tbuckley/cabot-search huggingface dataset:
Diagnosis and management of Silver–Russell syndrome: first international consensus statement
Authors: Emma L. Wakeling, Frédéric Brioude, Oluwakemi Lokulo-Sodipe, Susan M. O'Connell, Jennifer Salem, Jet Bliek, Ana P. M. Canton, Krystyna H. Chrzanowska, Justin H. Davies, Renuka P. Dias, Béatrice Dubern, Miriam Elbracht, Eloise Giabicani, Adda Grimberg, Karen Grønskov, Anita C. S. Hokken-Koelega, Alexander A. Jorge, Masayo Kagami, Agnes Linglart, Mohamad Maghnie, Klaus Mohnike, David Monk, Gudrun E. Moore, Philip G. Murray, Tsutomu Ogata, Isabelle Oliver Petit, Silvia Russo, Edith Said, Meropi Toumba, Zeynep Tümer, Gerhard Binder, Thomas Eggermann, Madeleine D. Harbison, I. Karen Temple, Deborah J. G. Mackay, Irène Netchine
Journal: Nature Reviews Endocrinology (2016)
Acute Aortic Dissection and Intramural Hematoma
Authors: Firas F. Mussa, Joshua D. Horton, Rameen Moridzadeh, Joseph Nicholson, Santi Trimarchi, Kim A. Eagle
Journal: JAMA (2016)

<h3>Importance</h3> Acute aortic syndrome (AAS), a potentially fatal pathologic process within the aortic wall, should be suspected in patients presenting with severe thoracic pain and hypertension. AAS, including aortic dissection (approximately 90% of cases) and intramural hematoma, may be complicated by poor perfusion, aneurysm, or uncontrollable pain and hypertension. AAS is uncommon (approximately 3.5-6.0 per 100 000 patient-years) but rapid diagnosis is imperative as an emergency surgical procedure is frequently necessary. <h3>Objective</h3> To systematically review the current evidence on diagnosis and treatment of AAS. <h3>Evidence Review</h3> Searches of MEDLINE, EMBASE, and the Cochrane Register of Controlled Trials for articles on diagnosis and treatment of AAS from June 1994 to January 29, 2016, were performed. Only clinical trials and prospective observational studies of 10 or more patients were included. Eighty-two studies (2 randomized clinical trials and 80 observational) describing 57 311 patients were reviewed. <h3>Findings</h3> Chest or back pain was the most commonly reported presenting symptom of AAS (61.6%-84.8%). Patients were typically aged 60 to 70 years, male (50%-81%), and had hypertension (45%-100%). Sensitivities of computerized tomography and magnetic resonance imaging for diagnosis of AAS were 100% and 95% to 100%, respectively. Transesophageal echocardiography was 86% to 100% sensitive, whereas D-dimer was 51.7% to 100% sensitive and 32.8% to 89.2% specific among 6 studies (n = 876). An immediate open surgical procedure is needed for dissection of the ascending aorta, given the high mortality (26%-58%) and proximity to the aortic valve and great vessels (with potential for dissection complications such as tamponade). An RCT comparing endovascular surgical procedure to medical management for uncomplicated AAS in the descending aorta (n = 61) revealed no dissection-related deaths in either group. Endovascular surgical procedure was better than medical treatment (97% vs 43%,<i>P</i> &lt; .001) for the primary end point of "favorable aortic remodeling" (false lumen thrombosis and no aortic dilation or rupture). The remaining evidence on therapies was observational, introducing significant selection bias. <h3>Conclusions and Relevance</h3> Because of the high mortality rate, AAS should be considered and diagnosed promptly in patients presenting with acute chest or back pain and high blood pressure. Computerized tomography, magnetic resonance imaging, and transesophageal echocardiography are reliable tools for diagnosing AAS. Available data suggest that open surgical repair is optimal for treating type A (ascending aorta) AAS, whereas thoracic endovascular aortic repair may be optimal for treating type B (descending aorta) AAS. However, evidence is limited by the paucity of randomized trials.
Clinical outcomes of metastatic breast cancer patients with triple-negative phenotype who received platinum-containing chemotherapy
Authors: S. Yi, J. Uhm, E. Cho, S. Lee, M. Park, H. Jun, Y. Park, J. Ahn, Y. Im, W. Kang, K. Park
Journal: Journal of Clinical Oncology (2008)

1008 Background: Breast cancers comprise a heterogeneous group of tumors that are diverse in behavior and clinical outcome. Triple-negative (TN) breast cancers are defined as a lack of expression of estrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). TN breast cancers have many similarities to BRCA1-associated breast cancers, which suggest that dysfunction in BRCA1 pathways might be related with sensitivity to DNA damaging agents, such as platinum compounds. Methods: We retrospectively analyzed the clinical outcomes in patients with metastatic breast cancer who received the platinum-containing chemotherapy as first or second line treatment, focused on TN phenotype. Results: 257 patients with metastatic breast cancer received platinum-containing chemotherapy at Samsung Medical Center from 1999 to 2006. The receptor status of ER, PgR, HER2 were available for histological review in 198 patients. Among them, 106 patients were treated with platinum-containing regimen as first or second line treatment for metastatic disease. 36 of 106 revealed TN phenotype. The involvement of visceral organs of TN breast cancer was similar to other phenotypes at that time of relapse or metastases. Two out of 67 patients with measurable lesions achieved complete response (CR) and 24 patients did partial response. One of 2 CR cases was TN and the other was ER+/PgR+/HER2-. The overall response rate of TN phenotype was 38.8% and the disease control rate was 67.2%, which did not show statistical difference from those of other phenotypes. However, TN group showed shorter overall survival (OS) after platinum-containing chemotherapy (p=0.005) than other phenotypes of breast cancers. Furthermore, OS from the relapse of TN group was poorer than others (p=0.002). Conclusions: The response to platinum-containing chemotherapy in patients with TN phenotype was not inferior to that of other phenotypes of breast cancers. However, they showed shorter OS. Therefore, the implication of TN phenotype of breast cancer as poor prognostic factor is uncertain whether it is related to the rapid growing characteristics of tumor itself or the resistance to drug therapy, and further studies are warranted. No significant financial relationships to disclose.
Decriminalising sex work in the UK
Authors: Pippa Grenfell, Janet Eastham, Georgina Perry, Lucy Platt
Journal: BMJ (2016)

Cutting support services will jeopardise health benefits of proposed decriminalisation

Last month the UK House of Commons Home Affairs Committee called for street soliciting and the sharing of premises by sex workers to be decriminalised, and for associated convictions and cautions to be deleted.1 The recommendations have been hailed as a victory for sex workers’ rights and for evidence over ideology.2 However, the public health gains that could be achieved through this progressive approach will be undermined by ongoing cuts to specialist health and support services for sex workers, amid a government led ideological realignment of resources.

The select committee’s recommendations have the potential to redress extensive harms that sex workers have experienced as a criminalised population, particularly if they are coupled with measures to remove penalties against clients. Enabling sex workers to share premises would increase safety at work.3 Removing penalties for soliciting and kerb crawling would relieve economic pressure, provide more time to negotiate services and screen out potentially violent clients, and lessen the need to work in isolated areas4—all factors linked to an increased risk of violence and sexual ill health.5 …
High throughput profiling of leukemia and lymphoma cell lines using small molecules: In search of conserved and novel chemical scaffold signatures effective for specific diseases
Authors: Mark G. Frattini, David Shum, Ruth Santos, Asma Ahmed, Hakim Djaballah, Thomas J. Kelly
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4636 

Hematopoietic malignancies are associated with recurrent molecular abnormalities that confer or contribute to cellular transformation. Among the associated mutations, point mutations in signaling molecules and balanced translocations involving transcription factors are among the most common and specific. Immortalized cell lines with such aberrations are widely used in the laboratory to model different aspects of both leukemogenesis and lymphomagenesis. We reasoned that specific mutations should be associated with discrete profiles of drug sensitivities. To test this hypothesis, we developed a sensitive proliferation assay suitable for high-throughput screening using Alamar blue reduction as an indicator of cellular viability. The assay was miniaturized and validated for 384-well microtiter plates. We have begun screening established leukemia and lymphoma cell lines against the Sloan-Kettering Institute small molecule library which includes 200,000 compounds from both synthetic and natural origins. Our results indicate that several of the tested cell types can be distinguished by their sensitivity to specific classes of small molecules. We are now extending our screening to an expanded repertoire of cell lines representing several different types of leukemia and lymphoma. We expect this approach will aid in the development of tailored treatment strategies and novel drug discovery for these common hematopoietic malignancies.
Invasive Fungal Infections in Acute Promyelocytic Leukemia Patients. Results of a Prospective Multicenter Study in Italy
Authors: Maria Stamouli, Alessandro Busca, Luisa Verga, Anna Candoni, Chiara Cattaneo, Gianpaolo Nadali, Maria Enza Mitra, Mario Delia, Sergio Storti, Antonio Spadea, Maria Rosaria De Paolis, Adriana Vacca, Prassede Salutari, Annamaria Nosari, Cecilia Caramatti, Carlo Castagnola, Anna Chierichini, Lorella Melillo, Luca Facchini, Roberta Di Blasi, Monica Cesarini, Maria Grazia Garzia, Bruno Martino, Vincenzo Perriello, Massimo Offidani, Marco Picardi, Nicola Vianelli, Morena Caira, Franco Aversa, Valentina Mancini, Leonardo Potenza, Rosa Fanci, Marco Sanna, Antonella Ferrari, Adriano Venditti, Vincenzo Pavone, Mario Tumbarello, Livio Pagano
Journal: Blood (2014)
Inhibitor of the CREB Proto-Oncogene Suppresses AML Cell Proliferation and Induces Apoptosis In Vitro and In Vivo
Authors: Bryan Mitton, Alan Ikeda, Kazunari Yamada, Bingbing Li, Qiuhua Fan, Elliot Landaw, Xiangshu Xiao, Kathleen M Sakamoto
Journal: Blood (2010)
Daclatasvir plus sofosbuvir, with or without ribavirin, achieved high sustained virological response rates in patients with HCV infection and advanced liver disease in a real-world cohort
Authors: Tania M Welzel, Jörg Petersen, Kerstin Herzer, Peter Ferenci, Michael Gschwantler, Heiner Wedemeyer, Thomas Berg, Ulrich Spengler, Ola Weiland, Marc van der Valk, Jürgen Rockstroh, Markus Peck-Radosavljevic, Yue Zhao, Maria Jesus Jimenez-Exposito, Stefan Zeuzem
Journal: Gut (2016)

<h3>Objective</h3> We assessed the effectiveness and safety of daclatasvir (DCV) plus sofosbuvir (SOF), with or without ribavirin (RBV), in a large real-world cohort, including patients with advanced liver disease. <h3>Design</h3> Adults with chronic HCV infection at high risk of decompensation or death within 12 months and with no available treatment options were treated in a European compassionate use programme. The recommended regimen was DCV 60 mg plus SOF 400 mg for 24 weeks; RBV addition or shorter duration was allowed at physicians9 discretion. The primary endpoint was sustained virological response at post-treatment week 12 (SVR12). <h3>Results</h3> Of the 485 evaluable patients, 359 received DCV+SOF and 126 DCV+SOF+RBV. Most patients were men (66%), white (93%) and treatment-experienced (70%). The most frequent HCV genotypes were 1b (36%), 1a (33%) and 3 (21%), and 80% of patients had cirrhosis (42% Child–Pugh B/C; 46% Model for End-Stage Liver Disease score &gt;10). SVR12 (modified intention-to-treat) was achieved by 91% of patients (419/460); 1 patient had virological breakthrough and 13 patients relapsed. Virological failure was not associated with treatment group (adjusted risk difference DCV+SOF minus DCV+SOF+RBV: 1.06%; 95% CI −2.22% to 4.35%). High SVR12 was observed regardless of HCV genotype or cirrhosis, liver transplant or HIV/HCV coinfection status. Twenty eight patients discontinued treatment due to adverse events (n=18) or death (n=10) and 18 died during follow-up. Deaths and most safety events were associated with advanced liver disease and not considered treatment related. <h3>Conclusions</h3> DCV+SOF with or without RBV achieved high SVR12 and was well tolerated in a diverse cohort of patients with severe liver disease. <h3>Trial registration number</h3> NCT0209966.
A role for MALT1 activity in Kaposi’s sarcoma-associated herpes virus latency and growth of primary effusion lymphoma
Authors: L Bonsignore, K Passelli, C Pelzer, M Perroud, A Konrad, M Thurau, M Stürzl, L Dai, J Trillo-Tinoco, L Del Valle, Z Qin, M Thome
Journal: Leukemia (2016)

Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi’s sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-κB, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-κB activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-κB activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.
Optogenetic defibrillation terminates ventricular arrhythmia in mouse hearts and human simulations
Authors: Tobias Bruegmann, Patrick M. Boyle, Christoph C. Vogt, Thomas V. Karathanos, Hermenegild J. Arevalo, Bernd K. Fleischmann, Natalia A. Trayanova, Philipp Sasse
Journal: Journal of Clinical Investigation (2016)

Ventricular arrhythmias are among the most severe complications of heart disease and can result in sudden cardiac death. Patients at risk currently receive implantable defibrillators that deliver electrical shocks to terminate arrhythmias on demand. However, strong electrical shocks can damage the heart and cause severe pain. Therefore, we have tested optogenetic defibrillation using expression of the light-sensitive channel channelrhodopsin-2 (ChR2) in cardiac tissue. Epicardial illumination effectively terminated ventricular arrhythmias in hearts from transgenic mice and from WT mice after adeno-associated virus-based gene transfer of ChR2. We also explored optogenetic defibrillation for human hearts, taking advantage of a recently developed, clinically validated in silico approach for simulating infarct-related ventricular tachycardia (VT). Our analysis revealed that illumination with red light effectively terminates VT in diseased, ChR2-expressing human hearts. Mechanistically, we determined that the observed VT termination is due to ChR2-mediated transmural depolarization of the myocardium, which causes a block of voltage-dependent Na+ channels throughout the myocardial wall and interrupts wavefront propagation into illuminated tissue. Thus, our results demonstrate that optogenetic defibrillation is highly effective in the mouse heart and could potentially be translated into humans to achieve nondamaging and pain-free termination of ventricular arrhythmia.
Parenteral vs Epidural Analgesia for Postoperative Pain—Reply
Authors: Christopher L. Wu, Brian M. Block, Andrew J. Rowlingson, Spencer S. Liu, Anne R. Cowan, John A. Cowan
Journal: JAMA (2004)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Mutations in desmoglein 1 cause diverse inherited palmoplantar keratoderma phenotypes: implications for genetic screening
Authors: M.-L. Lovgren, M.A. McAleer, A.D. Irvine, N.J. Wilson, S. Tavadia, M.E. Schwartz, C. Cole, A. Sandilands, F.J.D. Smith, M. Zamiri
Journal: British Journal of Dermatology (2016)

The inherited palmoplantar keratodermas (PPKs) are a heterogeneous group of genodermatoses, characterized by thickening of the epidermis of the palms and soles. No classification system satisfactorily unites clinical presentation, pathology and molecular pathogenesis. There are four patterns of hyperkeratosis - striate, focal, diffuse and punctate. Mutations in the desmoglein 1 gene (DSG1), a transmembrane glycoprotein, have been reported primarily in striate, but also in focal and diffuse PPKs. We report seven unrelated pedigrees with dominantly inherited PPK owing to mutations in the DSG1 gene, with marked phenotypic variation. Genomic DNA from each family was isolated, and individual exons amplified by polymerase chain reaction. Sanger sequencing was employed to identify mutations. Mutation analysis identified novel mutations in five families (p.Tyr126Hisfs*2, p.Ser521Tyrfs*2, p.Trp3*, p.Asp591Phefs*9 and p.Met249Ilefs*6) with striate palmar involvement and varying focal or diffuse plantar disease, and the recurrent mutation c.76C>T, p.Arg26*, in two families with variable PPK patterns. We report one recurrent and five novel DSG1 mutations, causing varying patterns of PPK, highlighting the clinical heterogeneity arising from mutations in this gene.
Correction: Deletion of <i>Slam</i> locus in mice reveals inhibitory role of SLAM family in NK cell responses regulated by cytokines and LFA-1
Authors: Huaijian Guo, Stacey A. Cranert, Yan Lu, Ming-Chao Zhong, Shaohua Zhang, Jun Chen, Rui Li, Sarah E. Mahl, Ning Wu, Dominique Davidson, Stephen N. Waggoner, André Veillette
Journal: The Journal of Experimental Medicine (2016)

Signaling lymphocytic activation molecule (SLAM) family receptors (SFRs) can mediate either activating or inhibitory effects during natural killer cell (NK cell) activation. In this study, we addressed the global role, regulation, and mechanism of action of the SLAM family in NK cells by analyzing a mouse lacking the entire ∼400-kilobase Slam locus, which encodes all six SFRs and CD48, the ligand of SFR 2B4. This mouse displayed enhanced NK cell activation responses toward hematopoietic target cells. Analyses of mice lacking individual SFRs showed that the inhibitory function of the Slam locus was due solely to 2B4 and was not influenced positively or negatively by other SFRs. Differences in NK cell responses between recognition of targets expressing or lacking ligands for SFRs were enhanced by IL-12 but suppressed by type I interferon. Cytokines also changed the levels of SLAM-associated protein adaptors, which prevent the inhibitory function of SFRs. The enhanced activation responses of SFR-deficient NK cells were dependent on integrin LFA-1 but not on DNAM-1 or NKG2D. SFR-mediated inhibition prevented the generation of activated forms of LFA-1. Hence, the Slam locus has an overall inhibitory role during NK cell activation that is solely dependent on 2B4. This effect is influenced by cytokines and leads to suppression of LFA-1 activity.
Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015
Authors: Jie Zhou, Jie Wu, Xianqiao Zeng, Guofeng Huang, Lirong Zou, Yingchao Song, Divya Gopinath, Xin Zhang, Min Kang, Jinyan Lin, Benjamin J Cowling, William G. Lindsley, Changwen Ke, Joseph Sriyal Malik Peiris, Hui-Ling Yen
Journal: Eurosurveillance (2016)

Zoonotic infections by avian influenza viruses occur at the human–poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls.
Methylphenidate for Attention-Deficit/Hyperactivity Disorder—Reply
Authors: Ole Jakob Storebø, Erik Simonsen, Christian Gluud
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Wait-List Outcomes for Adults With Congenital Heart Disease Listed for Heart Transplantation in the U.S.
Authors: Laith I. Alshawabkeh, Nan Hu, Knute D. Carter, Alexander R. Opotowsky, KellyAnn Light-McGroary, Joseph E. Cavanaugh, Heather L. Bartlett
Journal: Journal of the American College of Cardiology (2016)