tbuckley/cabot-search huggingface dataset:
Caveolin-1–derived peptide limits development of pulmonary fibrosis
Authors: Amarnath Satheesh Marudamuthu, Yashodhar Prabhakar Bhandary, Liang Fan, Vijay Radhakrishnan, BreAnne MacKenzie, Esther Maier, Shwetha Kumari Shetty, M.R. Nagaraja, Venkadesaperumal Gopu, Nivedita Tiwari, Yajie Zhang, Alan B. Watts, Robert O. Williams, Gerald J Criner, Sudhir Bolla, Nathaniel Marchetti, Steven Idell, Sreerama Shetty
Journal: Science Translational Medicine (2019)

CSP7, a caveolin-1–derived peptide, targets injured alveolar epithelial cells and activated lung fibroblasts to mitigate pulmonary fibrosis.
Validation of the Eighth Edition TNM Lung Cancer Staging System
Authors: Joseph K. Hwang, Barbara J. Page, David Flynn, Linda Passmore, Elizabeth McCaul, Jaccalyne Brady, Ian A. Yang, Henry Marshall, Morgan Windsor, Rayleen V. Bowman, Rishendran Naidoo, Tracey Guan, Shoni Philpot, Michael E. Blake, Kwun M. Fong
Journal: Journal of Thoracic Oncology (2019)

IntroductionWe performed a validation study at our institution, the International Union Against Cancer (Union for International Cancer Control latest version of TNM Classification of Malignant Tumors Eighth Edition).MethodsData were collected from the Queensland Oncology Online registry of NSCLC or SCLC cases between 2000 and 2015 and validated against the Queensland Integrated Lung Cancer Outcomes Project registry using case identification number, first name, last name, and date of birth. Where data were available, cases were classified according to the Union for International Cancer Control TNM seventh edition stage groupings and then compared with the eighth edition groupings. Kaplan-Meier curves were plotted, and the log-rank test of survival differences was performed with SPSS version 25 (IBM Corp, Armonk, NY).ResultsOf the 3636 cases, 3352 and 1031 had complete clinical and pathologic staging, respectively. Median survival time was found to reduce with increasing clinical stage: seventh edition (IA: 88, IB: 44, IIA: 31, IIB: 18, IIIA: 15, IIIB: 8, and IV: 5 mo) versus eighth edition TNM stage (IA1: not reached, IA2: 88, IA3: 53, IB: 56, IIA: 36, IIB: 22, IIIA: 14, IIIB: 9, IIIC: 8, IVA: 6, and IVB: 3 mo). A similar overall pattern was reflected in the pathologic stage: seventh edition (IA: 124, IB: 110, IIA: 48, IIB: 42, IIIA: 26, IIIB: 31, and IV: 27 mo) versus eighth edition (IA1: not reached, IA2: 122, IA3: 125, IB: 144, IIA: 98, IIB: 57, IIIA: 31, IIIB: 24, and IVA: 7 mo). The log-rank test for survival curves was significant at p < 0.001.ConclusionsOur external validation study confirms the prognostic accuracy of the eighth edition TNM lung cancer classification. Our analyses also indicated that IIIB, IIIC, and IVA stage groups had similar survival outcomes and suggest further research for refinement.
DNA vaccination before conception protects Zika virus–exposed pregnant macaques against prolonged viremia and improves fetal outcomes
Authors: Koen K. A. Van Rompay, Rebekah I. Keesler, Amir Ardeshir, Jennifer Watanabe, Jodie Usachenko, Anil Singapuri, Christina Cruzen, Eliza Bliss-Moreau, Ashley M. Murphy, JoAnn L. Yee, Helen Webster, Maria Dennis, Tulika Singh, Holly Heimsath, Danilo Lemos, Jackson Stuart, Kaitlyn M. Morabito, Bryant M. Foreman, Katherine E. Burgomaster, Amy T. Noe, Kimberly A. Dowd, Erin Ball, Kevin Woolard, Pietro Presicce, Suhas G. Kallapur, Sallie R. Permar, Kathryn E. Foulds, Lark L. Coffey, Theodore C. Pierson, Barney S. Graham
Journal: Science Translational Medicine (2019)

A Zika virus vaccine administered to macaques before conception reduces maternal viremia and improves fetal outcomes.
Improving birth and death data for African decision making
Authors: John Nkengasong, Eduardo Gudo, Ivalda Macicame, Xadreque Maunze, Agbessi Amouzou, Kathryn Banke, Scott Dowell, Ilesh Jani
Journal: The Lancet Global Health (2019)

The scarcity of current, complete, and accurate primary data on causes of death in most of sub-Saharan Africa restricts the ability of countries to measure progress against many of the Sustainable Development Goal targets, measure the impact of programmatic interventions, prioritise and plan to address their health needs, and achieve the goals of the Africa Agenda 2063.1 On Aug 10, 2018, the first African Civil Registration and Vital Statistics (CRVS) Day was celebrated, underscoring the importance of working towards compulsory, universal CRVS systems across the continent.
Sphingosine kinase and sphingosine-1-phosphate receptor signaling pathway in inflammatory gastrointestinal disease and cancers: A novel therapeutic target
Authors: Olga A. Sukocheva, Hideki Furuya, Mei Li Ng, Markus Friedemann, Mario Menschikowski, Vadim V. Tarasov, Vladimir N. Chubarev, Sergey G. Klochkov, Margarita E. Neganova, Arduino A. Mangoni, Gjumrakch Aliev, Anupam Bishayee
Journal: Pharmacology & Therapeutics (2019)
Comparison of Patient Age Groups in Transplantation for Myelodysplastic Syndrome
Authors: Ehab Atallah, Brent Logan, Min Chen, Corey Cutler, Joachim Deeg, Meagan Jacoby, Richard Champlin, Taiga Nishihori, Dennis Confer, James Gajewski, Stephanie Farnia, Peter Greenberg, Erica Warlick, Daniel Weisdorf, Wael Saber, Mary M. Horowitz, J. Douglas Rizzo
Journal: JAMA Oncology (2019)

<h3>Importance</h3> In 2010, the US Centers for Medicare &amp; Medicaid Services (CMS) indicated that data regarding efficacy of allogeneic hematopoietic stem cell transplantation (HCT) in the CMS beneficiary population with myelodysplastic syndrome (MDS) were currently insufficient, but that coverage would be provided for patients enrolled in a clinical study that met its criteria for Coverage with Evidence Development (CED). <h3>Objective</h3> The Center for International Bone Marrow Transplant Research (CIBMTR) submitted a study concept comparing the outcomes of patients aged 55 to 64 years vs aged 65 years or older who met those criteria, effectively providing coverage by CMS for HCT for MDS. <h3>Design, Setting, and Participants</h3> Data on patients aged 65 years or older were prospectively collected and their outcomes compared with patients aged 55 to 64 years. Patients were enrolled in the study from December 15, 2010, to May 14, 2014. The results reported herein were analyzed as of September 4, 2017, with a median follow-up of 47 months. The study was conducted by the CIBMTR. It comprises a voluntary working group of more than 420 centers worldwide that contribute detailed data on allogeneic and autologous HCT and cellular therapies. <h3>Interventions</h3> Patients with MDS received HCT according to institutional guidelines and preferences. <h3>Main Outcomes and Measures</h3> The primary outcome was overall survival (OS); secondary outcomes included nonrelapse mortality (NRM), relapse-free survival, and acute and chronic graft vs host disease. <h3>Results</h3> During the study period, 688 patients aged 65 years or older underwent HCT for MDS and were compared with 592 patients aged 55 to 64 years. Other than age, there were no differences in patient and disease characteristics between the groups. On univariate analysis, the 3-year NRM rate was 28% vs 25% for the 65 years or older group vs those aged 55 to 64 years, respectively. The 3-year OS was 37% vs 42% for the 65 years or older group vs the 55 to 64 years age group, respectively. On multivariable analysis after adjusting for excess risk of mortality in the older group, age group had no significant association with OS (HR, 1.09; 95% CI, 0.94-1.27;<i>P</i> = .23) or NRM (HR, 1.19; 95% CI, 0.93-1.52;<i>P</i> = .16). <h3>Conclusions and Relevance</h3> Older patients with MDS undergoing HCT have similar OS compared with younger patients. Based on current data, we would recommend coverage of HCT for MDS by the CMS. <h3>Trial Registration</h3> ClinicalTrials.gov identifier:NCT01166009
Association of Postdisaster Depression and Posttraumatic Stress Disorder With Mortality Among Older Disaster Survivors of the 2011 Great East Japan Earthquake and Tsunami
Authors: Xiaoyu Li, Jun Aida, Hiroyuki Hikichi, Katsunori Kondo, Ichiro Kawachi
Journal: JAMA Network Open (2019)

Depression and posttraumatic stress disorder (PTSD) represent 2 common mental health sequelae of natural disasters. However, to date, no studies have examined whether postdisaster depression and PTSD are associated with increased risk of mortality among community-dwelling survivors of natural disasters.To assess whether postdisaster depression and PTSD were associated with mortality in older disaster survivors.In this cohort study, prospective data were retrieved from older Japanese adults in Iwanuma City, Miyagi Prefecture, which was directly affected by the 2011 Great East Japan Earthquake and Tsunami. The baseline was established 7 months before the disaster (August 2010), and follow-up surveys were conducted approximately 2.5 years afterward (October 1, 2013, to January 31, 2014). Invitations were mailed to every citizen 65 years or older in Iwanuma City. Mortality data were obtained through March 4, 2017. Data analysis was performed from December 1, 2018, to June 30, 2019.Postdisaster depression (Geriatric Depression Scale Short Form score ≥5) and PTSD (Screening Questionnaire for Disaster Mental Health PTSD subscale score ≥4) were measured in 2013.Mortality data were obtained by linkage to the national long-term care insurance database. Cox proportional hazards regression models were adjusted for predisaster sociodemographic characteristics, health behaviors, social cohesion, predisaster depression, and disaster experiences.The response rate for the baseline survey was 59.0% (5058 of 8567 individuals), and the follow-up rate was 82.1% (3594 of 4380 eligible respondents). A total of 2965 individuals (mean [SD] age, 73.4 [6.2] years; 1621 [54.7%] female) participated in the study. The mean (SD) follow-up since the 2013 survey was 3.3 (0.5) years. Overall, 974 (32.8%) reported postdisaster depression and 747 (25.2%) reported PTSD. In adjusted models, depression was associated with more than double the risk of mortality (hazard ratio, 2.29; 95% CI, 1.54-3.42); PTSD was not associated with increased risk of mortality (hazard ratio, 1.10; 95% CI, 0.73-1.64). When evaluating the association of the 4-category comorbid depression and PTSD variable with mortality, survivors with depression only (HR, 2.24; 95% CI, 1.43-3.49) as well as those with comorbid depression and PTSD (HR, 2.54; 95% CI, 1.50-4.27) were at increased risk of death during the follow-up period compared with those with neither depression nor PTSD.Depression, but not PTSD, was associated with mortality during 3.3 years of follow-up among older disaster survivors. These findings suggest that long-term mental health consequences of natural disasters may exist and that treating depression in older survivors of disasters may be beneficial.
Neural correlates of temporal updating and reasoning in association with neuropsychiatric disorders
Authors: Natsuki Ueda, Takashi Hanakawa
Journal: Behavioral and Brain Sciences (2019)

Abstract Here we argue how Hoerl &amp; McCormack's dual system proposal may change the current view about the neural correlates underlying temporal information processing. We also consider that the concept of the dual system may help characterize various timing disabilities in neuropsychiatric disorders from the new perspective.
Abstract PR13: Macrophage metabolism inhibits pancreatic cancer therapy
Authors: Christopher J. Halbrook, Rosa Menjivar, Galloway Thurston, Marina Pasca di Magliano, Costas Lyssiotis
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) is projected to become the 3rd most prevalent cancer-related death in the United States in 2016, contrasting a relatively low incidence rate. The lethality of PDA is largely due to a lack of effective treatment options. A principal barrier in PDA treatment is the physiology of the tumors, characterized by a densely fibrotic stroma, rich with immune cell infiltration. The majority of these immune cells are immunosuppressive myeloid cells, including macrophages. These macrophages within the tumor, termed tumor-associated macrophages (TAMs), are strongly immunosuppressive, inhibiting both infiltration and activation of cytotoxic T cells. While immunotherapy has emerged as a promising strategy to treat other solid tumors, immune suppression has rendered PDA refractory to such approaches. Accordingly, much effort has been made to understand the role of TAMs in pancreatic tumorigenesis and tumor maintenance. Several studies have identified pathways by which PDA cells recruit and polarize macrophages into TAMs and the effects that TAMs have on the tumor microenvironment. Depletion of TAMs leads to the inhibition or regression of tumor growth, mediated largely by increased infiltration of cytotoxic T cells into the tumor. In addition to signaling proteins, metabolic byproducts can also influence cellular crosstalk in the tumor microenvironment; however, this has not been described in the context of PDA. Utilizing reciprocal conditioned media approaches combined with LC/MS metabolomics, we have profiled the metabolic crosstalk between cancer cells and macrophage cultures and found TAMs release metabolites that can regulate the response of PDA cells to chemotherapy. We further noted several additional metabolic pathways by which TAMs can deplete important nutrients in the microenvironment to directly inhibit T-cell activity. Taken together, these data provide mechanistic insight into previous reports that macrophages can drive immune and chemoresistance in PDA. Furthermore, these results also suggest that further development of interventions that target either PDA-mediated polarization of TAMs or TAM-mediated inhibition of therapy represent opportunities to improve the efficacy of currently available treatment options. This abstract is also being presented as Poster A36. Citation Format: Christopher J. Halbrook, Rosa Menjivar, Galloway Thurston, Marina Pasca di Magliano, Costas Lyssiotis. Macrophage metabolism inhibits pancreatic cancer therapy [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr PR13.
Implementation of Genetic Screening to Prevent Severe Cutaneous Adverse Drug Reactions Is Crucial—Rebuttal From the Devil’s Antagonist—Reply
Authors: Sherrie J. Divito
Journal: JAMA Dermatology (2019)

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Autologous stem cell transplant in older patients with multiple myeloma (MM): Analysis of the nationwide inpatient sample (NIS).
Authors: Tanya Marya Wildes, Anita Hellstrom, Ravi Vij, Pamela Owens, Graham A. Colditz
Journal: Journal of Clinical Oncology (2012)

e18551 Background: Autologous stem cell transplant (ASCT) improves survival in MM patients &lt;65 years and is applied to select patients ≥ age 65. We hypothesized that comorbidities (CM) are associated with increased length of stay (LOS), hospital charges, toxicity, and in-hospital mortality in older patients with MM undergoing ASCT. Methods: This is a retrospective cohort study of patients over the age of 65 with MM admitted to U.S. hospitals for ASCT in the 2008 NIS. CM were coded using the Comorbidity Software; toxicities were determined by ICD-9-CM codes. Relationships between CM and toxicities, LOS, hospital charges, and in-hospital mortality were analyzed. Results: 206 patients MM ≥ 65 years who underwent ASCT were identified. Median age was 68 years (range 65-82). As defined by Elixhauser (Medical Care 1998), 83.5% of patients had ≥ 1 CM. Median LOS was 17 days (range 1-152). Median total charges were $162,998 (range $4289-$953,789). The most common complications coded were: neutropenic fever (29.6%), diarrhea (28.6%), bacteremia (13.6%), mucositis (8.7%) and pneumonia (6.8%). In-hospital mortality was &lt;5% (precise percentage cannot be reported due to cell size &lt;10). Elixhauser CM did not predict LOS, total charges, in-hospital mortality, or toxicities. When CM were restricted to those in the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI, Sorror et al 2005), only 35.4% of patients had CM. The presence of CM using a modified HCT-CI was associated with longer LOS (23.5 vs 17.6 days, p=0.0047) higher mean total charges [$189,896 (95% CI $154,333-225,459) vs $148,234 (95%CI $121,887-174,581), p=0.02] and increased risk of “complications of transplant” or “delirium” codes (p=0.035; precise percentage cannot be reported due to cell size &lt;10). Conclusions: ASCT was well-tolerated with low in-hospital mortality in a population-based cohort of older patients with MM.The Elixhauser CM method did not predict outcomes. Using a modified HCT-CI CM index predicted longer LOS, greater hospital charges, and some toxicities, highlighting differences in the utility of different CM indices. Further investigation must define the optimal CM index for studying hematopoietic cell transplantation using administrative data.
Abstract B46: Targeting pancreatic cancer organoids with dual BET and CBP/P300 inhibitor NEO2734
Authors: Nikolina Radulovich, Laura Tamblyn, Heewon Seo, Benjamin Haibe-Kains, Mathieu Lupien, Francis Gilles, Ming S. Tsao
Journal: Cancer Research (2019)

Abstract Pancreatic ductal adenocarcinoma (PDA) has a dismal prognosis due to largely ineffective therapeutics available for this disease. Recently, inhibitors of bromodomain and extraterminal domain (BET) inhibitors have been shown to have therapeutic efficacy against various malignancies, including PDA. Here we present data on sensitivity of PDA patient-derived organoids (PDO) to a novel dual BET and CBP/P300 inhibitor, NEO2734 (Epigene Therapeutics Inc.). Our cell viability screen on a panel of 30 PDOs derived from PDA patient and xenograft tumor tissue revealed differential drug sensitivities to NEO2734 inhibitor. Antitumor effect of NEO2734 on the most sensitive PPTO.2 model was further confirmed in vivo using patient-derived xenograft PPTO.2 model. To identify potential biomarkers associated with differential sensitivities of PDA PDOs to NEO2734 inhibitor, we generated gene expression profiles from 13 PDOs derived from primary patient tumors. Using the probabilistic concordance index (C-index), 13 genes (Bonferroni corrected P&amp;lt;1.0E-10) were identified as potential therapeutic targets. Among the biomarkers identified, we found three associations with known BET inhibitor target genes, including CA9 (C-index= 0.38, PBonferroni= 2.7E-19), which is known to be downregulated by BET inhibitor and coexpressed with the target gene BRDT. Furthermore, the biomarker SLC7A2 (0.28, 3.4E-37) has a known genetic interaction with BRD4, and ABCB6 (0.31, 1.5E-27) is predicted to be coexpressed with CREBBP. Overall, this work reveals that dual BET and CBP/P300 inhibitor, NEO2734, could be a novel therapeutic option for a subset of PDA patients. Citation Format: Nikolina Radulovich, Laura Tamblyn, Heewon Seo, Benjamin Haibe-Kains, Mathieu Lupien, Francis Gilles, Ming S. Tsao. Targeting pancreatic cancer organoids with dual BET and CBP/P300 inhibitor NEO2734 [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B46.
Outcomes of Pregnancies in Patients with Sickle-Cell Disease : Update from European Non-Interventional, Multicentric, Prospective Escort-HU Study
Authors: Frédéric Galactéros, Giovanna Cannas, Pablo Bartolucci, Ersi Voskaridou, Laure Joseph, Emmanuelle Bernit, Justine Gellen-Dautremer, Corinne Charneau, Stephanie Ngo, Anoosha Habibi
Journal: Blood (2019)
Failed endoscopic ultrasound-guided gallbladder drainage due to severe bleeding immediately rescued by redo-drainage under contrast-harmonic guidance
Authors: Andrea Lisotti, Anna Cominardi, Igor Bacchilega, Pietro Fusaroli
Journal: Endoscopy (2019)

Endoscopic ultrasound-guided gallbladder drainage (EUS-GBD) was first described in 2007 [1] and is considered the treatment of choice for acute cholecystitis in patients unsuitable for surgery [2] [3]. EUS-GBD was recently demonstrated to be safe and effective even in patients with cirrhosis [4] [5].
128TiP VCN-01 plus durvalumab in subjects with recurrent/metastatic head &amp; neck squamous cell carcinoma (R/M HNSCC): Phase I clinical trial
Authors: M. Jove, I. Braña, M. Taberna, A. Hernando-Calvo, J. Brenes Castro, E. Garralda, M. Plana Serrahima, M. Maños Pujol, G. Capella, R. Alemany, E. Blasi, C. Blasco, M. Cascallo Piqueras, R. Mesia Nin
Journal: Annals of Oncology (2019)
N6-methyladenosine regulates the stability of RNA:DNA hybrids in human cells
Authors: Abdulkadir Abakir, Tom C. Giles, Agnese Cristini, Jeremy M. Foster, Nan Dai, Marta Starczak, Alejandro Rubio-Roldan, Miaomiao Li, Maria Eleftheriou, James Crutchley, Luke Flatt, Lorraine Young, Daniel J. Gaffney, Chris Denning, Bjørn Dalhus, Richard D. Emes, Daniel Gackowski, Ivan R. Corrêa, Jose L. Garcia-Perez, Arne Klungland, Natalia Gromak, Alexey Ruzov
Journal: Nature Genetics (2019)