. Bulut, K. K. Oğuz, U. Kalyoncu, O. Karadag
Journal: Annals of the Rheumatic Diseases (2020)

Background: Inflammatory lesions of orbital disease encompass a wide spectrum of clinical entities including rheumatic disorders. Objectives: To describe our experiences in adult patients who applied to a tertiary rheumatology center due to orbital disease. Methods: This is a retrospective descriptive study and data were extracted from patient’ charts. We described the clinical, laboratory, radiologic, histopathological presentations and final diagnoses of patients with inflammatory orbital disease who applied to our rheumatology clinic between January 2014 and December 2019. Results: Thirty-eight patients (Female: 63.2%) were identified; median age at onset of orbital symptoms was 44.5 (min.-max 5-72) years. Swelling (57.9%) and orbital pain (47.4%) were the most common symptoms, followed by erythema (13.2%), vision loss (13.2%), proptosis (7.9%) and diplopia (%7.9). Table summarizes the demographic and clinical characteristics of the patients. Imaging (MRG) was performed in all patients and 63.2% had an orbital biopsy. Orbital imaging revealed extraocular muscles (71.1%), lacrimal glands (50.0%) and optic nerve (42.1%) involvement. Of patients 34.2% had bilateral and 18.4% had retroorbital involvement. The final diagnoses of patients were: IgG4-related disease (34.2%, n =13), idiopathic orbital inflammatory pseudotumor (36.8%, n = 14), granulomatosis with polyangiitis (18.4%, n =7), Sjogren’s syndrome (n=1), relapsing polychondritis (n=1), thyroid-associated orbitopathy (n=1) and fungal granulomatous angiitis (n=1). Conclusion: Inflammatory lesions of the orbit are rare and the diagnosis may be challenging. Differential diagnosis is based on clinical, laboratory, radiologic and histopathologic findings. Although IgG4-related disease is a relatively new diagnostic cause for orbital inflammation, it should be considered more in differential diagnosis. Figure: Disclosure of Interests: Melek Seren Aksun: None declared, Taha Koray Sahin: None declared, Ertugrul Cagri Bolek: None declared, Levent Kiliç: None declared, Elif Günay Bulut: None declared, Kader Karli Oğuz: None declared, Umut Kalyoncu Consultant of: Abbvie, Amgen, Janssen, Lilly, Novartis, UCB, Omer Karadag: None declared
Three centuries since the discovery of Vater’s Papilla
Authors: Tilman Pickartz, Quang Trung Tran, Markus M. Lerch
Journal: Gut (2020)

In 1720 Abraham Vater (1684–1751) published the first description of the Papilla at the junction of the common bile duct and the pancreatic duct that today bares his name.1 It would remain his most clinically relevant discovery, particularly since the introduction of endoscopic papillotomy in the 1970s2 and the recognition of endoscopic retrograde cholangio-pancreatography (ERCP)-induced pancreatitis as a significant disease risk.3 The anatomy of the papilla is not uniform among mammals. The rabbit has completely separate junctions of both ducts with the intestine4 and the mouse carries no smooth muscle sphincter.5 Closest to the human anatomy is probably the American Opossum,6 which has therefore been used experimentally to study the mechanisms involved in gallstone-induced pancreatitis.7 The papilla of Vater has remained the subject of many investigations in humans,8 because its impairment …
Human CD16+ monocytes promote a pro-atherosclerotic endothelial cell phenotype via CX3CR1–CX3CL1 interaction
Authors: Eva Roy-Chowdhury, Nicolas Brauns, Alexandra Helmke, Johannes Nordlohne, Jan Hinrich Bräsen, Jessica Schmitz, Julia Volkmann, Susanne V Fleig, Kristina Kusche-Vihrog, Hermann Haller, Sibylle von Vietinghoff
Journal: Cardiovascular Research (2020)

Monocytes are central for atherosclerotic vascular inflammation. The human non-classical, patrolling subtype, which expresses high levels of CD16 and fractalkine receptor CX3CR1, strongly associates with cardiovascular events. This is most marked in renal failure, a condition with excess atherosclerosis morbidity. The underlying mechanism is not understood. This study investigated how human CD16+ monocytes modulate endothelial cell function.
Incidental Detection of Elastofibroma Dorsi With 68Ga-FAPI-46 and 18F-FDG PET/CT in a Patient With Esophageal Cancer
Authors: Artineh Hayrapetian, Mark D. Girgis, Jane Yanagawa, Samuel W. French, Heinrich R. Schelbert, Martin S. Auerbach, Johannes Czernin, Jeremie Calais
Journal: Clinical Nuclear Medicine (2020)

A 71-year-old man underwent 18F-FDG and 68Ga-FAPI-46 PET/CT for initial staging prior to surgery of a squamous cell carcinoma of the lower esophagus under the prospective study NCT04147494. Both scans showed increased uptake in the mid and distal esophagus without evidence of metastatic disease. A soft tissue right infrascapular mass with mild 18F-FDG and moderate 68Ga-FAPI-46 uptake was incidentally found. The patient underwent robotic-assisted Ivor-Lewis esophagectomy and excision of the right infrascapular mass. Histopathology of the right chest wall mass confirmed the diagnosis of elastofibroma.
Parallel Murine and Human Plaque Proteomics Reveals Pathways of Plaque Rupture
Authors: Tomáš Vaisar, Jie H. Hu, Nathan Airhart, Kate Fox, Jay Heinecke, Roberto F. Nicosia, Ted Kohler, Zachary E. Potter, Gabriel M. Simon, Melissa M. Dix, Benjamin F. Cravatt, Sina A. Gharib, David A. Dichek
Journal: Circulation Research (2020)

Plaque rupture is the proximate cause of most myocardial infarctions and many strokes. However, the molecular mechanisms that precipitate plaque rupture are unknown.By applying proteomic and bioinformatic approaches in mouse models of protease-induced plaque rupture and in ruptured human plaques, we aimed to illuminate biochemical pathways through which proteolysis causes plaque rupture and identify substrates that are cleaved in ruptured plaques.We performed shotgun proteomics analyses of aortas of transgenic mice with macrophage-specific overexpression of urokinase (SR-uPA+/0 mice) and of SR-uPA+/0 bone marrow transplant recipients, and we used bioinformatic tools to evaluate protein abundance and functional category enrichment in these aortas. In parallel, we performed shotgun proteomics and bioinformatics studies on extracts of ruptured and stable areas of freshly harvested human carotid plaques. We also applied a separate protein-analysis method (protein topography and migration analysis platform) to attempt to identify substrates and proteolytic fragments in mouse and human plaque extracts. Approximately 10% of extracted aortic proteins were reproducibly altered in SR-uPA+/0 aortas. Proteases, inflammatory signaling molecules, as well as proteins involved with cell adhesion, the cytoskeleton, and apoptosis, were increased. ECM (Extracellular matrix) proteins, including basement-membrane proteins, were decreased. Approximately 40% of proteins were altered in ruptured versus stable areas of human carotid plaques, including many of the same functional categories that were altered in SR-uPA+/0 aortas. Collagens were minimally altered in SR-uPA+/0 aortas and ruptured human plaques; however, several basement-membrane proteins were reduced in both SR-uPA+/0 aortas and ruptured human plaques. Protein topography and migration analysis platform did not detect robust increases in proteolytic fragments of ECM proteins in either setting.Parallel studies of SR-uPA+/0 mouse aortas and human plaques identify mechanisms that connect proteolysis with plaque rupture, including inflammation, basement-membrane protein loss, and apoptosis. Basement-membrane protein loss is a prominent feature of ruptured human plaques, suggesting a major role for basement-membrane proteins in maintaining plaque stability.
Targeting EGFR activity in tumor-derived endothelial cells.
Authors: Dhara N. Amin, Kyoko Hida, Diane R. Bielenberg, Michael Klagsbrun
Journal: Cancer Research (2006)

5704  The target cells for anti-cancer Epidermal Growth Factor Receptor (EGFR) inhibitors, Iressa, Tarceva, and Erbitux are typically thought to be tumor cells. We provide evidence that tumor-derived endothelial cells (TECs) can also be direct-targets of anti-EGFR therapeutics. TECs isolated from xenografts of melanoma, liposarcoma, and breast carcinoma express EGFR at higher levels than normal endothelial cells (NECs). EGFR expressed on the TECs is activated by members of the EGF family of ligands (EGF, HB-EGF, TGFΑ). EGFR on the TECs acts in a heterodimer with the oncogene ErbB2 and activation of these receptors is coupled to MAPK activation. TECs display increased proliferation in a dose dependent manner to EGF, whereas the NECs are non-responsive to EGF. EGFR kinase inhibitor, AG1478, inhibits both EGF induced cell proliferation as well as exponential growth of TECs in complete media. Melanoma cells themselves were negative for EGFR expression and non-responsive to EGF. Melanoma derived ECs (Mel-ECs) are selective targets of anti-EGFR drugs since their normal counterparts the Skin-ECs are not as sensitive to the EGFR kinase inhibitor. In vivo expression of EGFR and activated-EGFR in ECs of EGFR negative melanoma xenografts was observed by immunohistochemical analyses. Our data suggests that anti-EGFR therapeutics may be effective in patients tested negative for EGFR immunoreactivity on their tumor cells, through the targeting of these drugs to the tumor vasculature.
FRI0445 HLA-B27 IN POSTSTREPTOCOCCAL REACTIVE ARTHRITIS WITH ENTHESITIS
Authors: I. Naishtetik, L. Khimion, O. Yashchenko, P. Dolinskiy
Journal: Annals of the Rheumatic Diseases (2020)

Background: Poststreptococcal reactive arthritis (PSRA) is a very common diagnosis in rheumatology practice, which develops after recent pharyngeal streptococcal infection and characterized by aseptic inflammation in one or more joints and periarticular involvement. Now no diagnostic criteria have been agreed [2,4]; association of the expression of HLA-B27 and PSRA is not clear [1,3]. Objectives: In our study we analyzed the features of PSRA in presence of HLA-B27. Methods: 88 patients (48 female and 40 male) aged between 18-55 years with complains of pain, tender and swollen joints developed after recent pharyngeal streptococcal infection underwent standard physical and laboratory rheumatological examinations. Acute rheumatic fever and other inflammatory arthritis were excluded. Results: 60 patients (68,2%) had oligo-polyarthralgia, 10 patients (11,4%) - monoarthritis, 24 patients (27,3%) had asymmetrical olygoarthritis, 4 patients (4,5%) had polyarthritis, enthesitis was found in 4 (4,5%) patients, tenosynovitis of the palmar flexor tendons in 10 cases (11,4%) and the peroneal tendons of the ankles in 5 patients (5,7%), one-sided sacroiliitis (confirmed by MRI) in 5 patients (5,7%).The mean level of ASL-O was 542 U/ml, CRP -15 mg/L, ESR - 34 mm/H; HLA-B27 was present in 24 (30,7%) patients. HLA-B27 positivity was connected to enthesitis, sacroiliitis, more joint involvement with higher levels of ESR and CRP. Conclusion: 30% of patients with poststreptococcal reactive arthritis are HLA-B27 positive, the presence of HLA-B27 leads to more frequent development of enthesitis, polyarthritis and sacroiliitis with higher level of inflammatory activity which dictate the need for longer supervision of such patients for possible triggering of ankylosing spondylitis development. References: [1]Ahmed S, Ayoub EM, ScorniK JC, Wang C-Y, She J-X. Poststreptococcal reactive arthritis. Clinical characteristics and association with YLA-DR alleles. Arthritis Rheum 1998; 41:1096-102.9[ [2]Gibofsky A, Khanna A, Suh E, et al. The genetics of rheumatic fever: Relationship to streptococcal infection and autoimmune disease. J Rheumatol Suppl. 1991;30:1–5. [PubMed] [Google Scholar] [3]Leitch DN, Holland CD/ Reactive arthritis, beta-hemolytic Streptococcus and Staphylococcus aureus. Br J Rheumatol 1996;35:912. [4]Mackie SL, Keat A. Poststreptococcal reactive arthritis: what is it and how do we know? Rheumatology (Oxford) 2004;43:949–54. 10.1093/rheumatology/keh225 [PubMed]. Disclosure of Interests: None declared
Media Coverage and Care-Seeking for Transgender and Gender-Diverse Youth
Authors: Stephen T. Russell
Journal: JAMA Network Open (2020)

Ken C. Pang, PhD; Nastasja M. de Graaf, MSc; Denise Chew, MD; Monsurul Hoq, MSc, MPH; David R. Keith, PhD; Polly Carmichael, PhD; Thomas D. Steensma, PhD