tbuckley/cabot-search huggingface dataset:
Abstract PO-019: Radiotherapy in cancer is associated with a deletion signature that contributes to poor patient outcomes
Authors: Emre Kocakavuk, Kevin J. Anderson, Frederick S. Varn, Kevin C. Johnson, Samirkumar B. Amin, Erik. P. Sulman, Martijn Lolkema, Floris P. Barthel, Roel G.W. Verhaak
Journal: Clinical Cancer Research (2021)

Abstract Diffuse gliomas are highly aggressive brain tumors that invariably relapse despite treatment with chemo- and radiotherapy. Treatment with alkylating chemotherapy can drive tumors to develop a hypermutator phenotype. In contrast, the genomic effects of radiation therapy (RT) remain unknown. We analyzed the mutational spectra following treatment with ionizing radiation in sequencing data from 190 paired primary-recurrent gliomas from the Glioma Longitudinal Analysis (GLASS) dataset and 3693 post-treatment metastatic tumors from the Hartwig Medical Foundation (HMF). We identified a significant increase in the burden of small deletions following radiation therapy that was independent of other factors. These novel deletions demonstrated distinct characteristics when compared to pre-existing deletions present prior to RT-treatment and deletions in RT-untreated tumors. Radiation therapy-acquired deletions were characterized by a larger deletion size (GLASS and metastatic cohort, P=1.2e-02 and P=8e-11, respectively; Mann-Whitney U test), an increased distance to repetitive DNA elements (P&amp;lt;2.2e-16, Kolmogorov-Smirnov test) and a reduction in microhomology at breakpoints (P=3.2e-02, paired Wilcoxon signed-rank test). These observations suggested that canonical non-homologous end joining (c-NHEJ) was the preferred pathway for DNA double strand break repair of RT-induced DNA damage. Furthermore, radiotherapy resulted in frequent chromosomal deletions and significantly increased frequencies of CDKN2A homozygous deletions. Finally, a high burden of RT-associated deletions was associated with worse clinical outcomes (GLASS and metastatic cohort, P &amp;lt; 1e-04 and P = 2.6e-02, respectively; Wald test). Our results suggest that effective repair of RT-induced DNA damage is detrimental to patient survival and that inhibiting c-NHEJ may be a viable strategy for improving the cancer-killing effect of radiotherapy. Taken together, the identified genomic scars as a result of radiation therapy reflect a more aggressive tumor with increased levels of resistance to follow up treatments. Citation Format: Emre Kocakavuk, Kevin J. Anderson, Frederick S. Varn, Kevin C. Johnson, Samirkumar B. Amin, Erik. P. Sulman, Martijn Lolkema, Floris P. Barthel, Roel G.W. Verhaak. Radiotherapy in cancer is associated with a deletion signature that contributes to poor patient outcomes [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-019.
Acute Pulmonary Emboli and Covid-19
Authors: N. Johl, D. Ap-Emyr, M. Jones, K. Hardingham, E. King, C. Carder, A. Marin, C. Corscadden, K. Pink, J. Underwood
Journal: Thorax (2021)

Introduction An increased risk of pulmonary emboli (PE) has been reported in COVID-19 disease, possibly as a result of a hypercoagulable state  Superadded PE's may exacerbate respiratory failure and lead to increased morbidity and mortality  The objective of this study was to review the detection rates for PE in patients with COVID-19 undergoing CTPA scanning  Secondary objectives were to explore correlations between PE diagnosis, serum markers and radiological COVID-19 severity  Methods A total of 325 patients had a CTPA performed between 30/03/2020-15/05/2020  Data was retrospectively collected on patient demographics, COVID-19 status, radiological severity (British Society of Thoracic Imaging classification), PE location and biochemical markers (D-Dimer, Troponin-I, CRP, Ferritin)  Results 122/325 patients were diagnosed with COVID-19 either radiologically (n=20, 16%) or by RT-PCR (n=102, 84%)  The PE detection rate on imaging was significantly higher in those with COVID-19 than those without (32/122 [26%] and 27/203 [13%] respectively [p=0 005])  617 patients were hospitalised with COVID-19 during this period (total PE incidence 5 2% [32/617])  Radiological severity of COVID-19 lung disease was not associated with PE detection (p=0 94)  Initial quantitative D-Dimer's were significantly higher in COVID-19 patients with PE than those without (median 4390 [range 761-20,000] and 930 [range 110-20,000] respectively [p<0 001])  Higher D-Dimer levels were associated with increased PE detection rates on CT imaging (Abstract P253 figure 1)  COVID-19 associated PE's were more likely to be unilateral (16/32 compared to 5/27 in COVID-19 negative group [p=0 025]) and trended towards more distal vessels (p=0 09)  Accounting for age, an additional PE diagnosis did not significantly affect in-hospital COVID-19 mortality (OR 1 54 [CI 0 52-3 94], [p=0 38])  Conclusion Our results demonstrate increased detection of PE in COVID-19  Emboli are more likely to be unilateral, and more distally located  We postulate this may be due to higher rates of in-situ thrombosis rather than distant embolisation of clots  The radiological severity of COVID-19 lung disease does not appear to be strongly linked to PE detection rates which may suggest the hypercoagulable state in COVID-19 is independent from the inflammatory lung process  Patients with COVID-19 and co-existent PE's have significantly higher DDimer's, and further evaluation is needed into their use as a screening tool
Mutational Landscape and Clinical Outcome Associated with Different Rearrangements Involving 11q23/ MLL in De Novo Acute Myeloid Leukemia (AML)
Authors: Marius Bill, Ann-Kathrin Eisfeld, Krzysztof Mrózek, Jessica Kohlschmidt, Deedra Nicolet, Christopher J. Walker, James S. Blachly, Andrew Carroll, Jonathan E. Kolitz, Eunice S. Wang, Bayard L. Powell, Richard M. Stone, Albert de la Chapelle, John C. Byrd, Clara D. Bloomfield
Journal: Blood (2017)
The USPSTF 2021 Recommendations on Screening for Asymptomatic Vitamin D Deficiency in Adults
Authors: Sherri-Ann M. Burnett-Bowie, Anne R. Cappola
Journal: JAMA (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 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
Differentiating Type 1 and Type 2 Myocardial Infarction
Authors: Marc S. Sabatine
Journal: JAMA Cardiology (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 Cardiology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Cardiology journal
Rethinking Routine Peripheral Intravenous Line Placement
Authors: Tarik Silk, Joseph Windheim, Somil Chugh
Journal: JAMA Internal Medicine (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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
MAV(S)erick mitochondria: an unconventional role for mitochondrial antiviral signalling protein in pulmonary fibrosis
Authors: Ram P. Naikawadi, Paul J. Wolters
Journal: European Respiratory Journal (2021)

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, age-related interstitial lung disease. Incidence of IPF in the USA ranges between 14 and 63 per 100 000 people [1]. The average survival rate from the time of diagnosis is 3–5 years. IPF is associated with several genetic and environmental factors. Genes associated with a risk for developing IPF generally fall into two categories: epithelial cell genes ( e.g. MUC5B , DSP , SFTPA2 , ABCA3 ) or genes involved in telomere maintenance ( e.g. TERT , TERC , RTEL1 ) [2, 3]. Mitochondrial antiviral signalling protein (MAVS) mediates pulmonary fibrosis by regulating cGAS-STING and senescence programming <https://bit.ly/35Tijjj>
Dynamic real time in vivo CAR T cell tracking: Clinical and preclinical studies using a novel dual PET-MR imaging agent
Authors: Ritu Singla, Dominic Wall, Samuel Anderson, Nicholas Zia, James C Korte, Lucy Kravets, Gerard McKiernan, Jeanne Butler, Amanda Gammilonghi, Jyoti Arora, Ben Solomon, Rodney Hicks, Timothy Cain, Phillip Darcy, Carleen Cullinane, Paul Neeson, Rajesh Ramanathan, Ravi S Hukla, Vipul Bansal, Simon Harrison
Journal: Cancer Research (2020)
Low‐affinity but high‐avidity interactions may offer an explanation for IgE‐mediated allergen cross‐reactivity
Authors: Xinyue Chang, Lisha Zha, Alexandra Wallimann, Mona O. Mohsen, Pascal Krenger, Xuelan Liu, Monique Vogel, Martin F. Bachmann
Journal: Allergy (2021)

Abstract Background Allergy is a global disease with overall frequencies of &gt;20%. Symptoms vary from irritating local itching to life‐threatening systemic anaphylaxis. Even though allergies are allergen‐specific, there is a wide range of cross‐reactivities (eg apple and latex) that remain largely unexplained. Given the abilities of low‐affinity IgG antibodies to inhibit mast cells activation, here we elucidate the minimal affinity of IgE antibodies to induce type I hypersensitivity. Methods Three mature (high‐affinity) IgE antibodies recognizing three distinct epitopes on Fel d 1, the major cat allergen, were back‐mutated to germline conformation, resulting in binding to Fel d 1 with low affinity. The ability of these IgE antibodies to activate mast cells in vitro and in vivo was tested. Results We demonstrate that affinities as low as 10 −7 M are sufficient to activate mast cells in vitro and drive allergic reactions in vivo . Low‐affinity IgE antibodies are able to do so, since they bind allergens bivalently on the surface of mast cells, leading to high‐avidity interactions. Conclusions These results suggest that the underlying mechanism of allergen cross‐reactivity may be low‐affinity but high‐avidity binding between IgE antibodies and cross‐reactive allergen.
Octogenarian newly diagnosed multiple myeloma patients without geriatric impairments: the role of age &gt;80 in the IMWG frailty score
Authors: Mattia D'Agostino, Alessandra Larocca, Massimo Offidani, Anna Marina Liberati, Gianluca Gaidano, Maria Teresa Petrucci, Daniele Derudas, Andrea Capra, Renato Zambello, Nicola Cascavilla, Paolo de Fabritiis, Vanessa Innao, Francesca Bonello, Francesca Patriarca, Giulia Benevolo, Nicola Giuliani, Gabriele Aitoro, Tommasina Guglielmelli, Francesco Di Raimondo, Paolo Corradini, Pellegrino Musto, Roman Hájek, Pieter Sonneveld, Mario Boccadoro, Sara Bringhen
Journal: Blood Cancer Journal (2021)
CircLIFR synergizes with MSH2 to attenuate chemoresistance via MutSα/ATM-p73 axis in bladder cancer
Authors: Hui Zhang, Xingyuan Xiao, Wenjie Wei, Chao Huang, Miao Wang, Liang Wang, Yuanqiao He, Jiayin Sun, Yangkai Jiang, Guosong Jiang, Xiaoping Zhang
Journal: Molecular Cancer (2021)

Abstract Background Cisplatin (CDDP) has become a standard-of-care treatment for muscle-invasive bladder cancer (MIBC), while chemoresistance remains a major challenge. Accumulating evidence indicates that circular RNAs (circRNAs) are discrete functional entities. However, the regulatory functions as well as complexities of circRNAs in modulating CDDP-based chemotherapy in bladder cancer are yet to be well revealed. Methods Through analyzing the expression profile of circRNAs in bladder cancer tissues, RNA FISH, circRNA pull-down assay, mass spectrometry analysis and RIP, circLIFR was identified and its interaction with MSH2 was confirmed. The effects of circLIFR and MSH2 on CDDP-based chemotherapy were explored by flow cytometry and rescue experiments. Co-IP and Western blot were used to investigate the molecular mechanisms underlying the functions of circLIFR and MSH2. Biological implications of circLIFR and MSH2 in bladder cancer were implemented in tumor xenograft models and PDX models. Results CircLIFR was downregulated in bladder cancer and expression was positively correlated with favorable prognosis. Moreover, circLIFR synergizing with MSH2, which was a mediator of CDDP sensitivity in bladder cancer cells, positively modulated sensitivity to CDDP in vitro and in vivo. Mechanistically, circLIFR augmented the interaction between MutSα and ATM, ultimately contributing to stabilize p73, which triggered to apoptosis. Importantly, MIBC with high expression of circLIFR and MSH2 was more sensitive to CDDP-based chemotherapy in tumor xenograft models and PDX models. Conclusions CircLIFR could interact with MSH2 to positively modulate CDDP-sensitivity through MutSα/ATM-p73 axis in bladder cancer. CircLIFR and MSH2 might be act as promising therapeutic targets for CDDP-resistant bladder cancer.
Identification of Progression-Associated Mutations in Chronic Myeloid Leukemia (CML) By Comparative Genomic Analysis
Authors: Shady Adnan Awad, Matti Kankainen, Samuli Eldfors, Bhagwan Yadav, Soili Kytölä, Pekka Ellonen, Mahmoud Kamel, Caroline A Heckman, Kimmo Porkka, Satu Mustjoki
Journal: Blood (2017)
A Deferred-Vaccination Design to Assess Durability of COVID-19 Vaccine Effect After the Placebo Group Is Vaccinated
Authors: Dean Follmann, Jonathan Fintzi, Michael P. Fay, Holly E. Janes, Lindsey R. Baden, Hana M. El Sahly, Thomas R. Fleming, Devan V. Mehrotra, Lindsay N. Carpp, Michal Juraska, David Benkeser, Deborah Donnell, Youyi Fong, Shu Han, Ian Hirsch, Ying Huang, Yunda Huang, Ollivier Hyrien, Alex Luedtke, Marco Carone, Martha Nason, An Vandebosch, Honghong Zhou, Iksung Cho, Erin Gabriel, James G. Kublin, Myron S. Cohen, Lawrence Corey, Peter B. Gilbert, Kathleen M. Neuzil
Journal: Annals of Internal Medicine (2021)

Multiple candidate vaccines to prevent COVID-19 have entered large-scale phase 3 placebo-controlled randomized clinical trials, and several have demonstrated substantial short-term efficacy. At some point after demonstration of substantial efficacy, placebo recipients should be offered the efficacious vaccine from their trial, which will occur before longer-term efficacy and safety are known. The absence of a placebo group could compromise assessment of longer-term vaccine effects. However, by continuing follow-up after vaccination of the placebo group, this study shows that placebo-controlled vaccine efficacy can be mathematically derived by assuming that the benefit of vaccination over time has the same profile for the original vaccine recipients and the original placebo recipients after their vaccination. Although this derivation provides less precise estimates than would be obtained by a standard trial where the placebo group remains unvaccinated, this proposed approach allows estimation of longer-term effect, including durability of vaccine efficacy and whether the vaccine eventually becomes harmful for some. Deferred vaccination, if done open-label, may lead to riskier behavior in the unblinded original vaccine group, confounding estimates of long-term vaccine efficacy. Hence, deferred vaccination via blinded crossover, where the vaccine group receives placebo and vice versa, would be the preferred way to assess vaccine durability and potential delayed harm. Deferred vaccination allows placebo recipients timely access to the vaccine when it would no longer be proper to maintain them on placebo, yet still allows important insights about immunologic and clinical effectiveness over time.
Countering the obesity and non-communicable diseases epidemic in the Pacific region: a critical policy review
Authors: Cath Conn, Daysha Tonumaipe'a, Radilaite Cammock
Journal: The Lancet Planetary Health (2021)

BackgroundPacific countries are facing an obesity and non-communicable diseases epidemic, and increased susceptibility to the effects of climate change. Studies attribute this epidemic to low-quality diets, and solutions are usually focused on changing eating patterns. There is a growing appreciation of the role of the global food system in contributing to the epidemic and in the fight against climate change.MethodIn this critical policy review, we reviewed policy documents and peer-reviewed research relating to the food systems in the Pacific region with a focus on two locations, Fiji and Auckland, New Zealand. We used the three pillars of sustainability—economic, environmental, and social—as a framework for analysis. Crucially, indigenous knowledge, in the form of Māori principles of guardianship of the environment (Kaitiakitanga) and the Pacific concept of healthy spaces (Vā), informed the discussion.FindingsFrom our analysis, we found the non-communicable disease crisis in the Pacific region to be symptomatic of global food and economic systems that concentrate on consumption. Underdeveloped infrastructure and an absence of incentives and investment are eroding local agriculture and Pacific food security. This negative situation is counter to indigenous values, which are protective of the natural order. Addressing non-communicable diseases is still largely viewed by health services as a behavioural issue to be addressed through health promotion with a focus on lifestyle changes rather than broader systemic change, addressing determinants of health, and rethinking of societal values.InterpretationPolicy in the Pacific region needs to urgently and overtly adopt multisectoral approaches integrating those that address food production, trade, climate change and sustainability, and health interventions. Governments must assume more proactive leadership in creating sustainable food environments, signifying a clear shift from individualistic behavioural approaches to systemic change. Pacific communities are changing, becoming more mobile, urbanised, with greater access to education, and digital connectivity. With a youthful demographic and rich indigenous traditions, there are strong opportunities for collaboration and innovation to develop and maintain Pacific sustainable and healthy food systems that are relevant to local communities.FundingNew Zealand Ministry of Finance, Aid and Trade (MFAT), Wellington, and Auckland University of Technology.
ABO Genetic Variation in Neanderthals and Denisovans
Authors: Fernando A Villanea, Emilia Huerta-Sanchez, Keolu Fox
Journal: Molecular Biology and Evolution (2021)

Variation at the ABO locus was one of the earliest sources of data in the study of human population identity and history, and to this day remains widely genotyped due to its importance in blood and tissue transfusions. Here, we look at ABO blood type variants in our archaic relatives: Neanderthals and Denisovans. Our goal is to understand the genetic landscape of the ABO gene in archaic humans, and how it relates to modern human ABO variation. We found two Neanderthal variants of the O allele in the Siberian Neanderthals (O1 and O2), one of these variants is shared with an European Neanderthal, who is a heterozygote for this O1 variant and a rare cis-AB variant. The Denisovan individual is heterozygous for two variants of the O1 allele, functionally similar to variants found widely in modern humans. Perhaps more surprisingly, the O2 allele variant found in Siberian Neanderthals can be found at low frequencies in modern Europeans and Southeast Asians, and the O1 allele variant found in Siberian and European Neanderthal is also found at very low frequency in modern East Asians. Our genetic distance analyses suggest both alleles survive in modern humans due to inbreeding with Neanderthals. We find that the sequence backgrounds of the surviving Neanderthal-like O alleles in modern humans retain a higher sequence divergence than other surviving Neanderthal genome fragments, supporting a view of balancing selection operating in the Neanderthal ABO alleles by retaining highly diverse haplotypes compared with portions of the genome evolving neutrally.