tbuckley/cabot-search huggingface dataset:
Multicenter Phase I/II Study of Nivolumab Combined with Paclitaxel Plus Ramucirumab as Second-line Treatment in Patients with Advanced Gastric Cancer
Authors: Takako Eguchi Nakajima, Shigenori Kadowaki, Keiko Minashi, Tomohiro Nishina, Takeharu Yamanaka, Yuichiro Hayashi, Naoki Izawa, Kei Muro, Shuichi Hironaka, Takeshi Kajiwara, Yutaka Kawakami
Journal: Clinical Cancer Research (2020)

We conducted a phase I/II study to investigate the safety and efficacy of nivolumab with paclitaxel plus ramucirumab.Patients with advanced gastric cancer (AGC) refractory to first-line chemotherapy were included. Patients received nivolumab (3 mg/kg on days 1 and 15) combined with paclitaxel (80 mg/m2 on days 1, 8, and 15) and ramucirumab (8 mg/kg on days 1 and 15) every 4 weeks. After feasibility evaluation in six patients (phase I), 37 additional patients were enrolled in the phase II part with the primary endpoint of 6-month progression-free survival (PFS) rate with two-sided 80% confidence interval (CI). The combined positive score (CPS) was defined as the number of programmed death-ligand 1-positive cells divided by the total number of viable tumor cells multiplied by 100.Forty-three patients were enrolled. Of these, 60.5% had CPS ≥ 1. Dose-limiting toxicities were observed in two patients, and the recommended dose was determined as level 1. Thirty-nine (90.7%) patients experienced treatment-related adverse events (AEs) grade ≥3 and 14 (32.6%) patients experienced immune-related AEs grade ≥3. The overall response rate was 37.2% (95% CI, 23.0%-53.5%) and the 6-month PFS rate was 46.5% (80% CI, 36.4%-55.8%; P = 0.067). Median survival time was 13.1 months (95% CI, 8.0-16.6 months): 13.8 months (95% CI, 8.0-19.5 months) in patients with CPS ≥ 1 and 8.0 months (95% CI, 4.8-24.1 months) in patients with CPS < 1.Nivolumab with paclitaxel plus ramucirumab demonstrated promising antitumor activity with manageable toxicities as second-line treatment for AGC.
Evaluation of US Hospital Episode Spending for Acute Inpatient Conditions After the Patient Protection and Affordable Care Act
Authors: Andrew M. Ibrahim, Ushapoorna Nuliyalu, Emily J. Lawton, Stephen O’Neil, Justin B. Dimick, Baris Gulseren, Shashank S. Sinha, John M. Hollingsworth, Tedi A. Engler, Andrew M. Ryan
Journal: JAMA Network Open (2020)

Under the Patient Protection and Affordable Care Act (ACA), US hospitals were exposed to a number of reforms intended to reduce spending, many of which, beginning in 2012, targeted acute care hospitals and often focused on specific diagnoses (eg, acute myocardial infarction, heart failure, and pneumonia) for Medicare patients. Other provisions enacted in the ACA and under budget sequestration (beginning in 2013) mandated Medicare fee cuts.To evaluate the association between the enactment of ACA reforms and 30-day price-standardized hospital episode spending.This policy evaluation included index discharges between January 1, 2008, and August 31, 2015, from a national random 20% sample of Medicare beneficiaries. Data analysis was performed from February 1, 2019 to July 8, 2020.Payment reforms after passage of the ACA.30-day price-standardized episode payments. Three alternative estimation approaches were used to evaluate the association between reforms following the ACA and episode spending: (1) a difference-in-difference (DID) analysis among acute care hospitals, comparing spending for diagnoses commonly targeted by ACA programs with nontargeted diagnoses; (2) a DID analysis comparing acute care hospitals and critical access hospitals (not exposed to reforms); and (3) a generalized synthetic control analysis, comparing acute care and critical access hospitals. Supplemental analysis examined the degree to which Medicare fee cuts contributed to spending reductions.A total of 7 634 242 index discharges (4 525 630 [59.2%] female patients; mean [SD] age, 79.31 [8.02] years) were included. All 3 approaches found that reforms following the ACA were associated with a significant reduction in episode spending. The DID estimate comparing targeted and untargeted diagnoses suggested that reforms following the ACA were associated with a -$431 (95% CI, -$492 to -$369; -2.87%) change in total spending, while the generalized synthetic control analysis suggested that reforms were associated with a -$1232 (95% CI, -$1488 to -$965; -10.12%) change in total episode spending, amounting in a total annual savings of $5.68 billion. Cuts to Medicare fees accounted for most of these savings.In this policy evaluation, the ACA was associated with large reductions in US hospital episode spending.
Selective Heart Rate Inhibition Improves Single-Ventricular Stroke Volume, Function, and Efficiency During Exercise
Authors: Bram Ruijsink, Mari N. Velasco Forte, Phuoc Duong, Esther Puyol-Antón, Kuberan Pushparajah, Alessandra Frigiola, David Nordsletten, Reza Razavi
Journal: JACC. Cardiovascular imaging (2020)
Cancer cells employ an evolutionarily conserved polyploidization program to resist therapy
Authors: K.J. Pienta, E.U. Hammarlund, R.H. Austin, R. Axelrod, J.S. Brown, S.R. Amend
Journal: Seminars in Cancer Biology (2020)

Unusually large cancer cells with abnormal nuclei have been documented in the cancer literature since 1858. For more than 100 years, they have been generally disregarded as irreversibly senescent or dying cells, too morphologically misshapen and chromatin too disorganized to be functional. Cell enlargement, accompanied by whole genome doubling or more, is observed across organisms, often associated with mitigation strategies against environmental change, severe stress, or the lack of nutrients. Our comparison of the mechanisms for polyploidization in other organisms and non-transformed tissues suggest that cancer cells draw from a conserved program for their survival, utilizing whole genome doubling and pausing proliferation to survive stress. These polyaneuploid cancer cells (PACCs) are the source of therapeutic resistance, responsible for cancer recurrence and, ultimately, cancer lethality.
15324 Long-term management of moderate to severe plaque psoriasis: Maintenance of treatment success following cessation of fixed combination halobetasol propionate 0.01% and tazarotene 0.045% lotion in patients with baseline body surface area of 6%-12%
Authors: Linda Stein Gold, Jonathan S. Weiss, Lawrence J. Green, Leon Kircik, Tina Lin PharMD, Susan Harris
Journal: Journal of the American Academy of Dermatology (2020)
Abstract IA19: Dietary Control of Stem Cells in Physiology and Disease
Authors: Omer H. Yilmaz
Journal: Cancer Research (2020)

Abstract Organismal diet has a profound impact on tissue homeostasis and health in mammals. Adult stem cells mediate many aspects of tissue adaptation by balancing self-renewal and differentiation divisions to alter tissue composition in response to the environment. Because somatic stem cells may respond to organismal physiology to orchestrate tissue remodeling and some cancers are understood to arise from transformed stem cells, these findings raise the possibility that organismal diet, stem cell function, and cancer initiation are interconnected. Here I will present work from my group that describes our emerging view of how diet, metabolites and nutrient-sensing pathways instruct mammalian intestinal stem cell fate in homeostasis, adaptation to diet and diseases such as cancer. Citation Format: Omer H. Yilmaz. Dietary Control of Stem Cells in Physiology and Disease [abstract]. In: Abstracts: AACR Special Virtual Conference on Epigenetics and Metabolism; October 15-16, 2020; 2020 Oct 15-16. Philadelphia (PA): AACR; Cancer Res 2020;80(23 Suppl):Abstract nr IA19.
High-purity magnesium pin enhances bone consolidation in distraction osteogenesis via regulating Ptch protein activating Hedgehog-alternative Wnt signaling
Authors: Musha Hamushan, Weijie Cai, Yubo Zhang, Zun Ren, Jiafei Du, Shaoxiang Zhang, Changli Zhao, Pengfei Cheng, Xiaonong Zhang, Hao Shen, Pei Han
Journal: Bioactive Materials (2020)

Magnesium alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. Magnesium has been proven to promote distraction osteogenesis. However, its mechanism of promoting distraction osteogenesis is not thoroughly studied. In this work, a high-purity magnesium pin developed and applied in rat femur distraction osteogenesis. Mechanical test, radiological and histological analysis suggested that high-purity magnesium pin can promote distraction osteogenesis and shorten the consolidation time. Further RNA sequencing investigation found that alternative Wnt signaling was activated. In further bioinformatics analysis, it was found that the Hedgehog pathway is the upstream signaling pathway of the alternative Wnt pathway. We found that Ptch protein is a potential target of magnesium and verified by molecular dynamics that magnesium ions can bind to Ptch protein. In conclusion, HP Mg implants have the potential to enhance bone consolidation in the DO application, and this process might be via regulating Ptch protein activating Hedgehog-alternative Wnt signaling.
16405 Abrocitinib treatment in patients with moderate to severe atopic dermatitis: Consistency of efficacy responses from randomized, controlled phase 3 and phase 2b clinical trials
Authors: Eric L. Simpson, Melinda Gooderham, Brett King, Susan C. Taylor, David Rosmarin, Svitlana Tatulych, Chudy Nduaka, David Williams, Weidong Zhang, Ricardo Rojo
Journal: Journal of the American Academy of Dermatology (2020)
308P The genomic landscape of non-small cell lung cancer (NSCLC) in East Asia using circulating tumour DNA (ctDNA) in clinical practice
Authors: B.C. Cho, H.H.F. Loong, C-M. Tsai, M.L.P. Teo, K. Park, H.R. Kim, M. Lee, S. Olsen
Journal: Annals of Oncology (2020)
Optimizing the Use of Telemedicine in Oncology Care: Postpandemic Opportunities
Authors: Karen E. Knudsen, Cheryl Willman, Robert Winn
Journal: Clinical Cancer Research (2020)

Abstract Utilization of telehealth as part of the cancer care delivery continuum dramatically escalated in response to the COVID-19 pandemic at major cancer centers across the globe. The rapid shift toward telehealth visits for nontreatment cancer care provided immediate benefit through reducing unnecessary risk of exposure, overcoming transportation barriers faced by both patients and caregivers, and fast-tracking care transformation. As such, delineating the impact of telehealth on access, health equity, quality, and outcomes will be essential for refining the use of digital strategies and telehealth toward optimizing cancer care. Herein, experiences to date with telehealth usage for oncology care are reviewed, and priorities are outlined for postpandemic opportunities to improve the lives of patients with cancer through telemedicine.
Author Correction: Early detection and tracking of bulbar changes in ALS via frequent and remote speech analysis
Authors: Gabriela M. Stegmann, Shira Hahn, Julie Liss, Jeremy Shefner, Seward Rutkove, Kerisa Shelton, Cayla Jessica Duncan, Visar Berisha
Journal: npj Digital Medicine (2020)

A Correction to this paper has been published: https://doi.org/10.1038/s41746-020-00364-6.
13920 Slow micrographic Mohs surgery for lentigo maligna: A retrospective study of 36 cases
Authors: Iván Checa Recio, Consuelo Sánchez Herreros, Jaime Martinez Mariscal, Pablo Cobo Rodríguez, Adriana Martín Fuentes, David Lujan Rodriguez, Esther de Eusebio Murillo
Journal: Journal of the American Academy of Dermatology (2020)
Bile acids profile, histopathological indices and genetic variants for non-alcoholic fatty liver disease progression
Authors: Nisreen Nimer, Ibrahim Choucair, Zeneng Wang, Ina Nemet, Lin Li, Janet Gukasyan, Taylor L. Weeks, Naim Alkhouri, Nizar Zein, W.H. Wilson Tang, Michael A. Fischbach, J. Mark Brown, Hooman Allayee, Srinivasan Dasarathy, Valentin Gogonea, Stanley L. Hazen
Journal: Metabolism (2020)
Sources and transmission routes of campylobacteriosis: A combined analysis of genome and exposure data
Authors: Lapo Mughini-Gras, Roan Pijnacker, Claudia Coipan, Annemieke C. Mulder, Adriana Fernandes Veludo, Sharona de Rijk, Angela H.A.M. van Hoek, Ralph Buij, Gerard Muskens, Miriam Koene, Kees Veldman, Birgitta Duim, Linda van der Graaf-van Bloois, Coen van der Weijden, Sjoerd Kuiling, Anjo Verbruggen, Joke van der Giessen, Marieke Opsteegh, Menno van der Voort, Greetje A.A. Castelijn, Franciska M. Schets, Hetty Blaak, Jaap A. Wagenaar, Aldert L. Zomer, Eelco Franz
Journal: Journal of Infection (2020)

ObjectivesTo determine the contributions of several animal and environmental sources of human campylobacteriosis and identify source-specific risk factors.Methods1417 Campylobacter jejuni/coli isolates from the Netherlands in 2017–2019 were whole-genome sequenced, including isolates from human cases (n = 280), chickens/turkeys (n = 238), laying hens (n = 56), cattle (n = 158), veal calves (n = 49), sheep/goats (n = 111), pigs (n = 110), dogs/cats (n = 100), wild birds (n = 62), and surface water (n = 253). Questionnaire-based exposure data was collected. Source attribution was performed using core-genome multilocus sequence typing. Risk factors were determined on the attribution estimates.ResultsCases were mostly attributed to chickens/turkeys (48.2%), dogs/cats (18.0%), cattle (12.1%), and surface water (8.5%). Of the associations identified, never consuming chicken, as well as frequent chicken consumption, and rarely washing hands after touching raw meat, were risk factors for chicken/turkey-attributable infections. Consuming unpasteurized milk or barbecued beef increased the risk for cattle-attributable infections. Risk factors for infections attributable to environmental sources were open water swimming, contact with dog faeces, and consuming non-chicken/turkey avian meat like game birds.ConclusionsPoultry and cattle are the main livestock sources of campylobacteriosis, while pets and surface water are important non-livestock sources. Foodborne transmission is only partially consistent with the attributions, as frequency and alternative pathways of exposure are significant.
Decreased Global Strains of LV in Asymptomatic Female Duchenne Muscular Dystrophy Gene Carriers Using CMR-FT
Authors: Lucia Masárová, Mary Luz Mojica-Pisciotti, Roman Panovský, Vladimír Kincl, Martin Pešl, Lukáš Opatřil, Jan Máchal, Jan Novák, Tomáš Holeček, Lenka Juříková, Věra Feitová
Journal: JACC. Cardiovascular imaging (2020)
245P Clinicopathological features including response to platinum-based chemotherapy in endometrial carcinomas involving SWI/SNF complex inactivation
Authors: I. Tanimoto, K. Sudo, M. Kato, H. Yoshida, Y. Chiba, Y. Kojima, T. Okuya, H. Okuma, T. Nishikawa, M. Tanioka, T. Shimoi, E. Noguchi, Y. Fujiwara, T. Kato, K. Yonemori
Journal: Annals of Oncology (2020)
17139 Comparative cost-effectiveness for tildrakizumab and other targeted therapies for the treatment of moderate to severe plaque psoriasis in the United States
Authors: Xiaoying Jia, Alan Mendelsohn, Justin Carrico, Thor-Henrik Brodtkorb, Yang Zhao, Steven Feldman, April Armstrong, Jashin J. Wu
Journal: Journal of the American Academy of Dermatology (2020)
Differences in Cardiac Remodeling Associated With Race: Implications for Pre-Participation Screening and the Unfavorable Situation of Black Athletes⁎⁎Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Authors: Antonio Pelliccia
Journal: Journal of the American College of Cardiology (2008)
American College of Rheumatology Clinical Guidance for Multisystem Inflammatory Syndrome in Children Associated With SARS–CoV‐2 and Hyperinflammation in Pediatric COVID‐19: Version 2
Authors: Lauren A. Henderson, Scott W. Canna, Kevin G. Friedman, Mark Gorelik, Sivia K. Lapidus, Hamid Bassiri, Edward M. Behrens, Anne Ferris, Kate F. Kernan, Grant S. Schulert, Philip Seo, Mary Beth F. Son, Adriana H. Tremoulet, Rae S. M. Yeung, Amy S. Mudano, Amy S. Turner, David R. Karp, Jay J. Mehta
Journal: Arthritis & Rheumatology (2020)

Objective To provide guidance on the management of Multisystem Inflammatory Syndrome in Children (MIS‐C), a condition characterized by fever, inflammation, and multiorgan dysfunction that manifests late in the course of severe acute respiratory syndrome coronavirus 2 (SARS–CoV‐2) infection. Recommendations are also provided for children with hyperinflammation during coronavirus disease 2019 (COVID‐19), the acute, infectious phase of SARS–CoV‐2 infection. Methods The Task Force was composed of 9 pediatric rheumatologists and 2 adult rheumatologists, 2 pediatric cardiologists, 2 pediatric infectious disease specialists, and 1 pediatric critical care physician. Preliminary statements addressing clinical questions related to MIS‐C and hyperinflammation in COVID‐19 were developed based on evidence reports. Consensus was built through a modified Delphi process that involved anonymous voting and webinar discussion. A 9‐point scale was used to determine the appropriateness of each statement (median scores of 1–3 for inappropriate, 4–6 for uncertain, and 7–9 for appropriate). Consensus was rated as low, moderate, or high based on dispersion of the votes. Approved guidance statements were those that were classified as appropriate with moderate or high levels of consensus, which were prespecified before voting. Results The first version of the guidance was approved in June 2020, and consisted of 40 final guidance statements accompanied by a flow diagram depicting the diagnostic pathway for MIS‐C. The document was revised in November 2020, and a new flow diagram with recommendations for initial immunomodulatory treatment of MIS‐C was added. Conclusion Our understanding of SARS–CoV‐2–related syndromes in the pediatric population continues to evolve. This guidance document reflects currently available evidence coupled with expert opinion, and will be revised as further evidence becomes available.
<i>Neospora caninum:</i> a new class of biopharmaceuticals in the therapeutic arsenal against cancer
Authors: Louis Lantier, Agathe Poupée-Beaugé, Anne di Tommaso, Céline Ducournau, Mathieu Epardaud, Zineb Lakhrif, Stéphanie Germon, Françoise Debierre-Grockiego, Marie-Noëlle Mévélec, Arthur Battistoni, Loïs Coënon, Nora Deluce-Kakwata-Nkor, Florence Velge-Roussel, Céline Beauvillain, Thomas Baranek, Gordon Scott Lee, Thibault Kervarrec, Antoine Touzé, Nathalie Moiré, Isabelle Dimier-Poisson
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Microorganisms that can be used for their lytic activity against tumor cells as well as inducing or reactivating antitumor immune responses are a relevant part of the available immunotherapy strategies. Viruses, bacteria and even protozoa have been largely explored with success as effective human antitumor agents. To date, only one oncolytic virus—T-VEC—has been approved by the US Food and Drug Administration for use in biological cancer therapy in clinical trials. The goal of our study is to evaluate the potential of a livestock pathogen, the protozoan Neospora caninum, non-pathogenic in humans, as an effective and safe antitumorous agent. Methods/Results We demonstrated that the treatment of murine thymoma EG7 by subcutaneous injection of N. caninum tachyzoites either in or remotely from the tumor strongly inhibits tumor development, and often causes their complete eradication. Analysis of immune responses showed that N. caninum had the ability to 1) lyze infected cancer cells, 2) reactivate the immunosuppressed immune cells and 3) activate the systemic immune system by generating a protective antitumor response dependent on natural killer cells, CD8-T cells and associated with a strong interferon (IFN)-γ secretion in the tumor microenvironment. Most importantly, we observed a total clearance of the injected agent in the treated animals: N. caninum exhibited strong anticancer effects without persisting in the organism of treated mice. We also established in vitro and an in vivo non-obese diabetic/severe combined immunodeficiency mouse model that N. caninum infected and induced a strong regression of human Merkel cell carcinoma. Finally, we engineered a N. caninum strain to secrete human interleukin (IL)-15, associated with the alpha-subunit of the IL-15 receptor thus strengthening the immuno-stimulatory properties of N. caninum . Indeed, this NC1-IL15hRec strain induced both proliferation of and IFN-γ secretion by human peripheral blood mononuclear cells, as well as improved efficacy in vivo in the EG7 tumor model. Conclusion These results highlight N. caninum as a potential, extremely effective and non-toxic anticancer agent, capable of being engineered to either express at its surface or to secrete biodrugs. Our work has identified the broad clinical possibilities of using N. caninum as an oncolytic protozoan in human medicine.
14157 Speed of improvement in genital psoriasis, genital itch, sexual impact, and health-related quality of life in patients with moderate to severe genital psoriasis treated with ixekizumab
Authors: Joseph F. Merola, Lyn Guenther, Peter Foley, Russel Burge, Kyoungah See, Missy McKean-Matthews, Gaia Gallo, Caitriona Ryan
Journal: Journal of the American Academy of Dermatology (2020)
Hypersensitivity reactions to platinum‐based compounds in the context of pressurized intraperitoneal aerosol chemotherapy (PIPAC): Description and management
Authors: Amélie Gauthier, Farid Mankouri, Pascal Demoly, Olivia Sgarbura, Anca Mirela Chiriac
Journal: Allergy (2020)

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神経ペプチド作動性ニューロンにおけるER脂質欠損はParkinson病における睡眠パターンを損なう【JST・京大機械翻訳】
Authors: S Valadas Jorge, Esposito Giovanni, Vandekerkhove Dirk, Miskiewicz Katarzyna, Deaulmerie Liesbeth, Raitano Susanna, Seibler Philip, Klein Christine, Verstreken Patrik
Journal: Neuron (2018)