tbuckley/cabot-search huggingface dataset:
A Middle-aged Man With Aortic and Mitral Valve Endocarditis
Authors: Hourmazd Haghbayan, Eric A. Coomes
Journal: JAMA Cardiology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
A New Multi-Factor Risk Score System Depending on Gene Mutation and Overexpression for Predicting the Outcome in AML1-ETO-Positive Acute Myeloid Leukemia
Authors: Guo-Pan Yu, Changxin Yin, Fuqun Wu, Dan Xu, Zhongxin Zheng, Ling Jiang, Fang Chen, Xuejie Jiang, Qifa Liu, Fanyi Meng
Journal: Blood (2017)
The multi-kinase inhibtor Sorafenib interacts synergistically with the HDAC inhibitor Vorinostat to induce apoptosis in CML cells in association with downregulation of MCL-1 and p21CIP1
Authors: Girija Dasmahapatra, Tri Nguyen, Mohamed Rahmani, Yun Dai, Nitin Yerram, Paul Dent, Steven Grant
Journal: Cancer Research (2007)

2485  Interactions between the multi-kinase inhibitor Sorafenib (Bay 43-9006; Bayer Pharmaceuticals) and the histone deacetylase inhibitor (HDACI) Vorinostat (Merck Pharmaceuticals) were examined in CML cells. Pretreatment of K562 or LAMA84 for 24 hr with a subtoxic concentration of Vorinostat (1.5-2.0 μM) followed by a marginally toxic concentration of Sorafenib (7.5 μM; 24 hr) resulted in a highly synergistic induction of apoptosis, and loss of clonogenic survival. Simultaneous exposure also resulted in greater than additive antileukemic effects, but these were slightly less pronounced as those observed with sequential treatment. This regimen potently induced apoptosis in imatinib mesylate-resistant cells including those expressing the T315I Bcr/Abl mutation or amplified Lyn, as well as in primary CD34+ CML patient-derived samples. In contrast, synergism was not observed in normal bone marrow mononuclear cells. Sequential but not individual treatment with Sorafenib/Vorinostat resulted in pronounced mitochondrial dysfunction (i.e. cytochrome c, Smac and AIF release), caspase 8 activation, PARP cleavage, downregulation of Mcl-1, and attenuation of p21CIP1 induction. Enforced expression of Mcl-1 substantially circumvented Sorafenib/Vorinostat lethality while ecotopic expression of p21CIP1 partially but significantly protected cells from this regimen. Downregulation of Mcl-1 was entirely caspase-independent whereas attenuation of p21CIP1 induction was partially caspase-dependent. Furthermore, RT-PCR analysis revealed that Mcl-1 downregulation was largely transcription-independent, whereas p21CIP1 down-regulation displayed a transcriptional component. Together, these findings indicate that combined exposure to Vorinostat and Sorafenib potently induces mitochondrial injury and apoptosis in CML cells, including those resistant to imatinib mesylate, through a process that involves downregulation of Mcl-1 and p21CIP1. They also suggest that a strategy combining Vorinostat and Sorafenib warrants further attention in CML, particularly in disease resistant to imatinib mesylate therapy.
Reply to Byung Kwan Park's Letter to the Editor re: Baris Turkbey, Andrew B. Rosenkrantz, Masoom A. Haider, et al. Prostate Imaging Reporting and Data System Version 2.1: 2019 Update of Prostate Imaging Reporting and Data System Version 2. Eur Urol 2019;76:329–40
Authors: Andrew B. Rosenkrantz, Baris Turkbey, Jelle Barentsz, Jeffrey C. Weinreb
Journal: European Urology (2019)
Monocytic Myeloid-Derived Suppressor Cells (Mo-MDSC) Are Increased but Not M1 or M2 TAM Macrophages in the Bone Marrow of Patients with BCR-ABL Negative Myeloid Neoplasm (MPN)
Authors: Chi Chen, Andrei Bandarchuk, Ching Wong, Vladimir K. Gotlieb, Hamza Minhas, Gardith Joseph, Sophia Tribie, Jen-Chin Wang
Journal: Blood (2017)
Assessment of Nonradioactive Multispectral Optoacoustic Tomographic Imaging With Conventional Lymphoscintigraphic Imaging for Sentinel Lymph Node Biopsy in Melanoma
Authors: Ingo Stoffels, Philipp Jansen, Maximilian Petri, Lukas Goerdt, Titus J. Brinker, Klaus G. Griewank, Thorsten D. Poeppel, Dirk Schadendorf, Joachim Klode
Journal: JAMA Network Open (2019)

The metastatic status of sentinel lymph nodes (SLNs) is the most relevant prognostic factor in breast cancer, melanoma, and other tumors. The conventional standard to label SLNs is lymphoscintigraphy with technetium Tc 99m. A worldwide shortage and known disadvantages of Tc 99m have intensified efforts to establish alternative, nonradioactive imaging techniques.To assess a new nonradioactive method using multispectral optoacoustic tomographic (MSOT) imaging in comparison with conventional lymphoscintigraphic imaging for SLN biopsy (SLNB) in melanoma.Analysis of a cross-sectional study was conducted at the University Hospital-Essen, Skin Cancer Center, Essen, Germany. Between June 2, 2014, and February 22, 2019, 83 patients underwent SLNB with an additional preoperative indocyanine green (ICG) application. Sentinel lymph node basins were preoperatively identified by MSOT imaging, and ICG-labeled SLNs were intraoperatively detected using a near-infrared camera. The surgeons were blinded to the lymphoscintigraphic imaging results in the beginning of the SLNB. Use of a γ probe was restricted until the SLNB procedure was attempted by the nonradioactive method.Concordance of SLN basins and SLNs identified by MSOT imaging plus near-infrared camera vs lymphoscintigraphic imaging plus single-photon emission computed tomographic or computed tomographic imaging was assessed.Of the 83 patients (mean [SD] age, 54.61 [17.53] years), 47 (56.6%) were men. In 83 surgical procedures, 165 SLNs were excised. The concordance rate of ICG-labeled and Tc 99m-marked detected SLN basins was 94.6% (n = 106 of 112). Intraoperatively, 159 SLNs were detected using a near-infrared camera and 165 were detected by a γ probe, resulting in a concordance rate of 96.4%. Multispectral optoacoustic tomographic imaging visualized SLNs in all anatomic regions with high penetration depth (5 cm).The findings of this study suggest that nonradioactive SLN detection via MSOT imaging allows identification of SLNs at a frequency equivalent to that of the current radiotracer conventional standard. Multispectral optoacoustic tomographic imaging appears to be a viable nonradioactive alternative to detect SLNs in malignant tumors.
PCSK9 Antibody Alirocumab Attenuates Arterial Wall Inflammation Without Changes in Circulating Inflammatory Markers
Authors: Renate M. Hoogeveen, Tjerk S.J. Opstal, Yannick Kaiser, Lotte C.A. Stiekema, Jeffrey Kroon, Remco J.J. Knol, Willem A. Bax, Hein J. Verberne, Jan H. Cornel, Erik S.G. Stroes
Journal: JACC. Cardiovascular imaging (2019)
ICON 2019: International Scientific Tendinopathy Symposium Consensus: Clinical Terminology
Authors: Alex Scott, Kipling Squier, Hakan Alfredson, Roald Bahr, Jill L Cook, Brooke Coombes, Robert-Jan de Vos, Siu Ngor Fu, Alison Grimaldi, Jeremy S Lewis, Nicola Maffulli, SP Magnusson, Peter Malliaras, Sean Mc Auliffe, Edwin H G Oei, Craig Robert Purdam, Jonathan D Rees, Ebonie Kendra Rio, Karin Gravare Silbernagel, Cathy Speed, Adam Weir, Jennifer Moriatis Wolf, Inge van den Akker-Scheek, Bill T Vicenzino, Johannes Zwerver
Journal: British Journal of Sports Medicine (2019)

Persistent tendon pain that impairs function has inconsistent medical terms that can influence choice of treatment.1 When a person is told they have tendinopathy by clinician A or tendinitis by clinician B, they might feel confused or be alarmed at receiving what they might perceive as two different diagnoses. This may lead to loss of confidence in their health professional and likely adds to uncertainty if they were to search for information about their condition. Clear and uniform terminology also assists inter-professional communication. Inconsistency in terminology for painful tendon disorders is a problem at numerous anatomical sites.

Historically, the term ‘tendinitis’ was first used to describe tendon pain, thickening and impaired function (online supplementary figure S1). The term ‘tendinosis’ has also been used in a small number of publications, some of which were very influential.2 3 Subsequently, ‘tendinopathy’ emerged as the most common term for persistent tendon pain.4 5 To our knowledge, experts (clinicians and researchers) or patients have never engaged in a formal process to discuss the terminology we use. We believe that health professionals have not yet agreed on the appropriate terminology for painful tendon conditions.

### Supplementary data

[bjsports-2019-100885supp001.pdf] 

The authors of this paper, a group of international clinical and research experts from different disciplines, aimed to achieve a consensus in terminology for persistent tendon disorders. We ran a Delphi and consensus process that culminated in a face-to-face meeting at the fifth International Scientific Tendinopathy Symposium (ISTS) in Groningen, the Netherlands, on 26 September 2018 (placeholder for sentence about the other two papers and accompanying editorial if they get accepted). Here, we present the resulting consensus statements on terminology for persistent tendon pain.

Our two-stage Delphi design, consensus process consisted of an online survey followed by a face-to-face meeting. One of us (AS) drafted 11 statements about terminology …
Editor's Note: Toll-Like Receptors on Tumor Cells Facilitate Evasion of Immune Surveillance
Authors: Bo Huang, Jie Zhao, Hongxing Li, Kai-Li He, Yibang Chen, Lloyd Mayer, Jay C. Unkeless, Huabao Xiong
Journal: Cancer Research (2019)

The editors were made aware of concerns by a reader regarding potential manipulation of data in [this article][1] ([1][2]). An internal review by the editors determined that lanes 2–4 of the β-actin Western blot image in Fig. 2C (MC26 cells) were rotated and duplicated in lanes 2–4 of the β-
Reconsidering the Association Between Infection-Related Health Care Use and Occurrence of Eating Disorders: Chicken or Egg?—Reply
Authors: Lauren Breithaupt, Ole Köhler-Forsberg, Liselotte Petersen
Journal: JAMA Psychiatry (2019)

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 Psychiatry 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 Psychiatry journal
Safety, tolerability, pharmacokinetics, and pharmacodynamics of the afucosylated, humanized anti-EPHA2 antibody DS-8895a: a first-in-human phase I dose escalation and dose expansion study in patients with advanced solid tumors
Authors: Kohei Shitara, Taroh Satoh, Satoru Iwasa, Kensei Yamaguchi, Kei Muro, Yoshito Komatsu, Tomohiro Nishina, Taito Esaki, Jun Hasegawa, Yasuyuki Kakurai, Emi Kamiyama, Tomoko Nakata, Kota Nakamura, Hayato Sakaki, Ichinosuke Hyodo
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Erythropoietin-producing hepatocellular receptor A2 (EPHA2) is overexpressed on the cell surface in many cancers and predicts poor prognosis. DS-8895a is a humanized anti-EPHA2 IgG1 monoclonal antibody afucosylated to enhance antibody-dependent cellular cytotoxicity activity. We conducted a two-step, phase I, multicenter, open-label study to determine the safety, tolerability, and pharmacokinetics of DS-8895a in patients with advanced solid tumors. <h3>Methods</h3> Step 1 was a dose escalation cohort in advanced solid tumor patients (six dose levels, 0.1–20 mg/kg) to determine Step 2 dosing. Step 2 was a dose expansion cohort in EPHA2-positive esophageal and gastric cancer patients. DS-8895a was intravenously administered every 2 weeks for the duration of the study, with a 28-day period to assess dose-limiting toxicity (DLT). Safety, pharmacokinetics, tumor response, and potential biomarkers were evaluated. <h3>Results</h3> Thirty-seven patients (Step 1: 22, Step 2: 15 [9: gastric cancer, 6: esophageal cancer]) were enrolled. Although one DLT (Grade 4 platelet count decreased) was observed in Step 1 (dose level 6, 20 mg/kg), the maximum tolerated dose was not reached; the highest dose (20 mg/kg) was used in Step 2. Of the 37 patients, 24 (64.9%) experienced drug-related adverse events (AEs) including three (8.1%) with Grade ≥ 3 AEs. Infusion-related reactions occurred in 19 patients (51.4%) but were manageable. All patients discontinued the study (evident disease progression, 33; AEs, 4). Maximum and trough serum DS-8895a concentrations increased dose-dependently. One gastric cancer patient achieved partial response and 13 patients achieved stable disease. Serum inflammatory cytokines transiently increased at completion of and 4 h after the start of DS-8895a administration. The proportion of CD16-positive natural killer (NK) cells (CD3<sup>−</sup>CD56<sup>+</sup>CD16<sup>+</sup>) decreased 4 h after the start of DS-8895a administration, and the ratio of CD3<sup>−</sup>CD56<sup>+</sup>CD137<sup>+</sup> to CD3<sup>−</sup>CD56<sup>+</sup>CD16<sup>+</sup> cells increased on day 3. <h3>Conclusions</h3> Twenty mg/kg DS-8895a infused intravenously every 2 weeks was generally safe and well tolerated in patients (<i>n</i> = 21) with advanced solid tumors. The exposure of DS-8895a seemed to increase dose-dependently and induce activated NK cells. <h3>Trial registration</h3> Phase 1 Study of DS-8895a in patients with advanced solid tumors (NCT02004717; 7 November 2013 to 2 February 2017); retrospectively registered on 9 December 2013.
Evolution of the Cholesterol Biosynthesis Pathway in Animals
Authors: Tingting Zhang, Dongwei Yuan, Jun Xie, Yongxing Lei, Jianguo Li, Gangqi Fang, Ling Tian, Jiacheng Liu, Yingying Cui, Min Zhang, Youli Xiao, Yongzhen Xu, Jianzhen Zhang, Maoyan Zhu, Shuai Zhan, Sheng Li
Journal: Molecular Biology and Evolution (2019)

Cholesterol plays essential roles in animal development and disease progression. Here, we characterize the evolutionary pattern of the canonical cholesterol biosynthesis pathway (CBP) in the animal kingdom using both genome-wide analyses and functional experiments. CBP genes in the basal metazoans were inherited from their last common eukaryotic ancestor and evolutionarily conserved for cholesterol biosynthesis. The genomes of both the basal metazoans and deuterostomes retain almost the full set of CBP genes, while Cnidaria and many protostomes have independently experienced multiple massive losses of CBP genes that might be due to the geologic events during the Ediacaran period, such as the appearance of an exogenous sterol supply and the frequent perturbation of ocean oxygenation. Meanwhile, the indispensable utilization processes of cholesterol potentially strengthened the maintenance of the complete set of CBP genes in vertebrates. These results strengthen both biotic and abiotic roles in the macroevolution of a biosynthesis pathway in animals.
Borrelia miyamotoi infection leads to cross-reactive antibodies to the C6 peptide in mice and men
Authors: J. Koetsveld, A.E. Platonov, K. Kuleshov, A. Wagemakers, D. Hoornstra, W. Ang, S. Szekeres, G.L.A. van Duijvendijk, E. Fikrig, M.E. Embers, H. Sprong, J.W. Hovius
Journal: Clinical Microbiology and Infection (2019)

Borrelia miyamotoi is a relapsing fever Borrelia, transmitted by hard (Ixodes) ticks, which are also the main vector for Borrelia burgdorferi. A widely used test for serodiagnosis of Lyme borreliosis is an enzyme immunoassay (EIA) based on the C6 peptide of the B. burgdorferi sl VlsE protein. We set out to study C6 reactivity upon infection with B. miyamotoi in a large well-characterized set of B. miyamotoi disease (BMD) patient sera and in experimental murine infection.We performed in silico analyses, comparing the C6-peptide to immunodominant B. miyamotoi variable large proteins (Vlps). Next, we determined C6 reactivity in sera from mice infected with B. miyamotoi and in a unique longitudinal set of 191 sera from 46 BMD patients.In silico analyses revealed similarity of the C6 peptide to domains within B. miyamotoi Vlps. Cross-reactivity against the C6 peptide was confirmed in 21 out of 24 mice experimentally infected with B. miyamotoi. Moreover, 35 out of 46 BMD patients had a C6 EIA Lyme index higher than 1.1 (positive). Interestingly, 27 out of 37 patients with a C6 EIA Lyme index higher than 0.9 (equivocal) were negative when tested for specific B. burgdorferi sl antibodies using a commercially available immunoblot.We show that infection with B. miyamotoi leads to cross-reactive antibodies to the C6 peptide. Since BMD and Lyme borreliosis are found in the same geographical locations, caution should be used when relying solely on C6 reactivity testing. We propose that a positive C6 EIA with negative immunoblot, especially in patients with fever several weeks after a tick bite, warrants further testing for B. miyamotoi.
Combination immunotherapy and radiotherapy causes an abscopal treatment response in a mouse model of castration resistant prostate cancer
Authors: Stephanie O. Dudzinski, Brent D. Cameron, Jian Wang, Jeffrey C. Rathmell, Todd D. Giorgio, Austin N. Kirschner
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Prostate cancer is poorly responsive to immune checkpoint inhibition, yet a combination with radiotherapy may enhance the immune response. In this study, we combined radiotherapy with immune checkpoint inhibition (iRT) in a castration-resistant prostate cancer (CRPC) preclinical model. <h3>Methods</h3> Two Myc-CaP tumor grafts were established in each castrated FVB mouse. Anti-PD-1 or anti-PD-L1 antibodies were given and one graft was irradiated 20 Gy in 2 fractions. <h3>Results</h3> In CRPC, a significant increase in survival was found for radiation treatment combined with either anti-PD-1 or anti-PD-L1 compared to monotherapy. The median survival for anti-PD-L1 alone was 13 days compared to 30 days for iRT (<i>p</i> = 0.0003), and for anti-PD-1 alone was 21 days compared to 36 days for iRT (<i>p</i> = 0.0009). Additional treatment with anti-CD8 antibody blocked the survival effect. An abscopal treatment effect was observed for iRT in which the unirradiated graft responded similarly to the irradiated graft in the same mouse. At 21 days, the mean graft volume for anti-PD-1 alone was 2094 mm<sup>3</sup> compared to iRT irradiated grafts 726 mm<sup>3</sup> (<i>p</i> = 0.04) and unirradiated grafts 343 mm<sup>3</sup> (<i>p</i> = 0.0066). At 17 days, the mean graft volume for anti-PD-L1 alone was 1754 mm<sup>3</sup> compared to iRT irradiated grafts 284 mm<sup>3</sup> (<i>p</i> = 0.04) and unirradiated grafts 556 mm<sup>3</sup> (<i>p</i> = 0.21). Flow cytometry and immunohistochemistry identified CD8+ immune cell populations altered by combination treatment in grafts harvested at the peak effect of immunotherapy, 2–3 weeks after starting treatment. <h3>Conclusions</h3> These data provide preclinical evidence for the use of iRT targeting PD-1 and PD-L1 in the treatment of CRPC. Immune checkpoint inhibition combined with radiotherapy treats CPRC with significant increases in median survival compared to drug alone: 70% longer for anti-PD-1 and 130% for anti-PD-L1, and with an abscopal treatment effect. <h3>Precis</h3> Castration-resistant prostate cancer in a wild-type mouse model is successfully treated by X-ray radiotherapy combined with PD-1 or PD-L1 immune checkpoint inhibition, demonstrating significantly increased median overall survival and robust local and abscopal treatment responses, in part mediated by CD8 T-cells.
Clinical and biologic factors associated with time to progression in patients treated by first-line palliative FOLFOX chemotherapy in metastatic colorectal cancer.
Authors: Wieslaw Bal, Michal Jarzab, Ewa Stobiecka, Jadwiga Zebracka, Marta Mianowska, Malgorzata Oczko-Wojciechowska, Dagmara Rusinek, Tomasz Tyszkiewicz, Elzbieta Nowara, Barbara Jarzab, Rafal Tarnawski
Journal: Journal of Clinical Oncology (2012)

e14159 Background: Chemotherapy is the mainstay of treatment patients with metastatic colorectal cancer. The choice of first-line treatment is difficult, especially when cost-effectiveness is the primary constraint. Thus, the optimal use of the clinical and biological factors influencing prognosis would be beneficial. The aim of our study was to identify factors affecting the time to progression (TTP) after first-line FOLFOX chemotherapy in palliative setting. Methods: The study is a retrospective analysis of the series of consecutive patients from large cancer center in south of Poland. The analysis was carried out in the group of 180 patients (37.2% of women), treated between 2007-2010 by FOLFOX-4 regimen and followed-up with the median time of observation 16.3 month. Patients received chemotherapy with median time of 5.0 months, median 10 cycles. Progression was defined as PD by RECIST criteria, death due to disease or sympomatic deterioration. 94 paraffin blocks were available for KRAS testing and gene expression analysis by real-time PCR. Results: The median TTP (counted from beginning of chemotherapy) was 8.6 month, the median TTP from the end of treatment was 3.4 month. We tested the wide range of clinical variables associated with both disease and and patient status by multivariate Cox regression analysis. Two most potent independent negative predictors were identified: the presence of massive lymph node involvement as assessed in CT scan before palliative treatment (&gt;10 nodes enlarged) – hazard ratio 2.82, p&lt;0.001; and tumor grade in histopathological assessment (grade 3 vs. grade 1-2) – hazard ratio 2.76, p=0.003. KRAS status was not prognostic for the TTP; Ki67 gene expression measurement by quantitative RT-PCR did not predict better that the routine assessment of grade. Patients with either grade 3 or lymph node involvement showed significantly shorter TTP (median 5.7 months vs 9.7 months in patients with none of these factors). Conclusions: High tumor grade and the massive involvement of lymph nodes worsen prognosis and shorten time to progression in patients treated with first line palliative FOLFOX chemotherapy.