tbuckley/cabot-search huggingface dataset:
Quantitative Proteomics and Metabolomics Reveal Biomarkers of Disease as Potential Immunotherapy Targets and Indicators of Therapeutic Efficacy
Authors: Melanie A. MacMullan, Zachary S. Dunn, Nicolas Graham, Lili Yang, Pin Wang
Journal: Theranostics (2019)

Quantitative mass spectrometry (MS) continues to deepen our understanding of the immune system, quickly becoming the gold standard for obtaining high-throughput, quantitative data on biomolecules.The development of targeted and multiplexed assays for biomarker quantification makes MS an attractive tool both for diagnosing diseases and for quantifying the effects of immunotherapeutics.Because of its accuracy, the use of MS for identifying biomarkers of disease reduces the potential for misdiagnosis and overtreatment.Advances in workflows for sample processing have drastically reduced processing time and complexities due to sample preparation, making MS a more accessible technology.In this review, we present how recent developments in proteomics and metabolomics make MS an essential component of enhancing and monitoring the efficacy of immunotherapeutic treatments.
How I remove polyps larger than 20 mm
Authors: Michael J. Bourke, Pradeep Bhandari
Journal: Endoscopy (2019)

PUBLICATION INFORMATIONThis article is being published jointly in Gastrointestinal Endoscopy and Endoscopy.Copyright © 2019 by the American Society for Gastrointestinal Endoscopy and Georg Thieme Verlag KG
Nanoparticle Delivery of Immunostimulatory Agents for Cancer Immunotherapy
Authors: Jia Zhuang, Maya Holay, Joon Ho Park, Ronnie H. Fang, Jie Zhang, Liangfang Zhang
Journal: Theranostics (2019)

Immunostimulatory agents, including adjuvants, cytokines, and monoclonal antibodies, hold great potential for the treatment of cancer. However, their direct administration often results in suboptimal pharmacokinetics, vulnerability to biodegradation, and compromised targeting. More recently, encapsulation into biocompatible nanoparticulate carriers has become an emerging strategy for improving the delivery of these immunotherapeutic agents. Such approaches can address many of the challenges facing current treatment modalities by endowing additional protection and significantly elevating the bioavailability of the encapsulated payloads. To further improve the delivery efficiency and subsequent immune responses associated with current nanoscale approaches, biomimetic modifications and materials have been employed to create delivery platforms with enhanced functionalities. By leveraging nature-inspired design principles, these biomimetic nanodelivery vehicles have the potential to alter the current clinical landscape of cancer immunotherapy.
Lung function and asthma control in school-age children managed in UK primary care: a cohort study
Authors: David KH Lo, Caroline S Beardsmore, Damian Roland, Mathew Richardson, Yaling Yang, Lesley Danvers, Andrew Wilson, Erol A Gaillard
Journal: Thorax (2019)

Background Spirometry and fraction of exhaled nitric oxide (FeNO) are commonly used in specialist centres to monitor children with asthma. The National Institute for Health and Care Excellence recommends spirometry for asthma monitoring from 5 years in all healthcare settings. There is little spirometry and FeNO data in children managed for asthma in UK primary care to support their use. Objectives To study the prevalence of abnormal spirometry and FeNO in children with asthma managed in primary care and to explore their relationship with asthma control and unplanned healthcare attendances (UHA). Methods Prospective observational cohort study in children aged 5–16 years with suspected or doctor-diagnosed asthma attending an asthma review in UK general practice. Spirometry, FeNO, asthma control test (ACT) scores and number of UHAs were studied. Results Of 612 children from 10 general practices, 23.5% had abnormal spirometry, 36.0% had raised FeNO ≥35 parts per billion and 41.8% reported poor control. Fifty-four per cent of children reporting good asthma control had abnormal spirometry and/or raised FeNO. At follow-up, the mean number of UHAs fell from 0.31/child in the 6 months preceding review to 0.20/child over the 6 months following review (p=0.0004). Median ACT scores improved from 20 to 22 (p=0.032), and children’s ACT from 21 to 23 (p&lt;0.0001). Conclusions Abnormal lung function and FeNO are common in children attending for asthma review in primary care and relate poorly to symptom scores. A symptoms-based approach to asthma monitoring without objective testing is likely to miss children at high risk of future severe asthma attacks.
Thymopentin ameliorates dextran sulfate sodium-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes
Authors: Qiuhua Cao, Xinghua Gao, Yanting Lin, Chongxiu Yue, Yue Wang, Fei Quan, Zixuan Zhang, Xiaoxuan Liu, Yuan Lu, Yanling Zhan, Hongbao Yang, Xianjing Li, Di Qin, Lutz Birnbaumer, Kun Hao, Yong Yang
Journal: Theranostics (2019)

Background: Ulcerative colitis (UC) is a chronic inflammatory gastrointestinal disease, notoriously challenging to treat.Previous studies have found a positive correlation between thymic atrophy and colitis severity.It was, therefore, worthwhile to investigate the effect of thymopentin (TP5), a synthetic pentapeptide corresponding to the active domain of the thymopoietin, on colitis.Methods: Dextran sulfate sodium (DSS)-induced colitis mice were treated with TP5 by subcutaneous injection.Body weight, colon length, colon weight, immune organ index, disease activity index (DAI) score, and the peripheral blood profile were examined.The immune cells of the spleen and colon were analyzed by flow cytometry.Histology was performed on isolated colon tissues for cytokine analysis.Bacterial DNA was extracted from mouse colonic feces to assess the intestinal microbiota.Intestinal lamina propria mononuclear cells (LPMCs), HCT116, CT26, and splenocytes were cultured and treated with TP5.Results: TP5 treatment increased the body weight and colon length, decreased the DAI score, and restored colon architecture of colitic mice.TP5 also decreased the infiltration of immune cells and expression levels of pro-inflammatory cytokines such as IL-6.Importantly, the damaged thymus and compromised lymphocytes in peripheral blood were significantly restored by TP5.Also, the production of IL-22, both in innate and adaptive lymphoid cells, was triggered by TP5.Given the critical role of IL-22 in mucosal host defense, we tested the effect of TP5 on mucus barrier and gut microbiota and found that the number of goblet cells and the level of Mucin-2 expression were restored, and the composition of the gut microbiome was normalized after TP5 treatment.The critical role of IL-22 in the protective effect of TP5 on colitis was further confirmed by administering the anti-IL-22 antibody (αIL-22), which completely abolished the effect of TP5.Furthermore, TP5 significantly increased the expression level of retinoic acid receptor-related orphan receptor γ (RORγt), a transcription factor for IL-22.Consistent with this, RORγt inhibitor abrogated the upregulation of IL-22 induced by TP5. Conclusion:TP5 exerts a protective effect on DSS-induced colitis by triggering the production of IL-22 in both innate and adaptive lymphocytes.This study delineates TP5 as an immunomodulator that may be a potential drug for the treatment of UC.
Prognostic value of FLT3 mutations among different cytogenetic subgroups in acute myeloid leukemia (AML)
Authors: F. P. Santos, W. Qiao, J. E. Cortes, D. Jones, F. Ravandi, D. Verma, H. Kantarjian, G. Borthakur
Journal: Journal of Clinical Oncology (2009)

7015 Background: Mutations of the FLT3 gene (in special internal tandem duplication -ITD) are common in normal karyotype AML (NK-AML) and are associated with shorter relapse free and overall survival (OS). The frequency of FLT3 mutations is lower in other cytogenetic subgroups and the impact on outcome is unclear. Methods: The records of patients (pts) with newly diagnosed AML (from 2003 to 2007) were reviewed. Pts were divided among three cytogenetic subgroups: Good-risk (t(8;21), Inv(16)/t(16;16)) Intermediate-Risk (Diploid,-Y) and Poor Risk (-5,-7, 11q abnormalities). FLT3 ITD and tyrosine kinase domain (TKD) mutations were determined on baseline DNA samples by a PCR based method with 1% sensitivity. Since the frequencies of FLT3 mutations were lower in good- and poor-risk subgroups, ITD/TKD mutations were considered together in the analysis, while in the intermediate risk group they were analyzed separately. Survival curves stratified by FLT3 mutation were estimated by Kaplan Meier plots and compared by logrank test. A Cox model was fit for OS, and non-significant variables were eliminated in a step-down fashion with a p- value cut-off of p = .10. Results: A total of 481 pts were included (65 pts=good risk, 272 pts=intermediate risk and 144 pts= poor risk). Prevalence of FLT3 mutations is shown in the Table. No difference was found in median OS between FLT3-mutated and FLT3- wild type pts in the good risk group (not reached (NR) vs NR, P = 0.57) nor in the poor risk group (55 vs 24 weeks, P = 0.44). In intermediate risk, OS was worse in FLT3-ITD positive pts (33 vs 89 weeks, P &lt; 0.0001) but not in FLT3-TKD positive pts (77 vs 70 weeks, P = 0.89). In the Cox model, FLT3 mutations were prognostic for OS only in intermediate risk pts with FLT3-ITD (HR 2.63, P &lt; 0.0001). Conclusions: In our cohort of pts, FLT3 mutations did not have a prognostic impact in AML with good and poor risk karyotype. [Table: see text] No significant financial relationships to disclose.
Perspectives on Recent Progress in Focused Ultrasound Immunotherapy
Authors: Natasha D. Sheybani, Richard J. Price
Journal: Theranostics (2019)

Immunotherapy holds tremendous promise as a strategy for eradicating solid tumors.However, poor T cell infiltration and persistence within most solid tumor microenvironments, as well as mechanisms of adaptive resistance, continue to severely limit the accessibility of most immunotherapies to a broad patient population.This limitation perpetuates the demand for allied therapeutic strategies.Among such strategies is focused ultrasound (FUS), a non-invasive, non-ionizing technique for precisely targeted acoustic energy deposition into tissues.FUS has gained remarkable attention over recent years as a modality for elicitation of immune mechanisms in cancer and other pathologies.In 2017, we published a comprehensive review paper detailing existing evidence for immune modulation and therapy with FUS, as well as impending challenges and opportunities of consideration for the field.Over the last two years, a multitude of clinical trials have come online to explore safety, feasibility, and efficacy of FUS for cancers of the brain and periphery -including the first clinical trial to combine FUS with immunotherapy.Moreover, the last two years have seen a surge in FUS immunotherapy presentations at therapeutic ultrasound scientific meetings.Given the burst of activity in this field, we submit that an update on FUS immunotherapy progress is timely.In this review, we offer an updated overview and perspectives on scientific and clinical development in the FUS immunotherapy domain.
<sup>18</sup>F-Labeled, PSMA-Targeted Radiotracers: Leveraging the Advantages of Radiofluorination for Prostate Cancer Molecular Imaging
Authors: Rudolf A. Werner, Thorsten Derlin, Constantin Lapa, Sara Sheikbahaei, Takahiro Higuchi, Frederik L. Giesel, Spencer Behr, Alexander Drzezga, Hiroyuki Kimura, Andreas K. Buck, Frank M. Bengel, Martin G. Pomper, Michael A. Gorin, Steven P. Rowe
Journal: Theranostics (2019)

Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with 68 Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world.However, recent years have witnessed the start of a shift from 68 Ga-to 18 F-labeled PSMA-targeted compounds.The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic.First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite 68 Ge/ 68 Ga generator.Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production.Moreover, 18 F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions.In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy.Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron.In light of these advantageous characteristics, 18 F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available.We have aimed to provide a concise overview of emerging 18 F-labeled PSMA-targeted radiotracers undergoing active clinical development.Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available 18 F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
Treatment of First-Episode Schizophrenia in a Young Woman
Authors: Robert A. McCutcheon, Tiago Reis Marques, Oliver D. Howes
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Clinical usefulness of human serum nonmercaptalbumin to mercaptalbumin ratio as a biomarker for diabetic complications and disability in activities of daily living in elderly patients with diabetes
Authors: Saki Fukuhara, Keiko Yasukawa, Masaya Sato, Hitoshi Ikeda, Yukihiro Inoguchi, Tomoaki Etoh, Mitsunori Masakado, Fumio Umeda, Yutaka Yatomi, Teruaki Yamauchi, Toyoshi Inoguchi
Journal: Metabolism (2019)
Eligibility and Radiologic Assessment in Adjuvant Clinical Trials in Bladder Cancer
Authors: Andrea B. Apolo, Matthew I. Milowsky, Lauren Kim, Brant A. Inman, Ashish M. Kamat, Gary Steinberg, Mohammadhadi Bagheri, Venkatesh P. Krishnasamy, Jamie Marko, Colin P. Dinney, Rick Bangs, Randy F. Sweis, Virginia Ellen Maher, Amna Ibrahim, Ke Liu, Ryan Werntz, Frank Cross, Julia A. Beaver, Harpreet Singh, Richard Pazdur, Gideon M. Blumenthal, Seth P. Lerner, Dean F. Bajorin, Jonathan E. Rosenberg, Sundeep Agrawal
Journal: JAMA Oncology (2019)

To harmonize eligibility criteria and radiographic disease assessments in clinical trials of adjuvant therapy for muscle-invasive bladder cancer (MIBC).National experts in bladder cancer clinical trial research, including medical and urologic oncologists, radiologists, biostatisticians, and patient advocates, convened at a public workshop on November 28, 2017, to discuss eligibility, radiographic entry criteria, and assessment of disease recurrence in adjuvant clinical trials in patients with MIBC.The key workshop conclusions for adjuvant MIBC clinical trials included the following points: (1) patients with urothelial carcinoma with divergent histologic differentiation should be allowed to enroll; (2) neoadjuvant chemotherapy is defined as at least 3 cycles of neoadjuvant cisplatin-based combination chemotherapy; (3) patients with muscle-invasive, upper-tract urothelial carcinoma should be included in adjuvant trials of MIBC; (4) patients with severe renal insufficiency can enroll into trials using agents that are not renally excreted; (5) patients with microscopic surgical margins can be included; (6) patients should undergo a standard bilateral lymph node dissection prior to enrollment; (7) computed tomographic (CT) imaging should be performed within 4 weeks prior to enrollment. For patients with renal insufficiency who cannot undergo CT imaging with contrast, noncontrast chest CT and magnetic resonance imaging of the abdomen and pelvis with gadolinium should be done; (8) biopsy of indeterminate lesions to evaluate for malignant disease should be done when feasible; (9) a uniform approach to evaluate indeterminate radiographic lesions when biopsy is not feasible should be included in any trial design; (10) a uniform approach to determining the date of recurrence is important in interpreting adjuvant trial results; and (11) new high-grade, upper-tract primary tumors and new MIBC tumors should be considered recurrence events.A uniform approach to eligibility criteria, definitions of no evidence of disease, and definitions of disease recurrence may lead to more consistent interpretations of adjuvant trial results in MIBC.
Excess mucus viscosity and airway dehydration impact COPD airway clearance
Authors: Vivian Y. Lin, Niroop Kaza, Susan E. Birket, Harrison Kim, Lloyd J. Edwards, Jennifer LaFontaine, Linbo Liu, Marina Mazur, Stephen A. Byzek, Justin Hanes, Guillermo J. Tearney, S. Vamsee Raju, Steven M. Rowe
Journal: European Respiratory Journal (2019)

The mechanisms by which cigarette smoking impairs airway mucus clearance are not well understood. We recently established a ferret model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) exhibiting chronic bronchitis. We investigated the effects of cigarette smoke on mucociliary transport (MCT). Adult ferrets were exposed to cigarette smoke for 6 months, with in vivo mucociliary clearance measured by technetium-labelled DTPA retention. Excised tracheae were imaged with micro-optical coherence tomography. Mucus changes in primary human airway epithelial cells and ex vivo ferret airways were assessed by histology and particle tracking microrheology. Linear mixed models for repeated measures identified key determinants of MCT. Compared to air controls, cigarette smoke-exposed ferrets exhibited mucus hypersecretion, delayed mucociliary clearance (−89.0%, p&lt;0.01) and impaired tracheal MCT (−29.4%, p&lt;0.05). Cholinergic stimulus augmented airway surface liquid (ASL) depth (5.8±0.3 to 7.3±0.6 µm, p&lt;0.0001) and restored MCT (6.8±0.8 to 12.9±1.2 mm·min −1 , p&lt;0.0001). Mixed model analysis controlling for covariates indicated smoking exposure, mucus hydration (ASL) and ciliary beat frequency were important predictors of MCT. Ferret mucus was hyperviscous following smoke exposure in vivo or in vitro , and contributed to diminished MCT. Primary cells from smokers with and without COPD recapitulated these findings, which persisted despite the absence of continued smoke exposure. Cigarette smoke impairs MCT by inducing airway dehydration and increased mucus viscosity, and can be partially abrogated by cholinergic secretion of fluid secretion. These data elucidate the detrimental effects of cigarette smoke exposure on mucus clearance and suggest additional avenues for therapeutic intervention.
Clinical Utility of Plasma Cell-Free DNA in Adult Patients with Newly Diagnosed Glioblastoma: A Pilot Prospective Study
Authors: Stephen J. Bagley, S. Ali Nabavizadeh, Jazmine J. Mays, Jacob E. Till, Jeffrey B. Ware, Scott Levy, Whitney Sarchiapone, Jasmin Hussain, Timothy Prior, Samantha Guiry, Theresa Christensen, Stephanie S. Yee, MacLean P. Nasrallah, Jennifer J.D. Morrissette, Zev A. Binder, Donald M. O'Rourke, Andrew J. Cucchiara, Steven Brem, Arati S. Desai, Erica L. Carpenter
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The clinical utility of plasma cell-free DNA (cfDNA) has not been assessed prospectively in patients with glioblastoma (GBM). We aimed to determine the prognostic impact of plasma cfDNA in GBM, as well as its role as a surrogate of tumor burden and substrate for next-generation sequencing (NGS). Experimental Design: We conducted a prospective cohort study of 42 patients with newly diagnosed GBM. Plasma cfDNA was quantified at baseline prior to initial tumor resection and longitudinally during chemoradiotherapy. Plasma cfDNA was assessed for its association with progression-free survival (PFS) and overall survival (OS), correlated with radiographic tumor burden, and subjected to a targeted NGS panel. Results: Prior to initial surgery, GBM patients had higher plasma cfDNA concentration than age-matched healthy controls (mean 13.4 vs. 6.7 ng/mL, P &amp;lt; 0.001). Plasma cfDNA concentration was correlated with radiographic tumor burden on patients' first post-radiation magnetic resonance imaging scan (ρ = 0.77, P = 0.003) and tended to rise prior to or concurrently with radiographic tumor progression. Preoperative plasma cfDNA concentration above the mean (&amp;gt;13.4 ng/mL) was associated with inferior PFS (median 4.9 vs. 9.5 months, P = 0.038). Detection of ≥1 somatic mutation in plasma cfDNA occurred in 55% of patients and was associated with nonstatistically significant decreases in PFS (median 6.0 vs. 8.7 months, P = 0.093) and OS (median 5.5 vs. 9.2 months, P = 0.053). Conclusions: Plasma cfDNA may be an effective prognostic tool and surrogate of tumor burden in newly diagnosed GBM. Detection of somatic alterations in plasma is feasible when samples are obtained prior to initial surgical resection.