tbuckley/cabot-search huggingface dataset:
Metabolic Imaging of the Human Brain with Hyperpolarized 13C Pyruvate Demonstrates 13C Lactate Production in Brain Tumor Patients
Authors: Vesselin Z. Miloushev, Kristin L. Granlund, Rostislav Boltyanskiy, Serge K. Lyashchenko, Lisa M. DeAngelis, Ingo K. Mellinghoff, Cameron W. Brennan, Vivian Tabar, T. Jonathan Yang, Andrei I. Holodny, Ramon E. Sosa, YanWei W. Guo, Albert P. Chen, James Tropp, Fraser Robb, Kayvan R. Keshari
Journal: Cancer Research (2018)

Abstract Hyperpolarized (HP) MRI using [1-13C] pyruvate is a novel method that can characterize energy metabolism in the human brain and brain tumors. Here, we present the first dynamically acquired human brain HP 13C metabolic spectra and spatial metabolite maps in cases of both untreated and recurrent tumors. In vivo production of HP lactate from HP pyruvate by tumors was indicative of altered cancer metabolism, whereas production of HP lactate in the entire brain was likely due to baseline metabolism. We correlated our results with standard clinical brain MRI, MRI DCE perfusion, and in one case FDG PET/CT. Our results suggest that HP 13C pyruvate-to-lactate conversion may be a viable metabolic biomarker for assessing tumor response. Significance: Hyperpolarized pyruvate MRI enables metabolic imaging in the brain and can be a quantitative biomarker for active tumors. Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/14/3755/F1.large.jpg. Cancer Res; 78(14); 3755–60. ©2018 AACR.
A nano-cocrystal strategy to improve the dissolution rate and oral bioavailability of baicalein
Authors: Jiaxin Pi, Shuya Wang, Wen Li, Dereje Kebebe, Ying Zhang, Bing Zhang, Dongli Qi, Pan Guo, Nan Li, Zhidong Liu
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Baicalein (BE) is one of the main active flavonoids representing the variety of pharmacological effects including anticancer, anti-inflammatory and cardiovascular protective activities, but it's very low solubility, dissolution rate and poor oral absorption limit the therapeutic applications. In this work, a nano-cocrystal strategy was successfully applied to improve the dissolution rate and bioavailability of BE. Baicalein-nicotinamide (BE-NCT) nano-cocrystals were prepared by high pressure homogenization and evaluated both in vitro and in vivo. Physical characterization results including scanning electron microscopy, dynamic light scattering, powder X-ray diffraction and differential scanning calorimetry demonstrated that BE-NCT nano-cocrystals were changed into amorphous state with mean particle size of 251.53 nm. In the dissolution test, the BE-NCT nano-cocrystals performed 2.17-fold and 2.54-fold enhancement than BE coarse powder in FaSSIF-V2 and FaSSGF. Upon oral administration, the integrated AUC0 − t of BE-NCT nano-cocrystals (6.02-fold) was significantly higher than BE coarse powder (1-fold), BE-NCT cocrystals (2.87-fold) and BE nanocrystals (3.32-fold). Compared with BE coarse powder, BE-NCT cocrystals and BE nanocrystals, BE-NCT nano-cocrystals possessed excellent performance both in vitro and in vivo evaluations. Thus, it can be seen that nano-cocrystal is an appropriate novel strategy for improving dissolution rate and bioavailability of poor soluble natural products such as BE.
Letter by Cattaneo and von Kügelgen Regarding Article, “International Expert Consensus on Switching Platelet P2Y <sub>12</sub> Receptor-Inhibiting Therapies”
Authors: Marco Cattaneo, Ivar von Kügelgen
Journal: Circulation (2018)

To the Editor: P2Y 12 receptors play a prominent role in platelet aggregation and are important targets for pharmacotherapy in the treatment of patients with acute coronary syndromes. 1A recent article summarizes the guidelines for switching between P2Y 12 receptor inhibitors during the treatment. 2Clinically used P2Y 12 receptor inhibitors include the prodrugs clopidogrel and prasugrel causing an irreversible receptor blockade and the reversible acting antagonists ticagrelor and cangrelor. 1,2We would like to draw the attention of the readers to evidence supporting the view that ticagrelor binds to a site overlapping with the ADP binding site.This is in contrast to the description given by Angiolillo et al. 2 Experimental data indicate a competitive mode of interaction of ticagrelor against ADP (shown for concentrations of ticagrelor up to 300 nmol/L; Figure 5 of Hoffman et al 3 ).Moreover, a mutagenesis analysis suggests the interaction of ticagrelor with the residue Cys194 of the receptor protein 3 that is in proximity to the agonist binding site as identified by crystallography. 4This binding site is also close to residue Cys97 that interacts with the active metabolites of clopidogrel and prasugrel. 5Overlapping binding sites are likely to be involved in drug-drug interactions when switching between P2Y 12 receptor inhibitors.
Correlation of Lyme Disease–Associated IgG4 Autoantibodies With Synovial Pathology in Antibiotic‐Refractory Lyme Arthritis
Authors: Katherine B. Sulka, Klemen Strle, Jameson T. Crowley, Robert B. Lochhead, Robert Anthony, Allen C. Steere
Journal: Arthritis & Rheumatology (2018)

Objective To determine whether IgG subclasses of Borrelia burgdorferi antibodies differ from those of 3 Lyme disease ( LD )–associated autoantibodies. Methods IgG antibody subclasses were determined by enzyme‐linked immunosorbent assay in serum samples from 215 patients with features representative of each of the 3 stages of LD . Antibody and cytokine profiles were measured in matched serum and synovial fluid ( SF ) samples from patients with Lyme arthritis. Synovial tissue from patients with antibiotic‐refractory arthritis was examined for histologic features, IgG subclasses of plasma cells, and messenger RNA ( mRNA ) subclass expression. Results B burgdorferi antibodies were primarily of the IgG1 and IgG3 subclasses, and the levels increased as the infection progressed. In contrast, LD ‐associated autoantibodies were mainly of the IgG2 and IgG4 subclasses, and these responses were found primarily in patients with either antibiotic‐refractory or antibiotic‐responsive arthritis, particularly in SF . However, compared with the responsive group, the inflammatory milieu in SF in the refractory group was enriched for cytokines representative of innate, Th1, Th2, and Th17 responses. Synovial tissue in a subgroup of patients with refractory arthritis showed marked expression of mRNA for IgG4 antibodies and large numbers of IgG4‐staining plasma cells. IgG4 autoantibodies in SF to each of the 3 LD ‐associated autoantigens correlated with the magnitude of obliterative microvascular lesions and fibrosis in the tissue. Conclusion Our findings indicate that the subclasses of IgG antibodies to B burgdorferi differ from those of LD ‐associated autoantibodies. Furthermore, the correlation of IgG4 autoantibodies with specific synovial pathology in the refractory group suggests a role for these autoantibodies, either protective or pathologic, in antibiotic‐refractory Lyme arthritis.
ベルリン-フランクフルト-ミュンスター(BFM)型ファーストライン治療後の小児および青少年における再発性または難治性未分化大細胞型リンパ腫: BFM-群研究
Authors: Woessmann Willi, Zimmermann Martin, Lenhard Meike, Burkhardt Birgit, Rossig Claudia, Kremens Bernhard, Lang Peter, Attarbaschi Andishe, Mann Georg, Oschlies Ilske, Klapper Wolfram, Reiter Alfred
Journal: Journal of Clinical Oncology (2011)
Emerging Treatment Options for Acute Lymphoblastic Leukemia: Focus on CAR T-Cell Therapy
Authors: Patrick A. Brown, Bijal Shah
Journal: Journal of the National Comprehensive Cancer Network (2018)

Acute lymphoblastic leukemia (ALL) comprises a heterogeneous group of diseases with different morphologic, cytogenetic, and molecular subgroups, some of which have significant therapeutic implications. It typically presents with an aggressive clinical course, and among adults, responds poorly to standard chemotherapy, and carries a high risk for relapse. Despite the significant progress made in inducing remission, frequent relapses remain a challenge. Novel drugs, such as potent later-generation tyrosine kinase inhibitors, antibody-drug conjugates, bispecific monoclonal antibodies, and chimeric antigen receptor (CAR) T-cell therapies, are being investigated in patients with ALL. This summary describes therapies currently approved for the treatment of patients with ALL, identifies emerging targeted immunotherapies for patients with ALL, and discusses adverse events and mechanisms of resistance.
Community-Based Services to Improve Testing and Linkage to Care Among Non–U.S.-Born Persons with Chronic Hepatitis B Virus Infection — Three U.S. Programs, October 2014–September 2017
Authors: Aaron M. Harris, Ruth Link-Gelles, Karen Kim, Edwin Chandrasekar, Su Wang, Nicole Bannister, Perry Pong, Eric Chak, Moon S. Chen, Christopher Bowlus, Noele P. Nelson
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

The United States commemorates National Hepatitis Awareness Month each May, and May 19 is designated as Hepatitis Testing Day.Viral hepatitis still persists as a major public health threat despite availability of preventive measures such as vaccines and therapies, including a curative treatment for hepatitis C virus (HCV) infection.New cases of hepatitis B virus (HBV) and HCV infections are on the rise, largely among persons who inject drugs, with some attributed to the current U.S. opioid epidemic (1).Recent hepatitis A outbreaks have also occurred among unvaccinated injection drug users and homeless persons (2).Since August 2016, CDC has responded to hepatitis A outbreaks with high HBV/HCV co-infection, hospitalization, and mortality rates in multiple states (https://www.cdc.gov/hepatitis/outbreaks/2017March-HepatitisA.htm).New cases of perinatal HBV infection also continue (1); recently, CDC updated recommendations to strengthen vaccination among newborns and manage pregnant women (3).This issue of MMWR includes an article about the promising outcomes of three HBV programs that implemented community-based services to improve HBV testing, linkage to care, and treatment among persons born in intermediate-high prevalence countries (4).
Delivery of small interfering RNA against Nogo-B receptor via tumor-acidity responsive nanoparticles for tumor vessel normalization and metastasis suppression
Authors: Bin Wang, Yanping Ding, Xiaozheng Zhao, Xuexiang Han, Na Yang, Yinlong Zhang, Ying Zhao, Xiao Zhao, Mohammad Taleb, Qing Robert Miao, Guangjun Nie
Journal: Biomaterials (2018)
Comparing the use and timing of palliative care services in COPD and lung cancer: a population-based survey
Authors: Charlotte Scheerens, Kim Beernaert, Peter Pype, Joachim Cohen, Luc Deliens, Kenneth Chambaere
Journal: European Respiratory Journal (2018)

Palliative care is a proven approach to enhance quality of life and care both for people with severe chronic obstructive pulmonary disease (COPD) [1] and those with lung cancer [2], and it is encouraged to start palliative care early in the disease trajectory [3, 4]. Similar symptoms occur in both diseases, such as pain, insomnia, fatigue, low mood and dyspnoea [5], with a study reporting even worse physical and emotional functioning for COPD than for lung cancer [6]. These symptoms signal palliative care needs [6], and require treatment focused on symptom management and psychosocial support for more than just the terminal phase. A high use of healthcare resources in COPD is found, related to a tendency towards aggressive and life-prolonging care [7]. Difficulties in predicting disease trajectories and unclear prognosis have been suggested as explanations for why people with COPD are referred less often for palliative care [8]. Palliative care services are used mainly as terminal care in lung cancer and COPD, with less and later use for COPD <http://ow.ly/j38v30jxbhv>
Abstract 12475: Mechanisms of Akt1-mediated Hypothermia Protection After Cardiac Arrest: Metabolism, Inflammation and Contractile Function
Authors: Jing Li, Huashan Wang, Chunpei Lee, Sy-Jou Chen, Xiangdong Zhu, Yuanyu Qian, Ryan H Bunney, David G Beiser, Terry L Vanden Hoek
Journal: Circulation (2016)

Introduction: Induction of intra-arrest cooling (IC) improves cardiac, neurological and survival outcomes in preclinical models of cardiac arrest. Previous studies demonstrate that IC protection is mediated by Akt1 activation through initiating survival signaling. Hypothesis: We hypothesize that IC-induced Akt1 activation modulates protective calcium cycling proteins, metabolic, and inflammatory pathways. Methods: Adult female Akt1 +/- underwent 8 min of KCl-induced asystolic arrest and were randomized to receive IC (30 ± 0.5°C) or normothermia (NT) before CPR (n = 10 per group). 72 h survival and mean blood pressure (MAP) were measured. Indicators of glucose utilization, inflammatory responses and contractile function in heart and brain of Akt1 +/+ and Akt1 +/- mice were assessed (n=5 per group). Results: No difference on survival was seen for IC and NT treated Akt1 +/- mice. IC induced transient improvement in MAP at 30 min following resuscitation (53.6 ± 2.2 vs 71.2 ± 2.6 mmHg p&lt;0.05) and increased phospholamban phosphorylation in the heart of Akt1 +/+ mice which were not seen in Akt1 +/- mice. Compared to IC-treated Akt1 +/+ , pyruvate dehydrogenase phosphorylation and sorbitol accumulation were significantly increased, and NAD and ATP contents were markedly reduced in the hearts and brains of Akt1 +/- mice. IC significantly inhibited IκBα degradation and NF-κB nuclear translocation, and reduced concentrations of blood lactate and Pre-B cell Colony Enhancing Factor in Akt1 +/+ mice, but not Akt1 +/- mice. Conclusion: Akt1 is a critical mediator for TH protection during early post resuscitation in heart and brain through regulating calcium regulatory proteins, enhancing glucose utilization and downregulating inflammatory responses.
A Simple, Evidence-Based Approach to Help Guide Diagnosis of Heart Failure With Preserved Ejection Fraction
Authors: Yogesh N.V. Reddy, Rickey E. Carter, Masaru Obokata, Margaret M. Redfield, Barry A. Borlaug
Journal: Circulation (2018)

Diagnosis of heart failure with preserved ejection fraction (HFpEF) is challenging in euvolemic patients with dyspnea, and no evidence-based criteria are available. We sought to develop and then validate noninvasive diagnostic criteria that could be used to estimate the likelihood that HFpEF is present among patients with unexplained dyspnea to guide further testing.
Percutaneous Coronary Intervention in 2018
Authors: Deepak L. Bhatt
Journal: JAMA (2018)

This JAMA Clinical Update reviews the evolution of procedures for treating coronary artery stenosis since 1977 and the role of percutaneous coronary intervention (PCI) in the management of acute coronary syndromes (NSTEMI and STEMI), stable and unstable angina, and stable multivessel disease.
Evidence-based nutritional and pharmacological interventions targeting chronic low-grade inflammation in middle-age and older adults: A systematic review and meta-analysis
Authors: C. Custodero, R.T. Mankowski, S.A. Lee, Z. Chen, S. Wu, T.M. Manini, J. Hincapie Echeverri, C. Sabbà, D.P. Beavers, J.A. Cauley, M.A. Espeland, R.A. Fielding, S.B. Kritchevsky, C.K. Liu, M.M. McDermott, M.E. Miller, R.P. Tracy, A.B. Newman, W.T. Ambrosius, M. Pahor, S.D. Anton
Journal: Ageing Research Reviews (2018)
Oral propranolol in the treatment of proliferating infantile haemangiomas: British Society for Paediatric Dermatology consensus guidelines
Authors: L. Solman, M. Glover, P.E. Beattie, H. Buckley, S. Clark, J.E. Gach, A. Giardini, I. Helbling, R.J. Hewitt, B. Laguda, S.M. Langan, A.E. Martinez, R. Murphy, L. Proudfoot, J. Ravenscroft, H. Shahidullah, L. Shaw, S.B. Syed, L. Wells, C. Flohr
Journal: British Journal of Dermatology (2018)

Infantile haemangiomas (IH) are the most common vascular tumours of infancy. Despite their frequency and potential complications, there are currently no unified U.K. guidelines for the treatment of IH with propranolol. There are still uncertainties and diverse opinions regarding indications, pretreatment investigations, its use in PHACES (posterior fossa malformations–haemangiomas–arterial anomalies–cardiac defects–eye abnormalities–sternal cleft and supraumbilical raphe) syndrome and cessation of treatment. To provide unified guidelines for the treatment of IH with propranolol. This study used a modified Delphi technique, which involved an international treatment survey, a systematic evidence review of the literature, a face‐to‐face multidisciplinary panel meeting and anonymous voting. The expert panel achieved consensus on 47 statements in eight categories, including indications and contraindications for starting propranolol, pretreatment investigations, starting and target dose, monitoring of adverse effects, the use of propranolol in PHACES syndrome and how to stop treatment. These consensus guidelines will help to standardize and simplify the treatment of IH with oral propranolol across the U.K. and assist in clinical decision‐making.
Premature Cardiac Disease and Death After Preterm Preeclampsia in Women Whose Infant Was Small for Gestational Age
Authors: Kathleen Stergiopoulos, Fabio V. Lima, Cecilia Avila
Journal: JAMA Cardiology (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 Cardiology 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 Cardiology journal
PTU-039 Anaemia – should all patients have radiological investigations?
Authors: N Mirza, B Elgizoli, G Williams, MH Mir, C Tan, S Khalid
Journal: Gut (2017)

Introduction  BSG guideline for anaemia does not recommended use of routine radiological investigations to rule out non gastrointestinal malignancies. It advocates the use of radiological testing to rule out GI cancer only, if patient is not suitable to have endoscopy. We audited the data of patients who were referred for endoscopic investigations for anaemia. We aimed to identify whether there is any role of routine imaging in these patients and how likely are we to miss GI cancers when patients are not suitable to have endoscopic investigations.  Method  We analysed data retrospectively for patients who underwent endoscopic investigations for Anaemia over a six month period in 2015. Further data was collected through pathology and radiology reporting system until July 2016 to analyse the yield of radiological imaging. 335 patients had bidirectional endoscopic investigations and 52 patients under the age of 50 and 56 patients with no radiological investigations were excluded.  Results  227 patients above the age 50 were included who had both endoscopy and radiological investigations. We found ratio of 2:1 of GI malignancy to non GI malignancy. A total of 11 malignancies were found with 7 colorectal and 4 extra gastrointestinal cancers including 1 pancreatic, 1 adrenal and 2 renal. 1 patient with renal malignancy also had stomach ulcer as a possible cause of anaemia. No GI malignancy was missed on radiological investigations and we found virtual endoscopy as good as endoscopic examination for diagnostic evaluation. Gastroscopies did not identify any cancer and unless patient is symptomatic it may have low yield in this group of patients  Conclusion  We found high yield of non GI malignancies in our cohort and suggest that all patients should have radiological investigations.  No cancers were missed on CT imaging and it is reasonable to employ this in line with BSG guidelines, when patient is not suitable to have endoscopic investigations.  Disclosure of Interest  None Declared
Not as distinct as you think: Reasons to doubt that morality comprises a unified and objective conceptual category
Authors: Jordan Theriault, Liane Young
Journal: Behavioral and Brain Sciences (2018)

Abstract That morality comprises a distinct and objective conceptual category is a critical claim for Stanford's target article. We dispute this claim. Statistical conclusions about a distinct moral domain were not justified in prior work, on account of the “stimuli-as-fixed-effects” fallacy. Furthermore, we have found that, behaviorally and neurally, morals share more in common with preferences than facts.
Retinal Vasculitis in Takayasu’s Arteritis
Authors: Priya Bajgai, Ramandeep Singh
Journal: New England Journal of Medicine (2018)

A 25-year-old woman with Takayasu’s arteritis presented to the ophthalmology clinic with gradual, painless loss of vision in both eyes that was suggestive of retinal vasculitis. Retinal blood flow before and after treatment is shown in videos.
The Problem of the Indeterminate Thyroid Nodule
Authors: Peter Angelos
Journal: JAMA Surgery (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 Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Hepatocellular Carcinoma: Updates to Screening and Diagnosis
Authors: Anne M. Covey
Journal: Journal of the National Comprehensive Cancer Network (2018)

<section class="abstract"><p id="P1">In what is considered to be "a global problem," liver cancer has tripled in incidence in the United States over the past 20 to 30 years, and is now present in 7 per 100,000 Americans. Thus, screening for disease should be at the forefront to effectively treat high-risk populations. At the 2018 NCCN 23rd Annual Conference, Dr. Anne M. Covey discussed the updated NCCN Guidelines for the screening and diagnosis of hepatocellular carcinoma, which place ultrasound as the most cost-effective and least toxic primary screening option, with a screening interval of approximately 6 months for individuals considered to be at high risk. </section>