tbuckley/cabot-search huggingface dataset:
Estimating the effect of moving meat-free products to the meat aisle on sales of meat and meat-free products: A non-randomised controlled intervention study in a large UK supermarket chain
Authors: Carmen Piernas, Brian Cook, Richard Stevens, Cristina Stewart, Jennifer Hollowell, Peter Scarborough, Susan A. Jebb
Journal: PLoS Medicine (2021)

Background Reducing meat consumption could bring health and environmental benefits, but there is little research to date on effective interventions to achieve this. A non-randomised controlled intervention study was used to evaluate whether prominent positioning of meat-free products in the meat aisle was associated with a change in weekly mean sales of meat and meat-free products. Methods and findings Weekly sales data were obtained from 108 stores: 20 intervention stores that moved a selection of 26 meat-free products into a newly created meat-free bay within the meat aisle and 88 matched control stores. The primary outcome analysis used a hierarchical negative binomial model to compare changes in weekly sales (units) of meat products sold in intervention versus control stores during the main intervention period (Phase I: February 2019 to April 2019). Interrupted time series analysis was also used to evaluate the effects of the Phase I intervention. Moreover, 8 of the 20 stores enhanced the intervention from August 2019 onwards (Phase II intervention) by adding a second bay of meat-free products into the meat aisle, which was evaluated following the same analytical methods. During the Phase I intervention, sales of meat products (units/store/week) decreased in intervention (approximately −6%) and control stores (−5%) without significant differences (incidence rate ratio [IRR] 1.01 [95% CI 0.95–1.07]. Sales of meat-free products increased significantly more in the intervention (+31%) compared to the control stores (+6%; IRR 1.43 [95% CI 1.30–1.57]), mostly due to increased sales of meat-free burgers, mince, and sausages. Consistent results were observed in interrupted time series analyses where the effect of the Phase II intervention was significant in intervention versus control stores. Conclusions Prominent positioning of meat-free products into the meat aisle in a supermarket was not effective in reducing sales of meat products, but successfully increased sales of meat-free alternatives in the longer term. A preregistered protocol ( https://osf.io/qmz3a/ ) was completed and fully available before data analysis.
Individual risk prediction of urinary incontinence after prostatectomy and impact on treatment choice in patients with localized prostate cancer
Authors: C.N. Tillier, R.D. Vromans, A.H. Boekhout, H. Veerman, B.M. Wollersheim, H.A.M. Van Muilekom, T.N. Boellaard, P.J. Van Leeuwen, L.V. Van De Poll, H.G. Van Der Poel
Journal: European Urology (2021)
Publisher Correction: Leveraging breeding programs and genomic data in Norway spruce (Picea abies L. Karst) for GWAS analysis
Authors: Zhi-Qiang Chen, Yanjun Zan, Pascal Milesi, Linghua Zhou, Jun Chen, Lili Li, BinBin Cui, Shihui Niu, Johan Westin, Bo Karlsson, Maria Rosario García-Gil, Martin Lascoux, Harry X. Wu
Journal: Genome biology (2021)
Endoscopic negative pressure therapy for a broad rectal fistula using pull-through open-pore film and polyurethane foam drains
Authors: Johannes Müller, Anna-Maria Goerdt, Christian T. Müller, Gunnar Loske
Journal: Endoscopy (2021)

A 63-year-old man presented with a large acute pararectal abscess, with a broad suprasphincter fistula. Initial emergency surgical treatment consisted of opening the abscess and insertion of a loop drain ([Fig. 1]). Further therapy was performed by endoscopic negative pressure therapy (ENPT), sequentially using open-pore foam drains (OPDs) and open-pore film drains (OFDs) in a novel pull-through technique [1] [2] [3].
Abstract 1610: Local delivery of anti CTLA4 mediates cDC1 dependent eradication of HNSCC with limited IRAEs in a preclinical model of oral squamous cell carcinoma
Authors: Mara Gilardi, Zhiyong Wang, Victoria H. Wu, Miguel Angel Lopez-Ramirez, Fernando Soto-Alvarez, Robert Saddawi-Konefka, Dana Steffen, Marco Proietto, Zbigniew Mikulski, Haruka Miki, Jayanth Shankara Narayanan, Alfredo Molinolo, Joseph Wang, J. Silvio Gutkind
Journal: Cancer Research (2021)

Abstract Head and neck squamous cell carcinoma (HNSCC) ranks 6th in cancer incidence worldwide and has a five-year survival rate of only 63%. Despite advances in curative-intent therapies over the past three decades, rates of recurrence exceed 50% and long-term toxicities remain unacceptably morbid. Immunotherapies - principally immune checkpoint inhibitors (ICI) such as αPD-1 and αCTLA-41 antibodies which restore endogenous antitumor T cell immunity - offer the greatest promise for achieving durable response in HNSCC. However, the clinical application of ICI has been limited by immune-related adverse events (irAEs), which is a consequence of compromised peripheral immune tolerance after ICI therapy. Although irAEs are often reversible they can become severe, at best prompting premature termination of therapy or at worst becoming life-threatening. To address the off-target irAEs inherent to systemic ICI therapy, we developed a novel, local delivery strategy based upon an array of soluble microneedles (MN). Leveraging our recently reported syngeneic, tobacco-signature murine HNSCC model, we characterized the αCTLA-41 anti-tumor response as both CD8 T cell- and conventional dendritic cell type 1-dependent. When comparing αCTLA-4 therapy delivered in the traditional systemic format or with our local-MN delivery system, we found that while both routes of delivery led to &amp;gt;90% tumor responses, local-MN delivery achieved responses with lower total dosing while also limiting distribution of αCTLA-41 antibody from areas distal to draining lymphatic basins. Employing the previously described Foxp3-GFP-DTR GEMM developed for interrogation of murine irAEs, we found that local-MN protected animals from irAEs observed with systemic therapy. Taken together, our findings support the exploration of the microneedle array as a viable delivery strategy for ICI treatment in HNSCC. Citation Format: Mara Gilardi, Zhiyong Wang, Victoria H. Wu, Miguel Angel Lopez-Ramirez, Fernando Soto-Alvarez, Robert Saddawi-Konefka, Dana Steffen, Marco Proietto, Zbigniew Mikulski, Haruka Miki, Jayanth Shankara Narayanan, Alfredo Molinolo, Joseph Wang, J. Silvio Gutkind. Local delivery of anti CTLA4 mediates cDC1 dependent eradication of HNSCC with limited IRAEs in a preclinical model of oral squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1610.
Abstract 1324: Evaluation of KIF14 in a chemotherapeutic resistant breast cancer cell line
Authors: Keeley Cleghorn, Catherine E. Steding
Journal: Cancer Research (2021)

Abstract The purpose of this study is to elucidate the mechanisms of KIF14 in acquired paclitaxel chemoresistance in a breast cancer cell line by evaluating its expression, activity, and regulatory network. Chemoresistance remains the single greatest cause of therapeutic failure in cancer therapeutics. Development of chemoresistance for compounds that often only suppress growth and do not eliminate tumors has been shown to correlate with more severe clinical phenotypes. Paclitaxel, the microtubule stabilizing compound, has been shown to be of particular importance in the study of chemoresistance as its therapeutic efficacy has been directly shown to be tempered by resistance. Whole transcriptome analysis of long-term chemoresistant breast cancer cells generated at Indiana State University identified a gene not previously reported to play a role in the acquired chemoresistance of breast cancer, kinesin family member 14, KIF14 (Table 1). A knockdown of KIF14 in a chemoresistant breast cancer cell line was performed using Lipofectamine™ 3000 Transfection Reagent. Western Analysis and RT- PCR was performed to confirm the expression of the gene both before and after knockdown was performed. Once expression alterations were confirmed, a proliferation assay, population doubling assay, and a colony formation assay were performed to explore the effects of the gene knockdown in response to paclitaxel treatment. Findings from these studies identify a potential role for KIF14 and microtubule dynamics in acquired chemoresistance against paclitaxel. KIF14 sequencing analysis performed using Illumina HiSeq4000 technology in chemoresistant cellsGeneLog2 Fold Change in Resistant CellsP-valueFDRKIF141.592.83x10-154.18x10-14 Citation Format: Keeley Cleghorn, Catherine E. Steding. Evaluation of KIF14 in a chemotherapeutic resistant breast cancer cell line [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1324.
Short time delay between prostate biopsy for prostate cancer assessment and Holmium laser enucleation of the prostate (HoLEP) correlates with worse perioperative outcomes
Authors: P. Piazza, L. Bianchi, M. Giampaoli, M. Droghetti, C. Casablanca, A. Ercolino, C. Beretta, D. Recenti, E. Balestrazzi, S. Puliatti, G. Rosiello, M. Amato, D. Romagnoli, D. D’Agostino, C. Gaudiano, R. Golfieri, A. Porreca, A. Mottrie, R. Schiavina, E. Brunocilla
Journal: European Urology (2021)
Immunogenomic determinants of tumor microenvironment correlate with superior survival in high-risk neuroblastoma
Authors: Riyue Bao, Stefani Spranger, Kyle Hernandez, Yuanyuan Zha, Peter Pytel, Jason J Luke, Thomas F Gajewski, Samuel L Volchenboum, Susan L Cohn, Ami V Desai
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Tumor-infiltrating CD8 + T cells and neoantigens are predictors of a favorable prognosis and response to immunotherapy with checkpoint inhibitors in many types of adult cancer, but little is known about their role in pediatric malignancies. Here, we analyzed the prognostic strength of T cell-inflamed gene expression and neoantigen load in high-risk neuroblastoma. We also compared transcriptional programs in T cell-inflamed and non-T cell-inflamed high-risk neuroblastomas to investigate possible mechanisms of immune exclusion. Methods A defined T cell-inflamed gene expression signature was used to categorize high-risk neuroblastomas in the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) program (n=123), and the Gabriella Miller Kids First (GMKF) program (n=48) into T cell-inflamed, non-T cell-inflamed, and intermediate groups. Associations between the T cell-inflamed and non-T cell-inflamed group, MYCN amplification, and survival were analyzed by Cox proportional hazards models. Additional survival analysis was conducted after integrating neoantigen load predicted from somatic mutations. Pathways activated in non-T cell-inflamed relative to T cell-inflamed tumors were analyzed using causal network analysis. Results Patients with T cell-inflamed high-risk tumors showed improved overall survival compared with those with non-T cell-inflamed tumors (p&lt;0.05), independent of MYCN amplification status, in both TARGET and GMKF cohorts. Higher neoantigen load was also associated with better event-free and overall survival (p&lt;0.005) and was independent of the T cell-inflamed signature. Activation of MYCN, ASCL1, SOX11, and KMT2A transcriptional programs was inversely correlated with the T cell-inflamed signature in both cohorts. Conclusions Our results indicate that tumors from children with high-risk neuroblastoma harboring a strong T cell-inflamed signature have a more favorable clinical outcome, and neoantigen load is a prognosis predictor, independent of T cell inflammation. Strategies to target SOX11 and other signaling pathways associated with non-T cell-inflamed tumors should be pursued as potential immune-potentiating interventions.
Abstract 2500: The Forkhead-like protein Dach1 governs sensitivity to WEE1 kinase and PARP inhibitors
Authors: Zhiping Li, Xuanmao Jiao, A. Gordon Robertson, Anthony W. Ashton, Andrew Kossenkov, Hao Chen, Lai Yee Phoon, Li Lan, Richard G. Pestell
Journal: Cancer Research (2021)

Abstract Molecular analysis of all cancer types in the cancer genome atlas (TCGA) demonstrated that multiple pathways may be disrupted within a given tumor including PCa. Prostate cancer (PCa), the second leading cause of death in American men, includes distinct genetic subtypes with distinct therapeutic vulnerabilities. Substratification of PCa into genetic subtypes, forms the basis of rational therapy for PCa. Known genetic drivers to PCa include deletions of target genes (PTEN and NKX3.1 deletions), rearrangements/fusions of multiple genes (including TMPRSS2 and the oncogenic ETS transcription factor, ERG) and genetic predisposing factors (including germline DNA-repair gene mutations). An increasingly common finding in PCa are defects in DNA repair. The Drosophila Dac gene was initially cloned as dominant inhibitor of Elipse. The human homologue, DACH1, encodes a winged helix/Forkhead DNA-binding protein that binds in chromatin to FOXM1 sites. Herein, reduced expression of DACH1 is shown in PCa, correlating with DACH1 promoter methylation. Homozygous deletion of DACH1 occurred in up to 18% of human PCa, associated with increased AR activity, increased somatic copy-number alteration and poor prognosis. DACH1 increased DNA repair, as shown in comet assays, enhancing nonhomologous end joining (NHEJ) while reducing homology directed repair (HDR) in DNA repair reporter assays. Laser wounding showed DACH1 was recruited to sites of DNA damage, augmenting the recruitment of Ku70/Ku80. In Dach1 deletion cells reduced expression of Dach1 was associated with resistance to inhibitors of Poly-(ADP)-ribose polymerase (PARP) and enhanced sensitivity to inhibitors of WEE1 kinase and DNA-PK. The abundance of DACH1 in prostate cancer may define a subclass of prostate cancer warranting selective therapies. Citation Format: Zhiping Li, Xuanmao Jiao, A. Gordon Robertson, Anthony W. Ashton, Andrew Kossenkov, Hao Chen, Lai Yee Phoon, Li Lan, Richard G. Pestell. The Forkhead-like protein Dach1 governs sensitivity to WEE1 kinase and PARP inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2500.
2021 American College of Rheumatology/Vasculitis Foundation Guideline for the Management of Antineutrophil Cytoplasmic Antibody–Associated Vasculitis
Authors: Sharon A. Chung, Carol A. Langford, Mehrdad Maz, Andy Abril, Mark Gorelik, Gordon Guyatt, Amy M. Archer, Doyt L. Conn, Kathy A. Full, Peter C. Grayson, Maria F. Ibarra, Lisa F. Imundo, Susan Kim, Peter A. Merkel, Rennie L. Rhee, Philip Seo, John H. Stone, Sangeeta Sule, Robert P. Sundel, Omar I. Vitobaldi, Ann Warner, Kevin Byram, Anisha B. Dua, Nedaa Husainat, Karen E. James, Mohamad A. Kalot, Yih Chang Lin, Jason M. Springer, Marat Turgunbaev, Alexandra Villa‐Forte, Amy S. Turner, Reem A. Mustafa
Journal: Arthritis & Rheumatology (2021)

To provide evidence-based recommendations and expert guidance for the management of antineutrophil cytoplasmic antibody-associated vasculitis (AAV), including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA).Clinical questions regarding the treatment and management of AAV were developed in the population, intervention, comparator, and outcome (PICO) format (47 for GPA/MPA, 34 for EGPA). Systematic literature reviews were conducted for each PICO question. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the quality of evidence and formulate recommendations. Each recommendation required ≥70% consensus among the Voting Panel.We present 26 recommendations and 5 ungraded position statements for GPA/MPA, and 15 recommendations and 5 ungraded position statements for EGPA. This guideline provides recommendations for remission induction and maintenance therapy as well as adjunctive treatment strategies in GPA, MPA, and EGPA. These recommendations include the use of rituximab for remission induction and maintenance in severe GPA and MPA and the use of mepolizumab in nonsevere EGPA. All recommendations are conditional due in part to the lack of multiple randomized controlled trials and/or low-quality evidence supporting the recommendations.This guideline presents the first recommendations endorsed by the American College of Rheumatology and the Vasculitis Foundation for the management of AAV and provides guidance to health care professionals on how to treat these diseases.
Abstract 846: Associations of dietary and lifestyle oxidative balance scores with all-cancer, all-CVD, and all-cause mortality risk among older women: The Iowa Women's Health Study
Authors: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, Boberd M. Bostick
Journal: Cancer Research (2021)

Abstract Background: Substantial basic science evidence suggests that oxidative stress may play a role in aging-related health outcomes, including cancer and cardiovascular diseases (CVD), and oxidative stress markers were linked with all-cancer, all-CVD, and all-cause mortality in epidemiologic studies. However, the associations of many individual dietary and lifestyle anti-/pro-oxidant exposures with mortality are inconsistent. Oxidative balance scores (OBS) that incorporated multiple dietary and lifestyle factors were previously developed and reported to reflect the collective oxidative effects of multiple exposures. Methods: We investigated associations of 11-component dietary and 4-component (physical activity, adiposity, alcohol, and smoking) lifestyle OBS (higher scores were considered more anti-oxidative) with all-cancer, all-CVD, and all-cause mortality among women 55 - 69 years of age at baseline in the prospective Iowa Women's Health Study (1986 - 2012). We assessed OBS-mortality associations using multivariable Cox proportional hazards regression. Results: Of the 34,137 cancer-free women included in the analytic cohort, 18,058 died (4,521 from cancer, and 6,825 from CVD) during a mean/median 22.0/26.1 person-years of follow up. Among participants in the highest relative to the lowest lifestyle OBS quintiles, the adjusted hazards ratios and their 95% confidence intervals for all-cancer, all-CVD, and all-cause mortality were 0.47 (0.43, 0.52), 0.54 (0.54, 0.58), and 0.50 (0.48, 0.53) (all Ptrend &amp;lt; 0.001), respectively. The associations of the dietary OBS with mortality were close to null. Conclusion: Our findings, combined with results from previous studies, suggest that a predominance of antioxidant over pro-oxidant lifestyle exposures may be associated with lower all-cancer, all-CVD, and all-cause mortality risk. Citation Format: Ziling Mao, Anna E. Prizment, DeAnn Lazovich, Boberd M. Bostick. Associations of dietary and lifestyle oxidative balance scores with all-cancer, all-CVD, and all-cause mortality risk among older women: The Iowa Women's Health Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 846.
Mapping phenotypic and aetiological associations between ADHD and physical conditions in adulthood in Sweden: a genetically informed register study
Authors: Ebba Du Rietz, Isabell Brikell, Agnieszka Butwicka, Marica Leone, Zheng Chang, Samuele Cortese, Brian M D'Onofrio, Catharina A Hartman, Paul Lichtenstein, Stephen V Faraone, Ralf Kuja-Halkola, Henrik Larsson
Journal: The Lancet Psychiatry (2021)

Emerging evidence suggests increased risk of several physical health conditions in people with ADHD. Only a few physical conditions have been thoroughly studied in relation to ADHD, and there is little knowledge on associations in older adults in particular. We aimed to investigate the phenotypic and aetiological associations between ADHD and a wide range of physical health conditions across adulthood.
Factor V Atlanta: A Novel Mutation in the F5 Gene Reveals Potential New Cis-Acting Elements Involved in Regulating FV-Short and TFPI Levels
Authors: Karen L Zimowski, Michelle D. Ho, Jordan E Shields, Gabriela Denning, Teodolinda Petrillo, Navdeep Jhita, Angel A Rivera, Miguel A Escobar, Christine L Kempton, Christopher B Doering, Rodney M Camire
Journal: Blood (2017)
Genomic atlas of the proteome from brain, CSF and plasma prioritizes proteins implicated in neurological disorders
Authors: Chengran Yang, Fabiana H. G. Farias, Laura Ibanez, Adam Suhy, Brooke Sadler, Maria Victoria Fernandez, Fengxian Wang, Joseph L. Bradley, Brett Eiffert, Jorge A. Bahena, John P. Budde, Zeran Li, Umber Dube, Yun Ju Sung, Kathie A. Mihindukulasuriya, John C. Morris, Anne M. Fagan, Richard J. Perrin, Bruno A. Benitez, Herve Rhinn, Oscar Harari, Carlos Cruchaga
Journal: Nature Neuroscience (2021)
Bone Marrow Transplant Product Quality Has Decreased Over Time— a Retrospective Examination of NMDP Collected Bone Marrow Products from 1994-2016
Authors: Nicole L. Prokopishyn, Deidre M. Kiefer, Michael A Pulsipher, Galen E. Switzer, Nirali N Shah, Paul V. O'Donnell, Brent R. Logan, Dennis L. Confer, Bronwen E. Shaw
Journal: Blood (2017)
Abstract 1933: Improved DAMP assays for the in vitro assessment of immunogenic cell death
Authors: Andrew L. Niles, Kevin R. Kupcho, Dan F. Lazar, James J. Cali
Journal: Cancer Research (2021)

Abstract The extracellular levels of damage-associated molecular patterns (DAMPs) released during immunogenic cell death (ICD) are positively correlated with the magnitude and efficacy of the resulting in vivo immune response. Therefore, extracellular ATP (eATP) and high mobility group box 1 (HMGB1) have been identified as key biomarkers for their predictive capacity during in vitro ICD screening activities. Current methods for identifying eATP and HMGB1 inducers are laborious, costly, and hampered by poor throughput. To overcome these challenges, we developed easy-to-use, homogeneous, bioluminescent assays that measure dose-dependent release of these immunostimulatory agents directly in cell culture. The eATP assay utilizes an optimized ATP detection chemistry that can be employed directly to assess live-cell kinetic responses for up to 24 h, with even longer exposures supported by a staggered reagent addition approach. The HMGB1 assay measures the protein's concentration at exposure endpoint in the same sample well using complementary luciferase fragment-labelled monoclonal antibodies. We tested the utility of the assays using U20S, Jurkat and U937 cells dosed with serial dilutions of known ICD inducers (doxorubicin, idarubicin, mitoxantrone, and bortezomib). The resulting data suggest the potency of eATP and HMGB1 release is dependent upon cell model and agent but can be reproducibly and robustly measured in 96 and 384 well environments. Further, the eATP assay produced remarkable early dose-dependent response resolution whereas the HMGB1 data provided a confirmatory post-mortem ICD parameter. This new ICD biomarker detection workflow may help to efficiently define and rank-order the capacity of new chemical entities to induce apoptosis and immunogenic cell death. Citation Format: Andrew L. Niles, Kevin R. Kupcho, Dan F. Lazar, James J. Cali. Improved DAMP assays for the in vitro assessment of immunogenic cell death [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1933.