tbuckley/cabot-search huggingface dataset:
Contribution of extended family history in assessment of risk for breast and colon cancer.
Authors: Benjamin Lev Solomon, Tiffany Rounds, Marie Wood
Journal: Journal of Clinical Oncology (2014)

1564 Background: Family history is important for identifying candidates for advanced screening and referral for cancer genetic counseling. We identified the percentage of individuals who would not receive recommended screening or referral if only a 1st degree family history was obtained. Methods: Family histories were obtained from 626 women getting mammography at the University of Vermont between 5/00-5/01 using a validated questionnaire. ACS guidelines were used to determine eligibility for advanced breast and colon cancer screening. Eligibility for referral for genetic counseling for hereditary breast and colon cancer was determined using FHS-7 and Amsterdam II screening criteria, respectively. Results: 499 histories were reviewed (127 histories were excluded due to incorrect completion, personal history of cancer or no family history of cancer). For high risk breast cancer screening, 8 individuals met guidelines using 1st degree family history with an additional 10 meeting criteria when family history was extended. For high risk colon cancer screening, 50 individuals met criteria using 1st degree family history with an additional 12 meeting criteria when the family history was extended. Using only 1st degree family history misses candidates for advanced screening: 55% for breast and 24% for colon cancer screening. 63 individuals met criteria for counseling for hereditary breast cancer using 1st degree family history with an additional 51 and 52 when 2nd and 3rd degree family history were included, respectively. Ten individuals met guidelines for referral for counseling for hereditary colon cancer using 1st degree family history with 21 additional meeting criteria when including 2nd degree family history. 62% of candidates for genetic counseling for hereditary breast cancer and 67% of candidates for hereditary colon cancer were missed when using only 1st degree family history. Conclusions: This is one of the first studies to demonstrate that 1st degree family history alone is not adequate for identification of all candidates for high risk screening and referral for genetic counseling for hereditary breast and colon cancer syndromes. Given our small sample, larger studies are required to confirm these findings.
The Impact of a Bayesian Penalized Likelihood Reconstruction Algorithm on the Evaluation of Indeterminate Pulmonary Nodules by Dual–Time Point 18F-FDG PET/CT
Authors: Tiago Sampaio Vieira, Diogo Borges Faria, Fernando Azevedo Silva, Francisco Pimentel, José Pereira de Oliveira
Journal: Clinical Nuclear Medicine (2017)

We present the case of a patient with history of colon cancer, referred for the evaluation of indeterminate pulmonary nodules by F-FDG PET/CT. A dual-time point protocol was performed, and images were reconstructed using VUE Point HD and a Bayesian-penalized likelihood reconstruction algorithm (Q.Clear). Visually, the quality of the images was considered better when Q.Clear was used with β value of 200, uptake in the smallest nodule (7 mm) was clearly visible only with Q.Clear reconstruction, and uptake in the smaller nodules was best defined in the delayed time point acquisition. Quantitative parameters were also higher for Q.Clear.
GPs use pen and paper after IT systems are shut down as precaution
Authors: Ingrid Torjesen
Journal: BMJ (2017)

Many general practices had no access to their IT systems over the weekend because they had been told to shut down their computers as a precaution, rather than because they had been infected by the “ransomware” that paralysed the IT systems of dozens of hospital trusts in England and Scotland.1

NHS Digital and NHS England would not say how many practices in England had been infected by the virus that struck on 12 May or say where they were located. In Scotland, health boards confirmed that a few practices had been hit by the virus, including two in NHS Dumfries and Galloway and two in NHS Grampian.

An NHS Grampian spokeswoman said that the attacks had had only a minor impact on the two practices affected and that no computer that stored clinical information had been compromised. “We are keen from a security point of view not to go into too much detail,” she said.

Emma …
Abstract 200: Novel Cardiac Dyssynchrony Metrics Based on Ultrasound Images and Fibrosis
Authors: Greg Shearer, Todd Hanson, Julie Eclov, Sam Courtier, Steve Ortmeier, Dan Ewert
Journal: Circulation Research (2015)

Ventricular stiffening is a component of heart failure with preserved ejection fraction. This study focuses on building a dyssynchrony metric based on ultrasound images obtained from normal and fibrotic mouse hearts. The objective is to evaluate the association between regional fibrosis and ventricular wall dynamics as an indicator for the gradient of cardiac dyssynchrony. Ultrasound images were obtained from a previous study in which mice were given thoracic aortic constriction to induce heart failure that included ventricular stiffening and fibrosis. Ultrasound video (frame rate 4.3ms) along the short axis of the mouse heart was captured using commercial software. On each short axis frame, six points were selected and traced on the endocardial wall. Each radial displacement pair is plotted in a loop diagram against one another in 15 unique combinations. A loop whose points are close to the ideal line u = v corresponds to synchronous wall movement, while the area enclosed by the loop is proportional to time dyssynchrony. The inferior free wall and the section nearest the interventricular septum had 35% (26,48) interstitial fibrosis compared to the IS itself which had 9% (7, 13) in hearts with 25% fibrosis, and the contrast had the most variance (8.7%, P&lt;0.0001). Strong predictors of the contrasting fibrosis included the trace perimeter and the maximal normalized displacement, but more pragmatically, the differences between the two conditions are apparent and consistent. Figure 1 is the set of (u,v) pairs measured over the course of a heartbeat where u is the radial displacement of heart segment x measured when segment y had radial displacement v.
A DPP-IV-resistant glucagon-like peptide-2 dimer with enhanced activity against radiation-induced intestinal injury
Authors: Jintao Gu, Shuo Liu, Nan Mu, Tonglie Huang, Wangqian Zhang, Huadong Zhao, Zhen Shu, Cun Zhang, Qiang Hao, Weina Li, Xiaochang Xue, Wei Zhang, Yingqi Zhang
Journal: Journal of Controlled Release (2017)
Cancer of the Breast
Authors: I. Craig Henderson, George P. Canellos
Journal: New England Journal of Medicine (1980)

Newer Forms of Hormone Therapy: AntiestrogensAntiestrogens were developed as antifertility drugs. Instead, they induce ovulation in infertile women, and they may also cause regression of breast-cancer lesions. One of these drugs, tamoxifen, has been approved for general use in the treatment of breast cancer. Two others, nafoxidine and clomiphene, have been studied extensively in clinical trials.187 Tamoxifen is usually administered as a 10-mg tablet twice daily, even though its biologic half-life exceeds seven days.188 If the effect of tamoxifen depends on its competition with estrogen for binding sites in tumor-cell cytoplasm, we would expect to see a dose response . . .
Therapeutic Response of Metastatic Colorectal Cancer Harboring a<i>KRAS</i>Missense Mutation After Combination Chemotherapy With the EGFR Inhibitor Panitumumab
Authors: Emil Lou, Donna D'Souza, Andrew C. Nelson
Journal: Journal of the National Comprehensive Cancer Network (2017)

Over the past decade, subset analyses of retrospective and prospective clinical studies have determined that KRAS-mutated metastatic colorectal cancers do not respond effectively to inhibition of epidermal growth factor receptor (EGFR) with the EGFR-targeting monoclonal antibodies cetuximab or panitumumab. Within the past few years, the scope of tested variants in the KRAS oncogene has expanded significantly, and testing of all RAS family genes has become more widely available in clinical laboratories. Expert consensus guidelines have recommended not using EGFR inhibitors in patients with KRAS-mutated tumors. However, with increasing identification of low-prevalence variants, it is conceivable that some RAS mutations do not provide equivalent resistance to EGFR inhibition compared with the most prevalent mutations at codons 12, 13, and 61. This report describes a case of a patient with metastatic colon cancer harboring the p.A59T variant of KRAS, with objective radiographic response (36% decrease per RECIST 1.1) and carcinoembryonic antigen biomarker response to panitumumab therapy given with FOLFIRI chemotherapy. We propose that A59T represents one potential exception to the guidelines that KRAS mutant tumors fail to respond to therapy with EGFR inhibitors, altering the paradigm of using this generalized approach.
Novel Deceased Donor Perfusion Model for High-Fidelity Simulation in Vascular Surgery
Authors: J. Hunter Mehaffey, Eric J. Charles, Leora T. Yarboro
Journal: JAMA Surgery (2017)

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 Surgery 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 Surgery journal
MOLECULAR GENETICS OF HYPERTROPHIC CARDIOMYOPATHY
Authors: A. J. Marian, M.D, R. Roberts, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Hypertrophic cardiomyopathy (HCM) is genetically and phenotypically a heterogeneous disease. Genes identified include the β myosin heavy chain gene (βMHC) on chromosome 14q1, the troponin T gene on chromosome 1q, and the α tropomyosin gene on chromosome 15q. In addition, a fourth locus is present on chromosome 11q11, but the gene remains to be identified. More than 35 missense mutations in the βMHC, 3 mutations in troponin T, and 2 mutations in α tropomyosin gene in HCM patients have been identified. Functional studies have shown that the mutant βMHC protein has impaired acto-myosin interaction and that expression of the mutant myosin disrupts the assembly of sarcomere in feline cardiocytes. Genotype-phenotype correlations of βMHC mutations have shown that mutations such as Arg403Gln, Arg453Cys, and Arg719Trp are associated with a high incidence of sudden cardiac death and a significantly decreased life expectancy, whereas mutations Gly256Glu and Leu908Val have a near-normal life span. Preclinical genetic diagnosis should help in genetic counseling and therapeutic stratification.
Spontaneous Recovery of Rosai-Dorfman Disease on FDG PET/CT
Authors: Qianqian Xue, Weibing Miao
Journal: Clinical Nuclear Medicine (2017)

Rosai-Dorfman disease is a rare systemic proliferative disorder of histiocytes, which mainly manifests as lymphadenopathy but also often involves extranodal tissues. Rosai-Dorfman disease was often self-limited. We hereby report a case of Rosai-Dorfman disease involving both the lymph nodes and the lungs, which was spontaneously resolved on FDG PET/CT.
Large‐scale computational models of liver metabolism: How far from the clinics?
Authors: Tanja Cvitanović, Matthias C. Reichert, Miha Moškon, Miha Mraz, Frank Lammert, Damjana Rozman
Journal: Hepatology (2017)

Understanding the dynamics of human liver metabolism is fundamental for effective diagnosis and treatment of liver diseases. This knowledge can be obtained with systems biology/medicine approaches that account for the complexity of hepatic responses and their systemic consequences in other organs. Computational modeling can reveal hidden principles of the system by classification of individual components, analyzing their interactions and simulating the effects that are difficult to investigate experimentally. Herein, we review the state‐of‐the‐art computational models that describe liver dynamics from metabolic, gene regulatory, and signal transduction perspectives. We focus especially on large‐scale liver models described either by genome scale metabolic networks or an object‐oriented approach. We also discuss the benefits and limitations of each modeling approach and their value for clinical applications in diagnosis, therapy, and prevention of liver diseases as well as precision medicine in hepatology. (H epatology 2017;66:1323‐1334).
Pedometer Step Count Targets during Pulmonary Rehabilitation in Chronic Obstructive Pulmonary Disease. A Randomized Controlled Trial
Authors: Claire M. Nolan, Matthew Maddocks, Jane L. Canavan, Sarah E. Jones, Veronica Delogu, Djeya Kaliaraju, Winston Banya, Samantha S. C. Kon, Michael I. Polkey, William D.-C. Man
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: Increasing physical activity is a key therapeutic aim in chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) improves exercise capacity, but there is conflicting evidence regarding its ability to improve physical activity levels.Objectives: To determine whether using pedometers as an adjunct to PR can enhance time spent in at least moderate-intensity physical activity (time expending ≥3 metabolic equivalents [METs]) by people with COPD.Methods: In this single-blind randomized controlled trial, participants were assigned 1:1 to receive a control intervention (PR comprising 8 wk, two supervised sessions per week) or the trial intervention (PR plus pedometer-directed step targets, reviewed weekly for 8 wk). In the randomization process, we used minimization to balance groups for age, sex, FEV1 percent predicted, and baseline exercise capacity and physical activity levels. Outcome assessors and PR therapists were blinded to group allocation. The primary analysis was based on the intention-to-treat principle.Measurements and Main Results: The primary outcome was change from baseline to 8 weeks in accelerometer-measured daily time expending at least 3 METs. A total of 152 participants (72% male; mean [SD] FEV1 percent predicted, 50.5% [21.2]; median [first quartile, third quartile] time expending ≥3 METs, 46 [21, 92] min) were enrolled and assigned to the intervention (n = 76) or control (n = 76) arm. There was no significant difference in change in time expending at least 3 METs between the intervention and control groups at 8 weeks (median [first quartile, third quartile] difference, 0.5 [−1.0, 31.0] min; P = 0.87) or at the 6-month follow-up (7.0 [−9, 27] min; P = 0.16).Conclusions: Pedometer-directed step-count targets during an outpatient PR program did not enhance moderate-intensity physical activity levels in people with COPD.Clinical trial registered with www.clinicaltrials.gov (NCT01719822).
Abstract 255: A Normokalemic Nondepolarizing Cardioplegia Minimizes Myocardial Injury and Improves Cardiac Function in a Large Animal Model of Donation After Cardiocirculatory Death
Authors: Christopher W White, Ayyaz Ali, Bo Xiang, Simon Colah, Paul Mundt, Rakesh Arora, Trevor Lee, Steven Large, Ganghong Tian, Darren Freed
Journal: Circulation Research (2012)

Background: Procurement of donor hearts is typically preceded by delivery of a cold hyperkalemic cardioplegia (CP) that achieves arrest by depolarization of the membrane potential. This method has no intrinsic cardioprotective properties and may exacerbate ischemia-reperfusion (IR) injury. A tepid adenosine-lidocaine (AL) non-depolarizing CP has been shown to limit IR injury and improve myocardial functional recovery in a small animal model of orthotopic heart transplantation. We sought to determine the impact of AL CP on myocardial injury and function, in a porcine model of donation after cardio-circulatory death (DCD). Methods: Female Yorkshire pigs (60 kg) were subjected to a hypoxic cardiac arrest. Following a 15-minute standoff period donor hearts were procured, resuscitated ex-vivo, and transplanted into a recipient animal. Hearts in group 1 (N=7) were protected with a cold blood-Plegisol CP, perfused with a blood-crystalloid solution during ex-vivo assessment, and arrested with a cold blood-Plegisol CP prior to transplantation. Hearts in group 2 (N=5) were protected with a tepid AL-STEEN CP and perfused with a blood-STEEN solution in a continuous fashion during ex-vivo assessment and transplantation. Results: Animals in group 2 had a significantly longer ex-vivo perfusion time compared to those in group 1 (174±29 vs. 135±45 min, p&lt;0.05), yet they demonstrated significantly less weight gain (14±4 vs. 25±8 grams/hour, p&lt;0.05). Further, animals in group 2 exhibited less troponin I release during ex-vivo perfusion and had significantly better diastolic function following wean from cardiopulmonary bypass (left ventricular end-diastolic pressure volume relationship 0.115±0.052 vs. 0.508±0.223, p&lt;0.05). However, there was no significant difference in level of calpain activity between groups (171.3±68.6 vs. 140.12±50.6, p=0.36). Conclusion: A tepid non-depolarizing AL CP results in less myocardial edema during ex-vivo perfusion, minimizes myocardial injury, and improves diastolic function following transplantation of DCD hearts, but fails to eliminate the activation of calcium-dependent proteases. Further studies should investigate if a calpain inhibitor delivered at reperfusion could further minimize IR injury in DCD hearts.
Platelets in inflammation and atherogenesis
Authors: M. Gawaz
Journal: Journal of Clinical Investigation (2005)

Platelets represent an important linkage between inflammation, thrombosis, and atherogenesis. Inflammation is characterized by interactions among platelets, leukocytes, and ECs. These interactions trigger autocrine and paracrine activation processes that lead to leukocyte recruitment into the vascular wall. Platelet-induced chronic inflammatory processes at the vascular wall result in development of atherosclerotic lesions and atherothrombosis. This Review highlights the molecular machinery and inflammatory pathways used by platelets to initiate and accelerate atherothrombosis.
Use of Arterial Transfer Functions for the Derivation of Central Aortic Waveform Characteristics in Subjects With Type 2 Diabetes and Cardiovascular Disease
Authors: Alberto P. Avolio, John R. Cockcroft, Michael F. O’Rourke
Journal: Diabetes Care (2004)

In a recent editorial, Mather and Lewanczuk (1) describe the potential value of a generalized transfer function to synthesize the ascending aortic pressure wave from the radial pressure waveform, as recorded indirectly by applanation tonometry. The Food and Drug Administration (FDA) had previously accepted validity under different conditions of a generalized transfer function used in a commercial device: “The SphygmoCor SCOR-Px can calculate the calibrated ascending aortic pressure waveform using the radial artery pressure waveform recorded noninvasively from a radial artery tonometer and a brachial cuff measurement” (2). On the basis of an accompanying article by Hope et al. (3) in Diabetes Care , editorialists expressed concern regarding whether such an approach was applicable in diabetic subjects.

There are serious flaws in the report of Hope et al. (3) Their transfer function is …
Cyclin D1 Restrains Oncogene-Induced Autophagy by Regulating the AMPK–LKB1 Signaling Axis
Authors: Mathew C. Casimiro, Gabriele Di Sante, Agnese Di Rocco, Emanuele Loro, Claudia Pupo, Timothy G. Pestell, Sara Bisetto, Marco A. Velasco-Velázquez, Xuanmao Jiao, Zhiping Li, Christine M. Kusminski, Erin L. Seifert, Chenguang Wang, Daniel Ly, Bin Zheng, Che-Hung Shen, Philipp E. Scherer, Richard G. Pestell
Journal: Cancer Research (2017)

Abstract Autophagy activated after DNA damage or other stresses mitigates cellular damage by removing damaged proteins, lipids, and organelles. Activation of the master metabolic kinase AMPK enhances autophagy. Here we report that cyclin D1 restrains autophagy by modulating the activation of AMPK. In cell models of human breast cancer or in a cyclin D1–deficient model, we observed a cyclin D1–mediated reduction in AMPK activation. Mechanistic investigations showed that cyclin D1 inhibited mitochondrial function, promoted glycolysis, and reduced activation of AMPK (pT172), possibly through a mechanism that involves cyclin D1-Cdk4/Cdk6 phosphorylation of LKB1. Our findings suggest how AMPK activation by cyclin D1 may couple cell proliferation to energy homeostasis. Cancer Res; 77(13); 3391–405. ©2017 AACR.
Abstract 72: Ca <sup>2+</sup> and Calmodulin-Dependent Protein Kinase II Mediate a Temporal Switch Between Cardiotoxic and Cardioprotective Signaling by β2-Adrenergic Receptors
Authors: Viswanathan Rajagopalan, Giovanni Fajardo, Mingming Zhao, Takashi Urashima, Daniel Bernstein
Journal: Circulation Research (2012)

Background: ß-adrenergic receptors (AR) play a critical role in cardiac function but also mediate adverse remodeling associated with chronic sympathetic stimulation in heart failure. Some studies have suggested cardiotoxic signaling through ß1-AR and cardioprotective through ß2-AR. However, ß2-AR can signal through both Gs &amp; Gi, partially dictated by the time course of activation. We sought to determine whether this temporal effect influenced the differential roles of ß1- &amp; ß2-AR in the pathogenesis of cardiomyopathy. Methods: We compared two models of oxidative stress-induced cardiomyopathy: acute doxorubicin (AD) 15 mg/kg in a single dose vs. chronic doxorubicin (CD) 2 mg/kg/wk x 8 wks in WT, ß1-AR-/- &amp; ß2-AR-/- mice. Endpoints were survival and cardiac size and function. Activation of AR signaling pathways was assessed by Western blot. Results: With AD, 100% of ß2-/- die within 20 min, an effect not seen in ß1-/- or WT. With CD, in contrast, ß2-/- were protected: WT survival t½ 42 d, 100% mortality 70 d, n=33; ß2-/- t½ 56 d, 100% mortality 109 d, n=44; ß1-/- t½ 54 d, 100% mortality 99 d, n=31 (log rank p&lt;0.0001). Fractional shortening declined and LV diastolic dimension increased by 2 wks in WT (13.9±2.5, 10.3±2.2%) whereas both were preserved in ß2-/- (5.0±1.7, p&lt;0.01; 4.8±1.5%) and ß1-/- (2±1.6, p&lt;0.001; 0.8±1.8, p&lt;0.01) at least until 4 wks. Total Ca2+ and calmodulin-dependent protein kinase II (CaMKII) was increased at baseline in both ß1-/- &amp; ß2-/- vs. WT. However, in ß2-/-, CaMKII was decreased with AD (0.74±0.1; p&lt;0.01), and increased with CD (1.3±0.05; p&lt;0.01). Similarly, CaMKII phosphorylation was decreased with AD (1.27±0.16) vs. baseline (1.95±0.19) and increased with CD (2.35±0.18, p&lt;0.001). With AD, p-p38 increased 20-fold in ß2-/-, but was normal in CD. In contrast, p-JNK was increased in CD in both ß2-/- (0.34±0.09) and ß1-/- vs. WT (0.1±0.04; p&lt;0.001). Conclusion: The differential role of ß2-AR in mediating cardioprotection/cardiotoxicity are more complex than initially thought. ß2-AR signaling exhibits a temporal switch depending on whether a stress is acute (cardioprotective) vs. chronic (cardiotoxic). This switch is mediated by differential activation of CaMKII and JNK (mediating cardioprotection) and p38 (mediating cardiotoxicity).