tbuckley/cabot-search huggingface dataset:
Abstract 15233: Exercise Reverses Endoplasmic Reticulum Stress-Associated Vascular Dysfunction in Mesentery Arteries in Atherosclerosis
Authors: Kwangchan Kim, Eunkyung Park, Jonghae Lee, Junyoung Hong, Yoonjung Park
Journal: Circulation (2016)

Introduction:  Endoplasmic reticulum (ER) stress, known as a disruption of ER homeostasis resulting in an accumulation of misfolded and unfolded protein response (UPR) is linked to cardiovascular diseases including atherosclerosis. Underlying mechanisms for mesenteric arterial dysfunction in atherosclerosis, major cause of chronic mesenteric ischemia, is unclear and no study has been done to investigate the effect of exercise on mesenteric arterial dysfunction in atherosclerosis.   Hypothesis:  We hypothesized that ER stress aggravates endothelial dysfunction in mesenteric arteries in atherosclerosis and exercise ameliorate those endothelial dysfunction.   Methods:  We used wild type (WT), wild type with exercise training, running on the treadmill for 12 weeks (WT-EX), apolipoprotein E knockout (ApoE KO) and ApoE KO with exercise training (ApoE KO-EX) mice. To test mesenteric artery function, endothelium-dependent (acetylcholine, ACh) vasodilation and endothelium-independent nitroprusside (SNP) vasodilation of isolated and pressurized mesenteric arteries were measured by a concentration-dependent manner. The vessels were incubated with endothelial nitric oxide synthase (eNOS) inhibitor,  N G-nitro-L-arginine methyl ester (L-NAME), ER stress inducer tunicamycin, ER stress inhibitor, Tudca, caspase-1 inhibitor (AC-YVARD-cmk) and uncoupling protein-2 (UCP-2) inhibitor, Genepin were incubated and ACh-induced dilation was measured to investigate the underlying mechanisms.   Results:  ACh-induced vasodilation was attenuated in ApoE KO compared to WT but exercise training improved the ACh-induced vasodilatation in ApoE KO-EX while endothelium-independent SNP-induced vasodilation was not different among the groups. Incubation of Tudca and AC-YVARD-cmk improved ACh-induced vasodilation in ApoE KO. ACh-induced vasodilation in the presence of L-NAME, tunicamycin and Genepin were reduced in WT, WT-EX and ApoE KO-EX, but not in ApoE KO.   Conclusions:  Our findings suggest that ER stress plays a significant role in vascular endothelial dysfunction in atherosclerotic mesenteric arteries and exercise restores it through ER stress and its downstream signaling pathways including NOS, UCP-2 and caspase-1.
Abstract 16578: Evaluation of Periprocedural Safety and Efficacy of Dabigatran, Rivaroxaban, Apixaban and Edoxaban During Catheter Ablation for Atrial Fibrillation
Authors: Shota Tohoku, Kenichi Hiroshima, Michio Nagashima, Junji Morita, Takahiro Iseda, Kengo Ando, Kenji Ando
Journal: Circulation (2016)

Backgrounds:  The data on direct comparison of the novel oral anticoagulants (NOACs); dabigatran, rivaroxaban apixaban and edoxaban with each other about periprocedural complications during catheter ablation (CA) for atrial fibrillation (Af) is still unclear. The aim of this study was to evaluate the periprocedural major complications in CA for Af between four different NOACs in the real world.   Methods:  A total of 1152 consecutive Af patiens (68% male; age 62.2 ± 10.7 years, paroxysmal Af 70.1%, persistent or chronic Af 29.9%) who underwent catheter ablation with NOACs at our institution were enrolled retrospectively. We divided them into four groups; dabigatran (D) group (n=516 [44.7%]), rivaroxaban (R) group (n=399 [34.6%]), apixaban (A) group (n=201 [17.4%]) and edoxaban (E) group (n= 36 [3.1%]). Outcome measures were thromboembolic events, gastric motility disorder or atrial-esophageal fistula and major bleeding complications defined as recommended by the current AHA/ACC/HRS guideline.   Results:  In A group, mean CHA 2 DS 2 -Vasc score was significantly higher than both in D group (2.13 ± 1.30 vs 1.59 ± 1.27, respectively; p   Conclusions:  Apixaban was used in patients with higher risk of thromboembolic and bleeding complications compared to dabigatran and rivaroxaban. The periprocedural major complication rates were similar between all four NOACs during Af ablation.
Abstract 17811: A Metabolomics Platform Optimized for Human Plasma Identifies Anandamide as a Biomarker of Nonalcoholic Steatohepatitis
Authors: W. Taylor Kimberly, John O’Sullivan, Anjali Nath, Michelle Keyes, Qiong Yang, Ramachandran Vasan, Randall Peterson, Thomas Wang, Kathleen Corey, Robert Gerszten
Journal: Circulation (2016)

Introduction:  Quantification of metabolites in plasma samples can highlight important metabolic pathways that are altered in disease states.   Hypothesis:  We developed a metabolomics approach to identify novel biomarkers of cardiometabolic traits in a large community-based cohort.   Methods:  Using liquid chromatography-tandem mass spectrometry, we developed a metabolite profiling method that minimizes pre-analytical sample processing and uses Amide Xbridge chromatography to separate and detect positively and negatively charged metabolites across a broad spectrum of chemical classes. We applied this method to 1,000 participants in the Framingham Heart Study Generation 3 cohort (mean age 40 years, 53% women) to identify novel metabolic alterations present in obesity and its complications. Regression analyses were performed with adjustment for age and sex.   Results:  We identified multiple novel associations of metabolites with cardiometabolic traits, including the endogenous cannabinoid, anandamide, which was associated with body mass index (p=3.64x10 -13 ), glucose (p=1.08x10 -6 ), homeostatic model assessment of insulin resistance (p=2.10x10 -7 ) and systolic blood pressure (p=1.95x10 -9 ). In follow-up studies in a hospital-based sample (N=72) of patients with obesity, higher plasma anandamide levels were independently associated with histologically-defined nonalcoholic steatohepatitis (OR 5.45, 95% CI 1.48-20.1, p=0.01), an obesity complication that must otherwise be diagnosed by liver biopsy.   Conclusion:  Our observations highlight both the role of anandamide in obesity and nonalcoholic steatohepatitis, and the utility of metabolomics-based approaches for illuminating novel markers of disease and metabolic dysregulation.
Paclitaxel and Pazopanib in Ovarian Cancer
Authors: Federica Tomao, Pierluigi Benedetti Panici, Silverio Tomao
Journal: JAMA Oncology (2018)

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 Oncology 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 Oncology journal
TRANSTRACHEAL CYANOACRYLATE GLUE INJECTION FOR THE MANAGEMENT OF MALIGNANT TRACHEOESOPHAGEAL FISTULA
Authors: P Somani, M Sharma
Journal: Endoscopy (2018)

A 56-year-old man presented with complain of intractable cough on swallowing for last 3 months. He had completed a course of chemoradiotherapy for carcinoma of middle one third of oesophagus four months back. The upper gastrointestinal endoscopy showed stricture at 23 cm in oesophagus. A small (˜ 4 mm diameter) fistula was noted just above stricture. Application of over-the-scope clip failed. A hydrophilic guide wire (0.032” inches diameter) was placed through the ERCP cannula into the fistula. Bronchoscopy revealed the presence of guidewire coming out from a fistulous tract in the posterior wall of the trachea above the tracheal bifurcation. The guide wire was grasped with a biopsy forceps. The guide wire was removed along with the scope from the mouth. The fluoroscopic image showed a curved course (length of the fistula was about 2.5 cm) of the guide wire. After assessment of the fistula by the track of the guidewire, two routes of glue injection were considered, Trans-tracheal and Trans-esophageal. Transesophageal route was considered risky due to an expected spillage of the glue within the trachea. Hence, the option of transtracheal glue injection was selected. The cannula and the scope were reintroduced through the trachea. The presence of the markers on the cannula were used to assess the depth of insertion of cannula within the fistula and to plan the site of injection of the glue. 1 ml of cyanoacrylate glue was injected while pulling the cannula out. 1 ml of distilled water was injected while pulling out the rest of the cannula to the tip of the fistula. After one hour, the patient started swallowing liquids without any cough. Patient has remained asymptomatic till now.
EBV‐positive diffuse large B‐cell lymphoma, not otherwise specified: 2018 update on diagnosis, risk‐stratification and management
Authors: Jorge J. Castillo, Brady E. Beltran, Roberto N. Miranda, Ken H. Young, Julio C. Chavez, Eduardo M. Sotomayor
Journal: American Journal of Hematology (2018)

Disease overview Epstein Barr virus‐positive (EBV+) diffuse large B‐cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 WHO classification of lymphoid neoplasms. EBV+ DLBCL, NOS, is an aggressive B‐cell lymphoma associated with chronic EBV infection, and a poor prognosis with standard chemotherapeutic approaches. Diagnosis The diagnosis is made through a careful pathological evaluation. Detection of EBV‐encoded RNA is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The differential diagnosis includes plasmablastic lymphoma, DLBCL associated with chronic inflammation, primary effusion lymphoma, HHV8+ DLBCL, NOS, and EBV+ mucocutaneuos ulcer. Risk‐stratification The International prognostic index (IPI) and the Oyama score can be used for risk‐stratification. The Oyama score includes age &gt;70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Management Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV‐negative DLBCL. EBV+ DLBCL, NOS, however, has a worse prognosis than EBV‐negative DLBCL in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.
Extracellular Vesicles Containing IL-4 Modulate Neuroinflammation in a Mouse Model of Multiple Sclerosis
Authors: Giacomo Casella, Federico Colombo, Annamaria Finardi, Hélène Descamps, Gerard Ill-Raga, Antonello Spinelli, Paola Podini, Mattia Bastoni, Gianvito Martino, Luca Muzio, Roberto Furlan
Journal: Molecular Therapy (2018)

Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery. We engineered a murine microglia cell line, BV-2, to release EVs overexpressing the endogenous "eat me" signal Lactadherin (Mfg-e8) on the surface to target phagocytes and containing the anti-inflammatory cytokine IL-4. A single injection of 107 IL-4+Mfg-e8+ EVs into the cisterna magna modulated established neuroinflammation and significantly reduced clinical signs in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Injected IL-4+Mfg-e8+ EVs target mainly phagocytes (i.e., macrophages and microglia) surrounding liquoral spaces, and their cargo promote the upregulation of anti-inflammatory markers chitinase 3-like 3 (ym1) and arginase-1 (arg1), significantly reducing tissue damage. Engineered EVs may represent a biological drug delivery tool able to deliver multiple functional molecules simultaneously to treat neuroinflammatory diseases. Extracellular vesicles (EVs) play a major role in cell-to-cell communication in physiological and pathological conditions, and their manipulation may represent a promising therapeutic strategy. Microglia, the parenchymal mononuclear phagocytes of the brain, modulate neighboring cells also through the release of EVs. The production of custom EVs filled with desired molecules, possibly targeted to make their uptake cell specific, and their administration in biological fluids may represent a valid approach for drug delivery. We engineered a murine microglia cell line, BV-2, to release EVs overexpressing the endogenous "eat me" signal Lactadherin (Mfg-e8) on the surface to target phagocytes and containing the anti-inflammatory cytokine IL-4. A single injection of 107 IL-4+Mfg-e8+ EVs into the cisterna magna modulated established neuroinflammation and significantly reduced clinical signs in the mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Injected IL-4+Mfg-e8+ EVs target mainly phagocytes (i.e., macrophages and microglia) surrounding liquoral spaces, and their cargo promote the upregulation of anti-inflammatory markers chitinase 3-like 3 (ym1) and arginase-1 (arg1), significantly reducing tissue damage. Engineered EVs may represent a biological drug delivery tool able to deliver multiple functional molecules simultaneously to treat neuroinflammatory diseases.
Dozens of US doctors charged in “historic” fraud crackdown
Authors: Owen Dyer
Journal: BMJ (2018)

Seventy six doctors—along with 89 other licensed healthcare professionals, including pharmacists and nurses—were among 601 people charged with healthcare fraud in a coordinated operation across the United States, the justice department has announced.

Attorney general Jeff Sessions, pointing to his announcement last July of over 400 arrests, including 56 doctors, said, “We are breaking records again by announcing the largest healthcare fraud takedown operation in American history.”

The various fraudulent schemes raked in over $2bn (£1.5bn, €1.7bn), the government alleges, much of it at taxpayer expense.

Of those arrested, 162 are charged with fraud that involved the prescription of opioids. Many …
Screening for Skin Cancer
Authors: Kirsten Bibbins-Domingo, David C. Grossman, Susan J. Curry, Karina W. Davidson, Mark Ebell, John W. Epling, Francisco A. R. García, Matthew W. Gillman, Alex R. Kemper, Alex H. Krist, Ann E. Kurth, C. Seth Landefeld, Carol M. Mangione, William R. Phillips, Maureen G. Phipps, Michael P. Pignone, Albert L. Siu
Journal: JAMA (2016)

<h3>Importance</h3> Basal and squamous cell carcinoma are the most common types of cancer in the United States and represent the vast majority of all cases of skin cancer; however, they rarely result in death or substantial morbidity, whereas melanoma skin cancer has notably higher mortality rates. In 2016, an estimated 76 400 US men and women will develop melanoma and 10 100 will die from the disease. <h3>Objective</h3> To update the 2009 US Preventive Services Task Force (USPSTF) recommendation on screening for skin cancer. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on the effectiveness of screening for skin cancer with a clinical visual skin examination in reducing skin cancer morbidity and mortality and death from any cause; its potential harms, including any harms resulting from associated diagnostic follow-up; its test characteristics when performed by a primary care clinician vs a dermatologist; and whether its use leads to earlier detection of skin cancer compared with usual care. <h3>Findings</h3> Evidence to assess the net benefit of screening for skin cancer with a clinical visual skin examination is limited. Direct evidence on the effectiveness of screening in reducing melanoma morbidity and mortality is limited to a single fair-quality ecologic study with important methodological limitations. Information on harms is similarly sparse. The potential for harm clearly exists, including a high rate of unnecessary biopsies, possibly resulting in cosmetic or, more rarely, functional adverse effects, and the risk of overdiagnosis and overtreatment. <h3>Conclusions and Recommendation</h3> The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for skin cancer in adults (I statement).
Type 2/Th2‐driven inflammation impairs olfactory sensory neurogenesis in mouse chronic rhinosinusitis model
Authors: Angela Rouyar, Marion Classe, Raphael Gorski, Marie‐Dominique Bock, Joelle Le‐Guern, Sandrine Roche, Valerie Fourgous, Anne Remaury, Pascal Paul, Clara Ponsolles, Dominique Françon, Laurence Rocheteau‐Beaujouan, Margerie Clément, El‐Bdaoui Haddad, Jean‐Claude Guillemot, Michel Didier, Bruno Biton, Cecile Orsini, Vincent Mikol, Maud Leonetti
Journal: Allergy (2018)

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is a chronic inflammatory disease often accompanied by impairment of sense of smell. This symptom has been somewhat overlooked, and its relationship to inflammatory cytokines, tissue compression, neuronal loss, and neurogenesis is still unclear.In order to elucidate potential mechanisms leading to CRS in humans, we have established a type 2/T helper type 2 cell (Th2)-mediated allergic CRS mouse model, based on house dust mite (HDM) and Staphylococcus aureus enterotoxin B (SEB) sensitization. The inflammatory status of the olfactory epithelium (OE) was assessed using histology, biochemistry, and transcriptomics. The sense of smell was evaluated by studying olfactory behavior and recording electro-olfactograms (EOGs).After 22 weeks, a typical type 2/Th2-mediated inflammatory profile was obtained, as demonstrated by increased interleukin (IL)-4, IL-5, and IL-13 in the OE. The number of mast cells and eosinophils was increased, and infiltration of these cells into the olfactory mucosa was also observed. In parallel, transcriptomic and histology analyses indicated a decreased number of immature olfactory neurons, possibly due to decreased renewal. However, the number of mature sensory neurons was not affected and neither the EOG nor olfactory behavior was impaired.Our mouse model of CRS displayed an allergic response to HDM + SEB administration, including the type 2/Th2 inflammatory profile characteristic of human eosinophilic CRSwNP. Although the sense of smell did not appear to be altered in these conditions, the data reveal the influence of chronic inflammation on olfactory neurogenesis, suggesting that factors unique to humans may be involved in CRSwNP-associated anosmia.
Metronomic ABI-007 therapy: antiangiogenic and antitumor activity of a nanoparticle albumin-bound paclitaxel
Authors: Sylvia S. Ng, Alex Sparreboom, Yuval Shaked, Christina Lee, Shan Man, Neil Desai, Patrick Soon-Shiong, William D. Figg, Robert S. Kerbel
Journal: Cancer Research (2005)

2988  Background: Metronomic chemotherapy, the low-dose and frequent administration of cytotoxic agents without prolonged drug-free breaks, is believed to target activated endothelial cells in the tumor vasculature. A number of preclinical studies have demonstrated the superior antitumor efficacy and the reduced toxicity of some metronomic regimens compared to their maximum tolerated dose (MTD) counterparts. It remains unclear whether all chemotherapeutic drugs exert similar effects or whether some are better suited for such regimens than others. Paclitaxel has been shown to inhibit angiogenesis when used at very low doses (Grant et al., Int. J. Cancer, 2003). However, it was also reported that clinically relevant concentrations of the formulation vehicle cremophor EL in Taxol nullify the antiangiogenic activity of paclitaxel, suggesting that this agent or other anticancer drugs formulated in cremophor EL may need to be used at much higher doses than anticipated to achieve effective metronomic chemotherapy (Ng et al., Cancer Res., 2004). As such, the advantage of the lack of undesirable side effects associated with low-dose paclitaxel regimens vs. conventional MTD chemotherapy may be compromised. ABI-007, a cremophor EL-free nanoparticle paclitaxel, could potentially alleviate the problem. Methods: The antiangiogenic activity of ABI-007 was assessed by the rat aortic ring, human umbilical vein endothelial cell (HUVEC) proliferation and tube formation assays. Optimal dose of ABI-007 for metronomic therapy was determined by measuring the levels of circulating endothelial progenitors (CEPs) in peripheral blood of Bal/c non-tumor bearing mice (n=5/ group; dosing: 1-30 mg/kg, i.p, qdx7) with flow cytometry (Shaked et al., Cancer Cell, in press). Subsequently, the antitumor effects of metronomic (qd; i.p.) and MTD (qdx5, 1 cycle; i.v.) ABI-007 and Taxol were evaluated and compared in SCID mice bearing human MDA-MD-231 breast and PC3 prostate cancer xenografts. Results: ABI-007 at 5 nM significantly (P
Single-Cell Transcriptomics of a Human Kidney Allograft Biopsy Specimen Defines a Diverse Inflammatory Response
Authors: Haojia Wu, Andrew F. Malone, Erinn L. Donnelly, Yuhei Kirita, Kohei Uchimura, Sai M. Ramakrishnan, Joseph P. Gaut, Benjamin D. Humphreys
Journal: Journal of the American Society of Nephrology (2018)

Background Single-cell genomics techniques are revolutionizing our ability to characterize complex tissues. By contrast, the techniques used to analyze renal biopsy specimens have changed little over several decades. We tested the hypothesis that single-cell RNA-sequencing can comprehensively describe cell types and states in a human kidney biopsy specimen. Methods We generated 8746 single-cell transcriptomes from a healthy adult kidney and a single kidney transplant biopsy core by single-cell RNA-sequencing. Unsupervised clustering analysis of the biopsy specimen was performed to identify 16 distinct cell types, including all of the major immune cell types and most native kidney cell types, in this biopsy specimen, for which the histologic read was mixed rejection. Results Monocytes formed two subclusters representing a nonclassical CD16+ group and a classic CD16− group expressing dendritic cell maturation markers. The presence of both monocyte cell subtypes was validated by staining of independent transplant biopsy specimens. Comparison of healthy kidney epithelial transcriptomes with biopsy specimen counterparts identified novel segment-specific proinflammatory responses in rejection. Endothelial cells formed three distinct subclusters: resting cells and two activated endothelial cell groups. One activated endothelial cell group expressed Fc receptor pathway activation and Ig internalization genes, consistent with the pathologic diagnosis of antibody-mediated rejection. We mapped previously defined genes that associate with rejection outcomes to single cell types and generated a searchable online gene expression database. Conclusions We present the first step toward incorporation of single-cell transcriptomics into kidney biopsy specimen interpretation, describe a heterogeneous immune response in mixed rejection, and provide a searchable resource for the scientific community.