bluuebunny/crossref_metadata_2025 huggingface dataset:
Neutrophil fluorescence in clozapine users is attributable to a 14kDa secretable protein
Authors: de With Sera A. J. , Man Wai H. , Maas Coen , ten Berg Maarten , Cahn Wiepke , Koekman Arnold C. , van Solinge Wouter W. , Tak Tamar
Published: August 2020

Clozapine is the only antipsychotic agent with demonstrated efficacy in refractory schizophrenia. However, use of clozapine is hampered by its adverse effects, including potentially fatal agranulocytosis. Recently, we showed an association between neutrophil autofluorescence and clozapine use. In this study, we evaluated the subcellular localization of clozapine‐associated fluorescence and tried to elucidate its source. Neutrophils of clozapine users were analyzed with fluorescence microscopy to determine the emission spectrum and localization of the fluorescence signal. Next, these neutrophils were stimulated with different degranulation agents to determine the localization of fluorescence. Lastly, isolated neutrophil lysates of clozapine users were separated by SDS‐PAGE and evaluated. Clozapine‐associated fluorescence ranged from 420 nm to 720 nm, peaking at 500‐550 nm. Fluorescence was localized in a large number of small loci, suggesting granular localization of the signal. Neutrophil degranulation induced by Cytochalasin B/fMLF reduced fluorescence, whereas platelet‐activating factor (PAF)/fMLF induced degranulation did not, indicating that the fluorescence originates from a secretable substance in azurophilic granules. SDS‐PAGE of isolated neutrophil lysates revealed a fluorescent 14kDa band, suggesting that neutrophil fluorescence is likely to be originated from a 14kDa protein/peptide fragment. We conclude that clozapine‐associated fluorescence in neutrophils is originating from a 14kDa soluble protein (fragment) present in azurophilic granules of neutrophils. This protein could be an autofluorescent protein already present in the cell and upregulated by clozapine, or a protein altered by clozapine to express fluorescence. Future studies should further explore the identity of this protein and its potential role in the pathophysiology of clozapine‐induced agranulocytosis.
Anti‐TMV activity and mode of action of three alkaloids isolated from Chelidonium majus
Authors: Guo Wenhui , Lu Xiang , Liu Bin , Yan He , Feng Juntao
Published: August 2020

BACKGROUND

Plant viral diseases are difficult to control and have caused serious damage to the agricultural industry. Recently, botanical biopesticides characterized by environment friendly, safe to non‐target organism and not as susceptible to produce drug resistance, have exhibited great potential to be developed as antiviral agents. To screen the natural products with antiviral effect, three alkaloids possessed anti‐tobacco mosaic virus (TMV) activity were isolated from Chelidonium majus and the modes of action were investigated.

RESULT

The anti‐TMV effect of crude extracts at 10 mg mL−1 was 51.73%. Bioassay‐guided fractionation and isolation of the compounds with anti‐TMV activity were performed on the methanol extract of C. majus yielding three bioactive alkaloids namely: chelerythrine (1), chelidonine (2), and sanguinarine (3). The results of bioassay showed that chelerythrine exhibited great inactivation, proliferation inhibition and protection effects against TMV at 0.5 mg mL−1 with the efficiency of 72.67%, 77.52% and 59.34%, respectively. Chelidonine at 0.1 mg mL−1 can provide 54.90% and 64.45% inhibitions on TMV through inducing resistance in two kinds of tobacco. Sanguinarine showed a weaker protection for resisting TMV in comparison to chelerythrine and chelidonine.

CONCLUSION

Chelerythrine and chelidonine displayed significant inhibitions on TMV with different modes of action. These results provided important evidence that the extracts in C. majus might be a potential source of new drugs in controlling virus disease agriculturally.
Phase II monitoring of survival times with categorical covariates
Authors: Keshavarz Maryam , Asadzadeh Shervin
Published: August 2020

Monitoring surgical outcomes is of paramount importance especially by accounting for health conditions of the patients prior to surgery. However, the problem arises as the effect of some covariates is pronounced but cannot be measured. In this paper, in order to deal with the effect of measured and unmeasured (categorical) covariates simultaneously, a class of survival analysis regression models called accelerated failure time (AFT) model and discrete frailty models is integrated and some Phase II risk‐adjusted control schemes are devised to monitor the patients' lifetime. Three monitoring procedures including the cumulative sum (CUSUM), exponentially weighted moving average (EWMA), and probability limits‐based control charts are developed in the presence and absence of censored observations. The performance analysis reveals that the proposed AFT frailty‐based CUSUM control chart outweighs the competing counterparts in detecting shifts under various scenarios. Subsequently, two CUSUM control charts have been constructed corresponding to the cases of neglecting both the unmeasured and measured covariates and ignoring just the unmeasured covariate. The results clearly indicate that the detection ability for both of the mentioned CUSUM control charts declines, and including the unmeasured and measured covariates is critical while monitoring surgical outcomes. Finally, a real case study in a cardiac surgical center in the United Kingdom has been provided to investigate the application of the proposed AFT frailty‐based CUSUM control scheme.
Interval dynamic reliability analysis of mechanical components under multistage load based on strength degradation
Authors: Jiang Changjie , Liu Xintian , Wang Xiaolan , Wang Xu , Su Shengchao
Published: August 2020

To further study the law of strength degradation, the residual strength degradation model is established based on the definition of fatigue damage, considering the interaction of various uncertain factors and time factors in service environment. Combined with equivalent damage model, a nonlinear cumulative damage model is proposed, which takes the interaction among loading loads into account and improves the accuracy of calculation. Additionally, the equivalent transformation of multistage load is studied using interval theory. According to the interval dynamic nonprobability reliability prediction model, a dynamic reliability analysis of the interval model is carried out. Dynamic reliability of the component is analyzed under multistage load accumulation damage to verify the effectiveness of the method.
Radiographic change over 11 years in a patient with asbestos‐related pleural disease
Authors: Hara Reina , Yano Yukihiro , Okabe Fukuko , Kuge Tomoki , Mori Masahide , Urasaki Koji
Published: August 2020

Asbestos‐related pulmonary conditions such as benign asbestos pleural effusion (BAPE) and diffuse pleural thickening (DPT) can develop after many years of asbestos exposure. These conditions cause progressing constrictive deficit in pulmonary function which may lead to respiratory failure and death. We report the case of a 72‐year‐old man with asbestos‐related BAPE and DPT which developed approximately 40 years after occupational asbestos exposure, leading to chronic respiratory failure and death. We were able to observe his clinical course including computed tomography (CT) scan evaluation over 11 years. In addition to this observation, moderate asbestos body concentration was confirmed in autopsy‐derived lung tissue. There are few case reports that showed radiographic course of asbestos‐related pulmonary disorder initiated as BAPE, followed by unilateral DPT and later bilateral DPT that was histologically proven with asbestos body. We consider his clinical course is important in managing this disease, especially in early phase.
SARS‐CoV: Lessons learned; opportunities missed for SARS‐CoV‐2
Authors: Davis Ian M.
Published: August 2020

SARS‐CoV‐2 and Covid‐19 have made a retrospective analysis of other coronavirus diseases important, so this article reviews the history of the SARS‐CoV viral disease from 2003. Standard and clinical chemistry diagnostics were developed in response to the outbreak. The response to SARS is examined to determine if there were lessons learned before it disappeared in June and July 2003. Various diagnostic approaches were developed and implemented to assist in the rapid identification of patients and treatment of their illness, yet many of the approaches required days or weeks from the onset of fever to show statistical significance. Most of the therapeutic methods used during the outbreak relied on treating symptoms of the underlying illness, such as lower respiratory infections and systemic infection, rather than effectively suppressing or curtailing replication of the virus. Retrospective studies are examined to determine how the SARS outbreak was viewed 10 years on and what the authors hoped would be instructive patterns for possible future pandemics. Implementation of some of these recommendations might have helped ease the current pandemic but were overlooked for budgetary reasons that seem short‐sighted at present.
Surface segregation effect for prevention of oxidation in Ni‐X (X=Sn, Sb) alloy by in situ photoelectron spectroscopy
Authors: Doi Takashi , Yoshigoe Akitaka
Published: August 2020

Ni‐base alloys has been widely used for chemical plants because of their high strength and excellent oxidation resistance. In particular, the addition of Sn and Sb in Ni‐base alloys significantly improves the metal dusting resistance. It is indicated that Sn and Sb are segregated on the alloy surface in the metal dusting environment; however, the details have not been clarified yet. The behavior of the Ni‐Sn and Ni‐Sb alloys under a high‐temperature oxidation environment was investigated by in situ X‐ray photoelectron spectroscopy (XPS). It was confirmed that Sn and Sb have been segregated at the surface of their alloys during oxidation in low oxygen potential, PO2, environment. These results indicate that Sn and Sb segregation improves the metal dusting resistance.
Sequential Growth as a Mechanism of Silver‐Glutathione Monolayer‐Protected Cluster Formation
Authors: Zaker Yeakub , Ashenfelter Brian A. , Bhattarai Badri , Diemler Nathan A. , Brewer Timothy R. , Bigioni Terry P.
Published: August 2020

Silver monolayer‐protected clusters (MPCs) are an important new class of small metal nanoparticles with discrete sizes and unique properties that are eminently tunable; however, a fundamental understanding of the mechanisms of MPC formation is still lacking. Here, the basic mechanism by which silver‐glutathione MPCs form is established by using real‐time in situ optical measurements and ex situ solution‐phase analyses to track MPC populations in the reaction mixture. These measurements identify that MPCs grow systematically, increasing in size sequentially as they transform from one known species to another, in contrast to existing models. In the new sequential growth model of MPC formation, the relative stability of each species in the series results in thermodynamic preferences for certain species as well as kinetic barriers to transformations between stable sizes. This model is shown to correctly predict the outcome of silver MPC synthetic reactions. Simple analytic expressions and simulations of rate equations are used to further validate the model and study its nature. The sequential growth model provides insights into how reactions may be directed, based on the interplay between relative MPC stabilities and reaction kinetics, providing tools for the synthesis of particular MPCs in high yield.
Probing the Irregular Lattice Strain‐Induced Electronic Structure Variations on Late Transition Metals for Boosting the Electrocatalyst Activity
Authors: Wu Tong , Sun Mingzi , Huang Bolong
Published: August 2020

Owing to the simplicity in practice and continuous fine‐tuning ability toward the binding strengths of adsorbates, the strain effect is intensively explored, especially focused on the modulation of catalytic activity in transition metal (TM) based electrocatalysts. Recently, more and more abnormal cases have been found that cannot be explained by the conventional simplified models. In this work, the strain effects in five late TMs, Fe, Co, Ni, Pd, and Pt are studied in‐depth regarding the facet engineering, the surface atom density, and the d‐band center. Interestingly, the irregular response of Fe lattice to the applied strain is identified, indicating the untapped potential of achieving the phase change by precise strain modulation. For the complicated high‐index facets, the surface atom density has become the pivotal factor in determining the surface stability and electroactivity, which identifies the potential of high entropy alloys (HEA) in electrocatalysis. The work supplies insightful understanding and significant references for future research in subtle modulation of electroactivity based on the precise facet engineering in the more complex facets and morphologies.
Retooling Cancer Nanotherapeutics’ Entry into Tumors to Alleviate Tumoral Hypoxia
Authors: Sun Xiao , Ni Nengyi , Ma Yanling , Wang Yan , Leong David Tai
Published: August 2020

Anti‐hypoxia cancer nanomedicine (AHCN) holds exciting potential in improving oxygen‐dependent therapeutic efficiencies of malignant tumors. However, most studies regarding AHCN focus on optimizing structure and function of nanomaterials with presupposed successful entry into tumor cells. From such a traditional perspective, the main barrier that AHCN needs to overcome is mainly the tumor cell membrane. However, such an oversimplified perspective would neglect that real tumors have many biological, physiological, physical, and chemical defenses preventing the current state‐of‐the‐art AHCNs from even reaching the targeted tumor cells. Fortunately, in recent years, some studies are beginning to intentionally focus on overcoming physiological barriers to alleviate hypoxia. In this Review, the limitations behind the traditional AHCN delivery mindset are addressed and the key barriers that need to be surmounted before delivery to cancer cells and some good ways to improve cell membrane attachment, internalization, and intracellular retention are summarized. It is aimed to contribute to Review literature on this emerging topic through refreshing perspectives based on this work and what is also learnt from others. This Review would therefore assist AHCNs researchers to have a quick overview of the essential information and glean thought‐provoking ideas to advance this sub‐field in cancer nanomedicine.
Engineering Solvation Complex–Membrane Interaction to Suppress Cation Crossover in 3 V Cu‐Al Battery
Authors: Wang Huimin , Sun Yang , Li Matthew , Li Gaoran , Xue Kaiming , Chen Zhongwei , Yu Denis Y. W.
Published: August 2020

Metal–metal batteries such as the 3 V Cu‐Al system are highly desirable for large‐scale energy storage owing to their low cost and excellent scalability of Cu and Al foils. However, the dissolved Cu cations will crossover from the cathode to the anode leading to poor electrochemical performance. In this work, it is demonstrated that the reversibility of the Cu‐Al battery depends strongly on the interaction of the Cu ions with the electrolyte solvent and subsequently the affinity of the solvated Cu ion with the membrane separator. Specifically, a series of common carbonate‐based electrolyte solvents are investigated via molecular dynamics and contact angle measurements to understand the interaction between the solvents and a polypropylene (PP) membrane, as well as that between cations and solvent. Among different solvents, fluoroethylene carbonate (FEC) is shown to drastically enhance the coulombic efficiency to 97%, compared to that of 27% with dimethyl carbonate. Remarkable cyclability of a 3 V Cu‐Al battery with 3 m LiTFSI FEC and PP membrane up to 1000 cycles is further demonstrated. This finding opens new opportunities for the development of low‐cost, high performance Cu‐Al systems for stationary applications.
DNA Nanostructures as Pt(IV) Prodrug Delivery Systems to Combat Chemoresistance
Authors: Zhong Yi‐Fang , Cheng Jin , Liu Yan , Luo Tao , Wang Yuqi , Jiang Kai , Mo Fangli , Song Jie
Published: August 2020

Cisplatin is a first‐line drug in clinical cancer treatment but its efficacy is often hindered by chemoresistance in cancer cells. Reduced intracellular drug accumulation is revealed to be a major mechanism of cisplatin resistance. Nanoscale drug delivery systems could help to overcome this problem because of their more active cellular uptake and more accurate tumor localization. DNA nanostructures have emerged as promising drug delivery systems because of their intrinsic biocompatibility and structural programmability. Herein, three diverse DNA nanostructures are constructed and their potential for cisplatin prodrug delivery is investigated. Results found that these DNA nanostructures could remarkably enhance the cellular internalization of platinum drugs and thus increase the anticancer activity, not only to regular lung cancer cells (A549), but more importantly to cisplatin‐resistant cancer cells (A549cisR). Further, in vivo studies also demonstrate that cisplatin prodrug loaded DNA nanostructures could effectively suppress tumor growth in both regular and cisplatin‐resistant tumor models. This study suggests that DNA nanostructures are effective carriers for platinum prodrug delivery to combat chemoresistance.
An automated framework for continuous development and testing of access control systems
Authors: Daoudagh Said , Lonetti Francesca , Marchetti Eda
Published: August 2020

Automated testing in DevOps represents a key factor for providing fast release of new software features assuring quality delivery. In this paper, we introduce DOXAT, an automated framework for continuous development and testing of access control mechanisms based on the XACML standard. It leverages mutation analysis for the selection and assessment of the test strategies and provides automated facilities for test oracle definition, test execution, and results analysis, in order to speedup and automate the Plan, Code, Build, and Test phases of DevOps process. We show the usage of the framework during the planning and testing phases of the software development cycle of a PDP example.
Improving Efficiency of Organic Solar Cells by Restricting the Rotation of Side Chain on Small Molecule Acceptor
Authors: Ouyang Jinyang , Zhang Bo , Zeng Guang , Zhang Jidong , Zhao Xiaoli , Yang Xiaoniu
Published: August 2020

Herein, three carbazole‐based small molecule acceptors (SMAs), named 4TC‐4F‐C8C8, 4TC‐4F‐C6C8, and 4TC‐4F‐C16, are synthesized to study the influence of side chain conformation on SMAs. The three acceptors exhibit similar optical and electrochemical properties, but different crystallization properties. 4TC‐4F‐C16 shows a high crystallinity due to the small steric hindrance of linear n‐hexadecyl (C16) side chain. The large steric hindrance and free rotation for the 2‐hexydecyl (C6C8) side chain seriously disturb the molecular packing and result in a low crystallinity for 4TC‐4F‐C6C8. Despite the large steric hindrance for the 1‐octylnonyl (C8C8) side chain, 4TC‐4F‐C8C8 shows a moderate crystallinity due to the large torsion barrier restricting the rotation of C8C8 side chain. Attributing to the ideal morphology and better crystalline ordering in blend film, organic solar cell based on poly[4,8‐bis(5‐(2‐ethylhexyl)thiophen‐2‐yl)benzo[1,2‐b:4,5‐b′]‐dithiophene‐alt‐N‐(2‐hexyldecyl)‐5′5‐bis[3‐(decylthio)thiophene‐2‐yl]‐2′2‐bithiophene‐3′3‐dicarboximide] (PBTIBDTT):4TC‐4F‐C8C8 displays a power conversion efficiency of 12.06%, higher than PBTIBDTT:4TC‐4F‐C6C8 (2.38%)‐ and PBTIBDTT:4TC‐4F‐C16 (9.53%)‐based devices. The work indicates that controlling the conformation of bulky side chain can tune the molecular packing of SMAs and the morphology of blend film, providing a new insight into the molecular design of SMAs.
Modulating Energy Level on an A‐D‐A′‐D‐A‐Type Unfused Acceptor by a Benzothiadiazole Core Enables Organic Solar Cells with Simple Procedure and High Performance
Authors: Yu Han , Qi Zhenyu , Li Xingye , Wang Zhen , Zhou Wentao , Ade Harald , Yan He , Chen Kai
Published: August 2020

Unfused‐ring acceptors (UFAs) have gained considerable research attention as they offer simple chemical structures through simplified synthesis methods, which would boost the commercialization of organic solar cells (OSCs). Recently, a new small molecule acceptor (SMA) named Y6 was reported, yielding high‐performance OSCs. Herein, the Y6‐like A‐DA′D‐A framework is developed to A‐D‐A′‐D‐A‐type backbone adopted in constructing UFAs. Two new Y6‐like UFAs are synthesized within four steps and the effect of noncovalent atoms at the central electron‐deficient core on material properties and device performances is studied. It is found that the introduction of fluorine atoms can bring larger red‐shift in the absorption spectra and better aggregation of the resulting UFA film states compared with those of oxygen atoms. Interestingly, the variations in the noncovalent interaction atoms induce different intermolecular charge transfer between donors and UFAs. When blended with another economical donor, PTQ10, F substitution at the benzothiadiazole ring is more effective than O substitution, leading to the increased short‐circuit current density (JSC) and higher efficiency of over 12%, among the best performances of UFA‐based OSCs. This contribution demonstrates the appropriate introduction of noncovalent interaction is a promising method for tuning energy levels, absorption, and aggregation of UFAs for high‐performance OSCs.
Periodontitis and diabetes reshape neuronal dendritic arborization in the thalamus and nucleus oralis in the rat
Authors: Flores‐Tochihuitl Julia , Márquez Villegas Beatriz , Peral Lemus Anahí Catalina , Andraca Hernández Cristian Jesús , Flores Gonzalo , Morales‐Medina Julio César
Published: August 2020

Diabetes is a metabolic disorder resulting in long‐term hyperglycemia that could induce oxidative stress as well as neural modifications in the central nervous system. Periodontal disease is highly comorbid with diabetes and in some cases, with exacerbated pain responses. Periodontal tissue is innervated by trigeminal afferents which extend to the nucleus oralis (NO) that sends input to the ventral posterior lateral thalamic nuclei (VPL). The present study aimed to evaluate the consequences of periodontitis, diabetes and both conditions on the dendritic morphology, spine type, and density in neurons of the NO and VPL in male and female rats. A quantitative neuromorphological analysis was performed using the Cox‐Golgi staining in male and female rats in four groups: naïve control, after a periodontitis procedure, diabetic, and diabetic with periodontitis. Periodontitis decreased the total dendritic length (TDL) in the NO of the male rat but no change in the female rat and no neuronal alterations were observed in the VPL of both male and female rats. In contrast, diabetes increased the number of spines in the NO and VPL and decreased TDL in the NO in both male and female rats. We observed that periodontitis induced a dimorphic effect in the NO, whereas diabetes induced a strong neuromorphological effect regardless of sex. Moreover, while periodontitis had a limited effect on the neuronal morphology, it dramatically modified the neural consequences in the VPL and NO when comorbid with diabetes. In conclusion, these neuroplastic modifications may be relevant to understand how diabetes exacerbates the outcome of periodontitis in humans, particularly in the female population.
Proton‐Gradient‐Driven Self‐Assembly of Porphyrin and In Situ Dynamic Analysis in a Microflow Platform
Authors: Kanzaki Chisako , Inagawa Arinori , Fukuhara Gaku , Okada Tetsuo , Numata Munenori
Published: August 2020

The front cover artwork is provided by group of Dr. Munenori Numata at the Kyoto Prefectural University (Japan). The image shows that the dynamics of supramolecular polymerization can be visualized in a space‐resolved manner along a microflow channel, similar to a snapshot taken of the assembly dynamics. Read the full text of the Article at 10.1002/syst.202000006.
Notes on the generic nameGraecobolanthus(Caryophylleae, Caryophyllaceae)
Authors: Zografidis Aris , Fragman‐Sapir Ori , Strid Arne , Dimopoulos Panayotis
Published: August 2020

Graecobolanthuswas proposed in 2018 as a new generic name for the Greek species of the genusBolanthus, the latter genus comprising the remaining species from Anatolia and the Levant according to the revising authors. However, the type of the two generic names, i.e.,Graecobolanthus graecusfrom Greece andBolanthus hirsutusfrom the Levant, undoubtedly belong to the same genus based on morphological and genetic similarity. Importantly,B. hirsutuswas not included in the molecular analysis by the revising authors. In summary, we note that (i)Graecobolanthusis taxonomically superfluous andBolanthusis the correct generic name of the Greek‐endemic species; (ii) an extendedPhrynellaand/or a new generic name might accommodate the Turkish taxa currently underBolanthus, which were located on a distinct phylogenetic branch in the study by the revising authors.
“The Old White Lady of Kew Gardens”, Hechtia argentea (Bromeliaceae: Hechtioideae), found her homeland in Mexico
Authors: Ramírez‐Morillo Ivón M. , Hornung‐Leoni Claudia T. , González Ledesma Manuel , Romero‐Soler Katya J.
Published: August 2020

Hechtia argentea was described from a cultivated pistillate plant of unknown origin. The type specimen consists of a leaf fragment and a portion of a pistillate inflorescence. Hechtia argentea is part of a group of species with rosettes that bloom laterally, showing variation in dimensions and structure of the inflorescences of both sexes through the different years of flowering. Delimitation of species becomes more complicated where staminate and/or pistillate plants of different species are frequently similar, making it essential to have all plant structures available for accurate identifications. We designate an epitype for Hechtia argentea, consisting of a staminate plant, allowing for the unambiguous identification of the species. Species in Hechtia have restricted geographical distributions; thus, we provide precise locality data for H. argentea within Megamexico based on herbarium specimens. The species is endemic to the Sierra Madre Oriental and Mexican Plateau biogeographical regions, in the Mexican States of Hidalgo and Querétaro. In addition, we include for the first time a complete morphological description of both morphs, line drawings and photos of the species in situ, as well as a map showing the known distribution. Finally, we present an evaluation of the risk of extinction following the IUCN criteria.
Quantitative trait loci‐based genomics‐assisted prediction for the degree of apple fruit cover color
Authors: Zheng Wenyan , Shen Fei , Wang Wuqian , Wu Bei , Wang Xuan , Xiao Chen , Tian Zhendong , Yang Xianglong , Yang Jing , Wang Yi , Wu Ting , Xu Xuefeng , Han Zhenhai , Zhang Xinzhong
Published: August 2020

Apple fruit cover color is an important appearance trait determining fruit quality, high degree of fruit cover color or completely red fruit skin is also the ultimate breeding goal. MdMYB1 has repeatedly been reported as a major gene controlling apple fruit cover color. There are also multiple minor‐effect genes affecting degree of fruit cover color (DFC). This study was to identify genome‐wide quantitative trait loci (QTLs) and to develop genomics‐assisted prediction for apple DFC. The DFC phenotype data of 9,422 hybrids from five full‐sib families of Malus asiatica ‘Zisai Pearl’, M. domestica ‘Red Fuji’, ‘Golden Delicious’, and ‘Jonathan’ were collected in 2014–2017. The phenotype varied considerably among hybrids with the same MdMYB1 genotype. Ten QTLs for DFC were identified using MapQTL and bulked segregant analysis via sequencing. From these QTLs, ten candidate genes were predicted, including MdMYB1 from a year‐stable QTL on chromosome 9 of ‘Zisai Pearl’ and ‘Red Fuji’. Then, kompetitive allele‐specific polymerase chain reaction (KASP) markers were designed on these candidate genes and 821 randomly selected hybrids were genotyped. The genotype effects of the markers were estimated. MdMYB1‐1 (represented by marker H162) exhibited a partial dominant allelic effect on MdMYB1‐2 and showed non‐allelic epistasis on markers H1245 and G6. Finally, a non‐additive QTL‐based genomics assisted prediction model was established for DFC. The Pearson's correlation coefficient between the genomic predicted value and the observed phenotype value was 0.5690. These results can be beneficial for apple genomics‐assisted breeding and may provide insights for understanding the mechanism of fruit coloration.
Toward refining Alzheimer's disease into overlapping subgroups
Authors: Hascup Erin R. , Hascup Kevin N.
Published: August 2020

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by progressive anterograde amnesia, cerebral atrophy, and eventual death. Current treatment has limited efficacy and cannot decelerate the disease progression. Clinical trials targeting the removal of the neuropathological hallmarks of AD, including accumulation of amyloid plaques or neurofibrillary tangles, have failed to modify disease progression. Without new or innovative hypotheses, AD is poised to become a public health crisis within this decade. We present an alternative hypothesis—that AD is the result of multiple interrelated causalities. The intention of this manuscript is to initiate a discussion regarding these multiple causalities and their overlapping similarities. The idea of creating subgroups allows for better identification of biomarkers across a narrower patient population for improved pharmacotherapeutic opportunities. The interrelatedness of many of these proposed subgroups indicates the complexity of this disorder. However, it also supports that no one single factor may initiate the cascade of events.
Comparative performance of AI methods for wind power forecast in Portugal
Authors: Godinho Miguel , Castro Rui
Published: August 2020

Because wind has a high volatility and the respective energy produced cannot be stored on a large scale because of excessive costs, it is of utmost importance to be able to forecast wind power generation with the highest accuracy possible. The aim of this paper is to compare 1‐h‐ahead wind power forecasts performance using artificial intelligence‐based methods, such as artificial neural networks (ANNs), adaptive neural fuzzy inference system (ANFIS), and radial basis function network (RBFN). The latter was implemented using three different learning algorithms: stochastic gradient descent (SGD), hybrid, and orthogonal least squares (OLS). The application dataset is the injected wind power in the Portuguese power systems throughout the years 2010–2014. The network architecture optimization and the learning algorithms are presented. An initial data analysis showed data seasonality; therefore, the wind power forecasts were performed according to the seasons of the year. The results showed that ANFIS was the best performer method, and ANN and RBFN‐OLS also showed strong performances. RBFN‐Hybrid and RBFN‐SGD performed poorly. In general, all methods outperformed persistence.
Treatment of wood industry wastewater by combined coagulation–flocculation–decantation and fenton process
Authors: Azimi Seyyedeh Cobra , Shirini Farhad , Pendashteh Alireza
Published: August 2020

In the present research, the efficiency of turbidity and chemical oxygen demand (COD) reduction from the wood industry wastewater (WIW) by the use of a combined coagulation–flocculation–decantation (CFD) – Fenton process was studied. Firstly, the performance of three coagulants such as ferric chloride (FeCl3), aluminum sulphate (alum), and polyaluminum chloride (PACl) was evaluated. The polyacrylamide (PAM) was used as a flocculant. The results showed that the polyaluminum chloride had a high removal efficiency. The COD reduction of 84.1% and turbidity removal of 82.0% of were obtained in coagulation–flocculation–decantation (CFD). Secondly, Fenton process was optimized, by the use of a response surface methodology (RSM), with application of a central composite design (CCD). The maximum turbidity and COD removal obtained by this process were 94.1% and 72.5% respectively, under optimal conditions ([Fe2+] = 250 mg/L, [H2O2] = 500 mg/L, pH 3.5, time 60 min). The kinetics of COD and turbidity removal were determined by the model of first order. In conclusion, the combination of coagulation–flocculation–decantation (CFD) – Fenton process presented as a remarkable method for wood wastewater treatment.

Practitioner points

A combination of coagulation–flocculation–decantation and Fenton process was introduced for the wood industry wastewater treatment.

A designed experimental approach for treatment of wood industry wastewater using a Fenton process was studied.

The yields of COD, BOD5, N‐NO3, P‐PO4, and dye removal were obtained according to the standard limits in Iran.
Addressing the Consequences of School Closure Due to COVID‐19 on Children's Physical and Mental Well‐Being
Authors: Hoffman Jessica A. , Miller Edward A.
Published: August 2020

Prolonged school closures are one of the most disruptive forces in the COVID‐19 era. School closures have upended life for children and families, and educators have been forced to determine how to provide distance learning. Schools are also an essential source of nonacademic supports in the way of health and mental health services, food assistance, obesity prevention, and intervention in cases of homelessness and maltreatment. This article focuses on the physical and emotional toll resulting from school closures and the withdrawal of nonacademic supports that students rely on. The COVID‐19 pandemic is shining a spotlight on how important schools are for meeting children's nonacademic needs. We argue that when students return to school there will be a more acute and wider‐spread need for school‐based nonacademic services and supports. Further, we expect that COVID‐19 will serve as a focusing event opening a window of opportunity for programmatic and policy change that improves nonacademic services and supports in the future.
Technical Universities: A Historical Perspective
Authors: Geschwind Lars , Broström Anders
Published: August 2020

This chapter provides an overview of the historical development of technical institutes and universities from their foundation in the late eighteenth century to the present time. Our account, which is focused on European experiences, shows that technical universities are characterized by their historical relations to the industrial revolution, and since that time their strong linkages to industry (from initially local to increasingly global). The chapter also highlights some persistent tensions and dilemmas related in part to this historical legacy, including the introduction of and relation to research, the balance between theory and application, and the ‘congestion’ in engineering programmes. Development over the last decades revolves around the profiles and scientific scope of technical universities. Over time, new areas have been introduced, mirroring their technical development and in some countries—as a consequence of external drivers and strategic agendas—eye-catching reorganisations and new initiatives have increased the portfolio way beyond the classical engineering subjects.
Anhang
Authors: Seibert Simon P. , Auerswald Karl
Published: August 2020

Im Anhang befinden sich Tabellen zur Wirksamkeit dezentraler Maßnahmen zur Abflussminderung und zu hydraulischen Eigenschaften unterschiedlicher Abflusstypen und Fließpfade. Der Anhang liefert alternative Verfahren zur Bestimmung des Scheitelabflusses (Verhältnisverfahren) und der Abflusshöhe (nach Lutz) und er beschreibt ergänzende Verfahren wie die Ableitung von Gebiets- und Bemessungsniederschlägen, die Bestimmung der Hydrologischen Bodengruppe, die Kartierung von Fließwegen im Gelände, hilfreiche Geodaten und Verfahren der Geodatenanalyse. Wegen der besonderen Bedeutung widmet sich ein Teil außerdem dem Wegebau und der Wasserführung.
Multiple point principle in the general Two-Higgs-Doublet model
Authors: Maniatis Markos , Sartore Lohan , Schienbein Ingo
Published: August 2020

Abstract

Based on the Multiple Point Principle, the Higgs boson mass has been predicted to be 135 ± 9 GeV — more than two decades ago. We study the Multiple Point Principle and its prospects with respect to the Two-Higgs-Doublet model (THDM). Applying the bilinear formalism we show that concise conditions can be given with a classification of different kinds of realizations of this principle. We recover cases discussed in the literature but identify also different realizations of the Multiple Point Principle.
hPSC-derived organoids: models of human development and disease
Authors: Frum Tristan , Spence Jason R.
Published: August 2020

Organoids derived from human pluripotent stem cells (hPSCs) have emerged as important models for investigating human-specific aspects of development and disease. Here we discuss hPSC-derived organoids through the lens of development—highlighting how stages of human development align with the development of hPSC-derived organoids in the tissue culture dish. Using hPSC-derived lung and intestinal organoids as examples, we discuss the value and application of such systems for understanding human biology, as well as strategies for enhancing organoid complexity and maturity.
Differenzialdiagnose „Zustand nach Hijama“
Authors: Jühling M. , Mahlke N. S. , König L. M. , Ritz-Timme S. , Mayer F.
Published: August 2020

Im Rahmen von Begutachtungen zu möglichen Folgen von Folterhandlungen fiel mehrfach der Befund gleichartiger Gruppierungen von über den Rücken verteilten, strichförmigen Narben auf. Ein ähnlich imponierendes, frischeres Verletzungsbild wurde bei einem weiteren Fall festgestellt und konnte auf „Hijama“ (blutiges Schröpfen) zurückgeführt werden. Die dargestellten Fälle zeigen, wie wichtig die Kenntnis von durch alternative Behandlungsmethoden provozierten Befunden ist.
The effect of breaking up prolonged sitting on paired associative stimulation-induced plasticity
Authors: Bojsen-Møller E. , Ekblom M. M. , Tarassova O. , Dunstan D. W. , Ekblom O.
Published: August 2020

Paired associative stimulation (PAS) can induce plasticity in the motor cortex, as measured by changes in corticospinal excitability (CSE). This effect is attenuated in older and less active individuals. Although a single bout of exercise enhances PAS-induced plasticity in young, physically inactive adults, it is not yet known if physical activity interventions affect PAS-induced neuroplasticity in middle-aged inactive individuals. Sixteen inactive middle-aged office workers participated in a randomized cross-over design investigating how CSE and short-interval intracortical inhibition (SICI) were affected by PAS preceded by 3 h of sitting (SIT), 3 h of sitting interrupted every 30 min by 3 min of frequent short bouts of physical activity (FPA) and 2.5 h of sitting followed by 25 min of moderate-intensity exercise (EXE). Transcranial magnetic stimulation was applied over the primary motor cortex (M1) of the dominant abductor pollicis brevis to induce recruitment curves before and 5 min and 30 min post-PAS. Linear mixed models were used to compare changes in CSE using time and condition as fixed effects and subjects as random effects. There was a main effect of time on CSE and planned within-condition comparisons showed that CSE was significantly increased from baseline to 5 min and 30 min post-PAS, in the FPA condition, with no significant changes in the SIT or EXE conditions. SICI decreased from baseline to 5 min post-PAS, but this was not related to changes in CSE. Our findings suggest that in middle-aged inactive adults, FPAs may promote corticospinal neuroplasticity. Possible mechanisms are discussed.
Validation of automated Alberta Stroke Program Early CT Score (ASPECTS) software for detection of early ischemic changes on non-contrast brain CT scans
Authors: Wolff Lennard , Berkhemer Olvert A. , van Es Adriaan C. G. M. , van Zwam Wim H. , Dippel Diederik W. J. , Majoie Charles B. L. M. , van Walsum Theo , van der Lugt Aad ,   for the MR CLEAN Investigators
Published: August 2020

Purpose

In ASPECTS, 10 brain regions are scored visually for presence of acute ischemic stroke damage. We evaluated automated ASPECTS in comparison to expert readers.

Methods

Consecutive, baseline non-contrast CT-scans (5-mm slice thickness) from the prospective MR CLEAN trial (n= 459, MR CLEAN Netherlands Trial Registry number: NTR1804) were evaluated. A two-observer consensus for ASPECTS regions (normal/abnormal) was used as reference standard for training and testing (0.2/0.8 division). Two other observers provided individual ASPECTS-region scores. The Automated ASPECTS software was applied. A region score specificity of ≥ 90% was used to determine the software threshold for detection of an affected region based on relative density difference between affected and contralateral region. Sensitivity, specificity, and receiver-operating characteristic curves were calculated. Additionally, we assessed intraclass correlation coefficients (ICCs) for automated ASPECTS and observers in comparison to the reference standard in the test set.

Results

In the training set (n= 104), with software thresholds for a specificity of ≥ 90%, we found a sensitivity of 33–49% and an area under the curve (AUC) of 0.741–0.785 for detection of an affected ASPECTS region. In the test set (n= 355), the results for the found software thresholds were 89–89% (specificity), 41–57% (sensitivity), and 0.750–0.795 (AUC). Comparison of automated ASPECTS with the reference standard resulted in an ICC of 0.526. Comparison of observers with the reference standard resulted in an ICC of 0.383–0.464.

Conclusion

The performance of automated ASPECTS is comparable to expert readers and could support readers in the detection of early ischemic changes.
The Impact of Accidental Hypothermia on Mortality in Trauma Patients Overall and Patients with Traumatic Brain Injury Specifically: A Systematic Review and Meta‐Analysis
Authors: Rösli David , Schnüriger Beat , Candinas Daniel , Haltmeier Tobias
Published: August 2020

Background

Accidental hypothermia is a known predictor for worse outcomes in trauma patients, but has not been comprehensively assessed in a meta‐analysis so far. The aim of this systematic review and meta‐analysis was to investigate the impact of accidental hypothermia on mortality in trauma patients overall and patients with traumatic brain injury (TBI) specifically.

Methods

This is a systematic review and meta‐analysis using the Ovid Medline/PubMed database. Scientific articles reporting accidental hypothermia and its impact on outcomes in trauma patients were included in qualitative synthesis. Studies that compared the effect of hypothermia vs. normothermia at hospital admission on in‐hospital mortality were included in two meta‐analyses on (1) trauma patients overall and (2) patients with TBI specifically. Meta‐analysis was performed using a Mantel–Haenszel random‐effects model.

Results

Literature search revealed 264 articles. Of these, 14 studies published 1987–2018 were included in the qualitative synthesis. Seven studies qualified for meta‐analysis on trauma patients overall and three studies for meta‐analysis on patients with TBI specifically. Accidental hypothermia at admission was associated with significantly higher mortality both in trauma patients overall (OR 5.18 [95% CI 2.61–10.28]) and patients with TBI specifically (OR 2.38 [95% CI 1.53–3.69]).

Conclusions

In the current meta‐analysis, accidental hypothermia was strongly associated with higher in‐hospital mortality both in trauma patients overall and patients with TBI specifically. These findings underscore the importance of measures to avoid accidental hypothermia in the prehospital care of trauma patients.
Study of the Portal Branches Arising from the Cranial Part of the Umbilical Portion of the Left Portal Vein: Implications for Anatomic Right Hepatic Trisectionectomy
Authors: Minami Takayuki , Ebata Tomoki , Yokoyama Yukihiro , Igami Tsuyoshi , Mizuno Takashi , Yamaguchi Junpei , Onoe Shunsuke , Watanabe Nobuyuki , Nagino Masato
Published: August 2020

Background

In “anatomic” right hepatic trisectionectomy for advanced perihilar cholangiocarcinoma, the left hepatic duct is divided at the left side of the umbilical portion (UP) of the left portal vein (LPV). For this reason, the left hepatic duct is completely detached from the UP after all division of the portal branches arising cranially from the UP. However, little is known about these thin portal branches.

Methods

Using 3D imaging processing software, we examined the portal branches arising cranially from the UP of the LPV in 100 patients who underwent multidetector row computed tomography (MDCT). Special attention was paid to the portal branch running to the left lateral sector, designated as the left cranio‐lateral branch.

Results

The left cranio‐lateral portal branch number was 0 in 57 patients, 1 in 32 patients, and 2 in 11 patients. Thus, 54 left cranio‐lateral branches were identified, arising from near the cul‐de‐sac of the UP, from near the elbow of the LPV, or from the UP trunk. The median volume of the territory supplied by the left cranio‐lateral portal branch was 21 mL (range, 5–47 mL), and the median ratio to the left lateral sector was 11.8% (range, 1.7–25.0%).

Conclusion

Approximately 40% of patients had the left cranio‐lateral portal branches arising cranially from the UP and running to the left lateral sector. When planning anatomic right hepatic trisectionectomy, the presence or absence of this branch should be checked by using 3D imaging with MDCT.
Cost-effectiveness of MR-mammography as a solitary imaging technique in women with dense breasts: an economic evaluation of the prospective TK-Study
Authors: Froelich Matthias F. , Kaiser Clemens G.
Published: August 2020

Objectives

To evaluate the economic implications of our previous study on the use of MR-mammography (MRM) as a solitary imaging tool in women at intermediate risk due to dense breasts.

Background

In our previous study, we found MRM to be a specific diagnostic tool with high accuracy in patients with dense breasts representing a patient collective at intermediate risk of breast cancer. For this study, we examined whether MRM is an economical alternative.

Methods

For the determination of outcomes and costs, a decision model based on potential diagnostic results of MRM was developed. Quality of life was estimated in a Markov chain model distinguishing between the absence of malignancy, the presence of malignancy, and death. Input parameters were utilized from the prospective TK-Study. To investigate the economic impact of MRM, overall costs in € and outcomes of MRM in quality-adjusted life years (QALYs) were estimated. A deterministic sensitivity analysis was performed.

Results

MRM was associated with expected costs of 1650.48 € in the 5-year period and an expected cumulative outcome of 4.69 QALYs. A true positive diagnosis resulted in significantly lower costs and a higher quality of life when compared to the consequences of a false negative result. In the deterministic sensitivity analysis, treatment costs had more impact on overall costs than the costs of MRM. The total costs per patient remained below 2500 € in the 5-year period.

Conclusion

MRM, as a solitary imaging tool in patients at intermediate risk due to dense breasts, is economically feasible.

Key Points

• In patients with dense breasts (i.e., patients at intermediate risk of breast cancer), the relative cost of MR-mammography examinations only had moderate impact on overall costs.

• This is due to cost-savings through the application of a sensitive imaging technique resulting in an optimized staging and therapy planning.

• MR-mammography, unaccompanied by mammography or ultrasound in patients with dense breasts, was economically feasible in our analysis.