bluuebunny/crossref_metadata_2025 huggingface dataset:
Serially measured circulating microRNAs and adverse clinical outcomes in patients with acute heart failure
Authors: van Boven Nick , Kardys Isabella , van Vark Laura C. , Akkerhuis K. Martijn , de Ronde Maurice W.J. , Khan Mohsin A.F. , Merkus Daphne , Liu Zhen , Voors Adriaan A. , Asselbergs Folkert W. , van den Bos Ewout‐Jan , Boersma Eric , Hillege Hans , Duncker Dirk J. , Pinto Yigal M. , Postmus Douwe
Published: September 2017

Aims

Previous studies have identified candidate circulating microRNAs (circmiRs) as biomarkers for heart failure (HF) using relatively insensitive arrays, validated in small cohorts. The present study used RNA sequencing to identify novel candidate circmiRs and compared these with previously identified circmiRs in a large, prospective cohort of patients with acute HF (AHF).

Methods and results

RNA sequencing of plasma from instrumented pigs was used to identify circmiRs produced by myocardium. Production of known myomiRs and microRNA (miR)‐1306‐5p was identified. The prognostic values of this and 11 other circmiRs were tested in a prospective cohort of 496 AHF patients, from whom blood samples were collected at up to seven time‐points during the study's 1‐year follow‐up. The primary endpoint was the composite of all‐cause mortality and HF rehospitalization. In the prospective AHF cohort, 188 patients reached the primary endpoint, and higher values of repeatedly measured miR‐1306‐5p were positively associated with risk for reaching the primary endpoint at the same time‐point [hazard ratio (HR) 4.69, 95% confidence interval (CI) 2.18–10.06], independent of clinical characteristics and NT‐proBNP. Baseline miR‐1306‐5p did not improve model discrimination/reclassification significantly compared with NT‐proBNP. For miR‐320a, miR‐378a‐3p, miR‐423‐5p and miR‐1254, associations with the primary endpoint were present after adjustment for age and sex (HR 1.38, 95% CI 1.12–1.70; HR 1.35, 95% CI 1.04–1.74; HR 1.45, 95% CI 1.10–1.92; HR 1.22, 95% CI 1.00–1.50, respectively). Rates of detection of myomiRs miR‐208a‐3p and miR‐499a‐5p were very low.

Conclusions

Repeatedly measured miR‐1306‐5p was positively associated with adverse clinical outcome in AHF, even after multivariable adjustment including NT‐proBNP. However, baseline miR‐1306‐5p did not add significant discriminatory value to NT‐proBNP. Low‐abundance, heart‐enriched myomiRs are often undetectable, which mandates the development of more sensitive assays.
Enrichment of Hydrogen Production from Biomass‐Gasification‐Derived Syngas over Spinel‐Type Aluminate‐Supported Nickel Catalysts
Authors: Chuang Kui‐Hao , Chen Bing‐Nan , Wey Ming‐Yen
Published: September 2017

Synthesis gas produced through biomass gasification can be converted into H2‐rich gas by catalytic methane decomposition or reforming reactions. In this study, we investigate the promotion of hydrogen production by the catalytic reforming of a model biomass‐gasification‐derived syngas over Ni/MAl2O4 (M=Mg, Ni, and Ca) catalysts. Three mesoporous spinel supports were synthesized by solution combustion. Ni/NiAl2O4 and Ni/CaAl2O4 exhibited better catalytic activities and stabilities for syngas reforming than the other catalysts. These results are ascribable to interactions between the metallic catalyst and spinel supports, and stronger interactions lead to smaller catalyst particles. The formation of coke deposits is associated with CH4 decomposition during the syngas reforming reaction. Clearly, H2 production is lower at 900 °C because of increased competition from the reverse water–gas shift reaction that shifts the reaction between CO2 and H2 toward the generation of CO and H2O.
Harvesting Energy from Human Activity: Ferroelectric Energy Harvesters for Portable, Implantable, and Biomedical Electronics
Authors: Zhang Guangzu , Li Mingyu , Li Honglang , Wang Qing , Jiang Shenglin
Published: September 2017

Energy harvesters based on ferroelectric materials, which are capable of converting mechanical and thermal energies into electric power, have drawn unprecedented attention in both academic and industrial fields because of their great potential in harvesting human‐activity‐induced and other energies of the human body to drive low‐power, personal, portable, and implantable electronics. Based on previous works that uncovered the features of advanced materials and the nanotechnologies for the fabrication of ferroelectric generators, we emphasize the potential of ferroelectric energy harvesters in biomedical applications, with not only traditional ferroelectrics but also newly developed ferroelectric biomaterials. In addition, the latest representative integration schemes of hybrid generators with ferroelectric materials are outlined, which could markedly extend the functions of energy harvesters, especially for implantable and biomedical applications.
Anti‐Freezing Aqueous Electrolyte for High‐Performance Co(OH)2 Supercapacitors at −30 °C
Authors: Deng Ting , Zhang Wei , Zhang Hengbin , Zheng Weitao
Published: September 2017

Cobalt hydroxide (Co(OH)2) is a promising electrode material for hybrid devices because of its intrinsic battery‐mimic mechanism for energy storage. However, conventional electrolytes suitable for Co(OH)2 will lead to performance failure in a harsh environment, which hinders its industrial application at ambient temperature. Here, we propose an anti‐freezing aqueous electrolyte composed of NaOH and a high concentration of NaClO4 for Co(OH)2 electrode, which can still fully function at −30 °C. At this temperature, the energy density of a Co(OH)2–active carbon hybrid capacitor can reach 16.52 Wh kg−1, which has a 72 % energy‐density retention at 20 °C. The hybrid capacitor shows excellent cyclability with the anti‐freezing electrolyte at −30 °C, presenting only 3.5 % drop of the capacitance after 500 cycles. This designed anti‐freezing electrolyte may put more pseudocapacitive materials into more practical use, particularly in northern harsh climates.
Simulation and 4D seismic studies of pressure management and CO2 plume control by means of brine extraction and monitoring at the Devine Test Site, South Texas, USA
Authors: Goudarzi Ali , Hosseini Seyyed A. , Sava Diana , Nicot Jean‐Philippe
Published: September 2017

Within the context of CO2 geological storage, excessive pressure build‐up is undesirable because it increases the risks of CO2 plume leaks into unwanted zones, reduces the storage capacity of the formation, and can limit the life of a storage project. In this study, we designed a brine extraction field pilot project for pressure management and plume control in the Hosston Formation at the Devine Test Site (DTS) in Texas. We investigated the possibility of using seismic and tracer data to monitor pressure front and injected fluids plume. Seismic surveys provide the volumetric coverage needed to understand the 3D subsurface fluid and pore pressure front movement; however, the limit of seismic detectability may be influenced by Hosston Formation initial pore pressure. The range of minimum pore pressure increase needed to produce detectable P‐wave and S‐wave seismic velocities is investigated. Simulation study of active pressure management system (APMS) and passive pressure management system (PPMS) at the DTS is performed using the numerical simulator CMG‐STARS to demonstrate the possibility of controlling pressure build up in the storage formation. The estimation of pore pressure increase from flow simulations will help us to understand if the pressure changes during brine injection and extraction can be detected using seismic response. Study findings show that 4D seismic is an appropriate monitoring tool considering the level of expected increase in pressure at the DTS and that, as expected, brine extraction is successful in controlling the pressure build up and potentially can steer the plume at the DTS. © 2017 Society of Chemical Industry and John Wiley & Sons, Ltd.
Progression of liver fibrosis is associated with non‐liver‐related mortality in patients with nonalcoholic fatty liver disease
Authors: Tada Toshifumi , Kumada Takashi , Toyoda Hidenori , Mizuno Kazuyuki , Sone Yasuhiro , Akita Tomoyuki , Tanaka Junko
Published: September 2017

In patients with nonalcoholic fatty liver disease (NAFLD), prognosis and outcome, especially non‐liver‐related mortality, remain incompletely elucidated. We clarified the mortality from all causes in patients with NAFLD. A total of 4,073 patients with NAFLD diagnosed by ultrasonography were enrolled. We investigated the causes of death and analyzed the mortality from non‐liver‐related diseases according to the degrees of steatosis and fibrosis using the competing risk method. We used the NAFLD fibrosis score (NFS) to assess fibrosis severity and the ultrasonography fatty liver score to evaluate steatosis severity. The numbers of patients with NFS indicating low, intermediate, and high probabilities of advanced fibrosis were 2,451 (60.2%), 1,462 (35.9%), and 160 (3.9%), respectively. Of the 4,073 patients, 179 died during follow‐up, but only nine deaths were due to liver‐related diseases. Of the remaining 170 patients who died due to non‐liver‐related diseases, 83 (48.8%), 42 (24.7%), and 45 (26.5%) patients died due to malignancies, cerebrovascular and cardiovascular diseases, and benign diseases (excluding cerebrovascular and cardiovascular diseases), respectively. Multivariate analysis showed that the intermediate and high NFS groups were independently associated with each disease category: hazard ratio (HR) 2.163 (95% confidence interval [CI], 1.354‐3.457) and HR 4.814 (95% CI, 2.323‐9.977) for malignancies; HR 2.265 (95% CI, 1.141‐4.497) and HR 8.482 (95% CI, 3.558‐20.220) for cerebrovascular and cardiovascular diseases; and HR 3.216 (95% CI, 1.641‐6.303) and HR 5.558 (95% CI, 1.923‐16.070) for benign diseases, respectively. Conversely, the status of steatosis was not associated with risk of mortality in multivariate analysis. Conclusion: Progression of liver fibrosis severity was associated with mortality from various non‐liver‐related causes in patients with NAFLD. (Hepatology Communications 2017;1:928–945)
Interleukin 8 mediates bcl‐xL‐induced enhancement of human melanoma cell dissemination and angiogenesis in a zebrafish xenograft model
Authors: Gabellini Chiara , Gómez‐Abenza Elena , Ibáñez‐Molero Sofia , Tupone Maria Grazia , Pérez‐Oliva Ana B. , de Oliveira Sofia , Del Bufalo Donatella , Mulero Victoriano
Published: September 2017

The protein bcl‐xL is able to enhance the secretion of the proinflammatory chemokine interleukin 8 (CXCL8) in human melanoma lines. In this study, we investigate whether the bcl‐xL/CXCL8 axis is important for promoting melanoma angiogenesis and aggressiveness in vivo, using angiogenesis and xenotransplantation assays in zebrafish embryos. When injected into wild‐type embryos, bcl‐xL‐overexpressing melanoma cells showed enhanced dissemination and angiogenic activity compared with control cells. Human CXCL8 protein elicited a strong proangiogenic activity in zebrafish embryos and zebrafish Cxcr2 receptor was identified as the mediator of CXCL8 proangiogenic activity using a morpholino‐mediated gene knockdown. However, human CXCL8 failed to induce neutrophil recruitment in contrast to its zebrafish homolog. Interestingly, the greater aggressiveness of bcl‐xL‐overexpressing melanoma cells was mediated by an autocrine effect of CXCL8 on its CXCR2 receptor, as confirmed by an shRNA approach. Finally, correlation studies of gene expression and survival analyses using microarray and RNA‐seq public databases of human melanoma biopsies revealed that bcl‐xL expression significantly correlated with the expression of CXCL8 and other markers of melanoma progression. More importantly, a high level of co‐expression of bcl‐xL and CXCL8 was associated with poor prognosis in melanoma patients. In conclusion, these data demonstrate the existence of an autocrine CXCL8/CXCR2 signaling pathway in the bcl‐xL‐induced melanoma aggressiveness, encouraging the development of novel therapeutic approaches for high bcl‐xL‐expressing melanoma.
Transfers of stimulus function during roulette wagering
Authors: Dixon Mark R. , Enoch Mary Rachel , Belisle Jordan
Published: September 2017

Twenty‐five recreational gamblers were initially asked to place bets on either red or black positions on a roulette board in a simulated casino setting. Each participant was then exposed to a stimulus pairing observing procedure which attempted to develop equivalence classes between one color (black or red) and traditionally positive words (e.g., love, happy, sex) and another color (black or red) and traditionally negative words (e.g., death, cancer, taxes), in the absence of consequence manipulations. Twenty‐one of the twenty‐five participants demonstrated greater response allocation to the color position on the roulette board that participated in a relational network with the positive words. Variations in sequencing of experimental conditions had no impact on poststimulus‐pairing wagers, but did impact tests for equivalence accuracy.
Potential hazards of fenvalerate in massive pollution influence the apoptosis sensitivity
Authors: Cui Zheng‐Guo , Jin Yu‐Jie , Sun Lu , Zakki Shahbaz Ahmad , Li Meng‐Ling , Feng Qian‐Wen , Kondo Takashi , Ogawa Ryohei , Inadera Hidekuni
Published: September 2017

Fenvalerate (Fen), a synthetic pyrethroid insecticide, is widely used in agricultural, domestic and veterinary applications. Fen induces abnormal cell proliferation and apoptosis, which are linked to its hazardous effects. However, this view is controversial and the underlying molecular mechanisms remain elusive. In the present study, the effects of Fen on cadmium (Cd)‐induced apoptosis and the associated molecular mechanisms were investigated in human myeloid leukemia U937 cells. U937 cells were treated with 50 μm cadmium chloride (CdCl2) with or without Fen pretreatment at 1–50 μm. Apoptosis was evaluated by externalization of phosphatidylserine on the plasma membrane. The expression levels of apoptosis‐related proteins, including Bcl‐2 family members were determined by western blot analysis. The results revealed that pretreatment with Fen at 20 μm for 12 hours significantly inhibited Cd‐induced apoptosis. Decreased expression of pro‐apoptotic Bcl‐2 family proteins (Noxa and Bid) and increased expression of anti‐apoptotic proteins (Bcl‐xL, Mcl‐1 and XIAP) were observed after combined treatment with Fen and CdCl2. Phosphorylation of ERK and AKT was increased, while phosphorylation of JNK was decreased by the combined treatment, compared with CdCl2 treatment alone. In conclusion, Fen decreased apoptotic sensitivity induced by Cd in U937 cells. This effect was associated with activation of ERK and AKT, suppression of JNK and changes in expression of Bcl‐2 family proteins and XIAP. The present findings suggest a potential influence of Fen on Cd toxicity via suppression of apoptosis. Fen decreased apoptotic sensitivity induced by Cd, and thus it may contribute carcinogenic risk and influence on cancer therapy.
Immunofluorescence and confocal microscopy for ex‐vivo diagnosis of melanocytic and non‐melanocytic skin tumors: A pilot study
Authors: Hartmann Daniela , Krammer Sebastian , Vural Secil , Bachmann Mario Raphael , Ruini Cristel , Sárdy Miklós , Ruzicka Thomas , Berking Carola , von Braunmühl Tanja
Published: September 2017

Background

Ex‐vivo confocal laser scanning microscopy (ex‐vivo CLSM) offers rapid examination of freshly excised tissue. During the conventional examination immunohistochemistry enables to distinguish various cell types. The possibility of immunofluorescent techniques could enhance the accuracy of the diagnosis performed by ex‐vivo CLSM.

Methods

The tissue probes from various skin tumors were stained with FITC‐labeled S‐100A10, Melan‐A and anti‐Ber‐EP4 antibodies before examination with ex‐vivo CLSM in the fluorescence and reflectance modes. Results were compared to negative controls and conventional histopathology. The staining protocols were evaluated by establishing a scoring system according to the signal intensity found in ex‐vivo CLSM.

Results

S100 immunostaining was successful in 55.6%. Dilution of 1:200 resulted in the best possible evaluation of the tumor. The best suitable protocol was protocol B (phosphate buffered saline [PBS], without blocking agent). Melan A immunostaining was positive in 66.7%, the best dilution was 1:500 and protocol B (PBS, without blocking agent) was the most suitable. Ber‐EP4 immunostaining presented a signal in 85.7%, the best dilutions were 1:200 and 1:500 and protocol A (PBS, with blocking agent) showed most optimal results.

Conclusion

The use of fluorescent‐labeled antibodies in ex‐vivo CLSM is possible and could improve intraoperative diagnostics of skin tumors.
Structural Insights into the Coordination and Extraction Mechanism of Nickel(II) with Dinonylnaphthalene Sulfonic Acid and n‐Hexyl 3‐Pyridinecarboxylate Ester as Extractants
Authors: Zhu Shan , Hu Huiping , Hu Jiugang , Li Jiyuan , Hu Fang , Wang Yongxi
Published: September 2017

In this work, a nickel(II) synergist complex with methyl isonicotinate (BI, a short chain analog of n‐hexyl 3‐pyridinecarboxylate ester) and naphthalene‐2‐sulfonic acid (HNS, a short chain analog of dinonylnaphthalene sulfonic acid) was synthesized and studied by single‐crystal X‐ray diffraction. The nickel(II) complex crystallizes in the monoclinic P21/n space group with the composition [Ni(H2O)4(BI)2](NS)2·2H2O. The Ni(II) ions of these crystallographically independent molecules lie on an inversion center, forming a trans‐form distorted octahedral coordination structure. The nickel(II) ions can coordinate with four water molecules and two BI ligands, resulting in a mono‐metallic structure [Ni(H2O)4(BI)2]2+. There is no direct interaction between nickel(II) and sulfonic oxygen atoms of the sulfonate anions, but hydrogen bonds form between sulfonic oxygen atoms and water molecules in the synergist complex. In order to further elucidate the solution structure of the nickel(II) complexes with the actual synergistic mixture containing n‐hexyl 3‐pyridinecarboxylate ester and dinonylnaphthalene sulfonic acid in the nonpolar organic phase, the nickel(II) complexes were studied by electrospray ionization mass spectrometry. The results indicated that the extracted nickel(II) complexes in the nonpolar solvent have a similar coordination structure as that of the crystalline nickel(II) synergist complex.
Management of dysfibrinogenemia in pregnancy: A case report
Authors: Yan Jie , Deng Donghong , Cheng Peng , Liao Lin , Luo Meiling , Lin Faquan
Published: September 2017

Background

Dysfibrinogenemia is a rare coagulation disorder caused by mutations in the fibrinogen gene that results in abnormal fibrinogen function. Dysfibrinogenemia has a wide spectrum of clinical manifestations including asymptomatic(55%), hemorrhage (25%), and thrombosis (20%).

Methods

We reported a 30‐year‐old woman with 35 weeks gestation. She was misdiagnosed with hypofibrinogenemia in a local hospital, and then she was treated with fibrinogen concentrate. However, she was diagnosed as dysfibrinogenemia in our hospital base on her low function fibrinogen level (0.55 g/L) and her normal immunologic fibrinogen level (3.80 g/L). This patient had neither bleeding symptom nor thromboembolic event. Her obstetrical history included one normal pregnancy in 2008 with uneventful full‐term delivery.

Results

Multidisciplinary experts suggested that there should be no specific intervention in this case because of the patient had no previous episodes of abnormal bleeding or thrombotic. She had an uneventful delivery with no abnormal bleeding symptom or thromboembolic.

Conclusion

Dysfibrinogenemia patients without personal or family history of bleeding and thromboembolic events, do not need specific therapeutic intervention.
Performance evaluation of the white cell precursor channel on the Sysmex XN hematology analyzer in HIV specimens
Authors: Schapkaitz Elise , Khoza Phoyisile
Published: September 2017

Background

Automated hematology analyzers generate white blood cell (WBC) suspect flags to indicate smears requiring manual review. In a human immunodeficiency virus (HIV) patient population with a high frequency of abnormal specimens, the usefulness of these flags depends on their sensitivity and specificity. The white cell precursor (WPC) channel on the Sysmex XN‐9000 analyzer (Sysmex Corporation, Kobe, Japan) has recently been introduced in order to distinguish immature cells such as blasts and abnormal lymphocytes.

Methods

The efficiency of the flags generated by WPC reflex testing was compared to the white cell differential (WDF) on the Sysmex XN‐9000 in 400 routine HIV samples.

Results

A flag was generated by the WDF channel in 346 (86.50%) samples. Addition of the WPC to the WDF resulted in a 20.99% reduction in the smear review rate. WPC analysis correctly identified the initial WDF flag in 59 (60.82%) samples with ‘blasts?’ or ‘abnormal lympho?’ flags. WPC showed an excellent sensitivity of 100%. However, the specificity remained poor. On investigation, samples with chronic infection/inflammation (35.00%) and lymphopenia (63.25%) were associated with a high false positive rate of 76.32% and 55.56%, respectively. WPC analysis removed 45 (51.72%) coexisting ‘atypical lympho?’ false positive WDF flags. The ‘atypical lympho?’ flag showed an increased sensitivity and specificity of 88.46% and 74.67%, respectively.

Conclusion

White cell precursor reflex testing showed improved flagging efficiency for the ‘atypical lympho?’ flag, which was a good indicator of reactive lymphocytes during chronic infection/inflammation. Nevertheless, the false positive rate for ‘abnormal lympho/blasts?’ was high in the presence of lymphopenia and infection.
Clinical evaluation of a multiparametricELISAas a rapid tool for routinely diagnosing IgG‐mediated autoimmune blistering dermatoses in ethnic Slavs
Authors: Gornowicz‐Porowska Justyna , Seraszek‐Jaros Agnieszka , Bowszyc‐Dmochowska Monika , Bartkiewicz Paweł , Kaczmarek Elżbieta , Dmochowski Marian
Published: September 2017

Background

Technical innovation of autoimmune blistering dermatoses (ABDs) diagnosis aimed at multiplex approach. Two multiparametricELISAtests are commercially available forABDs serology. The aim was to compare diagnostic accuracy of multiparametric and monospecificELISAs and to examine the diagnostic value/agreement of multivariantELISAin compliance with traditional diagnostic setup forABDs.

Methods

In total, 128 sera from suspectedABDs patients were studied (27 sera in order to compareELISAs). MultivariantELISA(detection of IgG against desmoglein 1 and 3 ‐DSG1/3;BP180,BP230, envoplakin, typeVIIcollagen), monovariantELISA, and statistical analysis were performed.

Results

With the use of sera from patients with suspectedABDs, the multiparametricELISAyield an agreement of 84% with traditional stepwise diagnostics. MultivariantELISAwithBP180 andBP230 showed 87.5% and 80% sensitivity, 87.5% and 91% specificity, 87.5% reliability as well as 87.5% and 80% positive predictive value, 87.5% and 91% negative predictive value, respectively, in relation to monospecificELISA. MultivariantELISAwithDSG1 andDSG3 showed 50% and 80% sensitivity, 100% and 80% specificity, 85% and 80% reliability as well as 100% and 57% positive predictive value, 82% and 92% negative predictive value, respectively, in relation to monospecificELISA. A better rate of agreement was observed amongELISAsystems withBP180 andBP230, than withELISAsystems withDSG1 andDSG3.

Conclusion

MultivariantELISAtest combined with clinical examinations andDIFis recommended as a minimal approach to diagnosingABDs in ethnic Slavs.
Microbial community dynamics reflect reactor stability during the anaerobic digestion of a very high strength and sulfate‐rich vinasse
Authors: Jiménez Janet , Barrera Ernesto L , De Vrieze Jo , Boon Nico , DeMeester Steven , Spanjers Henri , Romero Osvaldo Romero , Dewulf Jo
Published: September 2017

BACKGROUND

Microbial community dynamics during the anaerobic digestion of vinasse has been little studied. However, having knowledge about it is essential for early detection of reactor operational difficulties to apply preventive actions. This research studies the microbial community dynamics in the anaerobic digestion of vinasse, linking to experimental observations about product yields and organic matter degradation.

RESULTS

Methane and sulfide yields decreased with increasing SO42‐/COD ratio, while the fraction of organic matter degraded by sulfate reducing bacteria increased from 4.5 ± 0.3% to 27.1 ± 0.6%. The archaeal community showed that acetoclastic Methanosaetaceae were little affected by the increase of the SO42‐/COD ratio, in contrast to the Methanomicrobiales and Methanobacteriales population, which decreased during the experiment. The total bacterial diversity was influenced mainly by substrate composition, showing that the increase of the SO42‐/COD ratio above 0.10 shifted the bacterial community to a lower richness.

CONCLUSION

These results provide knowledge on the dynamics of the microbial communities, which can be useful to control the anaerobic digestion of sulfate‐rich vinasses, showing that reactor stability equates to the higher ratios between total methanogens and total bacteria gene copy numbers, whereas operational difficulties can be associated to lower bacterial richness and higher community organization. © 2017 Society of Chemical Industry
Kernel Multitask Regression for Toxicogenetics
Authors: Bernard Elsa , Jiao Yunlong , Scornet Erwan , Stoven Veronique , Walter Thomas , Vert Jean‐Philippe
Published: September 2017

The development of high‐throughputin vitroassays to study quantitatively the toxicity of chemical compounds on genetically characterized human‐derived cell lines paves the way topredictive toxicogenetics, where one would be able to predict the toxicity of any particular compound on any particular individual. In this paper we present a machine learning‐based approach for that purpose, kernel multitask regression (KMR), which combines chemical characterizations of molecular compounds with genetic and transcriptomic characterizations of cell lines to predict the toxicity of a given compound on a given cell line. We demonstrate the relevance of the method on the recent DREAM8 Toxicogenetics challenge, where it ranked among the best state‐of‐the‐art models, and discuss the importance of choosing good descriptors for cell lines and chemicals.
Pomegranate By‐Products in Colorectal Cancer Chemoprevention: Effects in Apc‐Mutated Pirc Rats and Mechanistic Studies In Vitro and Ex Vivo
Authors: Tortora Katia , Femia Angelo Pietro , Romagnoli Andrea , Sineo Irene , Khatib Mohamad , Mulinacci Nadia , Giovannelli Lisa , Caderni Giovanna
Published: September 2017

Scope

To investigate the effect of pomegranate mesocarp, a polyphenol‐rich by‐product of juice production, in colorectal cancer (CRC) chemoprevention.

Methods and results

A mesocarp decoction (PMD) is administered for 6 weeks in the diet to Pirc rats, mutated in Apc, a key‐gene in CRC. Mucin‐depleted foci (MDFs), as CRC biomarkers, are reduced in PMD‐fed rats compared to controls (MDF/colon: 34 ± 4 versus 47 ± 3, p = 0.02). There is an increase in apoptosis in MDFs from PMD‐treated rats compared to controls (2.5 ± 0.2 versus 1.6 ± 0.2, p < 0.01). To elucidate the involved mechanisms, two colon‐relevant metabolites of the polyphenolic and fiber PMD components, urolithin‐A (u‐A) and sodium butyrate (SB), are tested alone or in combination in vitro (colon cancer cells), and ex vivo in adenoma (AD) and normal mucosa (NM) from Pirc rats. u‐A 25 μm plus SB 2.5 mm (USB) causes a significant reduction in COX‐2 protein expression compared to untreated controls (about –70% in cancer cell cultures, AD, and NM), and a strong increase in C‐CASP‐3 expression in cells (about ten times), in AD and NM (+74 and +69%).

Conclusion

These data indicate a chemopreventive activity of PMD due, at least in part, to pro‐apoptotic and anti‐inflammatory action of its metabolites that could be exploited in high‐risk patients.
Influence of Kidney Transplant Status on Warfarin Dose, Anticoagulation Control, and Risk of Hemorrhage
Authors: Yanik Megan V. , Irvin Marguerite R. , Beasley T. Mark , Jacobson Pamala A. , Julian Bruce A. , Limdi Nita A.
Published: September 2017

Study Design

To assess whether warfarin dose requirement, anticoagulation control, and risk of hemorrhage differ in kidney transplant recipients (KTRs) compared with patients without kidney transplants (non‐KTRs).

Design

Analysis of data from the Warfarin Pharmacogenetics Cohort, a prospective cohort of first‐time warfarin users followed at two anticoagulation clinics.

Setting

Two outpatient anticoagulation clinics at two large, academic, tertiary care hospitals.

Patients

Adults aged 20 years or older starting warfarin for anticoagulation with a therapeutic international normalized ratio (INR) goal of 2–3 who were KTRs (n=65) or non‐KTRs (n=1630).

Measurements and Main Results

Warfarin dose requirement, anticoagulation control, and risk of hemorrhage were assessed in each group. KTRs required an approximately 20% lower warfarin dose (4.7 vs 5.6 mg/day, p=0.0005) compared with non‐KTRs. Genetic variants had similar effects on dose in both groups. Mean percentage of time in therapeutic range (PTTR) was similar among KTRs and non‐KTRs. Although the proportion of patients achieving good anticoagulation control (PTTR ≥ 60%) was low in both groups, it was similar among KTRs and non‐KTRs. KTRs had a higher risk of major hemorrhage (hazard ratio 2.1, p=0.0081), but this difference was not statistically significant after controlling for kidney function, clinical, and genetic factors.

Conclusion

KTRs initiating warfarin require lower doses and closer monitoring to optimize anticoagulation therapy. Additional studies are needed to confirm these findings.
DJ‐1 Regulates Differentiation of Human Mesenchymal Stem Cells into Smooth Muscle‐like Cells in Response to Sphingosylphosphorylcholine
Authors: Baek Suji , Lee Kang Pa , Jung Seung Hyo , Cui Long , Ko Kinarm , Kim Bokyung , Won Kyung Jong
Published: September 2017

Although multiple factors contribute to the differentiation of human mesenchymal stem cells (hMSCs) into various types of cells, the differentiation of hMSCs into smooth muscle cells (SMCs), one of central events in vascular remodeling, remains to be clarified. ROS participate in the differentiation of hMSCs into several cell types and were regulated by redox‐sensitive molecules including a multifunctional protein DJ‐1. Here, we investigated the correlation between altered proteins, especially those related to ROS, and SMC differentiation in sphingosylphosphorylcholine (SPC)‐stimulated hMSCs. Treatment with SPC resulted in an increased expression of SMC markers, namely α‐smooth muscle actin (SMA) and calponin, and an increased production of ROS in hMSCs. A proteomic analysis of SPC‐stimulated hMSCs revealed a distinctive alteration of the ratio between the oxidized and reduced forms of DJ‐1 in hMSCs in response to SPC. The increased abundance of oxidized DJ‐1 in SPC‐stimulated hMSCs was validated by immunoblot analysis. The SPC‐induced increase in the expression of α‐SMA was stronger in DJ‐1‐knockdown hMSCs than in control cells. Moreover, the expression of α‐SMA, and the calponin and generation of ROS in response to SPC were weaker in normal hMSCs than in DJ‐1‐overexpressing hMSCs. Exogenous H2O2 mimicked the responses induced by SPC treatment. These results indicate that the ROS‐related DJ‐1 pathway regulates the differentiation of hMSCs into SMCs in response to SPC.
The IL‐4 rs2070874 polymorphism may be associated with the severity of recurrent viral‐induced wheeze
Authors: Amat Flore , Louha Malek , Benet Marta , Guiddir Tamazoust , Bourgoin‐Heck Mélisande , Saint‐Pierre Philippe , Paluel‐Marmont Colombe , Fontaine Cécile , Lambert Nathalie , Couderc Rémy , Gonzalez Juan‐Ramon , Just Jocelyne
Published: September 2017

Background

Childhood recurrent wheezing and consequently asthma corresponds to various phenotypes. Our aim was to link genetic variants of asthma candidate genes to the phenotypes of early onset wheezing.

Study design

We included very young consecutive children presenting with recurrent wheezing who had been evaluated for the severity of wheezing, associated atopic comorbidities, and tested for biomarkers of atopy and inflammation. All were genotyped for 16 single nucleotide polymorphisms (SNPs) linked with asthma or atopy. An unsupervised hierarchical bottom‐up method was used for clustering the phenotypes and a multinomial logistic regression was performed for each individual SNP.

Results

We replicated the three phenotypes previously described Trousseau Asthma Program in 317 children aged 21.5 ± 7.9 months: cluster 1 (nonatopic uncontrolled severe wheeze), n = 207, a severe viral‐induced wheeze, cluster 2 (atopic multiple trigger wheeze), n = 61, with multiple allergic comorbidities, and cluster 3 (episodic viral wheeze), n = 49, a mild viral‐induced wheeze. The TT‐genotype of the IL‐4 rs2070874 polymorphism was significantly associated with the nonatopic uncontrolled severe wheeze compared to the episodic viral wheeze (OR 7.9; CI95% [2.5‐25.3]; P = 0.001).

Conclusion

Association between the TT‐genotype of IL‐4 rs2070874 polymorphism and a severe phenotype of viral‐induced wheeze further underlines the role IL‐4 plays in the inflammation pathway leading to viral respiratory infections.
Type I error probability spending for post–market drug and vaccine safety surveillance with binomial data
Authors: Silva Ivair R.
Published: September 2017

Type I error probability spending functions are commonly used for designing sequential analysis of binomial data in clinical trials, but it is also quickly emerging for near–continuous sequential analysis of post–market drug and vaccine safety surveillance. It is well known that, for clinical trials, when the null hypothesis is not rejected, it is still important to minimize the sample size. Unlike in post–market drug and vaccine safety surveillance, that is not important. In post–market safety surveillance, specially when the surveillance involves identification of potential signals, the meaningful statistical performance measure to be minimized is the expected sample size when the null hypothesis is rejected. The present paper shows that, instead of the convex Type I error spending shape conventionally used in clinical trials, a concave shape is more indicated for post–market drug and vaccine safety surveillance. This is shown for both, continuous and group sequential analysis.
The Contribution of Associate's Degree Holders to U.S. Earnings, Labor Quality, Productivity, and Overall Economic Growth
Authors: Gittell Ross , Samuels Jon D. , Tebaldi Edinaldo
Published: September 2017

There is substantial evidence on the importance of education as a driver of earnings, productivity, and economic growth. However, knowledge of the specific role of associate's degrees in U.S. economic growth is limited. We analyze the sources of U.S. economic growth and identify the contribution of associate's degree holders to improvements in earnings, labor quality, productivity, and overall economic growth. We find evidence that substitution toward workers with associate's degrees has increased U.S. earnings, aggregate labor quality, and productivity, and that these effects are concentrated in the health care, trade, and government sectors. While the average educational attainment of people entering the labor force has plateaued, our results suggest that shifting workers from some college to associate degrees could improve earnings, the quality of the workforce, productivity, and growth, potentially without more time spent in school.
Design of steel fiber reinforced concrete beams for shear using inverse analysis for determination of residual tensile strength
Authors: Foster Stephen J. , Agarwal Ankit , Amin Ali
Published: September 2017

The behavior of steel fiber reinforced concrete (SFRC) has been extensively investigated in the last four decades. For the most part, however, existing design models for shear are based on empirical equations where fiber–concrete is considered as a unique material and fibers and concrete components to shear are considered collectively, or where the concrete and fiber components to shear are considered separately and each are derived independently. As demonstrated in this paper, the problem with this latter approach is that the influence of the concrete and the fiber components are each affected by the other—that is, they are coupled. In this paper, a rational model is outlined for determining one‐way shear strength of SFRC beams and slabs. The model is developed from the modified compression field approach with due consideration given to the inter‐relationship between the concrete–steel–fiber components to the shear resistance. Introduced into the model is an inverse analysis method for determining the post‐cracking residual tensile strength of SFRC from prism bending tests, a core materials property needed for design. In determining this strength, due attention is provided to the influences of notches, specimen boundaries and bias in fiber orientation that occurs as part of the casting process. The results of the design model predictions are compared with a dataset of test specimens collected from the literature, with very good correlation observed.
Metabolic pathways at the crossroads of diabetes and inborn errors
Authors: Goetzman Eric S. , Gong Zhenwei , Schiff Manuel , Wang Yan , Muzumdar Radhika H.
Published: September 2017

Research over the past two decades has led to advances in our understanding of the genetic and metabolic factors that underlie the pathogenesis of type 2 diabetes mellitus (T2DM). While T2DM is defined by its hallmark metabolic symptoms, the genetic risk factors for T2DM are more immune‐related than metabolism‐related, and the observed metabolic disease may be secondary to chronic inflammation. Regardless, these metabolic changes are not benign, as the accumulation of some metabolic intermediates serves to further drive the inflammation and cell stress, eventually leading to insulin resistance and ultimately to T2DM. Because many of the biochemical changes observed in the pre‐diabetic state (i.e., ectopic lipid storage, increased acylcarnitines, increased branched‐chain amino acids) are also observed in patients with rare inborn errors of fatty acid and amino acid metabolism, an interesting question is raised regarding whether isolated metabolic gene defects can confer an increased risk for T2DM. In this review, we attempt to address this question by summarizing the literature regarding the metabolic pathways at the crossroads of diabetes and inborn errors of metabolism. Studies using cell culture and animal models have revealed that, within a given pathway, disrupting some genes can lead to insulin resistance while for others there may be no effect or even improved insulin sensitivity. This differential response to ablating a single metabolic gene appears to be dependent upon the specific metabolic intermediates that accumulate and whether these intermediates subsequently activate inflammatory pathways. This highlights the need for future studies to determine whether certain inborn errors may confer increased risk for diabetes as the patients age.
Nb-Based Nb-Al-Fe Alloys: Solidification Behavior and High-Temperature Phase Equilibria
Authors: Stein Frank , Philips Noah
Published: September 2017

High-melting Nb-based alloys hold significant promise for the development of novel high-temperature materials for structural applications. In order to understand the effect of alloying elements Al and Fe, the Nb-rich part of the ternary Nb-Al-Fe system was investigated. A series of Nb-rich ternary alloys were synthesized from high-purity Nb, Al, and Fe metals by arc melting. Solidification paths were identified and the liquidus surface of the Nb corner of the ternary system was established by analysis of the as-melted microstructures and thermal analysis. Complementary analysis of heat-treated samples yielded isothermal sections at 1723 K and 1873 K (1450 °C and 1600 °C).
The Impact of Microalgae in Food Science and Technology
Authors: Matos Ângelo Paggi
Published: September 2017

Microalgae (including cyanobacteria) are promising organisms for sustainable products for use as feedstocks for food, feed, fine chemicals, and biofuels. They can synthesize a broad range of products with medium‐ to high‐value market price such as β‐1,3‐glucan polysaccharide, single‐cell‐protein, carotenoids and phycobilin pigments, and long‐chain polyunsaturated fatty acids that are commercialized in the food industry as dietary supplements and functional foods, in the pharmaceutical and chemical industries as cosmaceuticals and flavorants, and in the therapeutic field as nutraceutical compounds. These microorganisms are also exceptional producers of omega‐3 and omega‐6 fatty acids such as eicosapentaenoic, docosahexaenoic, and arachidonic acids that have been linked to several human health benefits. The aim of this paper is to review the main existing high‐value products that can be derived from microalgae with a particular focus on food science and technology applications. It also describes the gross and fine chemical composition of various algal species and details the nutritive importance of selected constituents. Finally, nutritional quality standards and legislative provisions to ensure food safety in the use of algal biomass are presented.
Getting off the carousel: De-centring the curriculum in medical education
Authors: Whitehead Cynthia R.
Published: September 2017

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Marine vertebrate fauna from the late Eocene Samlat Formation of Ad-Dakhla, southwestern Morocco
Authors: ZOUHRI SAMIR , KHALLOUFI BOUZIANE , BOURDON ESTELLE , DE LAPPARENT DE BROIN FRANCE , RAGE JEAN-CLAUDE , M'HAÏDRAT LEILA , GINGERICH PHILIP D. , ELBOUDALI NAJIA
Published: September 2017

Late Eocene deposits of the Samlat Formation, south of Ad-Dakhla city, southwestern Morocco, have yielded a mixed marine and terrestrial vertebrate fauna. Abundant and diversified chondrichthyans and archaeocete whales have been found, as well as the remains of sirenians and proboscideans. Here we describe the rest of this fossil assemblage which includes actinopterygians, turtles, palaeophiid snakes, crocodiles and pelagornithid seabirds. Actinopterygians are represented by at least two large-sized taxa, a scombroid probably close to the extantAcanthocybiumor to the EoceneAramichthys, and a siluriform related to the Ariidae. Turtles include at least four species represented by shell fragments. This mixed coastal and continental turtle fauna includes one littoral species of Podocnemididae, one or two deep-sea species of Dermochelyidae and one deep-sea species of Cheloniidae. Another turtle species is assigned to the terrestrial Testudinidae. Fragmentary crocodilian remains indicate the presence of undetermined eusuchians tentatively referred to Gavialidae and/or to Crocodylidae. Snake vertebrae are tentatively attributed to the genusPterosphenus(Palaeophiidae) pending the discovery of new material. Avian remains belong to a large pseudo-toothed bird (Pelagornithidae). Pseudo-tooth morphology resembles that of the late Oligocene – Neogene genusPelagornis. Additional bird remains are needed for a more precise taxonomic assignment. The fossil assemblage and palaeoenvironment of the upper Eocene deposits of the Samlat Formation appear closely related to those of the upper Eocene – lower Oligocene deposits of the Fayum (Egypt). The initial overview of this fauna provides an important contribution to the study of vertebrate evolution in North Africa near the Eocene–Oligocene transition.
Effects of bamboo dominance and palm-heart harvesting on the phylogenetic structure of the seed and seedling communities in an old-growth Atlantic Forest
Authors: Schweizer Daniella , Rother Débora Cristina , Muler Ana Elena , Rodrigues Ricardo Ribeiro , Pizo Marco Aurélio , Brancalion Pedro H. S.
Published: September 2017

A comprehensive assessment of the effect of disturbances on tropical and subtropical forests is needed to better understand their impacts on forest structure and diversity. Although taxonomic and functional diversity measures have been successfully adopted in this context, phylogenetic diversity metrics are still poorly explored. We compared the phylogenetic structure of the seed rain and regenerating seedling community in patches of an old-growth Atlantic Forest remnant dominated or not by a ruderal bamboo species,Guadua tagoara. We sampled those patches before and after illegal harvesting of the palmEuterpe edulisthus assessing if the harvesting led to changes in the phylogenetic structure of the seed rain and the regenerating community in both patches. Bamboo-dominated patches showed a significantly higher presence of species in the seed rain that were more distantly related to each other in the phylogeny than expected by chance compared with patches without bamboos, but this difference disappeared after palm-heart harvesting. Contrary to what we expected, we did not find significant changes in the phylogenetic structure of seedlings before or after palm-heart harvesting. The phylogenetic structure at the tips of the phylogeny was random overall. The maintenance of a higher presence of far relatives in the phylogeny of the seedling community suggests, assuming trait conservatism, that despite bamboo dominance and palm-heart harvesting, functional diversity is being preserved at least in the early regenerating stages and in the time frame of the study. However, higher presence of pioneer taxa after palm-heart harvest indicates that this disturbance may lead old-growth areas to earlier successional stages.
X-ray powder diffraction data for acetamidinium formate C3H8N2O2, elimination of preferred orientation effect
Authors: Maixner J. , Kačer P.
Published: September 2017

X-ray powder diffraction data, unit-cell parameters, and space group for acetamidinium formate, C3H8N2O2, are reported [a = 6.4564(5) Å, c = 13.021 (3) Å, unit-cell volume V = 542.8(3) Å3, M.p. = 215(1)°C, ρc = 1.274 g.cm−3, ρm = 1.269 g.cm−3, Z = 4, and space group P43212]. The front-loaded technique got sample with strong preferred orientation because of plate-like shape of crystallites, so the capillary packing was used for final powder data collection. All measured lines were indexed and are consistent with the P43212 space group. No detectable impurities were observed.
Using data linkage to improve surveillance methods for acute hepatitis E infections in England and Wales 2010–2016
Authors: OESER C. , SAID B. , WARBURTON F. , IJAZ S. , TEDDER R. , MORGAN D.
Published: September 2017

Indigenous, foodborne transmission of hepatitis E has been increasing across industrialised countries. Public Health England has conducted enhanced surveillance in England and Wales since 2003.This report gives an account of acute infections from 2010 to 2016 and describes modification made to the methods of surveillance to account for changes in reporting behaviours and improve ascertainment.