tbuckley/cabot-search huggingface dataset:
TCT-458 Additional Diagnostic Value of CT Perfusion over Coronary CT Angiography in Stented Patients with Suspected In-stent Restenosis or Coronary Artery Disease Progression: ADVANTAGE study. Preliminary Results
Authors: Daniele Andreini, Saima Mushtaq, Gianluca Pontone, Edoardo Conte, Daniela Trabattoni, Paolo Mario Ravagnani, Piero Montorsi, Stefano Galli, Carlos Collet, Jeroen Sonck, Antonio Bartorelli
Journal: Journal of the American College of Cardiology (2018)
Abstract GS5-01: Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis
Authors: C Shah, V Verma, H Sayles, A Recht, F Vicini
Journal: Cancer Research (2018)

Abstract Background: Significant controversy exists regarding the appropriate minimum tumor-free margin width for patients undergoing breast-conserving therapy. The SSO-ASTRO guidelines recommend 'no ink on tumor' based upon a meta-analysis of 33 studies, but this had significant limitations. In order to address these concerns, a meta-analysis of all available data (using 31 of the initial studies) was performed but employing stricter criteria for acceptability and quality of evaluable studies. Methods: Study eligibility criteria were: (1) minimum follow-up of 50 months; (2) explicit pathologic criteria for defining margins; and (3) consistent endpoints associated with local recurrence. The compiled studies were analyzed using generalized linear mixed models for the outcome of local recurrence, with random effects for study and fixed effects for various patient and study characteristics. Results: The analysis incorporated 38 studies, which included 55,302 patients treated from 1968-2010. Two of the previous studies were excluded (one because of short follow-up, and the second because it was updated) with seven new studies added from the previous meta-analysis including an update of a previously included analysis. Median follow-up was 7.2 years. The median age of the cohort was 55 years, 74% of patients had T1 tumors, and 72% were node negative. The crude rate of local recurrence for patients with positive margins was 10.3%, compared to 3.8% for those with negative margins defined as no tumor on ink or wider (p&amp;lt;0.001). The crude rates of local recurrence decreased as the margin distance increased: 7.2% for patients with margins &amp;gt;0-&amp;lt;2 mm, 3.6% for margins of 2-5 mm (3.6%), and 3.2% for margins wider than 5 mm (p&amp;lt;0.001 for each). Use of endocrine therapy and increasing median study year were associated with a reduction in local recurrence in univariate models but not in multivariable analyses. Conclusions: The current meta-analysis indicates that having margin widths 2 mm or greater is associated with a lower risk of ipsilateral breast failure than narrower but uninvolved margins. It therefore fails to confirm that 'no-tumor on ink' is optimal. Further analyses are needed to clarify this issue, particularly to identify the critical minimum tumor-free margin for different patient subgroups. Citation Format: Shah C, Verma V, Sayles H, Recht A, Vicini F. Appropriate margins for breast conserving surgery in patients with early stage breast cancer: A meta-analysis [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS5-01.
GMC defends guidance on social media anonymity
Authors: Helen Jaques
Journal: BMJ (2013)

The General Medical Council (GMC) has defended its new guidance on social media for doctors in the face of criticism that its recommendation against anonymity online might infringe doctors’ human rights.

The regulator said that its advice that doctors should identify themselves by name on social media represents good practice, not a minimum standard. Doctors who do not identify themselves online will not be subject to fitness to practise proceedings, except potentially in cases where they use their anonymity to breach patient confidentiality or to bully or harass their colleagues, it has clarified.

The GMC’s new guidance on doctors’ use …
Tissue Markers for Acute Multiple Sclerosis Treatment Response—A Step Toward Personalized Medicine
Authors: Robert J. Fox
Journal: JAMA Neurology (2018)

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 Neurology 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 Neurology journal
Polyol Pathway Links Glucose Metabolism to the Aggressiveness of Cancer Cells
Authors: Annemarie Schwab, Aarif Siddiqui, Maria Eleni Vazakidou, Francesca Napoli, Martin Böttcher, Bianca Menchicchi, Umar Raza, Özge Saatci, Angela M. Krebs, Fulvia Ferrazzi, Ida Rapa, Katja Dettmer-Wilde, Maximilian J. Waldner, Arif B. Ekici, Suhail Ahmed Kabeer Rasheed, Dimitrios Mougiakakos, Peter J. Oefner, Ozgur Sahin, Marco Volante, Florian R. Greten, Thomas Brabletz, Paolo Ceppi
Journal: Cancer Research (2018)

Cancer cells alter their metabolism to support their malignant properties. In this study, we report that the glucose-transforming polyol pathway (PP) gene aldo-keto-reductase-1-member-B1 (AKR1B1) strongly correlates with epithelial-to-mesenchymal transition (EMT). This association was confirmed in samples from lung cancer patients and from an EMT-driven colon cancer mouse model with p53 deletion. In vitro, mesenchymal-like cancer cells showed increased AKR1B1 levels, and AKR1B1 knockdown was sufficient to revert EMT. An equivalent level of EMT suppression was measured by targeting the downstream enzyme sorbitol-dehydrogenase (SORD), further pointing at the involvement of the PP. Comparative RNA sequencing confirmed a profound alteration of EMT in PP-deficient cells, revealing a strong repression of TGFβ signature genes. Excess glucose was found to promote EMT through autocrine TGFβ stimulation, while PP-deficient cells were refractory to glucose-induced EMT. These data show that PP represents a molecular link between glucose metabolism, cancer differentiation, and aggressiveness, and may serve as a novel therapeutic target.Significance: A glucose-transforming pathway in TGFβ-driven epithelial-to-mesenchymal transition provides novel mechanistic insights into the metabolic control of cancer differentiation. Cancer Res; 78(7); 1604-18. ©2018 AACR.
Loss of cardiac Wnt/β-catenin signalling in desmoplakin-deficient AC8 zebrafish models is rescuable by genetic and pharmacological intervention
Authors: Alice Giuliodori, Giorgia Beffagna, Giulia Marchetto, Chiara Fornetto, Francesco Vanzi, Stefano Toppo, Nicola Facchinello, Mattia Santimaria, Andrea Vettori, Stefania Rizzo, Mila Della Barbera, Kalliopi Pilichou, Francesco Argenton, Gaetano Thiene, Natascia Tiso, Cristina Basso
Journal: Cardiovascular Research (2018)

Arrhythmogenic cardiomyopathy (AC) is an inherited heart disease characterized by life-threatening ventricular arrhythmias and fibro-fatty replacement of the myocardium. More than 60% of AC patients show pathogenic mutations in genes encoding for desmosomal proteins. By focusing our attention on the AC8 form, linked to the junctional protein desmoplakin (DSP), we present here a zebrafish model of DSP deficiency, exploited to identify early changes of cell signalling in the cardiac region. To obtain an embryonic model of Dsp deficiency, we first confirmed the orthologous correspondence of zebrafish Dsp genes (dspa and dspb) to the human DSP counterpart. Then, we verified their cardiac expression, at embryonic and adult stages, and subsequently we targeted them by antisense morpholino strategy, confirming specific and disruptive effects on desmosomes, like those identified in AC patients. Finally, we exploited our Dsp-deficient models for an in vivo cell signalling screen, using pathway-specific reporter transgenes. Out of nine considered, three pathways (Wnt/β-catenin, TGFβ/Smad3, and Hippo/YAP-TAZ) were significantly altered, with Wnt as the most dramatically affected. Interestingly, under persistent Dsp deficiency, Wnt signalling is rescuable both by a genetic and a pharmacological approach. Our data point to Wnt/β-catenin as the final common pathway underlying different desmosomal AC forms and support the zebrafish as a suitable model for detecting early signalling pathways involved in the pathogenesis of DSP-associated diseases, possibly responsive to pharmacological or genetic rescue.
Barriers to Breastfeeding for US Physicians Who Are Mothers
Authors: Nelya Melnitchouk, Rebecca E. Scully, Jennifer S. Davids
Journal: JAMA Internal Medicine (2018)

Barriers to Breastfeeding for US Physicians Who Are MothersThe benefits of breastfeeding for both women and infants are well established. 1Despite recommendations from the American Academy of Pediatrics and the World Health Organization, initiating and sustaining lactation remains a challenge for many women. 2Although 79% of mothers in the United States initiate breastfeeding, only 27% are still breastfeeding at 12 months postpartum. 3hysicians who are mothers face substantial challenges that may undermine efforts to sustain lactation after they return to work.5][6] Given the paucity of data on lacta-tion practices among physicians who are mothers, the aim of this study was to use a large representative nationwide cohort to evaluate the barriers to breastfeeding for physicians who are mothers.
Response to: ‘The reference levels of serum urate for clinically evident incident gout’ by Chen and Ding
Authors: Nicola Dalbeth, Amanda Phipps-Green, Christopher Frampton, Tuhina Neogi, William J Taylor, Tony R Merriman
Journal: Annals of the Rheumatic Diseases (2018)

Response to: 'The reference levels of serum urate for clinically evident incident gout' by Chen and DingWe thank Drs Chen and Ding 1 for their interest in our recent paper describing the relationship between serum urate concentrations and risk of developing incident gout. 2 They suggest that we calculate benchmark dose estimates for serum urate and gout risk.Benchmark dose estimates are used in the field of occupational epidemiology to evaluate the minimal levels of exposure to an environmental toxin needed to cause a prespecified increase in an adverse event.We are not aware of this approach being applied to clinical parameters that are not external exposures and are uncertain about validity of such an approach for serum urate, noting that all humans have some 'exposure' to urate, which is a circulating biochemical analyte.Estimation of the benchmark dose also requires a predetermined increase in risk (eg, 10% extra risk or change in the mean equal to one SD).At present, the clinically meaningful increase in gout risk is unknown.For these reasons, we have not provided benchmark dose estimates.
Günter Blobel: cell biologist who donated his Nobel prize money to the city of Dresden
Authors: Ned Stafford
Journal: BMJ (2018)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Günter Blobel: cell biologist who donated his Nobel prize money to the city of Dresden Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Growth factor therapy for decompensated cirrhosis: Much ado about nothing?
Authors: Cyriac Abby Philips, Philip Augustine, Sunil Mathew, Gopakumar C Valiathan, Solomon K John
Journal: Hepatology (2018)

Potential conflict of interest: Nothing to report. TO THE EDITOR: We read with interest, the study by Verma et al.1, on the utility of granulocyte colony‐stimulating factor (GCSF) and growth hormone (GH) (Group A) or GCSF alone (Group B) versus standard medical treatment (SMT) (Group C) in patients with decompensated cirrhosis (DC). The use of GCSF is well‐documented in acute on chronic liver failure, alcoholic hepatitis and reactivation of chronic hepatitis B, in which, control of acute insult along with exogenously administered growth factors lead to activation of hepatic progenitor and bone marrow‐derived cells to supplement hepatic regeneration.2 However, in DC, this proof of concept is lacking, which the authors try to bridge. The recommended dose of GCSF for mobilization of bone marrow cells is 10 µg/kg.4 The present study utilized suboptimal doses after the initial induction period that was less relevant to disease modulation in the long term. Persistence of elevated levels of CD34+ hematopoietic stem cells were not studied and the overall long‐term effect of presumed hypothesis of clinical improvement is not clear. Control of etiology improves clinical events and lowers liver stiffness (LSM) in compliant cirrhosis patients. In the present study, LSM in groups A, B and C decrease by 33.1, 31.4 and 5.4 kPa at the end of 12 months. This level of improvement may be biased; it is outside what would be expected as per current literature (Table 1) and requires the much‐lacking histological data to support its validity. Nutritional parameters in Group A and Group B improved over time in comparison to SMT, in which it worsened—an important observation closely related to improved outcomes, unexplained with the study treatment protocol. A recent study by Newsome et al.5 demonstrated that neither G‐CSF alone nor combined with autologous stem‐cell infusions improved liver function or stiffness in DC. The conclusion of the current study must be taken with a pinch of salt, since the study failed to address confounding factors and the degree of improvements remain to be validated by other independent groups of investigators. Table 1 - Changes in liver stiffness measurements from baseline at end of study follow‐up Author (Year) Etiology of Cirrhosis LSM Baseline (kPa) LSM at Follow‐Up Change in LSM Follow‐Up Period (Months) Fung (2010) Acute flare of chronic hepatitis B 16.8 6.9 9.9 12 Bardou‐Jacquet (2013) Abstinent alcoholics 15.5 11.7 3.8 8 Chekuri (2016) Hepatitis C 21.7 14 7.7 12 Sporea (2017) Hepatitis C 26.4 21.3 5.1 12 Singh (2018) Meta‐analysis of 24 studies, Hepatitis C ‐ ‐ 5.07 12 ‐ 24
STAT5A/B Blockade Sensitizes Prostate Cancer to Radiation through Inhibition of RAD51 and DNA Repair
Authors: Cristina Maranto, Vindhya Udhane, David T. Hoang, Lei Gu, Vitali Alexeev, Kareem Malas, Karmel Cardenas, Jonathan R. Brody, Ulrich Rodeck, Carmen Bergom, Ken A. Iczkowski, Ken Jacobsohn, William See, Sara M. Schmitt, Marja T. Nevalainen
Journal: Clinical Cancer Research (2018)

Abstract Purpose: The standard treatment for organ-confined prostate cancer is surgery or radiation, and locally advanced prostate cancer is typically treated with radiotherapy alone or in combination with androgen deprivation therapy. Here, we investigated whether Stat5a/b participates in regulation of double-strand DNA break repair in prostate cancer, and whether Stat5 inhibition may provide a novel strategy to sensitize prostate cancer to radiotherapy. Experimental Design: Stat5a/b regulation of DNA repair in prostate cancer was evaluated by comet and clonogenic survival assays, followed by assays specific to homologous recombination (HR) DNA repair and nonhomologous end joining (NHEJ) DNA repair. For HR DNA repair, Stat5a/b regulation of Rad51 and the mechanisms underlying the regulation were investigated in prostate cancer cells, xenograft tumors, and patient-derived prostate cancers ex vivo in 3D explant cultures. Stat5a/b induction of Rad51 and HR DNA repair and responsiveness to radiation were evaluated in vivo in mice bearing prostate cancer xenograft tumors. Results: Stat5a/b is critical for Rad51 expression in prostate cancer via Jak2-dependent mechanisms by inducing Rad51 mRNA levels. Consistent with this, genetic knockdown of Stat5a/b suppressed HR DNA repair while not affecting NHEJ DNA repair. Pharmacologic Stat5a/b inhibition potently sensitized prostate cancer cell lines and prostate cancer tumors to radiation, while not inducing radiation sensitivity in the neighboring tissues. Conclusions: This work introduces a novel concept of a pivotal role of Jak2–Stat5a/b signaling for Rad51 expression and HR DNA repair in prostate cancer. Inhibition of Jak2–Stat5a/b signaling sensitizes prostate cancer to radiation and, therefore, may provide an adjuvant therapy for radiation to reduce radiation-induced damage to the neighboring tissues. Clin Cancer Res; 24(8); 1917–31. ©2018 AACR.
Immunologic efficacy of E39 &amp; E39' vaccination in a phase I/IIa trial in ovarian and endometrial cancer patients.
Authors: Tommy A Brown, Kaitlin M. Peace, John W Myers, Timothy J Vreeland, Diane F Hale, Doreen O Jackson, Julia M Greene, John S Berry, Guy T Clifton, Garth S Herbert, George Earl Peoples
Journal: Journal of Clinical Oncology (2018)

75 Background: The treatment options for cancer are ever-evolving &amp; now include vaccines targeting tumor-specific immunogenic peptides to induce tumor cytolysis. Folate binding protein (FBP) is a tumor-associated antigen (TAA) highly expressed in most endometrial &amp; ovarian cancers (Ca), shielded from the normal immune system. The most promising FBP peptides are E39 &amp; an attenuated form, E39' (aka J65). In our most recent phase I/IIa trial we evaluated an E39+GM-CSF inoculation series at 3 doses (VG) vs controls (CG) as well as booster vaccination with E39 or E39' after the initial inoculation series. Here we present the immunologic data from this phase I/IIa trial. Methods: Patients (pts) with ovarian or endometrial Ca who were disease-free after standard of care therapy but at risk for recurrence were enrolled. HLA-A2+ pts were vaccinated in a 3+3 dose escalation of 100mcg, 500mcg, &amp; 1000mcg. The remaining pts received 1000mcg inoculations. Vaccine was given every 3-4 weeks for a total of 6 inoculums. Pts were then offered to participate in booster vaccination with 9 pts randomized to receive E39 &amp; 9 pts E39'. FBP expression level was measured on the resected disease. Overall immunologic response &amp; by subgroups was measured by delayed type hypersensitivity (DTH) &amp; ELISPOT in the VG. Results: A total of 29 pts were vaccinated. Mean DTH prior to the initial dose of E39 was 5.74mm &amp; after final dose was 10.33mm (p = 0.018). Mean overall ELISPOT change over time through 18 months was +69.1 when compared to baseline (p = 0.675). At 18 months, mean ELISPOT increased by 97.1 in 1000mcg vs -57.0 in &lt; 1000mcg dosed pts (p = 0.047) &amp; by +255.33 in pts with &gt; average initial DTH vs -0.75 in &lt; average initial DTH (p = 0.004) when compared to baseline. Immunological analyses were not significantly different between FBP hi/lo expression or E39 vs E39’ booster (p &gt; 0.05). Conclusions: E39 demonstrated significant overall immunogenicity on in vivo testing as measured by DTH. Ex vivo analysis (ELISPOT) suggests that E39 is more immunogenically efficacious in pts with &gt; average initial DTH &amp; those who are optimally dosed (1000mcg). FBP expression level &amp; E39 vs E39’ use in booster inoculations did not significantly impact in vivo or ex vivo immunogenicity. Clinical trial information: NCT01580696.
<i>What is travel medicine?</i>
Authors: Jane N Zuckerman
Journal: BMJ (2004)

<i>Got a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site</i>
Cardioprotection induced by a brief exposure to acetaldehyde: role of aldehyde dehydrogenase 2
Authors: Cintia Bagne Ueta, Juliane Cruz Campos, Rudá Prestes e Albuquerque, Vanessa Morais Lima, Marie-Hélène Disatnik, Angélica Bianchini Sanchez, Che-Hong Chen, Marisa Helena Gennari de Medeiros, Wenjin Yang, Daria Mochly-Rosen, Julio Cesar Batista Ferreira
Journal: Cardiovascular Research (2018)

We previously demonstrated that acute ethanol administration protects the heart from ischaemia/reperfusion (I/R) injury thorough activation of aldehyde dehydrogenase 2 (ALDH2). Here, we characterized the role of acetaldehyde, an intermediate product from ethanol metabolism, and its metabolizing enzyme, ALDH2, in an ex vivo model of cardiac I/R injury.We used a combination of homozygous knock-in mice (ALDH2*2), carrying the human inactivating point mutation ALDH2 (E487K), and a direct activator of ALDH2, Alda-1, to investigate the cardiac effect of acetaldehyde. The ALDH2*2 mice have impaired acetaldehyde clearance, recapitulating the human phenotype. Yet, we found a similar infarct size in wild type (WT) and ALDH2*2 mice. Similar to ethanol-induced preconditioning, pre-treatment with 50 μM acetaldehyde increased ALDH2 activity and reduced cardiac injury in hearts of WT mice without affecting cardiac acetaldehyde levels. However, acetaldehyde pre-treatment of hearts of ALDH2*2 mice resulted in a three-fold increase in cardiac acetaldehyde levels and exacerbated I/R injury. Therefore, exogenous acetaldehyde appears to have a bimodal effect in I/R, depending on the ALDH2 genotype. Further supporting an ALDH2 role in cardiac preconditioning, pharmacological ALDH2 inhibition abolished ethanol-induced cardioprotection in hearts of WT mice, whereas a selective activator, Alda-1, protected ALDH2*2 against ethanol-induced cardiotoxicity. Finally, either genetic or pharmacological inhibition of ALDH2 mitigated ischaemic preconditioning.Taken together, our findings suggest that low levels of acetaldehyde are cardioprotective whereas high levels are damaging in an ex vivo model of I/R injury and that ALDH2 is a major, but not the only, regulator of cardiac acetaldehyde levels and protection from I/R.