tbuckley/cabot-search huggingface dataset:
Abstract PD15-04: Trop-2 inactivation of E-cadherin drives triple negative breast cancer relapse
Authors: Saverio Alberti, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, Patrizia Querzoli, Massimo Pedriali, Laura Antolini, Emanuela Guerra
Journal: Cancer Research (2021)

Abstract Hundreds of proteins/genes have been linked to the metastatic phenotype. However, consistent markers of tumour aggressiveness and metastatic potential in breast cancer patients were not identified, not even including proteomic analysis and large-scale genome sequencing.Metastasis-associated genes were predicted to include not only drivers of the metastatic phenotype, but also secondary events, together with adaptive, counterbalancing changes. Thus, to identify candidates with a required role in metastatic diffusion, we looked for genes that were concordantly dysregulated across orthogonal cancer metastasis settings. This led us to identify Trop-2 as uniquely upregulated and associated to metastasis in experimental models of breast cancer, as well as in other solid tumors. We identified functional inactivation of E-cadherin by Trop-2 as the main motor of metastatic diffusion of such metastatic systems. Trop-2 binding to E-cadherin inactivated its cell-cell adhesion function, through release from the cytoskeleton, for activation of β-catenin transcriptional activity. This led to anti-apoptotic signaling, increased cell migration capacity and enhanced cancer cell survival. We showed that this mechanism led to metastatic diffusion of xenotransplants growing in immunosuppressed mice. An E-cadherin-inactivation metastasis program was then shown to be recapitulated in breast cancer patients, as well as in other solid tumors, over 24 independent case series, encompassing 13,042 primary tumours. Aggressive triple-negative breast cancers were shown to be driven toward global relapse by Trop-2 overexpression, through E-cadherin inactivation and activation of β-catenin transcriptional activity. No disease recurrence was observed in control cases over +12 years of follow-up. These finding lead to a novel paradigm of a Trop-2-driven, E-cadherin-inactivation program as a main metastasis driver in solid tumors. This may open far-reaching perspectives in diagnostic procedures and anti-cancer therapies. Citation Format: Saverio Alberti, Marco Trerotola, Valeria Relli, Rossano Lattanzio, Martina Ceci, Khouloud Boujnah, Valeria Garbo, Antonino Moschella, Patrizia Querzoli, Massimo Pedriali, Laura Antolini, Emanuela Guerra. Trop-2 inactivation of E-cadherin drives triple negative breast cancer relapse [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD15-04.
Dietary Diversification and Specialization in Neotropical Bats Facilitated by Early Molecular Evolution
Authors: Joshua H T Potter, Kalina T J Davies, Laurel R Yohe, Miluska K R Sanchez, Edgardo M Rengifo, Monika Struebig, Kim Warren, Georgia Tsagkogeorga, Burton K Lim, Mario dos Reis, Liliana M Dávalos, Stephen J Rossiter
Journal: Molecular Biology and Evolution (2021)

Abstract Dietary adaptation is a major feature of phenotypic and ecological diversification, yet the genetic basis of dietary shifts is poorly understood. Among mammals, Neotropical leaf-nosed bats (family Phyllostomidae) show unmatched diversity in diet; from a putative insectivorous ancestor, phyllostomids have radiated to specialize on diverse food sources including blood, nectar, and fruit. To assess whether dietary diversification in this group was accompanied by molecular adaptations for changing metabolic demands, we sequenced 89 transcriptomes across 58 species and combined these with published data to compare ∼13,000 protein coding genes across 66 species. We tested for positive selection on focal lineages, including those inferred to have undergone dietary shifts. Unexpectedly, we found a broad signature of positive selection in the ancestral phyllostomid branch, spanning genes implicated in the metabolism of all major macronutrients, yet few positively selected genes at the inferred switch to plantivory. Branches corresponding to blood- and nectar-based diets showed selection in loci underpinning nitrogenous waste excretion and glycolysis, respectively. Intriguingly, patterns of selection in metabolism genes were mirrored by those in loci implicated in craniofacial remodeling, a trait previously linked to phyllostomid dietary specialization. Finally, we show that the null model of the widely-used branch-site test is likely to be misspecified, with the implication that the test is too conservative and probably under-reports true cases of positive selection. Our findings point to a complex picture of adaptive radiation, in which the evolution of new dietary specializations has been facilitated by early adaptations combined with the generation of new genetic variation.
Abstract PS7-40: Triple negative breast cancer in New Orleans, part deux
Authors: Michelle M Loch, Mei-Chin Hsieh, Thomas Reske, Vivien Chen, Xiao-Cheng Wu
Journal: Cancer Research (2021)

Abstract Version 7/7/2020 with edit Triple-Negative Breast Cancer in New Orleans – part deaux Objectives: To update our previously reported findings with more current data from SEER 18 registries to compare race-specific incidence rates of triple-negative breast cancer (TNBC) in New Orleans (NO) and Louisiana (LA) with other SEER metro areas and identify the predictors of TNBC. Background: We previously reported significantly increased incidence rates of TNBC in black women (BW) in NO and LA than other SEER metro areas. Methods: We analyzed tumor characteristics of invasive female breast cancers diagnosed from 2011-2017 from SEER 18 for BW and white women (WW). We compared LA data with SEER 18 and metropolitan areas (Atlanta, Detroit, Los Angeles and San Francisco) as we did with our previous data set. Predictors of TNBC in NO and LA were identified in multivariate logistic regression adjusting for age, BMI, poverty, insurance, tumor size, Bloom-Richardson grade and AJCC stage. Results: The overall incidence rate of TNBC in BW was again significantly higher in NO (29.8 per 100,000) than any metro area and the SEER metro areas combined (23.9 per 100,000). Detroit again had the second highest rate (27.2) followed by San Francisco/Oakland (23.8) Los Angeles (22.3) and Atlanta (22.1). The multivariable analysis showed that younger age, large tumor size, high grade were associated with increased risk of TNBC in BW. Conclusions: The incidence rates of TNBC in BW in NO continue to be consistently higher compared to LA and other SEER 18 metro areas. This data reiterates the importance of ongoing translational research to broaden the understanding and optimize the treatment of this aggressive disease, especially in this vulnerable population. Citation Format: Michelle M Loch, Mei-Chin Hsieh, Thomas Reske, Vivien Chen, Xiao-Cheng Wu. Triple negative breast cancer in New Orleans, part deux [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-40.
Development of a human skin commensal microbe for bacteriotherapy of atopic dermatitis and use in a phase 1 randomized clinical trial
Authors: Teruaki Nakatsuji, Tissa R. Hata, Yun Tong, Joyce Y. Cheng, Faiza Shafiq, Anna M. Butcher, Secilia S. Salem, Samantha L. Brinton, Amanda K. Rudman Spergel, Keli Johnson, Brett Jepson, Agustin Calatroni, Gloria David, Marco Ramirez-Gama, Patricia Taylor, Donald Y. M. Leung, Richard L. Gallo
Journal: Nature Medicine (2021)
Cytoplasmic Localization of Prostate-Specific Membrane Antigen Inhibitors May Confer Advantages for Targeted Cancer Therapies
Authors: Jessica Matthias, Johann Engelhardt, Martin Schäfer, Ulrike Bauder-Wüst, Philipp T. Meyer, Uwe Haberkorn, Matthias Eder, Klaus Kopka, Stefan W. Hell, Ann-Christin Eder
Journal: Cancer Research (2021)

Abstract Targeted imaging and therapy approaches based on novel prostate-specific membrane antigen (PSMA) inhibitors have fundamentally changed the treatment regimen of prostate cancer. However, the exact mechanism of PSMA inhibitor internalization has not yet been studied, and the inhibitors' subcellular fate remains elusive. Here, we investigated the intracellular distribution of peptidomimetic PSMA inhibitors and of PSMA itself by stimulated emission depletion (STED) nanoscopy, applying a novel nonstandard live cell staining protocol. Imaging analysis confirmed PSMA cluster formation at the cell surface of prostate cancer cells and clathrin-dependent endocytosis of PSMA inhibitors. Following the endosomal pathway, PSMA inhibitors accumulated in prostate cancer cells at clinically relevant time points. In contrast with PSMA itself, PSMA inhibitors were found to eventually distribute homogeneously in the cytoplasm, a molecular condition that promises benefits for treatment as cytoplasmic and in particular perinuclear enrichment of the radionuclide carriers may better facilitate the radiation-mediated damage of cancerous cells. This study is the first to reveal the subcellular fate of PSMA/PSMA inhibitor complexes at the nanoscale and aims to inspire the development of new approaches in the field of prostate cancer research, diagnostics, and therapeutics. Significance: This study uses STED fluorescence microscopy to reveal the subcellular fate of PSMA/PSMA inhibitor complexes near the molecular level, providing insights of great clinical interest and suggestive of advantageous targeted therapies.
Incomplete grounding: the theory of symbolic separation is contradicted by pervasive stability in attitudes and behavior
Authors: Oleg Urminsky
Journal: Behavioral and Brain Sciences (2021)

Abstract The proposed theory is broad enough to accommodate the reduction or elimination of prior influences by a variety of acts symbolizing separation (including cleansing). However, it does not account for stability in psychological variables, and is contradicted by widely documented stability in people's actual attitudes and behavior over time, in multiple domains, despite people's pervasive everyday acts of symbolic separation.
A group of cationic amphiphilic drugs activates MRGPRX2 and induces scratching behavior in mice
Authors: Katharina Wolf, Helen Kühn, Felicitas Boehm, Lisa Gebhardt, Markus Glaudo, Konstantin Agelopoulos, Sonja Ständer, Philipp Ectors, Dirk Zahn, Yvonne K. Riedel, Dominik Thimm, Christa E. Müller, Sascha Kretschmann, Anita N. Kremer, Daphne Chien, Nathachit Limjunyawong, Qi Peng, Xinzhong Dong, Pavel Kolkhir, Jörg Scheffel, Mia Lykke Søgaard, Benno Weigmann, Markus F. Neurath, Tomasz Hawro, Martin Metz, Michael J.M. Fischer, Andreas E. Kremer
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 14110: Obesity and the Development of Atrial Fibrillation in Hispanics, African Americans and Non-Hispanic Whites
Authors: Eric H Shulman, Jay Chudow, Tina Shah, Krina Shah, Ariel Peleg, Dmitriy Nevelev, Faraj Kargoli, Lynn Zaremski, Cecilia Berardi, Andrea Natale, Jorge Romero, Luigi Di Biase, John Fisher, Andrew Krumerman, Kevin J Ferrick
Journal: Circulation (2017)

Introduction: No previous studies have examined the interaction between body mass index (BMI) and race/ethnicity with the risk of atrial fibrillation (AF). Hypothesis: There exists a relationship b...
Abstract PS4-32: Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer
Authors: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen
Journal: Cancer Research (2021)

Abstract Background: Expression of immune checkpoint receptors (ICR) on tumor infiltrating lymphocytes (TILSs) is associated with better response to immunotherapies via immune checkpoint inhibitors. Therefore, we investigated various ICR expressions on TILs in patients with locally advanced triple negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC). Methods: Expressions of ICRs were examined immunohistochemically by staining surgical specimen (n=61) using specific monoclonal antibodies for PDL-1, PD-1, TIM-3, LAG-3, CTLA-4. Positivity was defined staining &amp;gt;1% on TILs. Results: Median age was 49 (24-76) years. The majority patients were clinically T3-4 (n=31, 50.8%), and clinically N1-3 (n=58, 95.1%) before NAC. Of those, 82% were found to have CTLA-4 positivity, whereas TILs associated positivites for PD1, PDL-1, LAG3 and TIM-3 were 62.3%, 50.9%, 26.2%, 68.9%. High expression of CTLA-4 was found to be associated with a better chemotherapy response (OR=7.94, 95%CI: 0.9-70.12, p=0.06), whereas TIM-3 positivity was contrarly associated with a worse chemotherapy response (OR=0.253, 95%CI: 0.066-0.974, p=0.047) as measured by MDACC Residual Cancer Burden Index. At a 47-month follow-up, patients with ypN0 disease (DFS; HR=0.31, 95% CI: 0.12-0.83, p=0.02 and DSS; HR=0.21, 95% CI:0.07-0.62, p=0.005) and CTLA-4 high expression on TILs (DFS; HR=0.38, 95% CI=0.17-0.85, p=0.019 and DSS; HR=0.34, 95% CI:0.15-0.78, p=0.01) were found to have improved survival. Conclusions: These findings demonstrate that CTLA-4, PD-1, PDL-1 and TIM-3 were highly expressed in TNBC after NAC. Our results more favor an immuncheckpoint inhibitor therapy via CTLA-4 alone or in combination with other immune check point inhibitors against PDL-1 and/or TIM-3 in addition to NAC in advanced TNBC. Citation Format: Neslihan Cabioglu, Semen Onder, Gizem Oner, Hüseyin Karatay, Mustafa Tukenmez, Mahmut Muslumanoglu, Abdullah Igci, Yesim Eralp, Adnan Aydiner, Pinar Saip, Ekrem Yavuz, Vahit Ozmen. Tim3 expression on tumor infiltrating lymphocytes is associated with poor response to neoadjuvan chemotherapy in patients with locally advanced triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-32.
Air Pollution and Polyclonal Elevation of Serum Free Light Chains: An Assessment of Adaptive Immune Responses in the Prospective Heinz Nixdorf Recall Study
Authors: Simone Ohlwein, Frauke Hennig, Sarah Lucht, Börge Schmidt, Lewin Eisele, Marina Arendt, Ulrich Dührsen, Jan Dürig, Karl-Heinz Jöckel, Susanne Moebus, Barbara Hoffmann
Journal: Environmental Health Perspectives (2021)

Background: Residential exposure to air pollution (AP) has been shown to activate the immune system (IS). Although innate immune responses to AP have been studied extensively, investigations on the adaptive IS are scarce. Objectives: The aim of this study was to investigate the association between short- to long-term AP exposure and polyclonal free light chains (FLC) produced by plasma cells. Methods: We used repeated data from three examinations (t0: 2000–2003; t1: 2006–2008; and t2: 2011–2015) of the population-based German Heinz Nixdorf Recall cohort of initially 4,814 participants (45–75 y old). Residential exposure to total and source-specific particulate matter (PM) with an aerodynamic diameter of 10 or 2.5μm (PM10 and PM2.5 respectively), nitrogen dioxide (NO2), and particle number concentrations (accumulation mode; PNAM) was estimated using a chemistry transport model with different time windows (1- to 365-d mean ± standard deviation) before blood draw. We applied linear mixed models with a random participant intercept to estimate associations between total, traffic- and industry-related AP exposures and log-transformed FLC, controlling for examination time, sociodemographic and lifestyle variables, estimated glomerular filtration rate and season. Results: Analyzing 9,933 observations from 4,455 participants, we observed generally positive associations between AP exposures and FLC. We observed strongest associations with middle-term exposures, e.g., 3.0% increase in FLC (95% confidence interval: 1.8%, 4.3%) per interquartile range increase in 91-d mean of NO2 (14.1μg/m³). Across the different pollutants, NO2 showed strongest associations with FLC, followed by PM10 and PNAM. Effect estimates for traffic-related exposures were mostly higher compared with total exposures. Although NO2 and PNAM estimates remained stable upon adjustment for PM, PM estimates decreased considerably upon adjustment for NO2 and PNAM. Discussion: Our results suggest that middle-term AP exposures in particular might be positively associated with activation of the adaptive IS. Traffic-related PM, PNAM, and NO2 showed strongest associations. https://doi.org/10.1289/EHP7164
Emergency Intubation in Covid-19
Authors: Gentle Sunder Shrestha, Ninadini Shrestha, Ritesh Lamsal, Saurabh Pradhan, Anil Shrestha, Robert Canelli, Rafael Ortega
Journal: New England Journal of Medicine (2021)

Emergency Intubation in Covid-19 This video demonstrates the procedure for emergency endotracheal intubation in patients with suspected or proven Covid-19. Endotracheal intubation in such patients ...
Management of patients with multiple myeloma beyond the clinical-trial setting: understanding the balance between efficacy, safety and tolerability, and quality of life
Authors: Evangelos Terpos, Joseph Mikhael, Roman Hajek, Ajai Chari, Sonja Zweegman, Hans C. Lee, María-Victoria Mateos, Alessandra Larocca, Karthik Ramasamy, Martin Kaiser, Gordon Cook, Katja C. Weisel, Caitlin L. Costello, Jennifer Elliott, Antonio Palumbo, Saad Z. Usmani
Journal: Blood Cancer Journal (2021)

Abstract Treatment options in multiple myeloma (MM) are increasing with the introduction of complex multi-novel-agent-based regimens investigated in randomized clinical trials. However, application in the real-world setting, including feasibility of and adherence to these regimens, may be limited due to varying patient-, treatment-, and disease-related factors. Furthermore, approximately 40% of real-world MM patients do not meet the criteria for phase 3 studies on which approvals are based, resulting in a lack of representative phase 3 data for these patients. Therefore, treatment decisions must be tailored based on additional considerations beyond clinical trial efficacy and safety, such as treatment feasibility (including frequency of clinic/hospital attendance), tolerability, effects on quality of life (QoL), and impact of comorbidities. There are multiple factors of importance to real-world MM patients, including disease symptoms, treatment burden and toxicities, ability to participate in daily activities, financial burden, access to treatment and treatment centers, and convenience of treatment. All of these factors are drivers of QoL and treatment satisfaction/compliance. Importantly, given the heterogeneity of MM, individual patients may have different perspectives regarding the most relevant considerations and goals of their treatment. Patient perspectives/goals may also change as they move through their treatment course. Thus, the ‘efficacy’ of treatment means different things to different patients, and treatment decision-making in the context of personalized medicine must be guided by an individual’s composite definition of what constitutes the best treatment choice. This review summarizes the various factors of importance and practical issues that must be considered when determining real-world treatment choices. It assesses the current instruments, methodologies, and recent initiatives for analyzing the MM patient experience. Finally, it suggests options for enhancing data collection on patients and treatments to provide a more holistic definition of the effectiveness of a regimen in the real-world setting.
Factors Associated With the Weekend Effect on the Recovery of Patients Undergoing Elective Colorectal Surgery
Authors: Rucira Ooi, Setthasorn Zhi Yang Ooi
Journal: JAMA Surgery (2021)

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