tbuckley/cabot-search huggingface dataset:
Targeting HSP90 dimerization via the C terminus is effective in imatinib-resistant CML and lacks the heat shock response
Authors: Sanil Bhatia, Daniela Diedrich, Benedikt Frieg, Heinz Ahlert, Stefan Stein, Bertan Bopp, Franziska Lang, Tao Zang, Tobias Kröger, Thomas Ernst, Gesine Kögler, Andreas Krieg, Steffen Lüdeke, Hana Kunkel, Ana J. Rodrigues Moita, Matthias U. Kassack, Viktoria Marquardt, Friederike V. Opitz, Marina Oldenburg, Marc Remke, Florian Babor, Manuel Grez, Andreas Hochhaus, Arndt Borkhardt, Georg Groth, Luitgard Nagel-Steger, Joachim Jose, Thomas Kurz, Holger Gohlke, Finn K. Hansen, Julia Hauer
Journal: Blood (2018)
Real world experience with twelve weeks of therapy without ribavirin in genotype 1 HCV infected compensated cirrhotics
Authors: D. Zarebska-Michaluk, R. Flisiak, E. Janczewska, H. Berak, H. Andrzej, J. Jaroszewicz, A. Garlicki, M. Sitko, B. Dobracka, A. Czauz-Andrzejuk, D. Dybowska, W. Halota, M. Wtodzimierz, K. Tomasiewicz, M. Tudrujek, D. Zbigniew, B. Baka-Cwierz, T. Belica-Wdowik, I. Ortowska, S. Krzysztof, J. Bialkowska-Warzecha, B. Lorenc, R. Krygier, A. Piekarska, J. Citko, A. Gietka, A. Staniaszek, M. Wawrzynowicz-Syczewska, Ł. Laurans, Ł. Socha, M. Pawtowska
Journal: Journal of Hepatology (2018)
Langerhans and inflammatory dendritic epidermal cells in atopic dermatitis are tolerized toward <scp>TLR</scp>2 activation
Authors: K. Iwamoto, T. J. Nümm, S. Koch, N. Herrmann, N. Leib, T. Bieber
Journal: Allergy (2018)

Abstract Background The skin of atopic dermatitis ( AD ) patients presents a significant dysbalance of the microbiome with a high colonization by Staphylococcus aureus ( S. aureus ), which positively correlates with the severity of the disease. Objective Understanding the role of epidermal dendritic cells (DC) as link between the innate and the adaptive immune systems in AD . Methods Comparative phenotypic and functional analysis of TLR 2 on Langerhans cells ( LC ) and inflammatory dendritic epidermal cells ( IDEC ) in organotypic models as well as freshly isolated cells from healthy and AD skin. Results In situ analysis of freshly isolated LC and IDEC from AD skin revealed decreased TLR 2 expression compared to LC from healthy skin. In contrast to IDEC , LC from AD skin failed to display any evidence for in situ activation. Exposure to TLR 2 ligand Pam3Cys resulted in maturation and increased migratory activity of LC from normal skin. LC and IDEC from AD were unresponsive to TLR 2 ligand in that they failed to mature and displayed a high spontaneous migratory activity. Keratinocytes from both healthy and AD skin expressed similar levels of TLR 2. The production of IL ‐6 and IL ‐10 was impaired by Pam3Cys in supernatants from AD skin. IL ‐18 was significantly higher in supernatants from AD skin and not influenced by TLR 2 ligation, when compared to healthy skin. Conclusion Our results suggest that TLR 2‐mediated sensing of S. aureus ‐derived signals is strongly impaired in LC from AD skin. This phenomenon may partly contribute to the immune deviation in AD and the lack of S. aureus clearance.
Clinical-grade human liver mesenchymal stem cells reduce NAS score and fibrosis progression in advanced stage NASH pre-clinical model through immunomodulation
Authors: M.M. Binda, E. Corritore, L. Menchi, T. Baran, Y. Greiling, S. Michel, J. Tchelingerian, G. Mazza, E. Sokal
Journal: Journal of Hepatology (2018)
GP at Hand: commissioning group asks NHS England for extra £18m to cope with demand
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The clinical commissioning group (CCG) hosting the GP at Hand service has asked NHS England to provide an extra £18m (€20.5m; $24.4m) in funding to cope with the surge in patient demand.

The service, launched by the digital health company Babylon Health at a practice in Hammersmith, west London, has attracted almost 20 000 new patients since launching in November 2017. It allows people living outside the CCG’s catchment area to access virtual GP consultations 24 hours a day on their smartphones if they deregister with their existing practice.

The influx of new patients has led to a 10% overall increase …
Building a Stronger Care Loop Through mHealth Technology
Authors: Alexander G. Logan, S. Vanita Jassal
Journal: JAMA Internal Medicine (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 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
Association of Temporal Changes in Gestational Age With Perinatal Mortality in the United States, 2007-2015
Authors: Cande V. Ananth, Robert L. Goldenberg, Alexander M. Friedman, Anthony M. Vintzileos
Journal: JAMA Pediatrics (2018)

Whether the changing gestational age distribution in the United States since 2005 has affected perinatal mortality remains unknown.
3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy for post-traumatic stress disorder in military veterans, firefighters, and police officers: a randomised, double-blind, dose-response, phase 2 clinical trial
Authors: Michael C Mithoefer, Ann T Mithoefer, Allison A Feduccia, Lisa Jerome, Mark Wagner, Joy Wymer, Julie Holland, Scott Hamilton, Berra Yazar-Klosinski, Amy Emerson, Rick Doblin
Journal: The Lancet Psychiatry (2018)
Progress Toward Polio Eradication — Worldwide, January 2016–March 2018
Authors: Farrah Khan, S. Deblina Datta, Arshad Quddus, John F. Vertefeuille, Cara C. Burns, Jaume Jorba, Steven G.F. Wassilak
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 1988, when an estimated 350,000 cases of poliomyelitis occurred in 125 countries, the World Health Assembly resolved to eradicate polio globally. Transmission of wild poliovirus (WPV) continues uninterrupted in only three countries (Afghanistan, Nigeria, and Pakistan) (1), and among the three serotypes, WPV type 1 (WPV1) remains the only confirmed circulating type. This report describes global progress toward polio eradication during January 2016-March 2018, and updates previous reports (2). In 2017, 22 WPV1 cases were reported, a 41% decrease from the 37 WPV1 cases reported in 2016. As of April 24, 2018, eight WPV1 cases have been reported (seven in Afghanistan and one in Pakistan), compared with five cases during the same period in 2017. In Pakistan, continuing WPV1 transmission has been confirmed in multiple areas in 2018 by isolation from wastewater samples. In Nigeria, ongoing endemic WPV1 transmission was confirmed in 2016 (3); although WPV was not detected in 2017 or in 2018 to date, limitations in access for vaccination and surveillance in insurgent-held areas in northeastern Nigeria might permit continued undetected poliovirus transmission. Substantial progress toward polio eradication has continued in recent years; however, interruption of WPV transmission will require overcoming remaining challenges to reaching and vaccinating every missed child. Until poliovirus eradication is achieved, all countries must remain vigilant by maintaining high population immunity and sensitive poliovirus surveillance.
Unraveling the Complex Interplay Between T Cell Metabolism and Function
Authors: Ramon I. Klein Geltink, Ryan L. Kyle, Erika L. Pearce
Journal: Annual Review of Immunology (2018)

Metabolism drives function, on both an organismal and a cellular level. In T cell biology, metabolic remodeling is intrinsically linked to cellular development, activation, function, differentiation, and survival. After naive T cells are activated, increased demands for metabolic currency in the form of ATP, as well as biomass for cell growth, proliferation, and the production of effector molecules, are met by rewiring cellular metabolism. Consequently, pharmacological strategies are being developed to perturb or enhance selective metabolic processes that are skewed in immune-related pathologies. Here we review the most recent advances describing the metabolic changes that occur during the T cell lifecycle. We discuss how T cell metabolism can have profound effects on health and disease and where it might be a promising target to treat a variety of pathologies.
Mesenchymal stromal cells and macrophages in sepsis: new insights
Authors: Maya E. Kotas, Michael A. Matthay
Journal: European Respiratory Journal (2018)

Sepsis is a syndrome of acute organ dysfunction caused by the physiologic and pathophysiologic response to infection [1–3]. Although the specific clinical definition of sepsis continues to evolve, the entity has been recognised in some form or other for thousands of years. Yet, distressingly, over 30 million cases of sepsis still occur globally each year, resulting in over 5 million deaths, and inestimable disability [1, 3]. The pathophysiology of sepsis is perplexing, as some features indicate an overly exuberant inflammatory response, while others reveal relative immunosuppression [2, 4, 5]. These processes may be concurrent, or may be separated by space ( i.e. tissues) and time. Immune dysfunction likely triggers the coagulation abnormalities, endothelial and epithelial barrier disruption, and altered vasoactivity that culminate in multiorgan dysfunction. However, the specific cellular and molecular pathways that are responsible are incompletely understood. These uncertainties surrounding the pathophysiology of sepsis are highlighted by the lack of targeted therapies. With the exception of antibiotics, essentially all of the interventions for sepsis are supportive, rather than directed towards a specific pathophysiology. Thus, targeted therapies to reverse the tissue pathology that occurs during sepsis are needed. A better understanding of the effects of mesenchymal stromal cells on the function of macrophages may open up new therapeutic opportunities for treating sepsis <http://ow.ly/8eRx30j28iH>
Review of Computational Techniques for Performance Evaluation of RF Localization Inside the Human Body
Authors: Umair Khan, Sergey N. Makarov, Yunxing Ye, Ruijun Fu, Pranay Swar, Kaveh Pahlavan
Journal: IEEE Reviews in Biomedical Engineering (2018)

Location estimation within the human body by means of wireless signals is becoming popular for a variety of purposes, including wireless endoscopy using camera pills. The precision of wireless ranging in any medium is contingent upon the methodology employed. Two of the most popular wireless tracking methods are received signal strength (RSS) and time of arrival (TOA). The scope of this study is an assessment of the precision of TOA- and RSS-based ranging in the proximity of anthropomorphic tissue by means of simulation software designed to mimic signal transmission in the human body environment. Software simulations of wireless signals traveling within a human body are exceptionally challenging and require extensive computational resources. We created a rudimentary, MATLAB script using the finite-difference time-domain (FDTD) method to simulate the signal transmission inside and outside a human body and correlated the simulation outcomes of this script with the high-end commercial finite-element method (FEM) tool, ANSYS HFSS. First, we demonstrated that the FDTD modeling produces similar outcomes. Next, we employed the script to emulate the RSS and TOA of the wide bandwidth radio transmission within the human body for wireless ranging and estimated the accuracy of each technology. The precision of both methods was also evaluated with the Cramer-Rao lower bound (CRLB), which is frequently used to estimate the ranging methodologies and the effect of human tissue and its motion.
The impact of platelets on patients with hepatocellular carcinoma
Authors: B. Scheiner, S. Popp, F. Hucke, S. Bota, M. Peck, N. Rohr-Udilova, T. Reiberger, C. Müller, M. Trauner, W. Sieghart, M. Pinter
Journal: Journal of Hepatology (2018)
Additional perspectives on ‘ACL rupture is a single leg injury but a double leg problem…’
Authors: Anna Trulsson
Journal: British Journal of Sports Medicine (2018)

Additional perspectives on Commentary bjsports-2017-098502: ‘ACL rupture is a single leg injury but a double leg problem: too much focus on “symmetry” alone and that’s not enough!’1 

In the Commentary ‘ACL rupture is a single leg injury but a double leg problem…’, the authors argue that measurements of limb symmetry underestimate deficits. I mainly agree with the authors, but reason for when and how symmetry measurements should be used and also for the use of versatile test batteries . To choose adequate functional tests in the clinic and to design new test-batteries and rehabilitation programmes for individuals with ACL injury, I propose to look for answers and solutions in the extensive literature on motor control. Therefore, basics of motor control are recapitulated .

No consensus exists on how to decide when to return to sports.2 Often, strength and hop tests are used, calculating an LSI (the ratio of injured/non-injured sides), and LSI >90% is frequently suggested as a cut-off criteria.3 However, individuals with ACL reconstruction rarely reach 90% symmetry.4 Moreover, impaired capacity on both sides after ACL injury is well known, underestimating deficits measured as LSI. Therefore, measurements of preinjury capacity or normative data of non-injured controls have been suggested, since they may be more sensitive in predicting second ACL injuries.5 Therefore, to meet the concerns of the double leg problem I argue for that when LSI is used, it should be interpreted in combination with applicable normative data of controls or …
Neurobiology of Opioid Use Disorder and Comorbid Traumatic Brain Injury
Authors: Thomas R. Kosten, David P. Graham, David A. Nielsen
Journal: JAMA Psychiatry (2018)

<h3>Importance</h3> Treating patients with opioid use disorder (OUD) and traumatic brain injury illustrates 6 neurobiological principles about the actions of 2 contrasting opioid analgesics, morphine and fentanyl, as well as pharmacotherapies for OUD, methadone, naltrexone, and buprenorphine. <h3>Observations</h3> This literature review focused on a patient with traumatic brain injury who developed OUD from chronic morphine analgesia. His treatment is described in a neurobiological framework of 6 opioid action principles. <h3>Conclusions and Relevance</h3> The 6 principles are (1) coactivation of neuronal and inflammatory immune receptors (Toll-like receptor 4), (2) 1 receptor activating cyclic adenosine monophosphate and β-arrestin second messenger systems, (3) convergence of opioid and adrenergic receptor types on 1 second messenger, (4) antagonist (eg, naltrexone)–induced receptor trafficking, (5) genetic μ-opioid receptor variants influencing analgesia and tolerance, and (6) cross-tolerance vs receptor antagonism as the basis of OUD pharmacotherapy with methadone or buprenorphine vs naltrexone.
Laboratory testing in <i>BCR‐ABL1</i>‐like (Philadelphia‐like) B‐lymphoblastic leukemia/lymphoma
Authors: Bradford J. Siegele, Valentina Nardi
Journal: American Journal of Hematology (2018)

BCR-ABL1-like B-lymphoblastic leukemia/lymphoma (BCR-ABL1-like B-ALL), also known as Philadelphia-like (Ph-like) ALL, is a neoplasm of B-lineage lymphoblasts characterized by a pattern of gene expression similar to that of B-ALL with the BCR-ABL1 translocation but lacking the BCR-ABL1 fusion protein. The diagnosis of BCR-ABL1-like B-ALL is associated with a high rate of relapse and poor clinical outcomes. In recognition of the difficulty in screening these leukemias for diagnostic workup, the 2016 update/revision to the World Health Organization (WHO) 2008 edition included BCR-ABL1-like B-ALL as a provisional entity. This review addresses the various clinical considerations and methodologies currently used in the pathologic diagnosis, subclassification, and molecular characterization of cases of BCR-ABL1-like B-ALL, with particular attention paid to emerging methods useful in identification of molecular lesions potentially amenable to targeted therapy.
Shedding old assumptions and consolidating what we know: Toward an attention-based model of dreaming
Authors: Russell Conduit, Sheila Gillard Crewther, Grahame Coleman
Journal: Behavioral and Brain Sciences (2000)

Most current theoretical models of dreaming are built around an assumption that dream reports collected on awakening provide unbiased sampling of previous cognitive activity during sleep. However, such data are retrospective, requiring the recall of previous mental events from sleep on awakening. Thus, it is possible that dreaming occurs throughout sleep and differences in subsequent dream reports are owing to systematic differences in our ability to recall mentation on awakening. For this reason, it cannot be concluded with certainty that sleep cognition is more predominant or in any way different during REM compared to NREM sleep. It is our contention that REM sleep and ponto-geniculo-occipital (PGO) waves do not necessarily represent “pseudosensory” stimulation of the cortex in the generation of dreams, but might rather represent enhanced arousal of attention mechanisms during sleep, which results in the subsequent recall of attended mentation on awakening. [Hobson et al.; Nielsen; Revonsuo; Solms; Vertes &amp; Eastman]
Bile duct ligation–induced biliary hyperplasia, hepatic injury, and fibrosis are reduced in mast cell–deficient KitW‐sh mice
Authors: Laura Hargrove, Lindsey Kennedy, Jennifer Demieville, Hannah Jones, Fanyin Meng, Sharon DeMorrow, Walker Karstens, Taronish Madeka, John Greene, Heather Francis
Journal: Hepatology (2017)

Activated mast cells (MCs) release histamine (HA) and MCs infiltrate the liver following bile duct ligation (BDL), increasing intrahepatic bile duct mass (IBDM) and fibrosis. We evaluated the effects of BDL in MC‐deficient ( KitW‐sh ) mice. Wild‐type (WT) and KitW‐sh mice were subjected to sham or BDL for up to 7 days and KitW‐sh mice were injected with cultured mast cells or 1× phosphate‐buffered saline (PBS) before collecting serum, liver, and cholangiocytes. Liver damage was assessed by hematoxylin and eosin and alanine aminotransferase levels. IBDM was detected by cytokeratin‐19 expression and proliferation by Ki‐67 immunohistochemistry (IHC). Fibrosis was detected by IHC, hydroxyproline content, and by qPCR for fibrotic markers. Hepatic stellate cell (HSC) activation and transforming growth factor‐beta 1 (TGF‐β1) expression/secretion were evaluated. Histidine decarboxylase (HDC) and histamine receptor (HR) expression were detected by qPCR and HA secretion by enzymatic immunoassay. To evaluate vascular cells, von Willebrand factor (vWF) and vascular endothelial growth factor (VEGF)‐C expression were measured. In vitro , cultured HSCs were stimulated with cholangiocyte supernatants and alpha‐smooth muscle actin levels were measured. BDL‐induced liver damage was reduced in BDL KitW‐sh mice, whereas injection of MCs did not mimic BDL‐induced damage. In BDL KitW‐sh mice, IBDM, proliferation, HSC activation/fibrosis, and TGF‐β1 expression/secretion were decreased. The HDC/HA/HR axis was ablated in sham and BDL KitW‐sh mice. vWF and VEGF‐C expression decreased in BDL KitW‐sh mice. In KitW‐sh mice injected with MCs, IBDM, proliferation, fibrosis, and vascular cell activation increased. Stimulation with cholangiocyte supernatants from BDL WT or KitW‐sh mice injected with MCs increased HSC activation, which decreased with supernatants from BDL KitW‐sh mice. Conclusion : MCs promote hyperplasia, fibrosis, and vascular cell activation. Knockout of MCs decreases BDL‐induced damage. Modulation of MCs may be important in developing therapeutics for cholangiopathies. (H epatology 2017;65:1991‐2004).
Chemotherapy-Induced Peripheral Neuropathy in Long-term Survivors of Childhood Cancer
Authors: Tejaswi Kandula, Michelle Anne Farrar, Richard J. Cohn, David Mizrahi, Kate Carey, Karen Johnston, Matthew C. Kiernan, Arun V. Krishnan, Susanna B. Park
Journal: JAMA Neurology (2018)

In light of the excellent long-term survival of childhood cancer patients, it is imperative to screen for factors affecting health, function, and quality of life in long-term survivors.To comprehensively assess chemotherapy-induced peripheral neuropathy in childhood cancer survivors to define disease burden and functional effect and to inform screening recommendations.In this cross-sectional observational study, cancer survivors who were treated with chemotherapy for extracranial malignancy before age 17 years were recruited consecutively between April 2015 and December 2016 from a single tertiary hospital-based comprehensive cancer survivorship clinic and compared with healthy age-matched controls. Investigators were blinded to the type of chemotherapy. A total of 169 patients met inclusion criteria, of whom 48 (28.4%) were unable to be contacted or declined participation.Chemotherapy agents known to be toxic to peripheral nerves.The clinical peripheral neurological assessment using the Total Neuropathy Score was compared between recipients of different neurotoxic chemotherapy agents and control participants and was correlated with neurophysiological, functional, and patient-reported outcome measures.Of the 121 childhood cancer survivors included in this study, 65 (53.7%) were male, and the cohort underwent neurotoxicity assessments at a median (range) age of 16 (7-47) years, a median (range) 8.5 (1.5-29) years after treatment completion. Vinca alkaloids and platinum compounds were the main neurotoxic agents. Clinical abnormalities consistent with peripheral neuropathy were common, seen in 53 of 100 participants (53.0%) treated with neurotoxic chemotherapy (mean Total Neuropathy Score increase, 2.1; 95% CI, 1.4-2.9; P < .001), and were associated with lower limb predominant sensory axonal neuropathy (mean amplitude reduction, 5.8 μV; 95% CI, 2.8-8.8; P < .001). Functional deficits were seen in manual dexterity, distal sensation, and balance. Patient-reported outcomes demonstrating reduction in global quality of life and physical functioning were associated with the Total Neuropathy Score. Cisplatin produced long-term neurotoxicity more frequently than vinca alkaloids.Clinical abnormalities attributable to peripheral neuropathy were common in childhood cancer survivors and persisted long term, with concurrent deficits in patient-reported outcomes. Both the type of neurotoxic agent and a targeted clinical neurological assessment are important considerations when screening survivors for long-term neuropathy. Further development of peripheral neuropathy-specific pediatric assessment tools will aid research into neuroprotective and rehabilitative strategies.
Sorafenib increases the percentage and cytotoxicity of circulating NK cells in hepatocellular carcinoma patients
Authors: J. Hu, D. Xia, M. Zhang, E. Wang, L. Liu, Q. Wang, W. Bai, J. Tie, X. Li, J. Yuan, J. Niu, K. Li, C. He, W. Guo, H. Chen, X. Yuan, T. Yu, Z. Wang, B. Luo, N. Han, Y. Zhu, Z. Zhang, Z. Yin, D. Fan, K. Yang, G. Han
Journal: Journal of Hepatology (2018)
Identification of HBV genotypes and mutations associated to antiviral resistance and vaccine escape in serum and oral fluid samples from chronic hepatitis B patients
Authors: M.M. Portilho, A.C.D.F. Mendonça, B. Lago, C. Villela-Nogueira, L. Nabuco, C.A.P. Ivantes, L.L. Lewis-Ximenez, E. Lampe, L. Villar
Journal: Journal of Hepatology (2018)