tbuckley/cabot-search huggingface dataset:
Clinicopathological features and their impacts on the prognoses of patients with nonurothelial carcinoma: A hospital-based cancer registry in Japan.
Authors: Yoshiyuki Nagumo, Takahiro Kojima, Kosuke Kojo, Tomokazu Kimura, Shuya Kandori, Koji Kawai, Ayako Okuyama, Takahiro Higashi, Hiroyuki Nishiyama
Journal: Journal of Clinical Oncology (2020)

555 Background: Urothelial carcinoma (UC) is the most common histology of genitourinary (GU) tract cancer. Non-UC tumors in the GU tract appear to be more aggressive than UC at that location, but the clinicopathological features and their impacts on the prognoses of the non-UC patients are not known due to the low numbers of these patients. Methods: We used Hospital-Based Cancer Registry (HBCR) data in Japan to extract non-UC cases, i.e., patients with adenocarcinoma (AC), squamous cell carcinoma (SCC), or small cell carcinoma (SmCC) of the GU tract who were diagnosed in 2008–2009 with histological confirmation and had received first course of treatment. We retrospectively analyzed the clinicopathological features of these patients, stratified by the bladder and the upper urinary tract (UUT) as tumor locations. We used a Cox proportional hazards regression to identify prognostic factors associated with the overall survival (OS). Results: Of the 8,095 cases at the bladder and 2,580 cases at the UUT, 384 (4.7%) and 131 (5.1%) non-UC cases were identified, respectively. The proportions of histologic subtypes in the bladder were 1.7% AC, 2.4% SCC, and 0.7% SmCC. In the UUT group, these proportions were 1.3%, 3.4%, and 0.4%, respectively. At both tumor locations, the distribution of ages was similar across all subtypes, with the age peak in the 70s. More patients with non-UC were diagnosed at an advanced clinical stage compared to the patients with UC at either location. The 5-yr OS rates of the non-UC patients with a tumor in the bladder and at the UUT were 40% and 26%, whereas the corresponding 5-yr OS rates among the UC patients were 61% and 52%, respectively. A multivariate analysis revealed that the presence of non-UC was significantly associated with increased mortality (hazard ratio 1.66, 95% confidence interval 1.48–1.87) regardless of the tumor location. Conclusions: The clinicopathological features of the non-UC patients were similar between both tumor locations. The presence of non-UC was associated with poor prognosis regardless of the tumor location. A standard of care must be established for non-UC patients, since the prognoses of these patients are not satisfactory.
Biological Behavior Regulation of Gold Nanoparticles via the Protein Corona
Authors: Yu Ma, Jin Hong, Ya Ding
Journal: Advanced Healthcare Materials (2020)

Abstract One of the difficulties in the translation of gold nanoparticles (GNPs) into clinical practice is the formation of the protein corona (PC) that causes the discrepancy between the in vitro and in vivo performance of GNPs. The PC formed on the surface of GNPs gives them a biological identity instead of an initial synthetic one. In most instances, this biological identity increases the particle size, leads to more clearance by the reticuloendothelial system, and causes less uptake by target cells. However, the performance of GNPs can still be improved by rewriting their original surface chemistry via the PC. This review specifically focuses on discussing the main influence factors, including the biological environment and physicochemical properties of GNPs, which affect the production and status of the PC. The status of the PC such as the amount, thickness, and composition subsequently influence the biological behavior of GNPs, especially their cellular uptake, cytotoxicity, biodistribution, and tumor targeting. Further understanding and revealing the impacts of the PC on the biological behavior of GNPs can be a promising and important strategy to regulate and improve the performance of GNP‐based biosystems in the future.
Synaptic Plasticity Forms and Functions
Authors: Jeffrey C. Magee, Christine Grienberger
Journal: Annual Review of Neuroscience (2020)

Synaptic plasticity, the activity-dependent change in neuronal connection strength, has long been considered an important component of learning and memory. Computational and engineering work corroborate the power of learning through the directed adjustment of connection weights. Here we review the fundamental elements of four broadly categorized forms of synaptic plasticity and discuss their functional capabilities and limitations. Although standard, correlation-based, Hebbian synaptic plasticity has been the primary focus of neuroscientists for decades, it is inherently limited. Three-factor plasticity rules supplement Hebbian forms with neuromodulation and eligibility traces, while true supervised types go even further by adding objectives and instructive signals. Finally, a recently discovered hippocampal form of synaptic plasticity combines the above elements, while leaving behind the primary Hebbian requirement. We suggest that the effort to determine the neural basis of adaptive behavior could benefit from renewed experimental and theoretical investigation of more powerful directed types of synaptic plasticity.
Erratum for Research Article: “Single-cell RNA-seq and computational analysis using temporal mixture modeling resolves T <sub>H</sub> 1/T <sub>FH</sub> fate bifurcation in malaria” by T. Lönnberg, V. Svensson, K. R. James, D. Fernandez-Ruiz, I. Sebina, R. Montandon, M. S. F. Soon, L. G. Fogg, A. S. Nair, U. N. Liligeto, M. J. T. Stubbington, L.-H. Ly, F. Otzen Bagger, M. Zwiessele, N. D. Lawrence, F. Souza-Fonseca-Guimaraes, P. T. Bunn, C. R. Engwerda, W. R. Heath, O. Billker, O. Stegle, A. …
Journal: Science Immunology (2018)

Figure S26 has been updated.
32P Ageing Biomarkers in an Elderly Breast Cancer Population: Correlation with Comprehensive Geriatric Assessment (CGA)
Authors: B. Brouwers, S. Hatse, K. Corthouts, E. Swerts, C. Kenis, P. Neven, M. Christiaens, R. Paridaens, P. Schöffski, H. Wildiers
Journal: Annals of Oncology (2012)
Opportunities and challenges in long-read sequencing data analysis
Authors: Shanika L. Amarasinghe, Shian Su, Xueyi Dong, Luke Zappia, Matthew E. Ritchie, Quentin Gouil
Journal: Genome biology (2020)

Abstract Long-read technologies are overcoming early limitations in accuracy and throughput, broadening their application domains in genomics. Dedicated analysis tools that take into account the characteristics of long-read data are thus required, but the fast pace of development of such tools can be overwhelming. To assist in the design and analysis of long-read sequencing projects, we review the current landscape of available tools and present an online interactive database, long-read-tools.org, to facilitate their browsing. We further focus on the principles of error correction, base modification detection, and long-read transcriptomics analysis and highlight the challenges that remain.
Bile acid composition regulates GPR119-dependent intestinal lipid sensing and food intake regulation in mice
Authors: Sei Higuchi, Tiara R Ahmad, Donovan A Argueta, Pedro A Perez, Chen Zhao, Gary J Schwartz, Nicholas V DiPatrizio, Rebecca A Haeusler
Journal: Gut (2020)

Lipid mediators in the GI tract regulate satiation and satiety. Bile acids (BAs) regulate the absorption and metabolism of dietary lipid in the intestine, but their effects on lipid-regulated satiation and satiety are completely unknown. Investigating this is challenging because introducing excessive BAs or eliminating BAs strongly impacts GI functions. We used a mouse model (Cyp8b1-/- mice) with normal total BA levels, but alterations in the composition of the BA pool that impact multiple aspects of intestinal lipid metabolism. We tested two hypotheses: BAs affect food intake by (1) regulating production of the bioactive lipid oleoylethanolamide (OEA), which enhances satiety; or (2) regulating the quantity and localisation of hydrolysed fat in small intestine, which controls gastric emptying and satiation.We evaluated OEA levels, gastric emptying and food intake in wild-type and Cyp8b1-/- mice. We assessed the role of the fat receptor GPR119 in these effects using Gpr119-/- mice.Cyp8b1-/- mice on a chow diet showed mild hypophagia. Jejunal OEA production was blunted in Cyp8b1-/- mice, thus these data do not support a role for this pathway in the hypophagia of Cyp8b1-/- mice. On the other hand, Cyp8b1 deficiency decreased gastric emptying, and this was dependent on dietary fat. GPR119 deficiency normalised the gastric emptying, gut hormone levels, food intake and body weight of Cyp8b1-/- mice.BAs regulate gastric emptying and satiation by determining fat-dependent GPR119 activity in distal intestine.
Early diagnosis of prostate cancer, AABH (Aspartyl Asparaginyl β-hydroxylase), a predictive biomarker: A serum immunoassay and personalized medicine.
Authors: Kiarash Moshiri
Journal: Journal of Clinical Oncology (2020)

353 Background: Prostate Cancer (PC) is the most common form of cancer in men in the United States. In their lifetime, approximately 1 out of every 6 American men will develop PC. The chances of developing PC increase dramatically after age 50 with more than 70% of cases occurring in individuals over 65 years of age. Methods: We have investigated the use of aspartyl (asparaginyl) β-hydroxylase (AABH) as a cancer biomarker. We have developed a sandwich ELISA for its detection. Here this assay was utilized to screen sera from patients with prostate cancer and PSA values in various ranges. Results: AABH levels were assessed in sera from 263 individuals with PC and 73 men over 50 years of age not known to have cancer. The levels of AABH in the two groups were &gt;3.00 ng/ml and &lt;3.00 ng/ml, respectively. The overall sensitivity and specificity of the test were 97.5% and 96%. AABH and PSA levels were also compared. The AABH values and sensitivities in individuals with PC and PSA values in the ranges &lt;2 ng/ml, 2-4 ng/ml and &gt;4 ng/ml were &gt;3.00 ng/ml, 99% (n=115); &gt; 3.00 ng/ml, 98% (n=64) and &gt;3.00 ng/ml, 95% (n=114). Conclusions: The present study of AABH indicates that cancer group can be clearly distinguished from normal healthy controls. Moreover, the study indicates that AABH might be used to identify disease in individuals with questionable PSA values. These results support to the establishment of routine screening of serum AABH as a means to detect those who need referral for prostate biopsy. The use of AABH testing may enhance current prostate cancer screening practices by both identifying individuals with low but suspicious PSA values who should be recommended for biopsy and reducing the number of false positive biopsies indicated by positive PSA tests. Serum AABH levels are significantly elevated in individuals with prostate cancer. Using a cutoff value of 3ng/ml, overall sensitivity of the assay for prostate cancer is 97%. The test has a specificity of 96% in healthy men over 50 years of age. AABH is elevated in prostate cancer tissue but NOT in normal prostate or in Benign Prostatic Hyperplasia (BPH). Serum AABH levels are NOT correlate with PSA levels.
T-Cell–Derived miRNA-214 Mediates Perivascular Fibrosis in Hypertension
Authors: Ryszard Nosalski, Mateusz Siedlinski, Laura Denby, Eilidh McGinnigle, Michal Nowak, Aurelie Nguyen Dinh Cat, Laura Medina-Ruiz, Marco Cantini, Dominik Skiba, Grzegorz Wilk, Grzegorz Osmenda, Julie Rodor, Manuel Salmeron-Sanchez, Gerard Graham, Pasquale Maffia, Delyth Graham, Andrew H. Baker, Tomasz J. Guzik
Journal: Circulation Research (2020)

Rationale: Despite increasing understanding of the prognostic importance of vascular stiffening linked to perivascular fibrosis in hypertension, the molecular and cellular regulation of this process is poorly understood. Objectives: To study the functional role of microRNA-214 (miR-214) in the induction of perivascular fibrosis and endothelial dysfunction driving vascular stiffening. Methods and Results: Out of 381 miRs screened in the perivascular tissues in response to Ang II (angiotensin II)-mediated hypertension, miR-214 showed the highest induction (8-fold, P =0.0001). MiR-214 induction was pronounced in perivascular and circulating T cells, but not in perivascular adipose tissue adipocytes. Global deletion of miR-214 − /− prevented Ang II-induced periaortic fibrosis, Col1a1 , Col3a1, Col5a1 , and Tgfb1 expression, hydroxyproline accumulation, and vascular stiffening, without difference in blood pressure. Mechanistic studies revealed that miR-214 −/− mice were protected against endothelial dysfunction, oxidative stress, and increased Nox2, all of which were induced by Ang II in WT mice. Ang II-induced recruitment of T cells into perivascular adipose tissue was abolished in miR-214 −/− mice. Adoptive transfer of miR-214 −/− T cells into RAG1 −/− mice resulted in reduced perivascular fibrosis compared with the effect of WT T cells. Ang II induced hypertension caused significant change in the expression of 1380 T cell genes in WT, but only 51 in miR-214 −/− . T cell activation, proliferation and chemotaxis pathways were differentially affected. MiR-214 −/− prevented Ang II-induction of profibrotic T cell cytokines ( IL-17 , TNF-α, IL-9 , and IFN-γ ) and chemokine receptors (CCR1, CCR2, CCR4, CCR5, CCR6, and CXCR3). This manifested in reduced in vitro and in vivo T cell chemotaxis resulting in attenuation of profibrotic perivascular inflammation. Translationally, we show that miR-214 is increased in plasma of patients with hypertension and is directly correlated to pulse wave velocity as a measure of vascular stiffness. Conclusions: T-cell–derived miR-214 controls pathological perivascular fibrosis in hypertension mediated by T cell recruitment and local profibrotic cytokine release.
Long-term health-related quality-of-life outcomes in a racially diverse cohort of prostate cancer patients receiving retropubic versus robotic prostatectomy.
Authors: Galen Conti, Huai-Ching Kuo, John Paul Flores, Jason Frankel, Katherine Levie, Nathan Jung, Fernando Caumont, Timothy C. Brand, John E. Musser, Sean P. Stroup, Kevin R. Rice, George Kallingal, Christopher Porter, Inger L. Rosner, Jennifer Cullen
Journal: Journal of Clinical Oncology (2020)

37 Background: This study compared 5-year health-related quality of life (HRQoL) outcomes among prostate cancer (PCa) patients who underwent a robotic-assisted radical prostatectomy (RARP) versus a radical retropubic prostatectomy (RRP), with a focus on race-specific outcomes for Caucasian American (CA) compared to African American (AA) men. RARPs have almost replaced RRPs in recent years, with few long-term studies focused on HRQoL and race. Methods: A prospective cohort study of HRQoL was conducted on patients diagnosed with PCa from 2007 to 2017 and enrolled in the Center for Prostate Disease Research (CPDR) Multicenter National Database. HRQoL was assessed with the EPIC instrument. Temporal changes in urinary and sexual-related quality of life domain scores were compared across surgery type (RARP versus RRP) at pre-treatment (“baseline”), 1-, 2-, 3-, 4-, and 5 years post-baseline. Longitudinal HRQoL patterns were modeled using generalized estimating equations (GEE), adjusting for baseline HRQoL and key clinical characteristics. Results: Of 497 PCa patients who met study inclusion criteria, 68% had RARP and 32% had RRP, with 22% AA men and 88% CA men. Baseline HRQoL domains were comparable across race and surgery type. In adjusted GEE analysis, no differences were noted between AA and CA patients. However, treatment-related differences were observed over time in urinary function (UF) and incontinence (UI) (p=0.02 and p=0.03, respectively), with lower HRQoL scores in RARP vs. RRP patients. Upon dual stratification by surgery type and race, the differences for UF and UI persisted (p=0.01 and p=0.03, respectively) with poorest outcomes observed, and similar trajectories of decline, for AA patients who received RARP. Conclusions: In this 10+ year prospective cohort study, AA patients receiving RARP had the poorest UF and UI outcomes which continued to decline for 5 years post treatment. In light of these findings, AA men considering RARP might benefit from discussions with their providers to set expectations regarding long-term urinary outcomes; though these decrements in HRQoL may be overshadowed by the minimally invasive nature of RARP.
Airway Epithelium Gene Expression Endotyping of Asthma and Airway Obstruction in Urban Children
Authors: Matthew Altman, Sima Ramratnam, Daniel Jackson, Scott Presnell, Peter Gergen, Leonard Bacharier, Meyer Kattan, George O, Robert Wood, Agustin Calatroni, William Busse, Cynthia Visness, James Gern
Journal: Journal of Allergy and Clinical Immunology (2020)
Clinical-genomic sub-classification of high-risk prostate cancer: Implications for tailoring therapy and clinical trial design.
Authors: Vinayak Muralidhar, Mohammed Alshalalfa, Daniel Eidelberg Spratt, Yang Liu, R. Jeffrey Karnes, Edward M. Schaeffer, Elai Davicioni, Felix Y Feng, Eric A. Klein, Jeffrey J. Tosoian, Alejandro Berlin, Robert Benjamin Den, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2020)

337 Background: Current risk stratification schema have limited prognostic performance in predicting outcome within National Comprehensive Cancer Network (NCCN) high-risk to very high-risk prostate cancer. Methods: Two multicenter high-risk cohorts were used for training (n = 214) and validation (n = 151) of a novel RNA microarray-based integrated clinical-genomic Classifier Optimized for Outcome in High-risk Prostate cancer (COOHP) to classify patients as COOHP favorable high-risk, standard high-risk, or very high-risk. Cox analysis was used to model metastasis-free survival (MFS), prostate cancer-specific survival (PCSS), and overall survival (OS). Model performance was compared to prior sub-classification systems using time-dependent c-indices. Results: Among NCCN high/very high-risk patients in the training cohort, 11% were classified as COOHP favorable high-risk, 70% as COOHP standard high-risk, and 18% as COOHP very high-risk. Patients with COOHP favorable high-risk disease had better rates of 5-year MFS compared to those with COOHP standard high-risk disease (94% vs 76%, hazard ratio [HR] 0.10, p = 0.02), and patients with COOHP very high-risk disease had worse 5-year MFS compared to those with COOHP standard high-risk disease (34% vs 76%, HR 3.5, p &lt; 0.0001). Similarly, patients with COOHP very high-risk disease had worse 10-year PCSS compared to those with COOHP standard high-risk disease (36% vs 82%, HR 4.4, p &lt; 0.0001). The c-indices for 5-year MFS and 10-year PCSS in the training cohort were 0.80 and 0.74, significantly improved compared to prior clinical and clinical-genomic risk stratification systems (0.62-0.69 for 5-year MFS and 0.56-0.63 for 10-year PCSS). These results were consistent in the validation cohort, where 5-year MFS significantly varied among the three COOHP subgroups (100% vs 89% vs 79%, p = 0.020), as did 10-year OS (100% vs 71% vs 53%, p = .040). Conclusions: A clinical-genomic risk stratification system specifically designed to discriminate prognosis in high-risk prostate cancer better identified favorable high-risk and very high-risk subsets of disease compared to prior clinical and clinical-genomic stratification systems.
Abstract 10416: Comparing Two Cardiopulmonary Rehabilitation Models in Severe Heart Failure and Chronic Obstructive Pulmonary Disease
Authors: Cynthia M Dougherty, Bonnie G Steele, Robert L Burr
Journal: Circulation (2018)

Introduction: Chronic obstructive pulmonary disease (COPD) and heart failure with reduced ejection fraction (HFrEF) are among the top four contributors to illness, disability, and death in our rapi...
Evaluation of the high affinity IgE receptor alpha-IgG1 Fc fusion protein (FCER1A-Fc) as a topical ocular anti-allergic agent
Authors: Toshiki Homma, Kazumasa Yokoyama, Fumiaki Itoh, Takashi Sakamoto, Mika Yamagishi, Chisei Ra, Yasuhiko Suzuki, Yoichi Inada
Journal: Journal of Allergy and Clinical Immunology (2020)
Is This Where We Stand After Decades of Research to Develop More Personalized Treatments for Depression?
Authors: Gerard Sanacora
Journal: JAMA Psychiatry (2020)

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Dupilumab Treatment Improves Sense of Smell in Patients With Chronic Rhinosinusitis With Nasal Polyps – Pooled Results From the SINUS-24 and SINUS-52 Phase 3 Trials
Authors: Joaquim Mullol, Joseph Han, John Bosso, Leda Mannent, Nikhil Amin, Seong Cho, Claus Bachert
Journal: Journal of Allergy and Clinical Immunology (2020)
NEXT: A phase II, open-label study of nivolumab adjuvant to chemoradiation in patients (pts) with localized muscle invasive bladder cancer.
Authors: Sumati Gupta, Benjamin Louis Maughan, Christopher B. Dechet, William Thomas Lowrance, Brock O Neil, Kristine E. Kokeny, Shane Lloyd, Jonathan David Tward, Kenneth M. Boucher, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2020)

TPS605 Background: In pts with localized muscle invasive bladder cancer (MIBC), trimodality bladder preserving therapy (TMT), with transurethral resection of bladder tumor, radio-sensitizing chemotherapy and definitive radiation, has up to a 50% risk of local and systemic relapse during the 2-year post treatment phase. We hypothesize that by inhibiting immune checkpoints, chemo-radiation induced tumor specific immune response will be enhanced both locally and abscopally, resulting in better failure-free survival (FFS). In the NEXT trial, we evaluate the efficacy of nivolumab after completion of the TMT in this setting. Methods: Pts with localized MIBC who have completed standard TMT are eligible. Pts receive nivolumab 480 mg intravenously every 4 weeks for up to 12 doses. Treatment with nivolumab begins within 90 days of completion of TMT. Subjects undergo surveillance cystoscopic and scan based assessments on study. Archived tumor tissue at baseline and at relapse is obtained for correlative studies. The primary endpoint is 2-year FFS. Secondary endpoints include FFS at 2 years in patients with intact bladder, rate of radical cystectomy (RC), cystoscopic local control, distant FFS in patients with intact bladder and those that undergo RC, overall survival, toxicity and quality of life. Exploratory endpoints include to characterize changes in immune cell subsets that can be correlated with clinical outcome and to assess the correlation of response to PD-L1 expression in pretreatment tumor tissue in the study subjects. The planned sample size for this single arm, open label trial is 28 pts. Kaplan-Meier methods will be used to plot survival endpoints and cystoscopic local control rates. Exact binomial methods will be used to provide 6 months, 1-year and 2-year estimates for these endpoints. The sample size justification is based on the maximum width of a two-sided 95% binomial confidence interval for 2 year FFS. With 28 evaluable subjects, a 95% exact binomial confidence interval, estimated using the method of Clopper-Pearson, will extend no more than 20% from the observed FFS. Clinical trial information: NCT03171025.