tbuckley/cabot-search huggingface dataset:
Deep metric learning for otitis media classification
Authors: Josefine Vilsbøll Sundgaard, James Harte, Peter Bray, Søren Laugesen, Yosuke Kamide, Chiemi Tanaka, Rasmus R. Paulsen, Anders Nymark Christensen
Journal: Medical Image Analysis (2021)

In this study, we propose an automatic diagnostic algorithm for detecting otitis media based on otoscopy images of the tympanic membrane. A total of 1336 images were assessed by a medical specialist into three diagnostic groups: acute otitis media, otitis media with effusion, and no effusion. To provide proper treatment and care and limit the use of unnecessary antibiotics, it is crucial to correctly detect tympanic membrane abnormalities, and to distinguish between acute otitis media and otitis media with effusion. The proposed approach for this classification task is based on deep metric learning, and this study compares the performance of different distance-based metric loss functions. Contrastive loss, triplet loss and multi-class N-pair loss are employed, and compared with the performance of standard cross-entropy and class-weighted cross-entropy classification networks. Triplet loss achieves high precision on a highly imbalanced data set, and the deep metric methods provide useful insight into the decision making of a neural network. The results are comparable to the best clinical experts and paves the way for more accurate and operator-independent diagnosis of otitis media.
OA02.05 Local, Regional and Pulmonary Failures in the Randomised PET-Boost Trial for NSCLC Patients
Authors: S. Cooke, D. De Ruysscher, B. Reymen, M. Lambrecht, G. Fredberg Persson, C. Faivre-Finn, E. Dieleman, J. Van Diessen, K. Sikorska, F. Lalezari, J. Sonke, J. Belderbos
Journal: Journal of Thoracic Oncology (2021)
Vaccination and non-pharmaceutical interventions for COVID-19: a mathematical modelling study
Authors: Sam Moore, Edward M Hill, Michael J Tildesley, Louise Dyson, Matt J Keeling
Journal: The Lancet Infectious Diseases (2021)

The dynamics of vaccination against SARS-CoV-2 are complicated by age-dependent factors, changing levels of infection, and the relaxation of non-pharmaceutical interventions (NPIs) as the perceived risk declines, necessitating the use of mathematical models. Our aims were to use epidemiological data from the UK together with estimates of vaccine efficacy to predict the possible long-term dynamics of SARS-CoV-2 under the planned vaccine rollout.
Social media language of healthcare super-utilizers
Authors: Sharath Chandra Guntuku, Elissa V. Klinger, Haley J. McCalpin, Lyle H. Ungar, David A. Asch, Raina M. Merchant
Journal: npj Digital Medicine (2021)

Abstract An understanding of healthcare super-utilizers’ online behaviors could better identify experiences to inform interventions. In this retrospective case-control study, we analyzed patients’ social media posts to better understand their day-to-day behaviors and emotions expressed online. Patients included those receiving care in an urban academic emergency department who consented to share access to their historical Facebook posts and electronic health records. Super-utilizers were defined as patients with more than six visits to the Emergency Department (ED) in a year. We compared posts by super-utilizers with a matched group using propensity scoring based on age, gender and Charlson comorbidity index. Super-utilizers were more likely to post about confusion and negativity (D = .65, 95% CI-[.38, .95]), self-reflection (D = .63 [.35, .91]), avoidance (D = .62 [.34, .90]), swearing (D = .52 [.24, .79]), sleep (D = .60 [.32, .88]), seeking help and attention (D = .61 [.33, .89]), psychosomatic symptoms, (D = .49 [.22, .77]), self-agency (D = .56 [.29, .85]), anger (D = .51, [.24, .79]), stress (D = .46, [.19, .73]), and lonely expressions (D = .44, [.17, .71]). Insights from this study can potentially supplement offline community care services with online social support interventions considering the high engagement of super-utilizers on social media.
P84.10 The Impact of 3rd-Line ALK Inhibitors in ALK Positive NSCLC in Real-World Data
Authors: M. Moskovitz, E. Dudnik, Y. Rotenberg, N. Popovich-Hadari, M. Wollner, A. Zer, M. Gottfried, M. Mishaeli, S. Keren-Rosenberg, A. Onn, D. Urban, N. Peled, N. Maimon, J. Bar
Journal: Journal of Thoracic Oncology (2021)
Abstract 12675: Comprehensive Analysis of Cardiomyopathy and Arrhythmia Genes Yields Unanticipated Molecular Diagnoses
Authors: Tom Callis, Ana Morales, Rebecca Truty, Matteo Vatta, Ellen Regalado, Susan Rojahn, Ed Esplin, Robert Nussbaum
Journal: Circulation (2020)

Introduction: Professional societies recommend genetic testing to improve diagnosis and inform management of inherited cardiovascular disease, yet genetic testing is not widely utilized in cardiovascular practice. To reduce barriers to genetic testing and facilitate following of existing guidelines, we initiated a program of sponsored genetic testing with genetic counseling at no cost to patients suspected of having a genetic arrhythmia or cardiomyopathy. Here, we describe unanticipated molecular diagnoses provided by a comprehensive analysis of cardiomyopathy and arrhythmia genes. Methods: With IRB approval, de-identified genetic and clinical data provided by ordering clinicians were reviewed from 1,606 individuals referred for testing through the sponsored, no-charge Detect Cardiomyopathy and Arrhythmia genetic testing program between July 2019 and January 2020. Testing consisted of a cardiomyopathy and arrhythmia panel of up to 150 genes detecting single nucleotide, small indel, and exon-level deletion and duplication variants. Results: Overall, 20.5% (329/1606) of patients had a pathogenic or likely pathogenic (P/LP) variant identified. The most common reasons for referral were hypertrophic cardiomyopathy (40%), dilated cardiomyopathy (24%), and long QT syndrome (13%). The diagnostic yield was 25% (130/527) among patients whose healthcare provider reported a high or moderate index of clinical suspicion for a genetic cardiomyopathy, of whom 2% (2/130) had P/LP variants only in the arrhythmia gene KCNQ1 . Conversely, among patients with a high or moderate index of clinical suspicion for a genetic arrhythmia, the diagnostic yield was 20% (28/137), of which 18% (5/28) had P/LP variants only in the cardiomyopathy-associated genes MYBPC3 (2) and TTR (3). Conclusions: These data demonstrate that comprehensive genetic testing, without cost as a barrier, identifies clinically-relevant variants in 1 in 5 suspected cardiomyopathy or arrhythmia patients. Notably, genetic testing with a multi-condition panel yielded unanticipated molecular findings likely to change clinical management in up to 18% of genetically-positive patients. These unanticipated findings would have likely been missed by targeted, disease-specific panels.
<i>JAMA Neurology—</i>The Year in Review, 2020
Authors: S. Andrew Josephson
Journal: JAMA Neurology (2021)

The last 12 months have been unprecedented here at JAMA Neurology.In the setting of the coronavirus disease 2019 (COVID-19) pandemic, the journal had to rapidly evolve to handle a record number of manuscripts and respond to the needs of our readers to be informed of the most timely and important neurological information about the virus.We received more than 400 submissions related to COVID-19, and we were able to publish very quickly those select contributions that we felt truly were important for neurologists on the frontlines, including the initial experience of neurological complications from Wuhan province, China, and important observations on the pathobiology of nervous system involvement.The year was record setting (Table ) 1-4 for the 3498 manuscripts overall that we received, nearly 2500 of which were original research.While some of this nearly 50% growth in submissions was related to COVID-19 manuscripts, these only accounted for approximately half of the increase compared with the year before.With our impact factor rising again to 13.6, the quality of manuscripts across a diverse set of neurologic topics in JAMA Neurology has never been higher, including an ever-increasing number of clinical trials that directly impact neurologic practice.In the setting of these record numbers, the work of our editors, editorial board members, peer reviewers (whose names are listed herein), 5 and authors has never been so important and impressive.
P30.04 The Value of Clinical and Genetic Factors in Pain Management in EGFR Mutated Advanced Lung Adenocarcinoma Patients
Authors: M. Cavic, V. Jokic, K. Savic-Vujovic, Z. Bukumiric, R. Jankovic, D. Radosavljevic, J. Spasic
Journal: Journal of Thoracic Oncology (2021)
P35.01 Genomic Origin and Immune-related Status of Pulmonary Sarcomatoid Carcinoma
Authors: X. Liu, F. Wang, X. Chen, X. Hou, Q. Li, Z. Xie, Y. Liu, P. Li, L. Chang, Y. Guan, X. Zhang, S. Wang, C. Xu, H. Wang, X. Yi, J. Zhang, X. Xia, C. Moran, L. Chen
Journal: Journal of Thoracic Oncology (2021)
Gene therapy for a murine model of eosinophilic esophagitis
Authors: Anna E. Camilleri, Saparja Nag, Anthony R. Russo, Katie M. Stiles, Ronald G. Crystal, Odelya E. Pagovich
Journal: Allergy (2021)

Eosinophils are specialized granulocytic effector cells that store and release highly active mediators used in immune defense. Eosinophils are also implicated in the pathogenesis of allergic disorders, including eosinophilic esophagitis (EoE), a chronic disorder characterized by infiltration of eosinophils into the esophagus and release of mediators that damage tissue, resulting in gastrointestinal morbidity, food impaction, and dysphagia. Treatment with elimination diets and/or topical corticosteroid therapy slow disease progression, but are complicated by adverse effects, limited compliance, and loss of response to therapy. We hypothesized that a single administration of an adeno-associated virus (AAV) coding for an anti-eosinophil monoclonal antibody that induces eosinophil clearance (anti-Siglec-F) would treat on a persistent basis a murine model of EoE.A mouse model of peanut-induced EoE that mimics the human disease was established by sensitization and challenge with peanut extract. After challenge, these mice exhibited an EoE phenotype demonstrated by elevated levels of blood eosinophils, infiltration of eosinophils in the esophagus with associated esophageal remodeling and food impaction.The mice were treated with a single intravenous administration (1011 genome copies) of AAVrh.10mAnti-Eos, a serotype rh.10 AAV vector coding for an anti-Siglec-F monoclonal antibody. Vector administration resulted in persistent, high levels of anti-Siglec-F antibody expression. Administration of AAVrh.10mAnti-Eos to the mouse model of EoE reduced blood (P < 0.02) and esophageal eosinophil numbers (P < 0.002) protected from esophageal tissue remodeling and minimized food impaction.These results suggest that a single treatment with AAVrh.10mAnti-Eos has the potential to provide persistent therapeutic benefit to patients with EoE.
Transplantation of 3D MSC/HUVEC spheroids with neuroprotective and proangiogenic potentials ameliorates ischemic stroke brain injury
Authors: Ting-Wei Hsu, Yu-Jen Lu, Yu-Jie Lin, Yu-Ting Huang, Li-Hung Hsieh, Bing-Huan Wu, Yu-Chun Lin, Li-Chi Chen, Hsin-Wen Wang, Jui-Che Chuang, Yi-Qiao Fang, Chieh-Cheng Huang
Journal: Biomaterials (2021)
CLO21-029: Impact of Comorbidity Patterns on the Outcomes of Older Patients With Diffuse Large B- Cell Lymphoma
Authors: Karen Valdés-Díaz, Halbert Hernández-Negrín, Leonel Valdés-Leiva, Diana Martin-Oliva, Dianelys Pedraza-González
Journal: Journal of the National Comprehensive Cancer Network (2021)
MARCKS affects cell motility and response to BTK inhibitors in CLL
Authors: Laura Beckmann, Valeska Berg, Clarissa Dickhut, Clare Sun, Olaf Merkel, Johannes Bloehdorn, Sandra Robrecht, Marc Seifert, Alexandra da Palma Guerreiro, Julia Claasen, Stefan Loroch, Matteo Oliverio, Chingiz Underbayev, Lauren Vaughn, Daniel Thomalla, Malte F. Hülsemann, Eugen Tausch, Kirsten Fischer, Anna Maria Fink, Barbara Eichhorst, Albert Sickmann, Clemens M. Wendtner, Stephan Stilgenbauer, Michael Hallek, Adrian Wiestner, René P. Zahedi, Lukas P. Frenzel
Journal: Blood (2021)
Oncometabolites in Cancer: Current Understanding and Challenges
Authors: Yang Liu, Chunzhang Yang
Journal: Cancer Research (2021)

Abstract Oncometabolites are pathognomonic hallmarks in human cancers, including glioma, leukemia, neuroendocrine tumors, and renal cancer. Oncometabolites are aberrantly accumulated from disrupted Krebs cycle and affect the catalytic activity of α-ketoglutarate–dependent dioxygenases. Oncometabolites indicate distinct cancer-related patterns ranging from oncogenesis and metabolism to therapeutic resistance. Here we discuss the current understanding of oncometabolites as well as the controversies and challenges associated with oncometabolite-driven cancers. New insights into the relationship between cancer and oncometabolites will elucidate novel therapeutic avenues for improved cancer treatment.
Spending and Out-of-Pocket Prices for Brand-Name Drugs Among Commercially Insured Individuals in Massachusetts, 2015-2017
Authors: Micah B. Aaron, Anna D. Sinaiko
Journal: JAMA Network Open (2021)

b Patient share is the mean OOP price per 30-day prescription per drug-year divided by the point-of-service price per 30-day prescription per drug-year.
QIM21-091: Patterns of Health Portal Usage Among Patients With Cancer During the Year of Diagnosis: Results From the UWCCC Survivorship Program
Authors: Rebecca P. Luoh, Amye J. Tevaarwerk, Thevaa Chandereng, Elena M. Smith, Cibele Carroll, Hamid Emamekhoo, Mary E. Sesto
Journal: Journal of the National Comprehensive Cancer Network (2021)

"QIM21-091: Patterns of Health Portal Usage Among Patients With Cancer During the Year of Diagnosis: Results From the UWCCC Survivorship Program" published on 17 Mar 2021 by National Comprehensive Cancer Network.
Challenges in Paragangliomas and Pheochromocytomas: from Histology to Molecular Immunohistochemistry
Authors: C. Christofer Juhlin
Journal: Endocrine Pathology (2021)

Abstract Abdominal paragangliomas and pheochromocytomas (PPGLs) are rare neuroendocrine tumors of the infradiaphragmatic paraganglia and adrenal medulla, respectively. Although few pathologists outside of endocrine tertiary centers will ever diagnose such a lesion, the tumors are well known through the medical community—possible due to a combination of the sheer rarity, their often-spectacular presentation due to excess catecholamine secretion as well as their unrivaled coupling to constitutional susceptibility gene mutations and hereditary syndromes. All PPGLs are thought to harbor malignant potential, and therefore pose several challenges to the practicing pathologist. Specifically, a responsible diagnostician should recognize both the capacity and limitations of histological, immunohistochemical, and molecular algorithms to pinpoint high risk for future metastatic disease. This focused review aims to provide the surgical pathologist with a condensed update regarding the current strategies available in order to deliver an accurate prognostication of these enigmatic lesions.
FP07.12 Underdiagnosis of EGFR Exon 20 Insertion Mutation Variants: Estimates from NGS-based Real-World Datasets
Authors: J.M. Bauml, S. Viteri, A. Minchom, L. Bazhenova, S. Ou, M. Schaffer, N. Le Croy, R. Riley, P. Mahadevia, N. Girard
Journal: Journal of Thoracic Oncology (2021)
Phylogenetic Permulations: A Statistically Rigorous Approach to Measure Confidence in Associations in a Phylogenetic Context
Authors: Elysia Saputra, Amanda Kowalczyk, Luisa Cusick, Nathan Clark, Maria Chikina
Journal: Molecular Biology and Evolution (2021)

Abstract Many evolutionary comparative methods seek to identify associations between phenotypic traits or between traits and genotypes, often with the goal of inferring potential functional relationships between them. Comparative genomics methods aimed at this goal measure the association between evolutionary changes at the genetic level with traits evolving convergently across phylogenetic lineages. However, these methods have complex statistical behaviors that are influenced by nontrivial and oftentimes unknown confounding factors. Consequently, using standard statistical analyses in interpreting the outputs of these methods leads to potentially inaccurate conclusions. Here, we introduce phylogenetic permulations, a novel statistical strategy that combines phylogenetic simulations and permutations to calculate accurate, unbiased P values from phylogenetic methods. Permulations construct the null expectation for P values from a given phylogenetic method by empirically generating null phenotypes. Subsequently, empirical P values that capture the true statistical confidence given the correlation structure in the data are directly calculated based on the empirical null expectation. We examine the performance of permulation methods by analyzing both binary and continuous phenotypes, including marine, subterranean, and long-lived large-bodied mammal phenotypes. Our results reveal that permulations improve the statistical power of phylogenetic analyses and correctly calibrate statements of confidence in rejecting complex null distributions while maintaining or improving the enrichment of known functions related to the phenotype. We also find that permulations refine pathway enrichment analyses by correcting for nonindependence in gene ranks. Our results demonstrate that permulations are a powerful tool for improving statistical confidence in the conclusions of phylogenetic analysis when the parametric null is unknown.
Novel compound FLZ alleviates rotenone-induced PD mouse model by suppressing TLR4/MyD88/NF-κB pathway through microbiota–gut–brain axis
Authors: Zhe Zhao, Fangyuan Li, Jingwen Ning, Ran Peng, Junmei Shang, Hui Liu, Meiyu Shang, Xiu-Qi Bao, Dan Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Parkinson's disease (PD) is the second most common neurodegenerative disease, but none of the current treatments for PD can halt the progress of the disease due to the limited understanding of the pathogenesis. In PD development, the communication between the brain and the gastrointestinal system influenced by gut microbiota is known as microbiota-gut-brain axis. However, the explicit mechanisms of microbiota dysbiosis in PD development have not been well elucidated yet. FLZ, a novel squamosamide derivative, has been proved to be effective in many PD models and is undergoing the phase I clinical trial to treat PD in China. Moreover, our previous pharmacokinetic study revealed that gut microbiota could regulate the absorption of FLZ in vivo. The aims of our study were to assess the protective effects of FLZ treatment on PD and to further explore the underlying microbiota-related mechanisms of PD by using FLZ as a tool. In the current study, chronic oral administration of rotenone was utilized to induce a mouse model to mimic the pathological process of PD. Here we revealed that FLZ treatment alleviated gastrointestinal dysfunctions, motor symptoms, and dopaminergic neuron death in rotenone-challenged mice. 16S rRNA sequencing found that PD-related microbiota alterations induced by rotenone were reversed by FLZ treatment. Remarkably, FLZ administration attenuated intestinal inflammation and gut barrier destruction, which subsequently inhibited systemic inflammation. Eventually, FLZ treatment restored blood-brain barrier structure and suppressed neuroinflammation by inhibiting the activation of astrocytes and microglia in the substantia nigra (SN). Further mechanistic research demonstrated that FLZ treatment suppressed the TLR4/MyD88/NF-κB pathway both in the SN and colon. Collectively, FLZ treatment ameliorates microbiota dysbiosis to protect the PD model via inhibiting TLR4 pathway, which contributes to one of the underlying mechanisms beneath its neuroprotective effects. Our research also supports the importance of microbiota-gut-brain axis in PD pathogenesis, suggesting its potential role as a novel therapeutic target for PD treatment.
Prognostic Impact of Immunohistochemistry and MRD Results in Bone Marrow after Frontline Chemoimmunotherapy of Chronic Lymphocytic Leukemia (CLL): Results of Central Laboratory Analyses of the CLL10 Trial of the German CLL Study Group (GCLLSG)
Authors: Nadine Kutsch, Sebastian Böttcher, Sandra Robrecht, Jasmin Bahlo, Christian Maurer, Elisabeth Lange, Hubert Köppler, Michael G Kiehl, Martin Sökler, Rudolf Schlag, Ursula Vehling-Kaiser, Georg Köchling, Christoph Plöger, Michael Gregor, Torben Plesner, Ilske Oschlies, Marco Herling, Kirsten Fischer, Hartmut Döhner, Michael Kneba, Clemens-Martin Wendtner, Karl-Anton Kreuzer, Stephan Stilgenbauer, Anna Maria Fink, Michael Hallek, Wolfram Klapper, Barbara F. Eichhorst
Journal: Blood (2017)
OA04.03 Mobocertinib in NSCLC With EGFR Exon 20 Insertions: Results From EXCLAIM and Pooled Platinum-Pretreated Patient Populations
Authors: C. Zhou, S. Ramalingam, B. Li, J. Fang, T.M. Kim, S. Kim, J.C. Yang, G. Riely, T. Mekhail, D. Nguyen, M.R. Garcia Campelo, E. Felip, S. Jin, V. Bunn, J. Lin, H. Lin, M. Mehta, P. Jänne
Journal: Journal of Thoracic Oncology (2021)

Mobocertinib is a potent first-in-class tyrosine kinase inhibitor (TKI) designed to target EGFR exon 20 insertion (EGFRex20ins) mutations. We report first results from the EXCLAIM extension cohort of a phase 1/2 study (NCT02716116) and results in patients with EGFRex20ins-mutant NSCLC who received prior platinum-based therapy from the dose-escalation/expansion parts of the study and the EXCLAIM extension cohort.
P76.08 High Tumour PD-L1 Is Associated With Poor Outcomes in EGFR-Mutant Lung Cancer Treated With First Generation EGFR TKIs
Authors: J. Liu, M. Itchins, A. Nagrial, W. Cooper, M. De Silva, M. Barnet, W. Varikatt, V. Sivasubramaniam, A. Davis, A. Gill, P. Blinman, K. Lee, R. Hui, B. Gao, N. Pavlakis, S. Clarke, J. Lee, M. Boyer, S. Kao
Journal: Journal of Thoracic Oncology (2021)
Evidence Gaps in Cancer Survivorship Care: A Report From the 2019 National Cancer Institute Cancer Survivorship Workshop
Authors: Lisa Gallicchio, Emily Tonorezos, Janet S de Moor, Joanne Elena, Margaret Farrell, Paige Green, Sandra A Mitchell, Michelle A Mollica, Frank Perna, Nicole Gottlieb Saiontz, Li Zhu, Julia Rowland, Deborah K Mayer
Journal: JNCI Journal of the National Cancer Institute (2021)

Today, there are more than 16.9 million cancer survivors in the United States; this number is projected to grow to 22.2 million by 2030. Although much progress has been made in describing cancer survivors' needs and in improving survivorship care since the seminal 2006 Institute of Medicine report "From Cancer Patient to Cancer Survivor: Lost in Transition," there is a need to identify evidence gaps and research priorities pertaining to cancer survivorship. Thus, in April 2019, the National Cancer Institute convened grant-funded extramural cancer survivorship researchers, representatives of professional organizations, cancer survivors, and advocates for a 1-day in-person meeting. At this meeting, and in a subsequent webinar aimed at soliciting input from the wider survivorship community, evidence gaps and ideas for next steps in the following 6 areas, identified from the 2006 Institute of Medicine report, were discussed: surveillance for recurrence and new cancers, management of long-term and late physical effects, management of long-term and late psychosocial effects, health promotion, care coordination, and financial hardship. Identified evidence gaps and next steps across the areas included the need to understand and address disparities among cancer survivors, to conduct longitudinal studies as well as longer-term (>5 years postdiagnosis) follow-up studies, to leverage existing data, and to incorporate implementation science strategies to translate findings into practice. Designing studies to address these broad evidence gaps, as well as those identified in each area, will expand our understanding of cancer survivors' diverse needs, ultimately leading to the development and delivery of more comprehensive evidence-based quality care.