tbuckley/cabot-search huggingface dataset:
3D association of ER, PR and HER2 to aid sub-grouping of breast cancer patients
Authors: J. Zhang, J. Lv, G. Yu, L. Li, Y. Zhang, F. Tang
Journal: Annals of Oncology (2019)

Background: The success of molecular subtyping leads to numerous prognostic algorithms for personalized treatment of breast cancer patients. However, until now, immunohistochemistry (IHC)-based subtyping method still plays a dominant role in daily clinical practice. The discordance between mRNA based and protein based method is well recognized in the field. In this study, we aimed to reconcile these two types of subtyping methods by measuring ER, PR, Her2 and Ki67 as absolute and continuous variables in 1048 Formalin Fixed Paraffin Embedded (FFPE) specimens. Methods: Total protein from 2X15 mm FFPE slices provided by local hospitals sequentially and non-selectively were extracted and used for Quantitative Dot Blot (QDB) analysis using the same antibodies for IHC analysis, including SP1 for ER, 1E2 for PR, EP3 and 4b5 for Her2, and MIB1 and UMAB107 for Ki67. Purified recombinant proteins, either prepared in house, or acquired commercially, were used as protein standard to achieve absolute quantification of these biomarkers. Results: When using absolute and quantitative levels of ER, PR and Her2 as X, Y, and Z axes, we found the samples naturally segregated into three distinct groups. Those samples with high Her2 levels were exclusively wrapped around Z axis (Her2 group), while samples with ER or PR overexpression were spread at the ER and PR floor (HR group). This pattern persisted until a small block with ER < 0.2 nmole/g, PR < 0.8 nmole/g and Her2 <0.3 nmole/g can be observed with samples distributed inside randomly. We named this small block as corner group. Interestingly, when using 0.3 nmole/g as cutoff for Her2, we observed 93.6% concordance between results from QDB and 786 IHC scores provided from local hospitals. The corner group was also found to be most heterogeneous, with those samples with highest Ki67 levels exclusively accumulated within this group. Conclusions: We believe what we observed of the 3D distribution of samples by ER, PR and Her2 levels is the projection at protein levels of various molecular subtypes. Thus, the absolute and quantitative measurement of biomarkers at protein level may provide a simple, reliable 3D prognostic tool to incorporate what we have learned at both protein and mRNA level to be used in personalized treatment of breast cancer patients. Legal entity responsible for the study: Yantai Quanticision Diagnostics, Inc. Funding: Quanticision Diagnostics, Inc & Binzhou Medical University of China. Disclosure: J. Zhang, J. Lv Y. Zhang, F. Tang: Employee: Yantai Quanticision Diagnostics, Inc & Quanticision Diagnostics, Inc. who owned or has filed patent application for QDB plate and QDB method to measure biomarkers in FFPE specimens. All other authors have declared no conflicts of interest.
Treachery on the Rocks in the Pediatric Intensive Care Unit
Authors: Martí Pons-Odena, Alberto Medina, Vicent Modesto-Alapont
Journal: JAMA Pediatrics (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 Pediatrics 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 Pediatrics journal
Abstract 10068: Cardiorespiratory Fitness Modifies the Association Between Leisure-Time Physical Activity and the Risk of Sudden Cardiac Death Among Middle-Aged Men
Authors: Magnus J Hagnäs, Timo A Lakka, Sudhir Kurl, Timo H Mäkikallio, Kai Savonen, Rainer Rauramaa, Jari A Laukkanen
Journal: Circulation (2015)

Aim: We investigated whether cardiorespiratory fitness (CRF) modifies the association between leisure-time physical activity (LTPA) and the risk of sudden cardiac death (SCD) among middle-aged men. Methods: The participants were a population sample of 2656 Finnish men aged 42-60 years at baseline. The mean follow-up time was 21 years. LTPA was assessed with a questionnaire and was expressed in kilocalories per day (kcal/d). CRF was measured directly using respiratory gas analysis during maximal exercise test and was expressed in metabolic equivalents (METs). The participants were divided into following 4 groups using the lowest tertiles of CRF (7.9 METs) and LTPA (&lt; 191 kcal/d) as cut-offs: high CRF and LTPA, high CRF and low LTPA, low CRF and high LTPA and low CRF and LTPA. The risk of SCD was analysed using Cox regression models adjusted for age, smoking, alcohol consumption, body mass index, systolic blood pressure, low density lipoprotein cholesterol, C-reactive protein, prevalent type 2 diabetes and prevalent coronary heart disease. Results: Men with low CRF and low LTPA had a 1.8 (95% confidence interval 1.3-2.6, p=0.001) times higher risk of SCD than men with high CRF and high LTPA. The amount of LTPA did not significantly alter the risk of SCD among men with high CRF. Figure 1 shows the cumulative survival from SCD in the 4 groups. Conclusions: Our study shows that men with low CRF and low LTPA have increased risk of SCD. This finding emphasizes increasing LTPA to prevent SCD among men and particularly among those with low CRF.
Airway collagen conformational changes during acute bronchoconstriction in guinea-pig: a histochemical and ultrastuctural study
Authors: T. Mauad, E. A. Leick-Maldonado, E. G. Caldini, I. F. L. Tibério, G. S. Montes, Mílton de Arruda Martins, Paulo Hilário Nascimento Saldiva
Journal: American Journal of Respiratory and Critical Care Medicine (1996)
IMAGING CHARACTERISTICS RELATED TO DIFFICULTY OF CANNULATION IN ENDOSCOPIC RETROGRADE CHOLANGIO-PANCREATOGRAPHY
Authors: JM Lee, HS Lee, S Jang, HJ Jeon, SJ Choi, SH Kim, HS Choi, ES Kim, B Keum, YT Jeen, HJ Chun, CD Kim
Journal: Endoscopy (2019)

The aim of this study was to investigate the imaging characteristics and clinical factors related to difficulty of cannulation in endoscopic retrograde cholangio-pancreatography (ERCP).
DIAGNOSTIC PERFORMANCE OF CRYSTAL VIOLET CHROMOENDOSCOPY – RESULTS FROM A GERMAN CENTER
Authors: A Ebigbo, C Römmele, A Probst, G Braun, S Gölder, C Vollmer, T Weber, L Neuhaus, H Messmann
Journal: Endoscopy (2019)

The precise characterization of colorectal neoplasms is necessary because it influences the choice of treatment. Kudo's pit pattern classification has shown excellent diagnostic performance. In Germany, data on the use of crystal violet (CV) solution to describe the surface pattern of colorectal lesions is lacking. In this study, we describe the diagnostic outcomes of CV-chromoendoscopy on colorectal neoplasms.
No link between male infertility and HEV genotype 3 infection
Authors: Thomas Horvatits, Domenica Varwig-Janssen, Julian Schulze zur Wiesch, Rabea Lübke, Svenja Reucher, Sebastian Frerk, Marylyn M Addo, Stefan W Schneider, Ansgar W Lohse, Marc Luetgehetmann, Sven Pischke
Journal: Gut (2019)

With great interest we read the article ‘High prevalence of hepatitis E virus in semen of infertile male and causes testis damage’ recently published by Huang et al in GUT.1 The authors report a strikingly high rate of 28% of hepatitis E virus (HEV) RNA PCR positivity (all of them genotype 4 hour) in semen from infertile men from the Chinese Kunming region (n=185) and they could demonstrate HEV antigens in the testes and HEV-RNA in semen of acutely infected macaques.1 This finding is without precedence and has never been reported. Pathophysiologically, the high rate of HEV detection in semen of infertile men could only be explained by HEV persistence beyond the blood-testis barrier.

Duration of PCR positivity in semen has not been assessed by the authors neither in the infertile man nor in the macaques. Thus, it remains unclear …
Abstract 12519: Regulation of Cardiac Fibroblast Phenotype by Scleraxis
Authors: Rushita Bagchi, Patricia Roche, Ronen Schweitzer, Michael P Czubryt
Journal: Circulation (2014)

Cardiac fibroblasts constitute the primary extracellular matrix synthesis machinery in the myocardium. Activation of fibroblasts into a hyper-synthetic and contractile phenotype potentiates fibrosis, impairs cardiac function and contributes to heart failure. Our laboratory previously reported that the transcription factor scleraxis regulates human cardiac collagen Iα2 expression and has shown its up-regulation in the post-infarct scar. Here we demonstrate a novel regulatory role for scleraxis in governing cardiac fibroblast function and phenoconversion. Cell contractility assays using collagen gels demonstrated the abrogation of pro-fibrotic TGF-β-mediated contractility of myofibroblasts in response to scleraxis knockdown. The de novo expression of α-smooth muscle actin (αSMA) and its incorporation into stress fibers is a key feature of myofibroblasts - key causative cells of fibrosis. Scleraxis over-expression in isolated primary cardiac fibroblasts induced αSMA gene expression and stress fiber formation, and rescued the αSMA loss observed in cardiac fibroblasts from scleraxis null mice. Luciferase reporter assays demonstrated a significant transactivation of the αSMA gene promoter by scleraxis. Mutation analysis revealed that scleraxis interacts with two E-boxes within the αSMA promoter, a finding confirmed by chromatin immunoprecipitation of scleraxis in primary cardiac fibroblasts. An increase in scleraxis binding to the αSMA promoter was observed in cardiac myofibroblasts compared to fibroblasts, and also in response to TGF-β, further supporting a direct role of scleraxis in regulation of myofibroblast αSMA expression and its contractile phenotype. Gel shift assays also confirmed the direct interaction of scleraxis with E-boxes within the αSMA gene promoter. Our data indicates that scleraxis plays a required role in cardiac fibroblast phenotype and contractile function. Taken in context with our finding that scleraxis regulates expression of multiple extracellular matrix components, including fibrillar collagens, our data reveals that scleraxis exerts broad and potent pro-fibrotic effects on cardiac fibroblast form and function, and may thus represent a novel target for fibrosis therapy.
Determinants of the decline in mortality from acute stroke in England: linked national database study of 795 869 adults
Authors: Olena O Seminog, Peter Scarborough, F Lucy Wright, Mike Rayner, Michael J Goldacre
Journal: BMJ (2019)

Abstract Objectives To study trends in stroke mortality rates, event rates, and case fatality, and to explain the extent to which the reduction in stroke mortality rates was influenced by changes in stroke event rates or case fatality. Design Population based study. Setting Person linked routine hospital and mortality data, England. Participants 795 869 adults aged 20 and older who were admitted to hospital with acute stroke or died from stroke. Main outcome measures Stroke mortality rates, stroke event rates (stroke admission or stroke death without admission), and case fatality within 30 days after stroke. Results Between 2001 and 2010 stroke mortality rates decreased by 55%, stroke event rates by 20%, and case fatality by 40%. The study population included 358 599 (45%) men and 437 270 (55%) women. Average annual change in mortality rate was −6.0% (95% confidence interval −6.2% to −5.8%) in men and −6.1% (−6.3% to −6.0%) in women, in stroke event rate was −1.3% (−1.4% to −1.2%) in men and −2.1% (−2.2 to −2.0) in women, and in case fatality was −4.7% (−4.9% to −4.5%) in men and −4.4% (−4.5% to −4.2%) in women. Mortality and case fatality but not event rate declined in all age groups: the stroke event rate decreased in older people but increased by 2% each year in adults aged 35 to 54 years. Of the total decline in mortality rates, 71% was attributed to the decline in case fatality (78% in men and 66% in women) and the remainder to the reduction in stroke event rates. The contribution of the two factors varied between age groups. Whereas the reduction in mortality rates in people younger than 55 years was due to the reduction in case fatality, in the oldest age group (≥85 years) reductions in case fatality and event rates contributed nearly equally. Conclusions Declines in case fatality, probably driven by improvements in stroke care, contributed more than declines in event rates to the overall reduction in stroke mortality. Mortality reduction in men and women younger than 55 was solely a result of a decrease in case fatality, whereas stroke event rates increased in the age group 35 to 54 years. The increase in stroke event rates in young adults is a concern. This suggests that stroke prevention needs to be strengthened to reduce the occurrence of stroke in people younger than 55 years.
Vastus medialis obliquus (VMO) retraining or graduated loading programme for patellofemoral pain: different paradigm with similar results?
Authors: Kay M Crossley, Sallie M Cowan
Journal: British Journal of Sports Medicine (2019)

Our early research identified imbalance in vasti activation in people with patellofemoral pain (PFP) and that vasti retraining programmes could restore motor control and improve outcomes.1 2 For around a decade, many patients benefitted from this research and its translation into practice. However, it might be time to revisit this paradigm.

Consistent evidence from cadaver and modelling studies confirm that imbalance in medial (vastus medialis obliquus (VMO)) and lateral (vastus lateralis (VL)) quadriceps’ forces affect patellofemoral stress (ie, if the medial vasti force is relatively lower, there will be greater lateral patellofemoral stress).3 The evidence supporting an imbalance in vasti motor control is less clear. Although VMO onset delay is evident in many people with PFP, it is not present in everyone with this condition.4 5 Additionally, we have no evidence that altered vasti onset timing changes the muscle forces, and we cannot measure patellofemoral force in vivo. While the clinical relevance of subtle medial vasti onset delays (<20 …
Tornwaldt’s Cyst
Authors: Chien-Yu Huang, Bor-Hwang Kang
Journal: New England Journal of Medicine (2019)

A 60-year-old man presented with worsening nasal obstruction and postnasal drip. Nasopharyngoscopy showed a smooth, pink, cystic mass in the midline of nasopharynx, consistent with Tornwaldt’s cyst.
The predictive value of NHS PREDICT for triple negative breast cancer
Authors: M. Sobočan, U. Belak, N. Sikošek Čas, N. Kozar, K.K. Krajnc, I. Takac, D. Arko
Journal: Annals of Oncology (2019)

Background: Tools to support clinical decision making regarding breast cancer (BC) are becoming more available to clinicians. NHS PREDICT is a freely available web-based tool for prognostication and assistance in BC management. Recent research shows doubt in using the tool for BC subtypes. There is fear over the possibility of over- or undertreatment of patients. Methods: Ninety-four patients regardless of their ER (estrogen receptor), PR (progesterone receptor) and HER2 (human epidermal growth factor receptor 2) status were included in this study. Through using the platform NHS PREDICT 2.0 we evaluated through the pilot study the prediction of patients with newly diagnosed breast cancer. We evaluated the prediction of 10-year survival, benefit of surgical treatment, treatment with hormonal therapy, transtuzumab treatment and benefit of chemotherapy. Results: The median age at diagnosis was 60.10 years (SD 14.4). Patients were classified according to hormonal status: i) ER+ BC (n = 69), ii) ER+ and HER2+ BC (n = 8), iii) ER-, but HER2+ BC (n = 7) and iv) triple negative BC (n = 10). Overall 10-year survival for ER+, HER2- was 86.1 % (benefit of adjuvant chemotherapy adding 2.8 %), for ER- and HER2+ 83.7% (benefit of adjuvant chemotherapy adding 7.0 %) and for TNBC 77.4% (benefit of adjuvant chemotherapy 5.5 %). Overall data is represented in Table.Table216P Predict output on breast cancer subtypesBreast cancer subtypes10-year age adjusted overall survivalMean age at time of diagnosisBenefit of surgical treatment on survivalBenefit of hormonal therapy on survivalBenefit of chemotherapy on survivalBenefit of transtuzumab on survivalER+, PR+, Her2- (n = 69)86.1 (SD 15.1)58.7 (SD 13.2)73.32 (SD 16.3)3.71 (SD 2.8)2.8 (SD 2.1)/ER+, PR+, Her2 + (n = 8)88.9 (SD 11.0)57.6 (SD 12.1)64.9 (SD 20.9)6.5 (SD 3.7)4.7 (SD 2.8)3.6 (SD 2.1)ER-, PR-, Her2 + (n = 7)83.7 (SD 18.4)56.3 (SD 19.9)50.9 (SD 23.5)/7.0 (SD 1.7)7.0 (SD 2.0)ER-, PR-, Her2- (n = 10)77.4 (SD 21.8)62.5 (SD 17.7)52.9 (SD 23.2)/5.5 (SD 2.4)/ Open table in a new tab Conclusions: This pilot analysis estimates that overall survival was in accordance to available treatment data. TNBC 10-year survival was appropriate (decreased), but the tool estimated very low chemotherapy benefits for TNBC patients in comparison to other patient groups thus posing the risk of patient undertreatment. Legal entity responsible for the study: The University Medical Center Maribor. Funding: Supported through the Slovenian Research Agency Project (J3-9272). Disclosure: All authors have declared no conflicts of interest.
Estimated Quality of Life and Economic Outcomes Associated With 12 Cervical Cancer Screening Strategies
Authors: George F. Sawaya, Erinn Sanstead, Fernando Alarid-Escudero, Karen Smith-McCune, Steven E. Gregorich, Michael J. Silverberg, Wendy Leyden, Megan J. Huchko, Miriam Kuppermann, Shalini Kulasingam
Journal: JAMA Internal Medicine (2019)

Many cervical cancer screening strategies are now recommended in the United States, but the benefits, harms, and costs of each option are unclear.To estimate the cost-effectiveness of 12 cervical cancer screening strategies.The cross-sectional portion of this study enrolled a convenience sample of 451 English-speaking or Spanish-speaking women aged 21 to 65 years from September 22, 2014, to June 16, 2016, identified at women's health clinics in San Francisco. In this group, utilities (preferences) were measured for 23 cervical cancer screening-associated health states and were applied to a decision model of type-specific high-risk human papillomavirus (hrHPV)-induced cervical carcinogenesis. Test accuracy estimates were abstracted from systematic reviews. The evaluated strategies were cytologic testing every 3 years for women aged 21 to 65 years with either repeat cytologic testing in 1 year or immediate hrHPV triage for atypical squamous cells of undetermined significance (ASC-US), cytologic testing every 3 years for women age 21 to 29 years followed by cytologic testing plus hrHPV testing (cotesting), or primary hrHPV testing alone for women aged 30 to 65 years. Screening frequency, abnormal test result management, and the age to switch from cytologic testing to hrHPV testing (25 or 30 years) were varied. Analyses were conducted from both the societal and health care sector perspectives.Utilities for 23 cervical cancer screening-associated health states (cross-sectional study) and quality-adjusted life-years (QALYs) and total costs for each strategy.Utilities were measured in a sociodemographically diverse group of 451 women (mean [SD] age, 38.2 [10.7] years; 258 nonwhite [57.2%]). Cytologic testing every 3 years with repeat cytologic testing for ASC-US yielded the most lifetime QALYs and conferred more QALYs at higher costs ($2166 per QALY) than the lowest-cost strategy (cytologic testing every 3 years with hrHPV triage of ASC-US). All cytologic testing plus hrHPV testing (cotesting) and primary hrHPV testing strategies provided fewer QALYs at higher costs. Adding indirect costs did not change the conclusions. In sensitivity analyses, hrHPV testing every 5 years with genotyping triage beginning at age 30 years was the lowest-cost strategy when hrHPV test sensitivity was markedly higher than cytologic test sensitivity or when hrHPV test cost was equated to the lowest reported cytologic test cost ($14).Cytologic testing every 3 years for women aged 21 to 29 years with either continued cytologic testing every 3 years or switching to a low-cost hrHPV test every 5 years confers a reasonable balance of benefits, harms, and costs. Comparative modeling is needed to confirm the association of these novel utilities with cost-effectiveness.
Particularités de la cholangiopancréatografie rétrograde endoscopique (CPRE) chez le sujet âgé
Authors: M Yakoubi, M Medhioub, O Gharbi, L Hamzaoui, M Mahmoudi, A Khsiba, MM Azouz
Journal: Endoscopy (2019)

L'abord endoscopique des pathologies du carrefour bilio-pancréatique est à privilégier par rapport à la chirurgie chez le sujet âgé. Cependant, les données concernant sa faisabilité et ses particularités restent limitées.
The Proliferation of Reports on Clinical Scoring Systems
Authors: Douglas W. Challener, Larry J. Prokop, Omar Abu-Saleh
Journal: JAMA (2019)

This Viewpoint charts the rise in publications describing risk prediction tools, such as the FRAX, CHADS2, and SOFA scores, and discusses the implications of using algorithms for clinical decisions in the absence of evidence about the effects of the tools on patient care and outcomes.