tbuckley/cabot-search huggingface dataset:
Abstract P1-20-10: The role of micro-CT in imaging breast cancer specimens
Authors: Ankur Tiwari, Daniel DiCorpo, Kevin Hughes, James Michaelson
Journal: Cancer Research (2020)

Abstract Background: The goal of breast cancer surgery is to remove all cancer with a minimum of normal tissue, but the absence of full 3-dimensional information on the surgical specimen makes this difficult to achieve. Method: Micro CT is a high resolution, X-ray, 3D imaging method, used principally in material science and industry but little used in medicine. Results: We imaged and analyzed 173 partial mastectomies by Micro-CT (129 ductal carcinomas, 14 lobular carcinomas, 28 DCIS). Imaging was simple and rapid. Size of cancer image on Micro-CT was very similar to the size of cancer at specimen dissection. Micro-CT images of surgical specimens in cassettes revealed sizes and shapes very similar to cancer later seen on the slide. Micro CT images of multicentric/multifocal cancers appeared as separate, clearly non-contiguous, masses. Additional image realization was carried out with image analysis software, with which we created a variety of three-dimensional image visualizations seen by rotation, slicing, and various degrees of transparentness, achieved by volume rendering with adjustment of opacity and maximum intensity projection imaging modified by the transfer function, making viewing through the 3D mass possible. Video can be seen at https://youtu.be/1hyNmFDidO4. Micro-CT assessment found cancer to touch edge in 134 (77%) of cases, while assessment of the microscope slides revealed positivity in 114 (66%) of cases. Cases judged by the pathologist to be margin positive were margin positive by Micro CT 93% the time. Cancer occupied 0.45% of surface area for “Micro-CT-Only-Positive Cases” but more than three times as much space, at 1.55% when both the pathologist and the Micro-CT suggested cancer at the edge. Conclusions: Micro-CT provides full 3D images of partial mastectomy specimens, allowing one to identify, in a few minutes, and thus while the patient is in OR, margin positive cases, with information on where cancer touches the edge, in a fashion more accurate than possible from the histology slides alone. Citation Format: Ankur Tiwari, Daniel DiCorpo, Kevin Hughes, James Michaelson. The role of micro-CT in imaging breast cancer specimens [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-20-10.
Impact of the type of anthracycline and of stem cell transplantation in younger patients with acute myeloid leukaemia: Long‐term follow up of a phase <scp>III</scp> study
Authors: Frédéric Baron, Fabio Efficace, Laura Cannella, Petra Muus, Silvia Trisolini, Constantijn J. M. Halkes, Paola Fazi, Marco Vignetti, Jean‐Pierre Marie, Patrizia Chiusolo, Walter van der Velden, Edoardo La Sala, Umberto Vitolo, Xavier Thomas, Francois Lefrère, Francesco Di Raimondo, Jean‐Henri Bourhis, Giorgina Specchia, José E. Guimarães, Bernardino Allione, Radovan Vrhovac, Felicetto Ferrara, Marian Stevens‐Kroef, Liv Meert, Theo de Witte, Roelof Willemze, Sergio Amadori, Stefan Suciu
Journal: American Journal of Hematology (2020)

We provide a long-term evaluation of patients enrolled in the EORTC/GIMEMA AML-10 trial which included a total of 2157 patients, 15-60 years old, randomized to receive either daunorubicin (DNR, 50 mg/m2 ), mitoxantrone (MXR, 12 mg/m2 ), or idarubicin (IDA, 10 mg/m2 ) in addition to standard-dose cytarabine and etoposide for induction chemotherapy and intermediate dose cytarabine for consolidation. Younger patients who reached complete remission with complete (CR) or incomplete (CRi) recovery were then scheduled to receive an allogeneic hematopoietic stem cell transplantation (HSCT). That was if they had a HLA-identical sibling donor; in all other cases, an autologous HSCT had to be administered. At an 11-year median follow-up, the 5-year, 10-year and 15-year overall survival (OS) rates were 33.2%, 30.1% and 28.0%, respectively. No significant difference between the three randomized groups regarding OS was observed (P = .38). In young patients, 15-45 years old, no treatment difference (P = .89) regarding OS was observed, while in patients 46-60 years old, MXR and IDA groups had a trend for a longer OS as compared to the DNR group (P = .029). Among younger patients without a favorable MRC cytogenetic risk subgroup who achieved a CR/CRi after induction chemotherapy, those with a HLA-identical sibling donor had higher 10-year and 15-year OS rates than those without. In older patients who reached CR/CRi, the long-term outcomes of those with or without a donor was similar. In conclusion, long-term outcomes of the study confirmed similar OS in the three randomized groups in the whole cohort of patients.
Abstract ES11-1: The biology and plasticity of residual disease after neoadjuvant treatment
Authors: C Perou
Journal: Cancer Research (2020)

Abstract Breast cancer neoadjuvant treatment is becoming more prevalent, and has emerged as a valuable tool to downstage tumors, to identify predictors of responsiveness, and to potentially adapt therapeutic interventions to that individual’s residual disease if present. This has led to increasingly complex patient management and the development of many clinical trials specifically designed for those with residual disease. However, the basic biology of residual disease, how it relates to pre-treated disease, and how it could be used for prognostic and redictive benefits, are still relatively unknown. In this session I will cover a number of studies that have specifically studied breast tumors before and after neoadjuvant treatment, with a focus on changes within the tumor cell population, including acquisition of epithelial-to-mesenchymal (EMT) and stem-like properties. In addition, alterations to immune cell dynamics in the tumor microenvironment, the plasticity of post-treatment phenotypes, and how these features impact the treatment paradigm based upon residual disease, will also be discussed. Multiple factors likely contribute to the poor prognosis associated with residual disease. Human breast tumors that remain following either chemotherapy, or endocrine therapy, often show an enrichment of gene expression signatures associated with tumor-initiating cells and EMT, suggesting that intrinsic tumor characteristics may contribute to selection of resistant populations. Additionally, residual tumors may show a variety of genomic aberrations at higher frequency than found in primary tumors, suggesting that resistance pathways may be selected for during neoadjuvant treatment. Tumor extrinsic factors, particularly the interaction between tumor and immune cells, are also altered by breast cancer neoadjuvant therapies. Nevertheless, there is hope that these residual disease specific alterations may provide key susceptibilities to other treatments. Lastly, defining predictive biomarkers from residual disease has been difficult. In addition to the variety and complexity of resistance mechanisms that lead to residual disease, questions regarding tumor plasticity and the duration of post-treatment changes complicate the analysis of residual breast cancers specimens. An improved understanding of the biology of residual breast cancers will be critical as we develop novel treatment strategies for those with residual disease. Citation Format: C Perou. The biology and plasticity of residual disease after neoadjuvant treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES11-1.
Autophagy-associated circRNA circCDYL augments autophagy and promotes breast cancer progression
Authors: Gehao Liang, Yun Ling, Maryam Mehrpour, Phei Er Saw, Zihao Liu, Weige Tan, Zhenluan Tian, Wenjing Zhong, Wanyi Lin, Qing Luo, Qun Lin, Qiufang Li, You Zhou, Ahmed Hamai, Patrice Codogno, Jun Li, Erwei Song, Chang Gong
Journal: Molecular Cancer (2020)

Abstract Background Although both circular RNAs (circRNAs) and autophagy are associated with the function of breast cancer (BC), whether circRNAs regulate BC progression via autophagy remains unknown. In this study, we aim to explore the regulatory mechanisms and the clinical significance of autophagy-associated circRNAs in BC. Methods Autophagy associated circRNAs were screened by circRNAs deep sequencing and validated by qRT-PCR in BC tissues with high- and low- autophagic level. The biological function of autophagy associated circRNAs were assessed by plate colony formation, cell viability, transwells, flow cytometry and orthotopic animal models. For mechanistic study, RNA immunoprecipitation, circRNAs pull-down, Dual luciferase report assay, Western Blot, Immunofluorescence and Immunohistochemical staining were performed. Results An autophagy associated circRNA circCDYL was elevated by 3.2 folds in BC tissues as compared with the adjacent non-cancerous tissues, and circCDYL promoted autophagic level in BC cells via the miR-1275-ATG7/ULK1 axis; Moreover, circCDYL enhanced the malignant progression of BC cells in vitro and in vivo. Clinically, increased circCDYL in the tumor tissues and serum of BC patients was associated with higher tumor burden, shorter survival and poorer clinical response to therapy. Conclusions circCDYL promotes BC progression via the miR-1275-ATG7/ULK1-autophagic axis and circCDYL could act as a potential prognostic and predictive molecule for breast cancer patients.
Real-World Gluten Exposure in Patients With Celiac Disease on Gluten-Free Diets, Determined From Gliadin Immunogenic Peptides in Urine and Fecal Samples
Authors: Juan Pablo Stefanolo, Martín Tálamo, Samanta Dodds, María de la Paz Temprano, Ana Florencia Costa, María Laura Moreno, María Inés Pinto-Sánchez, Edgardo Smecuol, Horacio Vázquez, Andrea Gonzalez, Sonia Isabel Niveloni, Eduardo Mauriño, Elena F. Verdu, Julio César Bai
Journal: Clinical Gastroenterology and Hepatology (2020)
Hybrid Epithelial–Mesenchymal Phenotypes Are Controlled by Microenvironmental Factors
Authors: Gianluca Selvaggio, Sara Canato, Archana Pawar, Pedro T. Monteiro, Patrícia S. Guerreiro, M. Manuela Brás, Florence Janody, Claudine Chaouiya
Journal: Cancer Research (2020)

Abstract Epithelial-to-mesenchymal transition (EMT) has been associated with cancer cell heterogeneity, plasticity, and metastasis. However, the extrinsic signals supervising these phenotypic transitions remain elusive. To assess how selected microenvironmental signals control cancer-associated phenotypes along the EMT continuum, we defined a logical model of the EMT cellular network that yields qualitative degrees of cell adhesions by adherens junctions and focal adhesions, two features affected during EMT. The model attractors recovered epithelial, mesenchymal, and hybrid phenotypes. Simulations showed that hybrid phenotypes may arise through independent molecular paths involving stringent extrinsic signals. Of particular interest, model predictions and their experimental validations indicated that: (i) stiffening of the extracellular matrix was a prerequisite for cells overactivating FAK_SRC to upregulate SNAIL and acquire a mesenchymal phenotype and (ii) FAK_SRC inhibition of cell–cell contacts through the receptor-type tyrosine-protein phosphatases kappa led to acquisition of a full mesenchymal, rather than a hybrid, phenotype. Altogether, these computational and experimental approaches allow assessment of critical microenvironmental signals controlling hybrid EMT phenotypes and indicate that EMT involves multiple molecular programs. Significance: A multidisciplinary study sheds light on microenvironmental signals controlling cancer cell plasticity along EMT and suggests that hybrid and mesenchymal phenotypes arise through independent molecular paths.
Novel BCL2 mutations in venetoclax-resistant, ibrutinib-resistant CLL patients with BTK/PLCG2 mutations
Authors: Fabienne Lucas, Karylin Larkin, C. Thomas Gregory, Shelley Orwick, Tzyy-Jye Doong, Arletta Lozanski, Gerard Lozanski, Shrilekha Misra, Apollinaire Ngankeu, Hatice Gulcin Ozer, Deepa Sampath, Shanmugapriya Thangavadivel, Selen A. Yilmaz, Kerry A. Rogers, John C. Byrd, Jennifer A. Woyach, James S. Blachly
Journal: Blood (2020)
Assessment of Predictive Scoring System for 90-Day Mortality Among Patients With Locally Advanced Head and Neck Squamous Cell Carcinoma Who Have Completed Concurrent Chemoradiotherapy
Authors: Kuan-Chou Lin, Tsung-Ming Chen, Kevin Sheng-Po Yuan, Alexander T. H. Wu, Szu-Yuan Wu
Journal: JAMA Network Open (2020)

<h3>Importance</h3> There is currently no system to predict 90-day morality among patients with locally advanced head and neck squamous cell carcinoma (HNSCC) after the completion of concurrent chemoradiotherapy (CCRT). <h3>Objective</h3> To validate the accuracy of a predictive scoring system for 90-day mortality among patients with locally advanced HNSCC who have completed CCRT. <h3>Design, Setting, and Participants</h3> This prognostic study included 16 029 patients with HNSCC who completed CCRT between January 2006 and December 2015. Data were extracted from the Taiwan Cancer Registry Database. A risk scoring system was developed based on significant risk factors and corresponding risk coefficients. Data analysis was conducted from June 2018 to February 2019. <h3>Exposures</h3> Mortality within 90 days of completion of definitive CCRT. <h3>Main Outcomes and Measures</h3> The 90-day mortality rate after completion of CCRT and the accuracy of the scoring system, based on a comparison of mortality rates between training and test data sets. <h3>Results</h3> Among 16 029 patients with locally advanced HNSCC, 1068 (6.66%; 1016 [95.1%] men; mean [SD] age, 55.11 [11.45] years) died before reaching the 90-day threshold, and 14 961 (93.4%; 14 080 [94.1%] men; mean [SD] age, 52.07 [9.99] years) survived. Multivariable analysis revealed that being aged 50 years or older (adjusted hazard ratio [aHR], 1.263; 95% CI, 1.104-1.445;<i>P</i> &lt; .001), being aged 70 years or older (aHR, 2.183; 95% CI, 1.801-2.645;<i>P</i> &lt; .001), having pneumonia (aHR, 1.946; 95% CI, 1.636-2.314;<i>P</i> &lt; .001), having sepsis (aHR, 3.005; 95% CI, 2.503-3.607;<i>P</i> &lt; .001), having hemiplegia (aHR, 1.430; 95% CI, 1.085-1.884;<i>P</i> = .01), having moderate or severe renal disease (aHR, 2.054; 95% CI, 1.643-2.568;<i>P</i> &lt; .001), having leukemia (aHR, 4.541; 95% CI, 1.132-8.207;<i>P</i> = .03), and having non-HNSCC metastatic solid cancers (aHR, 1.457; 95% CI, 1.292-1.644;<i>P</i> &lt; .001) were significant risk factors for 90-day mortality. Risk scores were categorized as very low risk (score of 0), low risk (score 1-3), moderate risk (score 4-6), and high risk (score ≥7), with 90-day mortality rates of 3.37%, 5.00% to 10.98%, 16.15% to 29.13%, and 33.93% to 37.50%, respectively. Mortality rates for patients with the same risk score in the training and test data sets were similar (score of 0, 3.27% vs 3.66%; score of 6, 27.42% vs 25.00%). <h3>Conclusions and Relevance</h3> In this prognostic study, a 90-day mortality scoring system accurately predicted 90-day mortality among patients with locally advanced HNSCC who completed CCRT.
Lower respiratory tract infection in the community: associations between viral aetiology and illness course
Authors: L.M. Vos, R. Bruyndonckx, N.P.A. Zuithoff, P. Little, J.J. Oosterheert, B.D.L. Broekhuizen, C. Lammens, K. Loens, M. Viveen, C.C. Butler, D. Crook, K. Zlateva, H. Goossens, E.C.J. Claas, M. Ieven, A.M. Van Loon, T.J.M. Verheij, F.E.J. Coenjaerts
Journal: Clinical Microbiology and Infection (2020)
Covid-19: why is the UK government ignoring WHO’s advice?
Authors: Allyson M Pollock, Peter Roderick, KK Cheng, Bharat Pankhania
Journal: BMJ (2020)

<h3>Abstract</h3> A group of biologists, ARTIC Network, has proposed a multiplexed PCR primer set for whole-genome analysis of the novel coronavirus, SARS-CoV-2, soon after the start of COVID-19 epidemics was realized. The primer set was adapted by many researchers worldwide and has already contributed to the high-quality and prompt genome epidemiology of this rapidly spreading viral disease. We have also seen the great performance of their primer set and protocol; the primer set amplifies all desired 98 PCR amplicons with fairly small amplification bias from clinical samples with relatively high viral load. However, we also observed an acute drop of reads derived from some amplicons especially amplicon 18 and 76 in “pool 2” as a sample’s viral load decreases. We suspected this low coverage issue was due to dimer formation between primers targeting those two amplicons. Indeed, replacement of just one of those primers, nCoV-2019_76_RIGHT, to a newly designed primer resulted in a drastic improvement of coverages at both regions targeted by the amplicons 18 and 76. Given this result, we further replaced four primers in “pool 1” with each respective alternative. These modifications also improved coverage in eight amplicons particularly in samples with low viral load. The results of our experiments clearly indicate that primer dimer formation is one critical cause of coverage bias in ARTIC protocol. Importantly, some of the problematic primers are detectable by observing primer dimers in raw NGS sequence reads and replacing them with alternatives as shown in this study. We expect a continuous improvement of the ARTIC primer set will extend the limit for completion of SARS-CoV-2 genomes to samples with lower viral load, that supports better genomic epidemiology and mitigation of spread of this pathogen.
Somatic <i>SMAD3</i>-activating mutations cause melorheostosis by up-regulating the TGF-β/SMAD pathway
Authors: Heeseog Kang, Smita Jha, Aleksandra Ivovic, Nadja Fratzl-Zelman, Zuoming Deng, Apratim Mitra, Wayne A. Cabral, Eric P. Hanson, Eileen Lange, Edward W. Cowen, James Katz, Paul Roschger, Klaus Klaushofer, Ryan K. Dale, Richard M. Siegel, Timothy Bhattacharyya, Joan C. Marini
Journal: The Journal of Experimental Medicine (2020)

Melorheostosis is a rare sclerosing dysostosis characterized by asymmetric exuberant bone formation. Recently, we reported that somatic mosaicism for MAP2K1-activating mutations causes radiographical “dripping candle wax” melorheostosis. We now report somatic SMAD3 mutations in bone lesions of four unrelated patients with endosteal pattern melorheostosis. In vitro, the SMAD3 mutations stimulated the TGF-β pathway in osteoblasts, enhanced nuclear translocation and target gene expression, and inhibited proliferation. Osteoblast differentiation and mineralization were stimulated by the SMAD3 mutation, consistent with higher mineralization in affected than in unaffected bone, but differing from MAP2K1 mutation–positive melorheostosis. Conversely, osteoblast differentiation and mineralization were inhibited when osteogenesis of affected osteoblasts was driven in the presence of BMP2. Transcriptome profiling displayed that TGF-β pathway activation and ossification-related processes were significantly influenced by the SMAD3 mutation. Co-expression clustering illuminated melorheostosis pathophysiology, including alterations in ECM organization, cell growth, and interferon signaling. These data reveal antagonism of TGF-β/SMAD3 activation by BMP signaling in SMAD3 mutation–positive endosteal melorheostosis, which may guide future therapies.
Digital phenotyping, behavioral sensing, or personal sensing: names and transparency in the digital age
Authors: David C. Mohr, Katie Shilton, Matthew Hotopf
Journal: npj Digital Medicine (2020)

Data from networked sensors, such as those in our phones, are increasingly being explored and used to identify behaviors related to health and mental health. While computer scientists have referred to this field as context sensing, personal sensing, or mobile sensing, medicine has more recently adopted the term digital phenotyping. This paper discusses the implications of these labels in light of privacy concerns, arguing language that is transparent and meaningful to the people whose data we are acquiring.
Urgent need of a management plan for survivors of COVID-19
Authors: Bartolome Celli, Leonardo M. Fabbri
Journal: European Respiratory Journal (2020)

Acute exacerbations of COPD (AECOPD) or "COPD crises" [1], are crucial events in the natural course of COPD. Although they can occur at any severity stage, their impact increases as patients develop more severe airflow limitation. Survivors of COVID-19 may be at increased risk of cardiovascular morbidity and mortality and should be carefully monitored <https://bit.ly/2UhVjoy>
SARS-CoV-2: a storm is raging
Authors: Savannah F. Pedersen, Ya-Chi Ho
Journal: Journal of Clinical Investigation (2020)

The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-α), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.
Effect of performance status on short-term and long-term outcomes after liver resection for hepatocellular carcinoma: A multicenter study
Authors: Han Wu, Hao Xing, Lei Liang, Chao Li, Wan Yee Lau, Ya-hao Zhou, Wei-min Gu, Hong Wang, Ting-hao Chen, Wan Yee Lau, Feng Shen, Tian Yang
Journal: International Journal of Surgery (2020)
Clinical and immunological features of severe and moderate coronavirus disease 2019
Authors: Guang Chen, Di Wu, Wei Guo, Yong Cao, Da Huang, Hongwu Wang, Tao Wang, Xiaoyun Zhang, Huilong Chen, Haijing Yu, Xiaoping Zhang, Minxia Zhang, Shiji Wu, Jianxin Song, Tao Chen, Meifang Han, Shusheng Li, Xiaoping Luo, Jianping Zhao, Qin Ning
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, and is now becoming a global threat. We aimed to delineate and compare the immunological features of severe and moderate COVID-19.
The Limitations of Pain Scales—Reply
Authors: Vito Giordano, Philipp Deindl, Monika Olischar
Journal: JAMA Pediatrics (2020)

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