bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salmonella contamination in a network of 10 pig farms interconnected within the same cooperative
Authors: Henry Alexandra , Letellier Ann , Côté Jean‐Charles , Desmarais Gabriel , Lachapelle Virginie , Bergeron Nadia , Lewandowsky Sylvette , Fravalo Philippe 
Published: September 2019

ObjectiveTo evaluate whether pig farms interconnected within the same cooperative share similar Salmonella contamination patterns.SettingTen finishing pig farms within a 100 km radius of a common slaughterhouse were selected. Their inclusion was based on their association to the same cooperative and the sharing of common resources: piglets, feed, swine transporters, slaughterhouse, technicians and veterinarians.ProcedureEach farm was visited three times over a 10‐month period. Pig faeces, the barn front door handle, the feed pipeline, mobile objects (shovel, balance and pig board), the landing stage, the concrete slab of the feed bins, the tire tracks left on the pathways by the animal feed truck, the pig delivery truck and the carcase knacker truck and the mudguards and cabin carpets of the veterinarian and technician vehicles on their arrival at the farm were all analysed for the presence of Salmonella.ResultsAll farms were not equally contaminated with Salmonella. Whereas some farms yielded up to 12 Salmonella isolates, other farms were Salmonella free. Some locations, most notably the landing stage, were more contaminated than others. Salmonella contamination was dynamic in time. Some contaminations seen on farms, on specific locations on the first visit, had disappeared on the second and third visits, but new contaminations were detected on different locations.ConclusionsContamination with Salmonella was not disseminated through the network of the 10 pig farms interconnected within the same cooperative but was rather most often restricted in time to specific locations on specific farms.
Effect of carbohydrases on growth performance, nutrient digestibility, blood profiles, and fecal microbiota in weanling pigs fed reduced energy diet
Authors: Ao Xiang , Zhang Song , Kim In Ho 
Published: September 2019

This study was conducted to evaluate the effect of carbohydrases on growth performance, nutrient digestibility, blood profiles, and fecal microbiota in weanling pigs fed reduced energy diet. A total of 160 crossbred [(Yorkshire × Landrace) × Duroc)] weanling pigs with an initial body weight (BW) of 7.23 ± 1.08 kg were used in this 42 d trial. Pigs were randomly allocated in one of the following four dietary treatments: (1) CON, basal diet [net energy (NE) 2545 kcal kg−1]; (2) LE, low-energy diet (NE 2470 kcal kg−1); (3) LEC1, LE + 0.1% carbohydrase; and (4) LEC2, LE + 0.2% carbohydrase based on the sex and BW. There were eight replications (pens) per treatment with five pigs (two male and three female) per pen. During day 0–7, pigs fed with LE diet had lower (P < 0.05) average daily gain (ADG) and average daily feed intake than those fed with CON and LEC2 diets. LE group reduced (P < 0.05) ADG throughout the experiment compared with CON and LEC2 groups. LE group reduced (P < 0.05) the digestibility of dry matter, nitrogen, and gross energy compared with LEC2 diet. Taken together, LE diet caused detrimental effects on growth performance and nutrient digestibility in weanlings, whereas the addition of carbohydrases (0.2%) partially counteracted these negative effects.
Effect of heat treatment and heat treatment in combination with lignosulfonate on in situ rumen degradability of canola cake crude protein, lysine, and methionine
Authors: Micek Piotr , Słota Katarzyna , Górka Paweł 
Published: September 2019

The aim of this study was to determine the effect of heat treatment alone or in combination with the addition of lignosulfonate (LSO3) on canola cake protein, lysine, and methionine degradation in the rumen. Cold-pressed canola cake was left untreated, heated at 90, 110, 130, or 150 °C, or processed with 5% of LSO3 (in dry matter) and then heated. Effective rumen degradability of crude protein (CP), lysine, and methionine was less for treated than untreated canola cake (P < 0.05) and decreased with increased temperature of heating, but particularly when canola cake was heated at 150 °C (quadratic, P < 0.01). In general, effective rumen degradability of CP, lysine, and methionine was less for canola cake heated at 130 °C in combination with LSO3 compared with canola cake heat treated only (quadratic × LSO3 interaction, P ≤ 0.07). Results of this study indicate that high temperature heating (130 °C or greater for 60 min) may be necessary to protect canola cake protein from degradation in the rumen, and the combination of heat treatment and LSO3 may be more effective in protecting canola cake protein, lysine, and methionine from degradation in the rumen than the use of heat treatment only.
Effect of flavor supplementation on growth performance, nutrient digestibility, blood profiles, and carcass quality in growing–finishing pigs
Authors: Ao Xiang , Lei Yan , Kim In Ho 
Published: September 2019

This study was conducted to evaluate the effect of supplementation of different flavors (apple and anise) on growth performance, nutrient digestibility, blood profiles, and carcass quality in growing–finishing pigs. A total of 96 growing pigs [(Yorkshire × Landrace) × Duroc] with an average body weight (BW) of 28.2 ± 0.7 kg were randomly assigned to one of the following three treatments: (1) CON, basal diet; (2) APF, basal diet + 0.05% apple flavor; (3) ANF, basal diet + 0.05% anise flavor, according to their BW and sex in this 15 wk experiment. There were eight replications (pens) per treatment and four pigs per pen (two barrows and two gilts). During week 0–5, pigs fed ANF diets had greater (p < 0.05) average daily gain (ADG) and average daily feed intake than those fed CON and APF diets. Dietary ANF treatment increased (p < 0.05) ADG during 0–15 wk compared with CON treatment. At the end of 5 wk, the apparent total tract digestibility of nitrogen in ANF treatment was improved (p < 0.05) compared with that in CON treatment. Dietary treatments did not affect the studied traits of carcass and meat quality. The inclusion of anise flavor increased ADG, but apple flavor had no effect on growth performance in growing–finishing pigs.
Gamma-induced background in the KATRIN main spectrometer
Authors: Altenmüller K. , Arenz M. , Baek W.-J. , Beck M. , Beglarian A. , Behrens J. , Berlev A. , Besserer U. , Blaum K. , Block F. , Bobien S. , Bode T. , Bornschein B. , Bornschein L. , Bouquet H. , Brunst T. , Buzinsky N. , Chilingaryan S. , Choi W. Q. , Deffert M. , Doe P. J. , Dragoun O. , Drexlin G. , Dyba S. , Eitel K. , Ellinger E. , Engel R. , Enomoto S. , Erhard M. , Eversheim D. , Fedkevych M. , Formaggio J. A. , Fränkle F. M. , Franklin G. B. , Friedel F. , Fulst A. , Gil W. , Glück F. , Ureña A. Gonzalez , Grössle R. , Gumbsheimer R. , Hackenjos M. , Hannen V. , Harms F. , Haußmann N. , Heizmann F. , Helbing K. , Herz W. , Hickford S. , Hilk D. , Hillesheimer D. , Howe M. A. , Huber A. , Jansen A. , Karl C. , Kellerer J. , Kernert N. , Kippenbrock L. , Klein M. , Kopmann A. , Korzeczek M. , Kovalík A. , Krasch B. , Kraus A. , Kraus M. , Lasserre T. , Lebeda O. , Lehnert B. , Letnev J. , Lokhov A. , Machatschek M. , Marsteller A. , Martin E. L. , Mertens S. , Mirz S. , Monreal B. , Neumann H. , Niemes S. , Osipowicz A. , Otten E. , Parno D. S. , Pollithy A. , Poon A. W. P. , Priester F. , Ranitzsch P. C.-O. , Rest O. , Robertson R. G. H. , Rodenbeck C. , Röllig M. , Röttele C. , Ryšavý M. , Sack R. , Saenz A. , Schimpf L. , Schlösser K. , Schlösser M. , Schlüter L. , Schrank M. , Seitz-Moskaliuk H. , Sibille V. , Slezák M. , Steidl M. , Steinbrink N. , Sturm M. , Suchopar M. , Tcherniakhovski D. , Telle H. H. , Thorne L. A. , Thümmler T. , Titov N. , Tkachev I. , Trost N. , Valerius K. , Vénos D. , Vianden R. , Hernández A. P. Vizcaya , Weber M. , Weinheimer C. , Weiss C. , Welte S. , Wendel J. , Wilkerson J. F. , Wolf J. , Wüstling S. , Zadoroghny S. , Zeller G. 
Published: September 2019

Abstract
The KATRIN experiment aims to measure the effective electron antineutrino mass $$m_{\overline{\nu }_e}$$mν¯e with a sensitivity of $${0.2}\,{\hbox {eV}/\hbox {c}^2}$$0.2eV/c2 using a gaseous tritium source combined with the MAC-E filter technique. A low background rate is crucial to achieving the proposed sensitivity, and dedicated measurements have been performed to study possible sources of background electrons. In this work, we test the hypothesis that gamma radiation from external radioactive sources significantly increases the rate of background events created in the main spectrometer (MS) and observed in the focal-plane detector. Using detailed simulations of the gamma flux in the experimental hall, combined with a series of experimental tests that artificially increased or decreased the local gamma flux to the MS, we set an upper limit of $${0.006}\,{\hbox {count}/\hbox {s}}$$0.006count/s (90% C.L.) from this mechanism. Our results indicate the effectiveness of the electrostatic and magnetic shielding used to block secondary electrons emitted from the inner surface of the MS.
Targeting the Metabolic Response to Statin-Mediated Oxidative Stress Produces a Synergistic Antitumor Response
Authors: McGregor Grace H. , Campbell Andrew D. , Fey Sigrid K. , Tumanov Sergey , Sumpton David , Blanco Giovanny Rodriguez , Mackay Gillian , Nixon Colin , Vazquez Alexei , Sansom Owen J. , Kamphorst Jurre J. 
Published: September 2019

Abstract

Statins are widely prescribed inhibitors of the mevalonate pathway, acting to lower systemic cholesterol levels. The mevalonate pathway is critical for tumorigenesis and is frequently upregulated in cancer. Nonetheless, reported effects of statins on tumor progression are ambiguous, making it unclear whether statins, alone or in combination, can be used for chemotherapy. Here, using advanced mass spectrometry and isotope tracing, we showed that statins only modestly affected cancer cholesterol homeostasis. Instead, they significantly reduced synthesis and levels of another downstream product, the mitochondrial electron carrier coenzyme Q, both in cultured cancer cells and tumors. This compromised oxidative phosphorylation, causing severe oxidative stress. To compensate, cancer cells upregulated antioxidant metabolic pathways, including reductive carboxylation, proline synthesis, and cystine import. Targeting cystine import with an xCT transporter–lowering MEK inhibitor, in combination with statins, caused profound tumor cell death. Thus, statin-induced ROS production in cancer cells can be exploited in a combinatorial regimen.

Significance:
Cancer cells induce specific metabolic pathways to alleviate the increased oxidative stress caused by statin treatment, and targeting one of these pathways synergizes with statins to produce a robust antitumor response.
See related commentary by Cordes and Metallo, p. 151
Targeting EZH2 Enhances Antigen Presentation, Antitumor Immunity, and Circumvents Anti–PD-1 Resistance in Head and Neck Cancer
Authors: Zhou Liye , Mudianto Tenny , Ma Xiaojing , Riley Rachel , Uppaluri Ravindra 
Published: September 2019

Abstract

Purpose:
Anti–programmed death-1 (PD-1) receptor–based therapeutics improve survival in patients with recurrent head and neck squamous cell carcinoma (HNSCC), but many do not benefit due to a low response rate. Herein, we identified EZH2 as a therapeutic target that enhanced tumor cell antigen presentation and subsequently sensitized resistant tumors to anti–PD-1 therapy.

Experimental Design:
EZH2 regulation of antigen presentation was defined using EZH2 inhibitors (GSK126 and EPZ6438) in human and mouse HNSCC cell lines. Mechanistic dissection of EZH2 in regulation of antigen presentation was investigated using flow cytometry, qRT-PCR, ELISA, and chromatin-immunoprecipitation assays. EZH2-deficient cell lines were generated using CRISPR-CAS9. GSK126 and anti–PD-1–blocking antibody were used in testing combinatorial therapy in vivo.

Results:
EZH2 expression was negatively correlated with antigen-processing machinery pathway components in HNSCC data sets in The Cancer Genome Atlas. EZH2 inhibition resulted in significant upregulation of MHC class I expression in human and mouse human papillomavirus–negative HNSCC lines in vitro and in mouse models in vivo. Enhanced antigen presentation on the tumor cells by EZH2 inhibitors or CRISPR–mediated EZH2 deficiency increased antigen-specific CD8+ T-cell proliferation, IFNγ production, and tumor cell cytotoxicity. Mechanistically, EZH2 inhibition reduced the histone H3K27me3 modification on the β-2-microglobulin promoter. Finally, in an anti–PD-1–resistant model of HNSCC, tumor growth was suppressed with combination therapy.

Conclusions:
Our results demonstrated that targeting EZH2 enhanced antigen presentation and was able to circumvent anti–PD-1 resistance. Thus, combining EZH2 targeting with anti–PD-1 may increase therapeutic susceptibility in HNSCC.
DNA Methylation Profiling Identifies Distinct Clusters in Angiosarcomas
Authors: Weidema Marije E. , van de Geer Ellen , Koelsche Christian , Desar Ingrid M.E. , Kemmeren Patrick , Hillebrandt-Roeffen Melissa H.S. , Ho Vincent K.Y. , van der Graaf Winette T.A. , Versleijen-Jonkers Yvonne M.H. , von Deimling Andreas , Flucke Uta E. 
Published: September 2019

AbstractPurpose:DNA methylation profiling has previously uncovered biologically and clinically meaningful subgroups within many tumor types, but was not yet performed in angiosarcoma. Angiosarcoma is a rare sarcoma with very heterogeneous clinical presentations, which may be based on differences in biological background. In this exploratory study, DNA methylation profiling of 36 primary angiosarcoma samples from visceral, deep soft tissue, radiation-induced, and UV-induced localizations was performed.Experimental Design:Primary angiosarcoma formalin-fixed paraffin-embedded samples from visceral, soft tissue, radiation-induced, and UV-induced origin were collected from a nationwide search for angiosarcoma in the Netherlands. DNA was extracted for methylation profiling with the Illumina Infinium MethylationEPIC array. Quality control assessment and unsupervised hierarchical clustering were performed. Copy-number profiles were generated and analyzed for chromosomal stability. Clinical data were obtained from the Netherlands Cancer Registry.Results:DNA methylation profiling by unsupervised hierarchical clustering of 36 angiosarcoma samples (6 visceral, 5 soft tissue, 14 radiation-induced, 11 UV-induced) revealed two main clusters (A and B), which were divided into four subclusters. The clusters largely corresponded with clinical subtypes, showing enrichment of UV-induced cases in cluster A1 and radiation-induced cases in cluster A2. Visceral and soft tissue cases almost exclusively fell into cluster B. Cluster A showed significantly increased chromosomal instability and better overall survival (22 vs. 6 months, P = 0.046) compared with cluster B.Conclusions:In this novel methylation profiling study, we demonstrated for the first time four different angiosarcoma clusters. These clusters correlated with clinical subtype, overall survival, and chromosomal stability.
Quantitative High-Throughput Screening Using an Organotypic Model Identifies Compounds that Inhibit Ovarian Cancer Metastasis
Authors: Kenny Hilary A. , Lal-Nag Madhu , Shen Min , Kara Betul , Nahotko Dominik A. , Wroblewski Kristen , Fazal Sarah , Chen Siquan , Chiang Chun-Yi , Chen Yen-Ju , Brimacombe Kyle R. , Marugan Juan , Ferrer Marc , Lengyel Ernst 
Published: September 2019

Abstract
The tumor microenvironment (TME) is a key determinant of metastatic efficiency. We performed a quantitative high-throughput screen (qHTS) of diverse medicinal chemistry tractable scaffolds (44,420 compounds) and pharmacologically active small molecules (386 compounds) using a layered organotypic, robust assay representing the ovarian cancer metastatic TME. This 3D model contains primary human mesothelial cells, fibroblasts, and extracellular matrix, to which fluorescently labeled ovarian cancer cells are added. Initially, 100 compounds inhibiting ovarian cancer adhesion/invasion to the 3D model in a dose-dependent manner were identified. Of those, eight compounds were confirmed active in five high-grade serous ovarian cancer cell lines and were further validated in secondary in vitro and in vivo biological assays. Two tyrosine kinase inhibitors, PP-121 and milciclib, and a previously unreported compound, NCGC00117362, were selected because they had potency at 1 μmol/L in vitro. Specifically, NCGC00117362 and PP-121 inhibited ovarian cancer adhesion, invasion, and proliferation, whereas milciclib inhibited ovarian cancer invasion and proliferation. Using in situ kinase profiling and immunoblotting, we found that milciclib targeted Cdk2 and Cdk6, and PP-121 targeted mTOR. In vivo, all three compounds prevented ovarian cancer adhesion/invasion and metastasis, prolonged survival, and reduced omental tumor growth in an intervention study. To evaluate the clinical potential of NCGC00117362, structure–activity relationship studies were performed. Four close analogues of NCGC00117362 efficiently inhibited cancer aggressiveness in vitro and metastasis in vivo. Collectively, these data show that a complex 3D culture of the TME is effective in qHTS. The three compounds identified have promise as therapeutics for prevention and treatment of ovarian cancer metastasis.
Modulating TAK1 Expression Inhibits YAP and TAZ Oncogenic Functions in Pancreatic Cancer
Authors: Santoro Raffaela , Zanotto Marco , Simionato Francesca , Zecchetto Camilla , Merz Valeria , Cavallini Chiara , Piro Geny , Sabbadini Fabio , Boschi Federico , Scarpa Aldo , Melisi Davide 
Published: September 2019

Abstract
YAP and TAZ are central determinants of malignancy; however, their functions remain still undruggable. We identified TGFβ-activated kinase 1 (TAK1) as a central hub integrating the most relevant signals sustaining pancreatic cancer aggressiveness and chemoresistance. Glycogen synthase kinase (GSK)3 is known to stabilize TAK1, and its inhibition causes a reduction in TAK1 levels. Here, we hypothesized that TAK1 could sustain YAP/TAZ program, and thus, modulation of TAK1 expression through the inhibition of GSK3 could impair YAP/TAZ functions in pancreatic cancer.
Differentially expressed transcripts between pancreatic cancer cells expressing scramble or TAK1-specific shRNA were annotated for functional interrelatedness by ingenuity pathway analysis. TAK1 expression was modulated by using different GSK3 inhibitors, including LY2090314. In vivo activity of LY2090314 alone or in combination with nab-paclitaxel was evaluated in an orthotopic nude mouse model.
Differential gene expression profiling revealed significant association of TAK1 expression with HIPPO and ubiquitination pathways. We measured a significant downregulation of YAP/TAZ and their regulated genes in shTAK1 cells. TAK1 prevented YAP/TAZ proteasomal degradation in a kinase independent manner, through a complex with TRAF6, thereby fostering their K63-ubiquitination versus K48-ubiquitination. Pharmacologic modulation of TAK1 by using GSK3 inhibitors significantly decreased YAP/TAZ levels and suppressed their target genes and oncogenic functions. In vivo, LY2090314 plus nab-paclitaxel significantly prolonged mice survival duration.
Our study demonstrates a unique role for TAK1 in controlling YAP/TAZ in pancreatic cancer. LY2090314 is a novel agent that warrants further clinical development in combination with nab-paclitaxel for the treatment of pancreatic cancer.
Prostate Tumor Cell–Derived IL1β Induces an Inflammatory Phenotype in Bone Marrow Adipocytes and Reduces Sensitivity to Docetaxel via Lipolysis-Dependent Mechanisms
Authors: Herroon Mackenzie K. , Diedrich Jonathan D. , Rajagurubandara Erandi , Martin Carly , Maddipati Krishna R. , Kim Seongho , Heath Elisabeth I. , Granneman James , Podgorski Izabela 
Published: September 2019

Abstract

Adipocyte–tumor cell cross-talk is one of the critical mediators of tumor progression and an emerging facilitator of therapy evasion. Tumor cells that metastasize to adipocyte-rich bone marrow take advantage of the interplay between metabolic and inflammatory pathways to activate prosurvival mechanisms that allow them to thrive and escape therapy. Using in vitro and in vivo models of marrow adiposity, we demonstrate that metastatic prostate carcinoma cells engage bone marrow adipocytes in a functional cross-talk that promotes IL1β expression in tumor cells. Tumor-supplied IL1β contributes to adipocyte lipolysis and regulates a proinflammatory phenotype in adipocytes via upregulation of COX-2 and MCP-1. We further show that the enhanced activity of the IL1β/COX-2/MCP-1 axis and a resulting increase in PGE2 production by adipocytes coincide with augmented hypoxia signaling and activation of prosurvival pathways in tumor cells, revealing a potential mechanism of chemoresistance. The major consequence of this interplay is the reduced response of prostate cancer cells to docetaxel, a phenomenon sensitive to the inhibition of lipolysis.

Implications:
Studies presented herein highlight adipocyte lipolysis as a tumor-regulated metabolic event that engages proinflammatory cross-talk in the microenvironment to promote prostate cancer progression in bone. Understanding the impact of bone marrow adipose tissue on tumor adaptation, survival, and chemotherapy response is fundamentally important, as current treatment options for metastatic prostate cancer are palliative.
Blood Microbiota Modification After Myocardial Infarction Depends Upon Low‐Density Lipoprotein Cholesterol Levels
Authors: Amar Jacques , Lelouvier Benjamin , Servant Florence , Lluch Jérôme , Burcelin Rémy , Bongard Vanina , Elbaz Meyer 
Published: September 2019

Background

The role of bacteria on the onset of cardiovascular disease has been suggested. Reciprocally, increased intestinal bacterial translocation and bloodstream infection are common comorbidities associated with heart failure and myocardial infarction (
MI
). In this context, the aim of this study was to analyze the blood microbiome in patients shortly after acute myocardial infarction.

Methods and Results

We carried out a case control study comparing 103 patients at high cardiovascular risk but free of coronary disease and 99 patients who had an
MI
. The blood microbiome was analyzed both quantitatively by 16S quantitative polymerase chain reaction and qualitatively by 16S targeted metagenomic sequencing specifically optimized for blood samples. A significant increase in blood bacterial 16S
rDNA
concentration was observed in patients admitted for
MI
. This increase in blood bacterial
DNA
concentration was independent of post‐
MI
left ventricular function and was more marked in patients with low‐density lipoprotein cholesterol ≥1 g/L. In addition, differences in the proportion of numerous bacterial taxa in blood were significantly modified with the onset of
MI
, thus defining a blood microbiota signature of
MI
. Among the bacterial taxa whose proportions are decreased in patients with
MI
, at least 6 are known to include species able to metabolize cholesterol.

Conclusions

These results could provide the basis for the identification of blood microbiome‐based biomarkers for the stratification of
MI
patients. Furthermore, these findings should provide insight into the mechanism underlying the negative correlation reported between low‐density lipoprotein cholesterol concentration and the prognosis at the acute onset of
MI
and mortality.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
02405468.