tbuckley/cabot-search huggingface dataset:
EANO–ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up of patients with leptomeningeal metastasis from solid tumours
Authors: E. Le Rhun, M. Weller, D. Brandsma, M. Van den Bent, E. de Azambuja, R. Henriksson, T. Boulanger, S. Peters, C. Watts, W. Wick, P. Wesseling, R. Rudà, M. Preusser
Journal: Annals of Oncology (2017)

These EANO–ESMO joint recommendations for the diagnosis and treatment of leptomeningeal metastasis (LM) from solid cancers represent the first European guideline initiative on this topic. LM is defined as the spread of tumour cells within the leptomeninges and the subarachnoid space, is synonymous with ‘neoplastic meningitis’ and can be further denoted by primary tumour as leptomeningeal carcinomatosis, gliomatosis or lymphomatosis. The recommendations address LM from solid tumours, but neither LM from primary brain tumours nor LM from lymphoma or leukaemia.
Autochthonous Crimean–Congo Hemorrhagic Fever in Spain
Authors: Anabel Negredo, Fernando de la Calle-Prieto, Eduardo Palencia-Herrejón, Marta Mora-Rillo, Jenaro Astray-Mochales, María P Sánchez-Seco, Esther Bermejo Lopez, Javier Menárguez, Ana Fernández-Cruz, Beatriz Sánchez-Artola, Elena Keough-Delgado, Eva Ramírez de Arellano, Fátima Lasala, Jakob Milla, Jose L Fraile, Maria Ordobás Gavín, Amalia Martinez de la Gándara, Lorenzo López Perez, Domingo Diaz-Diaz, M Aurora López-García, Pilar Delgado-Jimenez, Alejandro Martín-Quirós, Elena Trigo, Juan C Figueira, Jesús Manzanares, Elena Rodriguez-Baena, Luis Garcia-Comas, Olaia Rodríguez-Fraga, Nicolás García-Arenzana, Maria V Fernández-Díaz, Victor M Cornejo, Petra Emmerich, Jonas Schmidt-Chanasit, Jose R Arribas
Journal: New England Journal of Medicine (2017)

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed, viral, tickborne disease. In Europe, cases have been reported only in the southeastern part of the continent. We report two autochthonous cases in Spain. The index patient acquired the disease through a tick bite in the province of Ávila - 300 km away from the province of Cáceres, where viral RNA from ticks was amplified in 2010. The second patient was a nurse who became infected while caring for the index patient. Both were infected with the African 3 lineage of this virus. (Funded by Red de Investigación Cooperativa en Enfermedades Tropicales [RICET] and Efficient Response to Highly Dangerous and Emerging Pathogens at EU [European Union] Level [EMERGE].).
Transplanters drive CARs to the clinic by brewing ICE-T: the Moffitt roadmap
Authors: Frederick L. Locke, Claudio Anasetti
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Abstract</h3> Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapidly and safely bring industry sponsored pivotal trials to our patients and to prepare for additional cell therapy trials in solid and liquid tumors from both industry and our own investigators. We implemented a collaborative cross departmental program to provide clinical care and trial coordination for immune cell therapies. The Moffitt Immune Cell Therapy (ICE-T) program oversees and administers not only CAR T cell therapy for hematologic malignancies, but TIL and TCR therapy for solid tumor patients. Disease specific experts maintain oversight as principal investigators of these key trials yet the coordination and clinical care is centralized to leverage the expertise and infrastructure of our already robust Blood and Marrow Transplantation program.
NGR-hTNF and doxorubicin in relapsed small-cell lung cancer (SCLC).
Authors: Raffaele Cavina, Vanesa Gregorc, Silvia Novello, Francesco Grossi, Armando Santoro, Maria Grazia Viganò, Matteo G. Levra, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2012)

7085 Background: By selectively damaging tumor vasculature, NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is able to improve intratumoral uptake of doxorubicin (D). A phase I trial selected NGR-hTNF 0.8 µg/m 2 /day(d)1 and D 75 mg/m 2 /d1 every 3 weeks (q3w) for phase II. Methods: SCLC pts failing one or more platinum-based regimen received NGR-hTNF until progressive disease (PD) and D up to 550 mg/m 2 . This phase II trial (n=27 pts) had progression-free survival (PFS) as primary end point, with tumor response assessed q6w by RECIST, while secondary end points included adverse events (AEs), disease control rate (DCR), and overall survival (OS). Results: Among 28 pts enrolled (median age 63 years; M/F 19/9; PS 0/1-2 13/15; prior lines 1/2-3 20/8), 16 pts had platinum-resistant (R) disease (PD≤3 months) and 12 pts platinum-sensitive (S) disease (PD&gt;3 months). At baseline, median neutrophil to lymphocyte ratio (NLR) was 4 (range 1-20). A total of 114 cycles were given (range 1-10), with 13 pts (46%) having ≥ 4 cycles and 9 pts (32%) ≥ 6 cycles. No grade 3/4 AEs related to NGR-hTNF were noted, while grade 1/2 AEs were transient chills (61%). NGR-hTNF did not apparently increase D-related AEs. Median PFS was 3.2 months (95% CI 2.6-3.8) and 1-year OS rate was 34%. Overall, DCR was 55% (95% CI 35-74), comprising 6 partial responses (22%; median duration: 6.3 months) and 9 stable diseases (33%; median duration: 4.1 months). Mean changes from baseline in target tumor size after 2, 4, and 6 cycles were -9%, -29%, and -32%, respectively for R disease and -11%, -20%, and -43%, respectively for S disease. In pts pretreated with ≥ 2 lines, DCR was 75%, median PFS was 5.1 months, and 1-year OS rate was 44%. In pts with R or S disease, DCR were 50% and 58% (p=.72), median PFS were 2.7 and 4.1 months (p=.07), and 1-year OS rates were 27% and 42% (p=.65), respectively. At multivariate analyses, PFS was not related to baseline characteristics, while an improved OS was associated only with a low NLR. The 1-year OS rate was 48% in pts with NLR ≤ 4 and 10% in pts with NLR &gt; 4 (p=.007), while in pts with NLR ≤ 4, 1-year OS rate was 46% in R disease and 50% in S disease. Conclusions: This combination is well tolerated and active in platinum resistant and sensitive SCLC and further development is of interest.
Patellar and Achilles tendinopathies are predominantly peripheral pain states: a blinded case control study of somatosensory and psychological profiles
Authors: Melanie L Plinsinga, Cornelis P van Wilgen, Michel S Brink, Viana Vuvan, Aoife Stephenson, Luke J Heales, Rebecca Mellor, Brooke K Coombes, Bill T Vicenzino
Journal: British Journal of Sports Medicine (2017)

Case-control design.Tendinopathy is characterised by pain on tendon loading. In persistent cases of upper limb tendinopathy, it is frequently associated with central nervous system sensitisation, whereas less commonly linked in the case of persistent lower limb tendinopathies.Compare somatosensory and psychological profiles of participants with persistent patellar (PT) and Achilles tendinopathies (AT) with pain-free controls.A comprehensive battery of Quantitative Sensory Testing (QST) was assessed at standardised sites of the affected tendon and remotely (lateral elbow) by a blinded assessor. Participants completed the Victorian Institute of Sports Assessment, a health-related quality of life questionnaire, the Hospital Anxiety and Depression Scale and the Active Australia Questionnaire. Independent t-test and analysis of covariance (sex-adjusted and age-adjusted) were performed to compare groups.Participants with PT and AT did not exhibit differences from controls for the QST at the remote site, but there were differences at the affected tendon site. Compared with controls, participants with PT displayed significantly lower pressure pain threshold locally at the tendon (p=0.012) and fewer single limb decline squats before pain onset, whereas participants with AT only displayed fewer single heel raises before pain onset, but this pain was of a higher intensity.PT and AT appear to be predominantly local not widespread pain states related to loading of tendons without significant features of central sensitisation.Level 4.
Protease-Activated Receptor 1 (PAR-1) Inhibits Proliferation but Enhances Leukemia Stem Cell Activity in Acute Myeloid Leukemia
Authors: Susumu Goyama, Mahesh Shrestha, Janet Schibler, Leah Rosenfeldt, Whitney Miller, Eric O'Brien, Benjamin Mizukawa, Toshio Kitamura, Joseph S. Palumbo, James C. Mulloy
Journal: Blood (2016)
The role of mitochondrial estrogen receptor β in relapse of breast cancer.
Authors: Tae Hyun Kim, In-Sung Song, Jin Han
Journal: Journal of Clinical Oncology (2017)

e12540 Background: Breast cancer is the most common non-skin cancer in women. Breast cancers are heterogeneous, and treatment by subgroup based on hormone receptor and HER2 made a significant difference in clinical outcomes. Several studies have reported that estrogen receptor beta (ERβ) decreases during tumor development in the breast epithelium. However, the role of ERβ in relapse and metastasis of breast cancer is poorly understood. Methods: In this study, we retrospectively studied 30 case breast carcinomas divided luminal, HER2, and triple negative subtype. Among them, patients relapsed within 5 years are 6 cases. The expression of ERβ gene in breast cancer tissues (30 cases) was estimated using a quantitative PCR, and other marker (ERα, HER2, PR etc) was measured anonymously in formalin-fixed paraffin-embedded tumor sections, by using specific antibodies. Results: A low level of ERβ expression and mitochondrial translocation of ERβ was associated with relapse/metastasis of breast cancer. The ERβ depletion resulted in resistance in response to tamoxifen treatment of MCF-7 breast cancer cells. Conversely, the overexpression of mitochondrial ERβ enhanced the cell death by treatment of tamoxifen in MCF-7 cells. We found that ERβ localizes to the mitochondria via the interaction with Grp75 and improves mitochondrial oxygen consumption rate and ATP production in breast cancer cells. Finally, we showed that ERβ level was a low in the breast cancer stem cells (CD24 - CD44 + cells) compared with breast non-cancer stem cells (CD24 + CD44 - cells), whereas ERα level was a high. The overexpression of mitochondrial ERβ contribute to a decrease of sphere formation showing a tumorigenic ability. Conclusions: The mitochondrial ERβ contribute to suppress survival and stemness of cancer stem cells for relapse/metastasis, promising to the development of novel strategies for the treatment of breast cancer patients.
Shared Decision Making—The Importance of Diagnosing Preferences
Authors: Glyn Elwyn, Nan Cochran, Michael Pignone
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Henry Radcliffe Crocker—From the Elephant Man to the Textbook
Authors: Kishore L. Jayakumar, Jules B. Lipoff
Journal: JAMA Dermatology (2017)

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 Dermatology 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 Dermatology journal
Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Risk Factors
Authors: Simon Capewell, Christopher Dowrick
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Targeting of Antithrombin in Hemophilia A or B with RNAi Therapy
Authors: K. John Pasi, Savita Rangarajan, Pencho Georgiev, Tim Mant, Michael D. Creagh, Toshko Lissitchkov, David Bevan, Steve Austin, Charles R. Hay, Inga Hegemann, Rashid Kazmi, Pratima Chowdary, Liana Gercheva-Kyuchukova, Vasily Mamonov, Margarita Timofeeva, Chang-Heok Soh, Pushkal Garg, Akshay Vaishnaw, Akin Akinc, Benny Sørensen, Margaret V. Ragni
Journal: New England Journal of Medicine (2017)

Current hemophilia treatment involves frequent intravenous infusions of clotting factors, which is associated with variable hemostatic protection, a high treatment burden, and a risk of the development of inhibitory alloantibodies. Fitusiran, an investigational RNA interference (RNAi) therapy that targets antithrombin (encoded by SERPINC1), is in development to address these and other limitations.
Deregulated Genes in Hematopoietic Stem Cells Isolated from Spleen of Patients with Myelofibrosis
Authors: Paolo Catarsi, Francesca Cordero, Giulio Ferrero, Marco Beccuti, Valentina Poletto, Elisa Bonetti, Laura Villani, Margherita Massa, Gabriela Fois, Rita Campanelli, Umberto Magrini, Vittorio Rosti, Giovanni Barosi
Journal: Blood (2016)
A proteomic analysis of LRRK2 binding partners reveals interactions with multiple signaling components of the WNT/PCP pathway
Authors: Alena Salašová, Chika Yokota, David Potěšil, Zbyněk Zdráhal, Vítězslav Bryja, Ernest Arenas
Journal: Molecular Neurodegeneration (2017)

Autosomal-dominant mutations in the Park8 gene encoding Leucine-rich repeat kinase 2 (LRRK2) have been identified to cause up to 40% of the genetic forms of Parkinson's disease. However, the function and molecular pathways regulated by LRRK2 are largely unknown. It has been shown that LRRK2 serves as a scaffold during activation of WNT/β-catenin signaling via its interaction with the β-catenin destruction complex, DVL1-3 and LRP6. In this study, we examine whether LRRK2 also interacts with signaling components of the WNT/Planar Cell Polarity (WNT/PCP) pathway, which controls the maturation of substantia nigra dopaminergic neurons, the main cell type lost in Parkinson's disease patients.Co-immunoprecipitation and tandem mass spectrometry was performed in a mouse substantia nigra cell line (SN4741) and human HEK293T cell line in order to identify novel LRRK2 binding partners. Inhibition of the WNT/β-catenin reporter, TOPFlash, was used as a read-out of WNT/PCP pathway activation. The capacity of LRRK2 to regulate WNT/PCP signaling in vivo was tested in Xenopus laevis' early development.Our proteomic analysis identified that LRRK2 interacts with proteins involved in WNT/PCP signaling such as the PDZ domain-containing protein GIPC1 and Integrin-linked kinase (ILK) in dopaminergic cells in vitro and in the mouse ventral midbrain in vivo. Moreover, co-immunoprecipitation analysis revealed that LRRK2 binds to two core components of the WNT/PCP signaling pathway, PRICKLE1 and CELSR1, as well as to FLOTILLIN-2 and CULLIN-3, which regulate WNT secretion and inhibit WNT/β-catenin signaling, respectively. We also found that PRICKLE1 and LRRK2 localize in signalosomes and act as dual regulators of WNT/PCP and β-catenin signaling. Accordingly, analysis of the function of LRRK2 in vivo, in X. laevis revelaed that LRKK2 not only inhibits WNT/β-catenin pathway, but induces a classical WNT/PCP phenotype in vivo.Our study shows for the first time that LRRK2 activates the WNT/PCP signaling pathway through its interaction to multiple WNT/PCP components. We suggest that LRRK2 regulates the balance between WNT/β-catenin and WNT/PCP signaling, depending on the binding partners. Since this balance is crucial for homeostasis of midbrain dopaminergic neurons, we hypothesize that its alteration may contribute to the pathophysiology of Parkinson's disease.
Resistive or dynamic exercise stress testing of the pulmonary circulation and the right heart
Authors: Yoshiki Motoji, Kevin Forton, Beatrice Pezzuto, Vitalie Faoro, Robert Naeije
Journal: European Respiratory Journal (2017)

There has been recent revival of interest in exercise stress testing of the pulmonary circulation and the right ventricle (RV) for the differential diagnosis of dyspnoea or latent pre- or post-capillary pulmonary hypertension [1–3]. However, guidelines remain cautious because of persistent uncertainties about protocols and the limits of normal [4]. In fact, exercise protocols still vary, with either cycling [3, 6–8], weight lifting [5, 6] or even handgrip [9] modalities, with invasive [3, 5–7, 9] or non-invasive [7, 8, 10] measurements either during [3, 6–10] or after [5] the exercise stress. Furthermore, pulmonary artery pressure (PAP) has been reported either alone [5, 8] or as a function of either cardiac output (CO) [1–3, 7, 10], workload [7, 11] or oxygen uptake ( V′ O2) [12]. In the meantime, flow-corrected PAP during exercise emerges as the measurement of choice for pulmonary vascular function [1–3], and body position may not matter provided a sufficient number of exercise pressure-flow coordinates is generated to smoothen out higher baseline pulmonary vascular resistance (PVR) in the upright position [10], but there remains uncertainty about the most relevant measurements of RV function [7, 13, 14]. Although there is a rationale in favour of incremental dynamic exercise, there is currently no consensus about the optimal exercise modality. We therefore compared the cardiovascular and gas exchange effects of resistive (handgrip), mixed resistive/dynamic (weight lifting) or dynamic (cycling) exercise on the pulmonary circulation and the RV in healthy volunteers. Exercise stress testing of the pulmonary circulation and the right heart should be dynamic, not resistive <http://ow.ly/ZEyF30c9RlP>
Abstract 17012: Who is Today’s Alirocumab Patient? A Real World Perspective of Patients Prescribed Alirocumab in the United States
Authors: Dean Karalis, Usha Mallya, Joseph Elassal, Ameen Ghannam, Rishab Gupta, Susan Boklage
Journal: Circulation (2016)

Introduction:  In July 2015, the FDA approved alirocumab (ALI), a first in class PCSK9-inhibitor indicated for cholesterol lowering as adjunct to diet and maximum tolerated statin therapy for adults with clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Furthermore, in March 2016, the ACC released the expert consensus pathway on the role of non-statin therapies in LDL-C reduction. To understand early prescribing patterns, this study aims to describe the types of patients (pts) prescribed ALI.   Methods:  All adult pts with a written prescription (Rx) of ALI were included from Accenture’s Predictive Health Intelligence Environment dataset consisting of electronic medical records from 26 integrated delivery networks (IDN). Pts were further required to have one encounter with the IDN within 12 months prior to the first Rx of ALI (index), used to classify pts’ other lipid modifying treatment (LMT) and past medical history. Probable HeFH pts were identified using either the modified Dutch Lipid Criteria Network (score ≥ 6) or an LDL-C ≥190 mg/dL.   Results:  Among the 564 pts who met study criteria as of May 18, 2016, 69% had ASCVD, 13% were probable HeFH, and 18% were not identified as ASCVD or HeFH. The average age was 65.9 years (SD 10.1), 51% were male, and 74% Caucasian. About 79% had hypertension, 32% had diabetes, 14% had chronic kidney disease and 28% had a history of smoking. Prior to the ALI Rx, for those pts with an LDL-C value, the mean was 135.0 mg/dL (SD 57.5) with 72% having an LDL-C >100 mg/dL. About 72% of the pts had evidence of LMT during the prior 12 months to index; conversely, 28% of pts did not in the same period. Of those with LMT in this period, 29% were on high-intensity statins. Ezetimibe rxs were seen in 31% of pts with LMT, either alone or in combination with statins. Cardiologists were the specialists who prescribed ALI most often (43.1%).   Conclusions:  ALI was predominantly prescribed in pts with ASCVD whose LDL-C was high and far from clinical goals. In light of the new ACC consensus pathway for non-statins, there is still a large population of high-risk pts who have unmet lipid lowering needs and would benefit from alirocumab.
Inhibition of Alternative Complement Pathway in Target Organs Represents a Novel and Effective Approach to Control Gvhd While Sparing GVL Effect
Authors: Hung D Nguyen, Ali Alawieh, David A Bastian, Anusara Daenthanasanmak, Steven D Schutt, Supinya Iamsawat, Yongxia Wu, Atkinson Carl, Stephen Tomlinson, Xue-Zhong Yu
Journal: Blood (2016)