tbuckley/cabot-search huggingface dataset:
Oxygen-Enhanced MRI Accurately Identifies, Quantifies, and Maps Tumor Hypoxia in Preclinical Cancer Models
Authors: James P.B. O'Connor, Jessica K.R. Boult, Yann Jamin, Muhammad Babur, Katherine G. Finegan, Kaye J. Williams, Ross A. Little, Alan Jackson, Geoff J.M. Parker, Andrew R. Reynolds, John C. Waterton, Simon P. Robinson
Journal: Cancer Research (2015)

There is a clinical need for noninvasive biomarkers of tumor hypoxia for prognostic and predictive studies, radiotherapy planning, and therapy monitoring. Oxygen-enhanced MRI (OE-MRI) is an emerging imaging technique for quantifying the spatial distribution and extent of tumor oxygen delivery in vivo. In OE-MRI, the longitudinal relaxation rate of protons (ΔR1) changes in proportion to the concentration of molecular oxygen dissolved in plasma or interstitial tissue fluid. Therefore, well-oxygenated tissues show positive ΔR1. We hypothesized that the fraction of tumor tissue refractory to oxygen challenge (lack of positive ΔR1, termed "Oxy-R fraction") would be a robust biomarker of hypoxia in models with varying vascular and hypoxic features. Here, we demonstrate that OE-MRI signals are accurate, precise, and sensitive to changes in tumor pO2 in highly vascular 786-0 renal cancer xenografts. Furthermore, we show that Oxy-R fraction can quantify the hypoxic fraction in multiple models with differing hypoxic and vascular phenotypes, when used in combination with measurements of tumor perfusion. Finally, Oxy-R fraction can detect dynamic changes in hypoxia induced by the vasomodulator agent hydralazine. In contrast, more conventional biomarkers of hypoxia (derived from blood oxygenation-level dependent MRI and dynamic contrast-enhanced MRI) did not relate to tumor hypoxia consistently. Our results show that the Oxy-R fraction accurately quantifies tumor hypoxia noninvasively and is immediately translatable to the clinic.
Shades of T790M: Intratumor Heterogeneity in <i>EGFR</i>-Mutant Lung Cancer
Authors: Eiki Ichihara, Christine M. Lovly
Journal: Cancer Discovery (2015)

Abstract Summary: In the setting of recent exciting clinical results and numerous ongoing trials, Piotrowska and colleagues explore mechanisms of acquired resistance to the mutant-specific EGFR inhibitor rociletinib, and demonstrate that loss of T790M, EGFR amplification, and small-cell transformation are all clinically relevant mechanisms of drug resistance. The authors provide a new paradigm for using quantitative assessment of the EGFR T790M:activation mutation allele frequency ratio to prognosticate responses to rociletinib and also demonstrate that plasma-based assessments of circulating tumor DNA can be used to monitor drug response and the emergence of drug resistance. Cancer Discov; 5(7); 694–6. ©2015 AACR. See related article by Piotrowska et al., p. 713.
A genome-wide survey of DNA methylation in hexaploid wheat
Authors: Laura-Jayne Gardiner, Mark Quinton-Tulloch, Lisa Olohan, Jonathan Price, Neil Hall, Anthony Hall
Journal: Genome biology (2015)

DNA methylation is an important mechanism of epigenetic gene expression control that can be passed between generations. Here, we use sodium bisulfite treatment and targeted gene enrichment to study genome-wide methylation across the three sub-genomes of allohexaploid wheat. While the majority of methylation is conserved across all three genomes we demonstrate that differential methylation exists between the sub-genomes in approximately equal proportions. We correlate sub-genome-specific promoter methylation with decreased expression levels and show that altered growing temperature has a small effect on methylation state, identifying a small but functionally relevant set of methylated genes. Finally, we demonstrate long-term methylation maintenance using a comparison between the D sub-genome of hexaploid wheat and its progenitor Aegilops tauschii. We show that tri-genome methylation is highly conserved with the diploid wheat progenitor while sub-genome-specific methylation shows more variation.
HbA<sub>1c</sub>overtesting and overtreatment among US adults with controlled type 2 diabetes, 2001-13: observational population based study
Authors: Rozalina G McCoy, Holly K Van Houten, Joseph S Ross, Victor M Montori, Nilay D Shah
Journal: BMJ (2015)

What is the extent and effect of excessive testing for glycated hemoglobin (HbA1c) among adults with controlled type 2 diabetes?A retrospective analysis of data from a national administrative claims database included commercially insured individuals in the USA, 2001-13. Study patients were aged 18 years or older, had type 2 diabetes with stable glycemic control (two consecutive tests showing HbA1c<7.0% within 24 months), did not use insulin, had no history of severe hypoglycemia or hyperglycemia, and were not pregnant. HbA1c testing frequency was measured within 24 months after the second (index) HbA1c test, and classified as guideline recommended (≤ 2 times/year), frequent (3-4 times/year), and excessive (≥ 5 times/year). Changes in treatment regimen were ascertained within three months of the index test.Of 31,545 patients in the study cohort (mean age 58 years; mean index HbA1c 6.2%), HbA1c testing frequency was excessive in 6% and frequent in 55%. Despite good glycemic control at baseline, treatment was further intensified by addition of glucose lowering drugs or insulin in 8.4% of patients (comprising 13%, 9%, and 7% of those tested excessively, frequently, and per guidelines, respectively; P<0.001). Compared with guideline recommended testing, excessive testing was associated with treatment intensification (odds ratio 1.35 (95% confidence interval 1.22 to 1.50)). Excessive testing rates remained unchanged in 2001-08, but fell significantly after 2009. The odds of excessive testing was 46% lower in 2011 than in 2001-02. The study population is not representative of all US patients with type 2 diabetes because it was restricted to commercially insured adults with stable and controlled diabetes not receiving insulin treatment. The study design did not capture the underuse of HbA1c testing.In this US cohort of adults with stable and controlled type 2 diabetes, more than 60% received too many HbA1c tests, a practice associated with potential overtreatment with hypoglycemic drugs. Excessive testing contributes to the growing problem of waste in healthcare and increased patient burden in diabetes management.NDS and RGM are funded partly by the Agency for Healthcare Research and Quality (R18HS18339) and AcademyHealth Delivery System Science Fellowship (2013), respectively. No competing interests declared. Additional data are available from mccoy.rozalina@mayo.edu.
HIV-1 virological remission lasting more than 12 years after interruption of early antiretroviral therapy in a perinatally infected teenager enrolled in the French ANRS EPF-CO10 paediatric cohort: a case report
Authors: Pierre Frange, Albert Faye, Véronique Avettand-Fenoël, Erianna Bellaton, Diane Descamps, Mathieu Angin, Annie David, Sophie Caillat-Zucman, Gilles Peytavin, Catherine Dollfus, Jerome Le Chenadec, Josiane Warszawski, Christine Rouzioux, Asier Sáez-Cirión
Journal: The Lancet HIV (2015)
Cross-talk between LOX-1 and PCSK9 in vascular tissues
Authors: Zufeng Ding, Shijie Liu, Xianwei Wang, Xiaoyan Deng, Yubo Fan, Jiwani Shahanawaz, Robert J. Shmookler Reis, Kattayi I. Varughese, Tatsuya Sawamura, Jawahar L. Mehta
Journal: Cardiovascular Research (2015)

Lectin-like ox-LDL receptor-1 (LOX-1) plays an important role in inflammatory diseases, such as atherosclerosis. Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates LDL receptor degradation and influences serum LDL levels. The present study was designed to investigate the possible interaction between PCSK9 and LOX-1. In the first set of experiments, human vascular endothelial cells and smooth muscle cells were studied at baseline and after lipopolysaccharide (LPS) treatment (to create an inflammatory state). Both PCSK9 and LOX-1 were strongly induced by LPS treatment. To define the role of PCSK9 in LOX-1 expression, cells were transfected with siRNA against PCSK9, which resulted in reduced LOX-1 expression and function. On the other hand, cells exposed to recombinant hPCSK9 revealed enhanced LOX-1 expression (P < 0.05). To determine whether LOX-1 also regulates PCSK9, cultured cells in which LOX-1 was knocked down by siRNA expressed less PCSK9, whereas those transfected with hLOX-1 cDNA showed increased PCSK9 expression. The second set of experiments was carried out in wild-type (WT) and gene knockout (KO; LOX-1 and PCSK9) mice; LOX-1 KO mice showed much less PCSK9 (P < 0.05 vs. WT mice). PCSK9-KO mice showed much less LOX-1 (P < 0.05 vs. WT mice). Furthermore, we observed that mitochondrial reactive oxygen species (mtROS) plays an initiating role in the LOX-1/PCSK9 interaction, since mtROS induction enhanced and its inhibition reduced the expression of both PCSK9 and LOX-1. We also found that both LOX-1 and PCSK9 regulate adhesion molecules vascular cell adhesion molecule-1 expression. Finally, oxidized low-density lipoprotein and tumour necrosis factor-α, pro-inflammatory stimuli besides LPS, regulated PCSK9 expression that is mediated by the NF-κB signalling pathway. These observations suggest that LOX-1 and PCSK9 positively influence each other's expression, especially during an inflammatory reaction. mtROS appear to be important initiators of PCSK9/LOX-1 expression.
Replacing<i>DSM</i>Categorical Analyses With Dimensional Analyses in Psychiatry Research
Authors: Cindy M. Yee, Daniel C. Javitt, Gregory A. Miller
Journal: JAMA Psychiatry (2015)

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
Study might be better described as a cost description of screening
Authors: S. Walters
Journal: BMJ (1996)

Censuses and Surveys' omnibus survey shows that only 2 1% of families with children contain children from both a previous and the current partner.3This proportion is low because, although many people change partners, they tend to do so after they have had most of their children.An unknown proportion of families with lone mothers contain two or more children of different fathers; if this proportion were half it would represent an extra 4% of all families with children.This would make the cost of the two screening methods similar.The main reason, however, for preferring couple screening is not economic but medical.4In sequential screening 97% of women who are positive on screening will have a partner who is negative, some of whom will carry a mutation for cystic fibrosis that cannot be detected.These women may resent the anxiety generated by being identified as a carrier, with the resultant increased risk of an affected pregnancy but no diagnostic test available to resolve the uncertainty.This problem is avoided in couple screening, as carriers with non-carrier partners are regarded as being negative on screening.
P-057 A retrospective analysis for patients with HER2 positive gastric cancer who were treated with trastuzumab-based chemotherapy
Authors: J.H. Kang, J.H. Yi, I.G. Hwang, H.K. Ahn, S.I. Lee, Y.-W. Won, J.H. Ji, H.S. Kim, S.Y. Rha, S.Y. Oh, K.E. Lee, T.L. Lim, C.H. Maeng, S.T. Kim, J. Lee, J.O. Park, Y.-S. Park, H.Y. Lim, W.K. Kang, S.H. Park
Journal: Annals of Oncology (2015)
Cetuximab and Radiotherapy Versus Cisplatin and Radiotherapy for Locally Advanced Head and Neck Cancer: A Randomized Phase II Trial
Authors: Stefano Maria Magrini, Michela Buglione, Renzo Corvò, Luigi Pirtoli, Fabiola Paiar, Pietro Ponticelli, Alessia Petrucci, Almalina Bacigalupo, Monica Crociani, Luciana Lastrucci, Stefania Vecchio, Pierluigi Bonomo, Nadia Pasinetti, Luca Triggiani, Roberta Cavagnini, Loredana Costa, Sandro Tonoli, Marta Maddalo, Salvatore Grisanti
Journal: Journal of Clinical Oncology (2015)

Purpose No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy. Patients and Methods Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m 2 once per week or CTX 400 mg/m 2 as loading dose followed by CTX 250 mg/m 2 once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Results The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms. Conclusion CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.
Endobronchial metastasised endometrial stromal sarcoma
Authors: Xi-Qian Xing, Yi Xiao, Yan-Hong Liu, Yan-Li Li, Xu-Wei Wu
Journal: Thorax (2015)

A 43-year-old woman presented with cough and gradually aggravating exertional dyspnoea of 5 months’ duration. She had undergone a hysteromyomectomy for myoma uteri 3 years previously. Chest CT revealed a tightly packed elongated endobronchial soft tissue mass completely obstructing the right intermediate bronchus and a solitary round nodule, 3.6 cm×2.6 cm in size, in the medial basal segment of right lower lobe (figure 1). Bronchoscopy demonstrated total occlusion of the right intermediate bronchus by a smooth and polypoid tumour (see figure …
Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease
Authors: Qing Zhou, Hongying Wang, Daniella M Schwartz, Monique Stoffels, Yong Hwan Park, Yuan Zhang, Dan Yang, Erkan Demirkaya, Masaki Takeuchi, Wanxia Li Tsai, Jonathan J Lyons, Xiaomin Yu, Claudia Ouyang, Celeste Chen, David T Chin, Kristien Zaal, Settara C Chandrasekharappa, Eric P Hanson, Zhen Yu, James C Mullikin, Sarfaraz A Hasni, Ingrid E Wertz, Amanda K Ombrello, Deborah L Stone, Patrycja Hoffmann, Anne Jones, Beverly K Barham, Helen L Leavis, Annet van Royen-Kerkof, Cailin Sibley, Ezgi D Batu, Ahmet Gül, Richard M Siegel, Manfred Boehm, Joshua D Milner, Seza Ozen, Massimo Gadina, JaeJin Chae, Ronald M Laxer, Daniel L Kastner, Ivona Aksentijevich
Journal: Nature Genetics (2015)
Reply to A. Oguz et al
Authors: Ciara C. O’Sullivan, Eileen Holmes, Christine Campbell, Ian Bradbury, Jo Anne Zujewski, Richard D. Gelber
Journal: Journal of Clinical Oncology (2015)

We appreciate the interest of Oguz et al in our meta-analysis of five large adjuvant trials to compare the efficacy of chemotherapy and trastuzumab versus chemotherapy alone in patients with small human epidermal growth factor 2 (HER2)–positive breast cancers of 2 cm or smaller. Their questions are important, because they relate to the potential to reduce the intensity of standard treatment of patients with small HER2-positive breast cancers. We agree that there are limited prospective data about the prognosis of T1abN0 HER2-positive tumors. Few of these patients were included in the randomized adjuvant trastuzumab trials because of concerns about potential cardiotoxicity with trastuzumab in patients perceived to be at low risk of recurrence. Therefore, we cannot provide additional prognostic information for patients with T1abN0 HER2-positive breast cancers. Such information must be obtained from retrospective series or prospective cohort studies. In addition, the selection of chemotherapy regimens for patients with small HER2-positive tumors is important, and we observed heterogeneous outcomes among the trials for the hormone receptor (HR)–negative cohort, which may be due in part to the difference in timing of chemotherapy. Thus, we hesitate to make any additional conclusions, because patients were not randomly assigned to chemotherapy regimens. Finally, we agree that additional analyses of retrospective series and prospective cohort studies will be important to identify additional patient subgroups that may warrant less (or more) intensive treatments. For example, in a previous meta-analysis of five of the adjuvant randomized trastuzumab trials, we identified a subgroup of patients with HR-positive, HER2-positive tumors of 2 cm or smaller, and one or no positive lymph nodes, who had excellent prognoses when treated with trastuzumab and chemotherapy with or without endocrine therapy; the 5-year disease-free survival was 91%, and the 5-year overall survival was 97%. These results, we hope, will provide a benchmark for the design of future trials to evaluate less aggressive treatment approaches.
Radial Versus Femoral Access in Invasively Managed Patients With Acute Coronary Syndrome
Authors: Giuseppe Andò, Davide Capodanno
Journal: Annals of Internal Medicine (2015)

Background: Studies in patients with acute coronary syndrome (ACS) undergoing invasive management showed conflicting conclusions regarding the effect of access site on outcomes. Purpose: To summarize evidence from recent, high-quality trials that compared clinical outcomes occurring with radial versus femoral access in invasively managed adults with ACS. Data Sources: English-language publications in MEDLINE, EMBASE, and Cochrane databases between January 1990 and August 2015. Study Selection: Randomized trials of radial versus femoral access in invasively managed patients with ACS. Data Extraction: Two investigators independently extracted the study data and rated the risk of bias. Data Synthesis: Of 17 identified randomized trials, 4 were high-quality multicenter trials that involved a total of 17 133 patients. Pooled data from the 4 trials showed that radial access reduced death (relative risk [RR], 0.73 [95% CI, 0.59 to 0.90]; P = 0.003), major adverse cardiovascular events (RR, 0.86 [CI, 0.75 to 0.98]; P = 0.025), and major bleeding (RR, 0.57 [CI, 0.37 to 0.88]; P = 0.011). Radial procedures lasted slightly longer (standardized mean difference, 0.11 minutes) and had higher risk for access-site crossover (6.3% vs. 1.7%) than did femoral procedures. Limitation: Heterogeneity in outcomes definitions and potential treatment modifiers across studies, including operator experience in radial procedures and concurrent anticoagulant regimens. Conclusion: Compared with femoral access, radial access reduces mortality, major adverse cardiovascular events, and major bleeding in patients with ACS undergoing invasive management. Primary Funding Source: None. (PROSPERO registration number: CRD42015022031)
Genetic signature of breast cancer with lymphangitic spread to the chest wall: Results from a randomized phase II study combining bevacizumab with oral vinorelbine plus capecitabine (BEVIX).
Authors: G. Curigliano, M. Alkalay, M. A. Locatelli, L. Fumagalli, S. Giudici, F. Bertolini, V. Galimberti, G. Viale, F. Nole, A. Goldhirsch
Journal: Journal of Clinical Oncology (2010)

1078 Background: No surrogate biomarkers have been identified to predict response to an antiangiogenic agent for cancer treatment. Methods: We collected basal tissue samples from patients with lymphangitic spread to the chest wall with or without metastases, treated with bevacizumab in combination with sequential, and/or concurrent oral vinorelbine plus capecitabine. Gene expression profiling was performed using Affymetrix HG-U133 Plus 2.0 arrays. Data were analyzed using Partek Genomic Suite 6.4 and GeneSpring 7.0. Normal breast tissue was used as control. Results: Out of 46 planned, 45 patients have been enrolled. The data here reported are related to 20 patients included in the concurrent treatment arm. We observed 8 PR (40%) and 11 SD (55%). Global gene expression was analyzed in tumor samples from 18 patients bearing a triple negative phenotype. Compared with normal breast samples and breast tumors of other subtypes, this cohort displayed a specific gene expression profile, similar to that described for the basal-like subtype, including high expression levels of several cytokeratins, Aurora kinase A, Cyclin E and others. This profile did not include genes previously reported as differentially expressed in inflammatory breast cancers. We identified a set of genes which expression correlates with response to therapy. Conclusions: BEVIX is an active treatment for patients with breast cancer with lymphangitic spread to the chest wall. These tumors are characterized by a gene expression pattern similar to that of basal-like breast cancers. A set of genes whose expression levels predict response to treatment with bevacizumab in association to vinorelbine and capecitabine has been identified. The validity of this expression signature is currently being assessed. Supported by a grant of the Associazione Italiana per la Ricerca sul Cancro (AIRC) ad the Roche Italy. No significant financial relationships to disclose.
A Digital Dermoscopy Follow-up Illustration and a Histopathologic Correlation for Angulated Lines in Extrafacial Lentigo Maligna
Authors: Alexia Vanden Daelen, Ingrid Ferreira, Liliane Marot, Isabelle Tromme
Journal: JAMA Dermatology (2015)

The diagnosis of extrafacial lentigo maligna can be a challenge because the dermoscopic features are not well described. These features can share some of the criteria of superficial spreading melanoma and some of facial lentigo maligna; however, these features are often absent. A new dermoscopic pattern has recently been described as forming angulated lines.We report 4 cases of extrafacial lentiginous lesions in 3 patients in whom straight angulated lines have been observed as the only key for diagnosis. This is the first time, to our knowledge, that these lines were seen in the follow-up by digital dermoscopy during a lapse time of a few months. This morphologic change led to the excision of the lesion. The pathologic diagnosis of lentigo maligna was established in each case. Moreover, a histologic correlation of these straight angulated lines is documented.Angulated lines could be considered as a new warning sign during the follow-up of extrafacial lentigo. More studies are required to establish the sensitivity and specificity of this newly described dermoscopic feature.