tbuckley/cabot-search huggingface dataset:
MiR130b from Schlafen4<sup>+</sup> MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer
Authors: Lin Ding, Qian Li, Jayati Chakrabarti, Andres Munoz, Emmanuelle Faure-Kumar, Ramon Ocadiz-Ruiz, Nataliya Razumilava, Guiying Zhang, Michael H Hayes, Ricky A Sontz, Zoe Elena Mendoza, Swapna Mahurkar, Joel K Greenson, Guillermo Perez-Perez, Nguyen Thi Hong Hanh, Yana Zavros, Linda C Samuelson, Dimitrios Iliopoulos, Juanita L Merchant
Journal: Gut (2020)

The myeloid differentiation factor Schlafen4 (Slfn4) marks a subset of myeloid-derived suppressor cells (MDSCs) in the stomach during Helicobacter -induced spasmolytic polypeptide-expressing metaplasia (SPEM). Objective To identify the gene products expressed by Slfn4 + -MDSCs and to determine how they promote SPEM. Design We performed transcriptome analyses for both coding genes (mRNA by RNA-Seq) and non-coding genes (microRNAs using NanoString nCounter) using flow-sorted SLFN4 + and SLFN4 – cells from Helicobacter -infected mice exhibiting metaplasia at 6 months postinfection. Thioglycollate-elicited myeloid cells from the peritoneum were cultured and treated with IFNα to induce the T cell suppressor phenotype, expression of MIR130b and SLFN4. MIR130b expression in human gastric tissue including gastric cancer and patient sera was determined by qPCR and in situ hybridisation. Knockdown of MiR130b in vivo in Helicobacter -infected mice was performed using Invivofectamine. Organoids from primary gastric cancers were used to generate xenografts. ChIP assay and Western blots were performed to demonstrate NFκb p65 activation by MIR130b. Results MicroRNA analysis identified an increase in MiR130b in gastric SLFN4 + cells. Moreover, MIR130b colocalised with SLFN12L, a human homologue of SLFN4, in gastric cancers. MiR130b was required for the T-cell suppressor phenotype exhibited by the SLFN4 + cells and promoted Helicobacter- induced metaplasia. Treating gastric organoids with the MIR130b mimic induced epithelial cell proliferation and promoted xenograft tumour growth. Conclusion Taken together, MiR130b plays an essential role in MDSC function and supports metaplastic transformation.
CHROMATIX: computing the functional landscape of many-body chromatin interactions in transcriptionally active loci from deconvolved single cells
Authors: Alan Perez-Rathke, Qiu Sun, Boshen Wang, Valentina Boeva, Zhifeng Shao, Jie Liang
Journal: Genome biology (2020)

Chromatin interactions are important for gene regulation and cellular specialization. Emerging evidence suggests many-body spatial interactions play important roles in condensing super-enhancer regions into a cohesive transcriptional apparatus. Chromosome conformation studies using Hi-C are limited to pairwise, population-averaged interactions; therefore unsuitable for direct assessment of many-body interactions. We describe a computational model, CHROMATIX, which reconstructs ensembles of single-cell chromatin structures by deconvolving Hi-C data and identifies significant many-body interactions. For a diverse set of highly active transcriptional loci with at least 2 super-enhancers, we detail the many-body functional landscape and show DNase accessibility, POLR2A binding, and decreased H3K27me3 are predictive of interaction-enriched regions.
Prostate-Specific Membrane Antigen Expression in Primary Juvenile Nasal Angiofibroma—A Pilot Study
Authors: Pirabu Sakthivel, Alok Thakar, Arun Prashanth, Ashu Seith Bhalla, Aanchal Kakkar, Kapil Sikka, Chirom Amit Singh, Rajeev Kumar, Suresh Chandra Sharma, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2019)

Purpose Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer cells and is exploited for imaging and treatment of patients with prostate cancer. Prostate-specific membrane antigen expression is also demonstrated in the tumor-associated neovasculature endothelium. Juvenile nasal angiofibroma (JNA), being a similar highly vascular tumor, may also demonstrate significant PSMA expression, which may be utilized for its imaging and treatment. Methods In this prospective study, 25 clinicoradiologically diagnosed primary JNA patients underwent PSMA PET/CT scan. The scan was performed after 45 to 60 minutes of intravenous injection of 2 to 3 mCi (74–111 MBq) of 68 Ga-PSMA-HBED-CC on a dedicated PET/CT scanner. Low-dose CT scan was acquired from vertex to sternoclavicular joint (100 mA, 20 kVp, 3-mm slice thickness, 0.8 pitch). Images were reconstructed with iterative reconstruction technique (4 iterations, 24 subsets). The objective was to assess the intensity and pattern of PSMA uptake in primary JNA patients. Results All cases (n = 25) of primary JNA showed PSMA expression in the tumor (100%). The median PSMA SUVmax ratio of tumor to background was 4.57 (range, 2.08–7.27). Intracranial extension in 14 of 25 patients was prominently visualized because of absence of background uptake in the brain. Advanced stage tumors demonstrated greater uptake than early tumors ( P = 0.011). A statistically nonsignificant trend was noted for decreasing uptake with increasing age after normalizing for stage (Spearman correlation coefficient r = −0.08). Conclusions Assessment of PSMA expression in JNA by PSMA PET/CT opens up a new window of opportunity with respect to its radiological staging, vascularity assessment, and molecular characterization. A potential role in identification of the difficult residual-recurrent disease is anticipated and perhaps also in radioligand therapy for residual/recurrent JNA. Clinical Trials Registry of India (CTRI/2018/08/015479).
FDG PET/CT in Isolated Mediastinal Immunoglobulin G4–Related Disease
Authors: Vankadari Kousik, Rajender Kumar, Bhagwant Rai Mittal, Divya Aggarwal, Ashutosh Nath Aggarwal
Journal: Clinical Nuclear Medicine (2020)

Immunoglobulin G4-related disease is a fibroinflammatory condition that has the tendency to involve almost every organ of the body. We report the case of a young asymptomatic man with right suprahilar opacity on chest radiograph detected during routine annual health check-up. Mediastinoscopic sampling of the lesion was inconclusive. F-FDG PET/CT done to characterize the lesion revealed hypermetabolic mass with areas of necrosis in the right paratracheal location. Histopathologic examination from the FDG PET/CT-guided biopsy sample was suggestive of immunoglobulin G4-related disease.
PI3K Inhibitors Curtail MYC-Dependent Mutant p53 Gain-of-Function in Head and Neck Squamous Cell Carcinoma
Authors: Federica Ganci, Claudio Pulito, Sara Valsoni, Andrea Sacconi, Chiara Turco, Mahrou Vahabi, Valentina Manciocco, Emilia Maria Cristina Mazza, Jalna Meens, Christina Karamboulas, Anthony C. Nichols, Renato Covello, Raul Pellini, Giuseppe Spriano, Giuseppe Sanguineti, Paola Muti, Silvio Bicciato, Laurie Ailles, Sabrina Strano, Giulia Fontemaggi, Giovanni Blandino
Journal: Clinical Cancer Research (2020)

Mutation of TP53 gene is a hallmark of head and neck squamous cell carcinoma (HNSCC) not yet exploited therapeutically. TP53 mutation frequently leads to the synthesis of mutant p53 proteins with gain-of-function activity, associated with radioresistance and high incidence of local recurrences in HNSCC.Mutant p53-associated functions were investigated through gene set enrichment analysis in the Cancer Genome Atlas cohort of HNSCC and in a panel of 22 HNSCC cell lines. Mutant p53-dependent transcripts were analyzed in HNSCC cell line Cal27, carrying mutant p53H193L; FaDu, carrying p53R248L; and Detroit 562, carrying p53R175H. Drugs impinging on mutant p53-MYC-dependent signature were identified interrogating Connectivity Map (https://clue.io) derived from the Library of Integrated Network-based Cellular Signatures (LINCS) database (http://lincs.hms.harvard.edu/) and analyzed in HNSCC cell lines and patient-derived xenografts (PDX) models.We identified a signature of transcripts directly controlled by gain-of-function mutant p53 protein and prognostic in HNSCC, which is highly enriched of MYC targets. Specifically, both in PDX and cell lines of HNSCC treated with the PI3Kα-selective inhibitor BYL719 (alpelisib) the downregulation of mutant p53/MYC-dependent signature correlates with response to this compound. Mechanistically, mutant p53 favors the binding of MYC to its target promoters and enhances MYC protein stability. Treatment with BYL719 disrupts the interaction of MYC, mutant p53, and YAP proteins with MYC target promoters. Of note, depletion of MYC, mutant p53, or YAP potentiates the effectiveness of BYL719 treatment.Collectively, the blocking of this transcriptional network is an important determinant for the response to BYL719 in HNSCC.
The Genomes of the Livebearing Fish Species Poeciliopsis retropinna and Poeciliopsis turrubarensis Reflect Their Different Reproductive Strategies
Authors: Henri van Kruistum, Michael W Guernsey, Julie C Baker, Susan L Kloet, Martien A M Groenen, Bart J A Pollux, Hendrik-Jan Megens
Journal: Molecular Biology and Evolution (2020)

The evolution of a placenta is predicted to be accompanied by rapid evolution of genes involved in processes that regulate mother-offspring interactions during pregnancy, such as placenta formation, embryonic development, and nutrient transfer to offspring. However, these predictions have only been tested in mammalian species, where only a single instance of placenta evolution has occurred. In this light, the genus Poeciliopsis is a particularly interesting model for placenta evolution, because in this genus a placenta has evolved independently from the mammalian placenta. Here, we present and compare genome assemblies of two species of the livebearing fish genus Poeciliopsis (family Poeciliidae) that differ in their reproductive strategy: Poeciliopsis retropinna which has a well-developed complex placenta and P. turrubarensis which lacks a placenta. We applied different assembly strategies for each species: PacBio sequencing for P. retropinna (622-Mb assembly, scaffold N50 of 21.6 Mb) and 10× Genomics Chromium technology for P. turrubarensis (597-Mb assembly, scaffold N50 of 4.2 Mb). Using the high contiguity of these genome assemblies and near-completeness of gene annotations to our advantage, we searched for gene duplications and performed a genome-wide scan for genes evolving under positive selection. We find rapid evolution in major parts of several molecular pathways involved in parent-offspring interaction in P. retropinna, both in the form of gene duplications as well as positive selection. We conclude that the evolution of the placenta in the genus Poeciliopsis is accompanied by rapid evolution of genes involved in similar genomic pathways as found in mammals.
MTSS1 suppresses mammary tumor-initiating cells by enhancing RBCK1-mediated p65 ubiquitination
Authors: Min Cong, Yuan Wang, Yang Yang, Cheng Lian, Xueqian Zhuang, Xiaoxun Li, Peiyuan Zhang, Yingjie Liu, Jun Tang, Qifeng Yang, Xue Zhang, Hua Xiong, Ronggui Hu, Guohong Hu
Journal: Nature Cancer (2020)
A large-scale test of the link between intergroup contact and support for social change
Authors: Tabea Hässler, Johannes Ullrich, Michelle Bernardino, Nurit Shnabel, Colette Van Laar, Daniel Valdenegro, Simone Sebben, Linda R. Tropp, Emilio Paolo Visintin, Roberto González, Ruth K. Ditlmann, Dominic Abrams, Hema Preya Selvanathan, Marija Branković, Stephen Wright, Jorina von Zimmermann, Michael Pasek, Anna Lisa Aydin, Iris Žeželj, Adrienne Pereira, Nóra Anna Lantos, Mario Sainz, Andreas Glenz, Hana Oberpfalzerová, Michal Bilewicz, Anna Kende, Olga Kuzawinska, Sabine Otten, Edona Maloku, Masi Noor, Pelin Gul, Jessica Pistella, Roberto Baiocco, Margareta Jelic, Evgeny Osin, Orly Bareket, Dinka Corkalo Biruski, Jonathan E. Cook, Maneeza Dawood, Lisa Droogendyk, Angélica Herrera Loyo, Kaltrina Kelmendi, Luiza Mugnol Ugarte
Journal: Nature Human Behaviour (2020)
Si substituted hydroxyapatite nanorods on Ti for percutaneous implants
Authors: Kai Li, Yang Xue, Ting Yan, Lan Zhang, Yong Han
Journal: Bioactive Materials (2020)

An ideal intraosseous transcutaneous implant should form a tight seal with soft tissue, besides a requirement of osseointegration at the bone-fixed position. Si substituted hydroxyapatite (Si-HA) nanorods releasing Si ion and simulating nanotopography of natural tissue were designed on Ti to enhance fibroblast response
Radioguided Surgery for Meckel Diverticulum
Authors: Eva Medaer, Marc Miserez, Gert De Hertogh, Koen Van Laere, Christophe M. Deroose
Journal: Clinical Nuclear Medicine (2019)

Abstract We present the case of a 13-year-old boy with bleeding complications from a Meckel diverticulum (MD), which was scintigraphically confirmed. A first exploratory laparoscopy was unsuccessful in identifying the diverticulum. A new 99m Tc-pertechnetate scintigraphy (including SPECT/CT), 3 years later, suggested the anatomical location and was helpful during the surgical exploration for the MD by radioguided surgery. Radioguidance is helpful in pathologies characterized by small size or variable anatomical location. A MD with ectopic gastric mucosa can be distinguished from the rest of the small bowel based on selective 99m Tc-pertechnetate uptake in the gastric mucosa, with limited background activity.
Avadomide monotherapy in relapsed/refractory DLBCL: safety, efficacy, and a predictive gene classifier
Authors: Cecilia Carpio, Reda Bouabdallah, Loïc Ysebaert, Juan-Manuel Sancho, Gilles Salles, Raul Cordoba, Antonio Pinto, Mecide Gharibo, Drew Rasco, Carlos Panizo, Jose A. Lopez-Martin, Armando Santoro, Antonio Salar, Silvia Damian, Alejandro Martin, Gregor Verhoef, Eric Van den Neste, Maria Wang, Suzana Couto, Soraya Carrancio, Andrew Weng, Xuehai Wang, Frank Schmitz, Xin Wei, Kristen Hege, Matthew W. B. Trotter, Alberto Risueño, Tonia J. Buchholz, Patrick R. Hagner, Anita K. Gandhi, Michael Pourdehnad, Vincent Ribrag
Journal: Blood (2020)
TATTON: a multi-arm, phase Ib trial of osimertinib combined with selumetinib, savolitinib, or durvalumab in EGFR-mutant lung cancer
Authors: G.R. Oxnard, J.C.-H. Yang, H. Yu, S.-W. Kim, H. Saka, L. Horn, K. Goto, Y. Ohe, H. Mann, K.S. Thress, M.M. Frigault, K. Vishwanathan, D. Ghiorghiu, S.S. Ramalingam, M.-J. Ahn
Journal: Annals of Oncology (2020)
Co-occurrence of DNMT3A, NPM1, FLT3 mutations identifies a subset of acute myeloid leukemia with adverse prognosis
Authors: Matheus F. Bezerra, Aleide S. Lima, Maria-Riera Piqué-Borràs, Douglas R. Silveira, Juan L. Coelho-Silva, Diego A. Pereira-Martins, Isabel Weinhäuser, Pedro L. Franca-Neto, Lynn Quek, Anna Corby, Mayara M. Oliveira, Marinus M. Lima, Reijane A. de Assis, Paula de Melo Campos, Bruno K. Duarte, Israel Bendit, Vanderson Rocha, Eduardo M. Rego, Fabiola Traina, Sara T. Saad, Eduardo I. Beltrão, Marcos A. Bezerra, Antonio R. Lucena-Araujo
Journal: Blood (2020)
Association between hand-foot skin reaction (HFSR) and survival benefit of fruquintinib in FRESCO trial.
Authors: Jin Li, Shukui Qin, Yuxian Bai, Yanhong Deng, Lei Yang, Ruihua Xu, Zhendong Chen, Haijun Zhong, Hongming Pan, Weijian Guo, Yongqian Shu, Ying Yuan, Jianming Xu, Lin Shen, Ning Wang, Chao Zhu, Songhua Fan, Wei Gong, Wei Wang
Journal: Journal of Clinical Oncology (2019)

e15012 Background: In phase 3 FRESCO trial, fruquintinib demonstrated a statistically significant and clinically meaningful overall survival benefit in Chinese metastatic colorectal cancer (mCRC) patients. As a known adverse effect of vascular endothelial growth factor receptor (VEGFR) inhibitors, hand-foot skin reaction (HFSR) was commonly reported as a drug-related adverse event (AE) in fruquintinib group. This retrospective analysis explored whether HFSR in fruquintinib group is associated with survival benefit in FRESCO. Methods: This analysis used a subpopulation of intent-to-treat population who at least completed one cycle and entered cycle two of fruquintinib treatment. Patients randomized to receive fruquintinib 5 mg/day during the first 3 weeks of each 4-week cycle were divided into subgroups based on whether they reported HFSR. Overall survival (OS) and progression-free survival (PFS) were evaluated by Kaplan-Meier method. Hazard ratio (HR) was estimated through Cox proportional hazards model. P-value was generated from log-rank test. Results: Among a total of 255 fruquintinib-treated patients who at least completed one cycle and entered cycle two, 52% (n = 133) reported HFSR of any grade. The median time-to-onset of HFSR (any grade) was 21 days and approximate 75% patients reported HFSR after cycle two treatment completion. The baseline characteristics were well balanced between HFSR reported and non-reported subgroups. Patients who reported HFSR showed both OS and PFS benefit with statistical significant difference comparing with HFSR non-reported patients in fruquintinib group. Fruquintinib significantly decreased 43% death risk in HFSR reported patients and prolonged the median OS to 11.14 months in comparison with HFSR non-reported patients (median: 11.24 vs 7.54 months; HR = 0.57, 95% CI: 0.42-0.78; p &lt; 0.001). Similarly, Patients reported HFSR had a significantly longer PFS than those who did not reported HFSR in the fruquintinib group (median: 5.49 vs 3.48 months; HR = 0.70, 95% CI: 0.54-0.91; p = 0.008). Conclusions: This post-hoc analysis indicates that patients who had HFSR had a greater survival benefit from fruquintinib in Chinese mCRC patients. Clinical trial information: NCT02314819 .
Association of Potentially Modifiable Diabetes Care Factors With Glycemic Control in Patients With Insulin-Treated Type 2 Diabetes
Authors: Julie C. Lauffenburger, Jennifer Lewey, Saira Jan, Jessica Lee, Roya Ghazinouri, Niteesh K. Choudhry
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Numerous factors are associated with the ability of patients with type 2 diabetes to achieve optimal glycemic control. However, many of these factors are not modifiable by quality improvement interventions. In contrast, the structure of how diabetes care is delivered, such as whether patients visit an endocrinologist or how prescriptions are filled, is potentially modifiable, yet its associations with glycemic control have not been rigorously evaluated. <h3>Objective</h3> To investigate the association of diabetes care delivery with glycemic control in patients with type 2 diabetes using insulin. <h3>Design, Setting, and Participants</h3> This retrospective cohort study used baseline claims and laboratory insurer data within a large pragmatic trial to identify individuals with type 2 diabetes using insulin with data for at least 1 hemoglobin A<sub>1c</sub>(HbA<sub>1c</sub>) test result from before trial randomization (July 1, 2014, to October 5, 2016) and for key nonmodifiable patient factors as well as diabetes care delivery and behavioral factors measured before the HbA<sub>1c</sub>test. Analyses were conducted from February 4, 2017, to November 13, 2018. <h3>Main Outcomes and Measures</h3> Multivariable modified Poisson regression was used to evaluate the independent associations of nonmodifiable patient factors and potentially modifiable diabetes care delivery and patient behavioral factors with achieving adequate diabetes control (ie, HbA<sub>1c</sub>level &lt;8%). The extent of measured variation explained in glycemic control by these factors was also explored using pseudo<i>R</i><sup>2</sup>and C statistics. <h3>Results</h3> Of 1423 patients included, 565 (39.7%) were women, and the mean (SD) age was 56.4 (9.0) years. In total, 690 (48.5%) had HbA<sub>1c</sub>levels less than 8%. Age (relative risk [RR] per 1-unit increase, 1.01; 95% CI, 1.00-1.02), persistent use of basal insulin (RR, 1.20; 95% CI, 1.00-1.43), more frequent filling of glucose self-testing supplies (RR, 1.01; 95% CI, 1.01-1.02), visiting an endocrinologist (RR, 1.41; 95% CI, 1.19-1.67), and receipt of insulin prescriptions by mail order (RR, 1.23; 95% CI, 1.03-1.48) were all independently associated with adequate control. Measured potentially modifiable diabetes care factors explained more variation in adequate glycemic control than measured nonmodifiable patient factors (C statistic, 0.661 vs 0.598; pseudo<i>R</i><sup>2</sup> = 0.11 vs 0.04). <h3>Conclusions and Relevance</h3> These findings suggest that for patients with type 2 diabetes using insulin, the way in which care is delivered may be more strongly associated with achieving adequate control of HbA<sub>1c</sub>levels than patient factors that cannot be altered are. Given the potential for intervention, these care delivery factors could be the focus of efforts to improve diabetes outcomes.
Hepatocellular carcinoma prediction beyond year 5 of oral therapy in a large cohort of Caucasian patients with chronic hepatitis B
Authors: George V. Papatheodoridis, Vana Sypsa, George N. Dalekos, Cihan Yurdaydin, Florian Van Boemmel, Maria Buti, Jose Luis Calleja, Heng Chi, John Goulis, Spilios Manolakopoulos, Alessandro Loglio, Theodoros Voulgaris, Nikolaos Gatselis, Onur Keskin, Rhea Veelken, Marta Lopez-Gomez, Bettina E. Hansen, Savvoula Savvidou, Anastasia Kourikou, John Vlachogiannakos, Kostas Galanis, Ramazan Idilman, Rafael Esteban, Harry L.A. Janssen, Thomas Berg, Pietro Lampertico
Journal: Journal of Hepatology (2020)
経皮的冠動脈ステント留置術後の不明熱の原因としてカテーテルによる炎症性大動脈瘤損傷が疑われた一例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 柿野貴盛, 山本英雄, 宮田健二, 山本雲平, 坂本一郎, 折口秀樹, 多治見司, 毛利正博
Journal: Circulation (2008)
68Ga–Prostate-Specific Membrane Antigen Uptake in Cerebral Tuberculosis
Authors: Veronica Chi Ken Wong, Lily Shen, Elias Nasser, David Nicholas Adams, Robert Mansberg
Journal: Clinical Nuclear Medicine (2019)

Abstract A 71-year-old man with a history of high-risk prostate adenocarcinoma (Gleason score 4 + 5 = 9) treated with brachytherapy in 2016 was referred for a 68 Ga–prostate-specific membrane antigen (PSMA)–HBED–CC PET/CT scan for suspected cancer recurrence on a background of slowly rising serum prostate-specific antigen (0.95 ng/mL; reference, &lt;0.2 ng/mL). This revealed PSMA-avid dura-based hyperdense lesions in the brain, suggestive of cerebral metastases. Biopsy demonstrated the presence of acid-fast bacilli, and with further clinical and microbiological testing, a diagnosis of PSMA-avid cerebral tuberculous mycobacterium infection was made.