tbuckley/cabot-search huggingface dataset:
ICOSAPENT ETHYL (EICOSAPENTAENOIC ACID ETHYL ESTER) REDUCES POTENTIALLY ATHEROGENIC LIPID, LIPOPROTEIN, APOLIPOPROTEIN, AND INFLAMMATORY PARAMETERS IN HIGH-RISK, STATIN-TREATED PATIENTS WITH PERSISTENT ELEVATED TRIGLYCERIDES AND HIGH-SENSITIVITY C-REACTIVE PROTEIN: A POST HOC SUBANALYSIS OF THE ANCHOR STUDY
Authors: Michael Miller, Christie Ballantyne, Harold Bays, Craig Granowitz, Ralph Doyle, Rebecca Juliano, Sephy Philip
Journal: Journal of the American College of Cardiology (2018)
LONG-TERM PROGNOSTIC VALUE OF SINGLE-PHOTON EMISSION COMPUTED TOMOGRAPHY MYOCARDIAL PERFUSION IMAGING AFTER PRIMARY PCI FOR STEMI
Authors: Jeff Smit, Maaike Hermans, Aukelien C. Dimitriu-Leen, Alexander van Rosendael, Petra Dibbets-Schneider, Lioe-Fee de Geus-Oei, Bart Mertens, Martin Schalij, Jeroen J. Bax, Arthur Scholte
Journal: Journal of the American College of Cardiology (2018)
The African Palliative Care Association (APCA) Atlas of Palliative Care Development in Africa: a comparative analysis
Authors: John Y Rhee, Eduardo Garralda, Eve Namisango, Emmanuel Luyirika, Liliana de Lima, Richard A Powell, Carlos Centeno
Journal: The Lancet Global Health (2018)

BackgroundAlthough there are global studies on palliative care development, none report region-specific indicators of development for each country in Africa. We aimed to develop and deploy a set of indicators to measure the current state of palliative care development in Africa according to WHO's Public Health Strategy for integrating palliative care, including policies, availability and access to medicines, education, and service provision.MethodsQualitative interviews were conducted with 16 country experts between March and August, 2016. From those interviews, 367 indicators were derived, 130 after exclusion criteria and content analysis were performed. The country experts rated the indicators for validity and feasibility, a 14-member international committee of experts participated in a two-round modified UCLA-RAND Delphi consensus, and the coauthors ranked the indicators during November–December 2016. The final 19 indicators were further defined and sent to 66 key country informants from 51 African countries during January–March 2017.FindingsSurveys were received from 48 countries. Uganda, South Africa, and Kenya have the highest number of specialised hospice and palliative care services (71% of identified palliative care services); 19% (9/48) have no identified hospice and palliative care services. 22% (12/48) indicated having stand-alone palliative care policies, and 42% (20/48) reported having a dedicated person for palliative care in the Ministry. Zambia, Uganda, South Africa, Kenya, Ghana, and Egypt reported some official form of physician accreditation. Opioid consumption per capita was low (75% of countries had <1 mg consumption per head per year) compared to the global average (62 mg), with the highest consumption in Mauritius, South Africa, Namibia, and Morocco. 54% (26/48) reported having a national palliative care association. These data were used to build the African Palliative Care Association (APCA) Atlas of Palliative Care in Africa, the first comparative, quantitative, African-specific report on national palliative care development in African countries.InterpretationThere is limited palliative care development in Africa, but there is also a significant improvement in the number of countries with hospice and palliative care services, compared to previous reports. Improvements in advocacy were identified, with more than half of countries reporting a national palliative care association. Governments need to take the steps to improve education, increase the number of services, and ensure safe access to opioids.FundingArnhold Institute of Global Health at the Icahn School of Medicine at Mount Sinai, the African Palliative Care Association, the International Association for Hospice and Palliative Care, and the Institute for Culture and Society at the University of Navarra.
Loss of KCNK3 is a hallmark of RV hypertrophy/dysfunction associated with pulmonary hypertension
Authors: Mélanie Lambert, Angèle Boet, Catherine Rucker-Martin, Pedro Mendes-Ferreira, Véronique Capuano, Stéphane Hatem, Rui Adão, Carmen Brás-Silva, Aurélie Hautefort, Jean-Baptiste Michel, Peter Dorfmuller, Elie Fadel, Tom Kotsimbos, Laura Price, Philippe Jourdon, David Montani, Marc Humbert, Frédéric Perros, Fabrice Antigny
Journal: Cardiovascular Research (2018)

Mutations in the KCNK3 gene, which encodes for an outward-rectifier K+ channel, have been identified in patients suffering from pulmonary arterial hypertension (PAH), and constitute the first described channelopathy in PAH. In human PAH and experimental pulmonary hypertension (PH), we demonstrated that KCNK3 expression and function are severely reduced in pulmonary vascular cells, promoting PH-like phenotype at the morphologic and haemodynamic levels. Since KCNK3 channel is also expressed in both the human and rodent heart, we aimed to elucidate the pathophysiological role of KCNK3 channel in right ventricular (RV) hypertrophy (RVH) related to PH.Using whole-cell Patch-clamp technique, we demonstrated that KCNK3 is predominantly expressed in adult rat RV cardiomyocytes compared to the left ventricle cardiomyocytes and participates in the repolarizing phase of the RV action potential. We revealed a reduction in KCNK3 function prior to development of RVH and the rise of pulmonary vascular resistance. KCNK3 function is severely reduced in RV cardiomyocytes during the development of RVH in several rat models of PH (exposure to monocrotaline, chronic hypoxia, and Sugen/hypoxia) and chronic RV pressure overload (pulmonary artery banding). In experimental PH, we revealed a reduction in KCNK3 function before any rise in pulmonary vascular resistance and the development of RVH. KCNK3 mRNA level is also reduced in human RV tissues from PAH patients compared to non-PAH patients. In line with these findings, chronic inhibition of KCNK3 in rats with the specific inhibitor (A293) induces RV hypertrophy which is associated with the re-expression of foetal genes, RV fibrosis, RV inflammation, and subsequent loss of RV performance as assessed by echocardiography.Our data indicate that loss of KCNK3 function and expression is a hallmark of the RV hypertrophy/dysfunction associated with PH.
The incidental thyroid nodule
Authors: Sarah B. Fisher, Nancy D. Perrier
Journal: CA A Cancer Journal for Clinicians (2018)

Abstract Incidental thyroid nodules that are found on an imaging study performed for reasons other than thyroid pathology represent a common scenario encountered by health care providers. The initial workup for these nodules comprises a thorough history and physical examination, thyroid function tests, a dedicated thyroid ultrasound, and fine‐needle aspiration of any suspicious lesions. Management ranges from observation and reassurance to surgical resection and depends on the cytologic diagnosis. In cases of cytologically indeterminate or discordant nodules, surgical excision (lobectomy) offers a definitive diagnosis, although molecular testing or a reasonable period of observation may be useful as less invasive adjuncts. CA Cancer J Clin 2018;68:97‐105 . © 2018 American Cancer Society .
HYPERKALEMIA AFTER HOSPITALIZATION FOR HEART FAILURE WITH REDUCED EJECTION FRACTION: FINDINGS FROM THE ASTRONAUT TRIAL
Authors: Muthiah Vaduganathan, Manan Pareek, Kamya Sankar, Baljash Cheema, Haris Subacius, Gregg C. Fonarow, Scott Solomon, Eldrin Lewis, Aldo Maggioni, Michael Boehm, Faiez Zannad, Javed Butler, Mihai Gheorghiade
Journal: Journal of the American College of Cardiology (2018)
Motorcycle race doctors
Authors: Tim Moll
Journal: BMJ (2008)

Motorcycle racing carries the potential for serious injury and death. Consequently, the presence of doctors is mandatory at most race meetings. Working at motorcycle race meetings is both challenging and rewarding and surprisingly different from car meetings. Although similarities do exist, mechanisms, patterns, and frequency of injury are quite distinct. Injuries are much more common in motorcycle sport.

To discover the full range of UK motorcycle sport visit www.acu.org.uk. As well as information relating to all the various motorcycle disciplines, it contains invaluable frequently asked questions about …
Revisiting Antipsychotic Drug Actions Through Gene Networks Associated With Schizophrenia
Authors: Karolina Kauppi, Sara Brin Rosenthal, Min-Tzu Lo, Nilotpal Sanyal, Mian Jiang, Ruben Abagyan, Linda K. McEvoy, Ole A. Andreassen, Chi-Hua Chen
Journal: American Journal of Psychiatry (2018)

Objective: Antipsychotic drugs were incidentally discovered in the 1950s, but their mechanisms of action are still not understood. Better understanding of schizophrenia pathogenesis could shed light on actions of current drugs and reveal novel "druggable" pathways for unmet therapeutic needs. Recent genome-wide association studies offer unprecedented opportunities to characterize disease gene networks and uncover drug-disease relationships. Polygenic overlap between schizophrenia risk genes and antipsychotic drug targets has been demonstrated, but specific genes and pathways constituting this overlap are undetermined. Risk genes of polygenic disorders do not operate in isolation but in combination with other genes through protein-protein interactions among gene product. Method: The protein interactome was used to map antipsychotic drug targets (N=88) to networks of schizophrenia risk genes (N=328). Results: Schizophrenia risk genes were significantly localized in the interactome, forming a distinct disease module. Core genes of the module were enriched for genes involved in developmental biology and cognition, which may have a central role in schizophrenia etiology. Antipsychotic drug targets overlapped with the core disease module and comprised multiple pathways beyond dopamine. Some important risk genes like CHRN, PCDH, and HCN families were not connected to existing antipsychotics but may be suitable targets for novel drugs or drug repurposing opportunities to treat other aspects of schizophrenia, such as cognitive or negative symptoms. Conclusions: The network medicine approach provides a platform to collate information of disease genetics and drug-gene interactions to shift focus from development of antipsychotics to multitarget antischizophrenia drugs. This approach is transferable to other diseases.
The human noncoding genome defined by genetic diversity
Authors: Julia di Iulio, Istvan Bartha, Emily H. M. Wong, Hung-Chun Yu, Victor Lavrenko, Dongchan Yang, Inkyung Jung, Michael A. Hicks, Naisha Shah, Ewen F. Kirkness, Martin M. Fabani, William H. Biggs, Bing Ren, J. Craig Venter, Amalio Telenti
Journal: Nature Genetics (2018)
Utility of Baseline Transaminase Monitoring During Systemic Terbinafine Therapy for Pediatric Onychomycosis
Authors: David G. Li, Arash Mostaghimi
Journal: JAMA Dermatology (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 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
Intestine farnesoid X receptor agonist and the gut microbiota activate G‐protein bile acid receptor‐1 signaling to improve metabolism
Authors: Preeti Pathak, Cen Xie, Robert G. Nichols, Jessica M. Ferrell, Shannon Boehme, Kristopher W. Krausz, Andrew D. Patterson, Frank J. Gonzalez, John Y.L. Chiang
Journal: Hepatology (2018)

Bile acids activate farnesoid X receptor (FXR) and G protein-coupled bile acid receptor-1 (aka Takeda G protein-coupled receptor-5 [TGR5]) to regulate bile acid metabolism and glucose and insulin sensitivity. FXR and TGR5 are coexpressed in the enteroendocrine L cells, but their roles in integrated regulation of metabolism are not completely understood. We reported recently that activation of FXR induces TGR5 to stimulate glucagon-like peptide-1 (GLP-1) secretion to improve insulin sensitivity and hepatic metabolism. In this study, we used the intestine-restricted FXR agonist fexaramine (FEX) to study the effect of activation of intestinal FXR on the gut microbiome, bile acid metabolism, and FXR and TGR5 signaling. The current study revealed that FEX markedly increased taurolithocholic acid, increased secretion of fibroblast growth factors 15 and 21 and GLP-1, improved insulin and glucose tolerance, and promoted white adipose tissue browning in mice. Analysis of 16S ribosomal RNA sequences of the gut microbiome identified the FEX-induced and lithocholic acid-producing bacteria Acetatifactor and Bacteroides. Antibiotic treatment completely reversed the FEX-induced metabolic phenotypes and inhibited taurolithocholic acid synthesis, adipose tissue browning, and liver bile acid synthesis gene expression but further increased intestinal FXR target gene expression. FEX treatment effectively improved lipid profiles, increased GLP-1 secretion, improved glucose and insulin tolerance, and promoted adipose tissue browning, while antibiotic treatment reversed the beneficial metabolic effects of FEX in obese and diabetic mice.
Oxygen-generating Hybrid Polymeric Nanoparticles with Encapsulated Doxorubicin and Chlorin e6 for Trimodal Imaging-Guided Combined Chemo-Photodynamic Therapy
Authors: DanRong Hu, LiJuan Chen, Ying Qu, JinRong Peng, BingYang Chu, Kun Shi, Ying Hao, Lin Zhong, MengYao Wang, ZhiYong Qian
Journal: Theranostics (2018)

The combination of chemotherapy with photodynamic therapy (PDT) has attracted broad attention as it can overcome limitations of conventional chemo-treatment by using different modes of action. However, the efficacy of PDT to treat solid tumors is severely affected by hypoxia in tumors.
SIMPLE RENAL CYSTS AND AORTIC DISEASE IN MARFAN SYNDROME AND MATCHED CONTROLS
Authors: Noémie Tencé, Claire Bouleti, Florence Nicot, Olivier Milleron, Phalla Ou, Nicoletta Pasi, Florence Arnoult, Maria Tchitchinadze, Sabine Schmitt, Guillaume Jondeau
Journal: Journal of the American College of Cardiology (2018)
Tackling infiltration in paediatric glioma using histone deacetylase inhibitors, a promising approach
Authors: Lara Jackman, Emmanuel Ago, Marjorie Boissinot, Ronald Grigg, Filomena Esteves, Ruth Morton, Susan Short, Anke Brüning-Richardson
Journal: Neuro-Oncology (2018)

Targeting the migratory behaviour of invading cells in high grade paediatric gliomas represents an attractive combination therapy with current treatment options. Migration involves highly regulated microtubule dynamics that have been linked to the acetylation status of tubulin. MI192 is a selective histone deacetylase inhibitor that has previously been shown to modulate tubulin acetylation. The effect of MI192 on cell migration was investigated in two paediatric high grade glioma cell lines, SF188 and KNS42. Live cell imaging of 2D cell monolayers and 3D spheroid invasion assays were performed to assess the effect of MI192 on cell migration as well as immunofluorescence on 2D cell monolayers to measure changes in acetylated tubulin, proliferation, stemness and apoptosis. In SF188, compared to the untreated control, MI192 demonstrated anti-migratory effects in 3D spheroid assays. This was associated with elevated levels of tubulin acetylation by immunofluorescence and corresponded with distinct differences in cellular movement by live cell imaging. These effects were not due to increased rates of apoptosis. In KNS42, MI192 did not have anti-migratory effects in live cell imaging 2D experiments. In addition, in 3D only the highest concentration of MI192 (pre-determined to have an effect on cell viability) reduced cell migration. This corresponded to reduced Ki67 levels, increase in apoptosis and loss of stemness markers on immunofluorescence. SF188 and KNS42 exhibited different responses after exposure to MI192. SF188 was the more sensitive, with anti-migratory effects observed both in 2D and 3D, which were not a consequence of apoptosis. For KNS42, the main effect of MI192 was to push the cells towards differentiation and apoptosis, another previously described effect of this drug. These preliminary findings warrant further investigations into the mechanisms downstream of MI192 and its use as an anti-migratory and/or pro-differentiating agent.
A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors
Authors: Shota Fujimoto, Naoki Muguruma, Koichi Okamoto, Takeshi Kurihara, Yasushi Sato, Yoshihiko Miyamoto, Shinji Kitamura, Hiroshi Miyamoto, Takahiro Taguchi, Koichi Tsuneyama, Tetsuji Takayama
Journal: Theranostics (2018)

It is difficult to distinguish gastrointestinal stromal tumors (GISTs) from other types of submucosal tumors under conventional gastrointestinal endoscopy.We aimed to detect GISTs by molecular fluorescence imaging using a near-infrared (NIR) photosensitizer (IR700)-conjugated anti-c-KIT antibody and to treat GISTs by photoimmunotherapy with NIR irradiation as a non-invasive theranostic procedure.We also investigated the therapeutic mechanisms.Methods: Human GIST cell lines GIST-T1 and GIST-882M were incubated with IR700-conjugated anti-c-KIT antibody, IR700-12A8, and observed by confocal laser microscopy.Mice with GIST-T1 xenografts or rats with orthotopic xenografts were injected with IR700-12A8 or AF488-conjugated antibody, and observed under IVIS or autofluorescence imaging (AFI) endoscopy.GIST cells were treated with IR700-12A8 and NIR light in vitro and vivo, and cell viability, histology and apoptosis were evaluated.Results: Strong red fluorescence of IR700-12A8 was observed on the cell membrane of GIST cells and was gradually internalized into the cytoplasm.Tumor-specific accumulation of IR700-12A8 was observed in GIST-T1 xenografts in mice.Under AFI endoscopy, a strong fluorescence signal was observed in orthotopic GIST xenografts in rats through the normal mucosa covering the tumor.The percentage of dead cells significantly increased in a light-dose-dependent manner and both acute necrotic and late apoptotic cell death was observed with annexin/PI staining.Cleaved PARP expression was significantly increased after IR700-12A8-mediated NIR irradiation, which was almost completely reversed by NaN3.All xenograft tumors (7/7) immediately regressed and 4/7 tumors completely disappeared after IR700-12A8-mediated NIR irradiation.Histologic assessment and TUNEL staining revealed apoptosis in the tumors.Conclusion: NIR fluorescence imaging using IR700-12A8 and subsequent NIR irradiation could be a very effective theranostic technology for GIST, the underlying mechanism of which appears to involve acute necrosis and supposedly late apoptosis induced by singlet oxygen.
Current trials for frontline therapy of mantle cell lymphoma
Authors: Raphael E. Steiner, Jorge Romaguera, Michael Wang
Journal: Journal of Hematology & Oncology (2018)

Mantle cell lymphoma (MCL) is a rare and incurable subtype of non-Hodgkin's lymphoma that generally affects older individuals. However, the use of high-dose therapy and autologous stem cell transplant has improved significantly the prognosis of this hematological malignancy, but at the cost of increased toxicities, such as acute toxic death and secondary malignancies. But thanks to a rising understanding of the biology of MCL, the explosion of specifically targeted new efficacious agents, immunotherapy agents, and cellular therapies in the frontline setting, the prognosis of MCL is expected to improve dramatically.The initial treatment of MCL is currently not standardized and the therapeutic landscape of MCL is rapidly evolving. This review provides an extensive overview of the current frontline therapy trials for MCL and presents the results of innovative regimen, including some integrating novel agents and desintensified chemotherapy.
Backlog of missing GP letters is worse than feared
Authors: Gareth Iacobucci
Journal: BMJ (2018)

An investigation by government auditors into the loss of NHS patient files has found a backlog of almost 400 000 pieces of clinical correspondence that were not sent to GPs.

The National Audit Office (NAO) launched an inquiry after NHS England said in October 20171 that it had discovered 162 000 letters that had not been redirected to GPs. And this has risen to 374 000 after further review, says …
A Model Linking Sickle Cell Hemoglobinopathies and SMARCB1 Loss in Renal Medullary Carcinoma
Authors: Pavlos Msaouel, Nizar M. Tannir, Cheryl Lyn Walker
Journal: Clinical Cancer Research (2018)

Renal medullary carcinoma (RMC) is a highly aggressive malignancy that predominantly afflicts young adults and adolescents with sickle hemoglobinopathies. It is characterized by complete loss of expression of the chromatin remodeler and tumor suppressor SMARCB1 Despite therapy, the outcomes of patients with RMC remain very poor, highlighting the need to understand the etiology of this cancer, and develop new diagnostic, preventive, and therapeutic strategies. A key knowledge gap in RMC biology is why sickle hemoglobinopathies predispose to the development of this cancer. We propose a model wherein the extreme conditions of hypoxia and hypertonicity of the renal medulla, combined with regional ischemia induced by red blood cell sickling, activate DNA repair mechanisms to drive deletions and translocations in SMARCB1, which is localized in a fragile region of chromosome 22. This mechanism would explain the linkage between RMC and sickle hemoglobinopathies, as well as the age dependence and predilection of RMC toward the right kidney.Significance: This perspective proposes an integrated and testable model of renal medullary carcinoma pathogenesis. Insights provided by this model can additionally inform other malignancies arising from the renal medulla and/or associated with loss of the SMARCB1 tumor suppressor gene. Clin Cancer Res; 24(9); 2044-9. ©2018 AACR.