tbuckley/cabot-search huggingface dataset:
Pan-ERBB kinase inhibition augments CDK4/6 inhibitor efficacy in oesophageal squamous cell carcinoma
Authors: Jin Zhou, Zhong Wu, Zhouwei Zhang, Louisa Goss, James McFarland, Ankur Nagaraja, Yingtian Xie, Shengqing Gu, Ke Peng, Yong Zeng, Xiaoyang Zhang, Henry Long, Hiroshi Nakagawa, Anil Rustgi, J Alan Diehl, Matthew Meyerson, Kwok-Kin Wong, Adam Bass
Journal: Gut (2021)

Objective Oesophageal squamous cell carcinoma (OSCC), like other squamous carcinomas, harbour highly recurrent cell cycle pathway alterations, especially hyperactivation of the CCND1/CDK4/6 axis, raising the potential for use of existing CDK4/6 inhibitors in these cancers. Although CDK4/6 inhibition has shown striking success when combined with endocrine therapy in oestrogen receptor positive breast cancer, CDK4/6 inhibitor palbociclib monotherapy has not revealed evidence of efficacy to date in OSCC clinical studies. Herein, we sought to elucidate the identification of key dependencies in OSCC as a foundation for the selection of targets whose blockade could be combined with CDK4/6 inhibition. Design We combined large-scale genomic dependency and pharmaceutical screening datasets with preclinical cell line models, to identified potential combination therapies in squamous cell cancer. Results We identified sensitivity to inhibitors to the ERBB family of receptor kinases, results clearly extending beyond the previously described minority of tumours with EGFR amplification/dependence, specifically finding a subset of OSCCs with dual dependence on ERBB3 and ERBB2. Subsequently. we demonstrated marked efficacy of combined pan-ERBB and CDK4/6 inhibition in vitro and in vivo. Furthermore, we demonstrated that squamous lineage transcription factor KLF5 facilitated activation of ERBBs in OSCC. Conclusion These results provide clear rationale for development of combined ERBB and CDK4/6 inhibition in these cancers and raises the potential for KLF5 expression as a candidate biomarker to guide the use of these agents. These data suggested that by combining existing Food and Drug Administration (FDA)-approved agents, we have the capacity to improve therapy for OSCC and other squamous cancer.
Obstructive sleep apnoea
Authors: M. Greenstone, M. Hack
Journal: BMJ (2014)

#### Summary points

Although snoring and occasional apnoeic breath holding in sleep (obstructive sleep apnoea) is common, the diagnosis of obstructive sleep apnoea syndrome (OSAS) requires the presence of repetitive apnoeas and symptoms of sleep fragmentation, most commonly excessive daytime sleepiness. With increasing awareness of OSAS and portable diagnostic equipment, OSAS is no longer an esoteric diagnosis made only in specialist sleep centres but an easily recognised condition for which effective treatment is widely available. Obstructive sleep apnoea syndrome is also important from a public health perspective because of the increased risk of cardiovascular morbidity1 and road traffic incidents.2 This review is intended for non-specialists and describes the physiology and diagnosis of OSAS, the practicalities of treatment, and the identification of those patients who are likely to benefit.

#### Sources and selection criteria

We based this review on articles found by searching PubMed and the Cochrane Database of Systematic Reviews. Search terms included “obstructive sleep apnoea or obstructive sleep apnoea syndrome” and “driving or treatment”. The search was limited to articles in English and to studies carried out in adults. We gave priority to data from meta-analyses, reviews, and randomised controlled trials. We also included relevant reports and national guidelines.

Conventionally, an apnoea is a cessation of airflow for 10 seconds and is often associated with oxygen desaturation, whereas a lesser reduction in airflow is termed a hypopnoea. Sleep studies measure the apnoea/hypopnoea index (AHI), which is the number of respiratory events an hour. Community studies have used questionnaires and …
Transsarcolemmal calcium movements in arterially perfused rabbit right ventricle measured with extracellular calcium-sensitive dyes.
Authors: D WHilgemann, G ALanger
Journal: Circulation Research (1984)

Activation-dependent changes of mean extracellular calcium concentrations were monitored spectrophotometrically in arterially perfused right ventricle of rabbit via extracellular application of the calcium-sensitive absorption dyes, antipyrylazo III and tetramethylmurexide. After rest periods of 3 minutes or longer, 10% of total dye-accessible calcium (300-500 microM) is depleted cumulatively from the extracellular space by four to eight beats at 2 Hz stimulation. During continued stimulation, or during quiescence following a depletion response, mean extracellular calcium concentrations return toward the prestimulatory level in the course of 2-4 minutes. A single stimulation placed 2-30 seconds subsequent to rapid pacing results in a potentiated beat with an accompanying net increment of mean extracellular calcium. Total dye-accessible calcium can increase by at least 4% at such a beat, and depletion responses can be repeated immediately thereafter. During a sequence of such responses, extracellular calci...
Ionic currents activated during hyperpolarization of single right atrial myocytes from cat heart.
Authors: J YWu, JVereecke, ECarmeliet, S LLipsius
Journal: Circulation Research (1991)

Whole-cell recording techniques were used on single right atrial myocytes to study the ionic currents that may be responsible for the diverse diastolic voltage characteristics of atrial tissue. Ionic currents were activated by hyperpolarizing voltage pulses negative to -30 mV. In general, four different types of cells were identified based primarily on the ionic currents elicited during hyperpolarization. The first cell type exhibited an inward current that decayed with time at more negative voltages, reversed near the potassium equilibrium potential, inwardly rectified at more positive voltages, increased in elevated extracellular potassium, and was blocked by 3 mM barium or 10 mM cesium. This current was identified as the potassium current iK1. A second cell type exhibited a time-dependent inward current that increased at more negative voltages, had an activation range between -50 and -110 mV, had a reversal potential of -26 mV, and was blocked by 3 mM cesium. This current was identified as an if curren...
Dissociation between cellular K+ loss, reduction in repolarization time, and tissue ATP levels during myocardial hypoxia and ischemia.
Authors: G XYan, K AYamada, A GKléber, JMcHowat, P BCorr
Journal: Circulation Research (1993)

The mechanisms underlying the marked increase in [K+]o in response to ischemia are not fully understood. Accordingly, the present study was performed to assess the contribution of ATP-regulated K+ channels by using simultaneous measurements of cellular K+ efflux, [K+]o, transmembrane action potentials, and tissue ATP, ADP, phosphocreatine, and creatine content in a unique isolated, blood-perfused papillary muscle preparation during hypoxia compared with ischemia. During 15 minutes of hypoxic perfusion (PO2, 6.1 +/- 0.9 mm Hg) with normal [K+]o of 4.1 +/- 0.1 mM, action potential duration (APD) was not altered even though tissue ATP levels decreased markedly from 33.5 +/- 1.8 to 14.7 +/- 2.0 nmol.mg protein-1 (p < 0.01). Net cellular K+ efflux, based on measured differences of [K+] between the venous effluent and the perfusate, was 13.23 +/- 0.79 mumol.g wet wt-1 during hypoxia. In contrast, after 15 minutes of zero-flow ischemia, APD at 80% of repolarization (APD80) decreased by 47% from 171 +/- 5 to 92 +...
Nonavalent human papilloma virus vaccine for the treatment of multiple recalcitrant warts: An open-label study
Authors: Jun-Oh Shin, Jin-Hwa Son, Jungsoo Lee, Hoon-Soo Kim, Hyun-Chang Ko, Byung-Soo Kim, Moon-Bum Kim, Kihyuk Shin
Journal: Journal of the American Academy of Dermatology (2021)
Unusual Exclusion Criteria
Authors: Ming-Hua Li, Yong-Dong Li
Journal: Annals of Internal Medicine (2014)

Letters4 March 2014Unusual Exclusion CriteriaMing-Hua Li, MD, PhD and Yong-Dong Li, MD, PhDMing-Hua Li, MD, PhDFrom Sixth People's Hospital, Shanghai, China.Search for more papers by this author and Yong-Dong Li, MD, PhDFrom Sixth People's Hospital, Shanghai, China.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L14-5005-4 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We understand Dr. Tosiello's concern about the exclusion criteria, specifically what we called “going abroad” and “away on business.” The terminology that we used refers to the population that was not eligible when we conducted this screening survey. Local residents who were going abroad or on a long business trip were excluded due to ineligibility. “Going abroad” and “away on business” are indeed 2 detailed reasons for ineligibility and have nothing to do with participants being “politically detained.”In addition, as we mention in our article, several persons declined to participate in this study. However, all of the ... Author, Article, and Disclosure InformationAffiliations: From Sixth People's Hospital, Shanghai, China.Disclosures: None disclosed. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M13-0927. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPrevalence of Unruptured Cerebral Aneurysms in Chinese Adults Aged 35 to 75 Years Ming-Hua Li , Shi-Wen Chen , Yong-Dong Li , Yuan-Chang Chen , Ying-Sheng Cheng , Ding-Jun Hu , Hua-Qiao Tan , Qian Wu , Wu Wang , Zhen-Kui Sun , Xiao-Er Wei , Jia-Yin Zhang , Rui-Hua Qiao , Wen-Hong Zong , Yin Zhang , Wei Lou , Zhi-Yuan Chen , Yu Zhu , De-Rong Peng , Sui-Xin Ding , Xue-Fan Xu , Xu-Hong Hou , and Wei-Ping Jia Unusual Exclusion Criteria Lorraine Tosiello Unusual Exclusion Criteria Lorraine Tosiello Metrics 4 March 2014Volume 160, Issue 5Page: 368KeywordsConflicts of interest ePublished: 4 March 2014 Issue Published: 4 March 2014 Copyright & PermissionsCopyright © 2014 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Stimulation of DNA synthesis in rat A10 vascular smooth muscle cells by threonine-59 insulin-like growth factor I.
Authors: M ACascieri, G GChicchi, N SHayes, E ESlater
Journal: Circulation Research (1986)

The clonal smooth muscle cell line A10, derived from fetal rat aorta, binds 125I-insulin-like growth factor I at a Type 1 insulin-like growth factor receptor. Threonine-59 insulin-like growth factor I, multiplication stimulating activity, and insulin inhibit the binding with IC50 = 10 nM, 84 nM, and 500 nM, respectively. Insulin in high concentrations (greater than 5 microM) completely inhibits 125I-insulin-like growth factor I binding to A10 cells. Threonine-59 insulin-like growth factor I and insulin stimulate [3H]thymidine incorporation into DNA in A10 cells that had been growth arrested by incubation in serum-free media (DMEM/0.1% BSA) for 24-36 hours. The stimulation produced by the peptides is 50-60% of the stimulation produced by 10% fetal calf serum. Low levels of serum (0.1 and 0.5%) also stimulate DNA synthesis, and the effects of Threonine-59 insulin-like growth factor I and low serum are additive. The ED50 for the effects of Threonine-59 insulin-like growth factor I, multiplication stimulating...
Diversity of structural mitral valve alterations in hypertrophic cardiomyopathy.
Authors: H GKlues, B JMaron, A LDollar, W CRoberts
Journal: Circulation (1992)

BACKGROUNDHypertrophic cardiomyopathy (HCM) is characterized by an asymmetrically hypertrophied left ventricle and is regarded as a disease of cardiac muscle.METHODS AND RESULTSTo assess the possibility that the mitral valve itself may be involved in the disease process, we studied mitral valves from 94 patients with HCM and 45 normal control subjects. The area of the mitral leaflets was increased in patients with HCM compared with control subjects (12.9 +/- 3.7 versus 8.7 +/- 2.0 cm2; p less than 0.001). For the overall group of patients, this increase was largely caused by an increase in anterior leaflet length (2.2 +/- 0.5 cm for HCM versus 1.8 +/- 0.3 cm for control subjects; p less than 0.001), because circumference did not differ between the two groups. Mitral leaflet area was increased (greater than or equal to 12.0 cm2) in 55 (58%) of the 94 valves. In 12 of these 55 valves, both the anterior and posterior leaflets were enlarged; the other 43 valves had asymmetrical or segmental enlargement of eit...
From the authors:
Authors: L. Lehtimäki, H. Kankaanranta, S. Saarelainen, E. Moilanen
Journal: European Respiratory Journal (2010)

We were interested to read the paper by LEHTIMA ¨KI et al. [1] recently published in the European Respiratory Journal, in which those authors reported that ''high pre-treatment levels of J9aw,NO [bronchial nitric oxide flux] are related to symptom relief and improvement of airway obstruction'' when inhaled fluticasone is given to patients with chronic obstructive pulmonary disease (COPD).Their data complement those which we ourselves have recently published [2].
Simple optical evaluation criteria reliably identify the post-endoscopic mucosal resection scar for benign large non-pedunculated colorectal polyps without tattoo placement
Authors: Neal Shahidi, Sunil Gupta, Anthony Whitfield, Sergei Vosko, Owen McKay, Oliver Cronin, Simmi Zahid, Nicholas G. Burgess, Michael J. Bourke
Journal: Endoscopy (2021)

Recognition of the post-endoscopic mucosal resection (EMR) scar is critical for large (≥ 20 mm) non-pedunculated colorectal polyp (LNPCP) management. The utility of intraluminal tattooing to facilitate scar identification is unknown.We evaluated the ability of simple easy-to-use optical evaluation criteria to detect the post-EMR scar, with or without tattoo placement, in a prospective observational cohort of LNPCPs referred for endoscopic resection. The primary outcome was scar identification, further stratified by lesion size (20-39 mm, ≥ 40 mm) and histopathology (adenomatous, serrated).1023 LNPCPs underwent both successful EMR and first surveillance colonoscopy (median size 35 mm, IQR 30-50 mm); 124 (12.1 %) had an existing tattoo or a tattoo placed at the index EMR. The post-EMR scar was identified in 1020 patients (99.7 %). The presence of a tattoo did not affect scar identification (100.0 % vs. 99.7 %; P > 0.99). There was no difference for LNPCPs 20-39 mm, LNPCPs ≥ 40 mm, adenomatous LNPCPs, and serrated LNPCPs (all P > 0.99).The post-EMR scar can be reliably identified with simple easy-to-use optical evaluation criteria, without the need for universal tattoo placement.
Actionability of commercial laboratory sequencing panels for newborn screening and the importance of transparency for parental decision-making
Authors: Daniela M. DeCristo, Laura V. Milko, Julianne M. O’Daniel, Ann Katherine M. Foreman, Lonna F. Mollison, Bradford C. Powell, Cynthia M. Powell, Jonathan S. Berg
Journal: Genome Medicine (2021)

Abstract Background Newborn screening aims to identify individual patients who could benefit from early management, treatment, and/or surveillance practices. As sequencing technologies have progressed and we move into the era of precision medicine, genomic sequencing has been introduced to this area with the hopes of detecting variants related to a vastly expanded number of conditions. Though implementation of genomic sequencing for newborn screening in public health and clinical settings is limited, commercial laboratories have begun to offer genomic screening panels for neonates. Methods We examined genes listed on four commercial laboratory genomic screening panels for neonates and assessed their clinical actionability using an established age-based semi-quantitative metric to categorize them. We identified genes that were included on multiple panels or distinct between panels. Results Three hundred and nine genes appeared on one or more commercial panels: 74 (23.9%) genes were included in all four commercial panels, 45 (14.6%) were on only three panels, 76 (24.6%) were on only two panels, and 114 (36.9%) genes were listed on only one of the four panels. Eighty-two genes (26.5%) listed on one or more panels were assessed by our method to be inappropriate for newborn screening and to require additional parental decision-making. Conversely, 249 genes that we previously identified as being highly actionable were not listed on any of the four commercial laboratory genomic screening panels. Conclusions Commercial neonatal genomic screening panels have heterogeneous content and may contain some conditions with lower actionability than would be expected for public health newborn screening; conversely, some conditions with higher actionability may be omitted from these panels. The lack of transparency about how conditions are selected suggests a need for greater detail about panel content in order for parents to make informed decisions. The nuanced activity of gene list selection for genomic screening should be iteratively refined with evidence-based approaches to provide maximal benefit and minimal harm to newborns.
TCTAP A-023 When the Culprit is the Left Main: In-hospital and 12-month Outcomes of Left Main Percutaneous Coronary Intervention - A Single-center Experience
Authors: Mohammed Ali Osheiba, Alexander Zaphiriou, Sudhakar George, Adnan Nadir, Peter Ludman, Sagar Doshi, John Townend, Sohail Khan
Journal: Journal of the American College of Cardiology (2021)
Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs.
Authors: R EMcCaa, C SMcCaa, A CGuyton
Journal: Circulation Research (1975)

The aldosterone response to long-term infusion of angiotensin II and potassium was studied in intact conscious dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), and plasma cortisol concentration (PCC) were determined by radioimmunoassay. In ten dogs maintained on angiotension II infusion (5 ng/kg min-1) for 14 days, PAC increased from 6.9 plus or minus 2.9 to 18.6 plus or minus 4.7 ng/100 ml plasma (mean plus or minus SE) within ten minutes after beginning the infusion, reached a maximum level of 28.3 plus or minus 6.8 ng/100 ml plasma by one hour, and returned to control levels by six hours. PCC increased from 0.6 plus or minus 0.2 to 3.9 plus or minus 1.0 mu-g/ 100 ml plasma within one hour after angiotensin II infusion and returned to control levels by six hours. During the next 14 days of angiotensin infusion, PAC remained at control levels, PRA was undetectable by radioimmunoassay, and mean arterial blood pressure was elevated 29 plus or minus 4 mm Hg above control levels. In...
Shall The Journal be Removed to Washington?
Authors: L. L. Leeds
Journal: JAMA (1891)

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
Left ventricular systolic and diastolic function in coronary artery disease: effects of revascularization on exercise-induced ischemia.
Authors: J DCarroll, O MHess, H OHirzel, MTurina, H PKrayenbuehl
Journal: Circulation (1985)

Left ventricular systolic and diastolic function were studied before and after surgical revascularization in a group of 24 patients with stable angina who all had an excellent clinical response to surgery. With use of micromanometer left ventricular pressure measurements and ventricular volumes, calculated from biplane cineangiograms, left ventricular function at rest and during exercise before and after surgery was compared. Before surgery all patients had exercise-induced ischemia with new asynergy, a fall in ejection fraction from 57% to 49% (p less than .001), and a rise in left ventricular end-diastolic pressure from 23 to 37 mm Hg (p less than .001). Postoperative exercise resulted in no new asynergy and ejection fraction rose from 59% to 61% (p less than .05). Left ventricular end-diastolic pressure still rose from 17 to 25 mm Hg (p less than .01). Left ventricular pressure decay during exercise was greatly improved after revascularization and allowed maintenance of reduced early diastolic pressure...
An improved basis for enzymatic estimation of infarct size.
Authors: RRoberts, P DHenry, B ESobel
Journal: Circulation (1975)

Infarct size has been estimated from serial serum creatine phosphokinase (CPK) changes, but the contribution of noncardiac CPK may interfere. Results would also be influenced if CPK disappearance varied with hemodynamic changes. Since MB CPK is a marker more specific to myocardium. infarct size was estimated from serum MB changes in 16 patients. In addition, 21 chronically instrumented conscious dogs subjected to tachycardia, decreased cardiac output or hepatic or renal ischemia were studied to evaluate the dependence of CPK disappearance on hemodynamics. MB CPK in human tissue extracts and serum was quantified with a new, rapid, glass bead-batch adsorption technique, verified with CPK isoenzymes prepared from human myocardium. Among tissues surveyed, only myocardium contained appreciable MB CPK. Infarct size estimated from MB correlated with total serum CPK in patients with uncomplicated myocardial infarction (r=0.97, N=12). In patients with infarction given intramusclar injections, total CPK curves were...
Cord-like aortic valve vegetation in bacterial endocarditis. Demonstration by cardiac ultrasonography. Report of a case.
Authors: JYoshikawa, KTanaka, TOwaki, HKato
Journal: Circulation (1976)

The ultrasonic features in a case of bacterial endocarditis in which a highly mobile, cord-like vegetation, attached to the noncoronary cusp of the aortic valve, are reported. The echocardiogram demonstrated abnormal echo patterns in the left ventricular outflow tract in diastrole which were continuous with similar echoes in the aortic root. While these findings did not differ from the previously reported manifestations in cases of flailing aortic valve leaflets, the cardiac ultrasonogram distinguished this vegetative growth. Cardiac ultrasonography revealed a cord-like characteristic, showed the movement of the entire growth into the left ventricular outflow tract in diastole and into the aorta in systole, and allowed estimation of the size of the vegetation. We conclude that cardiac ultrasonography can help in differentiating aortic valve leaflet flail and vegetations in endocarditis.