tbuckley/cabot-search huggingface dataset:
Abstract IA-05: Deep learning radiomics in cancer imaging
Authors: Ahmed Hosny
Journal: Clinical Cancer Research (2021)

Abstract Radiographic medical images contain a vast wealth of information allowing for accurate non-invasive tumor characterization and ultimately improving cancer care. Radiomics enables the extraction of mineable high-dimensional features from images, quantification of tumor phenotypes for survival, recurrence, and treatment response prediction, and ultimately better patient stratification. Recent advances in AI, deep learning in particular, has allowed for the automated extraction of imaging features without the need for pre-definition. In this talk, we will be exploring deep learning radiomics applications in cancer patients from both single time point and longitudinal imaging data. We will also be identifying challenges regarding the stability, reproducibility, and transparency of such approaches. Citation Format: Ahmed Hosny. Deep learning radiomics in cancer imaging [abstract]. In: Proceedings of the AACR Virtual Special Conference on Artificial Intelligence, Diagnosis, and Imaging; 2021 Jan 13-14. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(5_Suppl):Abstract nr IA-05.
<i>SPOP</i> mutations in prostate cancer: Clinical and genomic features.
Authors: Mari Nakazawa, Mike Fang, Pedro Issacsson Velho, Emmanuel S. Antonarakis
Journal: Journal of Clinical Oncology (2021)

151 Background: Point mutations in the gene encoding speckle-type pox virus and zinc finger protein (SPOP) are the most frequently identified mutations in prostate cancer, occurring at a frequency of 6-15% across localized and disseminated cancers. Recently, SPOP gene alterations have gained attention as they appear to define a novel subclass of prostate cancers. Previous studies show that patients with mutant SPOP (mtSPOP) had superior responses to androgen deprivation therapy (ADT) and exhibit more favorable responses to abiraterone compared to wild type SPOP (wtSPOP). Methods: We retrospectively identified 59 prostate cancer patients at a single institution (Johns Hopkins) with somatic SPOP mutations from genomic testing of primary tumors (n=45), metastatic lesions (n=12), or liquid biopsies (n=2). Patient records were reviewed to determine baseline characteristics, therapies received, and clinical outcomes. The primary outcomes included best PSA response and progression-free survival (PFS) on ADT in the hormone sensitive prostate cancer (HSPC) setting and on abiraterone and/or enzalutamide in the first-line castration resistant prostate cancer (CRPC) setting. PFS was defined as either PSA, radiographic, or clinical progression. Results: The median age at diagnosis was 64 years (range 46 to 85). 17/59 (28.8%) were Black. F133 was the most frequently mutated residue, occurring in 33 (55.9%) instances (Table). There were two patients who harbored two mutations in the SPOP gene. The most frequently co-occurring mutation was in APC (15/59 [25.4%] patients), resulting in Wnt pathway activation. Concurrent ERG fusions were not observed with this cohort (0/59 [0%] patients). 41/59 (69.4%) were diagnosed with Gleason 8-10 disease. 21/59 (35.5%) were diagnosed with de novo metastatic disease. 50/59 (84.7%) patients received ADT for recurrent or metastatic disease. Median PFS on ADT was 40.7 (95% CI 23.4-71.9) months. Of the 27/59 (45.8%) patients who progressed to CRPC, 20/59 (33.9%) patients received abiraterone and 13/59 (22.0%) received enzalutamide; 9/59 (15.3%) patients received both agents. Median PFS was 7.8 (95% CI 6.7-NR) months on abiraterone and 7.3 (95% CI 3.2-NR) months on enzalutamide. Other notable therapies received in the CRPC setting include docetaxel (5/59 [8.5%] patients), cabazitaxel (5/59 [8.5%] patients), and PARP inhibitor olaparib or rucaparib (4/59 [6.8%] patients). Conclusions: SPOP mutations define a unique subset of prostate cancers enriched for black patients, high Gleason scores, absence of ERG fusions, and Wnt pathway activation. Clinical outcomes to first-line ADT appear longer than expected for genomically-unselected patients. [Table: see text]
Large volume paracentesis: to do or where to do?
Authors: Lucia Macken, Naaventhan Palaniyappan, Sumita Verma, Guruprasad Aithal
Journal: Gut (2021)

Siau et al question the recommended landmarks for performing large volume paracentesis (LVP) ‘at least 8 cm (laterally) from the midline and 5 cm above the symphysis (pubis)’.1 In their view, while this approach avoids puncturing vessels, there remains risk of injury to underlying solid organs.2

Our aim was to provide evidence-based guidance (https://blogs.bmj.com/gut/) where possible on the safest areas for performing therapeutic paracentesis.3 In fact, after systematically reviewing available evidence, our conclusion is that our recommended landmarks are appropriate.1 The most common (though still rare) complication overall after LVP remains bleeding (0%–2.7%) rather than organ …
Distinct plasma biomarkers confirm the diagnosis of mastocytosis and identify increased risk of anaphylaxis
Authors: Theo Gülen, Andrea Teufelberger, Maria Ekoff, Christine Möller Westerberg, Katarina Lyberg, Sven-Erik Dahlén, Barbro Dahlén, Gunnar Nilsson
Journal: Journal of Allergy and Clinical Immunology (2021)
Extensive Genome-Wide Phylogenetic Discordance Is Due to Incomplete Lineage Sorting and Not Ongoing Introgression in a Rapidly Radiated Bryophyte Genus
Authors: Olena Meleshko, Michael D. Martin, Thorfinn Sand Korneliussen, Christian Schröck, Paul Lamkowski, Jeremy Schmutz, Adam Healey, Bryan T. Piatkowski, A. Jonathan Shaw, David J. Weston, Kjell Ivar Flatberg, Péter Szövényi, Kristian Hassel, Hans K. Stenøien
Journal: Molecular Biology and Evolution (2021)

Abstract The relative importance of introgression for diversification has long been a highly disputed topic in speciation research and remains an open question despite the great attention it has received over the past decade. Gene flow leaves traces in the genome similar to those created by incomplete lineage sorting (ILS), and identification and quantification of gene flow in the presence of ILS is challenging and requires knowledge about the true phylogenetic relationship among the species. We use whole nuclear, plastid, and organellar genomes from 12 species in the rapidly radiated, ecologically diverse, actively hybridizing genus of peatmoss (Sphagnum) to reconstruct the species phylogeny and quantify introgression using a suite of phylogenomic methods. We found extensive phylogenetic discordance among nuclear and organellar phylogenies, as well as across the nuclear genome and the nodes in the species tree, best explained by extensive ILS following the rapid radiation of the genus rather than by postspeciation introgression. Our analyses support the idea of ancient introgression among the ancestral lineages followed by ILS, whereas recent gene flow among the species is highly restricted despite widespread interspecific hybridization known in the group. Our results contribute to phylogenomic understanding of how speciation proceeds in rapidly radiated, actively hybridizing species groups, and demonstrate that employing a combination of diverse phylogenomic methods can facilitate untangling complex phylogenetic patterns created by ILS and introgression.
ESE3/EHF, a promising target of rosiglitazone, suppresses pancreatic cancer stemness by downregulating CXCR4
Authors: Tianxing Zhou, Jing Liu, Yongjie Xie, Shuai Yuan, Yu Guo, Weiwei Bai, Kaili Zhao, Wenna Jiang, Hongwei Wang, Haotian Wang, Tiansuo Zhao, Chongbiao Huang, Song Gao, Xiuchao Wang, Shengyu Yang, Jihui Hao
Journal: Gut (2021)

The crosstalk between cancer stem cells (CSCs) and their niche is required for the maintenance of stem cell-like phenotypes of CSCs. Here, we identified E26 transformation-specific homologous factor (EHF) as a key molecule in decreasing the sensitivity of pancreatic cancer (PC) cells to CSCs' niche stimulus. We also explored a therapeutic strategy to restore the expression of EHF.We used a LSL-KrasG12D/+mice, LSL-Trp53R172H/+ and Pdx1-Cre (KPC) mouse model and samples from patients with PC. Immunostaining, flow cytometry, sphere formation assays, anchorage-independent growth assay, in vivo tumourigenicity, reverse transcription PCR, chromatin immunoprecipitation (ChIP) and luciferase analyses were conducted in this study.CXCL12 derived from pancreatic stellate cells (PSCs) mediates the crosstalk between PC cells and PSCs to promote PC stemness. Tumorous EHF suppressed CSC stemness by decreasing the sensitivity of PC to CXCL12 stimulus and inhibiting the crosstalk between PC and CSC-supportive niches. Mechanically, EHF suppressed the transcription of the CXCL12 receptor CXCR4. EHF had a cell autonomous role in suppressing cancer stemness by inhibiting the transcription of Sox9, Sox2, Oct4 and Nanog. Rosiglitazone suppressed PC stemness and inhibited the crosstalk between PC and PSCs by upregulating EHF. Preclinical KPC mouse cohorts demonstrated that rosiglitazone sensitised PDAC to gemcitabine therapy.EHF decreased the sensitivity of PC to the stimulus from PSC-derived CSC-supportive niche by negatively regulating tumorous CXCR4. Rosiglitazone could be used to target PC stem cells and the crosstalk between CSCs and their niche by upregulating EHF.
Molecular Pathology of Non-familial Follicular Epithelial–Derived Thyroid Cancer in Adults: From RAS/BRAF-like Tumor Designations to Molecular Risk Stratification
Authors: Paula Soares, Antónia Afonso Póvoa, Miguel Melo, João Vinagre, Valdemar Máximo, Catarina Eloy, José Manuel Cameselle-Teijeiro, Manuel Sobrinho-Simões
Journal: Endocrine Pathology (2021)
SARS-CoV-2 Infection Risk Among Active Duty Military Members Deployed to a Field Hospital — New York City, April 2020
Authors: Guy T. Clifton, Rituparna Pati, Florian Krammer, Eric D. Laing, Christopher C. Broder, Damodara R. Mendu, Mark P. Simons, Hua-Wei Chen, Victor A. Sugiharto, Anthony D Kang, Daniel Stadlbauer, Kathleen P. Pratt, Bradley C. Bandera, Darron K. Fritz, Eugene V. Millar, Timothy H. Burgess, Kevin K. Chung
Journal: MMWR Morbidity and Mortality Weekly Report (2021)
IL-6–based mortality prediction model for COVID-19: Validation and update in multicenter and second wave cohorts
Authors: Alberto Utrero-Rico, Javier Ruiz-Hornillos, Cecilia González-Cuadrado, Claudia Geraldine Rita, Berta Almoguera, Pablo Minguez, Antonio Herrero-González, Mario Fernández-Ruiz, Octavio Carretero, Juan Carlos Taracido-Fernández, Rosario López-Rodriguez, Marta Corton, José María Aguado, Luisa María Villar, Carmen Ayuso-García, Estela Paz-Artal, Rocio Laguna-Goya
Journal: Journal of Allergy and Clinical Immunology (2021)

Coronavirus disease 2019 (COVID-19) is a highly variable condition. Validated tools to assist in the early detection of patients at high risk of mortality can help guide medical decisions.We sought to validate externally, as well as in patients from the second pandemic wave in Europe, our previously developed mortality prediction model for hospitalized COVID-19 patients.Three validation cohorts were generated: 2 external with 185 and 730 patients from the first wave and 1 internal with 119 patients from the second wave. The probability of death was calculated for all subjects using our prediction model, which includes peripheral blood oxygen saturation/fraction of inspired oxygen ratio, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, IL-6, and age. Discrimination and calibration were evaluated in the validation cohorts. The prediction model was updated by reestimating individual risk factor effects in the overall cohort (N = 1477).The mortality prediction model showed good performance in the external validation cohorts 1 and 2, and in the second wave validation cohort 3 (area under the receiver-operating characteristic curve, 0.94, 0.86, and 0.86, respectively), with excellent calibration (calibration slope, 0.86, 0.94, and 0.79; intercept, 0.05, 0.03, and 0.10, respectively). The updated model accurately predicted mortality in the overall cohort (area under the receiver-operating characteristic curve, 0.91), which included patients from both the first and second COVID-19 waves. The updated model was also useful to predict fatal outcome in patients without respiratory distress at the time of evaluation.This is the first COVID-19 mortality prediction model validated in patients from the first and second pandemic waves. The COR+12 online calculator is freely available to facilitate its implementation (https://utrero-rico.shinyapps.io/COR12_Score/).
Onset of rheumatoid arthritis after COVID-19: coincidence or connected?
Authors: Veerle F A M Derksen, Theresa Kissel, Femke B G Lamers-Karnebeek, Arie E van der Bijl, Annemarie C Venhuizen, Tom W J Huizinga, René E M Toes, Anna H E Roukens, Diane van der Woude
Journal: Annals of the Rheumatic Diseases (2021)

Dravet syndrome (DS), previously known as severe myoclonic epilepsy in infancy (SMEI), is an epileptic encephalopathy that presents with prolonged seizures in the first year of life. The seizures often occur with fever or illness, and are frequently initially categorized as febrile seizures. The correct diagnosis of DS and appropriate follow-up are typically delayed. The EEG is normal at onset, and neuroimaging reveals no structural lesion. Early development is normal, but signs of regression appear in the second year of life and are often accompanied by convulsive status epilepticus, alternating hemiconvulsions, and myoclonic seizures. Diagnosis can be confirmed by genetic testing that is now available, and shows mutations within the <i>SCN1A</i> gene. Early recognition and diagnosis of DS and management with appropriate anticonvulsants and treatment plan may reduce the seizure burden and improve long-term developmental outcome.
Open-label, phase II study of ladiratuzumab vedotin (LV) for castration-resistant prostate cancer (SGNLVA-005, trial-in-progress).
Authors: Amna Falak Sher, Justine Yang Bruce, Nashat Y. Gabrail, Ian Churchill Anderson, Anna Patrikidou, Rachel E. Sanborn, Jae Yong Cho, Arielle Shebay Lee, Jong-Seok Lee, Louise M. Nott, Do-Youn Oh, Sang Cheul Oh, Sung Yong Oh, Yinghui Wang, Zejing Wang, Troy H. Guthrie
Journal: Journal of Clinical Oncology (2021)

TPS185 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer (Modi 2017). This study is currently evaluating the safety and efficacy of LV in different advanced solid tumors with various LIV-1 expression, including metastatic castration-resistant prostate cancer (mCRPC), advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with previously treated, locally advanced unresectable or metastatic advanced solid tumors, including mCRPC. Patients with mCRPC will receive LV administered as a 30 minute intravenous infusion (IV) at 1.25 mg/kg every 1 week. Up to 30 patients with mCRPC will be enrolled. Patients in the mCRPC cohort must have metastatic castration-resistant disease, have received no more than 1 prior line of androgen receptor-targeted therapy, have ≥28 days between androgen receptor-targeted therapy and start of study treatment, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. In addition, mCRPC patients with measurable and non-measurable disease are eligible if the protocol-defined criteria are met. mCRPC patients must not have BRCA gene mutations, prior cytotoxic chemotherapy in the metastatic mCRPC setting, prior radioisotope therapy, or radiotherapy to ≥30% of bone marrow. Patients are not preselected based on tumor LIV-1 expression. Their tumor samples will be analyzed for correlation between LIV-1 expression and response. Safety and efficacy will be monitored throughout the study. Study objectives include objective tumor response rate per RECIST 1.1 and prostate-specific antigen (PSA) response rate per Prostate Cancer Clinical Trials Working Group 3 (both primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.
Abstract 11310: Economic Impact of Increased Longevity in Insertable Cardiac Monitor Technology in Unexplained Syncope and Suspected Atrial Fibrillation Patients
Authors: Klaus K Witte, Laura M Sawyer, Sarah L Bermingham, Claudia Rinciog, Sarah C Rosemas, Stelios I Tsintzos, Matthew R Reynolds
Journal: Circulation (2019)

Introduction: The initial indication for the implantable cardiac monitor (ICM) was unexplained syncope; in this population early use of ICM is recommended following initial nondiagnostic workup. IC...
Sunitinib versus cabozantinib, crizotinib or savolitinib in metastatic papillary renal cell carcinoma (pRCC): Results from the randomized phase II SWOG 1500 study.
Authors: Sumanta K. Pal, Catherine Tangen, Ian Murchie Thompson, Naomi B. Haas, Daniel J. George, Daniel Yick Chin Heng, Brian M. Shuch, Mark N. Stein, Maria S. Tretiakova, Peter Humphrey, Adebowale Adeniran, Vivek Narayan, Georg A. Bjarnason, Ulka N. Vaishampayan, Ajjai Shivaram Alva, Tian Zhang, Scott Wesley Cole, Melissa Plets, John Wright, Primo "Lucky" N. Lara
Journal: Journal of Clinical Oncology (2021)

270 Background: MET signaling is a key molecular driver in pRCC. Given that there is no optimal therapy for metastatic pRCC, we sought to compare an existing standard (sunitinib) to putative MET kinase inhibitors. Methods: Eligible patients had pathologically verified pRCC, Zubrod performance status 0-1, and measurable metastatic disease. Patients may have received up to 1 prior systemic therapy excluding VEGF-directed agents. Patients were randomized 1:1:1:1 to receive either sunitinib 50 mg po qd (4 wks on/2 wks off), cabozantinib 60 mg po qd, crizotinib 250 mg po bid, or savolitinib 600 mg po qd. Patients were stratified by prior therapy and pRCC subtype (I vs II vs not otherwise specified [NOS]) based on local review. The primary objective was to compare progression-free survival (PFS) for each experimental arm versus sunitinib. With 41 eligible patients per arm, we estimated 85% power to detect a 75% improvement in median PFS with a 1-sided alpha of 0.10 using intent-to-treat analysis. A pre-planned futility analysis was performed after 50% of PFS events occurred. Secondary endpoints included toxicity, response rate, and overall survival. Results: Between 4/2016 and 12/2019, 152 patients were enrolled; 5 were ineligible. Median age was 66 (range:29-89) and 76% were male; 92% had no prior therapy. By local pathologic review, 18%, 54% and 28% of patients were characterized as having type I, type II and NOS histology, respectively. In contrast, the frequency of type I, type II, and NOS by central review was 30%, 45% and 25%, respectively. Accrual to the savolitinib and crizotinib arms was halted early for futility (PFS hazard ratio &gt; 1.0 for both); accrual continued to completion in the sunitinib and cabozantinib arms. Median PFS was significantly higher with cabozantinib relative to sunitinib (Table). Grade 3 or 4 adverse events occurred in 69%, 72%, 37% and 39% of patients receiving sunitinib, cabozantinib, crizotinib and savolitinib, respectively; one grade 5 adverse event was seen with cabozantinib. Overall survival and response data will be presented. Conclusions: In this multi-arm randomized trial, only cabozantinib resulted in a statistically significant and clinically meaningful prolongation of PFS in pRCC patients compared to sunitinib. These data support cabozantinib as a reference standard for eligible patients with metastatic pRCC. Clinical trial information: NCT02761057 . [Table: see text]
Are peas a safe food for lipid transfer protein allergic patients?
Authors: Claudia Alessandri, Ivana Giangrieco, Lisa Tuppo, Rosetta Ferrara, Danila Zennaro, Maria L. Bernardi, Michela Ciancamerla, Claudia Rafaiani, Chiara Rafaiani, Maurizio Tamburrini, Adriano Mari, Maria A. Ciardiello
Journal: Allergy (2021)

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SPOP mutation as a predictive marker for treatment of metastatic castration-resistant prostate cancer.
Authors: Andrew Stangl, Christopher Willner, Lucas Maahs, Charlotte Burmeister, Clara Hwang, Amanda Pilling
Journal: Journal of Clinical Oncology (2021)

160 Background: Predictive markers linking molecular background to treatment response and clinical outcomes are currently lacking in prostate cancer. Missense mutations in SPOP (speckle-type POZ protein) define a distinct molecular subtype, occurring in about 12% of both clinically localized and metastatic disease. SPOP mutations occur early in prostate tumorigenesis and facilitate dysregulation of the androgen-receptor (AR) signaling network, suggesting mutant SPOP can impact response to AR-directed therapies. We hypothesized that SPOP mutation will be associated with superior response to next-generation AR inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Methods: This is a retrospective study to evaluate patients who progressed to mCRPC and were treated with AR-targeted therapy (i.e. enzalutamide, abiraterone acetate). Eligibility criteria inlcuded androgen deprivation therapy, metastatic disease documented by bone lesion or soft tissue identified on imaging, castrate testosterone level ( &lt; 50g/dL), and evaluable tissue for DNA analysis. SPOP status was determined by next-generation sequencing. Time to PSA progression (PSA TTP) was defined per PCWG2 as PSA increase of 25% from nadir and a minimum of 2 ng/ml calculated from date of primary treatment initiation to the date of PSA progression. Overall survival (OS) was calculated from start of treatment to date of death. Statisitcal comparision of the SPOP mutant or wild-type was determined using Kaplan-Meier and independent t-test analysis. Results: The analysis included 69 men with mCRPC with previous or ongoing ADT and receipt of AR-directed therapy (aberaterone acetate, enzalutamide). SPOP status was determined for all patients: 7 patients SPOP mutant, 62 patients SPOP wild-type. Mutant SPOP was associated with significantly longer PSA TTP (22.5 vs. 9.7 months, p = 0.031) and improved OS (21 vs. 29 months, p = 0.12) with enzalutamide or abiraterone as compared to SPOP wild-type patients. Conclusions: Our data demonstrate that SPOP mutations predict for better outcomes with next-generation AR inhibitors in men with mCRPC. SPOP mutations are a prominent molecular sub-type with potential to impact clinical management in men with metastatic, therapy resistant prostate cancer.
The Polygenic Score Catalog as an open database for reproducibility and systematic evaluation
Authors: Samuel A. Lambert, Laurent Gil, Simon Jupp, Scott C. Ritchie, Yu Xu, Annalisa Buniello, Aoife McMahon, Gad Abraham, Michael Chapman, Helen Parkinson, John Danesh, Jacqueline A. L. MacArthur, Michael Inouye
Journal: Nature Genetics (2021)