bluuebunny/crossref_metadata_2025_split huggingface dataset:
FACIES HETEROGENEITIES IN A RAMP CARBONATE RESERVOIR ANALOGUE: A NEW HIGH‐RESOLUTION APPROACH FOR 3D FACIES MODELLING
Authors: Petrovic A. , Aigner T. , Pontiggia M. 
Published: March 2018

In contrast to the conventional view that facies distribution patterns on carbonate ramps are relatively simple, outcrop analogue studies point to a high degree of internal facies complexity. Depending on the diagenetic overprint, this complex pattern may result in reservoir compartmentalization due to the presence of interflow baffles. The often subseismic scale heterogeneities may not be included in conventional reservoir modelling. In order to evaluate how facies heterogeneities in shoal reservoirs can be modelled realistically, this paper presents a facies modelling workflow which includes a new approach to the design of training images for multiple‐point statistics (MPS). The workflow was developed in the course of a reservoir outcrop analogue study of a Ladinian (Middle Triassic) coquinadominated shoal complex in SW Germany which was deposited on an epicontinental, gently inclined carbonate ramp. The data set was based on an intensive field study and includes 3D facies and sequence stratigraphic analyses of the largest shoal complex in the Quaderkalk Formation (Upper Muschelkalk). This several metre thick shoal complex represents a subseismic scale, bioclast‐rich reservoir analogue and has a very heterogeneous facies pattern.Integrating 1D facies logs and sequence stratigraphic trends from tens of outcrop sections and cores, two nested 3D geocellular facies models were produced: (i) a large‐scale (30 × 30 km) model based on truncated Gaussian simulation (TGS); this formed the basis for (ii) a smaller‐scale (10 × 10 km), more detailed model based on multiple point statistics. In addition, a new approach for training image design was developed to honour small‐scale sequence stratigraphic trends and lateral facies patterns observed in modern analogues. Compared to facies patterns in modern analogues, the large‐scale model presents geologically‐feasible facies distribution patterns and geometries, and in addition shows a vertical facies distribution which is similar to the observed sequence stratigraphic architecture of the outcrop data‐set used. Due to the new training image design, the final small‐scale model has a distribution pattern of facies heterogeneities which looks similar to modern facies distributions in the offshore UAE and thus represents a valuable method of producing realistic reservoir facies models.The modelling workflow and the new approach for training image design presented will help to reduce uncertainties in the understanding and modelling of subsurface reservoirs by using a systematic combination of outcrop data and modern analogues, with the consistent application of sequence stratigraphic principles. In addition, this study emphasises the importance of careful training image design, derived from modern analogues, which can be used as realistic inputs in order to optimize multiple point simulations, and which may be applied to producing bioclastic reservoirs such as those located on the Arabian Plate or offshore Brazil.
Clinical use of plasma lactate concentration. Part 2: Prognostic and diagnostic utility and the clinical management of hyperlactatemia
Authors: Rosenstein Patricia G. , Tennent‐Brown Brett S. , Hughes Dez 
Published: March 2018

AbstractObjectiveTo review the current literature pertaining to the use of lactate as a prognostic indicator and therapeutic guide, the utility of measuring lactate concentrations in body fluids other than blood or plasma, and the clinical management of hyperlactatemia in dogs, cats, and horses.Data SourcesArticles were retrieved without date restrictions primarily via PubMed, Scopus, and CAB Abstracts as well as by manual selection.Human and Veterinary Data SynthesisIncreased plasma lactate concentrations are associated with increased morbidity and mortality. In populations with high mortality, hyperlactatemia is moderately predictive in identifying nonsurvivors. Importantly, eulactatemia predicts survival better than hyperlactatemia predicts death. Consecutive lactate measurements and calculated relative measures appear to outperform single measurements. The use of lactate as a therapeutic guide has shown promising results in people but is relatively uninvestigated in veterinary species. Increased lactate concentrations in body fluids other than blood should raise the index of suspicion for septic or malignant processes. Management of hyperlactatemia should target the underlying cause.ConclusionLactate is a valuable triage and risk stratification tool that can be used to separate patients into higher and lower risk categories. The utility of lactate concentration as a therapeutic target and the measurement of lactate in body fluids shows promise but requires further research.
Antibiotic Hybrids: the Next Generation of Agents and Adjuvants against Gram-Negative Pathogens?
Authors: Domalaon Ronald , Idowu Temilolu , Zhanel George G. , Schweizer Frank 
Published: March 2018

SUMMARY
The global incidence of drug-resistant Gram-negative bacillary infections has been increasing, and there is a dire need to develop novel strategies to overcome this problem. Intrinsic resistance in Gram-negative bacteria, such as their protective outer membrane and constitutively overexpressed efflux pumps, is a major survival weapon that renders them refractory to current antibiotics. Several potential avenues to overcome this problem have been at the heart of antibiotic drug discovery in the past few decades. We review some of these strategies, with emphasis on antibiotic hybrids either as stand-alone antibacterial agents or as adjuvants that potentiate a primary antibiotic in Gram-negative bacteria. Antibiotic hybrid is defined in this review as a synthetic construct of two or more pharmacophores belonging to an established agent known to elicit a desired antimicrobial effect. The concepts, advances, and challenges of antibiotic hybrids are elaborated in this article. Moreover, we discuss several antibiotic hybrids that were or are in clinical evaluation. Mechanistic insights into how tobramycin-based antibiotic hybrids are able to potentiate legacy antibiotics in multidrug-resistant Gram-negative bacilli are also highlighted. Antibiotic hybrids indeed have a promising future as a therapeutic strategy to overcome drug resistance in Gram-negative pathogens and/or expand the usefulness of our current antibiotic arsenal.
Diagnosis of sporadic neurofibromatosis type 2 in the paediatric population
Authors: Anand Geetha , Vasallo Grace , Spanou Maria , Thomas Saumya , Pike Michael , Kariyawasam Didu Sanduni , Mehta Sanjay , Parry Allyson , Durie-Gair Juliette , Nicholson James , Lascelles Karine , Everett Vanessa , Gibbon Frances Mary , Jarvis Nicola , Elston John , Evans Dafydd Gareth , Halliday Dorothy 
Published: March 2018

ObjectiveOnset of symptoms in severe sporadic neurofibromatosis type 2 (NF2) is typically within childhood; however, there is poor awareness of presenting features in young children, potentially resulting in delayed diagnosis and poorer outcome. We have reviewed presentation of sporadic paediatric NF2 to raise awareness of early features, highlighting those requiring further investigation.DesignPatients diagnosed with NF2 at age ≤16 and seen between 2012 and 2015 were notified via the British Paediatric Neurology Surveillance Unit or identified through the English NF2 service.ResultsEpidemiological data estimate that 1 in 110 611 births are affected with childhood-onset NF2. Notes of 32 patients with sporadic NF2 were reviewed. Of those presenting under the age of 5, 89% (17/19) had ocular, 74% (14/19) dermatological and 58% (11/19) neurological signs; in 84% (16/19) features were multisystemic. Sixty-six per cent (21/32) had ≥1 atypical feature, including cerebellar hypoplasia in three cases (9%) and focal cortical dysplasia in five out of seven seizure-related presentations. Five cases presented with a sometimes transient or intermittent cranial nerve mononeuropathy. The mean delay to diagnosis was 3.16 years; in eight cases (25%) this exceeded 6 years. Most significant delay occurred in mononeuropathy, ophthalmological and/or seizure presentations, with a mean delay of 3, 4.5 and 6 years, respectively. Eighty-four per cent (27/32) of cases needed intervention in childhood.ConclusionsAll non-vestibular schwannoma NF2 presentations in childhood had significant diagnostic delay. We emphasise the importance of detailed assessment of skin and eyes in unusual presentations and propose an aide to prompt timely referral to specialist services.
The liver as an organ at risk forToxoplasmatransmission during transplantation: myth or reality?
Authors: Autier Brice , Dion Sarah , Robert-Gangneux Florence 
Published: March 2018

AimToxoplasmosis following liver transplant with donor–recipient mismatch is rare, but is often life-threatening. However, there are no data on the frequency of cyst carriage in the liver, nor consensual chemoprophylaxis guidelines. This study aimed at describing frequency and localisation ofToxoplasmacysts in the liver in a mouse model of chronic infection to predict the risk in liver transplantation.MethodsHeart, brain and liver lobes of 21 mice chronically infected withToxoplasmawere collected for DNA extraction and amplification ofToxoplasma gondiirep529 sequence by real-time PCR.ResultsParasite DNA was detected in the liver of 19/21 mice (90.5%), with no preferential anatomical localisation, but with higher parasite loads in the papillary process. Parasite loads in the liver were far lower than in brain and heart. The number of infected lobes was inversely correlated to the total liver weight, but was independent of the brain parasite load and of the parasite strain.ConclusionsThe liver is a frequent site of cyst carriage, confirming that transplantation of an organ from a seropositive donor to seronegative recipient is at high risk for acquired toxoplasmosis. Systematic serological screening prior to transplantation and chemoprophylaxis in patients at risk are fully justified.
Model development: establishing pigs with homogenous microbial profile in the hind gut
Authors: Kiros Tadele G. , Pinloche Eric , D’Inca Romain , Auclair Eric , Van Kessel Andrew 
Published: March 2018

The considerable animal-to-animal variation in microbial profiles is a challenge in elucidating the role of gut microbiota in host metabolism. The main purpose of this study was, therefore, to develop a pig model with reduced animal-to-animal variation in gut microbial profile. Twelve piglets from four sows were reared conventionally and 12 piglets from four sows were reared artificially in high efficiency particulate air (HEPA) filtered isolators. All isolator-reared piglets were given an artificial colostrum formula containing the combined fecal material from all eight sows. All piglets were killed at 21 d of age and intestinal contents subjected to 16s rRNA gene-based terminal restriction fragment length polymorphism (T-RFLP) profiling. Resulting T-RFLP profiles clustered into two distinct groups representing the two treatment groups. Furthermore, Bray–Curtis dissimilarity distance values and Dice similarity indices showed reduced beta diversity in isolator-reared pigs indicating animal-to-animal variation was reduced in isolator-reared compared to conventional piglets. However, surprisingly, increased alpha diversity was observed in isolator-reared piglets compared with conventional piglets. In conclusion, the study demonstrated that rearing of piglets under conditions of controlled environment reduced animal-to-animal variation in the hindgut microbiota while paradoxically increasing within animal microbial diversity. Isolator rearing may be useful as a model to improve detection of treatment effects on gut microbiota.
Identification of serum metabolites associated with the risk of metritis in transition dairy cows
Authors: Hailemariam Dagnachew , Zhang Guanshi , Mandal Rupasri , Wishart David S. , Ametaj Burim N. 
Published: March 2018

In this study, we aimed to identify metabolite signatures that characterize metritis prior to, during, and after the disease incidence. Blood samples were collected from 100 Holstein cows at five time points before and after parturition. Six cows that developed metritis and 20 controls were selected for metabolomics analysis in a nested case-control study. Twenty nine serum metabolites were quantified using gas chromatography–mass spectroscopy. Results showed that similar panels of metabolites differentiated pre-metritic and control cows at 8 and 4 wk prepartum. The top most important metabolites that differentiated the two groups of cows at 8 wk prepartum were oxalate, ornithine, pyroglutamic acid, d-mannose, and glutamic acid, and at 4 wk prepartum were ornithine, pyroglutamic acid, d-mannose, glutamic acid, and phosphoric acid, suggesting their potential use as risk biomarkers for metritis. Area under the curve with values of 1.0 and 0.969 at 8 and 4 wk, respectively, indicated that those panels of metabolites have a very high sensitivity and specificity to be used as risk biomarkers for metritis. Overall, results showed that specific serum metabolite signatures can be used to screen cows for susceptibility to metritis during the dry off period, and to better understand the etiopathobiology of the disease.
Effects of the lipid-coated zinc oxide dietary supplement on intestinal mucosal morphology and gene expression associated with the gut health in weanling pigs challenged with enterotoxigenic Escherichia coli K88
Authors: Han Jeong Hee , Song Min Hye , Kim Ha Na , Jang Insurk , Lee C. Young , Park Byung-Chul 
Published: March 2018

Effects of a lipid-coated zinc oxide (ZnO) Shield Zn® (SZ) vs. ZnO were evaluated. Forty 25-d-old weanling pigs were fed a nursery diet supplemented with 100 mg kg−1 Zn with ZnO (ZnO-100), ZnO-2500, SZ-100, -200, or -400. All piglets were challenged orally with 5 × 108 colony-forming units of enterotoxigenic Escherichia coli K88 on day 7 and euthanized on day 14. The fecal consistency score (FCS) was less for the SZ group vs. ZnO-100 (P < 0.05). The intestinal villus height:crypt depth ratio and goblet cell density were greater for the SZ group vs. ZnO-100. By regression analyses, SZ-100 to -200 and SZ-300 to -400 were comparable to ZnO-2500 in the FCS and intestinal variables, respectively. The jejunal mucosal mRNA level did not differ between the SZ group and either ZnO group in insulin-like growth factor-I and multiple structural proteins and cytokines including zonula occludens protein (ZO) 1 and interleukin (IL) 10 except for lower ZO-1 and IL-10 mRNA levels for the SZ group than for ZnO-2500 and ZnO-100, respectively. The ZO-1 mRNA level regressed positively on the supplemental SZ concentration. Results suggest that SZ play a role in epithelial barrier function and inflammation by modulating the expression of ZO-1 and IL-10.
Organelle-Derived Acetyl-CoA Promotes Prostate Cancer Cell Survival, Migration, and Metastasis via Activation of Calmodulin Kinase II
Authors: Yu Guoyu , Cheng Chien-Jui , Lin Song-Chang , Lee Yu-Chen , Frigo Daniel E. , Yu-Lee Li-Yuan , Gallick Gary E. , Titus Mark A. , Nutt Leta K. , Lin Sue-Hwa 
Published: March 2018

Abstract
Although emerging evidence suggests a potential role of calcium/calmodulin-dependent kinase II (CaMKII) in prostate cancer, its role in prostate cancer tumorigenesis is largely unknown. Here, we examine whether the acetyl CoA-CaMKII pathway, first described in frog oocytes, promotes prostate cancer tumorigenesis. In human prostate cancer specimens, metastatic prostate cancer expressed higher levels of active CaMKII compared with localized prostate cancer. Correspondingly, basal CaMKII activity was significantly higher in the more tumorigenic PC3 and PC3-mm2 cells relative to the less tumorigenic LNCaP and C4-2B4 cells. Deletion of CaMKII by CRISPR/Cas9 in PC3-mm2 cells abrogated cell survival under low-serum conditions, anchorage-independent growth and cell migration; overexpression of constitutively active CaMKII in C4-2B4 cells promoted these phenotypes. In an animal model of prostate cancer metastasis, genetic ablation of CaMKII reduced PC3-mm2 cell metastasis from the prostate to the lymph nodes. Knockdown of the acetyl-CoA transporter carnitine acetyltransferase abolished CaMKII activation, providing evidence that acetyl-CoA generated from organelles is a major activator of CaMKII. Genetic deletion of the β-oxidation rate-limiting enzyme ACOX family proteins decreased CaMKII activation, whereas overexpression of ACOXI increased CaMKII activation. Overall, our studies identify active CaMKII as a novel connection between organelle β-oxidation and acetyl-CoA transport with cell survival, migration, and prostate cancer metastasis.
Significance: This study identifies a cell metabolic pathway that promotes prostate cancer metastasis and suggests prostate cancer may be susceptible to β-oxidation inhibitors. Cancer Res; 78(10); 2490–502. ©2018 AACR.
Visualization of Breast Cancer Metabolism Using Multimodal Nonlinear Optical Microscopy of Cellular Lipids and Redox State
Authors: Hou Jue , Williams Joshua , Botvinick Elliot L. , Potma Eric O. , Tromberg Bruce J. 
Published: March 2018

Abstract
Label-free nonlinear optical microscopy (NLOM) based on two-photon excited fluorescence (TPEF) from cofactors nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+) is widely used for high-resolution cellular redox imaging. In this work, we combined three label-free NLOM imaging methods to quantitatively characterize breast cancer cells and their relative invasive potential: (i) TPEF optical redox ratio (ORR = FAD+/NADH + FAD+), (ii) coherent Raman scattering of cellular lipids, and (iii) second harmonic generation of extracellular matrix (ECM) collagen. 3D spheroid models of primary mammary epithelial (PME) cells and breast cancer cell lines (T47D and MDA-MB-231) were characterized based on their unique ORR and lipid volume fraction signatures. Treatment with 17β-estradiol (E2) increased glycolysis in both PME and T47D ER+ breast cancer acini. However, PME cells displayed increased lipid content with no effect on ECM, while T47D cells had decreased lipid storage (P &lt; 0.001) and significant reorganization of collagen. By measuring deuterated lipids synthesized from exogenously administered deuterium-labeled glucose, treatment of T47D cells with E2 increased both lipid synthesis and consumption rates. These results confirm that glucose is a significant source for the cellular synthesis of lipid in glycolytic breast cancer cells, and that the combination of cellular redox and lipid fraction imaging endpoints is a powerful approach with new and complementary information content.
Significance: These findings provide unique insight into metabolic processes, revealing correlations between cancer metastasis and cellular redox state, lipid metabolism, and extracellular matrix. Cancer Res; 78(10); 2503–12. ©2018 AACR.
Report of the 14th International Conference on Malignant Lymphoma (ICML) Closed Workshop on Future Design of Clinical Trials in Lymphomas
Authors: Stathis Anastasios , Iasonos Alexia , Seymour John F. , Thieblemont Catherine , Ribrag Vincent , Zucca Emanuele , Younes Anas 
Published: March 2018

Abstract
The 14th ICML held in Lugano in June 2017 was preceded by a closed workshop (organized in collaboration with the American Association for Cancer Research and the European School of Oncology) where experts in preclinical and clinical research in lymphomas met to discuss the current drug development landscape focusing on critical open questions that need to be addressed in the future to permit a more efficient drug development paradigm in lymphoma. Topics discussed included both preclinical models that can be used to test new drugs and drug combinations, as well as the optimal design of clinical trials and the endpoints that should be used to facilitate accelerated progress. This report represents a summary of the workshop. Clin Cancer Res; 24(13); 2993–8. ©2018 AACR.
RIP1–HAT1–SIRT Complex Identification and Targeting in Treatment and Prevention of Cancer
Authors: Carafa Vincenzo , Nebbioso Angela , Cuomo Francesca , Rotili Dante , Cobellis Gilda , Bontempo Paola , Baldi Alfonso , Spugnini Enrico P. , Citro Gennaro , Chambery Angela , Russo Rosita , Ruvo Menotti , Ciana Paolo , Maravigna Luca , Shaik Jani , Radaelli Enrico , De Antonellis Pasquale , Tarantino Domenico , Pirolli Adele , Ragno Rino , Zollo Massimo , Stunnenberg Hendrik G. , Mai Antonello , Altucci Lucia 
Published: March 2018

Abstract
Purpose: Alteration in cell death is a hallmark of cancer. A functional role regulating survival, apoptosis, and necroptosis has been attributed to RIP1/3 complexes.
Experimental Design: We have investigated the role of RIP1 and the effects of MC2494 in cell death induction, using different methods as flow cytometry, transcriptome analysis, immunoprecipitation, enzymatic assays, transfections, mutagenesis, and in vivo studies with different mice models.
Results: Here, we show that RIP1 is highly expressed in cancer, and we define a novel RIP1/3–SIRT1/2–HAT1/4 complex. Mass spectrometry identified five acetylations in the kinase and death domain of RIP1. The novel characterized pan-SIRT inhibitor, MC2494, increases RIP1 acetylation at two additional sites in the death domain. Mutagenesis of the acetylated lysine decreases RIP1-dependent cell death, suggesting a role for acetylation of the RIP1 complex in cell death modulation. Accordingly, MC2494 displays tumor-selective potential in vitro, in leukemic blasts ex vivo, and in vivo in both xenograft and allograft cancer models. Mechanistically, MC2494 induces bona fide tumor-restricted acetylated RIP1/caspase-8–mediated apoptosis. Excitingly, MC2494 displays tumor-preventive activity by blocking 7,12-dimethylbenz(α)anthracene–induced mammary gland hyperproliferation in vivo.
Conclusions: These preventive features might prove useful in patients who may benefit from a recurrence-preventive approach with low toxicity during follow-up phases and in cases of established cancer predisposition. Thus, targeting the newly identified RIP1 complex may represent an attractive novel paradigm in cancer treatment and prevention. Clin Cancer Res; 24(12); 2886–900. ©2018 AACR.