tbuckley/cabot-search huggingface dataset:
Sex Differences in Immunity
Authors: Nicole M. Wilkinson, Ho-Chung Chen, Melissa G. Lechner, Maureen A. Su
Journal: Annual Review of Immunology (2022)

Strong epidemiological evidence now exists that sex is an important biologic variable in immunity. Recent studies, for example, have revealed that sex differences are associated with the severity of symptoms and mortality due to coronavirus disease 2019 (COVID-19). Despite this evidence, much remains to be learned about the mechanisms underlying associations between sex differences and immune-mediated conditions. A growing body of experimental data has made significant inroads into understanding sex-influenced immune responses. As physicians seek to provide more targeted patient care, it is critical to understand how sex-defining factors (e.g., chromosomes, gonadal hormones) alter immune responses in health and disease. In this review, we highlight recent insights into sex differences in autoimmunity; virus infection, specifically severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; and cancer immunotherapy. A deeper understanding of underlying mechanisms will allow the development of a sex-based approach to disease screening and treatment.
Coverage of COVID-19 Vaccine Counseling for Children and Youths
Authors: Melissa Suran
Journal: JAMA (2022)

Increased Use of Medicare Telehealth During the PandemicTelehealth visits for Medicare beneficiaries have increased significantly since the COVID-19 pandemic began, according to a report from the US Department of Health and Human Services (HHS).Researchers in HHS' Office of the Assistant Secretary for Planning and Evaluation reviewed 2019 and 2020 Medicare health care utilization trends.The authors found that overall Medicare Part B visits-when accounting for both in-person and telehealthdecreased from 1.1 billion in 2019 to approximately 989 million in 2020.However, 2020 telehealth visits increased to 52.7 million from approximately 840 000 in 2019.Ninetytwo percent of telehealth visits occurred in beneficiaries' homes, which generally wasn't permitted before the pandemic.To reduce COVID-19 exposure in health care environments, the US Centers for Medicare & Medicaid Services (CMS) authorized waivers in March 2020 that expanded telehealth services for Medicare beneficiaries.These waivers allowed for telehealth inhome visits, services in urban areas, and audio-only interaction for some services.HHS' report noted that in 2020, a greater proportion of beneficiaries in urban than rural areas used telehealth services.Whereas Massachusetts, Vermont, Rhode Island, New Hampshire, and Connecticut were among states with the highest use of telehealth services in 2020, those with the lowest use included Tennessee, Nebraska, Kansas, North Dakota, and Wyoming.White Medicarebeneficiariesweremorelikelytouse telehealth services than Black beneficiaries.Among clinicians, behavioral health specialists had the highest increase in telehealth visits.In 2019, only 1% of visits to behavioral health specialists were telehealth; in 2020, the percentage jumped to 38.1%.By the end of 2020, telehealth visits to behavioral specialists were as common as inperson visits."This report provides valuable insights into telehealth usage during the pandemic," CMS Administrator Chiquita Brooks-LaSure, MPP, said in a statement."CMS will use these insights-along with input from people with Medicare and providers across the country-toinformfurtherMedicaretelehealthpolicies."Coverage of COVID-19 Vaccine Counseling for Children and Youths
Proteomics as a tool to gain next level insights into photo-crosslinkable biopolymer modifications
Authors: Nele Pien, Fabrice Bray, Tom Gheysens, Liesbeth Tytgat, Christian Rolando, Diego Mantovani, Peter Dubruel, Sandra Van Vlierberghe
Journal: Bioactive Materials (2022)

The distribution of photo-crosslinkable moieties onto a protein backbone can affect a biomaterial's crosslinking behavior, and therefore also its mechanical and biological properties. A profound insight in this respect is essential for biomaterials exploited in tissue engineering and regenerative medicine. In the present work, photo-crosslinkable moieties have been introduced on the primary amine groups of: (i) a recombinant collagen peptide (RCPhC1) with a known amino acid (AA) sequence, and (ii) bovine skin collagen (COL BS) with an unknown AA sequence. The degree of substitution (DS) was quantified with two conventional techniques: an ortho-phthalic dialdehyde (OPA) assay and 1H NMR spectroscopy. However, neither of both provides information on the exact type and location of the modified AAs. Therefore, for the first time, proteomic analysis was evaluated herein as a tool to identify functionalized AAs as well as the exact position of photo-crosslinkable moieties along the AA sequence, thereby enabling an in-depth, unprecedented characterization of functionalized photo-crosslinkable biopolymers. Moreover, our strategy enabled to visualize the spatial distribution of the modifications within the overall structure of the protein. Proteomics has proven to provide unprecedented insight in the distribution of photo-crosslinkable moieties along the protein backbone, undoubtedly contributing to superior functional biomaterial design to serve regenerative medicine.
Effectiveness and Safety of Ticagrelor Implementation in Patients with Acute Coronary Syndrome undergoing Percutaneous Coronary Intervention: A Cohort Study in Western Denmark
Authors: Pernille Gro Thrane, Kevin Kris Warnakula Olesen, Morten Würtz, Christine Gyldenkerne, Morten Madsen, Lisette Okkels Jensen, Bent Raungaard, Henrik Toft Sørensen, Troels Thim, Steen Dalby Kristensen, Michael Maeng
Journal: The Lancet Regional Health - Europe (2022)

Ticagrelor was introduced in Denmark in 2011 after randomised data showed its superiority over clopidogrel for patients with acute coronary syndrome (ACS). We assessed the effectiveness and safety of ticagrelor implementation in ACS patients undergoing percutaneous coronary intervention (PCI).
Charlson Comorbidity Index: A Critical Review of Clinimetric Properties
Authors: Mary E. Charlson, Danilo Carrozzino, Jenny Guidi, Chiara Patierno
Journal: Psychotherapy and Psychosomatics (2022)

The present critical review was conducted to evaluate the clinimetric properties of the Charlson Comorbidity Index (CCI), an assessment tool designed specifically to predict long-term mortality, with regard to its reliability, concurrent validity, sensitivity, incremental and predictive validity. The original version of the CCI has been adapted for use with different sources of data, ICD-9 and ICD-10 codes. The inter-rater reliability of the CCI was found to be excellent, with extremely high agreement between self-report and medical charts. The CCI has also been shown either to have concurrent validity with a number of other prognostic scales or to result in concordant predictions. Importantly, the clinimetric sensitivity of the CCI has been demonstrated in a variety of medical conditions, with stepwise increases in the CCI associated with stepwise increases in mortality. The CCI is also characterized by the clinimetric property of incremental validity, whereby adding the CCI to other measures increases the overall predictive accuracy. It has been shown to predict long-term mortality in different clinical populations, including medical, surgical, intensive care unit (ICU), trauma, and cancer patients. It may also predict in-hospital mortality, although in some instances, such as ICU or trauma patients, the CCI did not perform as well as other instruments designed specifically for that purpose. The CCI thus appears to be clinically useful not only to provide a valid assessment of the patient’s unique clinical situation, but also to demarcate major diagnostic and prognostic differences among subgroups of patients sharing the same medical diagnosis.
Survival outcomes after radical cystectomy versus conservative management for clinical T1 high grade non-muscle invasive micropapillary bladder cancer: A multicenter collaboration by the European Association of Urology–Young Academic Urologists
Authors: C. Lonati, P. Baumeister, L. Afferi, A. Mari, A. Minervini, W. Krajewski, S.M.H. Einerhand, F. Montorsi, A. Briganti, A. Antonelli, M. Rouprêt, A. Masson-Lecomte, S.F. Shariat, D. D’Andrea, F. Soria, R. Hurle, M.C. Mir, S. Zamboni, C. Simeone, T. Klatte, J.Y. Teoh, G.B. Schulz, A. Mattei, M. Moschini
Journal: European Urology (2021)
Boosting the combination of radiation and anti-pd-l1 with sting agonist in a preclinical muscle invasive bladder cancer murine model
Authors: G. Marcq, J. Huang, C. Tholomier, R. Kool, S. Shinde-Jadhav, R. Skowronski, F. Brimo, J.J. Mansure, W. Kassouf
Journal: European Urology (2021)
Phase II Trial of the Combination of Ixazomib, Lenalidomide, and Dexamethasone in High-Risk Smoldering Multiple Myeloma
Authors: Mark Bustoros, MD, Omar Nadeem, Adam S Sperling, Giada Bianchi, Lily Ardente, Robert A. Redd, Julia Prescott, Erin Frey, Kathleen Guimond, Rachel Styles, Kalvis Hornburg, Alexandra Savell, Nang Kham Su, Govind Bindra, Cody J Boehner, Kaitlen Reyes, Houry Leblebjian, Diane Warren, Nikhil C. Munshi, Jacob P. Laubach, Kenneth C. Anderson, Paul G. Richardson, Irene M. Ghobrial
Journal: Blood (2019)
Clinical and molecular characteristics associated with response to therapeutic PD-1/PD-L1 inhibition in advanced Merkel cell carcinoma
Authors: Ivelina Spassova, Selma Ugurel, Linda Kubat, Lisa Zimmer, Patrick Terheyden, Annalena Mohr, Hannah Björn Andtback, Lisa Villabona, Ulrike Leiter, Thomas Eigentler, Carmen Loquai, Jessica C Hassel, Thilo Gambichler, Sebastian Haferkamp, Peter Mohr, Claudia Pfoehler, Lucie Heinzerling, Ralf Gutzmer, Jochen S Utikal, Kai Horny, Hans-Ulrich Schildhaus, Daniel Habermann, Daniel Hoffmann, Dirk Schadendorf, Jürgen Christian Becker
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Based on its viral-associated or UV-associated carcinogenesis, Merkel cell carcinoma (MCC) is a highly immunogenic skin cancer. Thus, clinically evident MCC occurs either in immuno-compromised patients or based on tumor-intrinsic immune escape mechanisms. This notion may explain that although advanced MCC can be effectively restrained by treatment with PD-1/PD-L1 immune checkpoint inhibitors (ICIs), a considerable percentage of patients does not benefit from ICI therapy. Biomarkers predicting ICI treatment response are currently not available. Methods The present multicenter retrospective study investigated clinical and molecular characteristics in 114 patients with unresectable MCC at baseline before treatment with ICI for their association with therapy response (best overall response, BOR). In a subset of 21 patients, pretreatment tumor tissue was analyzed for activation, differentiation and spatial distribution of tumor infiltrating lymphocytes (TIL). Results Of the 114 patients, n=74 (65%) achieved disease control (BOR=complete response/partial response/stable disease) on ICI. A Bayesian cumulative ordinal regression model revealed absence of immunosuppression and a limited number of tumor-involved organ systems was highly associated with a favorable therapy response. Unimpaired overall performance status, high age, normal serum lactate dehydrogenase and normal serum C reactive protein were moderately associated with disease control. While neither tumor Merkel cell polyomavirus nor tumor PD-L1 status showed a correlation with therapy response, treatment with anti-PD-1 antibodies was associated with a higher probability of disease control than treatment with anti-PD-L1 antibodies. Multiplexed immunohistochemistry demonstrated the predominance of CD8 + effector and central memory T cells (T CM ) in close proximity to tumor cells in patients with a favorable therapy response. Conclusions Our findings indicate the absence of immunosuppression, a limited number of tumor-affected organs, and a predominance of CD8 + T CM among TIL, as baseline parameters associated with a favorable response to PD-1/PD-L1 ICI therapy of advanced MCC. These factors should be considered when making treatment decisions in MCC patients.
Estimated Cost of Circulating Tumor DNA for Posttreatment Surveillance of Human Papillomavirus–Associated Oropharyngeal Cancer
Authors: Roman O. Kowalchuk, Benjamin C. Kamdem Talom, Kathryn M. Van Abel, Daniel M. Ma, Mark R. Waddle, David M. Routman
Journal: JAMA Network Open (2022)

striking since only 10% to 15% of patients with HPV-associated OPSCC will develop recurrent disease. 5In addition, fewer imaging studies would reduce costs and ameliorate patient anxiety. 6cause ctDNA is a laboratory test, surveillance could be completed without a follow-up visit, further reducing costs and travel burden.Also, ctDNA offers a potential lead time of more than 3 months prior to biopsy-proven recurrence. 2 We strongly encourage further biomarker studies to involve ctDNA for posttreatment surveillance.Validation in HPV-associated OPSCC is underway (NCT04564989).Limitations of this analysis include the lack of a comparison of incremental costeffectiveness ratio, which is a result of the limited literature available in this field.Our analysis supports ctDNA as a low-cost posttreatment surveillance strategy for HPV-associated oropharyngeal cancer compared with imaging-based strategies.
There is a Need for a Universal Language in the Reporting and Grading of Complication and Intervention Events to Ensure Comparability and Improvement of Surgical Care
Authors: Christopher Soliman, Niranjan J. Sathianathen, Gianluca Giannarini, Patrick Y. Wuethrich, Henry Y.C. Pan, Benjamin C. Thomas, Philip Dundee, Marcus G. Cumberbatch, Rajesh Nair, Nathan Lawrentschuk, Marc A. Furrer
Journal: European Urology (2022)
Enhanced tendon healing by a tough hydrogel with an adhesive side and high drug-loading capacity
Authors: Benjamin R. Freedman, Andreas Kuttler, Nicolau Beckmann, Sungmin Nam, Daniel Kent, Michael Schuleit, Farshad Ramazani, Nathalie Accart, Anna Rock, Jianyu Li, Markus Kurz, Andreas Fisch, Thomas Ullrich, Michael W. Hast, Yann Tinguely, Eckhard Weber, David J. Mooney
Journal: Nature Biomedical Engineering (2022)
The role of immunoglobulin E and mast cells in hypertension
Authors: Weipeng Ge, Xiaoxiao Guo, Xiaomin Song, Junling Pang, Xuan Zou, Yonglin Liu, Yongliang Niu, Zhengqing Li, Hongmei Zhao, Ran Gao, Jing Wang
Journal: Cardiovascular Research (2022)

Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodelling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension.Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodelling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE-FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signalling pathway analyses of mouse bone marrow-derived MCs suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species production and decreased the levels of phosphorylated endothelial nitric oxide synthase in ECs, leading to endothelial dysfunction.Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE-FcεR1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.
The development and progress of nanomedicine for esophageal cancer diagnosis and treatment
Authors: Xiaokun Li, Lingmin Chen, Siyuan Luan, Jianfeng Zhou, Xin Xiao, Yushang Yang, Chengyi Mao, Pinhao Fang, Longqi Chen, Xiaoxi Zeng, Huile Gao, Yong Yuan
Journal: Seminars in Cancer Biology (2022)
Expanding uncapped translation and emerging function of circular RNA in carcinomas and noncarcinomas
Authors: Yan Wang, Chunjie Wu, Yu Du, Zhongwei Li, Minle Li, Pingfu Hou, Zhigang Shen, Sufang Chu, Junnian Zheng, Jin Bai
Journal: Molecular Cancer (2022)

Abstract Circular RNAs (circRNAs) are classified as noncoding RNAs because they are devoid of a 5’ end cap and a 3’ end poly (A) tail necessary for cap-dependent translation. However, increasing numbers of translated circRNAs identified through high-throughput RNA sequencing overlapping with polysome profiling indicate that this rule is being broken. CircRNAs can be translated in cap-independent mechanism, including IRES (internal ribosome entry site)-initiated pattern, MIRES (m 6 A internal ribosome entry site) -initiated patterns, and rolling translation mechanism (RCA). CircRNA-encoded proteins harbour diverse functions similar to or different from host proteins. In addition, they are linked to the modulation of human disease including carcinomas and noncarcinomas. CircRNA-related translatomics and proteomics have attracted increasing attention. This review discusses the progress and exclusive characteristics of circRNA translation and highlights the latest mechanisms and regulation of circRNA translatomics. Furthermore, we summarize the extensive functions and mechanisms of circRNA-derived proteins in human diseases, which contribute to a better understanding of intricate noncanonical circRNA translatomics and proteomics and their therapeutic potential in human diseases.
Monocentric experience of Robot-assisted radical nephrectomy with vena cava thrombectomy: Technique and results
Authors: L. Gobinet, L. Tesi, N.S. Vuong, L. Mosillo, M. Percot, L. Dupitout, H. Simeon, P. Blanc, E. Alezra, V. Estrade, G. Capon, F. Bladou, G. Robert, M. Gross Goupil, J-C. Bernhard
Journal: European Urology (2021)
The SARS-CoV-2 monoclonal antibody combination, AZD7442, is protective in nonhuman primates and has an extended half-life in humans
Authors: Yueh-Ming Loo, Patrick M. McTamney, Rosalinda H. Arends, Michael E. Abram, Anastasia A. Aksyuk, Seme Diallo, Daniel J. Flores, Elizabeth J. Kelly, Kuishu Ren, Richard Roque, Kim Rosenthal, Katie Streicher, Kevin M. Tuffy, Nicholas J. Bond, Owen Cornwell, Jerome Bouquet, Lily I. Cheng, James Dunyak, Yue Huang, Anton I. Rosenbaum, Venkatesh Pilla Reddy, Hanne Andersen, Robert H. Carnahan, James E. Crowe, Ana I. Kuehne, Andrew S. Herbert, John M. Dye, Helen Bright, Nicole L. Kallewaard, Menelas N. Pangalos, Mark T. Esser
Journal: Science Translational Medicine (2022)

Despite the success of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, there remains a need for more prevention and treatment options for individuals remaining at risk of coronavirus disease 2019 (COVID-19). Monoclonal antibodies (mAbs) against the viral spike protein have potential to both prevent and treat COVID-19 and reduce the risk of severe disease and death. Here, we describe AZD7442, a combination of two mAbs, AZD8895 (tixagevimab) and AZD1061 (cilgavimab), that simultaneously bind to distinct, nonoverlapping epitopes on the spike protein receptor binding domain to neutralize SARS-CoV-2. Initially isolated from individuals with prior SARS-CoV-2 infection, the two mAbs were designed to extend their half-lives and reduce effector functions. The AZD7442 mAbs individually prevent the spike protein from binding to angiotensin-converting enzyme 2 receptor, blocking virus cell entry, and neutralize all tested SARS-CoV-2 variants of concern. In a nonhuman primate model of SARS-CoV-2 infection, prophylactic AZD7442 administration prevented infection, whereas therapeutic administration accelerated virus clearance from the lung. In an ongoing phase 1 study in healthy participants (NCT04507256), a 300-mg intramuscular injection of AZD7442 provided SARS-CoV-2 serum geometric mean neutralizing titers greater than 10-fold above those of convalescent serum for at least 3 months, which remained threefold above those of convalescent serum at 9 months after AZD7442 administration. About 1 to 2% of serum AZD7442 was detected in nasal mucosa, a site of SARS-CoV-2 infection. Extrapolation of the time course of serum AZD7442 concentration suggests AZD7442 may provide up to 12 months of protection and benefit individuals at high-risk of COVID-19.
<i>ATM</i> Germline-Mutated Gastroesophageal Junction Adenocarcinomas: Clinical Descriptors, Molecular Characteristics, and Potential Therapeutic Implications
Authors: Tony El Jabbour, Maksym Misyura, Darren Cowzer, Michal Zimmermann, Victoria Rimkunas, Antonio Marra, Fatemeh Derakhshan, Pier Selenica, Megan Parilla, Jeremy S Setton, Ozge Ceyhan-Birsoy, Yelena Kemel, Amanda Catchings, Megha Ranganathan, Geoffrey Y Ku, Yelena Y Janjigian, Michael Zinda, Maria Koehler, Zsofia Stadler, Jinru Shia, Jorge S Reis-Filho, Diana Mandelker
Journal: JNCI Journal of the National Cancer Institute (2022)

Gastroesophageal junction (GEJ) adenocarcinoma is a rare cancer associated with poor prognosis. The genetic factors conferring predisposition to GEJ adenocarcinoma have yet to be identified.We analyzed germline testing results from 23 381 cancer patients undergoing tumor-normal sequencing, of which 312 individuals had GEJ adenocarcinoma. Genomic profiles and clinico-pathologic features were analyzed for the GEJ adenocarcinomas. Silencing of ATM and ATR was performed using validated short-interfering RNA species in GEJ, esophageal, and gastric adenocarcinoma cell lines. All statistical tests were 2-sided.Pathogenic or likely pathogenic ATM variants were identified in 18 of 312 patients (5.8%), and bi-allelic inactivation of ATM through loss of heterozygosity of the wild-type allele was detected in all (16 of 16) samples with sufficient tumor content. Germline ATM-mutated GEJ adenocarcinomas largely lacked somatic mutations in TP53, were more likely to harbor MDM2 amplification, and harbored statistically significantly fewer somatic single nucleotide variants (2.0 mutations/Mb vs 7.9 mutations/Mb; P < .001). A statistically significantly higher proportion of germline ATM-mutated than ATM-wild-type GEJ adenocarcinoma patients underwent a curative resection (10 [100%] vs 92 [86.8%], P = .04; Fisher's exact test.), A synthetic lethal interaction between short-interfering RNA silencing of ATM and ATR was observed in the models analyzed.Our results indicate that germline pathogenic variants in ATM drive oncogenesis in GEJ adenocarcinoma and might result in a distinct clinical phenotype. Given the high prevalence of germline ATM-mutated GEJ adenocarcinomas, genetic testing for individuals with GEJ adenocarcinomas may be considered to better inform prognostication, treatment decisions, and future cancer risk.
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Journal: JAMA Network Open (2022)

Byungkyu Lee, PhD; Kai-Cheng Yang, MS; Patrick Kaminski, MA; Siyun Peng, PhD; Meltem Odabas, PhD; Sumedha Gupta, PhD; Harold D. Green Jr, PhD; Yong-Yeol Ahn, PhD; Brea L. Perry, PhD
The effect of primary health care on tuberculosis in a nationwide cohort of 7·3 million Brazilian people: a quasi-experimental study
Authors: Gabriela S Jesus, Julia M Pescarini, Andrea F Silva, Ana Torrens, Wellington M Carvalho, Elzo P P Junior, Maria Y Ichihara, Mauricio L Barreto, Poliana Rebouças, James Macinko, Mauro Sanchez, Davide Rasella
Journal: The Lancet Global Health (2022)

Universal health coverage is one of the WHO End TB Strategy priority interventions and could be achieved-particularly in low-income and middle-income countries-through the expansion of primary health care. We evaluated the effects of one of the largest primary health-care programmes in the world, the Brazilian Family Health Strategy (FHS), on tuberculosis morbidity and mortality using a nationwide cohort of 7·3 million individuals over a 10-year study period.