tbuckley/cabot-search huggingface dataset:
Abstract 9301: The Association of Pulse Pressure With Brain Structure and Function in Healthy Individuals
Authors: Andy Schumann, Feliberto de la Cruz, Karl-Juergen Baer
Journal: Circulation (2021)

Introduction: Hypertension is associated to changes of structural and functional brain networks that lead to impairment of cognitive performance. Recently, pulse pressure (PP) has been suggested as cardiovascular risk factor in hypertension. Hypothesis: In this study, we tested whether elevated PP is accompanied by brain structural and functional changes in healthy individuals without hypertension. Methods: We investigated 115 healthy subjects (41±17 years, 55% females) without cardiovascular, neurological or psychiatric disorders. Structural and functional brain imaging was performed on a 3 Tesla Siemens Prisma. We assessed cognitive function using the MATRICS Consensus Cognitive Battery. Participants were categorized by PP in normal and high PP (PP&gt;50 mmHg) according to resting blood pressure measurements in the laboratory. The normal PP group was reduced to match the high PP group with respect to age, gender, and education level. From resting functional brain images, we extracted whole-brain network connectivity between 260 independent brain regions to estimate global graph-theoretical features for integration (efficiency), resilience (assortativity), and segregation (clustering coefficient). Cortical thickness and volume were extracted from structural images using the Freesurfer image analysis suite. Results: While subgroups did not differ in terms of heart rate variability, baroreflex sensitivity was decreased in the high PP group. Furthermore, subjects with high PP performed worse in the trail-making task that primarily assesses processing speed (p&lt;0.001, FDR-corr.). Graph theoretical analyses revealed that functional brain networks in subjects with high PP were less efficient, clustered and resilient than normal PP (all p&lt;0.001, FDR-corr.). There were no differences in brain structure between groups. However, we found a negative correlation of PP with cortical thickness in the lateral prefrontal cortex over all subjects, suggesting that high PP is associated with cortical thinning in this area (corrected for age, gender and education). Conclusion: Elevated PP is associated with an altered organization of functional brain networks, lower cortical thickness and decreased processing speed in healthy subjects.
Bacterial Meningitis — A Review of Selected Aspects
Authors: Morton N. Swartz, Philip R. Dodge
Journal: New England Journal of Medicine (1965)

Behçet's syndrome. Behçet's syndrome is characterized by recurrent oral and genital ulcerations and relapsing ocular lesions, including uveitis, iridocyclitis with hypopyon and thrombosis or hemorrhage of retinal vessels. More recently, less common manifestations such as Central-nervous-system disease, thrombophlebitis, arthritis, erythema nodosum, epididymitis and cutaneous and gastrointestinal ulcerations have been described.111, 118 , 119 Although the frequency of neurologic complications is only 10 to 25 per cent120 , 121 nervous-system involvement has been associated with a high mortality.118 The initial manifestations of Behçet's syndrome may occur from several weeks to several decades before the onset of neurologic involvement. Essentially all parts of the central nervous system, . . .
Phase 1 Single and Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers
Authors: Varsha Iyer, Elizabeth Merica, Sebastien Ronseaux, Tressa Gamache, Nancy J. Mulrow, Anja Belcijan, Michael U. Callaghan
Journal: Blood (2021)
Baseline VWF:Ag Level and Body Mass Index Are Inverse Influencing Factors of Annualized Total Bleeding Rate and Annualized Joint Bleeding Rate Respectively in Severe-Type Adult Patients with Hemophilia a (PwHA) with Episodic Treatment with rFVIII
Authors: Chia-Yau Chang, Shiue-Wei Lai, Mei-Mei Cheng, Jung-Tzu Ku, Shu-Hsia Hu, Jia-Ruey Tsai, Chen-Hua Tsai, Pei-Yi Lai, Yen-Lin Liu, Chao-Neng Cheng, Yeu-Chin Chen
Journal: Blood (2021)
Safety and Efficacy of Isavuconazole in Patients Aged 65 Years or Older with Invasive Fungal Disease: A Post-Hoc Analysis from the VITAL and Secure Studies
Authors: Xinhong Fei, Jingbo Wang, Kamal Hamed, Marc Engelhardt, Laura L. Kovanda, Jin Ju Huang, Jean Li Yan, Jalal A. Aram
Journal: Blood (2021)
51 A novel cross-site analysis of Vectra® Polaris™ multiplex fluorescence PD-1/PD-L1 immunohistochemistry on colorectal cancer with high and low microsatellite instability
Authors: Sara Pollan, Bethany Remeniuk, Arezoo Hanifi, Kristin Roman, Bei Hopkins, Natalie Monteiro, Harry Nunns, Erinn Parnell, Josette William, Qingyan Au
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Colorectal cancer (CRC) is the third most diagnosed cancer in the United States with a projected 52,980 deaths in 2021. 1 Microsatellite instability-high (MSI-H) CRCs with deficiencies in mismatch repair (MMR) are significantly associated with positive response to immunotherapy and improved outcomes when treated with immune checkpoint inhibitors. Programmed cell death ligand-1 (PD-L1) is an effective biomarker of MSI-H status to identify CRC patients who will respond to treatment, however, reproducible quantification of programmed cell death receptor-1 (PD-1)/PD-L1 in the tumor microenvironment (TME) across laboratory sites has been under-reported. 2–3 In this study, our group directly addressed this issue by interrogating PD-1/PD-L1 cross-site at Akoya Biosciences and NeoGenomics Laboratories by employing the MOTiF™ PD-1/PD-L1 Panel kit along with the Vectra Polaris imaging system. Methods Serial sections from 40 CRC samples with known MSI status were stained at Akoya and NeoGenomics Laboratories using a modified MOTiF PD-1/PD-L1 Lung Panel Kit on the Leica BOND RX. Sections were scanned using the Vectra Polaris imaging system at both sites. Inter-site staining reproducibility was assessed using image analysis algorithms developed with inForm tissue analysis software. Cell counts and densities were calculated using the R-script package PhenoptrReports and correlations were plotted per marker. Results The average signal intensity for all markers/Opal fluorophores was within the recommended ranges of 10–30 normalized counts, with the exception of Polaris 780, which has an advised range of 1–10. This indicates the protocol stained successfully and reproducibly across all serial sections at both sites. Inter-site concordance analysis of cell densities for each marker yielded an average R2 value of ≥0.70. H-Score of PD-L1 quantified at the cell membrane trended with MSI status (stable/high). Conclusions This study demonstrated that the MOTiF PD-1/PD-L1 Panel kit imaged in conjunction with the Vectra Polaris is not only a reliable assay that can be run across different sites, based on the concordant cross-site data, but that re-optimization of the kit allows for the assay panel to be successfully adapted to other cancers, such as CRC, which can then capture biological differences across a multitude of samples. References American Cancer Society https://www.cancer.org/cancer/colon-rectal-cancer/about/key-statistics.html Yi M, Jiao D, Xu H, Liu Q, Zhao W, Han X, et al. Biomarkers for predicting efficacy of PD-1/PD-L1 inhibitors. Mol Cancer 2018; 17 (1):129 Lemery S, Keegan P, Pazdur R. First FDA approval agnostic of cancer site - when a biomarker defines the indication. N Engl J Med 2017;377(15):1409–12.
Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia
Authors: Rong-Hui Han, He-Meng Huang, Hong Han, Hao Chen, Fei Zeng, Xiang Xie, Dan-Yong Liu, Yin Cai, Liang-Qing Zhang, Xin Liu, Zheng-Yuan Xia, Jing Tang
Journal: Military Medical Research (2021)

Abstract Background Administration of propofol, an intravenous anesthetic with antioxidant property, immediately at the onset of post-ischemic reperfusion (propofol postconditioning, P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion injury, while the underlying mechanism remains incompletely understood. The FoxO transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection, however, the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown. Methods Rat heart-derived H9c2 cells were exposed to high glucose (HG) for 48 h (h), then subjected to hypoxia/reoxygenation (H/R, composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol (P-PostC) at the onset of reoxygenation. After having identified the optical concentration of propofol, H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia. Results The results showed that HG with or without H/R decreased cell viability, increased lactate dehydrogenase (LDH) leakage and the production of reactive oxygen species (ROS) in H9c2 cells, all of which were significantly reversed by propofol (P-PostC), especially at the concentration of 25 µmol/L (P25) (all P &lt; 0.05, NC vs . HG; HG vs. HG + HR; HG + HR + P12.5 or HG + HR + P25 or HG + HR + P50 vs. HG + HR). Moreover, we found that propofol (P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression (all P &lt; 0.05, HG + HR + P25 vs . HG + HR). The protective effects of propofol (P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a (all P &lt; 0.05, HG + HR + P25 vs. HG + HR + P25 + siRNA-1 or HG + HR + P25 + siRNA-5). Conclusion It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.
The role of curettage as an intervention for basal cell carcinoma. Response to ‘Interventions for basal cell carcinoma: abridged Cochrane systematic review and GRADE assessments'
Authors: D. Mazzoni, J. Muir
Journal: British Journal of Dermatology (2021)

We read with interest the Cochrane review exploring management of basal cell carcinoma (BCC).1 Despite being the most common of all malignancies, few studies met the requirements for inclusion in this analysis. Even then, the evidence from randomised control trials was mainly low to moderate. According to the Cochrane review website, “Each Cochrane Review is a systematic review that has been prepared and supervised by a Cochrane Review Group (editorial team). It attempts to identify, appraise and synthesize all the empirical evidence that meets pre-specified eligibility criteria to answer a specific research question.”
Four-Fold Increased Mortality from Sars-Cov-2 Infection in Patients with Hematologic Versus Non-Hematologic Malignancies Treated at the Largest Tertiary COVID-19 Center in Chicago/Rush University Medical Center (March 1, 2020-December 31,2020)
Authors: Nicole K. Yun, Praneeth Chebrolu, Paul R. Yarnold, Joshua Thomas, James L. Coggan, Anmol Baranwal, Charles L. Bennett, Ankur Varma, Timothy M. Kuzel
Journal: Blood (2021)
Nutrition As a Predictor of Microbiome Injury in Allo-HCT
Authors: Anqi Dai, Peter A. Adintori, Melissa D Docampo, Corrado Zuanelli Brambilla, Marissa L. Buchan, Antonio L.C. Gomes, Marina D Burgos da Silva, Kate A Markey, Sean M Devlin, Annelie Clurman, John B Slingerland, Abigail J. Johnson, Dan Knights, Robert R. Jenq, Sergio A Giralt, Miguel-Angel Perales, Marcel van den Brink, Jonas Schluter, Jonathan U Peled
Journal: Blood (2021)
Serine and Threonine Phosphorylation Marks Proteins for Degradation By Clpxp
Authors: Yue Feng, Yulia Jitkova, Harjeet Soor, Suzanne Trudel, Kaitlin Lees, Kaylen Soriano, Siavash Vahidi, Andrei Yudin, Aaron D Schimmer
Journal: Blood (2021)
The Data Use Ontology to streamline responsible access to human biomedical datasets
Authors: Jonathan Lawson, Moran N. Cabili, Giselle Kerry, Tiffany Boughtwood, Adrian Thorogood, Pinar Alper, Sarion R. Bowers, Rebecca R. Boyles, Anthony J. Brookes, Matthew Brush, Tony Burdett, Hayley Clissold, Stacey Donnelly, Stephanie O.M. Dyke, Mallory A. Freeberg, Melissa A. Haendel, Chihiro Hata, Petr Holub, Francis Jeanson, Aina Jene, Minae Kawashima, Shuichi Kawashima, Melissa Konopko, Irene Kyomugisha, Haoyuan Li, Mikael Linden, Laura Lyman Rodriguez, Mizuki Morita, Nicola Mulder, Jean Muller, Satoshi Nagaie, Jamal Nasir, Soichi Ogishima, Vivian Ota Wang, Laura D. Paglione, Ravi N. Pandya, Helen Parkinson, Anthony A. Philippakis, Fabian Prasser, Jordi Rambla, Kathy Reinold, Gregory A. Rushton, Andrea Saltzman, Gary Saunders, Heidi J. Sofia, John D. Spalding, Morris A. Swertz, Ilia Tulchinsky, Esther J. van Enckevort, Susheel Varma, Craig Voisin, Natsuko Yamamoto, Chisato Yamasaki, Lyndon Zass, Jaime M. Guidry Auvil, Tommi H. Nyrönen, Mélanie Courtot
Journal: Cell Genomics (2021)

Human biomedical datasets that are critical for research and clinical studies to benefit human health also often contain sensitive or potentially identifying information of individual participants. Thus, care must be taken when they are processed and made available to comply with ethical and regulatory frameworks and informed consent data conditions. To enable and streamline data access for these biomedical datasets, the Global Alliance for Genomics and Health (GA4GH) Data Use and Researcher Identities (DURI) work stream developed and approved the Data Use Ontology (DUO) standard. DUO is a hierarchical vocabulary of human and machine-readable data use terms that consistently and unambiguously represents a dataset's allowable data uses. DUO has been implemented by major international stakeholders such as the Broad and Sanger Institutes and is currently used in annotation of over 200,000 datasets worldwide. Using DUO in data management and access facilitates researchers' discovery and access of relevant datasets. DUO annotations increase the FAIRness of datasets and support data linkages using common data use profiles when integrating the data for secondary analyses. DUO is implemented in the Web Ontology Language (OWL) and, to increase community awareness and engagement, hosted in an open, centralized GitHub repository. DUO, together with the GA4GH Passport standard, offers a new, efficient, and streamlined data authorization and access framework that has enabled increased sharing of biomedical datasets worldwide.
Advances in Clinical Management of Persistent Postconcussion Symptoms—The Danish National Clinical Guideline
Authors: Keith Owen Yeates, Kathryn J. Schneider, Noah D. Silverberg
Journal: JAMA Network Open (2021)

Hana Malá Rytter, PhD; Heidi J. Graff, PhD; Henriette K. Henriksen, PT; Nicolai Aaen, MSc; Jan Hartvigsen, PhD; Morten Hoegh, PhD; Ivan Nisted, MSc; Erhard Trillingsgaard Næss-Schmidt, PhD; Lisbeth Lund Pedersen, MSc, PT; Henrik Winther Schytz, MD, PhD, DMSc; Mille Møller Thastum, MSc, PhD; Bente Zerlang, OT; Henriette Edemann Callesen, PhD
The Impact of the COVID-19 Pandemic on the Diagnosis and Management of Patients with Classical Hodgkin Lymphoma: A Single-Center Experience
Authors: Selin Kucukyurt, Kübra Şahin, Umut Yılmaz, Abdülkadir Erçalışkan, Tuba Özkan Tekin, Damla Ortaboz, Tuğrul Elverdi, Ayşe Salihoğlu, Muhlis Cem Ar, Şeniz Öngören, Zafer Başlar, Ahmet Emre Eskazan
Journal: Blood (2021)
Upfront Autologous Stem Cell Transplantation (ASCT) Vs Carfilzomib-Cyclophosphamide-Dexamethasone (KCd) Consolidation in Transplant-Eligible, Newly Diagnosed (NDTE) Multiple Myeloma (MM): Results of the Cardamon Study According to Cytogenetic Risk
Authors: Kwee Yong, William Wilson, Marquita Camilleri, Karthik Ramasamy, Matthew Streetly, Jonathan Sive, Ceri A Bygrave, Michael Chapman, Ruth M. de Tute, Selina J Chavda, Elizabeth H Phillips, Maria del Mar Cuadrado, Gavin Pang, Richard Jenner, Tushhar Dadaga, Sumaiya Kamora, James Cavenagh, Laura Clifton-Hadley, Roger G Owen, Rakesh Popat
Journal: Blood (2021)
Chronic Lymphocytic Leukemia Comorbidity Index (CLL-CI), a Novel Comorbidity Measure, Predicts Outcomes in the Context of Targeted Agents and in a Large National Registry
Authors: Max J. Gordon, Andy Kaempf, Emelie Rotbain, Andrea Sitlinger, Geoffrey Shouse, Matthew Mei, Danielle M. Brander, Tareq Salous, Brian T. Hill, Michael Choi, Jonathon B. Cohen, Deborah M. Stephens, Dan O. Persky, Krish Patel, Mazyar Shadman, Byung Park, Carsten Utoft Niemann, Alexey V. Danilov
Journal: Blood (2021)
Combining CTLA-4 and angiopoietin-2 blockade in patients with advanced melanoma: a phase I trial
Authors: Patrick A Ott, Matthew Nazzaro, Kathleen L Pfaff, Evisa Gjini, Kristen D Felt, Jacquelyn O Wolff, Elizabeth I Buchbinder, Rizwan Haq, Ryan J Sullivan, Donald P Lawrence, David F McDermott, Mariano Severgnini, Anita Giobbie-Hurder, Scott J Rodig, F Stephen Hodi
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Angiogenic factors promote the growth of tumor vasculature, modulate lymphocyte trafficking into tumors, and inhibit maturation of dendritic cells. We hypothesized that MEDI3617, a human IgG1 kappa monoclonal antibody directed against human angiopoietin-2, in combination with tremelimumab (treme), an IgG2 monoclonal antibody blocking cytotoxic T-lymphocyte-associated protein- (CTLA-4), is safe in patients with advanced melanoma. Methods In a phase I, 3+3 dose escalation trial, patients with metastatic or unresectable melanoma received treme in combination with MEDI3617. The primary objectives of the study were safety and determination of recommended phase II dose (RP2D). The secondary objectives included determination of 6-month and 1-year overall survival and best overall response rate. Immune cell populations and soluble factors were assessed in peripheral blood and metastatic tumors using Fluorescence activated cell sorting (FACS), Luminex, and multiplexed immunofluorescence. Results Fifteen patients (median age: 62) were enrolled in the study (3 patients in cohort 1: treme at 10 mg/kg and MEDI3617 at 200 mg; and 12 patients in cohort 2: treme at 10 mg/kg and MEDI3617 at 600 mg). The most common all-grade treatment-related adverse events were rash, pruritus, fatigue, and extremity edema. No dose-limiting toxicities were observed. Cohort 2 was determined to be the RP2D. There were no patients with confirmed immune-related complete response or immune-related partial response. Six of 15 patients had immune-related stable disease, resulting in a disease control rate of 0.40 (95% CI 0.16 to 0.68). An increase in frequencies of circulating inducible T-cell costimulator (ICOS) + and human leukocyte antigen (HLA)-DR + CD4 + and CD8 + T cells and production of Interleukin-2 and Interleukin-10 was observed post therapy. Conclusions Tremelimumab in combination with MEDI3617 is safe in patients with advanced melanoma. Angiopoietin-2 inhibition in combination with immune checkpoint inhibition warrants further exploration. Trial registration number NCT02141542 .
Venetoclax Combined with Daunorubicin and Cytarabine (DAV) As Induction Therapy in De Novo Young Adult Acute Myeloid Leukemia
Authors: Huafeng Wang, Liping Mao, Wanzhuo Xie, Hongyan Tong, Min Yang, Gaixiang Xu, Xiujin Ye, Ying Lu, Juying Wei, Wenyuan Mai, De Zhou, Jie Jin, Hong-Hu Zhu
Journal: Blood (2021)
HBV antigens quantity: duration and effect on functional cure
Authors: Antonio Bertoletti, Carolina Boni
Journal: Gut (2021)

HBV is a DNA virus that coevolved with humans.1 Different from many other viruses that are detected only after amplification of their genetic material, HBV is characterised by the production of a progeny of infectious virions, but also of high concentrations (5–10 μg/mL) of viral proteins.

These proteins are ‘byproducts’ of the synthesis of the proteins coded by HBV core and HBV pre-S1, pre-S2 and S genes, the building blocks of the nucleocapsid (the internal part of the virus containing HBV–DNA) and of the HBV envelope. The proteins derived from the nucleocapsid gene and defined as HBcrAg are composed of truncated or immature forms of the nucleocapsid protein: the HBeAg (defined also as p17, a fully secreted form of truncated nucleoprotein), p22 (a longer version of p17) and HBcAg (incomplete core particles, a ‘naked’ HBV).2 The pre-S1, pre-S2 and S gene products are instead envelope components of the mature HBV virions but they are produced in large excess thereby giving rise also to a large quantity of defective non-infectious particles (spheres and filaments) (detailed molecular description reviewed in Bruss3). These non-infectious viral proteins (both HBcrAg and HBsAg) are secreted into the blood stream, impact host immunity and likely allow HBV to persist in humans more efficiently. For example, HBeAg appears (in animal models) to play a role in the suppression of nucleocapsid-specific T cells in vertical infection.4 The defective particles that constitute HBsAg have been instead hypothesised to have a broader effect on the host antiviral immunity. Defective particles act primarily as a decoy for protective anti-HBs antibodies, since they outnumber the infectious virions by 103–106-fold5 and can bind anti-HBs antibodies. HBsAg is also associated with selective defects of HBs-specific …
A Randomized, Double-Blind, Single-Dose Phase 1 Comparative Pharmacokinetic Study Comparing SB12 (Eculizumab Biosimilar) with Reference Eculizumab in Healthy Volunteers
Authors: Hyun A Lee, Hyerin Jang, Yeonsoo Kim, Deokyoon Jeong, Jieun Lee, Jin Ah Jung, Roberta Demichelis
Journal: Blood (2021)
Impact of Daratumumab Monotherapy on Bone Metabolism Parameters in Patients with Relapsed and/or Refractory Multiple Myeloma Who Have Received at Least Two Prior Lines of Therapy Including Lenalidomide and a Proteasome Inhibitor: Outcomes of the Phase 2 Rebuild Study
Authors: Evangelos Terpos, Efstathios Kastritis, Evdoxia Hatjiharissi, Eirini Katodritou, Evangelos Eleutherakis Papaiakovou, Evgenia Verrou, Maria Gavriatopoulou, Alexandros Leonidakis, Ioannis Ntanasis-Stathopoulos, Sosana Delimpasi, Marie-Christine Kyrtsonis, Maria Papaioannou, Argiris Symeonidis, Meletios A. Dimopoulos
Journal: Blood (2021)
Glucocorticoid-Resistant B-Cell Acute Lymphoblastic Leukemic Cells Can be Targeted By BCR-Signaling Inhibition
Authors: Jolanda Sarno, Pablo Domizi, Yuxuan Liu, Milton Merchant, Dorra Jedoui, Astraea Jager, Andrea Biondi, Giuseppe Gaipa, Alessio Felice Bava, Kara L. Davis
Journal: Blood (2021)
Molecular and functional architecture of striatal dopamine release sites
Authors: Aditi Banerjee, Cordelia Imig, Karthik Balakrishnan, Lauren Kershberg, Noa Lipstein, Riikka-Liisa Uronen, Jiexin Wang, Xintong Cai, Fritz Benseler, Jeong Seop Rhee, Benjamin H. Cooper, Changliang Liu, Sonja M. Wojcik, Nils Brose, Pascal S. Kaeser
Journal: Neuron (2021)