bluuebunny/crossref_metadata_2025 huggingface dataset:
Undiagnosed diabetes mellitus and tuberculosis infection: A population‐based, observational study from eastern China
Authors: Liu Qiao , Lu Peng , Martinez Leonardo , Peng Hong , Zhu Tao , Zhu Limei , Wang Jianming , Lu Wei
Published: October 2019

Background

China has the largest dual diabetes and tuberculosis epidemic globally. No studies from mainland China have assessed the relationship between tuberculosis infection and diabetes. We conducted a population‐based, observational study in eastern China to further explore this relationship.

Methods

A blood glucose, Quantiferon, and tuberculin skin test were administered at baseline. We compared tuberculosis infection in nondiabetics and diabetics. The cohort was additionally screened for tuberculosis progression over 5 years.

Results

Among 5405 participants, diabetics had elevated levels of Quantiferon and tuberculin positivity, largely driven by undiagnosed diabetics (compared with nondiabetics, adjusted odds ratios of 1.53; 95% confidence interval [CI], 1.05‐2.23 and 1.58; 95% CI, 1.07‐2.35 for tuberculin and Quantiferon positivity). During follow‐up, the annual tuberculosis incidence was three times higher for diabetics compared with the entire cohort.

Conclusions

These results suggest improving diabetic control through rapidly identifying undiagnosed diabetes may have indirect benefits to tuberculosis control. Targeting of preventive therapy to newly diagnosed diabetics at high‐risk for progressive tuberculosis in China should be considered.
A pilot study of preproinsulin peptides reactivity in Chinese patients with type 1 diabetes
Authors: Xian Yingxin , Xu Haixia , Gao Yifang , Yan Jinhua , Lv Jing , Ren Wenqian , Huang Qianwen , Jiang Ziyu , Xu Fen , Yao Bin , Weng Jianping
Published: October 2019

Background

The aim of our study is to investigate whether preproinsulin (PPI) could trigger a proinflammatory CD4+ T cell response in Chinese patients with type 1 diabetes (T1D).

Methods

Peripheral blood mononuclear cells were stimulated by a pool of 13 PPI peptides. Additional five PPI peptides previously proved to be antigenic in other cohorts of patients with T1D were also used. PPI reactive T cell responses were measured by interferon (IFN)‐γ ELISPOT assay.

Results

Fifty‐one Chinese patients with T1D were enrolled in this study and 72.34% of them were positive for at least one islet autoantibody. The stimulation index (SI) value of IFN‐γ response to PPI peptide pool or peptides with dominant epitopes was below 3 in patients when SI≥3 was used as the positive cut‐off value. Two peptides (B9‐23 and C19‐A3) restricted to DQ8 or DR4 molecule failed to induce positive IFN‐γ response in patients with high‐risk HLA‐DQ8 or HLA‐DR4/DR9 alleles. RNA‐seq analysis of PPI specific CD4+ T cell lines further showed that most of the IFN‐γ associated genes remained unchanged.

Conclusions

This is the first report of CD4+ T cell epitope mapping of PPI in Chinese T1D. The lack of positive IFN‐γ response to PPI peptides indicates that PPI might not be the principal antigenic candidate for autoreactive CD4+ T cells in Chinese T1D. Therefore, the efficacy of PPI‐based immunotherapies in attenuating proinflammatory CD4+ T cell response requires further investigation.
Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin
Authors: Adeghate Ernest , Lotfy Mohamed , D'Souza Crystal , Alseiari Saleh Meqbel , Alsaadi Abdulla Ali , Qahtan Saif Abdo
Published: October 2019

The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon‐like peptide‐1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.
A possible new oxidation marker for hair adulteration: Detection of PTeCA (1H‐pyrrole‐2,3,4,5‐tetracarboxylic acid) in bleached hair
Authors: Eisenbeiss Lisa , Binz Tina M. , Baumgartner Markus R. , Steuer Andrea E. , Kraemer Thomas
Published: October 2019

Hair analysis has become a valuable tool in forensic toxicology to assess drug or alcohol abstinence. Yet, hair adulteration by cosmetic products presents a major challenge for forensic hair analysis. Oxidative treatments, e.g. bleaching, may lead to analyte loss and thereby to false negative results. Currently, the eumelanin degradation product 1H‐pyrrole‐2,3,5‐tricarboxylic acid (PTCA) serves as a marker for oxidative hair treatment, but requires the definition of cut‐off values. To investigate further eumelanin degradation products as markers for oxidative hair treatment, hair samples with and without in vitro bleaching (hydrogen peroxide (H2O2) concentrations 1.9% up to 12%; incubation times 15 min, 30 min, 60 min) were analyzed by liquid chromatography coupled to high‐resolution time of flight mass spectrometry (HPLC‐HRMS). The distribution of eumelanin degradation products along the hair shaft was investigated for routine applicability after segmentation of cosmetically untreated hair samples and authentically treated hair samples. The signals of the eumelanin degradation products PTCA, 1H‐pyrrole‐2,3,4‐tricarboxylic acid (isoPTCA), and 1H‐pyrrole‐2,3,4,5‐tetracarboxylic acid (PTeCA) were found to be significantly elevated after in vitro bleaching already with low H2O2 concentrations and after short incubation times. In contrast to PTCA and isoPTCA, PTeCA was not detectable in cosmetically untreated segments up to 12 cm from hair root and was only formed through the oxidation process. The results of the study show that the detection of PTeCA within the proximal 3 to 6 cm segment can be applied to reliably detect hair adulteration attempts through hair bleaching.
Development and validation of a method to confirm the exogenous origin of prednisone and prednisolone by GC‐C‐IRMS
Authors: Iannella Loredana , Botrè Francesco , Colamonici Cristiana , Curcio Davide , de la Torre Xavier
Published: October 2019

Prednisone and prednisolone are two anti‐inflammatory steroidal drugs listed by the World Anti‐Doping Agency (WADA) within the class of glucocorticoids, which are prohibited “in competition” and when administered systemically. Their presence in collected urine samples may be attributed, if no exogenous administration has occurred, to an in situ microbial formation from endogenous steroids. In this work, a gas chromatography coupled to carbon isotope ratio mass spectrometry (GC‐C‐IRMS) method was developed and validated to distinguish an exogenous origin from an endogenous one. Eight prednisone/prednisolone pharmaceutical preparations commercially available in Italy were analysed to establish an exogenous δ13C value reference range (−28.96 ± 0.39‰). No more than 25 mL of urine was processed and no derivatization nor intentional steroids structure modifications were performed before the GC‐C‐IRMS analysis. A first HPLC purification step was set up to isolate the three endogenous reference compounds (ERCs) selected (tetrahydro‐11‐deoxycortisol (THS), pregnanediol (PD), and pregnanetriol (PT)), while a second LC purification was necessary to separate prednisone from prednisolone. In the GC‐C‐IRMS analysis, two different GC run methods were set up to guarantee better sensitivity and selectivity for each compound. Both prednisone and prednisolone showed signals (m/z 44) with amplitudes within the method linearity range to a lower urinary concentration of 20 ng/mL (< WADA reporting level, 30 ng/mL). The method was fully validated according to WADA requirements. As a proof of concept, urine samples collected from two excretion studies in healthy male volunteers, after a prednisone or prednisolone administration, were analysed by the proposed method, demonstrating its applicability for the analysis of real samples.
Analysis of luteinizing hormone (LH): Validation of a commercial ELISA kit for LH analysis and quantification in doping control samples
Authors: Mäkelä Riika , Leinonen Antti , Suominen Tina
Published: October 2019

Luteinizing hormone (LH) is a dimeric glycoprotein produced and secreted by the pituitary gland, with a molecular weight of approximately 30 000 Da. The main clinical use for exogenous LH‐administration is typically linked to the treatment of infertility, in both men and women. The desired effect of LH misuse in sport is due to the enhancement of testicular production of testosterone. Elevated LH levels may also indicate the usage of gonadotropin‐releasing factors or estrogen blockers. Therefore, LH is listed by the World Anti‐Doping Agency (WADA) as a prohibited substance in male athletes, and according to the WADA technical document, laboratories should determine the the total LH concentrations in urine. The TD lists two different assays that are suitable for measuring total LH in urine, Delfia and Siemens Immulite. Other fit‐for‐purpose assays can be used, as long as they are capable of detecting total LH in urine. In case an assay not listed in the TD will be used, population‐based reference values have to be determined in the validation procedure.

In this study a new immunoassay was validated for the measurement of LH in urine. The assay (AccuBind ELISA Microwells, Luteinizing Hormone, Monobind Inc.), originally intended for serum, showed adequate sensitivity and was proven fit‐for‐purpose in routine doping control. Population‐based distribution of the assay was in good agreement with the results of Delfia and Immulite assays, for which the method‐specific cut‐off‐values are 40 IU/L (Delfia) and 60 IU/L (Siemens Immulite).
Investigation of the metabolism of the selective androgen receptor modulator LGD‐4033 in equine urine, plasma and hair following oral administration
Authors: Cutler Charlotte , Viljanto Marjaana , Hincks Pamela , Habershon‐Butcher Jocelyn , Muir Tessa , Biddle Simon
Published: October 2019

LGD‐4033 is one of a number of selective androgen receptor modulators (SARMs) that are being developed by the pharmaceutical industry to provide the therapeutic benefits of anabolic androgenic steroids, without the less desirable side effects. Though not available therapeutically, SARMs are available for purchase online as supplement products. The potential for performance enhancing effects associated with these products makes them a significant concern with regards to doping control in sports. The purpose of this study was to investigate the metabolism of LGD‐4033 in the horse following oral administration, in order to identify the most appropriate analytical targets for doping control laboratories. LGD‐4033 was orally administered to two Thoroughbred horses and urine, plasma and hair samples were collected and analysed for parent drug and metabolites. LC‐HRMS was used for metabolite identification in urine and plasma. Eight metabolites were detected in urine, five of which were excreted only as phase II conjugates, with the longest detection time being observed for di‐ and tri‐hydroxylated metabolites. The parent compound could only be detected in urine in the conjugated fraction. Seven metabolites were detected in plasma along with the parent compound where mono‐hydroxylated metabolites provided the longest duration of detection. Preliminary investigations with hair samples using LC–MS/MS analysis indicated the presence of trace amounts of the parent compound and one of the mono‐hydroxylated metabolites. In vitro incubation of LGD‐4033 with equine liver microsomes was also performed for comparison, yielding 11 phase I metabolites. All of the metabolites observed in vivo were also observed in vitro.
Erythroferrone as a sensitive biomarker to detect stimulation of erythropoiesis
Authors: Ramirez Cuevas Kelvin , Schobinger Céline , Gottardo Emeric , Voss Sven Christian , Kuuranne Tiia , Tissot Jean‐Daniel , Favrat Bernard , Townsend Nathan , Leuenberger Nicolas
Published: October 2019

Erythroferrone (ERFE) is a glycoprotein hormone secreted by erythroblasts in response to erythropoietin stimulation. ERFE suppresses the hepatic synthesis of the master iron‐regulatory hormone, hepcidin. The impact of erythropoiesis stimulation on ERFE secretion in humans is poorly understood. This paucity of information is due in part to the lack of available means for ERFE quantification in serum samples. The present study tested a new sensitive sandwich immunoassay for human ERFE. This assay was used to demonstrate that injection of various erythropoiesis stimulating agents (ESAs) increased the blood ERFE levels in healthy volunteers. After exogenous stimulation of erythropoiesis, ERFE increased up to 8‐fold with a detection window of 13 days. The impact of one unit of blood withdrawal on erythropoiesis stimulation of ERFE was also tested. ERFE significantly increased after blood withdrawal in subjects injected with both iron and saline solution, suggesting that iron supplementation did not mask the ERFE increase after blood withdrawal. The effects of exercise‐induced muscle damage on ERFE was assessed by comparing ERFE levels with creatine kinase levels in samples from subjects with heavy exercise loads, and determined that this was not a confounder. The ERFE assay is a sensitive means to investigate the connection between iron metabolism and erythropoiesis in humans, and to detect ESA abuse in the antidoping field.
Habitat suitability analysis of Pengba fish in Loktak Lake and its river basin
Authors: Khwairakpam Eliza , Khosa Rakesh , Gosain Ashvani , Nema Arvind
Published: October 2019

Deterioration of water quality condition of lakes and rivers can be harmful to the health of aquatic life forms. This study presents habitat suitability analysis of Pengba fish (Osteobrama belangiri) species in Loktak Lake and its river basin. Pengba is the state fish of Manipur with a restricted distribution range in India, Myanmar and China. This fish species is endemic to a limited habitat range and is currently assessed as a near threatened species and has been reduced dramatically from the Northeast region of India. Water quality parameters of the lake and the nine rivers were used to assess habitat suitability using MIKE 11 ECO Lab and MIKE 21 ECO Lab. Simulated water quality parameters were integrated using a geographic information system (GIS)‐based, weighted overlay tool. The suitability of the fish species in the lake and nine rivers draining into the lake were divided into different zones of habitat suitability. This will help in framing conservation strategies, which, in turn, is expected to facilitate and aid in harmonizing eco‐sustainability services.
A 3D analysis of spatial habitat metrics about the confluence of Negro and Solimões rivers, Brazil
Authors: Gualtieri Carlo , Abdi Reza , Ianniruberto Marco , Filizola Naziano , Endreny Theodore A.
Published: October 2019

Confluences are integral features in rivers characterized by complex 3D changes in flow hydrodynamics and bed morphology and provide important ecological functions.

This paper presents the first known analysis of 3D spatial habitat metrics, based on hydraulic complexity, using data from the Negro and Solimões rivers confluence in the Amazon Basin, during high‐ and low‐flow conditions. The analysis was conducted using two bioenergetics metrics M2 and M3 computed for ~1‐m2 cells within each cross section. M2 is related to the drag force on a fish moving between two locations in the river, whereas M3 is related to the energy needed by a fish to remain in a location without spinning.

M2 provides useful spatial analysis of the confluence, and its longitudinal distribution as well as its uniformity parameters in the river cross sections showed a peak downstream the junction and a rapid decay in the central confluence hydrodynamic zone. This trend corresponded with the classic hydrodynamic features as well as with literature observed patterns of biotic assemblages downstream of river confluences. At the entrance of the Amazon channel, M2 peaks corresponded to the largest concentration of fish larvae demonstrating that the metric could be used to identify hot spots for aquatic species richness. The 3D derived M2 values were larger in magnitude than M2 values derived from depth‐averaged velocity data. The longitudinal distribution of M3 metric peaked immediately downstream of the confluence, and the M3 helical flow cells corresponded with areas where dolphins congregate to feed and could exert less energy to remain in this zone. The study demonstrated that a 3D analysis of velocity gradients is able to reveal and explain observed patterns of species abundance and richness beyond those captured by a 2D analysis.
A Laccase/Chitosan‐Lambda‐Carrageenan Based Voltammetric Biosensor for Phenolic Compound Detection
Authors: Chakroun Galai Hajer , Rassas Ilhem , Namour Philippe , Bonhomme Anne , Raimondi Gaetan , Besbes Hentati Salma , Jaffrezic‐Renault Nicole
Published: October 2019

In this contribution, a new concept of voltammetric catechol biosensor, based on the encapsulation of laccase (LAC) in a chitosan+lambda‐carrageenan (CHIT+CAR) polyelectrolyte complex (PEC) employing a simple coacervation process is presented. Chitosan (CHIT) was prepared from α‐chitin extracted from shrimp shells and lambda‐carrageenan (CAR) was extracted from red algae, both polysaccharides and PEC being characterized using FTIR spectrometry and electrochemistry. Cyclic voltammetry was utilized to determine the analytical features of the laccase (LAC) biosensor for catechol detection. The linear range was from 10−20 M to 10−14 M with a sensitivity of 1.55 mA/p[catechol] and a limit of detection of 3×10−21 M.The laccase biosensor exhibits good repeatability (RSD 2.38 %) and stability (four weeks). The developed biosensor was tested by applying it to the evaluation of the total polyphenolic content in natural oil samples.
4‐nitrophenol exposure in T24 human bladder cancer cells promotes proliferation, motilities, and epithelial‐to‐mesenchymal transition
Authors: Dong Fulu , Chen Lu , Wang Rui , Yang Weiping , Lu Tingting , Zhang Yonghui
Published: October 2019

Although health hazards of 4‐nitrophenol (PNP) exposure have been reported, the adverse effects of PNP exposure on cancer biological features are still unknown. We investigated the effects of administration of PNP in T24 human bladder cancer cells. The results showed that PNP exposure promoted cellular proliferation, migration and invasion, inhibited adhesion and apoptosis in vitro. Using quantitative real‐time PCR, we found that (1) the mRNA expression levels of cell‐cycle regulators PCNA, cyclin D1 and COX‐2 were increased in PNP‐treated cells compared to controls, however, that of pro‐apoptotic gene Bax was decreased; (2) the expression level of EMT‐associated gene E‐cadherin was decreased in PNP‐treated cells, whereas those of N‐cadherin, vimentin, snail, and slug were increased; (3) the expression levels of cancer‐promoting genes HIF‐1, IL‐1β, VEGFα and K‐Ras were enhanced, but those of tumor suppressors p53, PTEN and BRCA were decreased. There was a positive association between PNP exposure times and the promotion effects. Finally, we found that the expression level of PPARγ (γ1 isoform) was increased in PNP‐treated T24 cells. GW9662, a specific PPARγ antagonist, attenuated PNP‐induced cell migration and invasion. These findings indicate that PNP exposure may promote bladder cancer growth and progression involving PPARγ signaling. PPARγ is a potential target for development of novel intervention study on environment pollution. Environ. Mol. Mutagen. 61:316–328, 2020. © 2019 Wiley Periodicals, Inc.
Coastal ridge constructive processes at a multi‐decadal scale in Barreta Island (southern Portugal)
Authors: Herrero Xabier , Costas Susana , Kombiadou Katerina
Published: October 2019

Multiple ridges across prograding coasts may display variable geometries, commonly expressed through varying elevations. Changes in ridge elevation have been traditionally related to the occurrence of fluctuating progradation rates, which might, in turn, be driven by shifting environmental conditions.

Here, we explore the geometry and growth mechanisms of multiple ridges, generated at Barreta Island (Ria Formosa, southern Portugal), as a consequence of the rapid progradation of the island over the last 70 years, following the artificial fixation of the downdrift Faro‐Olhão inlet with jetties in 1955. The variability in the morphology of these features was analysed in combination with available wind and wave data, in order to better distinguish growth mechanisms and understand the main parameters determining the final geometry of the observed ridges.

The results suggest that (1) most of the identified ridges fall in the beach ridge classification, as they have been mostly built by marine processes, and (2) the parameters derived from, or closely related to wave climate variability (e.g. progradation rates, storm occurrence) can jointly explain most of the observed morphological changes, while aeolian processes played a secondary role. Indeed, ridge geometry appears mainly controlled by progradation rates, with higher ridges associated with lower progradation rates. Progradation rate, in turn, is mostly related to longshore wave power, storminess, and the occurrence storm groups. Yet, the final configuration of ridges can also be affected by runup levels and onshore winds. Therefore, establishing the relation between ridge geometry and wave climate is not a straightforward task, because of the complex processes and interactions that control coastal morphodynamics. © 2019 John Wiley & Sons, Ltd.
26Al/10Be ratios reveal the source of river sediments in the Kimberley, NW Australia
Authors: Cazes Gaël , Fink David , Codilean Alexandru T. , Fülöp Réka‐Hajnalka , Fujioka Toshiyuki , Wilcken Klaus M.
Published: October 2019

We use cosmogenic 10Be and 26Al in both bedrock and fluvial sediments to investigate controls on erosion rates and sediment supply to river basins at the regional scale in the Kimberley, NW Australia. The area is characterised by lithologically controlled morphologies such as cuestas, isolated mesas and extensive plateaus made of slightly dipping, extensively jointed sandstones. All sampled bedrock surfaces at plateau tops, ridgelines, and in the broader floodplain of major rivers over the region show similar slow lowering rates between 0.17 and 4.88 m.Myr‐1, with a mean value of 1.0 ± 0.6 m.Myr‐1 (n=15), whilst two bedrock samples collected directly within river‐beds record rates that are one to two orders of magnitude higher (14.4 ± 1.5 and 20.9 ± 2.5 m.Myr‐1, respectively). Bedrock 26Al/10Be ratios are all compatible with simple, continuous sub‐aerial exposure histories. Modern river sediment yield lower 10Be and 26Al concentrations, apparent 10Be basin‐wide denudation rates ranging between 1.8 and 7.7 m.Myr‐1, with a median value of 2.6 m.Myr‐1, more than double the magnitude of bedrock erosion rates. 26Al/10Be ratios of the sediment samples are lower than those obtained for bedrock samples. We propose that these depleted 26Al/10Be ratios can largely be explained by the supply of sediment to river basins from the slab fragmentation and chemical weathering of channel gorge walls and plateau escarpments that result in diluting the cosmogenic nuclide concentration in river sediments measured at the basin outlets. The results of a mass‐balance model suggest that ~60–90% of river sediment in the Kimberley results from the breakdown and chemical weathering of retreating vertical sandstone rock‐walls in contrast to sediment generated by bedrock weathering and erosion on the plateau tops. This study emphasises the value of analysing two or more isotopes in basin‐scale studies using cosmogenic nuclides, especially in slowly eroding post‐orogenic settings. © 2019 John Wiley & Sons, Ltd.
Hidden in plain sight: How finding a lake in the Brazilian Pantanal improves understanding of wetland hydrogeomorphology
Authors: Merino Eder Renato , Assine Mario Luis
Published: October 2019

Wetlands are permanently or seasonally flooded areas which support countless species of plants and animals. The Pantanal, in central‐west Brazil is one of the largest freshwater wetlands in the world covering an area of ~150 000 km2. The relationships between geomorphology, hydrology, sedimentation, and vegetation cover are critical for understanding how the landscape constrains the dynamics of wetlands. We provide a detailed study of the geomorphology and surface hydrology of the Negro River Interfan System (NRIS), in the southern Pantanal, by applying multiple approaches (i.e. remote sensing analysis, geomorphological zonation and hydrosedimentological surveys). A multitemporal analysis of Landsat imagery produced an inundation frequency map (2000–2011 period) that revealed a permanently flooded area in the central portion of the NRIS. A hidden fluvial lake was previously undetected due to the accumulation of floating mats and floating meadows of macrophytes. The Negro and Aquidauana feeder rivers exhibit remarkable differences in channel planform, water discharge, and sediment load. The Negro River presents a distributary pattern with marginal levees with decreasing elevation as it progrades into the lake and remains as a subaqueous landform conditioning the water flow downstream. The lake outflow to the Paraguay River occurs mainly by sheet flow during flood seasons and through small tributary channels during dry months. The lake's geometry is outlined by east–northeast and west–northwest straight borders, suggesting that the area is tectonically controlled. A cloud‐based worldwide water surface database (1984–2015) revealed frequent channel changes within the NRIS. Recent channel avulsions in the lower course of the Negro River are noteworthy mainly because the former river channel at the confluence with the Paraguay River is no longer connected with the Negro River channel. © 2019 John Wiley & Sons, Ltd.
Synergic integration of desalination and electric vehicle loads with hybrid micro‐grid sizing and control: An Island Case Study
Authors: Tu Tu , Rajarathnam Gobinath P. , Vassallo Anthony M.
Published: October 2019

This study addresses the feasibility, sizing, and scheduling of an island micro‐grid involving photovoltaic, wind turbine, diesel generator, and battery energy storage systems. In addition, the end‐use demand is expanded beyond residential electricity loads, as the full electrification on domestic water supply and transportation, in the forms of desalination and electric vehicles (EVs), are proposed in this study with integration to a renewable energy system focused micro‐grid. A mixed integer linear programming model is constructed to explore the mutual interactions of desalination plant, vehicle‐to‐grid enabled EVs and residential load deferring on a micro‐grid. A case study in Bruny Island, Australia was incorporated in the study, based on the existing infrastructure and future planning. Multiple scenarios were run utilizing real‐world, fine resolution time‐series data. Results were compared to investigate the impact of the polygeneration configuration and potential economic savings on household affordability. Our study displayed the advantage of electrifying and integrating household resources into the micro‐grid, such as transportation and water filtration. The integration created a greater diversity in electricity end‐uses, allowed for better scheduling and Renewable System management. In addition, the cost‐benefit analysis of stationary battery storage units was modeled against the other forms of energy storage, such as electric vehicles and seawater desalination plant, with findings suggesting the potential economic advantage of storage other than grid connected batteries in a residential precinct.
Accelerated inactivation of M13 bacteriophage using millijoule femtosecond lasers
Authors: Berchtikou Aziz , Greschner Andrea A. , Tijssen Peter , Gauthier Marc A. , Ozaki Tsuneyuki
Published: October 2019

Irradiation of femtosecond (fs) pulse lasers in the visible and near‐infrared ranges have been proposed as a promising approach for inactivating viruses. However, in order to achieve significant virus inactivation, past works have required relatively long irradiation times (1 hour or longer), even for small volumes. Given its advantages compared with other techniques, there is an urgent need to shorten the time required to inactivate viruses using fs laser technology. In this study, we investigate the inactivation of purified M13 bacteriophage in phosphate‐buffered saline with large active volume (1 cm3), and short exposure time (several minutes), using lasers with 20 mJ/pulse energy at various wavelengths (800, 400 nm or both 800 and 400 nm combined). For an exposure time of 15 and 2 minute, the use of a 400 nm wavelength laser results in a high load reduction of 5.8 ± 0.3 and 2.9 ± 0.15, respectively, on the log10 scale of viability. We show that virus inactivation using the 400 nm laser is much more efficient compared with that using an 800 nm laser, or the simultaneous irradiation of 400 and 800 nm lasers. Higher pathogen inactivation is observed for lasers with shorter pulse duration, whereas at longer pulse durations, the inactivation is reduced. For millijoule‐energy fs laser irradiation, the M13 bacteriophage inactivation, via the reduction of the functionality of M13 bacteriophages, is accompanied with relatively small amounts of genetic damage.
Infrared biomarkers of impaired cystic fibrosis transmembrane regulator protein biogenesis
Authors: Bellisola Giuseppe , Caldrer Sara , Cestelli‐Guidi Mariangela , Cinque Gianfelice
Published: October 2019

The mid‐infrared (IR) spectra of human cystic fibrosis (CF) cells acquired by Fourier transform infrared microspectroscopy were compared with those of non‐CF cells. Within the 1700 to 1480 cm−1 spectral domain of amides, unsupervised explorative principal component analysis identified a few variables reflecting quantitative and qualitative vibrations arising from protein secondary structures and amino acid side chains. Their pattern reflected α‐helix to β‐sheet transitions in bronchial epithelial cells and in immortalized peripheral blood mononuclear cells from patients with R1162X missense or in‐frame F508del mutations in the cystic fibrosis transmembrane regulator gene (Cftr). Similar transitions have been described in IR spectra of cells, tissues and body fluids of patients affected with some neurodegenerative diseases characterized by the accumulation of misfolded protein aggregates. The variables pattern was able to distinguish CF cells from non‐CF cells and was modified by molecular compounds used to rescue the unbalanced folding process of mutated cystic fibrosis transmembrane regulator (CFTR) anion channel. To our knowledge, this is the first experimental evidence of spectroscopic biomarkers of the impaired biogenesis of CFTR by IR microanalysis in the spectra of human CF bronchial epithelial and lymphoblastoid cells.
In vitro and in vivo biocompatibility of calcium‐phosphate scaffolds three‐dimensional printed by stereolithography for bone regeneration
Authors: Le Guéhennec Laurent , Van hede Dorien , Plougonven Erwan , Nolens Grégory , Verlée Bruno , De Pauw Marie‐Claire , Lambert France
Published: October 2019

Stereolithography (SLA) is an interesting manufacturing technology to overcome limitations of commercially available particulated biomaterials dedicated to intra‐oral bone regeneration applications. The purpose of this study was to evaluate the in vitro and in vivo biocompatibility and osteoinductive properties of two calcium‐phosphate (CaP)‐based scaffolds manufactured by SLA three‐dimensional (3D) printing. Pellets and macro‐porous scaffolds were manufactured in pure hydroxyapatite (HA) and in biphasic CaP (HA:60‐TCP:40). Physico‐chemical characterization was performed using micro X‐ray fluorescence, scanning electron microscopy (SEM), optical interferometry, and microtomography (μCT) analyses. Osteoblast‐like MG‐63 cells were used to evaluate the biocompatibility of the pellets in vitro with MTS assay and the cell morphology and growth characterized by SEM and DAPI‐actin staining showed similar early behavior. For in vivo biocompatibility, newly formed bone and biodegradability of the experimental scaffolds were evaluated in a subperiosteal cranial rat model using μCT and descriptive histology. The histological analysis has not indicated evidences of inflammation but highlighted close contacts between newly formed bone and the experimental biomaterials revealing an excellent scaffold osseointegration. This study emphasizes the relevance of SLA 3D printing of CaP‐based biomaterials for intra‐oral bone regeneration even if manufacturing accuracy has to be improved and further experiments using biomimetic scaffolds should be conducted.
PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway
Authors: Li Pei , Wang Jing , Zhao Xia , Ru Jing , Tian Tian , An Yun , Tang Liying , Bai Yuzhi
Published: October 2019

Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low‐density lipoprotein (ox‐LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox‐LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase‐9/‐3 activation. In addition, ox‐LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox‐LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox‐LDL and knockdown of PTEN could attenuate ox‐LDL‐mediated endothelial cell damage. Furthermore, we found that ox‐LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMP‐activated protein kinase (AMPK)–cAMP‐response element‐binding protein (CREB)–Mitofusin‐2 (Mfn2) axis. When the AMPK–CREB–Mfn2 pathway was inhibited, PTEN deletion‐associated HUVECs protection was significantly reduced, suggesting that the AMPK–CREB–Mfn2‐mitophagy axis is required for PTEN deletion‐mediated endothelial cell survival under ox‐LDL. Taken together, our results indicate that ox‐LDL‐induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK–CREB–Mfn2‐mitophagy signaling pathway.
Extended 36‐joint sonographic examination: What it reveals about bone erosions in patients with rheumatoid arthritis
Authors: Tan York Kiat , Li HuiHua , Allen John C. , Thumboo Julian
Published: October 2019

Purpose

To identify joints commonly exhibiting bone erosions using an extended 36‐joint sonographic (US) examination in patients with rheumatoid arthritis (RA) and to study bone erosion in relation to US‐detected joint inflammation.

Methods

In this cross‐sectional study, power Doppler (PD) and gray‐scale (GS) joint inflammation scores (semi‐quantitative [0‐3] grading) at each joint recess were summed to obtain a combined US score (CUS). Bone erosion was scored as present/absent. Generalized Estimating Equations were used to compare mean US scores between joint recesses with and without bone erosion.

Results

Bone erosion was found in 144/1080 (13.3%) joints and 189/1800 (10.5%) joint recesses in 30 RA patients. The five joints most frequently associated with bone erosion were: wrist, n = 49/144 (34.0%); first MTPJ, n = 19/144 (13.2%); thumb IPJ, n = 13/144 (9.0%); second MCPJ, n = 11/144 (7.6%); and third MCPJ, n = 11/144 (7.6%). Mean (95% CI) US scores for joint recesses with and without bone erosion were PD: 0.36 (0.21, 0.50) vs 0.01 (0.00, 0.02); GS: 1.77 (1.54, 2.00) vs 0.47 (0.40, 0.55); and CUS: 2.13 (1.78, 2.47) vs 0.49 (0.41, 0.57) (all differences significant at P < .001).

Conclusion

The five joints most frequently showing bone erosion were identified. Joint recesses with bone erosion are more likely to exhibit greater PD and GS joint inflammation severity.
The impact of flipped classrooms on student achievement in engineering education: A meta‐analysis of 10 years of research
Authors: Lo Chung Kwan , Hew Khe Foon
Published: October 2019

Background

The flipped classroom has become more widely used in engineering education. However, a systematic and quantitative assessment of its achievement outcomes has not been conducted to date.

Purpose

To address this gap, we examined the findings from comparative articles published between 2008 and 2017 through a meta‐analysis to summarize the overall effects of the flipped classroom on student achievement in engineering education.

Scope/Method

We searched and analyzed journal and conference publications on flipped classroom studies in engineering education in K‐12 and higher education contexts. Twenty‐nine comparative interventions were included in a meta‐analysis involving 2,590 students exposed to flipped classroom and 2,739 students exposed to traditional lectures. A content analysis was also conducted to determine how the flipped engineering classroom benefits student learning.

Conclusions

The meta‐analysis comparing these 29 traditional—flipped interventions in relation to student achievement showed an overall significant effect in favor of the flipped classroom over traditional lecturing (Hedges' g = 0.289, 95% CI [0.165, 0.414], p < .001). A moderator analysis showed that the effect of the flipped classroom was further enhanced when instructors offered a brief review at the start of face‐to‐face classes. Our qualitative findings suggest that self‐paced learning and more problem‐solving activities were the two most frequently reported benefits that promoted student learning. Based on quantitative and qualitative support, several implications are identified for future practice, such as offering a brief in‐class review of preclass materials. Some recommendations for future research are also provided.
Outcome of portosystemic shunt surgery on pre‐existing cholangiopathy in children with extrahepatic portal vein obstruction
Authors: Ravindranath Aathira , Sen Sarma Moinak , Yachha Surender Kumar , Lal Richa , Singh Somesh , Srivastava Anshu , Poddar Ujjal , Neyaz Zafar , Behari Anu
Published: October 2019

Background

This study was performed to assess the effect of portosystemic shunt surgery (PSS) on portal cavernoma cholangiopathy (PCC) in children with extrahepatic portal vein obstruction (EHPVO).

Methods

Children with EHPVO and PCC (unfit for Meso‐Rex shunt) underwent magnetic resonance cholangiogram (MRC) and magnetic resonance portovenogram (MRPV) before non‐selective PSS. PCC was graded by modified Llop classification. Those with patent shunt were re‐evaluated at least 6 months after surgery with MRC, MRPV and compared with pre‐shunt images.

Results

Twenty‐five children underwent PSS (central end to side splenorenal shunt with splenectomy [n = 24], mesocaval shunt [n = 1]). Pre‐surgery MRC showed PCC grade I in 11, grade II in 1 and grade III in 13. MRPV showed superior mesenteric vein (SMV) block in 20. Re‐assessment for PCC 18 (6 to 54) months after surgery showed grade I in 6 and grade III in 19. Thus, PCC was progressive in 6 and static in 19. Density of peribiliary collaterals decreased in 5 (SMV patent, static PCC), increased in 3 and remained unchanged in 17. Splenomegaly‐related problems, gastroesophageal varices and other intra‐abdominal (esophageal, perisplenic and perigastric) collaterals ameliorated in all.

Conclusion

Non‐selective PSS decompresses esophago‐gastro‐splenic venous circuit effectively but fails to ameliorate cholangiopathy and peribiliary collaterals. Persistence of cholangiopathy is attributable to SMV block.
Predictive performance of Blumgart T staging for perihilar cholangiocarcinoma in a Japanese center
Authors: Ebata Tomoki , Mizuno Takashi , Yokoyama Yukihiro , Igami Tsuyoshi , Yamaguchi Junpei , Onoe Shunsuke , Watanabe Nobuyuki , Nagino Masato
Published: October 2019

Background

The Blumgart system has been used for local tumor assessment in perihilar cholangiocarcinoma to predict resectability and survival, and T3 tumors are considered unresectable disease. The aim was to validate the predictive performance of this system using a Japanese cohort.

Methods

Medical records of consecutive patients with perihilar cholangiocarcinoma between 2006 and 2016 were retrospectively reviewed. Resectability, surgical procedure, R0 resection rate, and survival were compared among T stages.

Results

Among 729 study patients, 191 patients had T1 tumors, 94 patients had T2 tumors, and 444 (60.9%) patients had T3 tumors according to the Blumgart T stage. Resection was performed in 513 (70.4%) patients; resectability rate decreased with the progression of T stage: 89.0% in T1, 79.8% in T2, and 60.4% in T3 tumors (P < 0.001). The incidences of left hepatic trisectionectomy and portal vein resection were 44.0% and 54.1%, respectively, in patients with T3 tumors, which were significantly greater than those of T1/2 tumors (P = 0.001 and P < 0.001). R0 resection reduced with advanced T stage: 92.4% in T1, 81.3% in T2, and 70.9% in T3 tumors (P < 0.001). The 5‐year survival rate was 53.4%, 38.4%, and 19.7% in T1, T2, and T3 tumors, respectively (P < 0.001); that was 59.6%, 48.6%, and 30.7%, respectively, in the resected cohort (P < 0.001).

Conclusion

Blumgart T stage was closely associated with the resectability rate, surgical procedures, R0 resection rate, and survival time, suggesting that the T stage works as well as a presurgical staging system. However, the unresectable classification of T3 tumors should be revised.
Robust association between vascular habitats and patient prognosis in glioblastoma: An international multicenter study
Authors: del Mar Álvarez‐Torres María , Juan‐Albarracín Javier , Fuster‐Garcia Elies , Bellvís‐Bataller Fuensanta , Lorente David , Reynés Gaspar , Font de Mora Jaime , Aparici‐Robles Fernando , Botella Carlos , Muñoz‐Langa Jose , Faubel Raquel , Asensio‐Cuesta Sabina , García‐Ferrando Germán A. , Chelebian Eduard , Auger Cristina , Pineda Jose , Rovira Alex , Oleaga Laura , Mollà‐Olmos Enrique , Revert Antonio J. , Tshibanda Luaba , Crisi Girolamo , Emblem Kyrre E. , Martin Didier , Due‐Tønnessen Paulina , Meling Torstein R. , Filice Silvano , Sáez Carlos , García‐Gómez Juan M.
Published: October 2019

Background

Glioblastoma (GBM) is the most aggressive primary brain tumor, characterized by a heterogeneous and abnormal vascularity. Subtypes of vascular habitats within the tumor and edema can be distinguished: high angiogenic tumor (HAT), low angiogenic tumor (LAT), infiltrated peripheral edema (IPE), and vasogenic peripheral edema (VPE).

Purpose

To validate the association between hemodynamic markers from vascular habitats and overall survival (OS) in glioblastoma patients, considering the intercenter variability of acquisition protocols.

Study Type

Multicenter retrospective study.

Population

In all, 184 glioblastoma patients from seven European centers participating in the NCT03439332 clinical study.

Field Strength/Sequence

1.5T (for 54 patients) or 3.0T (for 130 patients). Pregadolinium and postgadolinium‐based contrast agent‐enhanced T1‐weighted MRI, T2‐ and FLAIR T2‐weighted, and dynamic susceptibility contrast (DSC) T2* perfusion.

Assessment

We analyzed preoperative MRIs to establish the association between the maximum relative cerebral blood volume (rCBVmax) at each habitat with OS. Moreover, the stratification capabilities of the markers to divide patients into "vascular" groups were tested. The variability in the markers between individual centers was also assessed.

Statistical Tests

Uniparametric Cox regression; Kaplan–Meier test; Mann–Whitney test.

Results

The rCBVmax derived from the HAT, LAT, and IPE habitats were significantly associated with patient OS (P < 0.05; hazard ratio [HR]: 1.05, 1.11, 1.28, respectively). Moreover, these markers can stratify patients into "moderate‐" and "high‐vascular" groups (P < 0.05). The Mann–Whitney test did not find significant differences among most of the centers in markers (HAT: P = 0.02–0.685; LAT: P = 0.010–0.769; IPE: P = 0.093–0.939; VPE: P = 0.016–1.000).

Data Conclusion

The rCBVmax calculated in HAT, LAT, and IPE habitats have been validated as clinically relevant prognostic biomarkers for glioblastoma patients in the pretreatment stage. This study demonstrates the robustness of the hemodynamic tissue signature (HTS) habitats to assess the GBM vascular heterogeneity and their association with patient prognosis independently of intercenter variability.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2020;51:1478–1486.
Diagnostic accuracy of quantitative diffusion parameters in the pathological grading of hepatocellular carcinoma: A meta‐analysis
Authors: Yang Dawei , She Hualong , Wang Xiaopei , Yang Zhenghan , Wang Zhenchang
Published: October 2019

Background

Accurate preoperative assessment of the pathological grade of hepatocellular carcinoma (HCC) could greatly benefit prognostic predictions.

Purpose

To assess and compare the diagnostic accuracy of the apparent diffusion coefficient (ADC) and tissue diffusivity (D) for the noninvasive pathological grading of HCC.

Study Type

Meta‐analysis.

Data Sources

PubMed/Medline, EMBASE, the Web of Science, and the Cochrane Library were searched to find related original articles published up to May 30, 2019.

Field Strength/Sequence

Diffusion‐weighted imaging (DWI) and/or intravoxel incoherent motion (IVIM) were performed with a 1.5T or 3.0T scanner.

Assessment

The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodologic quality.

Statistical Tests

The bivariate random‐effects model was used to obtain the pooled sensitivity and specificity, and the area under summary receiver operating characteristic curve (AUROC) was obtained. Subgroup analyses were performed.

Results

A total of 16 original articles (1428 HCCs) were included. Most studies had a low to unclear risk of bias and minimal concerns regarding applicability. For the discrimination of well‐differentiated HCCs, the pooled sensitivity and specificity of the ADC value were 85% and 92%, respectively. For the discrimination of poorly differentiated HCCs, the pooled sensitivity and specificity of the ADC value and D were 84% and 80%, and 92% and 77%, respectively. The summary AUROC of D (0.94) was significantly higher than that of ADC (0.89) (z = –2.718, P = 0.007). The subgroup analyses identified three covariates including size, number of included lesions in the studies, and blindness to the reference standard as possible sources of heterogeneity.

Data Conclusion

This meta‐analysis showed that the ADC and D values had a high to excellent accuracy for the noninvasive pathological grading of HCCs and that the D value was superior to the ADC value for discriminating poorly differentiated HCCs.

Level of Evidence: 3

Technical Efficacy Stage: 2

J. Magn. Reson. Imaging 2020;51:1581–1593.