tbuckley/cabot-search huggingface dataset:
Endemic Scrub Typhus in South America
Authors: Thomas Weitzel, Sabine Dittrich, Javier López, Weerawat Phuklia, Constanza Martinez-Valdebenito, Katia Velásquez, Stuart D. Blacksell, Daniel H. Paris, Katia Abarca
Journal: New England Journal of Medicine (2016)

Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted by the larvae of trombiculid mites. Endemic scrub typhus was originally thought to be confined to the so called "tsutsugamushi triangle" within the Asia-Pacific region. In 2006, however, two individual cases were detected in the Middle East and South America, which suggested that the pathogen was present farther afield. Here, we report three autochthonous cases of scrub typhus caused by O. tsutsugamushi acquired on Chiloé Island in southern Chile, which suggests the existence of an endemic focus in South America. (Funded by the Chilean Comisión Nacional de Investigación Científica y Tecnológica and the Wellcome Trust.).
Translational impact of patient-derived glioblastoma tumorspheres.
Authors: Maurizio Martini, Quintino Giorgio D'Alessandris, Mauro Biffoni, Mariachiara Bucciarelli, Tonia Cenci, Ruggero De Maria, Luigi Maria Larocca, Lucia Ricci Vitiani, Roberto Pallini
Journal: Journal of Clinical Oncology (2016)

2025 Background: Advances from glioma stem-like cell research, though increasing our knowledge on glioblastoma biology, do not influence clinical decisions yet. We conducted this study to explore the translational power of patient-derived glioblastoma tumorsphere cultures, which are known to be enriched for glioma stem-like cells. Methods: The relationship between growth of tumorspheres and outcome of donor patients was investigated in 52 glioblastoma tumors treated with surgical resection followed by radiotherapy and temozolomide. The effect of radiation (6 to 60 Gy) and of temozolomide (3.9 mM to 1 mM) on tumorsphere cell viability was related with the survival of donor patients. Results: Generation of tumorspheres was a highly significant independent factor for poor overall survival and progression-free survival in glioblastoma patients (p < 0.0001 and p = 0.0010, respectively). In general, tumorsphere cells were highly resistant to both radiation and temozolomide. Significantly shorter progression-free survival of the donor patients was associated with LD50 > 12 Gy of matched tumorsphere cultures (p = 0.0484). In addition, the activating phosphorylation level of ATM, Rad17 and to a lesser extent of Chk2 checkpoint proteins, induced by to DNA damage, was higher in the radio-resistance tumorspheres in comparison to the sensitive ones. A direct relationship was found between sensitivity of tumorspheres to temozolomide and patient survival (p = 0.0167 and p = 0.0436 for overall survival and progression-free survival, respectively). Importantly, values for temozolomide IC50 < 50 mM, which are clinically meaningful since the plasma levels achieved in vivo are in this range, identified cases with significantly longer overall survival and progression-free survival (p = 0.0020 and p = 0.0016, respectively). Conclusions: Analysis of tumorsphere cultures does hold translational relevance by predicting the response of the parent tumor to radiation and, above all, to temozolomide. Dissecting the clonogenic core from the proliferating cell progenies in tumorspheres will orient future therapies for drug selection and treatment duration.
Le nouveau variant de la maladie de Creutzfeldt-Jakob
Authors: Dominique Dormont
Journal: Eurosurveillance (2000)

Les travaux de pathologie experimentale menes depuis plus de 10 ans indiquent que des proprietes biologiques de l'agent de l’encephalopathie spongiforme bovine (ESB), facteur etiologique du nouveau variant de la maladie de Creutzfeldt-Jakob (MCJ), sont particulieres. Contrairement au tableau classique de la MCJ, l’agent responsable du nouveau variant de MCJ est largement distribue en peripherie chez l’homme, ce qui impose de reconsiderer la securite des greffes, des medicaments d'origine humaine et bovine, et de la transfusion.
Sedation Interruption for Mechanically Ventilated Patients—Reply
Authors: Sangeeta Mehta, Lisa Burry, Deborah Cook, for the SLEAP Investigators
Journal: JAMA (2013)

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
Abstract POSTER-BIOL-1324A: Loss of DYRK1A promotes transformation of the fallopian tube epithelial cells by oncogenic ras
Authors: Larisa Litovchick, Siddharth Saini, Alison Karst, Lan Hu, Ronny Drapkin, James A. DeCaprio
Journal: Clinical Cancer Research (2015)

Abstract Purpose of the study: High-grade serous ovarian carcinoma (HGSOC) is an aggressive form of ovarian cancer that is characterized by nearly ubiquitous presence of somatic mutations in TP53 gene and widespread gene copy number variations. It is likely that some of these genetic alterations cooperate with TP53 mutations in the pathogenesis of HGSOC; however, the specific roles of individual genes that are frequently gained or lost in HGSOC are only beginning to emerge. We have previously characterised an important role of DYRK1A protein kinase in the ability of human cells to undergo G0/G1 cell cycle arrest and oncogenic-Ras induced senescence. DYRK1A is required for the assembly of the DREAM repressor complex that controls the genes involved in cell cycle progression; this function of DYRK1A could be promoted by LATS kinases of the Hippo tumor suppressor pathway. Analysis of the The Cancer Genome Atlas (TCGA) ovarian dataset revealed loss of heterozygosity (LOH) of DYRK1A gene in over 25% HGSOC tumors. Therefore, we sought to determine whether loss of DYRK1A function can contribute to ovarian carcinogenesis. Experimental Procedures: A panel of human ovarian cancer cell lines was used to determine the levels of DYRK1A and its ability to suppress cell proliferation. The fallopian tube epithelial cell (FTEC) cell lines with stable shRNA knock-down of DYRK1A were used in transformation assays with ovarian cancer-relevant oncogenes. Bioinformatics analysis of the TGCA ovarian oncogenomic dataset was applied to determine whether DYRK1A loss in HGSOC could lead to perturbation of any specific gene expression programs. Summary of Data: It was found that depletion of DYRK1A promotes oncogenic transformation of the FTEC cells expressing mutant p53R175H and oncogenic HRASG12V. Rescue of DYRK1A expression in these cells resulted in arrest of proliferation and senescence. DYRK1A protein levels were reduced in a subset of ovarian cancer cell lines; overexpression of active but not the kinase-inactive DYRK1A suppressed the proliferation of these cells. Gene Set Enrichment Analysis (GSEA) of the TCGA HGSOC dataset revealed upregulated expression of the DREAM target genes in a subset of samples with LOH of both DYRK1A and LATS1 genes. Conclusion: Our findings support the role of DYRK1A as an ovarian tumor supressor and suggest that loss of DYRK1A function in HGSOC could lead to activation of transcription of the genes involved in cell proliferation. Citation Format: Larisa Litovchick, Siddharth Saini, Alison Karst, Lan Hu, Ronny Drapkin, James A. DeCaprio. Loss of DYRK1A promotes transformation of the fallopian tube epithelial cells by oncogenic ras [abstract]. In: Proceedings of the 10th Biennial Ovarian Cancer Research Symposium; Sep 8-9, 2014; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(16 Suppl):Abstract nr POSTER-BIOL-1324A.
Molecular, immune and histopathological characterization of NSCLC based on PDL1 expression on tumor and immune cells and association with response to the anti-PDL1 antibody MPDL3280A.
Authors: Scott N. Gettinger, Marcin Kowanetz, Hartmut Koeppen, Ignacio Ivan Wistuba, Mark Kockx, Edward E. Kadel, Naiyer A. Rizvi, Alexander I. Spira, Fred R. Hirsch, Zachary Boyd, Mitchell Denker, Alexandra Minn, David S. Shames, Alan Sandler, Daniel S. Chen, Priti S. Hegde, David R. Spigel
Journal: Journal of Clinical Oncology (2015)

3015 Background: Programmed death ligand-1 (PD-L1) expression on tumor cells (TC) or tumor-infiltrating immune cells (IC) is associated with OS, PFS and ORR in patients with advanced NSCLC treated with MPDL3280A (Spigel et al, Spira et al, ASCO 2015, pending). In a phase I study, high PD-L1 expression on TC or IC (TC3 or IC3) was associated with a 45% ORR (RECIST v1.1) compared to a 14% ORR in patients without TC3 or IC3 NSCLC (Horn et al, ASCO 2015, pending). Methods: NSCLC specimens from both pre-treatment tumor samples across MPDL3280A trials (n = 498) and a non-trial cohort (n = 706) were evaluated for PD-L1 expression in TC and IC using the SP142 IHC assay. The specimens were scored as TC 0-3 and IC 0-3 based on increasing PD-L1 expression. A subset of samples was further characterized by histopathologic review, gene expression and epigenetic modifications. Results: TC3 or IC3, TC2/3 or IC2/3, and TC1/2/3 or IC1/2/3 tumors represented ≈ 20%, ≈ 40% and ≈ 65% of NSCLC, respectively. TC3 and IC3 tumors represented 2 distinct populations, with < 1% overlap. IC3 tumors demonstrated a high frequency of immune infiltrates within the tumor, stroma and tumor/stroma interface, with higher expression of B- and NK-cell signatures compared to TC3 tumors. In contrast, TC3 tumors featured distinct histopathologic characteristics, with a dense desmoplastic and sclerotic tumor microenvironment. TC3 tumors had a lower frequency of immune infiltrates, which when present were primarily located in the surrounding stroma. In addition, an inverse correlation was seen with PD-L1 promoter methylation and PD-L1 expression in TC, suggesting that PD-L1 may be influenced in part by epigenetic events in TC. Tumors that were TC0 and IC0 (≈ 35% of NSCLC) showed little to no evidence of immune infiltration or activation, consistent with immunologic ignorance. Conclusions: NSCLC can be classified into previously unrecognized, distinct molecular and histopathologic subsets that define sensitivity to treatment with PD-L1 targeted therapy. While expression of PD-L1 on TCs and/or ICs may confer sensitivity to MPDL3280A, the immunologic context and response to treatment may differ.
Long-Term, Cytokine-Free Ex Vivo Expansion of Human Cord Blood Mononuclear Cells Using a Novel Closed-Loop 3D Dual Hollow Fibre Perfused Bioreactor
Authors: Maria Rende, Hugo Macedo, Andrew G. Livingston, Kang Li, Nicki Panoskaltsis, Athanasios Mantalaris
Journal: Blood (2010)
Luis Guillermo Martinez Bustamante
Authors: Emily Spry
Journal: BMJ (2016)

Photo: Milos Petrovic

Luis Guillermo Martinez Bustamante, a Mexican born urologist, was a true global citizen, who contributed to international medical organisations throughout his career, which was sadly cut short when he was murdered by a patient while working at his Slovenian hospital.

Growing up in Monterrey, Mexico, “Memo” and his siblings were introduced to medicine an early age; his mother was a nurse and his father and uncle are physicians, as is his younger brother. Always smart and hardworking, Memo had a talent for languages that took him on a youth exchange trip to Italy, which sparked a love of Mediterranean …
Le projet EUVAC-NET: création et fonctionnement d’un réseau de surveillance communautaire pour les maladies infectieuses à prévention vaccinale
Authors: S Glismann, T Rønne, A E Tozzi
Journal: Eurosurveillance (2001)

Le reseau EUVAC-NET traite de la surveillance epidemiologique et de la lutte contre les maladies a prevention vaccinale. Sous la coordination du SSI au Danemark et en collaboration avec l’ISS en Italie, la rougeole et la coqueluche sont les deux maladies prioritairement ciblees par le reseau. Des projets de collaboration sont en cours avec le PHLS pour la surveillance d’Haemophilus influenzae b. EUVAC-NET regroupe les pays membres de l’Union europeenne, l’Islande, la Norvege et la Suisse.
Pomalidomide Augments Erythropoiesis and Fetal Hemoglobin Production in a Humanized Mouse Model of Sickle Cell Disease
Authors: Steffen E. Meiler, Marlene Wade, Zhong Chen, Preetha Ramalingam, Laure A Moutouhde Parseval, Laura G Corral, Ferdane Kutlar, Abdullah Kutlar
Journal: Blood (2008)
Nadeera Kesera De Silva
Authors: Alastair McKelvey
Journal: BMJ (2016)

Nadeera Kesera De Silva’s sudden untimely death at the age of 34 has denied research into oesophageal cancer a brilliant and gifted mind, and his family and friends a beloved man. Nadeera was midway into his PhD (funded by the National Institute for Health Research, NIHR) into oesophageal adenocarcinoma at the Medical Research Council’s cancer unit in Cambridge. In the 18 months of his research, he’d already presented his work at leading international meetings and published three papers. His most recent research contribution on the therapeutic significance of mutational signatures has been accepted for publication posthumously to Nature Genetics . Nadeera was using whole genome sequencing data from primary tumours to identify new therapeutic pathways. He also developed individualised assays to detect mutations in blood (ctDNA) from patients with preclinical evidence of relapse. He was designing a trial in which his assays …
Association of relapse of FLT3-ITD AML with normal karyotype with internal tandem duplication allelic burden, base-pair insertion length, and NPM1 status.
Authors: Sarah L Sammons, Soren Bentzen, Rawan Faramand, Vu Duong, Michael Tidwell, Edward A. Sausville, Maria R. Baer, Ashkan Emadi
Journal: Journal of Clinical Oncology (2015)

7014 Background: FMS-like tyrosine kinase internal tandem duplication (FLT3-ITD) mutation in normal karyotype AML (NK-AML) is a poor prognostic feature. The prognostic significance of the mutant to wild type allelic ratio and base pair insertion length (bpInsLng) of FLT3-ITD with or without Nucleophosmin (NPM1) mutation remains controversial in this population. Methods: The medical records of 149 patients with NK-AML were reviewed (2007-2014) including subject and disease characteristics, and treatment outcomes. Patients with any cytogenetic abnormality were excluded. Treatment failure was defined as relapsed or refractory disease after chemotherapy regardless of transplant. Death of any causes was considered an event. A FLT3-ITD mutation was detected as the presence of a migrating PCR product larger than the wild-type product (330-bp). ITD allelic burden (AB) was calculated as the ratio of ITD to wild type allele expressed as a percentage. Time to failure was analyzed using the Kaplan-Meier estimate and the Mantel-Cox logrank test. Patients who were alive with no evidence of disease at the last follow-up were treated as censored observations. The protocol was approved by the IRB. Results: The mean age of patients was 58±14 years (range 22-88). FLT3 mutation status was available in 139 cases; 45 (30.2%) carried FLT3-ITD with assessment of AB and bpInsLng available in 29. The median ITD AB was 33% (range 3-433). For the time to failure analysis patients were classified as low or high allelic burden using the median value as the cut point. The median length of the mutant fragment was 372-bp (range 345-500). NPM1 mutation was detected in 38 (26%) patients. In FLT3-ITD population regardless of NPM1 status, patients with AB higher than median value (33%) had significantly higher hazard rate of treatment failure than those with low AB (hazard ratio = 5.4, 95% CI: 1.5-19.5, p = 0.004). ITD bpInsLng lower or higher than the population median value did not predict treatment failure rate (p = 0.6). Conclusions: In patients with FLT3-ITD NK-AML, ITD AB > 33% can significantly predict higher relapse rate irrespective of mutant bpInsLng and NPM1 status.
Measuring Burden of Unhealthy Behaviours Using a Multivariable Predictive Approach: Life Expectancy Lost in Canada Attributable to Smoking, Alcohol, Physical Inactivity, and Diet
Authors: Douglas G. Manuel, Richard Perez, Claudia Sanmartin, Monica Taljaard, Deirdre Hennessy, Kumanan Wilson, Peter Tanuseputro, Heather Manson, Carol Bennett, Meltem Tuna, Stacey Fisher, Laura C. Rosella
Journal: PLoS Medicine (2016)

Behaviours such as smoking, poor diet, physical inactivity, and unhealthy alcohol consumption are leading risk factors for death. We assessed the Canadian burden attributable to these behaviours by developing, validating, and applying a multivariable predictive model for risk of all-cause death.A predictive algorithm for 5 y risk of death-the Mortality Population Risk Tool (MPoRT)-was developed and validated using the 2001 to 2008 Canadian Community Health Surveys. There were approximately 1 million person-years of follow-up and 9,900 deaths in the development and validation datasets. After validation, MPoRT was used to predict future mortality and estimate the burden of smoking, alcohol, physical inactivity, and poor diet in the presence of sociodemographic and other risk factors using the 2010 national survey (approximately 90,000 respondents). Canadian period life tables were generated using predicted risk of death from MPoRT. The burden of behavioural risk factors attributable to life expectancy was estimated using hazard ratios from the MPoRT risk model.The MPoRT 5 y mortality risk algorithms were discriminating (C-statistic: males 0.874 [95% CI: 0.867-0.881]; females 0.875 [0.868-0.882]) and well calibrated in all 58 predefined subgroups. Discrimination was maintained or improved in the validation cohorts. For the 2010 Canadian population, unhealthy behaviour attributable life expectancy lost was 6.0 years for both men and women (for men 95% CI: 5.8 to 6.3 for women 5.8 to 6.2). The Canadian life expectancy associated with health behaviour recommendations was 17.9 years (95% CI: 17.7 to 18.1) greater for people with the most favourable risk profile compared to those with the least favourable risk profile (88.2 years versus 70.3 years). Smoking, by itself, was associated with 32% to 39% of the difference in life expectancy across social groups (by education achieved or neighbourhood deprivation).Multivariable predictive algorithms such as MPoRT can be used to assess health burdens for sociodemographic groups or for small changes in population exposure to risks, thereby addressing some limitations of more commonly used measurement approaches. Unhealthy behaviours have a substantial collective burden on the life expectancy of the Canadian population.
HDL Cholesterol Efflux Does Not Predict Cardiovascular Risk in Hemodialysis Patients
Authors: Chantal Kopecky, Sanam Ebtehaj, Bernd Genser, Christiane Drechsler, Vera Krane, Marlies Antlanger, Johannes J. Kovarik, Christopher C. Kaltenecker, Mojtaba Parvizi, Christoph Wanner, Thomas Weichhart, Marcus D. Säemann, Uwe J.F. Tietge
Journal: Journal of the American Society of Nephrology (2016)

The cardioprotective effect of HDL is thought to be largely determined by its cholesterol efflux capacity, which was shown to inversely correlate with atherosclerotic cardiovascular disease in populations with normal kidney function. Patients with ESRD suffer an exceptionally high cardiovascular risk not fully explained by traditional risk factors. Here, in a post hoc analysis in 1147 patients with type 2 diabetes mellitus on hemodialysis who participated in the German Diabetes Dialysis Study (4D Study), we investigated whether the HDL cholesterol efflux capacity is predictive for cardiovascular risk. Efflux capacity was quantified by incubating human macrophage foam cells with apoB-depleted serum. During a median follow-up of 4.1 years, 423 patients reached the combined primary end point (composite of cardiac death, nonfatal myocardial infarction, and stroke), 410 patients experienced cardiac events, and 561 patients died. Notably, in Cox regression analyses, we found no association of efflux capacity with the combined primary end point (hazard ratio [HR], 0.96; 95% confidence interval [95% CI], 0.88 to 1.06; P =0.42), cardiac events (HR, 0.92; 95% CI, 0.83 to 1.02; P =0.11), or all-cause mortality (HR, 0.96; 95% CI, 0.88 to 1.05; P =0.39). In conclusion, HDL cholesterol efflux capacity is not a prognostic cardiovascular risk marker in this cohort of patients with diabetes on hemodialysis.
Water Concentration Analysis by Raman Spectroscopy to Determine the Location of the Tumor Border in Oral Cancer Surgery
Authors: Elisa M. Barroso, Roeland W.H. Smits, Cornelia G.F. van Lanschot, Peter J. Caspers, Ivo ten Hove, Hetty Mast, Aniel Sewnaik, José A. Hardillo, Cees A. Meeuwis, Rob Verdijk, Vincent Noordhoek Hegt, Robert J. Baatenburg de Jong, Eppo B. Wolvius, Tom C. Bakker Schut, Senada Koljenović, Gerwin J. Puppels
Journal: Cancer Research (2016)

Adequate resection of oral cavity squamous cell carcinoma (OCSCC) means complete tumor removal with a clear margin of more than 5 mm. For OCSCC, 85% of the surgical resections appear inadequate. Raman spectroscopy is an objective and fast tool that can provide real-time information about the molecular composition of tissue and has the potential to provide an objective and fast intraoperative assessment of the entire resection surface. A previous study demonstrated that OCSCC can be discriminated from healthy surrounding tissue based on the higher water concentration in tumor. In this study, we investigated how the water concentration changes across the tumor border toward the healthy surrounding tissue on freshly excised specimens from the oral cavity. Experiments were performed on tissue sections from 20 patients undergoing surgery for OCSCC. A transition from a high to a lower water concentration, from tumor (76% ± 8% of water) toward healthy surrounding tissue (54% ± 24% of water), takes place over a distance of about 4 to 6 mm across the tumor border. This was accompanied by an increase of the heterogeneity of the water concentration in the surrounding healthy tissue. The water concentration distributions between the regions were significantly different (P < 0.0001). This new finding highlights the potential of Raman spectroscopy for objective intraoperative assessment of the resection margins. Cancer Res; 76(20); 5945-53. ©2016 AACR.