tbuckley/cabot-search huggingface dataset:
CDK6 is an essential direct target of NUP98 fusion proteins in acute myeloid leukemia
Authors: Johannes Schmoellerl, Inês Amorim Monteiro Barbosa, Thomas Eder, Tania Brandstoetter, Luisa Schmidt, Barbara Maurer, Selina Troester, Ha Thi Thanh Pham, Mohanty Sagarajit, Jessica Ebner, Gabriele Manhart, Ezgi Aslan, Stefan Terlecki-Zaniewicz, Christa Van der Veen, Gregor Hoermann, Nicolas Duployez, Arnaud Petit, Helene Lapillonne, Alexandre Puissant, Raphael Itzykson, Richard Moriggl, Michael Heuser, Roland Meisel, Peter Valent, Veronika Sexl, Johannes Zuber, Florian Grebien
Journal: Blood (2020)
Going viral: doctors must tackle fake news in the covid-19 pandemic
Authors: Cathal O’Connor, Michelle Murphy
Journal: BMJ (2020)

“Duirt bean liom go nduirt bean lei—a woman told me that a woman told her”—Irish proverb.

The general public has been overwhelmed with information related to the novel coronavirus.1 In Ireland the medical community has noted a trend of messages containing incorrect information about covid-19 spreading rapidly through social media and messaging apps. Misinformation is defined as false information that is communicated without deliberate malice; disinformation is false information that is communicated with the intent to deceive.2 The …
Protective Effects of Dietary Intake of Antioxidants and Treatment-Related Toxicity in Childhood Leukemia: A Report From the DALLT Cohort
Authors: Elena J. Ladas, Traci M. Blonquist, Maneka Puligandla, Manuela Orjuela, Kristen Stevenson, Peter D. Cole, Uma H. Athale, Luis A. Clavell, Jean-Marie Leclerc, Caroline Laverdiere, Bruno Michon, Marshall A. Schorin, Jennifer Greene Welch, Barbara L. Asselin, Stephen E. Sallan, Lewis B. Silverman, Kara M. Kelly
Journal: Journal of Clinical Oncology (2020)

The benefits and risks of supplementation with antioxidants during cancer therapy have been a controversial area. Few studies have systematically evaluated dietary intake of antioxidants with toxicity and survival in childhood cancer. We sought to determine the role of dietary intake of antioxidants on rates of infections, mucositis, relapse, and disease-free survival during induction and postinduction phases of therapy among children and adolescents with acute lymphoblastic leukemia (ALL).We enrolled 794 children in a prospective clinical trial for treatment of ALL. Dietary intake was prospectively evaluated by a food frequency questionnaire. The association between dietary intake of antioxidants and treatment-related toxicities and survival were evaluated with the Benjamini-Hochberg false discovery rate (q) and logistic regression and the Kaplan-Meier method, respectively.Dietary surveys were available for analysis from 614 (77%), and 561 (71%) participants at diagnosis and at end of induction, respectively. Of 513 participants who completed the dietary surveys at both time points, 120 (23%) and 87 (16%) experienced a bacterial infection and 22 (4%) and 55 (10%) experienced mucositis during the induction or postinduction phases of treatment, respectively. Increased intake of dietary antioxidants was associated with significantly lower rates of infection and mucositis. No association with relapse or disease-free survival was observed. Supplementation was not associated with toxicity, relapse, or survival.Consumption of antioxidants through dietary intake was associated with reduced rates of infection or mucositis, with no increased risk of relapse or reduced survival. Dietary counseling on a well-balanced diet that includes an array of antioxidants from food sources alone may confer a benefit from infections and mucositis during treatment of childhood ALL.
Limiting Vulnerable Infants’ Secondhand Smoke Exposure
Authors: Anita Slomski
Journal: JAMA (2020)

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
Oncolytic measles virus therapy enhances tumor antigen-specific T-cell responses in patients with multiple myeloma
Authors: Nandakumar Packiriswamy, Deepak Upreti, Yumei Zhou, Rehan Khan, Amber Miller, Rosa M. Diaz, Cliona M. Rooney, Angela Dispenzieri, Kah-Whye Peng, Stephen J. Russell
Journal: Leukemia (2020)

Abstract Oncolytic virus therapy leads to immunogenic death of virus-infected tumor cells and this has been shown in preclinical models to enhance the cytotoxic T-lymphocyte response against tumor-associated antigens (TAAs), leading to killing of uninfected tumor cells. To investigate whether oncolytic virotherapy can increase immune responses to tumor antigens in human subjects, we studied T-cell responses against a panel of known myeloma TAAs using PBMC samples obtained from ten myeloma patients before and after systemic administration of an oncolytic measles virus encoding sodium iodide symporter (MV-NIS). Despite their prior exposures to multiple immunosuppressive antimyeloma treatment regimens, T-cell responses to some of the TAAs were detectable even before measles virotherapy. Measurable baseline T-cell responses against MAGE-C1 and hTERT were present. Furthermore, MV-NIS treatment significantly ( P &lt; 0.05) increased T-cell responses against MAGE-C1 and MAGE-A3. Interestingly, one patient who achieved complete remission after MV-NIS therapy had strong baseline T-cell responses both to measles virus proteins and to eight of the ten tested TAAs. Our data demonstrate that oncolytic virotherapy can function as an antigen agnostic vaccine, increasing cytotoxic T-lymphocyte responses against TAAs in patients with multiple myeloma, providing a basis for continued exploration of this modality in combination with immune checkpoint blockade.
Agreement Between 2-Dimensional Shear Wave and Transient Elastography Values for Diagnosis of Advanced Chronic Liver Disease
Authors: Christophe Cassinotto, Bruno Lapuyade, Boris Guiu, Hortense Marraud des Grottes, Lauranne Piron, Wassil Merrouche, Marie Irles-Depe, Nicolas Molinari, Victor De Ledinghen
Journal: Clinical Gastroenterology and Hepatology (2020)
Dynamics of anti-SARS-Cov-2 IgM and IgG antibodies among COVID-19 patients
Authors: Yu-Lin Lee, Chia-Hung Liao, Po-Yu Liu, Chien-Yu Cheng, Ming-Yi Chung, Chun-Eng Liu, Sui-Yuan Chang, Po-Ren Hsueh
Journal: Journal of Infection (2020)
Abstract 12113: Early Right Ventricular Response to Cardiac Resynchronization Therapy: Impact on Clinical Outcomes
Authors: Davide Stolfo, Elisabetta Tonet, Marco Merlo, Giulia Barbati, Marta Gigli, Bruno Pinamonti, Federica Ramani, Massimo Zecchin, Gianfranco Sinagra
Journal: Circulation (2015)

Introduction: Right ventricular (RV) dysfunction has been associated with a worse outcome in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT). However, evidences on the RV response to CRT are controversial and there are no data regarding the early effects of CRT on RV function (RVF). Hypothesis: We sought to investigate whether CRT favorably influences the RVF acutely after implantation, impacting on long-term outcomes. Methods: Patients who successfully underwent CRT implantation from January 2005 to January 2014 were retrospectively analyzed. RV dysfunction was defined by a RV-fractional area change&lt;35%. Post-procedural echocardiographic evaluation was performed at a median time of 2 days (IQR 1-6). Primary end-point was a composite of all-cause mortality and urgent heart transplantation. Results: A total of 194 patients with available pre- and post-procedural RVF assessment were included. Sixty-two (32%) presented an impaired RVF before procedure. Of them, 32% promptly normalized RVF following CRT. This occurred in parallel with a large improvement in pulmonary arterial pressure, mitral regurgitation, E/E’ ratio and diastolic function. Pre-implantation independent predictors of early RVF normalization were left-bundle branch block (p=0.034) and higher systolic blood pressure (p=0.026). Improvement in RVF was independently associated with a better long-term prognosis at multivariable analysis (HR 0.124; 95% CI 0.016-0.966, p=0.04), significantly increasing the accuracy of the long-term risk stratification compared to the baseline Cox model (p=0.04 at 48 months and p=0.048 at 96 months). Conclusions: Acute normalization of RVF can be observed after CRT along with hemodynamic improvement, resulting as independent predictor of transplant-free survival.
Cardiovascular comorbidity and its impact on patients with COVID-19
Authors: Wei-jie Guan, Wen-hua Liang, Jian-xing He, Nan-shan Zhong
Journal: European Respiratory Journal (2020)

We truly appreciate the comments from C.E. Leiva Sisnieguez and colleagues, who have performed a further analysis on the potential association between cardiovascular comorbidities and the clinical outcomes of coronavirus disease 2019 (COVID-19), particularly the mortality). We also applaud the suggestion to thoroughly adjust for potential confounding factors when interpreting the association between specific categories of cardiovascular comorbidities ( e.g. hypertension) and the clinical outcomes of COVID-19. To this end, we have attempted to incorporate the cardiovascular diseases (including coronary heart disease) into the multivariate regression model [1]. Findings of the model indicated a prominent collinearity between hypertension and coronary heart disease, and we have therefore elected to retain hypertension in the regression model for further analyses. Comorbid hypertension correlates with poorer outcomes in patients with COVID-19 <https://bit.ly/2zoT9f0>
Covid-19: Doctors performing resuscitation need higher level of PPE, says royal college
Authors: Gareth Iacobucci
Journal: BMJ (2020)

Doctors and nurses carrying out resuscitation on patients with covid-19 must be given the highest level of personal protective equipment (PPE), the Royal College of Physicians and Surgeons of Glasgow has urged.

The college said that UK public health agencies must change their guidance on the use of PPE and adopt stricter requirements to protect clinicians. It said that doctors or nurses who were required to carry out cardiopulmonary resuscitation should be equipped with the highest level of protection (level 3 PPE), which includes a respirator and visor.

The recommendation follows a statement on 20 April from the …
Pulmonary complications for women with sickle cell disease in pregnancy: systematic review and meta-analysis
Authors: Sivarajini Inparaj, Mickey Buckingham, Laura Oakley, Paul T Seed, Sebastian Lucas, Eugene Oteng-Ntim
Journal: Thorax (2020)

Background Sickle cell disease (SCD) is a multisystem disease characterised by vaso-occlusive crisis, chronic anaemia and a shorter lifespan. More patients with SCD are living till reproductive age and contemplating pregnancy. Pulmonary complications in pregnancy are significant causes of maternal morbidity and mortality but yet this has not been systematically quantified. A systematic review and meta-analysis were conducted to quantify the association between SCD and pulmonary complications in pregnancy. Methods MEDLINE, EMBASE, Web of Science, Cochrane and Maternity and Infant Care databases were searched for publications between January 1998 and April 2019. Observational studies involving at least 30 participants were included. Random-effects models were used for statistical meta-analysis. Findings Twenty-two studies were included in the systematic review and 18 in the quantitative analysis. The meta-analysis included 3964 pregnancies with SCD and 336 559 controls. Compared with women without SCD, pregnancies complicated by SCD were at increased risk of pulmonary thromboembolism (relative risk (RR) 7.74; 95% CI 4.65 to 12.89). The estimated prevalence of acute chest syndrome and pneumonia was 6.46% (95% CI 4.66% to 8.25%), with no significant difference between the HbSS and HbSC genotypes (RR 1.42; 95% CI 0.90 to 2.23). Interpretation This meta-analysis highlighted a strong association between SCD and maternal pulmonary complications. Understanding the risks of and the factors associated with pulmonary complications would aid preconceptual counselling and optimal management of the condition in pregnancy, thereby reducing associated maternal morbidity and mortality. PROSPERO registration number CRD42019124708.
Treatment Cessation in Chronic Myeloid Leukemia As a Part of Treatment Process: Toxicity Determined and Active Stop of Tyrosine Kinase Inhibitors
Authors: Anna G. Turkina, Ekaterina Yu. Chelysheva, Vasiliy Shuvaev, Galina Gusarova, Anastasia Bykova, Olga V. Lazareva, Oleg Shukhov, Adham Abdullaev, Irina Martynkevich, Kudrat Abdulkadyrov
Journal: Blood (2014)
The Impact of COVID-19 Outbreak on Uro-oncological Practice Across Europe: Which Burden of Activity Are We Facing Ahead?
Authors: Marco Oderda, Morgan Roupret, Giancarlo Marra, Axel S. Merseburger, Gianluca Oderda, Marco Falcone, Carlo Ceruti, Shahrokh F. Shariat, Paolo Gontero
Journal: European Urology (2020)
Exclusion of Cutaneous Lupus Erythematosus Subtypes From the 2019 European League Against Rheumatism/American College of Rheumatology Classifi cation Criteria for Systemic Lupus Erythematosus: Comment on the Article by Aringer et al
Authors: Lucio Zapata, Benjamin F. Chong
Journal: Arthritis & Rheumatology (2020)
FS222, a CD137/PD-L1 Tetravalent Bispecific Antibody, Exhibits Low Toxicity and Antitumor Activity in Colorectal Cancer Models
Authors: Matthew A. Lakins, Alexander Koers, Raffaella Giambalvo, Jose Munoz-Olaya, Robert Hughes, Emma Goodman, Sylwia Marshall, Francisca Wollerton, Sarah Batey, Daniel Gliddon, Mihriban Tuna, Neil Brewis
Journal: Clinical Cancer Research (2020)

With the increased prevalence in checkpoint therapy resistance, there remains a significant unmet need for additional therapies for patients with relapsing or refractory cancer. We have developed FS222, a bispecific tetravalent antibody targeting CD137 and PD-L1, to induce T-cell activation to eradicate tumors without the current toxicity and efficacy limitations seen in the clinic.A bispecific antibody (FS222) was developed by engineering CD137 antigen-binding sites into the Fc region of a PD-L1 IgG1 mAb. T-cell activation by FS222 was investigated using multiple in vitro assays. The antitumor efficacy, survival benefit, pharmacodynamics, and liver pharmacology of a murine surrogate molecule were assessed in syngeneic mouse tumor models. Toxicology and the pharmacokinetic/pharmacodynamic profile of FS222 were investigated in a non-human primate dose-range finding study.We demonstrated simultaneous binding of CD137 and PD-L1 and showed potent T-cell activation across CD8+ T-cell activation assays in a PD-L1-dependent manner with a CD137/PD-L1 bispecific antibody, FS222. FS222 also activated T cells in a human primary mixed lymphocyte reaction assay, with greater potency than the monospecific mAb combination. FS222 showed no signs of liver toxicity up to 30 mg/kg in a non-human primate dose-range finding study. A surrogate molecule caused significant tumor growth inhibition and survival benefit, concomitant with CD8+ T-cell activation, in CT26 and MC38 syngeneic mouse tumor models.By targeting CD137 agonism to areas of PD-L1 expression, predominantly found in the tumor microenvironment, FS222 has the potential to leverage a focused, potent, and safe immune response augmenting the PD-(L)1 axis blockade.
Global regulatory agility during covid-19 and other health emergencies
Authors: Tippi K Mak, John CW Lim, Prapassorn Thanaphollert, Gugu N Mahlangu, Emer Cooke, Murray M Lumpkin
Journal: BMJ (2020)

An Omani infant boy who presented in the neonatal period with cardiac failure secondary to hypertrophic cardiomyopathy is reported. He subsequently progressed to show features of a metabolic disorder with multisystem involvement and was diagnosed to have Type II glycogenosis (Pompe9s disease). The differential diagnosis and management of metabolic cardiomyopathy are outlined.
Cycled Phototherapy Dose-Finding Study for Extremely Low-Birth-Weight Infants
Authors: Cody Arnold, Jon E. Tyson, Claudia Pedroza, Wally A. Carlo, David K. Stevenson, Ronald Wong, Allison Dempsey, Amir Khan, Rafael Fonseca, Myra Wyckoff, Alvaro Moreira, Robert Lasky
Journal: JAMA Pediatrics (2020)

Cycled (intermittent) phototherapy (PT) might adequately control peak total serum bilirubin (TSB) level and avoid mortality associated with usual care (continuous PT) among extremely low-birth-weight (ELBW) infants (401-1000 g).To identify a cycled PT regimen that substantially reduces PT exposure, with an increase in mean peak TSB level lower than 1.5 mg/dL in ELBW infants.This dose-finding randomized clinical trial of cycled PT vs continuous PT among 305 ELBW infants in 6 US newborn intensive care units was conducted from March 12, 2014, to November 14, 2018.Two cycled PT regimens (≥15 min/h and ≥30 min/h) were provided using a simple, commercially available timer to titrate PT minutes per hour against TSB level. The comparator arm was usual care (continuous PT).Mean peak TSB level and total PT hours through day 14 in all 6 centers and predischarge brainstem auditory-evoked response wave V latency in 1 center. Mortality and major morbidities were secondary outcomes despite limited power.Consent was requested for 452 eligible infants and obtained for 305 (all enrolled) (mean [SD] birth weight, 749 [152] g; gestational age, 25.7 [1.9] weeks; 81 infants [27%] were multiple births; 137 infants [45%] were male; 112 [37%] were black infants; and 107 [35%] were Hispanic infants). Clinical and demographic characteristics of the groups were similar at baseline. After a preplanned interim analysis of 100 infants, the regimen of 30 min/h or more was discontinued, and the study proceeded with 2 arms. Comparing 128 infants receiving PT of 15 min/h or more with 128 infants receiving continuous PT among those surviving to 14 days, mean peak TSB levels were 7.1 vs 6.4 mg/dL (adjusted difference, 0.7; 95% CI, 0.4-1.1 mg/dL) and mean total PT hours were 34 vs 72 (adjusted difference, -39; 95% CI, -45 to -32). Wave V latency adjusted for postmenstrual age was similar in 37 infants receiving 15 min/h or more of PT and 33 infants receiving continuous PT: 7.42 vs 7.32 milliseconds (difference, 0.10; 95% CI, -0.11 to 0.30 millisecond). The relative risk for death was 0.79 (95% CI, 0.40-1.54), with a risk difference of -4.5% (95% CI, -10.9 to 2.0). Morbidities did not differ between groups.Cycled PT can substantially reduce total PT with little increase in peak TSB level. A large, randomized trial is needed to assess whether cycled PT would increase survival and survival without impairment in small, preterm infants.ClinicalTrials.gov Identifier: NCT01944696.
Procarcinogen Activation and Mutational Signatures Model the Initiation of Carcinogenesis in Human Urothelial Tissues In Vitro
Authors: Simon C. Baker, Andrew S. Mason, Jennifer Southgate
Journal: European Urology (2020)

Disparity between genome-wide mutations in bladder and other cancers where smoking is a risk factor raises questions about carcinogenesis in different epithelia. To develop an experimental model of bladder carcinogenesis, we clonally expanded in vitro differentiated normal human urothelial (NHU) cells following exposure to an exemplar procarcinogen and used whole-genome DNA sequencing to derive mutational signatures. Benzo[a]pyrene (BaP) was activated by endogenous cytochrome P450 (cytochrome P450 family 1 subfamily A member 1 [CYP1A1]) to create genomically modified NHU cells. Comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) showed that mutations induced by BaP in NHU cells were similar to smoking-associated signatures in bladder and other cancers, including single- and doublet-base substitution signatures characterised by C > A transversions (COSMIC_SBS4 and COSMIC_DBS2, respectively), and an insertion/deletion signature of C deletions in homopolymer regions (COSMIC ID3). Our study provides the first direct evidence that BaP is activated locally in the urothelium, initiating the well-described smoking-associated mutational signatures. An absence of other common bladder cancer (BLCA)-associated genomic signatures points strongly to other primary causes of BLCA, which the new experimental approach described here is well placed to investigate. Mutational signatures ignore whether genes are affected, but tissue-specific drivers (KMT2D, KMT2C, and CDKN1A) were significantly overmutated in this model, providing insight on the emergent selection pressures. In a carefully controlled laboratory setting, we exposed normal human urothelial tissues to a procarcinogen (benzo[a]pyrene) found in cigarette smoke. We show that the urothelial tissues activated the carcinogen and led to mutations forming across the genome in a characteristic pattern. This particular “mutational signature” is found in bladder tumours and other smoking-induced cancers (eg, lung); however, our study highlights that there are other unknown mutational processes in bladder cancer that is not the direct result of smoke carcinogens, and this will require further investigation.
Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors
Authors: Johanna Theruvath, Elena Sotillo, Christopher W. Mount, Claus Moritz Graef, Alberto Delaidelli, Sabine Heitzeneder, Louai Labanieh, Shaurya Dhingra, Amaury Leruste, Robbie G. Majzner, Peng Xu, Sabine Mueller, Derek W. Yecies, Martina A. Finetti, Daniel Williamson, Pascal D. Johann, Marcel Kool, Stefan Pfister, Martin Hasselblatt, Michael C. Frühwald, Olivier Delattre, Didier Surdez, Franck Bourdeaut, Stephanie Puget, Sakina Zaidi, Siddhartha S. Mitra, Samuel Cheshier, Poul H. Sorensen, Michelle Monje, Crystal L. Mackall
Journal: Nature Medicine (2020)