tbuckley/cabot-search huggingface dataset:
Abstract 3146: Heterogeneity of the antigen-expression pattern in primary and recurrent glioblastoma patients
Authors: Vera Dufner, Moritz Meyer-Hofmann, Jonas Feldheim, Katja Maurus, Camelia Monoranu, Thomas Nerreter, Michael Hudecek, Carsten Hagemann, Ralf-Ingo Ernestus, Mario Löhr
Journal: Cancer Research (2021)

Abstract Introduction: Immunotherapy leads to promising results in the treatment of glioblastoma (GBM) patients. Recent clinical trials revealed a survival benefit of patients treated with monospecific CAR-T-cells. However, antigen escape mechanisms due to heterogeneous surface expression of target antigens still constitute a critical hurdle in the immunotherapeutic treatment of GBM and are a major reason for non-response or relapse. Therefore, we aim to characterize GBM's heterogeneity, the intratumoral distribution and changes of surface antigens in relapse. Methods: We performed immunohistochemical staining of the ten in vitro and in vivo most targeted antigens in CAR-T cell therapy (HER2, EGFRvIII, CD70, B7H3, Il13Rα2, NY-ESO1, GD2, CD133, CSPG4 and EphA2). We analyzed 35 patients, who underwent surgery for primary (PT) as well as recurrent GBM (RL). To address intrapersonal heterogeneity, we examined five fields of view per slide. As controls, we stained cerebral, cerebellar and brain stem slides of three healthy specimens. We quantified the percentage of low, medium and high antigen expressing cells on each slide by applying a specialized macro in ImageJ. We further weighted this expression score by multiplication with 1 (low), 2 (medium) or 3 (high expression). Finally, we calculated the median expression values of all tumors combined for each antigen. Summary: Median values of EGFRvIII (PT: 0.14; RL: 0.73), HER2 (PT: 0.67; RL: 4.00) and NY-ESO1 (PT: 0.00; RL: 0.16) expression were very low. Antigen expression of CSPG4 (PT: 4.67; RL: 2.78), Il13Rα2 (PT: 3.84; RL: 2.78), GD2 (PT: 7.50; RL: 27.03) and B7H3 (PT: 8.81; RL: 16.62) was mild. CD133 (PT: 52.16; RL: 56.13), CD70 (PT: 19.18; RL: 25.02) and EphA2 (PT: 60.65; RL: 55.46) showed moderate antigen expression. None of the evaluated antigens displayed high expression. Median values of HER2 (p=0.005, Cohen's r=0.48), EGFRvIII (p=0.042, Cohen's r=0.344), and GD2 (p=0.013, Cohen's r=0.42) were significantly increased in RL compared to PT. We found significant intrapersonal expression differences for each antigen. However, none of the healthy brain tissue specimens expressed any of the ten antigens. Conclusions: Inter- and intrapersonal heterogeneity constitutes a major obstacle for the implementation of GBM immune therapies which avoid antigen escape mechanisms. Citation Format: Vera Dufner, Moritz Meyer-Hofmann, Jonas Feldheim, Katja Maurus, Camelia Monoranu, Thomas Nerreter, Michael Hudecek, Carsten Hagemann, Ralf-Ingo Ernestus, Mario Löhr. Heterogeneity of the antigen-expression pattern in primary and recurrent glioblastoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3146.
Lifting of COVID-19 restrictions in the UK and the Delta variant
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2021)

As The Lancet Respiratory Medicine went to press, the UK Government was preparing to lift nearly all of England's remaining lockdown restrictions. From July 19, 2021, there will be no legal requirement for people to wear masks in public places, sporting events and nightclubs will be free to function at full capacity, and the Government will not advise people to work from home if possible. People who have been fully vaccinated against COVID-19 will no longer be expected to isolate if they come into contact with someone infected with SARS-CoV-2, though isolation will still be mandatory for those who test positive for the virus.
Limitations of Using Questionnaires for Assessing the Prevalence of Psoriasis and Atopic Dermatitis Among Adults
Authors: Lea K. Nymand, Yuki M. F. Andersen, Jacob P. Thyssen, Alexander Egeberg
Journal: JAMA Dermatology (2021)

Questionnaire studies are important for estimating the prevalence of psoriasis and atopic dermatitis; however, validity among the adult population remains an important concern.To examine the test-retest accuracy of questionnaires for measuring psoriasis and atopic dermatitis prevalence in an adult population.This nationwide population-based cohort study administered questionnaires on psoriasis and atopic dermatitis to the same 2333 and 2312 randomly selected adults (≥18 years) in Denmark, respectively, at 2 different time points from May 15, 2018, to November 20, 2020. Data were analyzed from January 10 to January 28, 2021. To reduce the risk of participation bias, potential respondents were given information on the research project only after agreeing to participate.Participants were asked identical questions on psoriasis and atopic dermatitis in 2018 and in 2020. Responses were linked at the individual-level.The test-retest reliability (expressed by Cohen κ).The psoriasis questionnaire was completed by 2333 (mean [SD] age, 55.1 [16.2] years; 1338 [57.4%] women) participants in 2018 and in 2020. The atopic dermatitis questionnaire was completed by 2312 (mean [SD] age, 55.0 [16.2] years; 1326 [57.4%] women) participants in 2018 and in 2020. Among participants reporting a history of psoriasis, agreement between individual responses was high (κ = 0.7558); however, among those reporting a history of atopic dermatitis, agreement was low (κ = 0.4395). For psoriasis, prevalence changed from 7.8% to 8.0%; for atopic dermatitis, from 8.2% to 7.6%. Of participants who in 2018 reported dermatologist-diagnosed atopic dermatitis, 36.9% claimed in the 2020 questionnaire that they had never had atopic dermatitis. Analyses revealed substantial agreement for psoriasis responses across all age strata; for atopic dermatitis responses, the κ declined with increasing age, to 0.2613 for participants 65 or older.This cohort study found considerable agreement between responses over time when participants were asked about a history of psoriasis. When asked about a history of atopic dermatitis, responses over time were inconsistent. This inconsistency suggests that questionnaires on a history of atopic dermatitis will confer considerable risk of bias and misclassification.
Abstract 1905: <i>In vivo</i> CRISPR screen identifies tumor suppressors as drivers of tumor cell-intrinsic immune evasion
Authors: Chengyin Min, Ferdinandos Skoulidis, Wenrong Zhou, Jennifer Tsoi, Alan Huang, Matthew J. Goldstein
Journal: Cancer Research (2021)

Abstract Cancer cell-intrinsic genetic alterations that allow cancer cells to evade destruction by the immune system remain poorly characterized. Here we performed a pooled CRISPR-Cas9-based in vivo genetic screen targeted to a pre-defined set of tumor suppressor genes to mimic loss-of-function mutations in syngeneic tumor models. CRISPR edited tumor cells were implanted into immune-deficient or immune-competent C57BL/6 mice, a subset of which were treated with anti-PD1 to simulate increased immune pressure. Tumor samples at the endpoint were subjected to next generation sequencing analysis to identify tumor suppressor genes driving immune evasion. The screen confirmed previously identified immunotherapy targets such as CD47 and Adar as well as known drivers of immune resistance in the interferon signaling and antigen presentation pathways. Importantly, we identified loss of STK11/LKB1 and KEAP1 as drivers of immune resistance in syngeneic models. TIL profiling analysis suggests that STK11/LKB1 knockout induces a “cold” tumor microenvironment. STK11/LKB1 and/or KEAP1 genomic alterations are found in ~25% of non-squamous non-small cell lung cancer and have been reported as a major predictor of primary resistance to PD-1 blockade. Together, these data demonstrate that high-throughput in vivo genetic screens can identify tumor cell-intrinsic drivers of immune evasion and establish murine system relevant to the study of primary resistance to PD-1 axis immunotherapy and more generally, tumor cell-intrinsic immune evasion. Citation Format: Chengyin Min, Ferdinandos Skoulidis, Wenrong Zhou, Jennifer Tsoi, Alan Huang, Matthew J. Goldstein. In vivo CRISPR screen identifies tumor suppressors as drivers of tumor cell-intrinsic immune evasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1905.
Rapid resolution of COVID-19 after faecal microbiota transplantation
Authors: Jarosław Biliński, Katarzyna Winter, Marcin Jasiński, Anna Szczęś, Natalia Bilinska, Benjamin H Mullish, Ewa Małecka-Panas, Grzegorz W Basak
Journal: Gut (2021)

Recent publications demonstrate that SARS-CoV-2 may undergo prolonged shedding in stool, and that gut microbiome perturbations associate with COVID-19 severity.1 2 Faecal microbiota transplant (FMT) restores a damaged gut microbiome and may impact on immune responses,3 including in the respiratory system (‘gut–lung axis’)4; such microbiome-immune signalling may result in lung-epithelial resistance to SARS-CoV-2.5 We describe two interesting cases of patients treated with FMT primarily to treat Clostridioides difficile infection (CDI), but which coincidentally were performed just before initial symptoms of coexisting COVID-19 (figure 1).



Figure 1 
Timeline of the procedures performed in patients with CDI, which coincidentally occurred during COVID-19 early stage infection. Created with BioRender.com. CDI, Clostridioides difficile infection; ESBL, extended-spectrum beta-lactamase, FMT, faecal microbiota transplant.



Patient 1: an 80-year-old man with multiple comorbidities, including prior CDI, was admitted to hospital with pneumonia/sepsis. Following meropenem treatment, pneumonic features resolved, but CDI relapse occurred. Sequential vancomycin treatment and nasojejunal FMT were administered. On the day of FMT, he …
Abstract 1609: Peripheral NK-cell immunophenotypes predict progression in nasopharyngeal carcinoma patients
Authors: Xiao-Yun Li, Zi-Jian Lu, Hai-Qiang Mai
Journal: Cancer Research (2021)

Abstract Objective: The tumorigenesis is closely associated with the alteration in the expression of cell-surface proteins. As NK cells play a vital role in cancer immunotherapy, we thus conducted this study to characterize the immunophenotypes of circulating NK cells and to explore the association between NK phenotypes and disease prognosis. Methods: 249 nasopharyngeal carcinoma (NPC) patients and 11 healthy individuals were recruited in the study, whose peripheral blood samples were collected before treatment. Multi-color flow cytometry analysis was performed. The expression of four inhibitory receptors, PD-1, TIGIT, LAG-3, TIM-3, and four stimulatory receptors, NKp46, NKp30, CD226, NKG2D, were measured in three NK subsets, identified by the co-expression of CD56 and CD16 when gated on CD3-. The LASSO (least absolute shrinkage and selection operator) logistic regression model was used to screen out potential prognostic NK subtypes and calculate the NK-function index. Results: NPC patients exhibited distinct peripheral NK-cell distribution and altered expression of key receptors, as characterized by increased expression of PD-1 and TIGIT on CD56+CD16- cells and decreased expression of NKp46 on CD56+CD16- and CD56-CD16- cells. Four markers were selected from the LASSO model to calculate the NK-function index: PD1 and NKp46 on CD56-CD16+ NK cells, NKp46 on CD56+CD16- cells and NKG2D on CD56+CD16+ cells. Patients with low NK index had significantly shorter progression-free survival (PFS) and distant metastasis-free survival (DMFS), and the NK-function index was an independent prognostic factor for NPC patients. Conclusions: The immunophenotype of peripheral NK cells and its association with survival outcomes of NPC patients revealed its potential as a strong prognosticator for PFS and DMFS, and highlighted the important role of circulating immune environment, especially for the application of immunotherapy. Citation Format: Xiao-Yun Li, Zi-Jian Lu, Hai-Qiang Mai. Peripheral NK-cell immunophenotypes predict progression in nasopharyngeal carcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1609.
Anti-androgen therapy overcomes the time-delay in initiation of salvage radiation therapy and rescues the oncological outcomes in men with recurrent prostate cancer after radical prostatectomy: A post-hoc analysis of the RTOG 9601 trial data
Authors: A. Sood, J. Keeley, I. Palma-Zamora, M. Chien, D. Dalela, S. Arora, M. Jamil, N. Kovacevic, N. Corsi, W. Jeong, C.G. Rogers, Q-D. Trinh, J.O. Peabody, M. Menon, F. Abdollah
Journal: European Urology (2021)
Abstract 15769: Alpha1A-Adrenergic Receptors in Neuroprotection
Authors: Bat-Erdene Myagmar, Randell C Thomas, Megan D Montgomery, Jialing Liu, Stephen Massa, Paul C Simpson
Journal: Circulation (2011)

Background: Alpha-1A-adrenergic receptors (α1A-ARs) have a protective trophic role in the heart. α1A-AR levels are high in the brain, and neuroprotection by norepinephrine is known. Recently, α1A-A...
Abstract 2876: Adhesion GPCR CD97/ADGRE5 facilitates invasion in patient-derived glioma stem cells and induces changes in EGFR and Sox2 expression
Authors: Tatiana I. Slepak, Daniel G. Eichberg, Ana L. Pascoini, Ricardo J. Komotar, Michael E. Ivan
Journal: Cancer Research (2021)

Abstract The main obstacles for effective treatment of Glioblastoma (GBM) are high invasiveness and heterogeneity. Each GBM tumor is composed of multiple genetically distinct subpopulations of Glioma Stem Cells (GSCs), exhibiting high cell plasticity affecting their invasive and proliferative properties. Treatment interventions and changes in microenvironment force GSCs to adapt through gene expression that supports therapeutic resistance. Expression level of the surface receptor CD97/ADRGE5 positively correlates with poor GBM patient prognosis, but its role in this tumor has not been elucidated. Here, we examined the function of CD97 in primary GSCs derived from five GBM tumors, which belong to three major genetic subtypes. We manipulated CD97 levels in these GSCs by knockdown and overexpression and analyzed the following: (i) expression of stem and subtype markers, (ii) in vitro invasive properties, (iii) cell proliferation, (iv) expression of the key proteins that regulate GSCs cellular state and influence their adaptive behavior. Our data showed that CD97 knockdown in GSCs of mesenchymal and classical subtype reduced their invasion rate in vitro. CD97 signaling positively affected expression of Epidermal Growth Factor Receptor, the main driver of astrocyte-like fate in GSCs and changed the expression of the astrocytic marker GFAP. Finally, we discovered a possible link between CD97 and expression of transcription factor Sox2, the key regulator of the endothelial-to-mesenchymal transition process that plays a crucial role in initiation of cancer cell invasion. Citation Format: Tatiana I. Slepak, Daniel G. Eichberg, Ana L. Pascoini, Ricardo J. Komotar, Michael E. Ivan. Adhesion GPCR CD97/ADGRE5 facilitates invasion in patient-derived glioma stem cells and induces changes in EGFR and Sox2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2876.
Approval of Aducanumab for Alzheimer Disease—The FDA’s Perspective
Authors: Billy Dunn, Peter Stein, Patrizia Cavazzoni
Journal: JAMA Internal Medicine (2021)

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Training and assessment of medical specialists in clinical microbiology and infectious diseases in Europe
Authors: Nick J. Beeching, Hilpi Rautelin, Jean-Paul Stahl, Truls M. Leegaard
Journal: Clinical Microbiology and Infection (2021)

BackgroundThere is wide variation in the availability and training of specialists in the diagnosis and management of infections across Europe.ObjectivesTo describe and reflect on the current objectives, structure and content of European curricula and examinations for the training and assessment of medical specialists in Clinical (Medical) Microbiology (CM/MM) and Infectious Diseases (ID).SourcesNarrative review of developments over the past two decades and related policy documents and scientific literature.ContentResponsibility for curricula and examinations lies with the European Union of Medical Specialists (UEMS). The ID Section of UEMS was inaugurated in 1997 and the MM Section separated from Laboratory Medicine in 2008. The sections collaborate closely with each other and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Updated European Training Requirements (ETR) were approved for MM in 2017 and ID in 2018. These comprehensive curricula outline the framework for delivery of specialist training and quality control for trainers and training programmes, emphasizing the need for documented, regular formative reviews of progress of trainees. Competencies to be achieved include both specialty-related and generic knowledge, skills and professional behaviours. The indicative length of training is typically 5 years; a year of clinical training is mandated for CM/MM trainees and 6 months of microbiology laboratory training for ID trainees. Each Section is developing examinations using multiple choice questions to test the knowledge base defined in their ETR, to be delivered in 2022 following pilot examinations in 2021.ImplicationsThe revised ETRs and European examinations for medical specialists in CM/MM and ID provide benchmarks for national authorities to adapt or adopt locally. Through harmonization of postgraduate training and assessment, they support the promotion and recognition of high standards of clinical practice and hence improved care for patients throughout Europe, and improved mobility of trainees and specialists.
Natural polymer-derived photocurable bioadhesive hydrogels for sutureless keratoplasty
Authors: Xuan Zhao, Saiqun Li, Xinyue Du, Weihua Li, Qian Wang, Dalian He, Jin Yuan
Journal: Bioactive Materials (2021)

Keratoplasty is the gold standard treatment for visual impairment caused by corneal damage. The use of suturing as the bonding method is the source of many complications following keratoplasty. Currently available corneal adhesives do not have both adequate adhesive strength and acceptable biocompatibility. Herein, we developed a photocurable bioadhesive hydrogel which was composed of gelatin methacryloyl and oxidized dextran for sutureless keratoplasty. The bioadhesive hydrogel exhibited high light transmittance, resistance to enzymatic degradation and excellent biocompatibility. It also had higher adhesive strength than commercial adhesives (fibrin glue). In a rabbit model of lamellar keratoplasty, donor corneal grafts could be closely bonded to the recipient corneal bed and remained attached for 56 days by using of this in situ photopolymerized bioadhesive hydrogel. The operated cornea maintained transparent and noninflamed. Sutureless keratoplasty using bioadhesive hydrogel allowed rapid graft re-epithelialization, typically within 7 days.
Surgical treatment of male Lichen Sclerosus-related urethral strictures disease: State of the art
Authors: F. Esperto, W. Verla, A. Ploumidis, R. Barratt, R. La Rocca, N. Lumen, F.C. Juanatey, T. Greenwell, F.E. Martins, N. Osman, S. Riechardt, M. Waterloos, K. Dimitropoulos
Journal: European Urology (2021)
Abstract 829: Genetic risk factors for histiocytic sarcoma in a canine disease model
Authors: Jacquelyn M. Evans, Heidi G. Parker, Jocelyn Plassais, Gerard R. Rutteman, Elaine A. Ostrander
Journal: Cancer Research (2021)

Abstract Histiocytic sarcoma is a rare, aggressive hematopoietic malignancy of mature tissue histiocytes with a poorly understood etiology in humans. A histologically and clinically similar counterpart in dogs affects two breeds at unusually high frequency, with 20-25% of Flatcoated Retrievers and Bernese Mountain Dogs developing histiocytic sarcoma, while the disease is extremely rare in other breeds. In this study, we leveraged the canine model system to investigate genetic risk factors for histiocytic sarcoma in the Flatcoated Retriever. Population bottlenecks and artificial selection during breed formation within last 200 years have created the unique breed structure in dogs, characterized by long linkage disequilibrium and low within-breed genetic diversity. This allows for the identification of disease-associated traits with relatively few markers and individuals. We conducted multiple genome-wide association studies in Flatcoated Retrievers in which we identified two loci conferring risk for histiocytic sarcoma (177 cases and 132 controls, total). The first locus, on canine chromosome (CFA) 5, also colocalizes with previously identified risk for hemangiosarcoma and B-cell lymphoma, two hematopoietic malignancies in the closely related golden retriever breed. The second locus is unique to the Flatcoated Retriever and increases risk for histiocytic sarcoma in combination with CFA5. There have been multiple reports of human histiocytic sarcoma diagnosis concurrent with other hematological cancers, including lymphoma, suggested to be the result of transdifferentiation or a common neoplastic progenitor. Here we link germline predisposition for histiocytic sarcoma and B-cell lymphoma to the same locus in retrievers. Subsequent whole genome, transcriptome, and ChIP sequencing, highlighted candidate genes at each locus with roles in cell migration, as well as candidate regulatory variants with predicted impact on transcription factor binding. This comprehensive, multi-omics approach has been previously largely unexplored in the canine model. Here we advance our knowledge of the biology of histiocytic sarcoma, which will have direct impact on canine health and elucidate the genetic mechanisms underlying a rare human cancer. Citation Format: Jacquelyn M. Evans, Heidi G. Parker, Jocelyn Plassais, Gerard R. Rutteman, Elaine A. Ostrander. Genetic risk factors for histiocytic sarcoma in a canine disease model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 829.