bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of novel nomograms for predicting the survival of patients after surgical resection of pancreatic ductal adenocarcinoma
Authors: Li Ge , Chen Jiang‐Zhi , Chen Shi , Lin Sheng‐Zhe , Pan Wei , Meng Ze‐Wu , Cai Xin‐Ran , Chen Yan‐Ling
Published: March 2020

Background/Aims

Pancreatic ductal adenocarcinoma (PDAC) is associated with high mortality, even after surgical resection. The existing predictive models for survival have limitations. This study aimed to develop better nomograms for predicting overall survival (OS) and cancer‐specific survival (CSS) in PDAC patients after surgery.

Methods

A total of 6323 PDAC patients were retrospectively recruited from the Surveillance, Epidemiology, and End Results (SEER) database and randomly allocated into training, validation, and test cohorts. Multivariate Cox regression analysis was conducted to identify significant independent factors for OS and CSS, which were used for construction of nomograms. The performance was evaluated, validated, and compared with that of the 8th edition AJCC staging system.

Results

Ten independent factors were significantly correlated with OS and CSS. The 1‐, 3‐, and 5‐year OS rates were 40%, 20%, and 15%, and 1‐, 3‐, and 5‐year CSS rates were 45%, 24%, and 19%, respectively. The nomograms were calibrated well, with c‐indexes of 0.640 for OS and 0.643 for CSS, respectively. Notably, relative to the 8th edition AJCC staging system, the nomograms were able to stratify each AJCC stage into three prognostic subgroups for more robust risk stratification. Furthermore, the nomograms achieved significant clinical validity, exhibiting wide threshold probabilities and high net benefit. Performance assessment also showed high predictive accuracy and reliability.

Conclusions

The predictive ability and reliability of the established nomograms have been validated, and therefore, these nomograms hold potential as novel approaches to predicting survival and assessing survival risks for PDAC patients after surgery.
From 360° camera toward to virtual map app: Designing low‐cost pilot study
Authors: Netek Rostislav , Burian Tomas , Macecek Martin
Published: March 2020

Currently, virtual reality (VR) is a trend both in general and in specific fields such as interactive maps. The article aims to test the possibilities of deployment of low‐cost virtual reality environment for the 3D spatial panoramic application. It discusses and compares modern trends in hardware (panoramic cameras and glasses) and software in the field of virtual reality. Many panoramic map applications (e.g., the well‐known “Google Street View”) allow us to navigate through applications using VR headsets or on an ordinary 2D monitor. The main aim of the article is to design, develop, and deploy VR map application with different levels of user interaction. It presents two pilot studies with different user's interactivity and technical solutions: “simple” 2D‐based map with 360° panoramic photos and “true” 3D application for VR glasses. The article focuses on the possibilities of creating low‐cost map applications. Therefore, the working process “from camera toward to virtual map application” is described as followed‐up case studies.
Therapeutic Targeting of Cancer Metabolism with Triosephosphate Isomerase
Authors: Pekel Gonca , Ari Ferda
Published: March 2020

The increase in glycolytic flux in cancer, known as aerobic glycolysis, is one of the most important hallmarks of cancer. Therefore, glycolytic enzymes have importance in understanding the molecular mechanism of cancer progression. Triosephosphate isomerase (TPI) is one of the key glycolytic enzymes. Furthermore, it takes a part in gluconeogenesis, pentose phosphate pathway and fatty acid biosynthesis. To date, it has been shown altered levels of TPI in various cancer types, especially in metastatic phenotype. According to other studies, TPI might be considered as a potential therapeutic target and a cancer‐related biomarker in different types of cancer. However, its function in tumor formation and development has not been fully understood. Here, we reviewed the relationship between TPI and cancer for the first time
Halogenation‐Guided Chemical Screening Provides Insight into Tjipanazole Biosynthesis by the Cyanobacterium Fischerella ambigua
Authors: Chilczuk Tomasz , Schäberle Till F. , Vahdati Sahel , Mettal Ute , El Omari Mustafa , Enke Heike , Wiese Michael , König Gabriele M. , Niedermeyer Timo H. J.
Published: March 2020

Halogenated natural products (HNPs) show a wide range of interesting biological activities. Chemistry‐guided screening with a software tool dedicated to identifying halogenated compounds in HPLC‐MS data indicated the presence of several uncharacterised HNPs in an extract of the cyanobacterium Fischerella ambigua (Näg.) Gomont 108b. Three new natural products, tjipanazoles K, L, and M, were isolated from this strain together with the known tjipanazoles D and I. Taking into account the structures of all tjipanazole derivatives detected in this strain, reanalysis of the tjipanazole biosynthetic gene cluster allowed us to propose a biosynthetic pathway for the tjipanazoles. As the isolated tjipanazoles show structural similarity to arcyriaflavin A, an inhibitor of the clinically relevant multidrug‐transporter ABCG2 overexpressed by different cancer cell lines, the isolated compounds were tested for ABCG2 inhibitory activity. Only tjipanazole K showed appreciable transporter inhibition, whereas the compounds lacking the pyrrolo[3,4‐c] ring or featuring additional chloro substituents were found to be much less active.
A Selective Fluorogenic Peptide Substrate for the Human Mitochondrial ATP‐Dependent Protease Complex ClpXP
Authors: Sha Zhou , Fishovitz Jennifer , Wang Susan , Chilakala Sujatha , Xu Yan , Lee Irene
Published: March 2020

The goal of this work is to identify differences in the substrate determinants of two human mitochondrial matrix ATP‐dependent proteases, human ClpXP (hClpXP) and human Lon (hLon). This information allows the generation of protease‐specific peptide substrates that can be used as chemical biology tools to investigate the physiological functions of hClpXP. These enzymes play a role in protein quality control, but currently the physiological functions of human ClpXP are not well defined. In this study, the degradation profile of casein, an alanine positional scanning decapeptide library, and a specific peptide sequence found in an endogenous substrate of bacterial ClpXP by hClpXP as well as hLon were examined. Based on our findings, we generated a specific fluorogenic peptide substrate, FR‐Cleptide, for hClpXP with a kcat of 2.44±0.15 s−1 and Km=262±43 μM, respectively. The FR‐Cleptide substrate was successfully used to identify a leucine methyl ketone as a potent lead inhibitor, and to detect endogenous hClpXP activity in HeLa cell lysate. We propose that the fluorogenic peptide substrate is a valuable tool for quantitatively monitoring the activity of hClpXP in cell lysate, as well as mechanistic characterization of hClpXP. The peptide‐based chemical tools developed in this study will complement the substrates developed for human Lon in aiding the investigation of the physiological functions of the respective protease.
Evaluating Terminator Strength Based on Differentiating Effects on Transcription and Translation
Authors: He Zhiyun , Duan Yanting , Zhai Weiji , Zhang Xiaomei , Shi Jinsong , Zhang Xiaojuan , Xu Zhenghong
Published: March 2020

Transcription terminators play a role in terminating the progress of gene transcription, and are thus essential elements in the gene circuit. Terminators have two main functions: terminating gene transcription and improving the stability of gene transcripts during translation. We therefore considered the detailed characteristics of terminators in relation to their different roles in gene transcription and translation, including transcription shut‐down degree (α) and upstream mRNA protection capacity (β), and apparent termination efficiency (η) reflecting the overall regulatory effect of the terminator. Based on a dual‐reporter gene system, we constructed three terminator‐probe plasmids to investigate each characteristic in Escherichia coli. According to multiple regression analysis, the transcription shut‐down degree and the upstream mRNA protection capacity contributed almost equally to the apparent termination efficiency. Sequence analysis of 12 terminators demonstrated that the terminator sequence was dominated by GC bases, and that a high ratio of GC bases in the stem structure of terminators might be associated with a high degree of transcription shut‐down. This comprehensive characterization of terminators furthers our understanding of the role of terminators in gene expression and provides a guide for synthetic terminator design.
Transfemoral transcatheter puncture of interventricular septum in a swine model: A novel transfemoral‐venous access to left ventricle with the assistance of arterio‐venous circuit
Authors: Yan Chaowu , Wan Linyuan , Li Li , Li Hua , Du Baopeng , Hao Shijie
Published: March 2020

Objective

Via subclavian/jugular vein, successful puncture of interventricular septum (IVS) has been achieved transvenously. However, the approach was limited by acute entry‐angle. The study was conducted to investigate a novel transcatheter puncture of IVS via femoral access and transfemoral‐venous access to left ventricle (LV) through IVS.

Methods

Via femoral artery, transcatheter puncture of mid‐IVS was performed with a custom‐made nickel–titanium needle and 6F‐sheath in 16 healthy mini‐swine. Then femoral arterio‐venous circuit was established through IVS. After pre‐dilation of IVS, a 20F‐sheath was introduced into LV transvenously over‐the‐guidewire in 15 swine. Furthermore, transfemoral‐venous TAVR was attempted with the approach in another swine. IVS was evaluated postoperatively and was further confirmed pathologically 2 months later.

Results

All transcatheter puncture of IVS was performed successfully in LV and the mid‐IVS thickness was 7.67 ± 0.98 mm. In all swine, femoral arterio‐venous circuit was established via IVS, and a 20F‐sheath was introduced into LV and aorta transfemoral‐venously (entry‐angle: 145.3 ± 12.2° in front view). After the procedure, there was one swine with moderate tricuspid‐regurgitation and five swine with mild residual‐shunt (2.6 ± 0.7 mm). Two months later, residual‐shunt was still detected in three swine and the communication was confirmed pathologically. In other swine, no defect occurred and replacement‐scar was identified along puncture‐tract. In the swine underwent transfemoral‐venous TAVR, prosthetic valve was deployed successfully with good function.

Conclusions

Transfemoral transcatheter puncture of IVS is feasible and safe in a swine model, and large sheath can be introduced into LV transfemoral‐venously using the novel access with the aid of vessel circuit.
Transition Metal‐Catalyzed and Metal‐Free Cyclization Reactions of Alkynes with Nitrogen‐Containing Substrates: Synthesis of Pyrrole Derivatives
Authors: Neto Jose S. S. , Zeni Gilson
Published: March 2020

This review describes the efforts in the synthesis of pyrrole derivatives using the reaction of alkynes with nitrogen‐compounds under transition metal‐catalyzed and metal‐free conditions, in the past decade. We initially focused on the methods of preparation of pyrrole derivatives using reactions catalyzed by transition metal. In this part, we described the syntheses of 1‐pyrrolines, 2‐pyrrolines, 3‐pyrrolines, pyrroles, and pyrrolidines following an alphabetical order of the transition metal used for the synthesis. Subsequently, we presented the synthesis of these pyrrole derivatives under metal‐free conditions.
Recent Advances in Synthesis and Utilization of Ultra‐low Loading of Precious Metal‐based Catalysts for Fuel Cells
Authors: Lori Oran , Elbaz Lior
Published: March 2020

Cost of polymer electrolyte membrane fuel cells (PEMFC) is one of the most acute setbacks delaying this technology's worldwide deployment and commercialization. Platinum, the most common and effective catalyst for the oxygen reduction reaction (ORR), is a scarce element which accounts for more than 45 % of PEMFC stack cost. One of the preferred proposed paths to substantially reduce stack costs is by dramatically lowering precious metal loading in a membrane electrode assembly (MEA) to account for up to 11.3 gPt per midsize vehicle (US‐DOE 2020 target). This Minireview surveys the latest synthetical and methodical advances in making and utilizing ultra‐low loading precious metal ORR catalyst in PEM fuel cells.
Structural Designs and in‐situ X‐ray Characterizations of Metal Phosphides for Electrocatalysis
Authors: Zhang Youkui , Song Li
Published: March 2020

Electrocatalysis is one of the most attractive technologies for renewable energy storage and conversion to meet global energy demand. Thus it has attracted considerable research efforts for the development of inexpensive and efficient electrocatalysts. Recent research progress has demonstrated that the Earth‐abundant metal‐based phosphides are attractive materials for efficient electrocatalysis because of attractive features such as tunable structure and high activity. In this Minireview, we summarize the latest research progress of metal phosphide‐based materials as efficient electrocatalysts. The synthesis approaches of metal phosphides and the factors that influence structural reconstruction in certain reactions are reviewed and discussed. Specifically, advanced in‐situ X‐ray characterization techniques for metal phosphide research in the field of electrocatalysis are also highlighted. Finally, the current challenges and future perspectives for these materials are presented.
Synthesis of Dinuclear Mo−Fe Hydride Complexes and Catalytic Silylation of N2
Authors: Ishihara Kodai , Araki Yuna , Tada Mizuki , Takayama Tsutomu , Sakai Yoichi , Sameera W. M. C. , Ohki Yasuhiro
Published: March 2020

Two transition‐metal atoms bridged by hydrides may represent a useful structural motif for N2 activation by molecular complexes and the enzyme active site. In this study, dinuclear MoIV‐FeII complexes with bridging hydrides, CpRMo(PMe3)(H)(μ‐H)3FeCp* (2 a; CpR=Cp*=C5Me5, 2 b; CpR=C5Me4H), were synthesized via deprotonation of CpRMo(PMe3)H5 (1 a; CpR=Cp*, 1 b; CpR=C5Me4H) by Cp*FeN(SiMe3)2, and they were characterized by spectroscopy and crystallography. These Mo−Fe complexes reveal the shortest Mo−Fe distances ever reported (2.4005(3) Å for 2 a and 2.3952(3) Å for 2 b), and the Mo−Fe interactions were analyzed by computational studies. Removal of the terminal Mo−H hydride in 2 a–2 b by [Ph3C]+ in THF led to the formation of cationic THF adducts [CpRMo(PMe3)(THF)(μ‐H)3FeCp*]+ (3 a; CpR=Cp*, 3 b; CpR=C5Me4H). Further reaction of 3 a with LiPPh2 gave rise to a phosphido‐bridged complex Cp*Mo(PMe3)(μ‐H)(μ‐PPh2)FeCp* (4). A series of Mo−Fe complexes were subjected to catalytic silylation of N2 in the presence of Na and Me3SiCl, furnishing up to 129±20 equiv of N(SiMe3)3 per molecule of 2 b. Mechanism of the catalytic cycle was analyzed by DFT calculations.
From Specific γ‐CD/[Nb6Cl12(H2O)6]2+ Recognition to Biological Activity Tuning
Authors: Ivanov Anton A. , Pozmogova Tatiana N. , Solovieva Anastasiya O. , Frolova Tatiana S. , Sinitsyna Olga I. , Lundovskaya Olga V. , Tsygankova Alphiya R. , Haouas Mohamed , Landy David , Benassi Enrico , Shestopalova Lidiya V. , Falaise Clément , Cadot Emmanuel , Shestopalov Michael A. , Abramov Pavel A. , Sokolov Maxim N.
Published: March 2020

Specific molecular recognition of γ‐cyclodextrin (γ‐CD) by the cationic hexanuclear niobium [Nb6Cl12(H2O)6]2+ cluster complex in aqueous solutions results in a 1:1 supramolecular assembly {[Nb6Cl12(H2O)6]@γ‐CD}2+. NMR spectroscopy, isothermal titration calorimetry (ITC), and ESI‐MS were used to study the interaction between the inorganic cluster and the organic macrocycle. Such molecular association affects the biological activity of [Nb6Cl12(H2O)6]2+, decreasing its cytotoxicity despite enhanced cellular uptake. The 1:1 stoichiometry is maintained in solution over a large window of the reagents’ ratio, but crystallization by slow evaporation produces a 1:2 host–guest complex [Nb6Cl12(H2O)6@(γ‐CD)2]Cl2⋅20 H2O featuring the cluster encapsulated between two molecules of γ‐CD. The 1:2 complex was characterized by XRD, elemental analysis, IR spectroscopy, and thermogravimetric analysis (TGA). Quantum chemical calculations were performed to model host–guest interaction.
Equivalence of the Ellipticity Conditions for Geometric Variational Problems
Authors: De Rosa Antonio , Kolasiński Sławomir
Published: March 2020

We exploit the so‐called atomic condition, recently defined by De Philippis, De Rosa, and Ghiraldin and proved to be necessary and sufficient for the validity of the anisotropic counterpart of the Allard rectifiability theorem. In particular, we address an open question of this seminal work, showing that the atomic condition implies the strict Almgren geometric ellipticity condition. © 2020 Wiley Periodicals, Inc.
Performance study of sustained petascale direct numerical simulation on Cray XC40 systems
Authors: Hadri Bilel , Parsani Matteo , Hutchinson Maxwell , Heinecke Alexander , Dalcin Lisandro , Keyes David
Published: March 2020

We present in this paper a comprehensive performance study of highly efficient extreme scale direct numerical simulations of secondary flows, using an optimized version of Nek5000. Our investigations are conducted on various Cray XC40 systems, using a very high‐order spectral element method. Single‐node efficiency is achieved by auto‐generated assembly implementations of small matrix multiplies and key vector‐vector operations, streaming lossless I/O compression, aggressive loop merging, and selective single precision evaluations. Comparative studies across different Cray XC40 systems at scale, Trinity (LANL), Cori (NERSC), and ShaheenII (KAUST) show that a Cray programming environment, network configuration, parallel file system, and burst buffer all have a major impact on the performance. All three systems possess a similar hardware with similar CPU nodes and parallel file system, but they have different theoretical peak network bandwidths, different OSs, and different versions of the programming environment. Our study reveals how these slight configuration differences can be critical in terms of performance of the application. We also find that with 9216 nodes (294 912 cores) on Trinity XC40 the applications sustain petascale performance, as well as 50% of peak memory bandwidth over the entire solver (500 TB/s in aggregate). On 3072 Xeon Phi nodes of Cori, we reach 378 TFLOP/s with an aggregated bandwidth of 310 TB/s, corresponding to time‐to‐solution 2.11× faster than obtained with the same number of (dual‐socket) Xeon nodes.
Binuclear Lanthanide(III) Complexes with Chiral Ligands: Dynamic Equilibria in Solution and Binding with Nucleotides Studied by Spectroscopic Methods
Authors: Sahoo Jashobanta , Wu Tao , Klepetářová Blanka , Valenta Jan , Bouř Petr
Published: March 2020

Binuclear lanthanide complexes of Eu(III) and Sm(III) were obtained in the presence of chiral ligand 1,2‐(R,R+S,S)‐N,N’‐bis(2‐pyridylmethylene),2‐diamine. An unusual structure of the Eu(III) compound with two lanthanide atoms connected through two chlorines was determined by X‐ray crystallography. In solution, the dimer coexists with a monomeric complex, and the stability of the binuclear form depends on the solvent and concentration. The dimer‐monomer equilibrium was monitored by circularly polarized luminescence (CPL) measured on a Raman optical activity (ROA) spectrometer, where both forms provided large CPL anisotropic ratios of up to 5.6×10−2. Monomer formation was favored in water, whereas the dimer was stabilized in methanol. When mixed with adenosine phosphates, AMP gave much smaller CPL than ADP and ATP, indicating a high affinity of the Eu (III) complex for the phosphate group, which in connection with the ROA/CPL technique can be developed into a bioanalytical probe.
Fog‐SDN: A light mitigation scheme for DDoS attack in fog computing framework
Authors: Priyadarshini Rojalina , Kumar Barik Rabindra , Dubey Harishchandra
Published: March 2020

Cloud computing is one of the most tempting technologies in today's computing scenario as it provides a cost‐efficient solutions by reducing the large upfront cost for buying hardware infrastructures and computing power. Fog computing is an added support to cloud environment by leveraging with doing some of the less compute intensive task to be done at the edge devices, which reduces the response time for end user computing. But the vulnerabilities to these systems are still a big concern. Among several security needs, availability is one that makes the demanded services available to the targeted customers all the time. Availability is often challenged by external attacks like Denial of service (DoS) and distributed denial of service (DDoS). This paper demonstrates a novel source‐based DDoS mitigating schemes that could be employed in both fog and cloud computing scenarios to eliminate these attacks. It deploys the DDoS defender module which works on a machine learning–based light detection method, present at the SDN controller. This scheme uses the network traffic data to analyze, predict, and filter incoming data, so that it can send the filtered legitimate packets to the server and blocking the rest.
Malignant melanoma in a child with giant congenital melanocytic nevus and satellite flekers: A rare entity
Authors: Kumari Manju , Singh Mukul , Punhani Pallavi
Published: March 2020

Malignant melanomas in the pediatric age are remarkably rare representing 0.9% of various pediatric malignancies. Congenital nevi occur in 1 in 100 newborns, whereas giant congenital melanocytic nevus (GCMN) measuring more than 20 cm is seen in 1 in 20 000 cases. Very few cases of malignant melanoma arising from GCMN have been described in English literature. The risk of developing malignant melanoma from GCMN is believed to be directly proportional to the size of the nevus and varies from 2.6% to 20% depending on the size of nevus. We present a case of malignant melanoma in a 12‐year‐old female child who had a congenital giant nevus and multiple satellite flekers all over the body.
Evaluation of the neuropharmacological effects of Gardenin A in mice
Authors: Alonso‐Castro Angel J. , Gasca‐Martínez Deisy , Cortez‐Mendoza Laura V. , Alba‐Betancourt Clara , Ruiz‐Padilla Alan J. , Zapata‐Morales Juan R.
Published: March 2020

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1–25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital‐induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus‐maze, the light–dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant‐like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic‐like and antidepressant‐like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine‐induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic‐like actions with activity comparable to that of clonazepam in all experimental tests. The GABAA receptor antagonist bicuculline reversed the anxiolytic‐like effects of GA. Furthermore, GA showed significant antidepressant‐like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2‐adrenoceptor blocker, inhibited the antidepressant‐like actions of GA. In addition, GA (1–10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic‐like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant‐like actions of GA may be mediated by noradrenergic neurotransmission.
School‐entry language outcomes in late talkers with and without a family risk of dyslexia
Authors: Caglar‐Ryeng Ømur , Eklund Kenneth , Nergård‐Nilssen Trude
Published: March 2020

Children with familial risk (FR) of dyslexia and children with early language delay are known to be at risk for later language and literacy difficulties. However, research addressing long‐term outcomes in children with both risk factors is scarce. This study tracked FR and No‐FR children identified as late talkers at 2 years of age and reports development from 4;6 through 6 years. We examined the possible effects of FR‐status and late talking (LT) status, respectively, on language skills at school entry, and whether FR‐status moderated the associations between 4;6‐year and 6‐year language scores. Results indicated an effect of LT status on language at both ages, while FR status affected language skills at 6 years only. The interaction between LT and FR statuses was not significant, implying that LT status affected language skills independently of the child's FR status. A proportion of late talkers developed typical language at 6 years of age, while some FR children with typical vocabulary skills in toddlerhood had emerging developmental language disorder by school entry. FR status had a moderating effect on the association between expressive grammar at ages 4;6 and 6 years. Possible explanations for the effect of FR status on language skills are discussed. We highlight limitations in the study size and suggest how these preliminary findings can inform future research.
Genetic variation in an ephemeral mudflat species: The role of the soil seed bank and dispersal in river and secondary anthropogenic habitats
Authors: Böckelmann Jörg , Tremetsberger Karin , Šumberová Kateřina , Kohl Gudrun , Grausgruber Heinrich , Bernhardt Karl‐Georg
Published: March 2020

Many ephemeral mudflat species, which rely on a soil seed bank to build up the next generation, are endangered in their natural habitat due to the widespread regulation of rivers. The aim of the present study was to elucidate the role of the soil seed bank and dispersal for the maintenance of genetic diversity in populations of near‐natural river habitats and anthropogenic habitats created by traditional fish farming practices using Cyperus fuscus as a model. Using microsatellite markers, we found no difference in genetic diversity levels between soil seed bank and above‐ground population and only moderate differentiation between the two fractions. One possible interpretation is the difference in short‐term selection during germination under specific conditions (glasshouse versus field) resulting in an ecological filtering of genotypes out of the reservoir in the soil. River populations harbored significantly more genetic diversity than populations from the anthropogenic pond types. We suggest that altered levels and patterns of dispersal together with stronger selection pressures and historical bottlenecks in anthropogenic habitats are responsible for the observed reduction in genetic diversity. Dispersal is also supposed to largely prohibit genetic structure across Europe, although there is a gradient in private allelic richness from southern Europe (high values) to northern, especially north‐western, Europe (low values), which probably relates to postglacial expansion out of southern and/or eastern refugia.
Principal hydrology and water quality factors driving the development of plankton communities in a pilot city of China
Authors: Zhao Changsen , Pan Xu , Yang Shengtian , Sun Ying , Shao Nanfang
Published: March 2020

Healthy plankton communities form the basis of healthy aquatic ecosystems. By elucidating the mechanisms of mutual feedback between plankton and habitat processes and identifying key driving factors can enhance the success rate of ecosystem restoration. However, previous studies suffered from a lack of consideration for temporal and spatial variation in aquatic biome. In this study, three sets of samples were collected in May, September and October 2015 from 59 sampling sites in Jinan, a pilot city for water ecological civilization project, China. Canonical correspondence analysis was performed on the vast amount of data obtained from the samples to analyse the driving effects of various hydrological and water quality factors on plankton. The analysis results indicated that the development of plankton communities in Jinan were primarily driven by (1) hydrological factors of water depth, river width and flow velocity; (2) water quality physical factors of water temperature and conductivity and (3) water quality chemical factors of pH, chemical oxygen demand, biochemical oxygen demand, carbonate and sulphate contents. These results will provide in‐depth theoretical and technical direction for the restoration of aquatic ecosystems in the first pilot city in China and other regions worldwide.
Phenobarbital as alternate anticonvulsant for organophosphate‐induced benzodiazepine‐refractory status epilepticus and neuronal injury
Authors: Reddy Doodipala Samba , Perumal Dheepthi , Golub Victoria , Habib Andy , Kuruba Ramkumar , Wu Xin
Published: March 2020

Objective

Organophosphates (OPs) such as diisopropylfluorophosphate (DFP) and soman are lethal chemical agents that can produce seizures, refractory status epilepticus (SE), and brain damage. There are few optimal treatments for late or refractory SE. Phenobarbital is a second‐line drug for SE, usually after lorazepam, diazepam, or midazolam have failed to stop SE. Practically, 40 minutes or less is often necessary for first responders to arrive and assist in a chemical incident. However, it remains unclear whether administration of phenobarbital 40 minutes after OP intoxication is still effective. Here, we investigated the efficacy of phenobarbital treatment at 40 minutes postexposure to OP intoxication.

Methods

Acute refractory SE was induced in rats by DFP injection as per a standard paradigm. After 40 minutes, subjects were given phenobarbital intramuscularly (30‐100 mg/kg) and progression of seizure activity was monitored by video‐EEG recording. The extent of brain damage was assessed 3 days after DFP injections by neuropathology analysis of neurodegeneration and neuronal injury by unbiased stereology.

Results

Phenobarbital produced a dose‐dependent seizure protection. A substantial decrease in SE was evident at 30 and 60 mg/kg, and a complete seizure termination was noted at 100 mg/kg within 40 minutes after treatment. Neuropathology findings showed significant neuroprotection in 100 mg/kg cohorts in brain regions associated with SE. Although higher doses resulted in greater protection against refractory SE and neuronal damage, they did not positively correlate with improved survival rate. Moreover, phenobarbital caused serious adverse effects including anesthetic or comatose state and even death.

Significance

Phenobarbital appears as an alternate anticonvulsant for OP‐induced refractive SE in hospital settings. A careful risk‐benefit analysis is required because of negative outcomes on survival and cardio‐respiratory function. However, the need for sophisticated support and critical monitoring in hospital may preclude its use as medical countermeasure in mass casualty situations.
Long‐term large wood load fluctuations in two low‐order streams in Southern Chile
Authors: Iroumé Andrés , Cartagena Manuel , Villablanca Luisa , Sanhueza Daniel , Mazzorana Bruno , Picco Lorenzo
Published: March 2020

The eco‐hydrogeomorphic significance of large wood (LW) and its potential for increasing downstream hazards during extreme floods have been widely recognized. We used LW data collected for a 10‐year period from the two low‐order streams of Pichún (Pi) and Vuelta de Zorra (VZ) in Southern Chile to (a) determine if the abundance and dimensions of individual LW pieces change with time, (b) quantify wood load fluctuations during the 10‐year period, and (c) assess the role of LW recruitment from the riparian forests to explain wood load fluctuations during the study period. Nine years after the first survey, the number of LW pieces in Pi and VZ diminished by 60 and 40%, respectively. Despite the reduction in these numbers, in Pi, the LW dimensions did not change significantly during the study. In VZ, the dimensions exhibited statistically significant differences, despite being within the same class. In both catchments, the LW load fluctuated during a 10‐year period, but the drivers of change differed. Although tree toppling was the recruitment mechanism responsible for LW in both stream cases, the high wood load measured in Pi at the beginning of the study suggested massive tree recruitments before the first survey, followed by wood exports which were higher than inputs in the subsequent 10‐year period. In VZ, LW load decreased during the first 9 years (mean annual rate of ~9.2 m3 year−1) and then increased by ~12.1 m3 year−1 in year 10. At VZ, the inputs consisted of single trees that were recruited from the riparian area and by upstream flotation, while exports occurred by downstream fluvial transport. Wood inputs and exports occurred asynchronously and led to LW load fluctuations at decadal and annual intervals. Land management and tree species thus exert a major influence on wood inventory and budget in streams. © 2020 John Wiley & Sons, Ltd.
Experimental investigation on the influence of annular pool shape characteristics on n‐heptane ring fires
Authors: Li Cong , Yang Rui , Li Chengwu , Zhang Hui
Published: March 2020

The ring fire usually originates from the combustion of the annular‐distributed fuel, and it may occur in the low‐temperature environments such as the Arctic area and plateau area, which is kind of different from the conventional environment. In this paper, the annular pools with various shape characteristics were designed. The outside diameter ranged from 14.9 to 30.0 cm, the inside diameter increased from 0 to 24.5 cm, and the diameter ratio was from 0 to 0.858. A series of n‐heptane ring fire experiments were carried out. The results showed that for the annular pools with the same outside diameter, the mass loss rate (MLR) per unit area presents a piecewise trend with the diameter ratio. When the diameter ratio increases from 0 to 0.7, the MLR per unit area increases linearly because of the domination of air entrainment effect. When the diameter ratio is larger than 0.7, the MLR per unit area is independent of the annular shape due to the strong heat dissipation effect. Finally, a parameter named the outside circumference per unit area is put forward to characterize the annular pool. A corrected pressure modeling is established to normalize the ring fire with various shape characteristics.
A multipoint flux approximation with diamond stencil finite volume scheme for the two‐dimensional simulation of fluid flows in naturally fractured reservoirs using a hybrid‐grid method
Authors: Cavalcante Túlio de M. , Contreras Fernando Raul L. , Lyra Paulo R. M. , de Carvalho Darlan Karlo E.
Published: March 2020

Two‐phase flows of oil and water in naturally fractured reservoirs can be described by a system of nonlinear partial differential equations that comprises of an elliptic pressure equation and hyperbolic saturation equation coupled through the total velocity field. Modeling this problem is a great challenge, due to the complexity of the depositional environments, including inclined layers and fractures with different sizes and shapes, and random spatial distribution. In this work, to solve the pressure equation, we adopted a cell‐centered finite‐volume method with a multipoint flux approximation that uses the “diamond stencil” (MPFA‐D) coupled with a hybrid‐grid method (HyG) to deal with the fractures. The classical first‐order upwind method was used to solve the saturation equation, in its explicit and implicit versions. The MPFA‐D is a very robust and flexible formulation that is capable of handling highly heterogeneous and anisotropic domains using general polygonal meshes. In the strategy developed in this work, the mesh that discretize the domain must fit the spatial position of the fractures, so that they are associated to the control surfaces—as (n − 1)D cells—therefore, the calculation of the fluxes in these control surfaces is dependent on the pressures on fractures and on the adjacent volumes. In HyG, the fractures are expanded to nD in the computational domain. The proposed formulation presented quite remarkable results when compared with similar formulations using classical full pressure support and triangle pressure support methods, or even the with MPFA‐D itself when the fractures are treated as nD geometric entities.
Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: A sequential causal mediation analysis
Authors: Dashti S. Ghazaleh , Viallon Vivian , Simpson Julie A. , Karahalios Amalia , Moreno‐Betancur Margarita , English Dallas R. , Gunter Marc J. , Murphy Neil
Published: March 2020

Mechanisms underlying adiposity–colorectal cancer (CRC) association are incompletely understood. Using UK Biobank data, we investigated the role of C‐reactive protein (CRP), hemoglobin‐A1c (HbA1c) and (jointly) sex hormone‐binding globulin (SHBG) and testosterone, in explaining this association. Total effect of obesity versus normal‐weight (based on waist circumference, body mass index, waist–hip ratio) on CRC risk was decomposed into natural direct (NDE) and indirect (NIE) effects using sequential mediation analysis. After a median follow‐up of 7.1 years, 2070 incident CRC cases (men = 1,280; postmenopausal women = 790) were recorded. For men, the adjusted risk ratio (RR) for waist circumference (≥102 vs. ≤94 cm) was 1.37 (95% confidence interval [CI], 1.19–1.58). The RRsNIE were 1.08 (95% CI: 1.01–1.16) through all biomarkers, 1.06 (95% CI: 1.01–1.11) through pathways influenced by CRP, 0.99 (95% CI: 0.97–1.01) through HbA1c beyond (the potential influence of) CRP and 1.03 (95% CI: 0.99–1.08) through SHBG and testosterone combined beyond CRP and HbA1c. The RRNDE was 1.26 (95% CI: 1.09–1.47). For women, the RR for waist circumference (≥88 vs. ≤80 cm) was 1.27 (95% CI: 1.07–1.50). The RRsNIE were 1.08 (95% CI: 0.94–1.22) through all biomarkers, 1.08 (95% CI: 0.99–1.17) through CRP, 1.00 (95% CI: 0.98–1.02) through HbA1c beyond CRP and 1.00 (95% CI: 0.92–1.09) through SHBG and testosterone combined beyond CRP and HbA1c. The RRNDE was 1.18 (95% CI: 0.96–1.45). For men and women, pathways influenced by CRP explained a small proportion of the adiposity‐CRC association. Testosterone and SHBG also explained a small proportion of this association in men. These results suggest that pathways marked by these obesity‐related factors may not explain a large proportion of the adiposity‐CRC association.
Molecular diagnosis of alpha1‐antitrypsin deficiency: A new method based on Luminex technology
Authors: Ottaviani Stefania , Barzon Valentina , Buxens Amaya , Gorrini Marina , Larruskain Amaia , El Hamss Rachid , Balderacchi Alice M. , Corsico Angelo G. , Ferrarotti Ilaria
Published: March 2020

Background

Alpha1‐antitrypsin deficiency (AATD) is an under‐diagnosed hereditary disorder characterized by reduced serum levels of alpha1‐antitrypsin (AAT) and increased risk to develop lung and liver diseases at an early age. AAT is encoded by the highly polymorphic SERPINA1 gene. The most common deficiency alleles are S and Z, but more than 150 rare variants lead to low levels of the protein. To identify these pathological allelic variants, sequencing is required. Since traditional sequencing is expensive and time‐consuming, we evaluated the accuracy of A1AT Genotyping Test, a new diagnostic genotyping kit which allows to simultaneously identify and genotype 14 deficiency variants of the SERPINA1 gene based on Luminex technology.

Methods

A total of 418 consecutive samples with AATD suspicion and submitted to the Italian Reference laboratory between January and April 2016 were analyzed both by applying the diagnostic algorithm currently in use, and by applying A1AT Genotyping Test.

Results

The assay gave the following results: 101 samples (24.2%) were positive for at least one of the 14 deficiency variants, 316 (75.6%) were negative for all the variants analyzed. The identified mutations showed a 100% correlation with the results obtained with our diagnostic algorithm. Seventeen samples (4%) resulted negative for the assay but sequencing identified other rare pathological variants in SERPINA1 gene.

Conclusion

The A1AT Genotyping Test assay was highly reliable and robust and allowed shorter diagnostic times. In few cases, it has been necessary to sequence the SERPINA1 gene to identify other rare mutations not included in the kit.
Quercetin prevents alterations of behavioral parameters, delta‐aminolevulinic dehydratase activity, and oxidative damage in brain of rats in a prenatal model of autism
Authors: de Mattos Bruna da Silveira , Soares Mayara Sandrielly Pereira , Spohr Luiza , Pedra Nathalia Stark , Teixeira Fernanda Cardoso , de Souza Anita Avila , Stefanello Francieli Moro , Baldissarelli Jucimara , Gamaro Giovana Duzzo , Spanevello Roselia Maria
Published: March 2020

Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, and VPA+quercetin). Quercetin (50 mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40 days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders (ASDs).
Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa
Authors: Sher Rebecca , Dlamini Sipho , Muloiwa Rudzani
Published: March 2020

Introduction

Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa.

Methods

We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years.

Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospital HIV Clinic for at least 24 months between 2002 and 2016.

The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow‐up period.

Results and discussion

Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow‐up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens.

Total follow‐up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overall time with detectable VL was 370 PY. This comprised 22% of total follow‐up time, and 42% of the follow‐up time contributed by those who experienced detectable VL.

The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001).

There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL.

Conclusions

Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre‐empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state.
Matter–wave interference and deflection of tripeptides decorated with fluorinated alkyl chains
Authors: Schätti Jonas , Köhler Valentin , Mayor Marcel , Fein Yaakov Y. , Geyer Philipp , Mairhofer Lukas , Gerlich Stefan , Arndt Markus
Published: March 2020

Studies of neutral biomolecules in the gas phase allow for the study of molecular properties in the absence of solvent and charge effects, thus complementing spectroscopic and analytical methods in solution or in ion traps. Some properties, such as the static electronic susceptibility, are best accessed in experiments that act on the motion of the neutral molecules in an electric field. Here, we screen seven peptides for their thermal stability and electron impact ionizability. We identify two tripeptides as sufficiently volatile and thermostable to be evaporated and interfered in the long‐baseline universal matter‐wave interferometer. Monitoring the deflection of the interferometric molecular nanopattern in a tailored external electric field allows us to measure the static molecular susceptibility of Ala–Trp–Ala and Ala–Ala–Trp bearing fluorinated alkyl chains at C‐ and N‐termini. The respective values are
and
.