tbuckley/cabot-search huggingface dataset:
Colonic expression of <i>Ace2</i>, the SARS-CoV-2 entry receptor, is suppressed by commensal human microbiota
Authors: Adam Edwinson, Lu Yang, Jun Chen, Madhusudan Grover
Journal: Gut Microbes (2021)

Infection with severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Angiotensin-converting enzyme 2 (Ace2) is expressed in the gastrointestinal (GI) tract and a receptor for SARS-CoV-2, making the GI tract a potential infection site. This study investigated the effects of commensal intestinal microbiota on colonic Ace2 expression using a humanized mouse model. We found that colonic Ace2 expression decreased significantly upon microbial colonization. Humanization with healthy volunteer or dysbiotic microbiota from irritable bowel syndrome (IBS) patients resulted in similar Ace2 expression. Despite the differences in microbiota, no associations between α-diversity, β-diversity or individual taxa, and Ace2 were noted post-humanization. These results highlight that commensal microbiota play a key role in regulating intestinal Ace2 expression and the need to further examine the underlying mechanisms of this regulation.
Modeling the epidemiological impact of the UNAIDS 2025 targets to end AIDS as a public health threat by 2030
Authors: John Stover, Robert Glaubius, Yu Teng, Sherrie Kelly, Tim Brown, Timothy B. Hallett, Paul Revill, Till Bärnighausen, Andrew N. Phillips, Christopher Fontaine, Luisa Frescura, Jose Antonio Izazola-Licea, Iris Semini, Peter Godfrey-Faussett, Paul R. De Lay, Adèle Schwartz Benzaken, Peter D. Ghys
Journal: PLoS Medicine (2021)

UNAIDS has established new program targets for 2025 to achieve the goal of eliminating AIDS as a public health threat by 2030. This study reports on efforts to use mathematical models to estimate the impact of achieving those targets.We simulated the impact of achieving the targets at country level using the Goals model, a mathematical simulation model of HIV epidemic dynamics that includes the impact of prevention and treatment interventions. For 77 high-burden countries, we fit the model to surveillance and survey data for 1970 to 2020 and then projected the impact of achieving the targets for the period 2019 to 2030. Results from these 77 countries were extrapolated to produce estimates for 96 others. Goals model results were checked by comparing against projections done with the Optima HIV model and the AIDS Epidemic Model (AEM) for selected countries. We included estimates of the impact of societal enablers (access to justice and law reform, stigma and discrimination elimination, and gender equality) and the impact of Coronavirus Disease 2019 (COVID-19). Results show that achieving the 2025 targets would reduce new annual infections by 83% (71% to 86% across regions) and AIDS-related deaths by 78% (67% to 81% across regions) by 2025 compared to 2010. Lack of progress on societal enablers could endanger these achievements and result in as many as 2.6 million (44%) cumulative additional new HIV infections and 440,000 (54%) more AIDS-related deaths between 2020 and 2030 compared to full achievement of all targets. COVID-19-related disruptions could increase new HIV infections and AIDS-related deaths by 10% in the next 2 years, but targets could still be achieved by 2025. Study limitations include the reliance on self-reports for most data on behaviors, the use of intervention effect sizes from published studies that may overstate intervention impacts outside of controlled study settings, and the use of proxy countries to estimate the impact in countries with fewer than 4,000 annual HIV infections.The new targets for 2025 build on the progress made since 2010 and represent ambitious short-term goals. Achieving these targets would bring us close to the goals of reducing new HIV infections and AIDS-related deaths by 90% between 2010 and 2030. By 2025, global new infections and AIDS deaths would drop to 4.4 and 3.9 per 100,000 population, and the number of people living with HIV (PLHIV) would be declining. There would be 32 million people on treatment, and they would need continuing support for their lifetime. Incidence for the total global population would be below 0.15% everywhere. The number of PLHIV would start declining by 2023.
High endothelial venule is a surrogate biomarker for T-cell inflamed tumor microenvironment and prognosis in gastric cancer
Authors: Hyung Soon Park, Yoo Min Kim, Sewha Kim, Won Suk Lee, So Jung Kong, Hannah Yang, Beodeul Kang, Jaekyung Cheon, Su-Jin Shin, Chan Kim, Hong Jae Chon
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background High endothelial venule (HEV) is a specialized vasculature for lymphocyte trafficking. While HEVs are frequently observed within gastric cancer (GC), the vascular–immune interaction between HEV and tumor-infiltrating lymphocytes (TILs) has not been well elucidated. In this study, we aimed to unveil the potential value of HEVs as a surrogate marker for T-cell inflamed immune microenvironment in GC using a large number of prospectively collected surgical specimens of GC. Methods We included 460 patients with GC who underwent surgical resection. Nanostring PanCancer immune profiling was performed to evaluate the immunological phenotype of GCs. HEV density and three distinct patterns of TILs (Crohn-like lymphoid reaction, peritumoral lymphoid reaction, and intratumoral lymphoid reaction) were analyzed for their relationship and evaluated as prognostic factors for relapse-free survival (RFS) and overall survival (OS). Results HEV-high GC revealed increased infiltration by immune cell subsets, including dendritic cells, CD8 + cytotoxic T cells, and CD4 + helper T cells. In addition, HEV-high GC demonstrated increased immune-modulating chemokines, type I or II interferon pathway, and immune checkpoints, all of which indicate the inflamed tumor microenvironment (TME). All three distinct patterns of TILs were associated with HEV density. In survival analysis, patients with HEV-high GC displayed significantly longer RFS and OS than those with HEV-low GC (p&lt;0.001 for RFS, p&lt;0.001 for OS). Multivariate analysis demonstrated that HEV was the most significant immunological prognostic factor for RFS (patients with high HEV compared with those with low HEV; HR 0.412, 95% CI 0.241 to 0.705, p=0.001) and OS (HR 0.547, 95% CI 0.329 to 0.909, p=0.02) after adjustment for age, stage, and TIL. Conclusion HEV is the most significant immunological prognosticator for RFS and OS in resected GC, indicating inflamed TME.
P32.01 Clinical Screening for COVID-19 in Asymptomatic Patients With Lung Cancer: Brazilian Experience From a Single Institution
Authors: C.H. Teixeira, C. Yen, T. Teixeira, E. Ferreira, R. Younes, A. Silva, A. Uchiyama, M. Lopes, C. Silva
Journal: Journal of Thoracic Oncology (2021)
HPV Vaccination Coverage Has Increased Among Adolescents
Authors: Bridget M. Kuehn
Journal: JAMA (2021)

Three-quarters of US adolescents were protected by at least 1 dose of the human papillomavirus (HPV) vaccine in 2020, an increase of more than 3% compared with coverage in 2019, according to data from the CDC's National Immunization Survey–Teen (NIS-Teen).
Studies on OPSPA
Authors: R. K. Maller, Charles Heidelberger
Journal: Cancer Research (1957)

1.  The syntheses of OPSPA-C14, morpholine-C14 hydrochloride, and OPSPA-P32 are described.

2.  The excretion and tissue distribution of radioactivity following administration of these substances to rats bearing the Flexner-Jobling carcinoma by intraperitoneal, intratumoral, and oral injection have been described.

3.  There was little excretion of radioactivity in the respiratory carbon dioxide and feces. The excretion was predominantly in the urine during the first 24 hours.

4.  There was no evidence of selective uptake in any tissues, including the tumor, by any mode of administration. Morpholine is found in the tissues to a considerably lesser extent than is OPSPA.

5.  Studies on the chemical fractionation of tissues revealed the presence of free drug or metabolites, materials that have bound to lipides and proteins, probably by direct chemical reactions, and the interaction with mixed nucleic acids, possibly during the process of biosynthesis. These interactions were considerably smaller following oral administration, as compared with effects following the other methods of administration.

6.  The amount of drug or metabolite causing the specific tumor-inhibitory effect must be minute.
MA04.03 A Phase II Study of Palbociclib for Recurrent or Refractory Advanced Thymic Epithelial Tumor (KCSG LU17-21)
Authors: H.A. Jung, M. Kim, J. Kim, Y.H. Choi, J. Cho, J.H. Park, K.U. Park, S. Park, J. Sun, S. Lee, J.S. Ahn, K. Park, M. Ahn
Journal: Journal of Thoracic Oncology (2021)
P59.03 Comparison of Two RNA-Based Platforms for Detection of Fusions and Met Splicing Variant in Non Small Cell Lung Cancer Samples
Authors: B. García Peláez, A. Gimenez-Capitán, M. Vives Usano, R. Roman, M. Garzón Ibañez, C. Aguado Esteban, S. Rodríguez, E. Aldeguer, N. Jordana Ariza, S. Viteri, A. Aguilar-Hernández, I. Moya, C. Cabrera, M. Catalán, M. Gonzalez-Cao, S. García Román, J. Bertrán- Alamillo, F. Garcia-Casabal, R. Rosell, M. Molina, C. Mayo-De-Las-Casas
Journal: Journal of Thoracic Oncology (2021)
Abstract 17041: Impact of Different Patterns of Left Ventricular Ballooning in Patients With Stress (Takotsubo) Cardiomyopathy: Single Center Clinical Experience
Authors: Ju Hyeon Kim, Yeong jin Jeong, Jinoh Park, Pil Hyung Lee, Jeong Yoon Jang, Sahmin Lee, Min Soo Cho, Yu Na Kim, Jae Seok Bae, Cheol Hyun Lee, Dae-Hee Kim, Jong-Min Song, Duk-Hyun Kang, Jae-Kwan Song, Kee-Joon Choi
Journal: Circulation (2015)

Introduction: Stress cardiomyopathy (SCMP) is characterized by acute reversible left ventricular (LV) dysfunction, and it is well accepted that SCMP can show various patterns with or without apical involvement. However, clinical data describing characteristics and outcomes according to the patterns of LV ballooning are lacking. Methods: We retrospectively identified 549 consecutive patients (age, 64±15 years; 328 female) with SCMP in a single tertiary hospital from Jan 2009 to June 2014. They were divided into 2 groups with typical apical ballooning (group 1) and atypical patterns sparing the LV apical segment (group 2). Clinical characteristics and outcomes including in-hospital mortality were explored. Results: Apical ballooning was most common (n=394, 71.8%) and group 2 included mid-ventricular ballooning (21.7%), basal ‘inverted’ ballooning (2.9%), global hypokinesia (1.8%), localized ballooning (1.1%), and isolated right ventricular ballooning (0.7%). Group 1 was characterized by higher mean age (67±13 vs. 55±17 years, p&lt;0.001) with higher prevalence of coronary risk factors including obesity, hypertension, hyperlipidemia and diabetes mellitus. Emotional stress was a triggering event in a very limited patients comprising &lt; 5%, whereas physical stress associated with underlying medical conditions comprised more than 70%. Distribution of triggering events was similar between groups. ECG abnormalities including T wave inversion, ST segment elevation, QT prolongation and atrial fibrillation were more frequent in group 1 than group 2 with lower LV ejection fraction. However, in-hospital mortality was comparable between groups (24% vs. 21%, p=0.52). Conclusions: Apical sparing ballooning develops in up to 30% of patients with SCMP. Younger age, favorable medical conditions, less severe ECG changes, and higher LV ejection fraction cannot translate to lower mortality in this group. Physicians’ vigilance is needed to improve clinical outcomes.
P59.31 A High Number of Co-Current Genetic Alterations Is Associated With Poor Survival in EGFR Mutated Metastatic NSCLC Patients
Authors: D. Heredia, L. Lara-Mejía, E. Varela-Santoyo, N. Hernández-Pedro, A. Cardona Zorrilla, G. Cruz-Rico, M. Ramos-Ramirez, L. Cabrera Miranda, F. Barrón, C. Izquierdo-Tolosa, O. Arrieta
Journal: Journal of Thoracic Oncology (2021)
81P Safety and effectiveness of apalutamide for the treatment of non-metastatic castration-resistant prostate cancer (nm-CRPC): Preliminary results from an open-label expanded access protocol (EAP)
Authors: S. Campos-Gomez, J.C. Ochoa, F. Cruz, A. Mota, M.A.J. Rios, J.A. Rinck, A. Bhaumik, M. Grings, A. Acerbi, K. Salomão, V. Fabricio, R. Gidekel
Journal: Annals of Oncology (2021)
KrasG12D induces changes in chromatin territories that differentially impact early nuclear reprogramming in pancreatic cells
Authors: Angela J. Mathison, Romica Kerketta, Thiago Milech de Assuncao, Elise Leverence, Atefeh Zeighami, Guillermo Urrutia, Timothy J. Stodola, Marina Pasca di Magliano, Juan L. Iovanna, Michael T. Zimmermann, Gwen Lomberk, Raul Urrutia
Journal: Genome biology (2021)

Pancreatic ductal adenocarcinoma initiation is most frequently caused by Kras mutations. Here, we apply biological, biochemical, and network biology methods to validate GEMM-derived cell models using inducible KrasG12D expression. We describe the time-dependent, chromatin remodeling program that impacts function during early oncogenic signaling. We find that the KrasG12D-induced transcriptional response is dominated by downregulated expression concordant with layers of epigenetic events. More open chromatin characterizes the ATAC-seq profile associated with a smaller group of upregulated genes and epigenetic marks. RRBS demonstrates that promoter hypermethylation does not account for the silencing of the extensive gene promoter network. Moreover, ChIP-Seq reveals that heterochromatin reorganization plays little role in this early transcriptional program. Notably, both gene activation and silencing primarily depend on the marking of genes with a combination of H3K27ac, H3K4me3, and H3K36me3. Indeed, integrated modeling of all these datasets shows that KrasG12D regulates its transcriptional program primarily through unique super-enhancers and enhancers, and marking specific gene promoters and bodies. We also report chromatin remodeling across genomic areas that, although not contributing directly to cis-gene transcription, are likely important for KrasG12D functions. In summary, we report a comprehensive, time-dependent, and coordinated early epigenomic program for KrasG12D in pancreatic cells, which is mechanistically relevant to understanding chromatin remodeling events underlying transcriptional outcomes needed for the function of this oncogene.
Tumor-dilated polymersome nanofactories for enhanced enzyme prodrug chemo-immunotherapy
Authors: Abd Al-Wali Mohammed M. Japir, Wendong Ke, Junjie Li, Jean Felix Mukerabigwi, Alhadi Ibrahim, Yuheng Wang, Xiang Li, Qinghao Zhou, Fathelrahman Mohammed, Zhishen Ge
Journal: Journal of Controlled Release (2021)
Commensal segmented filamentous bacteria-derived retinoic acid primes host defense to intestinal infection
Authors: Vivienne Woo, Emily M Eshleman, Seika Hashimoto-Hill, Jordan Whitt, Shu-En Wu, Laura Engleman, Taylor Rice, Rebekah Karns, Joseph E Qualls, David B Haslam, Bruce A Vallance, Theresa Alenghat
Journal: Cell Host & Microbe (2021)
P68.14 Sensitivity to Statin in EMT-Induced NCI-H322M Cells is Further Enhanced by Simultaneous Downregulation of HMGCR Expression
Authors: K. Warita, T. Ishikawa, A. Sugiura, J. Tashiro, Y. Hosaka, T. Warita, Z. Oltvai
Journal: Journal of Thoracic Oncology (2021)
Repeated vaccination against SARS-CoV-2 elicits robust polyfunctional T cell response in allogeneic stem cell transplantation recipients
Authors: Patrick Harrington, Katie J. Doores, Chandan Saha, Jamie Saunders, Fiona Child, Richard Dillon, Sukran Saglam, Kavita Raj, Donal McLornan, Daniele Avenoso, Shahram Kordasti, Amy O’Reilly, Andreas Espehana, Thomas Lechmere, Hataf Khan, Michael H. Malim, Claire Harrison, Varun Mehra, Hugues de Lavallade
Journal: Cancer Cell (2021)
Profound differences in IgE and IgG recognition of micro‐arrayed allergens in hyper‐IgE syndromes
Authors: Victoria Garib, Meriem Ben‐Ali, Michael Kundi, Mirela Curin, Roukaya Yaakoubi, Imen Ben‐Mustapha, Najla Mekki, Renate Froeschl, Thomas Perkmann, Rudolf Valenta, Mohamed‐Ridha Barbouche
Journal: Allergy (2021)

Abstract Background The specificities of IgE and IgG for allergen molecules in patients with inborn errors of immunity (IEI) have not been investigated in detail. Objective To study IgE and IgG antibody specificities in patients with defined hyper‐IgE syndromes (HIES) using a comprehensive panel of allergen molecules. Methods We used chips containing micro‐arrayed allergen molecules to analyze allergen‐specific IgE and IgG levels in sera from two groups of HIES patients: Autosomal recessive mutations in phosphoglucomutase‐3 (PGM3); Autosomal dominant negative mutations of STAT3 (STAT3); and age‐matched subjects with allergic sensitizations. Assays with rat basophil leukemia cells transfected with human FcεRI were performed to study the biological relevance of IgE sensitizations. Results Median total IgE levels were significantly lower in the sensitized control group (212.9 kU/L) as compared to PGM3 (5042 kU/L) and STAT3 patients (2561 kU/L). However, PGM3 patients had significantly higher allergen‐specific IgE levels and were sensitized to a larger number of allergen molecules as compared to STAT3 patients. Biological relevance of IgE sensitization was confirmed for PGM3 patients by basophil activation testing. PGM3 patients showed significantly lower cumulative allergen‐specific IgG responses in particular to milk and egg allergens as compared to STAT3 patients and sensitized controls whereas total IgG levels were comparable to STAT3 patients and significantly higher than in controls. Conclusion The analysis with multiple micro‐arrayed allergen molecules reveals profound differences of allergen‐specific IgE and IgG recognition in PGM3 and STAT3 patients which may be useful for classification of IEI and clinical characterization of patients.
Multi-layer pseudo-supervision for histopathology tissue semantic segmentation using patch-level classification labels
Authors: Chu Han, Jiatai Lin, Jinhai Mai, Yi Wang, Qingling Zhang, Bingchao Zhao, Xin Chen, Xipeng Pan, Zhenwei Shi, Zeyan Xu, Su Yao, Lixu Yan, Huan Lin, Xiaomei Huang, Changhong Liang, Guoqiang Han, Zaiyi Liu
Journal: Medical Image Analysis (2022)

Tissue-level semantic segmentation is a vital step in computational pathology. Fully-supervised models have already achieved outstanding performance with dense pixel-level annotations. However, drawing such labels on the giga-pixel whole slide images is extremely expensive and time-consuming. In this paper, we use only patch-level classification labels to achieve tissue semantic segmentation on histopathology images, finally reducing the annotation efforts. We propose a two-step model including a classification and a segmentation phases. In the classification phase, we propose a CAM-based model to generate pseudo masks by patch-level labels. In the segmentation phase, we achieve tissue semantic segmentation by our propose Multi-Layer Pseudo-Supervision. Several technical novelties have been proposed to reduce the information gap between pixel-level and patch-level annotations. As a part of this paper, we introduce a new weakly-supervised semantic segmentation (WSSS) dataset for lung adenocarcinoma (LUAD-HistoSeg). We conduct several experiments to evaluate our proposed model on two datasets. Our proposed model outperforms five state-of-the-art WSSS approaches. Note that we can achieve comparable quantitative and qualitative results with the fully-supervised model, with only around a 2% gap for MIoU and FwIoU. By comparing with manual labeling on a randomly sampled 100 patches dataset, patch-level labeling can greatly reduce the annotation time from hours to minutes. The source code and the released datasets are available at: https://github.com/ChuHan89/WSSS-Tissue.
P43.01 Three-Dimensional Virtual Planning for Nodule Resection in Solid Organs: A Systematic Review and Meta-Analysis
Authors: P.A. Schulze, M. Zanon, S.P. Altmayer, G. Watte, G. Pacini, E. Marchiori, D. Pinto Filho, B. Hochhegger
Journal: Journal of Thoracic Oncology (2021)
Abstract 212: Globular Domain of Adiponectin Attenuates Post-Ischemia Myocardial Oxidative/Nitrative Stress in an AMPK-Independent Fashion
Authors: Yajing Wang, Erhe Gao, Ling Tao, Wayne B Lau, Yuexing Yuan, Barry J Goldstein, Rong Tian, Walter Koch, Xin L Ma
Journal: Circulation (2008)

Reduced plasma adiponectin (APN) level not only contributes to the increased incidence of MI in diabetic patients, but also plays a causative role in increased cardiac injury after MI in these patients. However, singling mechanisms by which APN achieves its cardioprotection remains incompletely understood. Here, we investigated the role of AMP activated protein kinase (AMPK), the molecule that transfers APN’s metabolic signaling, in APN’s cardioprotection. Male adult mice with cardiac specific overexpression of a dominant negative AMPK α 2 subunit (AMPK-DN) or wild type (WT) littermates controls were subjected to 30 min of MI followed by reperfusion (R) and treated with vehicle (V) or globular domain of APN (gAPN, 2 μg/g) 10 min before R. Comparing with WT mice, MI/R caused greater cardiac injury including larger infarct size, more apoptosis and poorer cardiac function (P&lt;0.05) in AMPK-DN mice. Treatment of WT mice with gAPN significantly attenuated MI/R injury (P&lt;0.01). Most interestingly, although the metabolic regulatory effect of gAPN is completely lost in AMPK-DN mice, a significant portion of cardioprotection of gAPN retained in the transgenic animals. Specifically, treatment of AMPK-DN mice with gAPN reduced infarct size (54±4.7% vs. 81±3.6% in V group, P&lt;0.01), decreased apoptosis (lesser TUNEL positive labeling, weaker DNA fragmentation, and lower caspase 3 activity. P value all &lt;0.01) and improved cardiac function after MI/R (higher LVEF, lower LVEDP and higher dP/dt max . P value all &lt;0.01). To further delineate the mechanisms responsible for gAPN’s AMPK-independent cardioprotection, effect of gAPN on cardiac oxidative/nitrative stress following MI/R were examined. Treatment of AMPK-DN mice with gAPN reduced superoxide and nitric oxide overproduction, decreased peroxynitrite formation (from 0.38±0.04 to 0.23±0.02 ng/mg protein in WT and from 0.50±0.06 to 0.32±0.02 ng/mg protein in AMPK-DN mice), and inhibited NADPH oxidase and iNOS expression to the same extent as that seen in WT mice. Taken together, our results demonstrated for the first time that a significant portion of gAPN cardioprotection is not mediated by the traditional AMPK signaling pathway and that the anti-oxidative/anti-nitrative effects of gAPN are AMPK-independent.