tbuckley/cabot-search huggingface dataset:
NPI-0052:Development of a novel orally available proteasome inhibitor
Authors: Ta-Hsiang Chao, Dharminder Chauhan, Benjamin Nicholson, Laurence Catley, Gordafaried Deyanat-Yazdi, G. Kenneth Lloyd, Saskia T. C. Neuteboom, Kenneth C. Anderson, Michael A. Palladino
Journal: Cancer Research (2005)

6152  NPI-0052 is a potent, structurally novel, small molecule proteasome inhibitor isolated from the fermentation broth of a Salinosporasp. NPI-0052 shares a common bicyclic γ-lactam-β-lactone ring structure with Omuralide and PS-519, two known 20S proteasome inhibitors. NPI-0052 specifically inhibits all three major proteolytic activities of purified human 20S proteasome with EC50 values ranging from 3 nM to 400 nM. Furthermore, NPI-0052 demonstrates potent anti-tumor activity against a panel of human tumor cell lines. Among the tested cell lines, NPI-0052 is the most active against the multiple myeloma (MM) cell lines. The effects of NPI-0052 were also investigated on MM cells freshly isolated from patients relapsing after multiple prior therapies including Dexamethasone, Velcade® (Bortezomib) and Thalidomide. Results from DNA fragmentation assays demonstrated that NPI-0052 induces apoptosis in patient MM cells refractory to conventional and Bortezomib therapies. In contrast, NPI-0052 did not affect the viability of normal human peripheral blood mononuclear cells. When analyzed in vivo, NPI-0052 inhibits the chymotrypsin-like activity of murine whole blood 20S proteasomes in a dose-dependent manner after oral or i.v. administration. The effect of NPI-0052 on the 20S proteasome activity in whole blood cells was also evaluated after repeated oral dosing. The weights of the mice were monitored to access tolerability of the dosing schedules. These studies showed that twice weekly oral dosing of NPI-0052 at 0.25 mg/kg and 0.5 mg/kg for up to seven consecutive treatment resulted in minimal body weight loss, while a sustained inhibition of the 20S proteasome was established. Treatment of MM tumor bearing mice with NPI-0052 at 0.25 mg/kg or 0.5mg/kg was very well tolerated and resulted in significant inhibition of MM tumor growth, prolonged survival and a high percentage of tumor cures in these mice. In summary, NPI-0052 inhibits all three major protease-like activities of the 20S proteasome and induces apoptosis of patient MM cells resistant to conventional and Bortezomib therapies in vitro. NPI-0052 is orally active, inhibits MM tumor growth, prolongs survival and resulted in tumor cured in vivo.
Stroke Complicating Infective Endocarditis After Transcatheter Aortic Valve Replacement
Authors: David del Val, Mohamed Abdel-Wahab, Norman Mangner, Eric Durand, Nikolaj Ihlemann, Marina Urena, Costanza Pellegrini, Francesco Giannini, Tomasz Gasior, Wojtek Wojakowski, Martin Landt, Vincent Auffret, Jan Malte Sinning, Asim N. Cheema, Luis Nombela-Franco, Chekrallah Chamandi, Francisco Campelo-Parada, Erika Munoz-Garcia, Howard C. Herrmann, Luca Testa, Kim Won-Keun, Juan Carlos Castillo, Alberto Alperi, Didier Tchetche, Antonio L. Bartorelli, Samir Kapadia, Stefan Stortecky, Ignacio Amat-Santos, Harindra C. Wijeysundera, John Lisko, Enrique Gutiérrez-Ibanes, Vicenç Serra, Luisa Salido, Abdullah Alkhodair, Ugolino Livi, Tarun Chakravarty, Stamatios Lerakis, Victoria Vilalta, Ander Regueiro, Rafael Romaguera, Utz Kappert, Marco Barbanti, Jean-Bernard Masson, Frédéric Maes, Claudia Fiorina, Antonio Miceli, Susheel Kodali, Henrique B. Ribeiro, Jose Armando Mangione, Fabio Sandoli de Brito Jr, Guglielmo Mario Actis Dato, Francesco Rosato, Maria-Cristina Ferreira, Valter Correia de Lima, Alexandre Siciliano Colafranceschi, Alexandre Abizaid, Marcos Antonio Marino, Vinicius Esteves, Julio Andrea, Roger R. Godinho, Fernando Alfonso, Helene Eltchaninoff, Lars Søndergaard, Dominique Himbert, Oliver Husser, Azeem Latib, Hervé Le Breton, Clement Servoz, Isaac Pascual, Saif Siddiqui, Paolo Olivares, Rosana Hernandez-Antolin, John G. Webb, Sandro Sponga, Raj Makkar, Annapoorna S. Kini, Marouane Boukhris, Philippe Gervais, Axel Linke, Lisa Crusius, David Holzhey, Josep Rodés-Cabau
Journal: Journal of the American College of Cardiology (2021)
Dysbiotic gut microbiota in patients with inflammatory rosacea: another clue towards the existence of a brain–gut–skin axis
Authors: O.M. Moreno‐Arrones, D. Ortega‐Quijano, V. Perez‐Brocal, D. Fernandez‐Nieto, N. Jimenez, E. las Heras, A. Moya, B. Perez‐Garcia
Journal: British Journal of Dermatology (2021)
Epidemiology of brain metastases and leptomeningeal disease
Authors: Nayan Lamba, Patrick Y Wen, Ayal A Aizer
Journal: Neuro-Oncology (2021)

Abstract Brain metastases affect a significant percentage of patients with advanced extracranial malignancies. Yet, the incidence of brain metastases remains poorly described, largely due to limitations of population-based registries, a lack of mandated reporting of brain metastases to federal agencies, and historical difficulties with delineation of metastatic involvement of individual organs using claims data. However, in 2016, the Surveillance Epidemiology and End Results (SEER) program released data relating to the presence vs absence of brain metastases at diagnosis of oncologic disease. In 2020, studies demonstrating the viability of utilizing claims data for identifying the presence of brain metastases, date of diagnosis of intracranial involvement, and initial treatment approach for brain metastases were published, facilitating epidemiologic investigations of brain metastases on a population-based level. Accordingly, in this review, we discuss the incidence, clinical presentation, prognosis, and management patterns of patients with brain metastases. Leptomeningeal disease is also discussed. Considerations regarding individual tumor types that commonly metastasize to the brain are provided.
IMPACT OF THE OUTPATIENT PRITIKIN INTENSIVE CARDIAC REHABILITATION PROGRAM ON DEPRESSION AND CARDIAC SELF-EFFICACY
Authors: Kristin M. McKenzie, Lauren Park, Elena Deych, Susan B. Racette, Eric J. Lenze, Michael Rich, Lisa de las Fuentes, Jennifer Jonagan, Serene Rashdi, Nidhi Talpade, Kristin Mongomery, Linda Peterson
Journal: Journal of the American College of Cardiology (2021)
Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine
Authors: Yael Shostak, Noa Shafran, Moshe Heching, Dror Rosengarten, Osnat Shtraichman, Dorit Shitenberg, Shai M Amor, Dafna Yahav, Haim Ben Zvi, Barak Pertzov, Mordechai R Kramer
Journal: The Lancet Respiratory Medicine (2021)
The Influence of Ligand Density and Degradability on Hydrogel Induced Breast Cancer Dormancy and Reactivation
Authors: Cindy J. Farino Reyes, Shantanu Pradhan, John H. Slater
Journal: Advanced Healthcare Materials (2021)

Abstract The role of hydrogel properties in regulating the phenotype of triple negative metastatic breast cancer is investigated using four cell lines: the MDA‐MB‐231 parental line and three organotropic sublines BoM‐1833 (bone‐tropic), LM2‐4175 (lung‐tropic), and BrM2a‐831 (brain‐tropic). Each line is encapsulated and cultured for 15 days in three poly(ethylene glycol) (PEG)‐based hydrogel formulations composed of proteolytically degradable PEG, integrin‐ligating RGDS, and the non‐degradable crosslinker N‐vinyl pyrrolidone. Dormancy‐associated metrics including viable cell density, proliferation, metabolism, apoptosis, chemoresistance, phosphorylated‐ERK and ‐p38, and morphological characteristics are quantified. A multimetric classification approach is implemented to categorize each hydrogel‐induced phenotype as: 1) growth, 2) balanced tumor dormancy, 3) balanced cellular dormancy, or 4) restricted survival, cellular dormancy. Hydrogels with high adhesivity and degradability promote growth. Hydrogels with no adhesivity, but high degradability, induce restricted survival, cellular dormancy in the parental line and balanced cellular dormancy in the organotropic lines. Hydrogels with reduced adhesivity and degradability induce balanced cellular dormancy in the parental and lung‐tropic lines and balanced tumor mass dormancy in bone‐ and brain‐tropic lines. The ability to induce escape from dormancy via dynamic incorporation of RGDS is also presented. These results demonstrate that ECM properties and organ‐tropism synergistically regulate cancer cell phenotype and dormancy.
Radionuclide-based molecular imaging allows CAR-T cellular visualization and therapeutic monitoring
Authors: Fuqiang Shao, Yu Long, Hao Ji, Dawei Jiang, Ping Lei, Xiaoli Lan
Journal: Theranostics (2021)

Chimeric antigen receptor T cell (CAR-T) therapy is a new and effective form of adoptive cell therapy that is rapidly entering the mainstream for the treatment of CD19-positive hematological cancers because of its impressive effect and durable responses. Huge challenges remain in achieving similar success in patients with solid tumors. The current methods of monitoring CAR-T, including morphological imaging (CT and MRI), blood tests, and biopsy, have limitations to assess whether CAR-T cells are homing to tumor sites and infiltrating into tumor bed, or to assess the survival, proliferation, and persistence of CAR-T cells in solid tumors associated with an immunosuppressive microenvironment. Radionuclide-based molecular imaging affords improved CAR-T cellular visualization and therapeutic monitoring through either a direct cellular radiolabeling approach or a reporter gene imaging strategy, and endogenous cell imaging is beneficial to reflect functional information and immune status of T cells. Focusing on the dynamic monitoring and precise assessment of CAR-T therapy, this review summarizes the current applications of radionuclide-based noninvasive imaging in CAR-T cells visualization and monitoring and presents current challenges and strategic choices.
Vadadustat in Patients with Anemia and Non–Dialysis-Dependent CKD
Authors: Glenn M. Chertow, Pablo E. Pergola, Youssef M.K. Farag, Rajiv Agarwal, Susan Arnold, Gabriel Bako, Geoffrey A. Block, Steven Burke, Fausto P. Castillo, Alan G. Jardine, Zeeshan Khawaja, Mark J. Koury, Eldrin F. Lewis, Tim Lin, Wenli Luo, Bradley J. Maroni, Kunihiro Matsushita, Peter A. McCullough, Patrick S. Parfrey, Prabir Roy-Chaudhury, Mark J. Sarnak, Amit Sharma, Bruce Spinowitz, Carol Tseng, James Tumlin, Dennis L. Vargo, Kimberly A. Walters, Wolfgang C. Winkelmayer, Janet Wittes, Kai-Uwe Eckardt
Journal: New England Journal of Medicine (2021)

Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production.
COMPARISON OF LEFT ATRIAL APPENDAGE SIZE USING COMPUTED TOMOGRAPHY VS. TRANSESOPHAGEAL ECHOCARDIOGRAPHY FOR WATCHMAN DEVICE IMPLANTATION
Authors: Yasar Sattar, Bachar Ahmad, Abdul-Rahman Suleiman, Muhammad Aamir, Abed Jabr, Nathan Zaher, Mohamed Zghouzi, Fnu Zafrullah, Waqas Ullah, M. Chadi Alraies
Journal: Journal of the American College of Cardiology (2021)
Germline Mutations in CTLA4 and Spectrum of Bone Marrow Features Overlapping with Aplastic Anemia and Large Granular Lymphocyte Lymphocytosis
Authors: Laura M Wake, Changqing Xie, Weixin Wang, Kristian T. Schafernak, V. Koneti Rao, Neal S. Young, Danielle M. Townsley, Gulbu Uzel, Katherine R Calvo
Journal: Blood (2017)
ASSOCIATION OF BMI ON WITH CLINICAL OUTCOMES IN PATIENTS WITH CORONARY DISEASE AND ADVANCED CHRONIC KIDNEY DISEASE: INSIGHTS FROM THE ISCHEMIA-CKD TRIAL
Authors: Evgeny Kretov, Zhen Huang, Mandeep Sidhu, Sean O'Brien, Jerome Fleg, Aleksei Prokhorikhin, Roy Mathew, David Maron, Judith Hochman, Sripal Bangalore
Journal: Journal of the American College of Cardiology (2021)
Association of Early Life Exposure to Antibiotics With Risk of Atopic Dermatitis in Sweden
Authors: Mwenya Mubanga, Cecilia Lundholm, Brian M. D’Onofrio, Marlene Stratmann, Anna Hedman, Catarina Almqvist
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Atopic dermatitis is associated with substantial morbidity in childhood. Further understanding of the underlying factors contributing to its onset is needed. <h3>Objective</h3> To assess the association of exposure to antibiotics in the prenatal period and early childhood with risk of atopic dermatitis in a nationwide population in Sweden. <h3>Design, Setting, and Participants</h3> This Swedish nationwide, register-based, prospective cohort study used data on mother-child pairs from the Swedish Medical Birth Register linked to other national registers for information on health, socioeconomic, and demographic data. Participants were followed up until an atopic dermatitis outcome, emigration, death, or the end of the study on December 31, 2015. Data for all singleton children and discordant siblings born between March 1, 2006, and December 31, 2010, were included. Data were analyzed from June 1, 2020, to October 31, 2020. <h3>Exposures</h3> Maternal exposure to systemic antibiotics during pregnancy as well as the child's exposure to systemic antibiotics during the first year of life, as defined by a dispensed prescription in the Swedish Prescribed Drug Register. <h3>Main Outcomes and Measures</h3> Time-to-event analyses were used to estimate the risk of outcome using attained age as a time scale. Atopic dermatitis was defined based on diagnoses in the National Patient Register and medication listed in the Swedish Prescribed Drug Register. Sibling-control analysis was performed to account for shared familial factors. <h3>Results</h3> Among the 722 767 singleton children, the mean (SD) age was 5.8 (2.4) years and 351 589 (48.6%) were female. During the follow-up period, 153 407 children (21.2%) were exposed to antibiotics in utero and 172 405 children (23.8%) were exposed during the first year of life. The risk of atopic dermatitis among children exposed to prenatal antibiotics was greater than that among children who were not exposed (adjusted hazard ratio [aHR], 1.10; 95% CI, 1.09-1.12). In the sibling-control analysis, no association was observed (aHR, 0.96; 95% CI; 0.92-1.00). Exposure to antibiotics during the first year of life was associated with a greater risk of atopic dermatitis (aHR, 1.52; 95% CI, 1.50-1.55), with attenuated associations in the sibling-control analysis (aHR, 1.24; 95% CI, 1.20-1.29). <h3>Conclusions and Relevance</h3> In this cohort study, exposure to antibiotics in early life was associated with an increased risk of atopic dermatitis in the general Swedish population, but this risk was partially confounded by familial factors. Research on the ways in which antibiotic use and other shared familial factors affect other atopic diseases may be warranted.
Optimization of Medication by Pharmacists in Older People With Multimorbidity for Improved Outcomes—Mirage or Reality?
Authors: Denis O’Mahony
Journal: JAMA Network Open (2021)

Thomas G. H. Kempen, MPharm; Maria Bertilsson, MSc; Nermin Hadziosmanovic, MSc; Karl-Johan Lindner, MPharm, PhD; Håkan Melhus, MD, PhD; Elisabet I. Nielsen, MPharm, PhD; Johanna Sulku, MPharm; Ulrika Gillespie, MPharm, PhD
Hyperpigmentation from Addison’s Disease
Authors: Farzahna Mohamed, Frederick J. Raal
Journal: New England Journal of Medicine (2021)

A 54-year-old man presented with confusion, vomiting, and progressive hyperpigmentation of the skin. The early-morning cortisol level and the serum level of corticotropin confirmed a diagnosis of primary adrenal insufficiency, or Addison’s disease.
Abstract 14515: Enhanced Expression of Renal Sodium-Glucose Cotransporter 2 (SGLT2) in Rats With Chronic Heart Failure: Role of Renal Nerves
Authors: Kenichi Katsurada, Shyam S Nandi, Neeru S Sharma, Kaushik P Patel
Journal: Circulation (2019)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are newly developed to treat type 2 diabetes. Recently, cardiovascular outcome studies demonstrated that SGLT2 inhibitors reduce heart failure (HF)...
GENDER-RELATED OUTCOMES IN PATIENTS WITH TAKOTSUBO CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Chanavuth Kanitsoraphan, Chol Techorueangwiwat, Jakrin Kewcharoen, Pattara Rattanawong, Dipanjan Banerjee
Journal: Journal of the American College of Cardiology (2021)
One dose of SARS-CoV-2 vaccine exponentially increases antibodies in individuals who have recovered from symptomatic COVID-19
Authors: Riccardo Levi, Elena Azzolini, Chiara Pozzi, Leonardo Ubaldi, Michele Lagioia, Alberto Mantovani, Maria Rescigno
Journal: Journal of Clinical Investigation (2021)

BACKGROUNDThe COVID-19 vaccines currently in use require 2 doses to achieve optimal protection. Currently, there is no indication as to whether individuals who have been exposed to SARS-CoV-2 should be vaccinated, or whether they should receive 1 or 2 vaccine doses.METHODSWe tested the antibody response developed after administration of the Pfizer/BioNTech vaccine in 124 health care professionals, of whom 57 had a previous history of SARS-CoV-2 exposure with or without symptoms.RESULTSPostvaccine antibodies in SARS-CoV-2-exposed individuals increased exponentially within 5 to 18 days after the first dose compared to naive subjects (P < 0.0001). In a multivariate linear regression (LR) model we showed that the antibody response depended on the IgG prevaccine titer and on the exposure to SARS-CoV-2. In symptomatic SARS-CoV-2-exposed individuals, IgG reached a plateau after the second dose, and those who voluntarily refrained from receiving the second dose (n = 7) retained their antibody response. Gastrointestinal symptoms, muscle pain, and fever markedly positively correlated with increased IgG responses. By contrast, all asymptomatic/paucisymptomatic and unexposed individuals showed an important increase after the second dose.CONCLUSIONOne vaccine dose is sufficient in symptomatic SARS-CoV-2-exposed subjects to reach a high titer of antibodies, suggesting no need for a second dose, particularly in light of current vaccine shortage.TRIAL REGISTRATIONClinicalTrials.gov NCT04387929.FUNDINGDolce & Gabbana and the Italian Ministry of Health (Ricerca corrente).
Association Between Gender-Affirming Surgeries and Mental Health Outcomes
Authors: Anthony N. Almazan, Alex S. Keuroghlian
Journal: JAMA Surgery (2021)

Requests for gender-affirming surgeries are rapidly increasing among transgender and gender diverse (TGD) people. However, there is limited evidence regarding the mental health benefits of these surgeries.To evaluate associations between gender-affirming surgeries and mental health outcomes, including psychological distress, substance use, and suicide risk.In this study, we performed a secondary analysis of data from the 2015 US Transgender Survey, the largest existing data set containing comprehensive information on the surgical and mental health experiences of TGD people. The survey was conducted across 50 states, Washington, DC, US territories, and US military bases abroad. A total of 27 715 TGD adults took the US Transgender Survey, which was disseminated by community-based outreach from August 19, 2015, to September 21, 2015. Data were analyzed between November 1, 2020, and January 3, 2021.The exposure group included respondents who endorsed undergoing 1 or more types of gender-affirming surgery at least 2 years prior to submitting survey responses. The comparison group included respondents who endorsed a desire for 1 or more types of gender-affirming surgery but denied undergoing any gender-affirming surgeries.Endorsement of past-month severe psychological distress (score of ≥13 on Kessler Psychological Distress Scale), past-month binge alcohol use, past-year tobacco smoking, and past-year suicidal ideation or suicide attempt.Of the 27 715 respondents, 3559 (12.8%) endorsed undergoing 1 or more types of gender-affirming surgery at least 2 years prior to submitting survey responses, while 16 401 (59.2%) endorsed a desire to undergo 1 or more types of gender-affirming surgery but denied undergoing any of these. Of the respondents in this study sample, 16 182 (81.1%) were between the ages of 18 and 44 years, 16 386 (82.1%) identified as White, 7751 (38.8%) identified as transgender women, 6489 (32.5%) identified as transgender men, and 5300 (26.6%) identified as nonbinary. After adjustment for sociodemographic factors and exposure to other types of gender-affirming care, undergoing 1 or more types of gender-affirming surgery was associated with lower past-month psychological distress (adjusted odds ratio [aOR], 0.58; 95% CI, 0.50-0.67; P < .001), past-year smoking (aOR, 0.65; 95% CI, 0.57-0.75; P < .001), and past-year suicidal ideation (aOR, 0.56; 95% CI, 0.50-0.64; P < .001).This study demonstrates an association between gender-affirming surgery and improved mental health outcomes. These results contribute new evidence to support the provision of gender-affirming surgical care for TGD people.
Tafenoquine for the prevention of Plasmodium vivax malaria relapse
Authors: James A Watson, Narimane Nekkab, Michael White
Journal: The Lancet Microbe (2021)

Tafenoquine (Krintafel) is the first new drug to be approved for the treatment of relapsing Plasmodium vivax malaria in 70 years. Tafenoquine was engineered to be a metabolically stable and thus slowly eliminated version of the 8-aminoquinoline, primaquine, providing relapse prevention with a single dose as compared to 1–2 weeks of daily primaquine. Although it also causes protracted haemolysis in individuals with glucose-6-phosphate dehydrogenase deficiency, it has the potential to accelerate P vivax elimination.
Origins, Biology, and Diseases of Tissue Macrophages
Authors: Nehemiah Cox, Maria Pokrovskii, Rocio Vicario, Frederic Geissmann
Journal: Annual Review of Immunology (2021)

Tissue-resident macrophages are present in most tissues with developmental, self-renewal, or functional attributes that do not easily fit into a textbook picture of a plastic and multifunctional macrophage originating from hematopoietic stem cells; nor does it fit a pro- versus anti-inflammatory paradigm. This review presents and discusses current knowledge on the developmental biology of macrophages from an evolutionary perspective focused on the function of macrophages, which may aid in study of developmental, inflammatory, tumoral, and degenerative diseases. We also propose a framework to investigate the functions of macrophages in vivo and discuss how inherited germline and somatic mutations may contribute to the roles of macrophages in diseases.
The Pop-Gen Pipeline Platform: A Software Platform for Population Genomic Analyses
Authors: Andrew Webb, Jared Knoblauch, Nitesh Sabankar, Apeksha Sukesh Kallur, Jody Hey, Arun Sethuraman
Journal: Molecular Biology and Evolution (2021)

The Pop-Gen Pipeline Platform (PPP) is a software platform for population genomic analyses. The PPP was designed as a collection of scripts that facilitate common population genomic workflows in a consistent and standardized Python environment. Functions were developed to encompass entire workflows, including input preparation, file format conversion, various population genomic analyses, and output generation. The platform has also been developed with reproducibility and extensibility of analyses in mind. The PPP is an open-source package that is available for download and use at https://ppp.readthedocs.io/en/latest/PPP_pages/install.html.