tbuckley/cabot-search huggingface dataset:
Abstract DP-010: INTRAPERITONEAL CHEMOTHERAPY USE AND OUTCOMES: EXPLORATION OF UPMC OVARIAN CANCER REGISTRY DATA
Authors: Adambekov S, Wang S, Taylor S, Buckanovich R, Coffman L, Edwards RP, Linkov F
Journal: Clinical Cancer Research (2019)

Abstract BACKGROUND: Ovarian cancer (OC) is the deadliest gynecologic cancer. Despite randomized clinical trials showing improved survival for patients receiving intraperitoneal chemotherapy (IP), IP has not received a wide use outside of specialty hospitals. The aim of this study was to explore the impact of IP on OC patient survival and to evaluate whether treatment facility type impacted the outcomes. METHODS: Detailed demographic and clinical information on OC patients (N=2924) who underwent treatment in UPMC facilities between 2000-2016 was obtained from the UPMC Cancer Registry. Duplicate records, rare, grade 1, and non-epithelial tumors were excluded. Kaplan-Meier plots were constructed to compare 10-year survival rates based on the chemotherapy type (IP vs. no-IP), cancer grade, cancer stage, surgery type, neoadjuvant and treatment facility (specialized vs. community). Multivariable Gray's models and logistic regression model were fitted to evaluate the effect of different factors on survival and tumor recurrence respectively. Two tailed P-values &amp;lt;0.05 were considered significant. R software package was used to analyze the data. RESULTS: The final sample consisted from 1840 patients (250 IP and 1590 no-IP). IP chemotherapy was used only in 14% of OC patients and was associated with improved long-term survival. Similarly, cases reported by specialty treatment facilities (Magee and Passavant) had better survival compared to other hospitals. Multivariable Gray's model showed that IP and younger age were significantly associated with lower hazard of death, whereas higher cancer stage is significantly associated with higher hazard of death. Multivariable logistic regression showed that IP is not significantly associated with recurrence after adjusting for median income in the zip code of patient residence and cancer stage. CONCLUSIONS: These findings demonstrate enhanced long-term survival of patients treated with IP therapy at specialty centers. Increasing IP therapy use in clinical practice for OC patient treatment may be important strategy to improve OC outcomes. Citation Format: Adambekov S, Wang S, Taylor S, Buckanovich R, Coffman L, Edwards RP, Linkov F. INTRAPERITONEAL CHEMOTHERAPY USE AND OUTCOMES: EXPLORATION OF UPMC OVARIAN CANCER REGISTRY DATA [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr DP-010.
p38 Mitogen-activated protein kinase regulates chamber-specific perinatal growth in heart
Authors: Tomohiro Yokota, Jin Li, Jijun Huang, Zhaojun Xiong, Qing Zhang, Tracey Chan, Yichen Ding, Christoph Rau, Kevin Sung, Shuxun Ren, Rajan Kulkarni, Tzung Hsiai, Xinshu Xiao, Marlin Touma, Susumu Minamisawa, Yibin Wang
Journal: Journal of Clinical Investigation (2020)

In the mammalian heart, the left ventricle (LV) rapidly becomes more dominant in size and function over the right ventricle (RV) after birth. The molecular regulators responsible for this chamber-specific differential growth are largely unknown. We found that cardiomyocytes in the neonatal mouse RV had lower proliferation, more apoptosis, and a smaller average size compared with the LV. This chamber-specific growth pattern was associated with a selective activation of p38 mitogen-activated protein kinase (MAPK) activity in the RV and simultaneous inactivation in the LV. Cardiomyocyte-specific deletion of both the Mapk14 and Mapk11 genes in mice resulted in loss of p38 MAPK expression and activity in the neonatal heart. Inactivation of p38 activity led to a marked increase in cardiomyocyte proliferation and hypertrophy but diminished cardiomyocyte apoptosis, specifically in the RV. Consequently, the p38-inactivated hearts showed RV-specific enlargement postnatally, progressing to pulmonary hypertension and right heart failure at the adult stage. Chamber-specific p38 activity was associated with differential expression of dual-specific phosphatases (DUSPs) in neonatal hearts, including DUSP26. Unbiased transcriptome analysis revealed that IRE1α/XBP1-mediated gene regulation contributed to p38 MAPK-dependent regulation of neonatal cardiomyocyte proliferation and binucleation. These findings establish an obligatory role of DUSP/p38/IRE1α signaling in cardiomyocytes for chamber-specific growth in the postnatal heart.
High dose-rate brachytherapy of localized prostate cancer converts tumors from cold to hot
Authors: Simon P Keam, Heloise Halse, Thu Nguyen, Minyu Wang, Nicolas Van Kooten Losio, Catherine Mitchell, Franco Caramia, David J Byrne, Sue Haupt, Georgina Ryland, Phillip K Darcy, Shahneen Sandhu, Piers Blombery, Ygal Haupt, Scott G Williams, Paul J Neeson
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Prostate cancer (PCa) has a profoundly immunosuppressive microenvironment and is commonly immune excluded with few infiltrative lymphocytes and low levels of immune activation. High-dose radiation has been demonstrated to stimulate the immune system in various human solid tumors. We hypothesized that localized radiation therapy, in the form of high dose-rate brachytherapy (HDRBT), would overcome immune suppression in PCa. Methods To investigate whether HDRBT altered prostate immune context, we analyzed preradiation versus postradiation human tissue from a cohort of 24 patients with localized PCa that received HDRBT as primary treatment (RadBank cohort). We performed Nanostring immune gene expression profiling, digital spatial profiling, and high-throughput immune cell multiplex immunohistochemistry analysis. We also resolved tumor and nontumor zones in spatial and bioinformatic analyses to explore the immunological response. Results Nanostring immune profiling revealed numerous immune checkpoint molecules (eg, B7-H3, CTLA4, PDL1, and PDL2) and TGFβ levels were increased in response to HDRBT. We used a published 16-gene tumor inflammation signature (TIS) to divide tumors into distinct immune activation states (high: hot , intermediate and low: cold ) and showed that most localized PCa are cold tumors pre-HDRBT. Crucially, HDRBT converted 80% of these ‘cold’-phenotype tumors into an ‘intermediate’ or ‘hot’ class. We used digital spatial profiling to show these HDRBT-induced changes in prostate TIS scores were derived from the nontumor regions. Furthermore, these changes in TIS were also associated with pervasive changes in immune cell density and spatial relationships—in particular, between T cell subsets and antigen presenting cells. We identified an increased density of CD4 + FOXP3 + T cells, CD68 + macrophages and CD68 + CD11c + dendritic cells in response to HDRBT. The only subset change specific to tumor zones was PDL1 - macrophages. While these immune responses were heterogeneous, HDRBT induced significant changes in immune cell associations, including a gained T cell and HMWCK + PDL1 + interaction in tumor zones. Conclusion In conclusion, we showed HDRBT converted “cold” prostate tumors into more immunologically activated “hot” tissues, with accompanying spatially organized immune infiltrates and signaling changes. Understanding and potentially harnessing these changes will have widespread implications for the future treatment of localized PCa, including rational use of combination radio-immunotherapy.
Collaborative Ocular Tuberculosis Study Consensus Guidelines on the Management of Tubercular Uveitis—Report 2
Authors: Rupesh Agrawal, Ilaria Testi, Baharam Bodaghi, Talin Barisani-Asenbauer, Peter McCluskey, Aniruddha Agarwal, John H. Kempen, Amod Gupta, Justine R. Smith, Marc D. de Smet, Yew Sen Yuen, Sarakshi Mahajan, Onn Min Kon, Quan Dong Nguyen, Carlos Pavesio, Vishali Gupta, Rupesh Agrawal, Ilaria Testi, Baharam Bodaghi, Talin Barisani-Asenbauer, Peter McCluskey, Aniruddha Agarwal, John H. Kempen, Amod Gupta, Justine R. Smith, Yew Sen Yuen, Sarakshi Mahajan, Mamta Agarwal, Manisha Agarwal, Ashutosh Aggarwal, Kanika Aggarwal, Mukesh Agrawal, Hassan Al-Dhibi, Sofia Androudi, Fatma Asyari, Manohar Babu Balasundaram, Kalpana Babu Murthy, Edoardo Baglivo, Alay Banker, Reema Bansal, Soumyava Basu, Digamber Behera, Jyotirmay Biswas, Ester Carreño, Laure Caspers, Soon Phaik Chee, Romi Chhabra, Luca Cimino, Luz Elena Concha del Rio, Emmett T. Cunningham, Andrè Luiz Land Curi, Dipankar Das, Janet Davis, Marc DeSmet, Ekaterina Denisova, Alastair K. Denniston, Marie-Hélène Errera, Alejandro Fonollosa, Amala George, Debra A. Goldstein, Yan Guex Crosier, Dinesh Visva Gunasekeran, Avinash Gurbaxani, Alessandro Invernizzi, Hazlita M. Isa, Shah M.d. Islam, Nicholas Jones, Deeksha Katoch, Moncef Khairallah, Amit Khosla, Michal Kramer, Amitabh Kumar, Atul Kumar, Rina La Distia Nora, Richard Lee, Careen Lowder, Saurabh Luthra, Padmamalini Mahendradas, Dorine Makhoul, Shahana Mazumdar, Salil Mehta, Elisabetta Miserocchi, Manabu Mochizuki, Oli S. Mohamed, Cristina Muccioli, Marion R. Munk, Somasheila Murthy, Shishir Narain, Heloisa Nascimento, Piergiorgio Neri, Myhanh Nguyen, Annabelle A. Okada, Pinar Ozdal, Alan Palestine, Francesco Pichi, Dhananjay Raje, S.R. Rathinam, Andres Rousselot, Ariel Schlaen, Shobha Sehgal, H. Nida Sen, Aman Sharma, Kusum Sharma, Samir S. Shoughy, Nirbhai Singh, Ramandeep Singh, Masoud Soheilian, Sudharshan Sridharan, Jennifer E. Thorne, Christoph Tappeiner, Stephen Teoh, Maria Sofia Tognon, Ilknur Tugal-Tutkun, Mudit Tyagi, Harvey Uy, Daniel Vitor Vasconcelos Santos, Natasa Vidovic Valentincic, Mark Westcott, Ryoji Yanai, Bety Yanez Alvarez, Rahman Zahedur, Manfred Zierhut, Zheng Xian, Onn Min Kon, Quan Dong Nguyen, Carlos Pavesio, Vishali Gupta
Journal: Ophthalmology (2020)
Usefulness of endoscopic ultrasound-guided fine-needle biopsy for the diagnosis of autoimmune pancreatitis using a 22-gauge Franseen needle: a prospective multicenter study
Authors: Takuya Ishikawa, Hiroki Kawashima, Eizaburo Ohno, Hiroki Suhara, Daijuro Hayashi, Takeshi Hiramatsu, Hiroshi Matsubara, Takahisa Suzuki, Takamichi Kuwahara, Eri Ishikawa, Yoshie Shimoyama, Fumie Kinoshita, Yoshiki Hirooka, Mitsuhiro Fujishiro
Journal: Endoscopy (2020)

Abstract Background Detailed histological evaluation is important in the diagnosis of autoimmune pancreatitis (AIP). However, it remains challenging to obtain adequate tissue from the pancreas. Recently, several reports have suggested the usefulness of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using the new “core” needles for acquiring pancreatic tissue. We aimed to investigate the usefulness of EUS-FNB for diagnosing AIP with one such needle, a 22-gauge Franseen needle. Methods Patients who met the imaging diagnostic criteria for AIP based on the International Consensus Diagnostic Criteria (ICDC) were enrolled in the study. All patients underwent EUS-FNB with a 22-gauge Franseen needle. Histological findings were evaluated based on the ICDC, and the detection rates of level 1 and level 1 or 2 histology were calculated. Results 56 patients from 11 different institutions were enrolled in the final analysis (55 suspected to have type 1 AIP and one with type 2 AIP). Lymphoplasmacytic infiltration, obliterative phlebitis, storiform fibrosis, and &gt; 10 IgG4-positive cells per high-power field were detected in 55 (100 %), 24 (43.6 %), 40 (72.7 %), and 36 (65.5 %) of the 55 patients, respectively. The detection rates of level 1 and level 1 or 2 histology for AIP were 58.2 % (95 % confidence interval [CI] 44.1 % – 71.3 %) and 92.7 % (95 %CI 82.4 % – 98.0 %), respectively, which were apparently higher than our historical results (7.9 % [95 %CI 1.7 % – 21.4 %] and 62.2 % [95 %CI 46.5 % – 76.2 %], respectively) using a conventional needle. Conclusions EUS-FNB with a 22-gauge Franseen needle demonstrated favorable detection rates which would be clinically beneficial for the histological diagnosis of AIP.
Characteristics of Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status — United States, January 22–June 7, 2020
Authors: Sascha Ellington, Penelope Strid, Van T. Tong, Kate Woodworth, Romeo R. Galang, Laura D. Zambrano, John Nahabedian, Kayla Anderson, Suzanne M. Gilboa
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Data findings on pregnant and nonpregnant women with laboratory-confirmed SARS-CoV-2 infection and found that pregnant women are more likely admitted to an intensive care unit admission and to receive mechanical ventilation.
Associations between gut microbiota and genetic risk for rheumatoid arthritis in the absence of disease: a cross-sectional study
Authors: Philippa M Wells, Adewale S Adebayo, Ruth C E Bowyer, Maxim B Freidin, Axel Finckh, Till Strowig, Till Robin Lesker, Deshire Alpizar-Rodriguez, Benoit Gilbert, Bruce Kirkham, Andrew P Cope, Claire J Steves, Frances M K Williams
Journal: The Lancet Rheumatology (2020)

Rheumatoid arthritis is a chronic inflammatory autoimmune disease that is associated with reduced life expectancy. The disease is heritable and an extensive repertoire of genetic variants have been identified. The gut microbiota might represent an environmental risk factor for rheumatoid arthritis. We aimed to assess whether known rheumatoid arthritis risk alleles were associated with the gut microbiota in a large population who do not have rheumatoid arthritis.In this cross-sectional study done in the UK and Switzerland, we used genotyping and microbiota data from previous studies of the TwinsUK cohort, excluding participants who had ever had a diagnosis of rheumatoid arthritis, as well as their unaffected co-twins. We used blood samples for genotyping and stool samples for the assessment of the gut microbiota. We generated a polygenic risk score (PRS) for rheumatoid arthritis in 1650 TwinsUK participants without the disease, based on 233 GWAS-identified single nucleotide polymorphisms associated with rheumatoid arthritis. We validated the PRS using logistic regression against rheumatoid arthritis diagnosis in 2686 UK Biobank individuals with a confirmed diagnosis of rheumatoid arthritis. Amplicon sequence variants (ASVs) were generated from 16S rRNA gene sequencing of stool samples and assessed for association with the PRS for rheumatoid arthritis. We validated the findings in an independent sample comprised of first-degree relatives of patients with rheumatoid arthritis from the SCREEN-RA cohort. Differential abundance of ASVs present in more than 5% of samples, grouped by ASV taxon annotation, against the rheumatoid arthritis PRS as a continuous variable was assessed using fixed-effects covariates. To account for multiple testing, the false discovery rate calculation was applied to all p values to generate q values, with a significance threshold of 0·05 determined a priori.We found that presence of Prevotella spp were positively associated with the rheumatoid arthritis PRS in TwinsUK participants (q<1 × 10-7). This finding was validated in SCREEN-RA participants (n=133) carrying established shared epitope risk alleles (q=0·0011). We also found an association between Prevotella spp and presence of preclinical rheumatoid arthritis phases (q=0·021).Prevotella spp in the gut microbiota are associated with the rheumatoid arthritis genotype in the absence of rheumatoid arthritis, including in individuals at high risk of developing rheumatoid arthritis. Our findings suggest that host genotype is associated with microbiota profile before disease onset.Versus Arthritis.
Abstract 16376: Long-Term Results of Autologous Skeletal Myoblast Cell-Sheet Transplantation for End-Stage Ischemic Cardiomyopathy
Authors: Satoshi Kainuma, Shigeru Miyagawa, Koichi Toda, Yasushi Yoshikawa, Hiroki Hata, Daisuke Yoshioka, Takuji Kawamura, Ai Kawamura, Yoshiki Sawa
Journal: Circulation (2019)

Introduction: The recent Phase I clinical trial demonstrated that the skeletal myoblast cell-sheet transplantation was feasible and safe in cardiomyopathy patients, however its long-term therapeuti...
Eosinophilic granulomatosis with polyangiitis can manifest lacrimal and salivary glands swelling by granulomatous inflammation: a potential mimicker of IgG4-related disease
Authors: Mitsuhiro Akiyama, Yuko Kaneko, Tsutomu Takeuchi
Journal: Annals of the Rheumatic Diseases (2020)

Figure 1 Characteristics of EGPA complicated with Mikulicz disease-like manifestations.(A) Cases of EGPA complicated with lacrimal and salivary glands swelling along with elevated serum IgG4 levels.(B) Histopathological findings of the enlarged lacrimal and salivary glands of EGPA.EGPA, eosinophilic granulomatosis with polyangiitis.on August 12,
Exercise-induced 3′-sialyllactose in breast milk is a critical mediator to improve metabolic health and cardiac function in mouse offspring
Authors: Johan E. Harris, Kelsey M. Pinckard, Katherine R. Wright, Lisa A. Baer, Peter J. Arts, Eaman Abay, Vikram K. Shettigar, Adam C. Lehnig, Bianca Robertson, Kendra Madaris, Tyler J. Canova, Clark Sims, Laurie J. Goodyear, Aline Andres, Mark T. Ziolo, Lars Bode, Kristin I. Stanford
Journal: Nature Metabolism (2020)
Ivacaftor Reverses Airway Mucus Abnormalities in a Rat Model Harboring a Humanized G551D-CFTR
Authors: Susan E. Birket, Joy M. Davis, Courtney M. Fernandez-Petty, Alexander G. Henderson, Ashley M. Oden, LiPing Tang, Hui Wen, Jeong Hong, Lianwu Fu, Andre Chambers, Alvin Fields, Gojun Zhao, Guillermo J. Tearney, Eric J. Sorscher, Steven M. Rowe
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Animal models have been highly informative for understanding the characteristics, onset, and progression of cystic fibrosis (CF) lung disease. In particular, the CFTR
Tailored exercise is safe and beneficial for acutely hospitalised older adults with chronic obstructive pulmonary disease
Authors: Nicolás Martínez-Velilla, Pedro L. Valenzuela, Fabricio Zambom-Ferraresi, Mikel L. Sáez de Asteasu, Robinson Ramírez-Vélez, Antonio García-Hermoso, Alejandro Lucia, Mikel Izquierdo
Journal: European Respiratory Journal (2020)

COPD is predicted to affect approximately half of the older population in the next decade. The incidence of hospitalisations associated with this condition is also likely to rise, even surpassing those caused by major conditions (notably, ischaemic cardiomyopathy) [1]. In this context, the collateral effects of hospitalisation, even for a few days, must not be overlooked, especially in the oldest segment (>80 years). Nearly one third of older adults lose their ability to independently perform one or more activities of daily living from hospital admission to discharge even if successfully treated from the condition that caused hospitalisation, the so-called "hospital induced-disability". This condition has major short- and long-term consequences, notably an increased risk of re-admission and mortality. Moreover, hospitalised patients with COPD present with a proinflammatory profile ( i.e. elevated serum C-reactive protein (CRP)) and high range of variation in red blood cell volume ( i.e. elevated red blood cell distribution width (RDW)), both features associated with poorer outcomes [2]. Tailored exercise is safe and beneficial for acutely hospitalised older adults with chronic obstructive pulmonary disease <https://bit.ly/2YfnqXt> The authors would like to thank the patients and their families for their confidence in the research team.
Exposures Before Issuance of Stay-at-Home Orders Among Persons with Laboratory-Confirmed COVID-19 — Colorado, March 2020
Authors: Kristen Marshall, Grace M. Vahey, Emily McDonald, Jacqueline E. Tate, Rachel Herlihy, Claire M. Midgley, Breanna Kawasaki, Marie E. Killerby, Nisha B. Alden, J. Erin Staples, Alison J. Basile, Alyssa R. Beck, Karen L. Boroughs, Paul L. Burns, Cathy L. Buschmeier, Nathaniel M. Byers, Amanda E. Calvert, Trudy V. Chambers, David T. Dennis, Mary Ellen Fernandez, Katherine T. Ficalora, Kelly A. Fitzpatrick, Shannon Fleck-Derderian, Erik S. Foster, Christin H. Goodman, Garrett Heck, Claire Y-H. Huang, Amy J. Lambert, Aine Lehane, Jennifer A. Lehman, Kristine Lindell, Nicole P. Lindsey, Sarah E. Maes, Courtney Nawrocki, Nancy H. Nay, Kathleen A. Orloski, Lynn Osikowicz, Christina Parise, Lara C. Perinet, Mark A. Pilgard, Jordan A. Powers, María F. Rizzo, Brandy J. Russell, Tracey M. Semcer, Benjamin Skinner, Melanie Spillane
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

On March 26, 2020, Colorado instituted stay-at-home orders to reduce community transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). To inform public health messaging and measures that could be used after reopening, persons with laboratory-confirmed COVID-19 during March 9-26 from nine Colorado counties comprising approximately 80% of the state's population† (Adams, Arapahoe, Boulder, Denver, Douglas, El Paso, Jefferson, Larimer, and Weld) were asked about possible exposures to SARS-CoV-2 before implementation of stay-at-home orders. Among 1,738 persons meeting the inclusion criteria§ in the Colorado Electronic Disease Surveillance System, 600 were randomly selected and interviewed using a standardized questionnaire by telephone. Data collection during April 10-30 included information about demographic characteristics, occupations, and selected activities in the 2 weeks preceding symptom onset. During the period examined, SARS-CoV-2 molecular testing was widely available in Colorado; community transmission was documented before implementation of the stay-at-home order. At least three attempts were made to contact all selected patients or their proxy (for deceased patients, minors, and persons unable to be interviewed [e.g., those with dementia]) on at least 2 separate days, at different times of day. Data were entered into a Research Electronic Data Capture (version 9.5.13; Vanderbilt University) database, and descriptive analyses used R statistical software (version 3.6.3; The R Foundation).
Adenosine/A2B Receptor Signaling Ameliorates the Effects of Aging and Counteracts Obesity
Authors: Thorsten Gnad, Gemma Navarro, Minna Lahesmaa, Laia Reverte-Salisa, Francesca Copperi, Arnau Cordomi, Jennifer Naumann, Aileen Hochhäuser, Saskia Haufs-Brusberg, Daniela Wenzel, Frank Suhr, Naja Zenius Jespersen, Camilla Scheele, Volodymyr Tsvilovskyy, Christian Brinkmann, Joern Rittweger, Christian Dani, Mathias Kranz, Winnie Deuther-Conrad, Holger K. Eltzschig, Tarja Niemi, Markku Taittonen, Peter Brust, Pirjo Nuutila, Leonardo Pardo, Bernd K. Fleischmann, Matthias Blüher, Rafael Franco, Wilhelm Bloch, Kirsi A. Virtanen, Alexander Pfeifer
Journal: Cell Metabolism (2020)