tbuckley/cabot-search huggingface dataset:
Sotorasib Tackles <i>KRAS</i>G12C-Mutated Pancreatic Cancer
Journal: Cancer Discovery (2022)

The KRASG12C inhibitor sotorasib was associated with a 21.1% objective response rate and an 84.2% disease control rate among patients who had already received at least one therapy for pancreatic ductal adenocarcinoma. These data come from the phase I/II CodeBreaK100 trial.
Persistent symptoms after the first wave of COVID-19 in relation to SARS-CoV-2 serology and experience of acute symptoms: A nested survey in a population-based cohort
Authors: Olivier Robineau, Emmanuel Wiernik, Cédric Lemogne, Xavier de Lamballerie, Laetitia Ninove, Hélène Blanché, Jean-François Deleuze, Céline Ribet, Sofiane Kab, Marcel Goldberg, Gianluca Severi, Mathilde Touvier, Marie Zins, Fabrice Carrat
Journal: The Lancet Regional Health - Europe (2022)

Many patients report persistent symptoms after COVID-19. Our aim was to determine whether some of these symptoms were more associated with past SARS-CoV-2 infection compared to other conditions.This prospective survey was nested in CONSTANCES, a randomly selected French population-based cohort, started in 2012. All participants being followed-up by internet completed 2 questionnaires during the first wave of the pandemic focusing on the acute symptoms of their COVID-19-like illness. Serological tests for SARS-CoV-2 were then performed (May-Nov 2020). Between December 2020 and January 2021, participants completed a third questionnaire about symptoms that had lasted more than 2 months. Participants were classified into four groups according to both European Center for Diseases Control (ECDC) criteria for COVID-19 (ECDC+ or ECDC-) and serological SARS-CoV-2 test results (Sero+ or Sero-). To compare the risk of each persistent symptom among the groups, logistic regression models were adjusted for age, sex, educational level, comorbidities, and the number of acute symptoms declared during the first wave of the epidemic. A mediation analysis was performed to estimate the direct effect of the infection on persistent symptoms and its indirect effect via the initial clinical presentation.The analysis was performed in 25,910 participants. There was a higher risk of persistent dysgeusia/anosmia, dyspnea and asthenia in the ECDC+/Sero+ group than in the ECDC+/Sero- group (OR: 6.83 [4.47-10.42], 1.69 [1.07-2.6] and 1.48 [1.05-2.07], respectively). Abdominal pain, sensory symptoms or sleep disorders were at lower risk in the ECDC+/Sero+ group than in the ECDC+/Sero- group (0.51 [0.24-0.96], 0.40 [0.16-0.85], and 0.69 [0.49-0.95], respectively). The mediation analysis revealed that the association of the serological test results with each symptom was mainly mediated by ECDC symptoms (proportion mediated range 50-107%).A greater risk of persistent dysgeusia/anosmia, dyspnea and asthenia was observed in SARS-CoV-2 infected people. The initial clinical presentation substantially drives the association of positive serological test results with persistent symptoms.French National Research Agency.
Influence of Telomere Length on the Achievement of Deep Molecular Response With Imatinib in Chronic Myeloid Leukemia Patients
Authors: Natalia Estrada, Blanca Xicoy, Fabian Beier, Olga Garcia, Cristian Morales, Concepción Boqué, Miguel Sagüés, Mónica S. Ventura Ferreira, Rolando Vallansot, Sílvia Marcé, Marta Cabezón, Tim H. Brümmendorf, Lurdes Zamora
Journal: HemaSphere (2021)

Tyrosine kinase inhibitors have dramatically changed the outcome of chronic myeloid leukemia (CML), and nowadays, one of the main treatment goals is the achievement of deep molecular responses (DMRs), which can eventually lead to therapy discontinuation approaches. Few biological factors at diagnosis have been associated with this level of response. Telomere length (TL) in peripheral blood cells of patients with CML has been related to disease stage, response to therapy and disease progression, but little is known about its role on DMR. In this study, we analyzed if age-adjusted TL (referred as "delta-TL") at diagnosis of chronic phase (CP)-CML might correlate with the achievement of DMR under first-line imatinib treatment. TL from 96 CP-CML patients had been retrospectively analyzed at diagnosis by monochrome multiplex quantitative PCR. We observed that patients with longer age-adjusted telomeres at diagnosis had higher probabilities to achieve DMR with imatinib than those with shortened telomeres (P = 0.035 when delta-TL was studied as a continuous variable and P = 0.047 when categorized by the median). Moreover, patients carrying long telomeres also achieved major molecular response significantly earlier (P = 0.012). This study provides proof of concept that TL has a role in CML biology and when measured at diagnosis of CP-CML could help to identify patients likely to achieve DMR to first-line imatinib treatment.
NRG-GI004/SWOG-S1610: Colorectal cancer metastatic dMMR immuno-therapy (COMMIT) study—A randomized phase III study of atezolizumab (atezo) monotherapy versus mFOLFOX6/bevacizumab/atezo in the first-line treatment of patients (pts) with deficient DNA mismatch repair (dMMR) or microsatellite instability high (MSI-H) metastatic colorectal cancer (mCRC).
Authors: Caio Max Sao Pedro Rocha Lima, Greg Yothers, Samuel A. Jacobs, Hanna Kelly Sanoff, Deirdre Jill Cohen, Katherine A Guthrie, Norah Lynn Henry, Patricia A. Ganz, Scott Kopetz, Peter C. Lucas, Charles David Blanke, Norman Wolmark, Howard S. Hochster, Thomas J. George, Michael J. Overman
Journal: Journal of Clinical Oncology (2022)

TPS232 Background: Despite the superiority in progression-free survival (PFS) of inhibition of programmed cell death-1 (PD-1) pathway in dMMR/MSI-H as compared to chemotherapy with either anti-vascular endothelial growth factor receptor (VEGFr) or anti-epithelial growth factor receptor (EGFr) antibodies in mCRC, more pts had progressive disease as the best response in the anti-PD1 monotherapy arm (29.4% vs. 12.3%) with mean PFS of 13.7 months ( N Engl J Med 2020; 383:2207). We hypothesize that the dMMR/MSI-H mCRC pts may be more effectively treated by the combination of PD-1 pathway blockade and mFOLFOX6/bevacizumab (bev) rather than with anti-PD-1 therapy (atezo) alone. Preclinical work demonstrated synergistic effects between anti-PD-1/anti-VEGF and between oxaliplatin/anti-PD-1 in murine CRC models and phase II data showed activity of anti-PD-1/anti-VEGF in chemotherapy refractory colon cancer. Additionally, in other solid tumor malignancies, anti-PD1 plus anti-VEGFr (i.e., HCC and RCC) as well as anti-PD1 plus chemotherapy (i.e., gastric and esophageal cancers) combinations are standard first-line treatments. Methods: The redesigned COMMIT study was reactivated on 1/29/2021 as a two-arm prospective phase III open-label trial randomizing (1:1) mCRC dMMR/MSI-H (211 pts) to atezo monotherapy versus mFOLFOX6/bev+atezo combination. Assuming our control arm, atezo monotherapy, 48% PFS at 24 months, as assessed by site investigator, we have 80% power to detect a hazard ratio of 0.6 (equivalent to 64.4% PFS at 24 months) with alpha 0.025 one-sided. Stratification factors include BRAFV600E status, metastatic site, and prior adjuvant CRC therapy. Secondary endpoints include OS, objective response rate, safety profile, disease control rate, duration of response, and centrally-reviewed PFS. Health-related quality of life is an exploratory objective. Archived tumor tissue and blood samples will be collected for correlative studies. Key inclusion criteria are: mCRC without prior chemotherapy for advanced disease; dMMR tumor determined by local CLIA-certified IHC assay (MLH1/MSH2/MSH6/PMS2) or MSI-H by local CLIA-certified PCR or NGS panel; and measurable disease per RECIST. Enrollment actively continues to the target accrual of 211 patients randomized between the two immunotherapy arms. Support: U10CA180868, -180822, -180888, UG1CA189867, U24CA196067; Genentech, Inc. Clinical trial information: NCT02997228.
Reply to H. B et al
Authors: Anne-Sophie Defachelles, Emilie Bogart, Michela Casanova, Johannes H.M. Merks, Gianni Bisogno, Giuseppina Calareso, Soledad Gallego Melcon, Susanne Andrea Gatz, Marie-Cécile Le Deley, Kieran McHugh, Alicia Probst, Nathalie Rocourt, Rick R. van Rijn, Véronique Minard-Colin, Julia C. Chisholm
Journal: Journal of Clinical Oncology (2022)
The relationship between lipoprotein A and other lipids with prostate cancer risk: A multivariable Mendelian randomisation study
Authors: Anna Ioannidou, Eleanor L. Watts, Aurora Perez-Cornago, Elizabeth A. Platz, Ian G. Mills, Timothy J. Key, Ruth C. Travis, Konstantinos K. Tsilidis, Verena Zuber
Journal: PLoS Medicine (2022)

Background Numerous epidemiological studies have investigated the role of blood lipids in prostate cancer (PCa) risk, though findings remain inconclusive to date. The ongoing research has mainly involved observational studies, which are often prone to confounding. This study aimed to identify the relationship between genetically predicted blood lipid concentrations and PCa. Methods and findings Data for low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides (TG), apolipoprotein A (apoA) and B (apoB), lipoprotein A (Lp(a)), and PCa were acquired from genome-wide association studies in UK Biobank and the PRACTICAL consortium, respectively. We used a two-sample summary-level Mendelian randomisation (MR) approach with both univariable and multivariable (MVMR) models and utilised a variety of robust methods and sensitivity analyses to assess the possibility of MR assumptions violation. No association was observed between genetically predicted concentrations of HDL, TG, apoA and apoB, and PCa risk. Genetically predicted LDL concentration was positively associated with total PCa in the univariable analysis, but adjustment for HDL, TG, and Lp(a) led to a null association. Genetically predicted concentration of Lp(a) was associated with higher total PCa risk in the univariable (OR weighted median per standard deviation (SD) = 1.091; 95% CI 1.028 to 1.157; P = 0.004) and MVMR analyses after adjustment for the other lipid traits (OR IVW per SD = 1.068; 95% CI 1.005 to 1.134; P = 0.034). Genetically predicted Lp(a) was also associated with advanced (MVMR OR IVW per SD = 1.078; 95% CI 0.999 to 1.163; P = 0.055) and early age onset PCa (MVMR OR IVW per SD = 1.150; 95% CI 1.015,1.303; P = 0.028). Although multiple estimation methods were utilised to minimise the effect of pleiotropy, the presence of any unmeasured pleiotropy cannot be excluded and may limit our findings. Conclusions We observed that genetically predicted Lp(a) concentrations were associated with an increased PCa risk. Future studies are required to understand the underlying biological pathways of this finding, as it may inform PCa prevention through Lp(a)-lowering strategies.
Rewiring of 3D Chromatin Topology Orchestrates Transcriptional Reprogramming and the Development of Human Dilated Cardiomyopathy
Authors: Yuliang Feng, Liuyang Cai, Wanzi Hong, Chunxiang Zhang, Ning Tan, Mingyang Wang, Cheng Wang, Feng Liu, Xiaohong Wang, Jianyong Ma, Chen Gao, Mohit Kumar, Yuanxi Mo, Qingshan Geng, Changjun Luo, Yan Lin, Haiyang Chen, Shuang-Yin Wang, Michael J. Watson, Anil G. Jegga, Roger A. Pedersen, Ji-dong Fu, Zhao V. Wang, Guo-Chang Fan, Sakthivel Sadayappan, Yigang Wang, Siim Pauklin, Feng Huang, Wei Huang, Lei Jiang
Journal: Circulation (2022)

Transcriptional reconfiguration is central to heart failure, the most common cause of which is dilated cardiomyopathy (DCM). The effect of 3-dimensional chromatin topology on transcriptional dysregulation and pathogenesis in human DCM remains elusive.
Automated interpretation of systolic and diastolic function on the echocardiogram: a multicohort study
Authors: Jasper Tromp, Paul J Seekings, Chung-Lieh Hung, Mathias Bøtcher Iversen, Matthew James Frost, Wouter Ouwerkerk, Zhubo Jiang, Frank Eisenhaber, Rick S M Goh, Heng Zhao, Weimin Huang, Lieng-Hsi Ling, David Sim, Patrick Cozzone, A Mark Richards, Hwee Kuan Lee, Scott D Solomon, Carolyn S P Lam, Justin A Ezekowitz
Journal: The Lancet Digital Health (2021)
Measuring and monitoring child health and wellbeing: recommendations for tracking progress with a core set of indicators in the Sustainable Development Goals era
Authors: Jennifer Requejo, Kathleen Strong, Ambrose Agweyu, Sk Masum Billah, Cynthia Boschi-Pinto, Sayaka Horiuchi, Zeina Jamaluddine, Marzia Lazzerini, Abdoulaye Maiga, Neil McKerrow, Melinda Munos, Lois Park, Joanna Schellenberg, Ralf Weigel
Journal: The Lancet Child & Adolescent Health (2022)
Disease-associated microglial activation prevents photoreceptor degeneration by suppressing the accumulation of cell debris and neutrophils in degenerating rat retinas
Authors: Juncai He, Yan Fu, Lingling Ge, Jiaman Dai, Yajie Fang, Yijian Li, Xianliang Gu, Zui Tao, Ting Zou, Minghui Li, Yong Liu, Haiwei Xu, Zheng Qin Yin
Journal: Theranostics (2022)

Retinitis pigmentosa initially presents as night blindness owing to defects in rods, and the secondary degeneration of cones ultimately leads to blindness. Previous studies have identified active roles of microglia in the pathogenesis of photoreceptor degeneration in RP. However, the contribution of microglia to photoreceptor degeneration remains controversial, partly due to limited knowledge of microglial phenotypes during RP. Rationale: In this study, we investigated the pathways of microglial activation and its contribution to photoreceptor degeneration in RP. Methods: A classic RP model, Royal College of Surgeons rat, was used to explore the process of microglial activation during the development of RP. An inhibitor of colony-stimulating factor 1 receptor (PLX3397) was fed to RCS rats for sustained ablation of microglia. Immunohistochemistry, flow cytometry, RT-qPCR, electroretinography and RNA-Seq were used to investigate the mechanisms by which activated microglia influenced photoreceptor degeneration. Results: Microglia were gradually activated to disease-associated microglia in the photoreceptor layers of RCS rats. Sustained treatment with PLX3397 ablated most of the disease-associated microglia and aggravated photoreceptor degeneration, including the secondary degeneration of cones, by downregulating the expression of genes associated with photoreceptor function and components and exacerbating the impairment of photoreceptor cell function. Disease-associated microglial activation promoted microglia to engulf apoptotic photoreceptor cell debris and suppressed the increase of infiltrated neutrophils by increasing engulfment and inhibiting CXCL1 secretion by Müller cells, which provided a healthier microenvironment for photoreceptor survival. Conclusions: Our data highlight a key role of disease-associated microglia activation in the suppression of rod and cone degeneration, which reduces secondary damage caused by the accumulation of dead cells and infiltrated neutrophils in the degenerating retina.
<i>Aspergillus</i> tracheobronchitis in COVID-19 patients with acute respiratory distress syndrome: a cohort study
Authors: Philipp Koehler, Saskia von Stillfried, Jorge Garcia Borrega, Frieder Fuchs, Jon Salmanton-García, Fabian Pult, Boris Böll, Dennis A. Eichenauer, Alexander Shimabukuro-Vornhagen, Oliver Kurzai, Peter Boor, Matthias Kochanek, Oliver A. Cornely
Journal: European Respiratory Journal (2022)

<b>Comprehensive work-up is needed for COVID-19 ARDS patients, especially when suspecting invasive fungal infections. <i>Aspergillus</i> tracheobronchitis has a substantial prevalence in patients with CAPA accounting for an overall mortality of 75% in this study.</b>https://bit.ly/3uF3FZU
Be Easy and Chill: Melanoma Cells Tell Lymph Node Fibroblasts to Relax
Authors: Amanda W. Lund
Journal: Cancer Research (2022)

Abstract Melanomas coopt tumor-draining lymph nodes to support metastatic potential and install immunosuppression. The specific mechanisms that mediate lymph node education, however, remain incompletely understood. In this issue, Rovera and colleagues describe the deactivation of contractile lymph node fibroblasts by dedifferentiated melanoma cells, leading to lymph node expansion and enhanced melanoma invasive potential. Fibroblastic reticular cell relaxation depended upon inhibition of constitutive JAK1/STAT3 and YAP/TAZ signaling, which was mediated in part by tumor secretion of the inflammatory cytokine, IL1. These data support an emerging hypothesis that intrinsic melanoma heterogeneity feeds forward to drive microenvironmental adaptations that mediate invasion and progression. See related article by Rovera et al., p. 1774
Humoral and cellular immune responses to two and three doses of SARS-CoV-2 vaccines in rituximab-treated patients with rheumatoid arthritis: a prospective, cohort study
Authors: Ingrid Jyssum, Hassen Kared, Trung T Tran, Anne T Tveter, Sella A Provan, Joseph Sexton, Kristin K Jørgensen, Jørgen Jahnsen, Grete B Kro, David J Warren, Eline B Vaage, Tore K Kvien, Lise-Sofie H Nissen-Meyer, Ane Marie Anderson, Gunnveig Grødeland, Espen A Haavardsholm, John Torgils Vaage, Siri Mjaaland, Silje Watterdal Syversen, Fridtjof Lund-Johansen, Ludvig A Munthe, Guro Løvik Goll
Journal: The Lancet Rheumatology (2021)
Phase 2B Study of Inhaled RVT-1601 for Chronic Cough in Idiopathic Pulmonary Fibrosis: A Multicenter, Randomized, Placebo-controlled Study (SCENIC Trial)
Authors: Fernando J. Martinez, Marlies S. Wijsenbeek, Ganesh Raghu, Kevin R. Flaherty, Toby M. Maher, Wim A. Wuyts, Michael Kreuter, Martin Kolb, Daniel C. Chambers, Charles Fogarty, Nesrin Mogulkoc, Ahmet S. Tutuncu, Luca Richeldi
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Rationale: Chronic cough remains a major and often debilitating symptom for patients with idiopathic pulmonary fibrosis (IPF). In a phase 2A study, inhaled RVT-1601 (cromolyn sodium) reduced daytime cough and 24-hour average cough counts in patients with IPF. Objectives: To determine the efficacy, safety, and optimal dose of inhaled RVT-1601 for the treatment of chronic cough in patients with IPF. Methods: In this multicenter, randomized, placebo-controlled phase 2B study, patients with IPF and chronic cough for ⩾8 weeks were randomized (1:1:1:1) to receive 10, 40, and 80 mg RVT-1601 three times daily or placebo for 12 weeks. The primary endpoint was change from baseline to end of treatment in log-transformed 24-hour cough count. Key secondary endpoints were change from baseline in cough severity and cough-specific quality of life. Safety was monitored throughout the study. Measurements and Main Results: The study was prematurely terminated owing to the impact of the coronavirus disease (COVID-19) pandemic. Overall, 108 patients (mean age 71.0 years, 62.9% males) received RVT-1601 10 mg (n = 29), 40 mg (n = 25), 80 mg (n = 27), or matching placebo (n = 27); 61.1% (n = 66) completed double-blind treatment. No statistically significant difference was observed in the least-square mean change from baseline in log-transformed 24-hour average cough count, cough severity, and cough-specific quality of life score between the RVT-1601 groups and the placebo group. The mean percentage change from baseline in 24-hour average cough count was 27.7% in the placebo group. Treatment was generally well tolerated. Conclusions: Treatment with inhaled RVT-1601 (10, 40, and 80 mg three times a day) did not provide benefit over placebo for the treatment of chronic cough in patients with IPF.
Could Neprilysin Be Already Inhibited by BNP in the LIFE Trial?—Reply
Authors: Douglas L. Mann, Adrian F. Hernandez, Eugene Braunwald
Journal: JAMA Cardiology (2022)

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 Cardiology 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 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 Cardiology journal
Screening of Organophosphate Flame Retardants with Placentation-Disrupting Effects in Human Trophoblast Organoid Model and Characterization of Adverse Pregnancy Outcomes in Mice
Authors: Chenke Xu, Haojia Ma, Fumei Gao, Chenhao Zhang, Wenxin Hu, Yingting Jia, Jun Xu, Jianying Hu
Journal: Environmental Health Perspectives (2022)

Abnormal placental development may result in adverse pregnancy outcomes and metabolic diseases in adulthood; however, it remains unknown whether and how xenobiotics affect human placentation.
Unsupervised brain imaging 3D anomaly detection and segmentation with transformers
Authors: Walter H.L. Pinaya, Petru-Daniel Tudosiu, Robert Gray, Geraint Rees, Parashkev Nachev, Sebastien Ourselin, M. Jorge Cardoso
Journal: Medical Image Analysis (2022)

Pathological brain appearances may be so heterogeneous as to be intelligible only as anomalies, defined by their deviation from normality rather than any specific set of pathological features. Amongst the hardest tasks in medical imaging, detecting such anomalies requires models of the normal brain that combine compactness with the expressivity of the complex, long-range interactions that characterise its structural organisation. These are requirements transformers have arguably greater potential to satisfy than other current candidate architectures, but their application has been inhibited by their demands on data and computational resources. Here we combine the latent representation of vector quantised variational autoencoders with an ensemble of autoregressive transformers to enable unsupervised anomaly detection and segmentation defined by deviation from healthy brain imaging data, achievable at low computational cost, within relative modest data regimes. We compare our method to current state-of-the-art approaches across a series of experiments with 2D and 3D data involving synthetic and real pathological lesions. On real lesions, we train our models on 15,000 radiologically normal participants from UK Biobank and evaluate performance on four different brain MR datasets with small vessel disease, demyelinating lesions, and tumours. We demonstrate superior anomaly detection performance both image-wise and pixel/voxel-wise, achievable without post-processing. These results draw attention to the potential of transformers in this most challenging of imaging tasks.