tbuckley/cabot-search huggingface dataset:
OS02.6.A The TeloDIAG: How telomeric parameters can help in glioma rapid diagnosis and liquid biopsies approaches
Authors: P Billard, C Guerriau, C Carpentier, F Juillard, N Grandin, P Lomonte, P Kantapareddy, M Barritault, R Rimokh, P Verrelle, D Maucort-Boulch, D Figarella-Branger, F Ducray, C Dehais, M Charbonneau, D Meyronet, D A Poncet
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND The integration of molecular markers into the WHO 2016 classification has clarified the complex diagnosis of gliomas. Among these biomarkers, the TERT promoter mutation and the loss of ATRX (ATRX loss) are mutually exclusive alterations associated with re-activation of telomerase or alternative lengthening of telomeres (ALT), respectively. Strangely, 25% of gliomas display neither or both these alterations, a situation referred to as abnormal telomere maintenance mechanism (aTMM). MATERIAL AND METHODS To investigate the TMM actually involved in gliomas, the C-circle (CC) assay was adapted to tumor (FFPE and frozen) samples. RESULTS We constructed a CC-based algorithm able to identify the TMM of 284 gliomas with either TERT or ATRX alteration, with a sensitivity of 100% and a specificity of 97.3%, and succeeded in deciphering the TMM involved in 122 aTMM gliomas. Additionally, the combination of the TMM, the mutational status of the Isocitrate dehydrogenase 1/2 (IDH) gene, and the histological grading was used as base for a new classification: TeloDIAG. Six subtypes are defined in this classification: tOD, tLGA, tGBM_IDHmt, tGBM, and tAIV, corresponding to oligodendroglioma, IDHmt low grade astrocytoma, IDHmt glioblastoma, and IDHwt glioblastoma, respectively, the last class gathers ALT+ IDHwt glioma. The TeloDIAG diagnosis is 99% concordant with the WHO classification for glioma displaying typical molecular characteristics (N=312). It modified the classification of 38% (N=156) discordant tumors, such as IDHwt Astrocytoma, aTMM tumors, or gliomas with unexpected TMM (e.g. TERTwt oligodendroglioma, ATRX loss GBM). Interestingly, 20% (N=69) of TERTwt, ATRXwt, or IDHwt GBM were actually tAIV, which is remarkable as tAIV-glioma patients’ survival tended to be longer (21.2 months) than tGBM patients’ survival (16.5 months). Importantly, CC in blood sampled from IDHmt astrocytoma patients was detected with a sensitivity of 56% and a specificity of 95% (N = 206). CONCLUSION In sum, the TeloDIAG is a new, simple, and efficient tool helping in glioma diagnosis and a promising option for liquid biopsy
Letter to the Editor: Is HBV genotype strongly associated with HCC risk in patients with chronic hepatitis B?
Authors: Rui Huang, Jiacheng Liu, Jian Wang, Jie Li, Chao Wu
Journal: Hepatology (2021)

We read the article by McMahon et al with great interest. The authors found that hepatitis B virus (HBV) genotype was strongly associated with hepatocellular carcinoma (HCC) incidence in the Hepatitis B Alaska cohort and suggested that HBV genotype should be considered in risk factor stratification of HCC. Although inspiring, several issues warrant further clarification.
Indatuximab ravtansine plus dexamethasone with lenalidomide or pomalidomide in relapsed or refractory multiple myeloma: a multicentre, phase 1/2a study
Authors: Kevin R Kelly, Sikander Ailawadhi, David S Siegel, Leonard T Heffner, George Somlo, Sundar Jagannath, Todd M Zimmerman, Nikhil C Munshi, Sumit Madan, Asher Chanan-Khan, Sagar Lonial, Suraj Chandwani, Ashot Minasyan, Markus Ruehle, Farima Barmaki-Rad, Afsaneh Abdolzade-Bavil, Faiza Rharbaoui, Eva Herrmann-Keiner, Thomas Haeder, Andrea Wartenberg-Demand, Kenneth C Anderson
Journal: The Lancet Haematology (2021)
Publisher Correction: Circuit and molecular architecture of a ventral hippocampal network
Authors: Mark M. Gergues, Kasey J. Han, Hye Sun Choi, Brandon Brown, Kelsey J. Clausing, Victoria S. Turner, Ilia D. Vainchtein, Anna V. Molofsky, Mazen A. Kheirbek
Journal: Nature Neuroscience (2021)
One-Year Committed Exercise Training Reverses Abnormal Left Ventricular Myocardial Stiffness in Patients With Stage B Heart Failure With Preserved Ejection Fraction
Authors: Michinari Hieda, Satyam Sarma, Christopher M. Hearon, James P. MacNamara, Katrin A. Dias, Mitchel Samels, Dean Palmer, Sheryl Livingston, Margot Morris, Benjamin D. Levine
Journal: Circulation (2021)

Individuals with left ventricular (LV) hypertrophy and elevated cardiac biomarkers in middle age are at increased risk for the development of heart failure with preserved ejection fraction. Prolonged exercise training reverses the LV stiffening associated with healthy but sedentary aging; however, whether it can also normalize LV myocardial stiffness in patients at high risk for heart failure with preserved ejection fraction is unknown. In a prospective, randomized controlled trial, we hypothesized that 1-year prolonged exercise training would reduce LV myocardial stiffness in patients with LV hypertrophy.Forty-six patients with LV hypertrophy (LV septum >11 mm) and elevated cardiac biomarkers (N-terminal pro-B-type natriuretic peptide [>40 pg/mL] or high-sensitivity troponin T [>0.6 pg/mL]) were randomly assigned to either 1 year of high-intensity exercise training (n=30) or attention control (n=16). Right-heart catheterization and 3-dimensional echocardiography were performed while preload was manipulated using both lower body negative pressure and rapid saline infusion to define the LV end-diastolic pressure-volume relationship. A constant representing LV myocardial stiffness was calculated from the following: P=S×[Exp {a (V-V0)}-1], where "P" is transmural pressure (pulmonary capillary wedge pressure - right atrial pressure), "S" is the pressure asymptote of the curve, "V" is the LV end-diastolic volume index, "V0" is equilibrium volume, and "a" is the constant that characterizes LV myocardial stiffness.Thirty-one participants (exercise group [n=20]: 54±6 years, 65% male; and controls (n=11): 51±6 years, 55% male) completed the study. One year of exercise training increased max by 21% (baseline 26.0±5.3 to 1 year later 31.3±5.8 mL·min-1·kg-1, P<0.0001, interaction P=0.0004), whereas there was no significant change in max in controls (baseline 24.6±3.4 to 1 year later 24.2±4.1 mL·min-1·kg-1, P=0.986). LV myocardial stiffness was reduced (right and downward shift in the end-diastolic pressure-volume relationship; LV myocardial stiffness: baseline 0.062±0.020 to 1 year later 0.031±0.009), whereas there was no significant change in controls (baseline 0.061±0.033 to 1 year later 0.066±0.031, interaction P=0.001).In patients with LV hypertrophy and elevated cardiac biomarkers (stage B heart failure with preserved ejection fraction), 1 year of exercise training reduced LV myocardial stiffness. Thus, exercise training may provide protection against the future risk of heart failure with preserved ejection fraction in such patients. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03476785.
Coaches Activating Reaching and Engaging Patients (CAREPlan): A randomized controlled trial combining two evidence-based interventions to improve goals of care documentation.
Authors: Divya Ahuja Parikh, Mary Khay Asuncion, Jennifer Hansen, Briththa Seevaratnam, Sana Indravadan Khateeb, Eben Lloyd Rosenthal, Winifred Teuteberg, Manali I. Patel
Journal: Journal of Clinical Oncology (2021)

2 Background: In our prior work, community or lay health worker-led goals of care interventions improved goals of care documentation by clinicians and decreased health care use at the end of life. Other studies have demonstrated improvements in provider-patient communication and goals of care documentation using the Serious Illness Care Program. The objective of this study was to determine whether the combination of these two interventions could improve goals of care documentation among patients with advanced stages of genitourinary cancers at an academic center. Methods: A randomized controlled trial was conducted from April 3, 2019, through October 30, 2019, among patients with metastatic or recurrent cancer on at least second line therapy in the urologic oncology clinics at Stanford Cancer Center. Patients were randomized to usual care or the intervention with a lay navigator trained to assist patients with establishing end-of-life care preferences using the Serious Illness Conversation Guide. The primary outcome was goals of care documentation by the primary oncologist. We used intent to treat analyses, descriptive statistics to compare demographic and clinical factors, and a logistic regression adjusting for imbalance to determine the effect on the primary outcome. Results: Two-hundred participants were randomized and included in the intent to treat analysis. Median age was 72 years, majority were male (n=175, 87.5%) and self-identified as non-Hispanic white (n=123, 61.5%). The majority had prostate cancer (n=110, 53.5%), followed by kidney cancer (n=51, 25.5%), and urothelial cancer (n=29, 14.5%) and most had stage IV disease at diagnosis (n=186, 93%). There were no significant differences in demographic or clinical factors except for gender; there were more females on the control arm (n=8 vs n=17, p=0.01) thus analysis of the primary outcome was adjusted for gender. The adjusted analysis showed that at 12 months post-enrollment, the intervention significantly increased goals of care documentation by the primary oncologist as compared to the control group (53.7% vs 32.6%, p=0.002). Conclusions: The CAREPlan program increased goals of care documentation by the primary oncologist at this single academic medical center. Clinical trial information: NCT03856463.
Scotland: class A drug users could be warned rather than face prosecution
Authors: Matthew Limb
Journal: BMJ (2021)

People caught in possession of class A drugs in Scotland could be given a police warning rather than face prosecution, in a marked government policy shift.

The police warning scheme which already applies to possession of class B and C drugs is being extended, it was confirmed this week. “Police officers may therefore choose to issue a recorded warning for simple possession offences for all classes of drugs,” Scotland’s Lord Advocate Dorothy Bain QC told the Holyrood parliament on 22 September. …
Radiation-Associated Coronary Disease in Young Cancer Survivors
Authors: James E. Bates, Ming Hui Chen, Louis S. Constine
Journal: JACC CardioOncology (2021)

adiotherapy (RT) is a critical component of breast cancer therapy, halving the risk of disease recurrence after lumpectomy.RT for breast cancer typically involves tangent fields: 2 opposed fields placed at a tangent to the chest wall on the site of the involved breast.For patients with left-sided breast cancer, this technique delivers a high radiation dose to a small anterior portion of the heart, and this often includes the left anterior descending coronary artery.For patients who require RT to the internal mammary chain nodes, heart RT dose is increased.Although modern techniques (deep inspiratory breath hold, lateral decubitus positioning, or proton therapy) may help reduce heart RT doses, they do not eliminate it.RT-related cardiac disease is a significant concern in nearly all patients receiving thoracic-directed RT.
Особливості стану верхніх відділів шлунково-кишкового тракту за даними ендоскопічного дослідження у хворих на хронічний криптогенний гепатит і цироз печінки
Authors: O.V. Simonova, L.Ya, Melnychenko, V.B. Yagmur
Journal: GASTROENTEROLOGY (2013)

Наведено дані щодо вивчення слизової оболонки стравоходу, шлунка й дванадцятипалої кишки хворих на криптогенний гепатит і цироз печінки. Виявлено зміни, обумовлені портальною гіпертензією (варикозне розширення вен стравоходу й шлунка, портальна гастропатія), і зміни, поєднані з хронічними дифузними запальними захворюваннями печінки (ознаки рефлюксної хвороби, ерозивні й геморагічні зміни слизової оболонки шлунка й дванадцятипалої кишки). Особливістю гастропатій при цирозах печінки, на відміну від гастропатій, що перебігають самостійно, були більш виражені інтенсивність і поширеність у шлунку еритематозних змін слизової, що пов’язано з формуванням портальної гіпертензії й коагулопатії і не корелює з вираженістю запалення на мікроскопічному рівні.
The evolution of the education module for men with metastatic prostate cancer (mPC) in the prostate cancer supportive care (PCSC) program.
Authors: Jennifer Marie Rauw, Sunil Parimi, Nikita Ivanov, Jessica Noble, Eugenia Wu, Monita Sundar, Jennifer Goulart, Celestia S. Higano
Journal: Journal of Clinical Oncology (2021)

279 Background: The PCSC Program was initiated in 2013 at the Vancouver Prostate Centre to provide a comprehensive program for patients and partners with prostate cancer. This program provides educational sessions (ES) and clinical services, including decision-making for primary therapy, sexual health, pelvic floor physiotherapy, hormone therapy, counseling, exercise, and nutrition for patients in BC, Canada. In 2016, the PCSC Program expanded to BC Cancer Victoria and in 2017 to other BC Cancer sites. In 2018, medical oncologists (MDs) in Victoria (JR, SP) developed an Education Module addressing treatment options for men with metastatic hormone sensitive (mHSPC) and metastatic castration resistant (mCRPC) disease. MDs delivered in-person ES in Victoria in 2018 and, in 2019, added a virtual platform (VP) option. From 3-5/2020, the ESs were on hold due to the COVID pandemic and parental leaves. In 6/2020, the ESs resumed only on VP, and the PCSC Oncology Nurse Practitioner (NP), NI, gave the presentations for the MDs on leave. In 10/2020, due to a changing standard of care for mHSPC, the PCSC team consolidated the two ESs into one. We report on the evolution of this Education Module in response to both the changing standard of care and the COVID pandemic. Methods: We prospectively collected attendance and patient characteristic metrics from all ES for men with mPC. We tracked presenter type (MD vs. NP) and prospectively collected anonymous patient satisfaction questionnaires. Results: From 1/2018 to 1/2021, 100 men registered for 27 ES; 81 men, 41 partners, and 2 family members actually attended. 48/75 (64%) men were white, 39/75 (52%) retired, and 56/75 (74.7%) married. 47 men attended 12 mHSPC ES, 13 men attended ten mCRPC ES, and 17 attended four consolidated ES. MDs presented 15 ES, and the NP presented 12 ES. Responses to questions on 70 satisfaction surveys were similar for MD vs. NP presenters. 9 responders to the recently added VP-specific questions said they agreed (4) or strongly agreed (5) that it was beneficial to watch the ES at home on a computer. The Table below shows attendance per site per year. Conclusions: The ESs for men with mPC were well-received. Although there was a VP option before COVID, attendance increased significantly after the lockdown as patients and providers became more familiar with VPs. Satisfaction surveys confirmed that an NP could deliver the ES rather than MD. Consolidation of the mHSPC and mCRPC ES reflected the changing standard of care and resulted in more efficient use of presenter time. Virtual delivery of the sessions provided greater access to those living in distant or remote areas of the province and those in lockdown during the COVID pandemic. [Table: see text]
Factors and Challenges in Understanding SARS-CoV-2 RNA Levels, Symptoms, and Transmissibility
Authors: Hiroyuki Kuroda
Journal: JAMA Pediatrics (2021)

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 Journals 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 2024 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
Safety and efficacy of oral levosimendan in people with amyotrophic lateral sclerosis (the REFALS study): a randomised, double-blind, placebo-controlled phase 3 trial
Authors: Merit Cudkowicz, Angela Genge, Nicholas Maragakis, Susanne Petri, Leonard van den Berg, Valtteri V Aho, Toni Sarapohja, Mikko Kuoppamäki, Chris Garratt, Ammar Al-Chalabi, Matthew Kiernan, Susan Mathers, Robert Henderson, Merrilee Needham, David Schultz, Wolfgang Löscher, Nenad Mitrovic, Jakob Rath, Philip Van Damme, Jan L. De Bleecker, Stéphanie Delstanche, Wendy Johnston, Lorne Zinman, Colleen O'Connell, Genevieve Matte, Annie Dionne, Lawrence Korngut, John Turnbull, Hannu Laaksovirta, Manu Jokela, Tero Tapiola, Marie-Hélène Soriani, Philippe Couratier, William Camu, Philippe Corcia, Albert Ludolph, Julian Großkreutz, Thomas Meyer, Matthias Boentert, Berthold Schrank, Johannes Prudlo, Robert Untucht, Orla Hardiman, Gabriele Siciliano, Adriano Chio', Letizia Mazzini, Maurizio Inghilleri, Claudia Caponnetto, Gabriele Mora, Jesús S Mora Pardina, Eva Farrero Munoz, Juan F Vázquez Costa, Eduardo Aguera Morales, Luis Varona, Peter Andersen, Caroline Ingre, Rune Johansson, Aleksandar Radunovic, Carolyn Young, Suma Babu, Aziz Shaibani, Nathan Staff, Tuan Vu, Michael Rivner, Stephen Scelsa, Kumaraswamy Sivakumar, Waqar Waheed, Daragh Heitzman, Sandeep Rana, Gary Pattee, Senda Ajroud-Driss, Elham Bayat, Edward Kasarskis, Dale J Lange, Michael Elliott, Brent Harris, Kevin Felice, Michael T Pulley, Justin Kwan, Martin Brown, John Ravits, Matthew Burford, Chafic Karam, Timothy Miller, Jinsy Andrews, Todd Levine, Eduardo Locatelli, James Wymer, Richard Bedlack, Dominic Fee, Namita Goyal, Bjorn Oskarsson, Leo McCluskey, James Caress, Michael Weiss, Adam Quick, Mark Bromberg, David Lacomis, Stephen Goutman, Kourosh Rezania, Gaurav Guliani, Kimberly Goslin, Jonathan S Katz
Journal: The Lancet Neurology (2021)
A phase 3 open-label, randomized multicenter study to evaluate efficacy and safety of secukinumab in pediatric patients with moderate to severe plaque psoriasis: 24-week results
Authors: Nina Magnolo, Külli Kingo, Vivian Laquer, John Browning, Adam Reich, Jacek C. Szepietowski, Deborah Keefe, Rafal Mazur, Prayashi Ghelani, Pascal Forrer, LindaAnn Wraith, Manmath Patekar
Journal: Journal of the American Academy of Dermatology (2021)
Beyond proteins: Ubiquitylation of lipopolysaccharide to fight bacteria
Authors: Yanqiu Gong, Litong Nie, Lunzhi Dai
Journal: MedComm (2021)

Mechanisms and functions of protein ubiquitylation and LPS ubiquitylation. LPS ubiquitylation serves as a scaffold to recruit E3 ligases for the ubiquitylation of the membrane of bacteria. Polyubiquitin coat on the bacterial cell surface is one type of “eat-me” signal recognized by the host cells. The abbreviations used in the figure are Pro, Protein; Ub, Ubiquitin; E1, Ubiquitin-activating enzymes; E2, Ubiquitin-conjugating enzymes; E3, Ubiquitin-ligating enzymes; LPS, lipopolysaccharide; RNF213, Ring Finger Protein 213; and LUBAC, linear ubiquitin chain assembly complex.
OS06.6A Inhibition of GBM invasion by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist Perampanel
Authors: K Sarnow, G Kanli, O Keunen, R Bjerkvig
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Extensive tumor cell invasion within the brain represents a major problem for effective treatment of glioblastomas (GBMs). The invasive processes can be divided into three types: Collective cell invasion, perivascular infiltration and single-cell invasion into the brain parenchyma. It has recently been shown that GBM cells have the ability to form synapses with neural cells pointing at an extensive communication network between brain cells GBM cells. This communication network can be mediated via the metabolites glutamine and glutamate both needed for GBM cell proliferation. In this context, it has been shown in preclinical models that Perampanel, an antiepileptic agent, functioning as non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor antagonist, has an inhibitory effect on GBM growth. In order to delineate how Perampanel affects GBM invasion, we here utilised a highly characterized 3D GBM-brain organoid invasion model where single-cell invasion was studied in real-time following Perampanel treatment. MATERIAL AND METHODS A brain coculture model, consisting of rat brain organoids expressing various markers of the human adult brain, where confronted with GFP-labelled tumor cells. By using time-lapse confocal microscopy, we quantified single-cell invasion patterns and speed of invasion using two glioma stem cell models (GSCs; BG5 and BG7). RESULTS Perampanel treatment significantly reduces tumor cell invasion into the brain organoids with the strongest effect seen in the most invasive GBM (BG5). Here, the single-tumor cell invasion ratio was reduced by 72 % compared to the control group (p=0.0033). In contrast, collective cell invasion was reduced by 19 % (p=0.028). Statistical analysis was performed using an unpaired sample t-test. CONCLUSION The AMPA glutamate receptor antagonist Perampanel significantly inhibits GBM invasion, suggesting an important role of the glutamate-glutamine cycle between the GBM cells and neurons in the invasion process. Moreover, this communication and exchange of metabolites seems to be more prominent where single GBM cells invade into the brain parenchyma compared to areas where collective invasion take place.
Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms
Authors: Chunyang Jiang, Na Zhang, Xiaoli Hu, Hongyan Wang
Journal: Molecular Cancer (2021)

Abstract As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. Lung cancer is a major malignant tumor that seriously threatens human health. The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. By promoting epithelial–mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application. In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in the near future.
Myeloid-Derived Suppressor Cell Subtypes Are Responsible for the Th2 Phenotype of T Cells in CLL
Authors: Gerardo Ferrer, Brendan Franca, Pui Yan Chiu, Stefano Vergani, Andrea Nicola Mazzarello, Florenca Palacios, Shihshih Chen, Davide Bagnara, Sophia Yancopoulos, Yun Liu, Aliki Xochelli, Xiao J. Yan, Jonathan E. Kolitz, Steven L. Allen, Jacqueline C. Barrientos, Kostas Stamatopoulos, Kanti Rai, Barbara Sherry, Nicholas Chiorazzi
Journal: Blood (2017)