tbuckley/cabot-search huggingface dataset:
Patch-based adaptive weighting with segmentation and scale (PAWSS) for visual tracking in surgical video
Authors: Xiaofei Du, Maximilian Allan, Sebastian Bodenstedt, Lena Maier-Hein, Stefanie Speidel, Alessio Dore, Danail Stoyanov
Journal: Medical Image Analysis (2019)

Vision-based tracking in an important component for building computer assisted interventions in minimally invasive surgery as it facilitates estimation of motion for instruments and anatomical targets. Tracking-by-detection algorithms are widely used for visual tracking, where the problem is treated as a classification task and a tracking target appearance model is updated over time using online learning. In challenging conditions, like surgical scenes, where tracking targets deform and vary in scale, the update step is prone to include background information in model appearance or to lack the ability to estimate change of scale, which degrades the performance of classifier. In this paper, we propose a Patch-based Adaptive Weighting with Segmentation and Scale (PAWSS) tracking framework that tackles both scale and background problems. A simple but effective colour-based segmentation model is used to suppress background information and multi-scale samples are extracted to enrich the training pool, which allows the tracker to handle both incremental and abrupt scale variations between frames. Experimentally, we evaluate our approach on Online Tracking Benchmark (OTB) dataset and Visual Object Tracking (VOT) challenge datasets, showing that our approach outperforms recent state-of-the-art trackers, and it especially improves successful rate score on OTB dataset, while on VOT datasets, PAWSS ranks among the top trackers while operating at real-time frame rates. Focusing on the application of PAWSS to surgical scenes, we evaluate on MICCAI 2015 challenge instrument tracking challenge and in vivo datasets, showing that our approach performs the best among all submitted methods and also has promising performance on in vivo surgical instrument tracking.
Abstract 4378: The association of enzymes related to cholesterol esters metabolism with hepatocellular carcinoma
Authors: Zhirong Liu, Akram Shalaby, Charu Subramony, Jinghe Mao, Xinchun Zhou
Journal: Cancer Research (2019)

Abstract Objectives: The roles of cholesteryl esters (CE) in the pathogenesis of hepatocellular carcinoma (HCC) have not been completely elucidated. This study is aimed to investigate differences in the expression level of enzymes involving in synthesis and degradation of CEs between benign hapatic tissues (BHT) and HCC, and between male and female patients from African American (AA) and Caucasian American (CA). Methods: TMAs were constructed with 97 BHT and 91 HCC samples from patients enrolled in the University of Mississippi Medical Center from 2010 to 2017. Immunochemistry (IHC) was performed on the TMAs for enzymes involved in CE synthesis (acyl CoA:cholesterol acyltransferase 1, ACAT1 and acyl CoA:cholesterol acyltransferase 2, ACAT2), and in CE degradation (lysosomal acid lipase, LAL and neutral cholesterol ester hydrolase 1, NCEH1) following the manufacturer’s instructions. The expression level for each enzyme was expressed as IHC score calculated with a scoring system. Two-tailed Student’s t-test was used to compare the difference in the expression level of each enzyme between two groups. Significant p value was set at p&amp;lt;0.05. Results: The IHC score of ACAT2 was significantly higher in HCC than in BHT in all population (6.21±2.42 vs (4.89.4±2.40, P=0.0006) and in stratified male population (6.15±2.33 vs 5.08±2.32, p=0.046), but not in stratified women, AA and CA populations. There was no significant difference in IHC score for ACAT1 between HCC and BHT in all population and populations stratified by race and gender. The IHC score of LAL was significantly higher in HCC as compared to BHT in all population (3.57±2.31 vs 2.40±1.30, P =0.0001) and in male population (3.33±2.01 vs 2.39±1.16, p=0.015), but not in stratified women, AA or CA population. The IHC score of NCEH1 was not significantly different between HCC and BHT in all studied population and population stratified by gender. However, it was disparate between AA and CA populations: The IHC score of NCEH1 was significantly lower in HCC than in BHT in AA population (5.59±2.04 vs 6.66±1.74, p=0.031) but it was higher in HCC than in BHT in CA population (6.84±1.96 vs 7.12±1.70, p&amp;gt;0.05). Conclusions: These results suggest that alterations in the expression levels of enzymes involving CE metabolism are associated with pathogenesis, progression and disparities in race and gender of HCC. This study also suggest that ACAT2 predominates CE synthesis as compared to ACAT1, and that LAL plays major role in CE degradation as compared to NCEH1 in association with HCC. Citation Format: Zhirong Liu, Akram Shalaby, Charu Subramony, Jinghe Mao, Xinchun Zhou. The association of enzymes related to cholesterol esters metabolism with hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4378.
A Novel Acquired Exon 20 EGFR M766Q Mutation in Lung Adenocarcinoma Mediates Osimertinib Resistance but is Sensitive to Neratinib and Poziotinib
Authors: Gina M. Castellano, Joseph Aisner, Stephen K. Burley, Brinda Vallat, Helena A. Yu, Sharon R. Pine, Shridar Ganesan
Journal: Journal of Thoracic Oncology (2019)
Resisting the Post-Truth Era: Maintaining a Commitment to Science and Social Justice in Bioethics
Authors: Drew B. A. Clark, Alice Virani, Diane Ehrensaft, Johanna Olson-Kennedy
Journal: The American Journal of Bioethics (2019)

A recent target article in the American Journal of Bioethics (AJOB) considered the right of transgender (trans) children to access pubertal suppression (Priest 2019). We were concerned by publicati...
Abstract 159: Chemokine receptor expression profiling of lymph node invasive versus lymph node non-invasive melanomas
Authors: David Z. Bushhouse, Kristian M. Hargadon
Journal: Cancer Research (2019)

Abstract Regional lymph nodes are one of the first sites of melanoma metastasis during tumor progression, and lymph node invasion by tumor cells is a poor prognostic factor in melanoma patients. We have employed models of lymph node invasive and lymph node non-invasive murine melanomas to investigate the potential role of chemokine/chemokine receptor signaling pathways in the regulation of tumor cell trafficking to regional lymph nodes. PCR array analyses identified several differentially expressed chemokine and chemokine receptor genes in the lymph node invasive B16-F1 melanoma versus the lymph node non-invasive D5.1G4 melanoma. Among these differentially expressed genes, Cxcr3, Cxcr6, Cxcr7, Cx3cr1, Cxcl10, and Cx3cl1 were all significantly upregulated at the RNA level in B16-F1 melanoma. We are currently validating these differential gene expression data at the protein level, and these findings will provide key insights into the potential role of these chemokines and chemokine receptors in the metastasis of melanoma cells to regional lymph nodes. Citation Format: David Z. Bushhouse, Kristian M. Hargadon. Chemokine receptor expression profiling of lymph node invasive versus lymph node non-invasive melanomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 159.
Abstract 2379: <i>In vivo</i> drug screening platform accelerated 4-1BB agonistic antibody development
Authors: Benny(Yi) Yang, Jian Ni, Yanan Li, Yuelei Shen, Qingcong Lin
Journal: Cancer Research (2019)

Abstract 4-1BB (TNFRSF9/CD137) belongs to the TNFR superfamily. 4-1BB is expressed by activated CD4 helper T cells, B cells, natural killer cells, natural killer T cells, dendritic cells, and activated endothelium. A majority of regulatory T cells (Tregs) also express 4-1BB, but it remains unclear whether agonistic antibody treatment exerts pro- or anti-suppressive effect on these cells. 4-1BB enhances tumor rejection because it is upregulated on T cells following activation and its engagement increases T cell proliferation and pro-inflammatory cytokine production. The clinical development of 4-1BB targeting therapy was slow due to the toxicity associated with overt immune activation. Fortunately, new therapeutic modalities using 4-1BB targeting aptamers as well as therapeutic combinations with other immuno-modulatory and traditional anti-cancer treatments have revived excitement for the use of 4-1BB agonists in the clinic. We focused on discovering novel 4-1BB therapeutic antibodies for cancer patients. Candidate molecules obtained through the classical hybridoma technology were screened by high-throughput flow cytometry. Then, we took the advantages of Biocytogen’s humanized mice and screened the purified antibodies in B-h4-1BB mice bearing MC-38 tumor cells. We found some antibodies that worked as equivalent as BMS’s Urelumab. To determine which isotype should be adopted, we engrafted the antigen binding domain onto various human Fc backbones. Interestingly, we found that the human IgG1 isotype appeared to be more effective against tumors than other isotypes in B-4-1BB mice bearing MC-38 tumors. This study provides a reliable basis for our follow-up mechanism research and clinical evaluation for this target. Citation Format: Benny(Yi) Yang, Jian Ni, Yanan Li, Yuelei Shen, Qingcong Lin. In vivo drug screening platform accelerated 4-1BB agonistic antibody development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2379.
Dynamics of Measurable Disease at Remission Determines Survival in Patients (Pts) with Philadelphia Chromosome Negative B-Cell Acute Lymphoblastic Leukemia (ALL)
Authors: Musa Yilmaz, Elias J. Jabbour, Xuemei Wang, Sanam Loghavi, Joseph David Khoury, Jeffrey L. Jorgensen, Farhad Ravandi, Nicholas J Short, Jorge E. Cortes, Guillermo Garcia-Manero, Tapan Kadia, Koji Sasaki, Marina Konopleva, Koichi Takahashi, Maria Khouri, Nitin Jain, Srdan Verstovsek, Zeev Estrov, Prithviraj Bose, Sherry Pierce, Rebecca Garris, Susan M. O'Brien, Hagop M. Kantarjian
Journal: Blood (2017)
Evidence for the induction of Th2 inflammation by group 2 innate lymphoid cells in response to prostaglandin D<sub>2</sub> and cysteinyl leukotrienes in allergic rhinitis
Authors: Ichiro Tojima, Koji Matsumoto, Hirotaka Kikuoka, Shiori Hara, Sayuri Yamamoto, Shino Shimizu, Hideaki Kouzaki, Takeshi Shimizu
Journal: Allergy (2019)

Abstract Background Group 2 innate lymphoid cells (ILC2s) play important roles in allergic inflammation. However, their roles in the pathophysiology of allergic rhinitis (AR) are poorly understood. Objective Prevalence of ILC2s in the inferior nasal turbinate (INT) tissues and the activating mechanisms of ILC2s were examined in patients with house dust mite (HDM)‐induced AR. Methods Eighteen patients with HDM‐induced AR and 13 control subjects were recruited. Fresh INT tissues and peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. Nasal lavage fluids (NLF) were collected at 10 minutes after the nasal provocation test (NPT) with HDM disc, and released mediators were measured by ELISA. Sorted ILC2s were cultured and stimulated with mediators associated with AR. Results The prevalence of ILC2s was significantly increased in nasal mucosa of patients with HDM‐induced AR, and it was positively correlated with the number of infiltrating eosinophils. ILC2s in the INT tissues expressed a prostaglandin D 2 (PGD 2 ) receptor, chemoattractant receptor‐homologous molecule‐expressed TH2 cells (CRTH2) and a cysteinyl leukotriene (cysLTs) receptor, CysLT1. After NPT, the number of eosinophils and concentrations of PGD 2 and cysLTs were significantly increased in the NLF from AR patients. PGD 2 and cysLTs significantly induced IL‐5 production from cultured PBMC‐derived ILC2s dose‐dependently. PGD 2 ‐induced and cysLTs‐induced productions of IL‐5 and IL‐13 from ILC2s were completely inhibited by ramatroban, a dual CRTH2 and thromboxane receptor antagonist, and montelukast, a CysLT1 antagonist, respectively. Conclusions PGD 2 ‐CRTH2 and cysLTs‐CysLT1 axes may activate tissue‐resident ILC2s to produce Th2 cytokines, IL‐5 and IL‐13, leading to the development of allergic inflammation in AR.
Тридцать лет на земской службе: штрихи к портрету Надежды Потаповны Кирпотенко — одной из первых женщин-врачей на Екатеринославщине
Authors: M.P. Chaban, Z.I. Shevtsova, V.V. Gaponov
Journal: GASTROENTEROLOGY (2019)

В статье впервые представлены жизненный путь, профессиональная и общественная деятельность Надежды Потаповны Кирпотенко — одной из первых женщин-врачей на Екатеринославщине (ныне — Днепропетровщине). Значительное внимание уделено изучению патронажной службы в конце ХІХ — начале ХХ века.
Minimal residual disease clinical monitoring and depth of response in multiple myeloma.
Authors: Joaquin Martinez-Lopez, Sandy Wai Kuan Wong, Nina Shah, Natasha Bahri, Kaili Zhou, Thomas G. Martin, Jeffrey Lee Wolf
Journal: Journal of Clinical Oncology (2019)

8026 Background: MRD assessment is a known surrogate marker for survival in multiple myeloma (MM). Most data come from patients enrolled in clinical trials. We present a single institution’s experience assessing MRD in patients receiving frontline therapy and therapy for relapsed disease. We describe the impact of depth, duration, and direction of response on prognosis. Methods: 181 MM patients at University of California, San Francisco (UCSF) from 2008 to 2016. 126 were newly diagnosed and 55 in ≥ 2nd line. MRD was assessed in patients achieving VGPR or better by IMWG criteria. MRD assessment was performed by NGS (Adaptive Biotechnologies, Seattle, WA). PFS curves were plotted by the Kaplan-Meier method, and the log-rank test was used to estimate statistical significance. Results: 398 MRD samples were analyzed. MRD was available at 3 time points for 59 patients and 2 time points for 36 patients. Median follow up was 26m. Overall, 66 of 181 patients (36%)achieved MRD- ( &lt; 10 -6 ) on one or more samples. In the newly diagnosed group, 43 of 126 (34%), achieved MRD- at least once. These patients had a prolonged PFS versus patients who were persistently MRD+ (NR vs 49m, p = 0.006). Of the 55 patients who received therapy for relapsed disease, 21 achieved MRD- (38%) and PFS was also prolonged versus patients who remained MRD+ (53m vs 23m, p = 0.03). We analyzed the effects of depth of response. Patients who were MRD- or who were MRD+, at a very low level (between 10 -5 and 10 -6 ), had a better prognosis than those with higher disease burdens ( &gt; 10 -5 ) (p = 0.001). Finally, we analyzed the effect of repeated MRD monitoring on PFS. Three categories were identified in newly diagnosed patients: (A) patients with ≥3 MRD- samples, (B) patients with continuously declining detectable clones, and (C) patients with a stable number of clones. Groups A and B had a more prolonged PFS than group C (NR vs 31m, p &lt; 0.0001). Conclusions: MRD assessment in a real-world setting has the same predictive power as that seen in clinical trials. MRD dynamics can accurately predict disease evolution and drive clinical decision-making. This study lends support to the concept of MRD-driven decision-making and helps validate the relevance of MRD.
Association Between Idiopathic Intracranial Hypertension and Risk of Cardiovascular Diseases in Women in the United Kingdom
Authors: Nicola J. Adderley, Anuradhaa Subramanian, Krishnarajah Nirantharakumar, Andreas Yiangou, Krishna M. Gokhale, Susan P. Mollan, Alexandra J. Sinclair
Journal: JAMA Neurology (2019)

Cardiovascular disease (CVD) risk has not been previously evaluated in a large matched cohort study in idiopathic intracranial hypertension (IIH).
Allogeneic stem cell transplantation (AlloSCT) for patients (pts) with acute leukemia following venetoclax-based therapy.
Authors: Akash Mukherjee, Denai R. Milton, Elias Jabbour, Marina Konopleva, Courtney Denton Dinardo, Alison Gulbis, Farhad Ravandi, Naval Guastad Daver, Tapan M. Kadia, Betul Oran, Uday R. Popat, Stefan O. Ciurea, Jin Im, Partow Kebriaei, Rohtesh S. Mehta, Hagop M. Kantarjian, Richard E. Champlin, Issa F. Khouri
Journal: Journal of Clinical Oncology (2019)

7047 Background: BCL-2 inhibitor Ven has shown a promising benefit in pts with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). There is paucity of information about the safety and efficacy of alloSCT post Ven. Methods: We conducted a retrospective analysis of 35 AML/ALL pts who received alloSCT following Ven-based therapies between 2013-2018 at MDA. Results: Median age at alloSCT was 60 years and 15 (43%) pts had an age-adjusted HCT-CI score ≥ 4. Disease diagnosis – AML (n = 31; 89%), ALL (n = 4; 11%). Disease status at transplant was CR1 (n = 17; 49%), CR2/CR3 (n = 9; 26%) or refractory (n = 9; 26%). 20/26 (77%) CR pts were MRD-negative. Median # of prior therapies was 2 (range 1-7) and 4 (11%) pts had failed a prior alloSCT. AML pts were classified by ELN 2017 criteria to have favorable, intermediate and adverse risks in 16%, 23% and 61% respectively. Ven was provided in combination of hypomethylating agents (HMA) or other chemotherapies in 26 (74%) and 9 (26%) pts, respectively. Among pts treated with Ven + HMA, some also received IDH1/2 inhibitors (n = 7, 20%), FLT3 inhibitors (n = 4; 11%) or anti-PD1 (n = 3, 9%). Median duration of Ven-based treatment was 2 months (range 0.5- 4.6). Ven was discontinued in 6 (17%) pts due to adverse events (n = 4) or progression (n = 2); the remaining pts (83%) continued their Ven-therapy as a bridge to alloSCT. The median time from last Ven dose and transplant was 26 days. Conditioning regimens were melphalan-based reduced intensity (n = 26, 74%), or busulfan-based myeloablative regimens (n = 9; 26%). Donor source was matched -unrelated (n = 14, 40%), -related (n = 9; 26%) or haplo- (n = 12; 34%). GVHD prophylaxis consisted of tacrolimus with either PT-Cy in 25 (71%) pts or methotrexate in 10 (29%) pts. All pts engrafted (median day 30 donor cells = 100%). Median days to ANC &gt; 500 and platelets &gt; 20K was 15.5 and 22.5, respectively. With a median follow up of 5.7 months (range 0.7-15.4), the 1-year rates of OS, PFS, and NRM were 71%, 63% and 3% respectively. CI of acute grade 2-4 and 3-4 GVHD were 26% and 3% respectively. Four pts died: 3 because of disease relapse and 1 of infection. Conclusions: AlloSCT is a safe and feasible consolidation treatment option in acute leukemia pts who were pre- treated with Ven, without excessive risk of NRM or acute GVHD. Larger prospective studies are required to validate our observations.
Abstract 350: Investigating the mechanisms of cellular uptake and metabolism of ICT2588, an MT-MMP-activated prodrug
Authors: Francis Mprah Barnieh, Amanda D. Race, Steven D. Shnyder, Paul M. Loadman, Robert A. Falconer
Journal: Cancer Research (2019)

Abstract ICT2588 is a non-toxic MT1-MMP-activated peptide prodrug of the potent vascular disrupting agent (VDA) azademethylcolchicine [1]. ICT2588 produces significant tumor-selective delivery (≥10-fold) of the toxic and potent azademethylcolchicine, as compared to the administration of azademethylcolchicine alone, in murine models of human colorectal, breast, lung and prostate cancers. In addition, ICT2588 exhibited reduced potential for toxicity, and cardiotoxicity in particular (a phenomenon associated with most VDAs) as a result of its metabolic stability in plasma and normal tissues [2]. ICT2588 is progressing towards clinical evaluation in the UK in 2019. In this study we aim to further investigate the cellular uptake and metabolism of ICT2588 and related compounds in MT1-MMP positive (HT1080) and MT1-MMP negative (MCF-7) cells in vitro. ICT2588 and related compounds were synthesized in-house and purified by preparative HPLC in excellent yield and purity. Activation of ICT2588 by recombinant MT1-MMP and its preferential metabolism in MT1-MMP positive tumor xenograft homogenates has been shown previously [1]. We are currently studying the mechanism of cellular uptake and metabolism of these peptide prodrugs by incubating these compounds in HT1080 and MCF-7 cell cultures. Cellular concentrations of ICT2588 and all metabolites identified were determined using RP-HPLC, mass spectrometry and immunofluorescent microscopy. We describe the first data on the cellular mechanism of uptake and metabolism of ICT2588 and related peptide prodrugs in cancer cells. Our findings have important implications in the future design of effective peptide-based tumor-targeted prodrugs. Reference: [1] Atkinson, J.M et al “Development of a tumor-targeted vascular disrupting agent activated by Membrane-type Matrix Metalloproteinases (MT-MMPs).” Cancer Research, 2010, 70, 6902-12. [2] Gill, J.H et al “Tumor-targeted prodrug ICT2588 demonstrates therapeutic activity against solid tumors and reduced potential for cardiovascular toxicity”. Mol Pharm. 2014,11:1294-300. Citation Format: Francis Mprah Barnieh, Amanda D. Race, Steven D. Shnyder, Paul M. Loadman, Robert A. Falconer. Investigating the mechanisms of cellular uptake and metabolism of ICT2588, an MT-MMP-activated prodrug [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 350.