bluuebunny/crossref_metadata_2025 huggingface dataset:
Flower pollination algorithm‐based energy‐efficient stable clustering approach for WSNs
Authors: Sharma Rajan , Mittal Nitin , Sohi Balwinder Singh
Published: January 2020

The advances in the size, cost of deployment, and user‐friendly interface of wireless sensor devices have given rise to many wireless sensor network (WSN) applications. WSNs need to use protocols for transmitting data samples from event regions to sink through minimum cost links. Clustering is a commonly used method of data aggregation in which nodes are organized into groups to reduce energy consumption. Nonetheless, cluster head (CH) has to bear an additional load in clustering protocols to organize different activities within the cluster. Proper CH selection and load balancing using efficient routing protocol is therefore a critical aspect for WSN's long‐term operation. In this paper, a threshold‐sensitive energy‐efficient cluster‐based routing protocol based on flower pollination algorithm (FPA) is proposed to extend the network's stability period. Using FPA, multihop communication between CHs and base station is used to achieve optimal link costs for load balancing distant CHs and energy minimization. Analysis and simulation results show that the proposed algorithm significantly outperforms competitive clustering algorithms in terms of energy consumption, stability period, and system lifetime.
When IRBs Say No to Participating in Research about Single IRBs
Authors: Klitzman Robert , Appelbaum Paul S. , Murray Alexandra , Pivovarova Ekaterina , Stiles Deborah F. , Lidz Charles W.
Published: January 2020

In response to a policy of the National Institutes of Health and requirements in the revised Common Rule, a protocol for a multisite study must be reviewed by a single institutional review board (IRB), rather than by the IRB at each study site. The goal of the single IRB approach is to increase the efficiency of IRB review of multisite research without jeopardizing protections for research subjects. Yet the extent to which these joint goals are being achieved is unclear. To better understand how single IRBs function, we recruited academic, government, and commercial single IRBs (N = 49) to participate in a study involving observation of protocol review meetings and/or interviews with their members, chairs, and administrators. Twenty (40.8%) agreed to participate, of which 50% agreed to both interviews and observation. While 81.8% (9/11) of academic and 50% (4/8) of government single IRBs participated in some way, only 23.3% (7/30) of commercial single IRBs did so. The four largest commercial single IRBs declined to participate. Because evaluation of single IRBs is important to inform development, implementation, monitoring, and refinement of federal policies, single IRBs should be encouraged to participate in research that examines how they function.
Quantifying the relative predation pressure on bumblebee nests by the European badger (Meles meles) using artificial nests
Authors: Roberts Bethany R. , Cox Ruth , Osborne Juliet L.
Published: January 2020

Bumblebee populations are declining. Factors that impact the size and success of colonies act by either limiting resource availability (bottom‐up regulation) or causing mortality, for example, pesticides, disease, and possibly predation (top‐down regulation). The impact of predation has not been quantified, and so, the current study used novel artificial nests as a proxy for wild bumblebee nests to quantify the relative predation pressure from badgers in two habitats: woodland and grassland, and at two nesting depths: surface and underground. Badgers occur across most parts of the UK and are known to predate on bumblebee nests. We found that significantly more artificial nests (pots containing bumblebee nest material) were dug up compared with control pots (pots without bumblebee nest material). This shows that artificial nests have the potential to be used as a method to study the predation of bumblebee nests by badgers. In a location of high badger density, predation pressure was greater in woodland than grassland, whereas no difference was observed in relation to nest depth. Woodland and grassland are shared habitats between bumblebees and badgers, and we suggest that higher predation may relate to activity and foraging behavior of badgers in woodland compared with grassland. We discuss how badger predation in different habitats could impact different bumblebee species according to their nesting behaviors. Understanding the relative impact of badger predation on bumblebee colonies provides key information on how such top‐down regulation affects bumblebee populations.
Synergistic prognostication of left ventricular hypertrophy and three‐dimensional mechanical dyssynchrony in heart failure
Authors: Doi Takahiro , Nakata Tomoaki , Yuda Satoshi , Hashimoto Akiyoshi
Published: January 2020

Aims

In this study, we investigated the prognostic interplay of left ventricular hypertrophy and mechanical dyssynchrony (LVMD), both of which can be measured three‐dimensionally by gated myocardial perfusion imaging (MPI), in patients with chronic systolic heart failure (HF).

Methods and results

In 829 consecutive HF patients with reduced left ventricular ejection fraction less than 50%, LVMD was evaluated as a standard deviation (phase SD) of regional onset of mechanical contraction phase angles. A phase histogram was created by Fourier phase analysis applied to regional time‐activity curves obtained by gated MPI. Left ventricular mass index (LVMI) was measured by Corridor 4DM version 6.0. Patients were followed up with a primary endpoint of lethal cardiac events (CE) for a mean interval of 34 months. CE were documented in 223 (27%) of the HF patients. The CE group had a greater phase SD and a greater LVMI than those in the non‐CE group. Patients in the CE group had a more advanced age, greater New York Heart Association (NYHA) functional class, left ventricular cavity size, and left atrial diameter or septal E/e' and lower kidney or cardiac function than did patients in the non‐CE group. Phase SD > 37 and LVMI > 122.7 g/m2 were identified as optimal cut‐off values by receiver operating characteristic analyses for discrimination of the most increased risk HF subgroup from others (P < 0.0001). When classified into four patient subgroups using both cut‐off values, HF patients with phase SD > 37 (LVMD) and LVMI > 122.7g/m2 had the highest CE rate among the subgroups (P < 0.0001). Univariate analysis and subsequent multivariate analysis with a Cox proportional hazards model showed that phase SD and LVMI were significant independent predictors of CE with hazard ratios of 1.038 (confidence interval [CI], 1.024–1.051, P < 0.0001) and 1.005 (CI, 1.001–1.008, P = 0.0073), respectively, as well as conventional clinical parameters such as age, NYHA class, estimated glomerular filtration rate (eGFR), and BNP concentration. Patients with increased phase SD and LVMI had incrementally improved prognostic values of clinical parameters including age, NYHA functional class, eGFR, and BNP with increases in the global χ2 value: 5.9 for age; 139.5 for age and NYHA; 157.9 for age, NYHA, and eGFR; 163.9 for age, NYHA, eGFR, and BNP; 183.4 for age, NYHA, eGFR, BNP, and phase SD; and 192.5 for age, NYHA, eGFR, BNP, phase SD, and LVMI.

Conclusions

Three‐dimensionally assessed LVMD has independent prognostic values and can improve the risk stratification of chronic HF patients synergistically in combination with conventional clinical parameters.
Promoting Effect of KIT‐6 to Support Ni‐Ce0.8Gd0.2O2‐δ as Efficient Coke‐Resistant Catalysts for Carbon Dioxide Reforming of Methane
Authors: Xiang Xianmei , Zhao Huahua , Yang Jian , Zhao Jun , Yan Liang , Song Huanling , Chou Lingjun
Published: January 2020

A series of Ni‐Ce0.8Gd0.2O2‐δ/KIT‐6 composites with various mass ratios were prepared by the impregnation approach. TEM and XRD characterization results revealed that the KIT‐6 support improved the distribution of Ni‐Ce0.8Gd0.2O2‐δ nanoparticles through the confinement effect of ordered mesopores of KIT‐6. XPS measurement showed that the concentration of surface oxygen vacancies in Ni‐Ce0.8Gd0.2O2‐δ/KIT‐6 composite was higher than that in KIT‐6‐free Ni‐Ce0.8Gd0.2O2‐δ. The catalytic test toward CO2 reforming of CH4 indicated that the Ni‐Ce0.8Gd0.2O2‐δ/KIT‐6 exhibited higher catalytic activity and stability over 100 h at 700 °C than Ni‐Ce0.8Gd0.2O2‐δ. The enhanced performance was demonstrated to be due to improved nickel dispersion and higher concentration of oxygen vacancies in Ni‐Ce0.8Gd0.2O2‐δ/KIT‐6, which reinforced the catalytic activity and decoking ability in the reforming reaction, thus boosting the durability of the catalyst.
Two‐Dimensional Uranyl Borates: From Conventional to Extreme Synthetic Conditions
Authors: Hao Yucheng , Kegler Philip , Albrecht‐Schmitt Thomas E. , Wang Shuao , Dong Qiang , Alekseev Evgeny V.
Published: January 2020

A systematic investigation of uranyl borates under different synthetic conditions resulted in five new 2D compounds, namely, (H3O)[(UO2)(BO3)], Li[(UO2)(BO3)]·(H2O), α‐K4[(UO2)5(BO3)2O4], β‐K4[(UO2)5(BO3)2O4] and K2.5[(UO2)5(BO3)2O2.5(OH)1.5]·(H2O)2.5. (H3O)[(UO2)(BO3)] and Li[(UO2)(BO3)]·(H2O) were obtained from hydrothermal reactions at 220 °C using the same mineralizer. Both materials possess the uranophane sheet topology with different symmetry of the unit cells. In the structure of (H3O)[(UO2)(BO3)] and Li[(UO2)(BO3)]·(H2O), UO7 pentagonal bipyramids share edges and vertexes with four BO3 planar triangles. α‐K4[(UO2)5(BO3)2O4] and β‐K4[(UO2)5(BO3)2O4] are polytypes. α‐K4[(UO2)5(BO3)2O4] was synthesized from a high‐temperature solid‐state reaction under ambient pressure; whereas β‐K4[(UO2)5(BO3)2O4] was obtained from a high‐temperature/high‐pressure (HT/HP) reaction. Both structures have an identical anion topology, but β‐K4[(UO2)5(BO3)2O4] crystallizes in space group with higher symmetry. In K2.5[(UO2)5(BO3)2O2.5(OH)1.5]·(H2O)2.5, which was obtained from a hydrothermal reaction, UO7 polyhedra share vertexes and edges with two independent BO3 triangles, forming the most complex uranyl borate layers among all five compounds. The different synthetic routes, novel topologies, thermal behavior and Raman spectra are discussed.
Visible‐Light‐Promoted Metal‐Free C‐H Trifluoromethylation of Imidazopyridines
Authors: Mi Xia , Kong Yuanfang , Yang Huaixia , Zhang Jingyu , Pi Chao , Cui Xiuling
Published: January 2020

A metal‐free photo redox C–H trifluorometlylation of imidazopyridines is described. The reaction is operationally simple and the easy‐handling CF3SO2Na serves as an effective fluoroalkyl radical precursor. Various functional groups were tolerated under blue LED light to access the desired products in satisfied yields at room temperature.
Mechanical characterization of vesicles and cells: A review
Authors: Morshed Adnan , Karawdeniya Buddini Iroshika , Bandara Y.M. Nuwan D.Y. , Kim Min Jun , Dutta Prashanta
Published: January 2020

Vesicles perform many essential functions in all living organisms. They respond like a transducer to mechanical stress in converting the applied force into mechanical and biological responses. At the same time, both biochemical and biophysical signals influence the vesicular response in bearing mechanical loads. In recent years, liposomes, artificial lipid vesicles, have gained substantial attention from the pharmaceutical industry as a prospective drug carrier which can also serve as an artificial cell‐mimetic system. The ability of these vesicles to enter through pores of even smaller size makes them ideal candidates for therapeutic agents to reach the infected sites effectively. Engineering of vesicles with desired mechanical properties that can encapsulate drugs and release as required is the prime challenge in this field. This requirement has led to the modifications of the composition of the bilayer membrane by adding cholesterol, sphingomyelin, etc. In this article, we review the manufacturing and characterization techniques of various artificial/synthetic vesicles. We particularly focus on the electric field‐driven characterization techniques to determine different properties of vesicle and its membranes, such as bending rigidity, viscosity, capacitance, conductance, etc., which are indicators of their content and mobility. Similarities and differences between artificial vesicles, natural vesicles, and cells are highlighted throughout the manuscript since most of these artificial vesicles are intended for cell mimetic functions.
Assessment and prediction of earthing resistance in domestic installation
Authors: Nti Isaac K. , Appiah Albert Y. , Nyarko‐Boateng Owusu
Published: January 2020

Before the introduction of the Ghana Electrical Wiring Regulations 2012 (L.I. 2008), most residential wiring within Sunyani Municipality was carried out by unlicensed artisans. This situation imposed a need to investigate the effectiveness of the earthing systems carried in the Sunyani municipality. Therefore, the current study sought to evaluate earthing resistance effectiveness within the Sunyani Municipality by measuring the earthing resistance of 1004 homes with an earthing resistance tester from January 2016 to April 2018. Again, we predict future resistance based on measured values. Out of 1004 buildings surveyed, 834 had an earthing system in place. Twenty‐eight buildings, recorded an earth electrode test within 0.0 to 10 Ω representing 3.36%. A high percentage (96.64%) had their earth electrode resistance above the acceptable value by the Energy Commission of Ghana. The results revealed that the overall effectiveness of earthing in the domestic installation in Sunyani Municipality is below average compared with Ghana Energy Commission benchmark.
Modeling the duration and size of extended attack wildfires as dependent outcomes
Authors: Xi Dexen DZ. , Dean C.B. , Taylor Stephen W.
Published: January 2020

Understanding the complex relationship between the duration and size of forest fires is important in order to better predict these key characteristics of fires for fire management purposes in a changing climate. Describing this relationship is also important for our fundamental understanding of fire science. Here, we develop and utilize novel techniques for characterizing the distribution of multiple outcomes related to a specific event, placed in the fire science context. In this framework, we jointly model time spent (duration), in days, and area burned (size), in hectares, from ground attack to final control of a fire as a bivariate survival outcome using two broad methodologies: a copula model that connects the two outcomes functionally and a joint modeling framework that connects the two outcomes with a shared random effect. We compare these two methodologies in terms of their utility and predictive power. We also consider how longitudinal environmental variables (e.g., precipitation, drought indices) are best incorporated in this context and the challenges related to the complexity of computation associated with the analysis of two outcomes considered jointly.
Study on failure models and fractal characteristics of shale under seepage‐stress coupling
Authors: Lou Yili , Wu Zhonghu , Sun Wenjibin , Yin Shuai , Wang Anli , Liu Hao , Zuo Yujun
Published: January 2020

The existence of bedding in shale plays an important role in the physical properties and destruction processes of shale. In order to study the failure mechanism of shale with different dip angles under the coupling of seepage and stress, the study uses RFPA2D‐Flow software to advance the seepage‐stress coupling numerical simulation for seven groups of different bedding direction shale. Research shows that (1) the compressive strength and elastic modulus of shale are significantly affected by the bedding directions. The compressive strength can be observed with the apparent anisotropy of the shale compressive strength with the change of the bedding angle α; the elastic modulus increase with the increase in α as a whole. (2) The ultimate failure mode of shale under different bedding angles can be divided into V type (0°), inverted V type (15°), multi‐line type (30°), oblique type I (45°, 90°), and oblique N type (60°, 75°); the failure of shale in each group direction is mainly tensile failure with a small amount of shear failure. It can be found that the spatial distribution of acoustic emission (AE) reflected the macroscopic failure mode of shale. (3) The fractal dimension can well reflect the failure mode of the sample. From the trend of the dip‐fractal dimension curve, the fractal dimension of the multi‐line type reach to maximum, which is 1.41 699, and the D value of the oblique type I is the smallest, between 1.28 191 and 1.286 181. And the values of the inverted V type, V type and oblique N type, between 1.286 181 and 1.41 699. Therefore, the larger the value is, the more complex the shale failure mode is.
A new concept for estimating the influence of vegetation on throughfall kinetic energy using aerial laser scanning
Authors: Senn Johannes Antenor , Fassnacht Fabian Ewald , Eichel Jana , Seitz Steffen , Schmidtlein Sebastian
Published: January 2020

Soil loss caused by erosion has enormous economic and social impacts. Splash effects of rainfall are an important driver of erosion processes; however, effects of vegetation on splash erosion are still not fully understood. Splash erosion processes under vegetation are investigated by means of throughfall kinetic energy (TKE). Previous studies on TKE utilized a heterogeneous set of plant and canopy parameters to assess vegetation's influence on erosion by rain splash but remained on individual plant‐ or plot‐levels. In the present study we developed a method for the area‐wide estimation of the influence of vegetation on TKE using remote sensing methods. In a literature review we identified key vegetation variables influencing splash erosion and developed a conceptual model to describe the interaction of vegetation and raindrops. Our model considers both amplifying and protecting effect of vegetation layers according to their height above the ground and aggregates them into a new indicator: the Vegetation Splash Factor (VSF). It is based on the proportional contribution of drips per layer, which can be calculated via the vegetation cover profile from airborne LiDAR datasets. In a case study, we calculated the VSF using a LiDAR dataset for La Campana National Park in central Chile. The studied catchment comprises a heterogeneous mosaic of vegetation layer combinations and types and is hence well suited to test the approach. We calculated a VSF map showing the relation between vegetation structure and its expected influence on TKE. Mean VSF was 1.42, indicating amplifying overall effect of vegetation on TKE that was present in 81% of the area. Values below 1 indicating a protective effect were calculated for 19% of the area. For future work, we recommend refining the weighting factor by calibration to local conditions using field‐reference data and comparing the VSF with TKE field measurements. © 2020 The Authors. Earth Surface Processes and Landforms published by John Wiley & Sons Ltd
Adverse Outcome Pathway Network–Based Assessment of the Interactive Effects of an Androgen Receptor Agonist and an Aromatase Inhibitor on Fish Endocrine Function
Authors: Ankley Gerald T. , Blackwell Brett R. , Cavallin Jenna E. , Doering Jon A. , Feifarek David J. , Jensen Kathleen M. , Kahl Michael D. , LaLone Carlie A. , Poole Shane T. , Randolph Eric C. , Saari Travis W. , Villeneuve Daniel L.
Published: January 2020

Predictive approaches to assessing the toxicity of contaminant mixtures have been largely limited to chemicals that exert effects through the same biological molecular initiating event. However, by understanding specific pathways through which chemicals exert effects, it may be possible to identify shared “downstream” nodes as the basis for forecasting interactive effects of chemicals with different molecular initiating events. Adverse outcome pathway (AOP) networks conceptually support this type of analysis. We assessed the utility of a simple AOP network for predicting the effects of mixtures of an aromatase inhibitor (fadrozole) and an androgen receptor agonist (17β-trenbolone) on aspects of reproductive endocrine function in female fathead minnows. The fish were exposed to multiple concentrations of fadrozole and 17β-trenbolone individually or in combination for 48 or 96 h. Effects on 2 shared nodes in the AOP network, plasma 17β-estradiol (E2) concentration and vitellogenin (VTG) production (measured as hepatic vtg transcripts) responded as anticipated to fadrozole alone but were minimally impacted by 17β-trenbolone alone. Overall, there were indications that 17β-trenbolone enhanced decreases in E2 and vtg in fadrozole-exposed fish, as anticipated, but the results often were not statistically significant. Failure to consistently observe hypothesized interactions between fadrozole and 17β-trenbolone could be due to several factors, including lack of impact of 17β-trenbolone, inherent biological variability in the endpoints assessed, and/or an incomplete understanding of interactions (including feedback) between different pathways within the hypothalamic–pituitary–gonadal axis. Environ Toxicol Chem 2020;39:913–922. © 2020 SETAC
Hiding in Plain Sight: Historical Fish Collections Aid Contemporary Parasite Research
Authors: Murphy Christina A , Gerth William , Pauk Kelci , Konstantinidis Peter , Arismendi Ivan
Published: January 2020

Natural history collections provide a wealth of information beyond the scope of their initial purpose, including a historical window into host–parasite relationships. For example, collections can reveal historical infections of fishes by the freshwater gill-maggot Salmincola californiensis, a parasite of increasing concern because of negative effects on salmonids that use large reservoirs in western North America. Here, we examined 1,241 preserved specimens collected between 1933 and 2014 from the Willamette River Basin, Oregon and deposited in the Oregon State Ichthyology Collection. We confirmed the historical presence and broad distribution of freshwater gill-maggot species affecting Cutthroat Trout Oncorhynchus clarkii, Rainbow Trout O. mykiss, Chinook Salmon O. tshawytscha, and Mountain Whitefish Prosopium williamsoni. In particular, S. californiensis was found infecting Pacific trout and Chinook Salmon. In addition, a previously undocumented freshwater gill-maggot species was discovered on Mountain Whitefish. The ability to both detect historical infections as well as to identify previously undocumented parasites demonstrates the value of historical collections for modern explorations of fish infections and highlights a need to keep archival representatives in mind when collecting fish.
Adherence to medical follow‐up recommendations reduces hospital admissions: Evidence from diabetic patients in France
Authors: Bussière Clémence , Sirven Nicolas , Rapp Thomas , Sevilla‐Dedieu Christine
Published: January 2020

The aim of this study was to document the extent to which diabetic patients who adhered to required medical follow‐ups in France experienced reduced hospital admissions over time. The main assumption was that enhanced monitoring and follow‐up of diabetic patients in the primary care setting could be a substitute for hospital use. Using longitudinal claim data of diabetic patients between 2010 and 2015 from MGEN, a leading mutuelle insurance company in France, we estimated a dynamic logit model with lagged measures of the quality of adherence to eight medical follow‐up recommendations. This model allowed us to disentangle follow‐up care in hospitals from other forms of inpatient care that could occur simultaneously. We found that a higher adherence to medical guidance is associated with a lower probability of hospitalization and that the take‐up of each of the eight recommendations may help reduce the rates of hospital admission. The reasons for the variation in patient adherence and implications for health policy are discussed.
Cooperation Between MYC and β‐Catenin in Liver Tumorigenesis Requires Yap/Taz
Authors: Bisso Andrea , Filipuzzi Marco , Gamarra Figueroa Gianni Paolo , Brumana Giulia , Biagioni Francesca , Doni Mirko , Ceccotti Giorgia , Tanaskovic Nina , Morelli Marco Jacopo , Pendino Vera , Chiacchiera Fulvio , Pasini Diego , Olivero Daniela , Campaner Stefano , Sabò Arianna , Amati Bruno
Published: January 2020

Background and Aims

Activation of MYC and catenin beta‐1 (CTNNB1, encoding β‐catenin) can co‐occur in liver cancer, but how these oncogenes cooperate in tumorigenesis remains unclear.

Approach and Results

We generated a mouse model allowing conditional activation of MYC and WNT/β‐catenin signaling (through either β‐catenin activation or loss of APC ‐ adenomatous polyposis coli) upon expression of CRE recombinase in the liver and monitored their effects on hepatocyte proliferation, apoptosis, gene expression profiles, and tumorigenesis. Activation of WNT/β‐catenin signaling strongly accelerated MYC‐driven carcinogenesis in the liver. Both pathways also cooperated in promoting cellular transformation in vitro, demonstrating their cell‐autonomous action. Short‐term induction of MYC and β‐catenin in hepatocytes, followed by RNA‐sequencing profiling, allowed the identification of a “Myc/β‐catenin signature,” composed of a discrete set of Myc‐activated genes whose expression increased in the presence of active β‐catenin. Notably, this signature enriched for targets of Yes‐associated protein (Yap) and transcriptional coactivator with PDZ‐binding motif (Taz), two transcriptional coactivators known to be activated by WNT/β‐catenin signaling and to cooperate with MYC in mitogenic activation and liver transformation. Consistent with these regulatory connections, Yap/Taz accumulated upon Myc/β‐catenin activation and were required not only for the ensuing proliferative response, but also for tumor cell growth and survival. Finally, the Myc/β‐catenin signature was enriched in a subset of human hepatocellular carcinomas characterized by comparatively poor prognosis.

Conclusions

Myc and β‐catenin show a strong cooperative action in liver carcinogenesis, with Yap and Taz serving as mediators of this effect. These findings warrant efforts toward therapeutic targeting of Yap/Taz in aggressive liver tumors marked by elevated Myc/β‐catenin activity.
Assessing the Time‐Dependent Impact of Performance Status on Outcomes After Liver Transplantation
Authors: Wallace David , Cowling Thomas , McPhail Mark J. , Brown Sarah E. , Aluvihare Varuna , Suddle Abid , Auzinger Georg , Heneghan Michael A. , Rowe Ian A. , Walker Kate , Heaton Nigel , van der Meulen Jan , Bernal William
Published: January 2020

Background and Aims

Identifying how the prognostic impact of performance status (PS) differs according to indication, era, and time period (“epoch”) after liver transplantation (LT) could have implications for selection and treatment of patients on the waitlist. We used national data from the United Kingdom and Ireland to assess impact of PS on mortality separately for HCC and non‐HCC recipients.

Approach and Results

We assessed pre‐LT PS using the 5‐point modified Eastern Cooperative Oncology Group scale and used Cox regression methods to estimate hazard ratios (HRs) that compared posttransplantation mortality in different epochs of follow‐up (0‐90 days and 90 days to 1 year) and in different eras of transplantation (1995‐2005 and 2006‐2016). 2107 HCC and 10,693 non‐HCC patients were included. One‐year survival decreased with worsening PS in non‐HCC recipients where 1‐year survival was 91.9% (95% confidence interval [CI], 88.3‐94.4) in those able to carry out normal activity (PS1) compared to 78.7% (95% CI, 76.7‐80.5) in those completely reliant on care (PS5). For HCC patients, these estimates were 89.9% (95% CI, 85.4‐93.2) and 83.1% (95% CI, 61.0‐93.3), respectively. Reduction in survival in non‐HCC patients with poorer PS was in the first 90 days after transplant, with no major effect observed between 90 days and 1 year. Adjustment for donor and recipient characteristics did not change the findings. Comparing era, post‐LT mortality improved for HCC (adjusted HR, 0.55; 95% CI, 0.40‐0.74) and non‐HCC recipients (0.48; 95% CI, 0.42‐0.55), but this did not differ according to PS score (P = 0.39 and 0.61, respectively).

Conclusions

Impact on mortality of the recipient’s pretransplant PS is principally limited to the first 3 months after LT. Over time, mortality has improved for both HCC and non‐HCC recipients and across the full range of PS.
Hepatocellular Carcinoma—How to Determine Therapeutic Options
Authors: Mehta Neil
Published: January 2020

Deciding on specific treatment strategies involves not only tumor stage, performance status, and severity of underlying liver disease, but additional factors such as biomarkers, organ availability, and radiographic tumor response to treatment. In this review, we present hepatocellular carcinoma (HCC) cases to highlight how to determine therapeutic options for HCC in specific scenarios, including resection versus liver transplant, choice of initial local regional treatment, tumor downstaging, and systemic therapies for advanced HCC.
Serum metabonomics analysis of quercetin against the toxicity induced by cadmium in rats
Authors: Jia Siqi , Guan Tong , Zhang Xia , Liu Yajing , Liu Yanli , Zhao Xiujuan
Published: January 2020

This study aimed to investigate the protective effect of quercetin against the toxicity induced by chronic exposure to low levels of cadmium in rats by an ultra performance liquid chromatography mass spectrometer. Rats were randomly divided into six groups as follows: control group (C), low dose of quercetin group (Q1: 10 mg/kg·bw), high dose of quercetin group (Q2: 50 mg/kg·bw), cadmium chloride group (D), low dose of quercetin plus cadmium chloride group (DQ1), and high dose of quercetin plus cadmium chloride group (DQ2). Cadmium chloride (CdCl2) was administered to rats by drinking water ad libitum in a concentration of 40 mg/L. The final amount of CdCl2 ingested was estimated from the water consumption data to be 4.85, 4.91, and 4.89 mg/kg·bw/day, for D, DQ1, and DQ2 groups, respectively. After a 12‐week treatment, the serum samples of rats were collected for metabonomics analysis. Ten potential biomarkers were identified for which intensities were significantly increased or reduced as a result of the treatment. These metabolites included isorhamnetin 4′‐O‐glucuronide, 3‐indolepropionic acid, tetracosahexaenoic acid, lysophosphatidylcholine (LysoPC) (20:5), lysoPC (18:3), lysophosphatidylethanolamine (LysoPE) (20:5/0:0), bicyclo‐prostaglandin E2, sulpholithocholylglycine, lithocholyltaurine, and glycocholic acid. Results indicated that quercetin exerted a protective effect against cadmium‐induced toxicity by regulating lipid and amino acid metabolism, enhancing the antioxidant defense system and protecting liver and kidney function.
Improving the predictive quality of time‐dependent density functional theory calculations of the X‐ray emission spectroscopy of organic molecules
Authors: Fouda Adam A. E. , Besley Nicholas A.
Published: January 2020

The simulation of X‐ray emission spectra of organic molecules using time‐dependent density functional theory (TDDFT) is explored. TDDFT calculations using standard hybrid exchange‐correlation functionals in conjunction with large basis sets can predict accurate X‐ray emission spectra provided an energy shift is applied to align the spectra with experiment. The relaxation of the orbitals in the intermediate state is an important factor, and neglect of this relaxation leads to considerably poorer predicted spectra. A short‐range corrected functional is found to give emission energies that required a relatively small energy shift to align with experiment. However, increasing the amount of Hartree–Fock exchange in this functional to remove the need for any energy shift led to a deterioration in the quality of the calculated spectral profile. To predict accurate spectra without reference to experimental measurements, we use the CAM‐B3LYP functional with the energy scale determined with reference to a Δself‐consistent field calculation for the highest energy emission transition.
Plasma level of miR‐99b may serve as potential diagnostic and short‐term prognostic markers in patients with acute cerebral infarction
Authors: Wu Xiaomu , Zhang Xiaohong , Li Dongqing , Zhu Ziyang
Published: January 2020

Objective

The aim of the present study is to explore the potential diagnostic and prognostic value of plasma levels of miR‐99 family for patients with acute cerebral infarction (ACI).

Methods

A total of 112 patients who have been diagnosed with ACI were enrolled in this study, and 112 healthy volunteers were served as the controls. The plasma of the patients and controls were collected, and total RNAs were isolated, and the expression levels of miR‐99a, miR‐99b, and miR‐100 in the plasma of patients and controls were compared determined by RT‐qPCR methods; moreover, the receiver operating characteristic (ROC) curve has been drawn to determine whether the plasma levels of miR‐99b can distinguish patients with ACI from the controls; furthermore, the short‐term prognosis of the patients was evaluated by glasgow outcome scale (GOS), and the correlation between the plasma levels of miR‐99b and the GOS of the patients was evaluated. Finally, the correlation between the plasma level of miR‐99 and VEGF of ACI patients was analyzed.

Results

It was observed that miR‐99b was significantly decreased in the plasma of ACI patients compared with the healthy controls (P < .01), while the plasma levels of miR‐99a and miR‐100 showed no significant differences between the patients with ACI and the healthy controls; moreover, the area under the curve (AUC) of miR‐99b for the diagnosis of ACI was 0.8882 (95% confidence interval (CI), 0.8451‐0.9313), suggesting that plasma level of miR‐99b is a sensitive marker to distinguish patients with ACI from the healthy volunteers; furthermore, the serum level of miR‐99b was negatively correlated with GOS score of the patients (r = −.56, P < .001); finally, the plasma level of miR‐99b was negatively correlated with the levels of VEGF (r = −.3013, P = .0012).

Conclusion

miR‐99b was down‐regulated in plasma of patients with ACI, and plasma level of miR‐99b may be a potential diagnostic and prognostic marker for the diagnosis and treatment of ACI.
Low‐intensity pulsed ultrasound affects growth, differentiation, migration, and epithelial‐to‐mesenchymal transition of colorectal cancer cells
Authors: Lucchetti Donatella , Perelli Luigi , Colella Filomena , Ricciardi‐Tenore Claudio , Scoarughi Gian Luca , Barbato Gaetano , Boninsegna Alma , De Maria Ruggero , Sgambato Alessandro
Published: January 2020

Ultrasound (US) offers potentially important opportunities from a therapeutic point of view. Thus, the study of the biological effects of US on cancer cells is important to understand the consequences of these changes on the malignant phenotype. This study aimed to investigate the effects of low‐intensity ultrasound (LIPUS) on the phenotype of colorectal cancer cell lines. Cell proliferation was evaluated by viability test and by evaluation of pERK expression, while cell motility using the scratch test. Cell differentiation was evaluated assessing alkaline phosphatase activity. Epithelial mesenchymal transition was assessed by analyzing the expression of Vimentin and E‐Cadherin. Release and uptake of extracellular vesicles (EVs) were evaluated by flow cytometry. LIPUS effects on the organization of cytoskeleton were analyzed by confocal microscopy and by evaluation of Rho GTPase expression. No alterations in vitality and clonogenicity were observed when the intermediate (0.4 MPa) and the lowest (0.035 MPa) acoustic intensities were administered while the treatment with high intensity (1 MPa) induced a reduction of both cell viability and clonogenicity in both cell lines in a frequency‐dependent manner. LIPUS promoted the differentiation of colon cancer cells, affected epithelial‐to‐mesenchymal transition, promoted the closure of a wound as well as increased the release of EVs compared with untreated cells. LIPUS‐induced increase in cell motility was likely due to a Rho GTPase‐dependent mechanism. Overall, the results obtained warrant further studies on the potential combined effect of LIPUS with differentiating agents and on their potential use in a clinical setting.
Transcriptional memory in skeletal muscle. Don't forget (to) exercise
Authors: Beiter Thomas , Nieß Andreas M. , Moser Dirk
Published: January 2020

Transcriptional memory describes an ancient and highly conserved form of cellular learning that enables cells to benefit from recent experience by retaining a mitotically inheritable but reversible memory of the initial transcriptional response when encountering an environmental or physiological stimulus. Herein, we will review recent progress made in the understanding of how cells can make use of diverse constituents of the epigenetic toolbox to retain a transcriptional memory of past states and perturbations. Specifically, we will outline how these mechanisms will help to improve our understanding of skeletal muscle plasticity in health and disease. We describe the epigenetic road map that allows skeletal muscle fibers to navigate through training‐induced adaptation processes, and how epigenetic memory marks can preserve an autobiographical history of lifestyle behavior changes, pathological challenges, and aging. We will further consider some key findings in the field of exercise epigenomics to emphasize major challenges when interpreting dynamic changes in the chromatin landscape in response to acute exercise and training.
Organizational readiness to implement population‐based screening and genetic service delivery for hereditary cancer prevention and control
Authors: Knerr Sarah , West Kathleen M. , Angelo Frank A.
Published: January 2020

Despite clinical guidelines, programs conducting population‐based screening and genetic service delivery for hereditary cancer prevention and control are rare in practice. We interviewed individuals (n = 13) instrumental in implementing seven unique clinical programs conducting either universal tumor screening for Lynch Syndrome or routine family history screening and provision of genetic services for hereditary breast and ovarian cancer in the United States. To characterize determinants of readiness to implement population‐based cancer genetic service delivery models, interviews and deductive codes drew on Weiner's theory of organizational readiness for change. Qualitative analysis identified themes across programs. The degree to which organizational stakeholders valued moving to a population‐based genetic service delivery model depended on the existence of aligned clinical guidelines at the time of program implementation. However, judgments of implementation capacity within the organization, particularly with respect to task demands and resource concerns, were more often barriers to readiness. Program champions were essential to facilitating readiness, frequently taking on substantial uncompensated work. These data suggest that developing interventions targeting change efficacy and cultivating practice change champions may be two promising ways to increase uptake of population‐based hereditary cancer screening and genetic service delivery in clinical practice.
Mortality of Japanese patients with Leigh syndrome: Effects of age at onset and genetic diagnosis
Authors: Ogawa Erika , Fushimi Takuya , Ogawa‐Tominaga Minako , Shimura Masaru , Tajika Makiko , Ichimoto Keiko , Matsunaga Ayako , Tsuruoka Tomoko , Ishige Mika , Fuchigami Tatsuo , Yamazaki Taro , Kishita Yoshihito , Kohda Masakazu , Imai‐Okazaki Atsuko , Okazaki Yasushi , Morioka Ichiro , Ohtake Akira , Murayama Kei
Published: January 2020

Leigh syndrome is a major phenotype of mitochondrial diseases in children. With new therapeutic options being proposed, assessing the mortality and clinical condition of Leigh syndrome patients is crucial for evaluating therapeutics. As data are scarce in Japan, we analysed the mortality rate and clinical condition of Japanese Leigh syndrome patients that we diagnosed since 2007. Data from 166 Japanese patients diagnosed with Leigh syndrome from 2007 to 2017 were reviewed. Patients' present status, method of ventilation and feeding, and degree of disability as of April 2018 was analysed. Overall, 124 (74.7%) were living, 40 (24.1%) were deceased, and 2 (1.2%) were lost to follow‐up. Median age of living patients was 8 years (1‐39 years). Median length of disease course was 91 months for living patients and 23.5 months for deceased patients. Nearly 90% of deaths occurred by age 6. Mortality rate of patients with onset before 6 months of age was significantly higher than that of onset after 6 months. All patients with neonatal onset were either deceased or bedridden. MT‐ATP6 deficiency caused by m.8993T>G mutation and MT‐ND5 deficiency induced a severe form of Leigh syndrome. Patients with NDUFAF6, ECHS1, and SURF1 deficiency had relatively mild symptoms and better survival. The impact of onset age on prognosis varied across the genetic diagnoses. The clinical condition of many patients was poor; however, few did not require mechanical ventilation or tube‐feeding and were not physically dependent. Early disease onset and genetic diagnosis may have prognostic value.
p67phox binds to a newly identified site in Nox2 following the disengagement of an intramolecular bond—Canaan sighted?
Authors: Bechor Edna , Zahavi Anat , Amichay Maya , Fradin Tanya , Federman Aya , Berdichevsky Yevgeny , Pick Edgar
Published: January 2020

Activation of the phagocyte NADPH oxidase involves a conformational change in Nox2. The effector in this process is p67phox and there is evidence for a change in the configuration of p67phox being required for binding to Nox2. To study this, we measured binding of p67phox to a library of Nox2 peptides and binding of NusA–Nox2 fusion proteins to p67phox. We found, serendipitously, that deletion of residues 259–279 in p67phox (p67phoxΔ(259–279)), endowed it with the ability to bind selectively to Nox2 peptide 369–383 (peptide 28). There was no binding to scrambled Nox2 peptide 28 and to Nox4 peptide 28. Binding was cysteine independent and resistant to reducing and alkylating agents. Truncations of peptide 28 revealed that the actual binding site consisted of residues 375–383. Binding of p67phoxΔ(259–279) to peptide 28 was mimicked by that of a (p67phox-RacGTP) chimera. Both p67phoxΔ(259–279) and the (p67pho–RacGTP) chimera bound a NusA–Nox2 fusion protein, comprising residues 375–383. Specific single residue deletion mutants, within the p67phox sequence 259–279, were also bound to Nox2 peptide 28. Peptides synthesized to correspond to the 259–279 sequence in p67phox, were found to autobind p67phox, suggesting that an intramolecular bond exists in p67phox, one pole of which was located within residues 259–279. We conclude that “resting” p67phox exists in a “closed” conformation, generated by an intramolecular bond. Deletion of specific residues within the 259–279 sequence, in vitro, or interaction with RacGTP, in vivo, causes “opening” of the bond and results in binding of p67phox to a specific, previously unknown, site in Nox2.
Neurotoxicity including posterior reversible encephalopathy syndrome after initiation of calcineurin inhibitors in transplanted methylmalonic acidemia patients: Two case reports and review of the literature
Authors: Molema Femke , Williams Monique , Langendonk Janneke , Darwish‐Murad Sarwa , van de Wetering Jacqueline , Jacobs Ed , Onkenhout Willem , Brusse Esther , van der Eerden Anke , Wagenmakers Margreet
Published: January 2020

Introduction

New neurological symptoms in methylmalonic acidemia (MMA) patients after liver and/or kidney transplantation (LKT) are often described as metabolic stroke‐like‐events. Since calcineurin inhibitors (CNIs) are a well‐known cause of new neurological symptoms in non‐MMA transplanted patients, we investigated the incidence of CNI‐induced neurotoxicity including posterior reversible encephalopathy syndrome (PRES) in post‐transplanted MMA patients.

Methods

We report the two MMA patients treated with LKT in our center. Additionally, we performed a systematic review of case reports/series of post‐transplanted MMA patients and determined if CNI‐induced neurotoxicity/PRES was a likely cause of new neurological symptoms. Definite CNI‐induced neurotoxicity was defined as new neurological symptoms during CNI treatment with symptom improvement after CNI dose reduction/discontinuation. PRES was defined as CNI‐induced neurotoxicity with signs of vasogenic edema on brain magnetic resonance imaging (MRI)‐scan post‐transplantation.

Results

Our two MMA patients both developed CNI‐induced neurotoxicity, one had PRES. In literature, 230 transplanted MMA patients were identified. Neurological follow‐up was reported in 54 of them, of which 24 were excluded from analysis since no anti‐rejection medication was reported. Thirty patients, all using CNI, were included. Sixteen patients (53%) had no new neurological symptoms post‐transplantation and five patients (17%) had definite CNI neurotoxicity of whom two had PRES. Including our cases this results in a pooled incidence of 22% (7/32) definite CNI neurotoxicity and 9% PRES (3/32) in post‐transplanted MMA patients on CNI.

Conclusion

In MMA post‐transplanted patients with new neurological symptoms CNI‐induced neurotoxicity/PRES should be considered. Early recognition of CNI‐induced neurotoxicity is essential to initiate dose reduction/discontinuation of CNI to minimize persistent neurologic damage and improve outcome.

Concise one sentence take home message

In all post‐transplanted MMA patients with new neurological symptoms CNI‐induced neurotoxicity/PRES should be considered, and directly reducing the dose/discontinuation of CNI is essential.
Emerging coronaviruses: Genome structure, replication, and pathogenesis
Authors: Chen Yu , Liu Qianyun , Guo Deyin
Published: January 2020

The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.
Cross‐species transmission of the newly identified coronavirus 2019‐nCoV
Authors: Ji Wei , Wang Wei , Zhao Xiaofang , Zai Junjie , Li Xingguang
Published: January 2020

The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.