tbuckley/cabot-search huggingface dataset:
Activation of <i>Notch</i> and <i>Myc</i> Signaling via B-cell–Restricted Depletion of <i>Dnmt3a</i> Generates a Consistent Murine Model of Chronic Lymphocytic Leukemia
Authors: Anat Biran, Shanye Yin, Helene Kretzmer, Elisa ten Hacken, Salma Parvin, Fabienne Lucas, Mohamed Uduman, Catherine Gutierrez, Nathan Dangle, Leah Billington, Fara Faye Regis, Laura Z. Rassenti, Arman Mohammad, Gabriela Brunsting Hoffmann, Kristen Stevenson, Mei Zheng, Elizabeth Witten, Stacey M. Fernandes, Eugen Tausch, Clare Sun, Stephan Stilgenbauer, Jennifer R. Brown, Thomas J. Kipps, John C. Aster, Andreas Gnirke, Donna S. Neuberg, Anthony Letai, Lili Wang, Ruben D. Carrasco, Alexander Meissner, Catherine J. Wu
Journal: Cancer Research (2021)

Abstract Chronic lymphocytic leukemia (CLL) is characterized by disordered DNA methylation, suggesting these epigenetic changes might play a critical role in disease onset and progression. The methyltransferase DNMT3A is a key regulator of DNA methylation. Although DNMT3A somatic mutations in CLL are rare, we found that low DNMT3A expression is associated with more aggressive disease. A conditional knockout mouse model showed that homozygous depletion of Dnmt3a from B cells results in the development of CLL with 100% penetrance at a median age of onset of 5.3 months, and heterozygous Dnmt3a depletion yields a disease penetrance of 89% with a median onset at 18.5 months, confirming its role as a haploinsufficient tumor suppressor. B1a cells were confirmed as the cell of origin of disease in this model, and Dnmt3a depletion resulted in focal hypomethylation and activation of Notch and Myc signaling. Amplification of chromosome 15 containing the Myc gene was detected in all CLL mice tested, and infiltration of high-Myc–expressing CLL cells in the spleen was observed. Notably, hyperactivation of Notch and Myc signaling was exclusively observed in the Dnmt3a CLL mice, but not in three other CLL mouse models tested (Sf3b1-Atm, Ikzf3, and MDR), and Dnmt3a-depleted CLL were sensitive to pharmacologic inhibition of Notch signaling in vitro and in vivo. Consistent with these findings, human CLL samples with lower DNMT3A expression were more sensitive to Notch inhibition than those with higher DNMT3A expression. Altogether, these results suggest that Dnmt3a depletion induces CLL that is highly dependent on activation of Notch and Myc signaling. Significance: Loss of DNMT3A expression is a driving event in CLL and is associated with aggressive disease, activation of Notch and Myc signaling, and enhanced sensitivity to Notch inhibition.
Effectiveness of Resource Groups for Improving Empowerment, Quality of Life, and Functioning of People With Severe Mental Illness
Authors: Cathelijn Tjaden, Cornelis L. Mulder, Wouter den Hollander, Stynke Castelein, Philippe Delespaul, Rene Keet, Jaap van Weeghel, Hans Kroon
Journal: JAMA Psychiatry (2021)

Although the importance of recovery-oriented care for people with severe mental illness (SMI) is widely acknowledged, essential elements such as personalization and involvement of significant others are not adequately implemented in practice.
FP01.01 The Association of Bevacizumab with a Decreased Risk of Brain Metastases in ECOG-ACRIN E1505 in Completely Resected Stage IB-IIIA NSCLC
Authors: J. Varlotto, Y. Wang, Z. Sun, H. Wakelee, S. Ramalingam, J. Schiller
Journal: Journal of Thoracic Oncology (2021)
Evaluating COVID-19 Vaccine-Related Messenger RNA in Breast Milk—Reply
Authors: Yarden Golan, Valerie J. Flaherman, Stephanie L. Gaw
Journal: JAMA Pediatrics (2021)

specialists and their distribution over a 16-year period.We found that all subspecialties grew and improved in terms of geographic distribution during our study period; we did not posit a causal factor.Overall, there do appear to be shortages and/or maldistribution in several pediatric subspecialties.Further research is certainly warranted.However, we feel available information should not be dismissed because it is overly nuanced or complex.We should not let the perfect (data source and its analysis) be the enemy of the good.
Dopamine receptor D2 antagonism normalizes profibrotic macrophage-endothelial crosstalk in non-alcoholic steatohepatitis
Authors: Jie Qing, Yafeng Ren, Yuwei Zhang, Mengli Yan, Hua Zhang, Dongbo Wu, Yongyuan Ma, Yutian Chen, Xiaojuan Huang, Qinkai Wu, Maryam Mazhar, Li Wang, Jian Liu, Bi-Sen Ding, Zhongwei Cao
Journal: Journal of Hepatology (2021)
P14.01 Phase 3 Study of First-Line Pembrolizumab ± Vibostolimab (anti-TIGIT) in Patients With PD-L1‒Positive Metastatic NSCLC
Authors: M.D. Hellmann, B.C. Cho, R. Juergens, Y. Cheng, G. De Castro, M. Erman, J.R. Bauman, T. Takahashi, P. Schwarzenberger, P. Zhang, M.C. Pietanza, J.C. Yang
Journal: Journal of Thoracic Oncology (2021)
P17.02 RATIONALE 307: A Subgroup Analysis of Tislelizumab Plus Chemo vs Chemo Alone As 1L Treatment for Stage IIIB Advanced Sq NSCLC
Authors: S. Lu, X. Yu, J. Wang, J. Zhao, Y. Yu, C. Hu, G. Feng, K. Ying, W. Zhuang, J. Zhou, J. Wu, S.J. Leaw, F. Bai, X. Lin
Journal: Journal of Thoracic Oncology (2021)
Time to fight the pandemic setbacks for caregiver academics
Authors: Fernanda Staniscuaski, Fernanda Reichert, Eugenia Zandonà, Rossana Colla Soletti, Camila Infanger, Pâmela Billig Mello-Carpes, Zélia Maria Da Costa Ludwig, Lívia Kmetzsch, Felipe Klein Ricachenevsky, Fernanda P. Werneck, Giulia Alessandra Wiggers, Ida Vanessa D. Schwartz, Eliade F. Lima, Alessandra Sayuri Kikuchi Tamajusuku, Adriana Neumann, Adriana Seixas, Alessandra Brandao, Leticia de Oliveira
Journal: Nature Human Behaviour (2021)
Detection and Characterization of Thrombosis in Humans Using Fibrin-Targeted Positron Emission Tomography and Magnetic Resonance
Authors: David Izquierdo-Garcia, Pauline Désogère, Anne L Philip, Choukri Mekkaoui, Rory B Weiner, Onofrio A Catalano, Yin-Ching Iris Chen, Doreen DeFaria Yeh, Moussa Mansour, Ciprian Catana, Peter Caravan, David E Sosnovik
Journal: JACC. Cardiovascular imaging (2021)
Genomic abnormalities of TP53 define distinct risk groups of paediatric B-cell non-Hodgkin lymphoma
Authors: Alexander M. Newman, Masood Zaka, Peixun Zhou, Alex E. Blain, Amy Erhorn, Amy Barnard, Rachel E. Crossland, Sarah Wilkinson, Amir Enshaei, Julian De Zordi, Fiona Harding, Mary Taj, Katrina M. Wood, Despina Televantou, Suzanne D. Turner, G. A. Amos Burke, Christine J. Harrison, Simon Bomken, Chris M. Bacon, Vikki Rand
Journal: Leukemia (2021)

Children with B-cell non-Hodgkin lymphoma (B-NHL) have an excellent chance of survival, however, current clinical risk stratification places as many as half of patients in a high-risk group receiving very intensive chemo-immunotherapy. TP53 alterations are associated with adverse outcome in many malignancies; however, whilst common in paediatric B-NHL, their utility as a risk classifier is unknown. We evaluated the clinical significance of TP53 abnormalities (mutations, deletion and/or copy number neutral loss of heterozygosity) in a large UK paediatric B-NHL cohort and determined their impact on survival. TP53 abnormalities were present in 54.7% of cases and were independently associated with a significantly inferior survival compared to those without a TP53 abnormality (PFS 70.0% vs 100%, p < 0.001, OS 78.0% vs 100%, p = 0.002). Moreover, amongst patients clinically defined as high-risk (stage III with high LDH or stage IV), those without a TP53 abnormality have superior survival compared to those with TP53 abnormalities (PFS 100% vs 55.6%, p = 0.005, OS 100% vs 66.7%, p = 0.019). Biallelic TP53 abnormalities were either maintained from the presentation or acquired at progression in all paired diagnosis/progression Burkitt lymphoma cases. TP53 abnormalities thus define clinical risk groups within paediatric B-NHL and offer a novel molecular risk stratifier, allowing more personalised treatment protocols.
Identifying Equitable Screening Mammography Strategies for Black Women in the United States Using Simulation Modeling
Authors: Christina Hunter Chapman, Clyde B. Schechter, Christopher J. Cadham, Amy Trentham-Dietz, Ronald E. Gangnon, Reshma Jagsi, Jeanne S. Mandelblatt
Journal: Annals of Internal Medicine (2021)

Background: Screening mammography guidelines do not explicitly consider racial differences in breast cancer epidemiology, treatment, and survival. Objective: To compare tradeoffs of screening strategies in Black women versus White women under current guidelines. Design: An established model from the Cancer Intervention and Surveillance Modeling Network simulated screening outcomes using race-specific inputs for subtype distribution; breast density; mammography performance; age-, stage-, and subtype-specific treatment effects; and non–breast cancer mortality. Setting: United States. Participants: A 1980 U.S. birth cohort of Black and White women. Intervention: Screening strategies until age 74 years with varying initiation ages and intervals. Measurements: Outcomes included benefits (life-years gained [LYG], breast cancer deaths averted, and mortality reduction), harms (mammographies, false positives, and overdiagnoses), and benefit–harm ratios (tradeoffs) by race. Efficiency (benefits per unit resource), mortality disparity reduction, and equity in tradeoffs were evaluated. Equitable strategies for Black women were defined as those with tradeoffs closest to benchmark values for screening White women biennially from ages 50 to 74 years. Results: Biennial screening from ages 45 to 74 years was most efficient for Black women, whereas biennial screening from ages 40 to 74 years was most equitable. Initiating screening 10 years earlier in Black versus White women reduced Black–White mortality disparities by 57% with similar LYG per mammogram for both populations. Selection of the most equitable strategy was sensitive to assumptions about disparities in real-world treatment effectiveness: The less effective treatment was for Black women, the more intensively Black women could be screened before tradeoffs fell short of those experienced by White women. Limitation: Single model. Conclusion: Initiating biennial screening in Black women at age 40 years reduces breast cancer mortality disparities and yields benefit–harm ratios that are similar to tradeoffs of White women screened biennially from ages 50 to 74 years. Primary Funding Source: National Cancer Institute at the National Institutes of Health.
Two-dose COVID-19 vaccination and possible arthritis flare among patients with rheumatoid arthritis in Hong Kong
Authors: Xue Li, Xinning Tong, Winnie Wan Yin Yeung, Peng Kuan, Samson Hin Hei Yum, Celine Sze Ling Chui, Francisco Tsz Tsun Lai, Eric Yuk Fai Wan, Carlos King Ho Wong, Esther Wai Yin Chan, Chak Sing Lau, Ian Chi Kei Wong
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To investigate the relationship between COVID-19 full vaccination (two completed doses) and possible arthritis flare. Methods Patients with rheumatoid arthritis (RA) were identified from population-based electronic medical records with vaccination linkage and categorised into BNT162b2 (mRNA vaccine), CoronaVac (inactive virus vaccine) and non-vaccinated groups. The risk of possible arthritis flare after vaccination was compared using a propensity-weighted cohort study design. We defined possible arthritis flare as hospitalisation and outpatient consultation related to RA or reactive arthritis, based on diagnosis records during the episode. Weekly prescriptions of rheumatic drugs since the launch of COVID-19 vaccination programme were compared to complement the findings from a diagnosis-based analysis. Results Among 5493 patients with RA (BNT162b2: 653; CoronaVac: 671; non-vaccinated: 4169), propensity-scored weighted Poisson regression showed no significant association between arthritis flare and COVID-19 vaccination ((BNT162b2: adjusted incidence rate ratio 0.86, 95% Confidence Interval 0.73 to 1.01); CoronaVac: 0.87 (0.74 to 1.02)). The distribution of weekly rheumatic drug prescriptions showed no significant differences among the three groups since the launch of the mass vaccination programme (all p values &gt;0.1 from Kruskal-Wallis test). Conclusions Current evidence does not support that full vaccination of mRNA or inactivated virus COVID-19 vaccines is associated with possible arthritis flare.
P59.19 MET Alterations and Co-Drivers With Poor Prognosis in Patients With Metastatic Non-Small Cell Lung Cancer
Authors: M. Ramos-Ramirez, N. Hernández-Pedro, L. Cabrera Miranda, C. Izquierdo-Tolosa, D. Diaz-Garcia, D. Heredia, L. Lara-Mejía, F. Barrón, O. Arrieta
Journal: Journal of Thoracic Oncology (2021)
No Strong Evidence on Liver Transplant for Colorectal Cancer Liver Metastasis Over Portal Vein Embolization Associated With Liver Resection—Reply
Authors: Svein Dueland, Sheraz Yaqub, Pål-Dag Line
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
Deemed consent for organ donation in Northern Ireland
Authors: Jordan A. Parsons, Bonnie Venter
Journal: The Lancet Regional Health - Europe (2021)

Shortages of organs for transplantation have led many countries to introduce systems of deemed consent for organ donation, whereby donation is the default upon death and an individual must provide express opposition to donation to prevent it. Despite a lack of clear supporting evidence, it is often suggested that deemed consent will contribute significantly to addressing the organ shortage. Northern Ireland appears set to be one of the next countries to pursue this route, with the Organ and Tissue Donation (Deemed Consent) Bill currently making its way through the Northern Ireland Assembly. If passed, this Bill will see Northern Ireland follow in the footsteps of the rest of the UK. In this viewpoint, we provide an overview of Northern Ireland's progress towards introducing deemed consent and argue two related points. First, that public awareness of the policy (if introduced) is vital to both its defensibility and longevity, and that this must be recognised through the imposition of a ministerial duty to focus on such awareness. Second, that policymakers in Northern Ireland ought to support the policy to ensure consistency across the UK in organ procurement, thereby preventing Northern Ireland from disproportionately benefitting from the UK-wide organ allocation system.
Acute urinary retention and risk of cancer: population based Danish cohort study
Authors: Maria Bisgaard Bengtsen, Dóra Körmendiné Farkas, Michael Borre, Henrik Toft Sørensen, Mette Nørgaard
Journal: BMJ (2021)

Abstract Objective To examine the risk of urogenital, colorectal, and neurological cancers after a first diagnosis of acute urinary retention. Design Nationwide population based cohort study. Setting All hospitals in Denmark. Participants 75 983 patients aged 50 years or older with a first hospital admission for acute urinary retention during 1995-2017. Main outcome measures Absolute risk of urogenital, colorectal, and neurological cancer and excess risk of these cancers among patients with acute urinary retention compared with the general population. Results The absolute risk of prostate cancer after a first diagnosis of acute urinary retention was 5.1% (n=3198) at three months, 6.7% (n=4233) at one year, and 8.5% (n=5217) at five years. Within three months of follow-up, 218 excess cases of prostate cancer per 1000 person years were detected. An additional 21 excess cases per 1000 person years were detected during three to less than 12 months of follow-up, but beyond 12 months the excess risk was negligible. Within three months of follow-up the excess risk for urinary tract cancer was 56 per 1000 person years, for genital cancer in women was 24 per 1000 person years, for colorectal cancer was 12 per 1000 person years, and for neurological cancer was 2 per 1000 person years. For most of the studied cancers, the excess risk was confined to within three months of follow-up, but the risk of prostate and urinary tract cancer remained increased during three to less than 12 months of follow-up. In women, an excess risk of invasive bladder cancer persisted for several years. Conclusions Acute urinary retention might be a clinical marker for occult urogenital, colorectal, and neurological cancers. Occult cancer should possibly be considered in patients aged 50 years or older presenting with acute urinary retention and no obvious underlying cause.
Interstitial Lung Disease Induced by Anti-ERBB2 Antibody-Drug Conjugates
Authors: Paolo Tarantino, Shanu Modi, Sara M. Tolaney, Javier Cortés, Erika P. Hamilton, Sung-Bae Kim, Masazaku Toi, Fabrice Andrè, Giuseppe Curigliano
Journal: JAMA Oncology (2021)

In the past decade, ERBB2 (formerly HER2)-directed antibody-drug conjugates (ADCs) have substantially changed treatment of both advanced and early-stage ERBB2-positive breast cancer. Novel conjugates are now showing activity in trials of other ERBB2-associated tumors, leading to the recent US Food and Drug Administration approval of trastuzumab deruxtecan for ERBB2-positive gastric cancer, as well as beneficial results in colorectal, lung, and bladder cancer. It is thus possible that anti-ERBB2 ADCs may become a treatment option for multiple types of tumors because many have at least some expression of ERBB2. Despite an improved overall therapeutic index, clinical observations have recently raised a concern regarding potential lung toxicity of anti-ERBB2 ADCs. Deaths related to interstitial lung disease (ILD) have been reported with variable incidence in trials testing anti-ERBB2 conjugates, warranting appropriate training of clinicians for the identification and management of this toxic effect.Although no specific guidelines are available for the diagnosis and management of ADC-related ILD, some recommendations can be derived based on general principles adopted for drug-induced and immunotherapy-related ILD. Overall, in symptomatic ILD, the ADC should be discontinued. Reintroduction of the conjugate can be considered only in asymptomatic cases after complete resolution. Corticosteroids represent the cornerstone of ILD treatment, and dosing should be adapted according to the severity of the event. Additional treatments can be considered based on the clinical scenario.This review summarizes the current knowledge on the pathogenesis and epidemiologic characteristics of anti-ERBB2 ADC-related lung toxicity, proposing strategies for its diagnosis and treatment. Earlier diagnosis and more adequate treatment of ADC-induced ILD may improve the therapeutic index of this important class of anticancer agents, allowing for a safe expansion of anti-ERBB2 ADCs across tumor types.
34P Validation of a new scoring system for molecular subtyping of gastric cancer
Authors: I.M. Cazacu, A. Filippi, V.M. Croitoru, S. Kitahara, A. Matsui, G. Lauwers, A. Sorop, L.G. Necula, L. Matei, C. Pechianu, A.E. Croitoru, V. Herlea, A. Saftoiu, D. Paul, M. Chivu-Economescu, S. Dima, D.G. Duda, I. Popescu
Journal: Annals of Oncology (2021)
High alcohol-producing <i>Klebsiella pneumoniae</i> causes fatty liver disease through 2,3-butanediol fermentation pathway <i>in vivo</i>
Authors: Nan-Nan Li, Wei Li, Jun-Xia Feng, Bing Du, Rui Zhang, Shu-Heng Du, Shi-Yu Liu, Guan-Hua Xue, Chao Yan, Jing-Hua Cui, Han-Qing Zhao, Yan-Ling Feng, Lin Gan, Qun Zhang, Wei-Wei Zhang, Di Liu, Chen Chen, Jing Yuan
Journal: Gut Microbes (2021)

High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production in vivo remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) Kpn and constructed an adh (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc Kpn W14 strain (W14Δadh) using CRISPR-Cas9 system. Subsequently, we established the mouse model via gavage administration of HiAlc Kpn W14 and W14 Δadh strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc Kpn W14-fed mice, W14Δadh-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol via the 2,3-butanediol fermentation pathway in HiAlc Kpn, which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes in vivo.
Free Paper Session : Hepatitis C ; Relative adrenal insufficiency predicts mortality in patients with Liver cirrhosis (초)
Authors: Jae Young Jang, Soung Won Jeong, Tae Hee Lee, Ji Eun Lee, Sae Hwan Lee, Sang Gyun Kim, Young Seok Kim, Young Deok Cho, Hong Soo Kim, Boo Sung Kim, Dong Ho Choi, So Young Jin, Yong Jae Kim
Journal: Clinical and Molecular Hepatology (2011)
P22.04 Prospective Validation of an Eight Gene mRNA Signature in Plasma for the Diagnosis of Early Stage Lung Cancer
Authors: A. Giménez Capitán, P. Rubinstein, F. Rubinstein, A. Aguilar-Hernández, J. Bracht, S. Viteri, C. Cabrera-Gálvez, M. Gonzalez-Cao, I. Moya, J. Valarezo, C. Mayo-De-Las-Casas, C. Pedraz, R. Boykin, S. Warren, R. Rosell, M. Molina
Journal: Journal of Thoracic Oncology (2021)
OA16.03 Matched Targeted Therapy by cfDNA of CSF Beyond Leptomeningeal Metastases Progression Upon Osimertinib in EGFR-Mutated NSCLC Patients
Authors: M. Zheng, Y. Li, H. Tu, H. Sun, K. Yin, J. Yang, X. Zhang, Q. Zhou, Y. Wu
Journal: Journal of Thoracic Oncology (2021)