bluuebunny/crossref_metadata_2025 huggingface dataset:
Wavelength‐Gated Photochemical Synthesis of Phenalene Diimides
Authors: Feist Florian , Walden Sarah L. , Alves Jessica , Kunz Susanna V. , Micallef Aaron S. , Brock Aidan J. , McMurtrie John C. , Weil Tanja , Blinco James P. , Barner‐Kowollik Christopher
Published: February 2021

Herein, we pioneer a wavelength‐gated synthesis route to phenalene diimides. Consecutive Diels–Alder reactions of methylisophthalaldehydes and maleimides afford hexahydro‐phenalene‐1,6‐diol diimides via 5‐formyl‐hexahydro‐benzo[f]isoindoles as the intermediate. Both photoreactions are efficient (82–99 % yield) and exhibit excellent diastereoselectivity (62–98 % d.r.). The wavelength‐gated nature of the stepwise reaction enables the modular construction of phenalene diimide scaffolds by choice of substrate and wavelength. Importantly, this synthetic methodology opens a facile avenue to a new class of persistent phenalenyl diimide neutral radicals, constituting a versatile route to spin‐active molecules.
A bio‐inspired gelatin‐based pH‐ and thermal‐sensitive magnetic hydrogel for in vitro chemo/hyperthermia treatment of breast cancer cells
Authors: Derakhshankhah Hossein , Jahanban‐Esfahlan Rana , Vandghanooni Somayeh , Akbari‐Nakhjavani Sattar , Massoumi Bakhshali , Haghshenas Babak , Rezaei Aram , Farnudiyan‐Habibi Amir , Samadian Hadi , Jaymand Mehdi
Published: February 2021

Gelatin (Gel)‐based pH‐ and thermal‐responsive magnetic hydrogels (MH‐1 and MH‐2) were designed and developed as novel drug delivery systems (DDSs) for cancer chemo/hyperthermia therapy. For this goal, Gel was functionalized with methacrylic anhydride (GelMA), and then copolymerized with (2‐dimethylaminoethyl) methacrylate (DMAEMA) monomer in the presence of methacrylate‐end capped magnetic nanoparticles (MNPs) as well as triethylene glycol dimethacrylate (TEGDMA; as crosslinker). Afterward, a thiol‐end capped poly(N‐isopropylacrylamide) (PNIPAAm‐SH) was synthesized through an atom transfer radical polymerization technique, and then attached onto the hydrogel through “thiol‐ene” click grafting. The preliminary performances of developed MHs for chemo/hyperthermia therapy of human breast cancer was investigated through the loading of doxorubicin hydrochloride (Dox) as an anticancer agent followed by cytotoxicity measurement of drug‐loaded DDSs using MTT assay by both chemo‐ and chemo/hyperthermia‐therapies. Owing to porous morphologies of the fabricated magnetic hydrogels according to scanning electron microscopy images and strong physicochemical interactions (e.g., hydrogen bonding) the drug loading capacities of the MH‐1 and MH‐2 were obtained as 72 ± 1.4 and 77 ± 1.8, respectively. The DDSs exhibited acceptable pH‐ and thermal‐triggered drug release behaviors. The MTT assay results revealed that the combination of hyperthermia therapy and chemotherapy has synergic effect on the anticancer activities of the developed DDSs.
Gene–environment interactions between air pollution and biotransformation enzymes and risk of birth defects
Authors: Padula Amy M. , Yang Wei , Schultz Kathleen , Lee Cecilia , Lurmann Fred , Hammond S. Katharine , Shaw Gary M.
Published: February 2021

Genetic and environmental factors have been observed to influence risks for birth defects, though few studies have investigated gene–environment interactions. Our aim was to examine the interaction terms of gene variants in biotransformation enzyme pathways and air pollution exposures in relation to risk of several structural birth defects. We evaluated the role of ambient air pollutant exposure (nitrogen dioxide [NO2], nitrogen oxide, carbon monoxide, particulate matter <10 [PM10] and <2.5 [PM2.5] microns) during pregnancy and 104 gene variants of biotransformation enzymes from infant bloodspots or buccal cells in a California population‐based case–control study in 1997–2006. Cases included cleft lip with or without cleft palate (N = 206), gastroschisis (N = 94), tetralogy of Fallot (N = 69), and dextro‐transposition of the great arteries (d‐TGA; N = 40) and were compared to 208 nonmalformed controls. Overall, the results were not consistent, though did highlight some associations for further investigation as indicated by Wald chi‐square test p value <.1. Increased risk of cleft lip was associated with exposure to high PM10 and two CYP gene variants. High PM2.5 and the variant of SLCO1B1 was associated with increased risk of teratology of Fallot. Higher NO2 and two gene variants, CYP2A6 and SLC01B1, were associated with increased risk of d‐TGA. Results for gastroschisis were inconsistent in direction and across pollutants. These exploratory results suggest that some individuals based on their genetic background may be more susceptible to the adverse effects of air pollution.
Taking “the boss” into the real world: Field interrater reliability of the Short‐Term Assessment of Risk and Treatability: Adolescent Version
Authors: De Beuf Tamara L. F. , de Ruiter Corine , Edens John F. , de Vogel Vivienne
Published: February 2021

There is emerging evidence that the performance of risk assessment instruments is weaker when used for clinical decision‐making than for research purposes. For instance, research has found lower agreement between evaluators when the risk assessments are conducted during routine practice. We examined the field interrater reliability of the Short‐Term Assessment of Risk and Treatability: Adolescent Version (START:AV). Clinicians in a Dutch secure youth care facility completed START:AV assessments as part of the treatment routine. Consistent with previous literature, interrater reliability of the items and total scores was lower than previously reported in non‐field studies. Nevertheless, moderate to good interrater reliability was found for final risk judgments on most adverse outcomes. Field studies provide insights into the actual performance of structured risk assessment in real‐world settings, exposing factors that affect reliability. This information is relevant for those who wish to implement structured risk assessment with a level of reliability that is defensible considering the high stakes.
Pre‐transplantation cytoreduction does not benefit advanced myelodysplastic syndrome patients after myeloablative transplantation with grafts from family donors
Authors: Sun Yu‐Qian , Xu Lan‐Ping , Liu Kai‐Yan , Zhang Xiao‐Hui , Yan Chen‐Hua , Jin Jian , Huang Xiao‐Jun , Wang Yu
Published: February 2021

Background

The role of pre‐hematopoietic stem cell transplantation (HSCT) cytoreduction with either induction chemotherapy (IC) or hypomethylating agents (HMAs) in treating advanced myelodysplastic syndrome (MDS) remains debatable. We aimed to evaluate pre‐HSCT strategies by comparing the endpoints related to disease control between advanced MDS patients with pre‐HSCT cytoreduction and those with best supportive care.

Methods

We described 228 consecutive advanced MDS patients who received HSCT from a haploidentical donor (HID, n = 162) or matched related donor (MSD, n = 66) with uniform myeloablative conditioning regimens between January 2015 and December 2018. Of these 228 patients, 131 (57.5%) were treated exclusively with pre‐HSCT best supportive care (BSC), 49 (22.5%) were given HMA, and 48 (21.1%) received both IC and HMA. Propensity score‐matching analysis, multivariate analyses, and subgroup analyses were performed to elucidate the impact of pre‐HSCT strategies on transplant outcomes.

Results

The 3‐year relapse‐free survival (RFS) rates were 78.2% and 70.0% for the BSC and cytoreduction cohorts (P = 0.189) and were 78.2%, 66.7%, and 73.2% for the BSC, HMA, and HMA+IC groups, respectively (P = 0.269). A propensity score‐matching analysis confirmed that the 3‐year RFS rates were 81.9%, 87.5%, and 66.9% for BSC, cytoreduction complete remission (CR), and cytoreduction non‐CR groups, respectively (P = 0.051). Multivariate analyses demonstrated that pre‐HSCT cytoreduction, older patient age, monosomal karyotype, and interval between diagnosis and HSCT were poor prognostic factors for RFS. In the subgroup analyses, BSC was associated with longer RFS compared to cytoreduction among the younger patients, those with international prognostic scoring system intermediate‐2/high risk at diagnosis, and those with intermediate/poor cytogenetics.

Conclusions

Different pre‐HSCT therapies did not yield discrepant post‐HSCT outcomes. No benefit in terms of post‐HSCT outcomes were correlated with pre‐HSCT cytoreduction in advanced MDS even for cytoreduction CR patients. Early referral to HSCT is essential for advanced MDS patients.
Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma
Authors: Hagiwara Sumitaka , Sasaki Eiichi , Hasegawa Yasuhisa , Suzuki Hidenori , Nishikawa Daisuke , Beppu Shintaro , Terada Hoshino , Sawabe Michi , Takahashi Masahide , Hanai Nobuhiro
Published: February 2021

Background

Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC).

Methods

The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme‐linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed.

Results

The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis‐positive and stage IV disease, in comparison to those with node metastasis‐negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse‐free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels.

Conclusions

The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.
DNA‐Targeted Metallodrugs: An Untapped Source of Artificial Gene Editing Technology
Authors: Fantoni Nicolò Zuin , Brown Tom , Kellett Andrew
Published: February 2021

DNA binding metal complexes are synonymous with anticancer drug discovery. Given the array of structural and chemical reactivity properties available through careful design, metal complexes have been directed to bind nucleic acid structures through covalent or noncovalent binding modes. Several recognition modes – including crosslinking, intercalation, and oxidation – are central to the clinical success of broad‐spectrum anticancer metallodrugs. However, recent progress in nucleic acid click chemistry coupled with advancement in our understanding of metal complex–nucleic acid interactions has opened up new avenues in genetic engineering and targeted therapies. Several of these applications are enabled by the hybridisation of oligonucleotide or polyamine probes to discrete metal complexes, which facilitate site‐specific reactivity at the nucleic acid interface under the guidance of the probe. This Review focuses on recent advancements in hybrid design and, by way of an introduction to this topic, we provide a detailed overview of nucleic acid structures and metal complex–nucleic acid interactions. Our aim is to provide readers with an insight on the rational design of metal complexes with DNA recognition properties and an understanding of how the sequence‐specific targeting of these interactions can be achieved for gene engineering applications.
Liquid film thickness of two‐phase slug flows in capillary microchannels: A review paper
Authors: Etminan Amin , Muzychka Yuri S. , Pope Kevin
Published: February 2021

Two‐phase Taylor flow has received considerable attention from researchers in recent decades due to its potential use in a wide variety of industrial and medical applications. A large number of experimental, analytical, and numerical efforts have been taken by researchers to understand the fundamental characteristics of two‐phase flows and the relevant transport phenomena. This paper presents a comprehensive review of the hydrodynamics, flow pattern, and liquid film thickness in two‐phase flows through mini‐ and microchannels with different cross‐sectional geometry. This paper also reviews correlations that predict liquid film thickness in microchannels for gas‐liquid and liquid‐liquid flows. The variations of liquid film thickness are plotted over a wide range of capillary numbers for both experimental and computational studies. This study shows that the effects of cross‐sectional area on the flow patterns and flow characteristics have not been sufficiently investigated by researchers, particularly for rectangular cross‐sectional areas with different aspect ratios.
Genetic‐based multi‐objective optimization of alkylation process by a hybrid model of statistical and artificial intelligence approaches
Authors: Mahmoudian Farimah , Moghaddam Amin Hedayati , Davachi Seyed Mohammad
Published: February 2021

The purpose of this research is to find the optimal operating point in the production process of the cumene. Therefore, the production process was optimized through statistical and genetic algorithm‐based methods. The performance of an alkylation reactor was optimized through maximizing the yield of cumene production. Response surface methodology (RSM) with design type of central composite was applied for design of experiment, modelling, and optimizing the process. The analysis of variance (ANOVA) was performed for finding the important operative parameters as well as their effects. The effects of three parameters including temperature, reactor length, and pressure on the alkylation process were investigated. Further, two types of feed‐forward neural network were applied to model the alkylation reactor. To develop the neural network model, leave‐one‐out method was used. The best prediction performance belonged to a fitting network with 2 and 8 neurons in the hidden layer, respectively. This model was used for optimizing the performance of the alkylation reactor. The statistical and artificial intelligence systems were capable of prediction of cumene production yield in different conditions with R2 of 0.9098 and 0.9986, respectively. Genetic algorithm‐based optimization was performed by the developed neural network model. The maximum accessible value of cumene production yield was 0.7771, which can be achieved when the temperature, length of reactor, and column pressure are 160°C, 2 m, and 4000 kPa, respectively. By finding the optimal operating point in the cumene production process, capital cost, energy consumption, and other operating costs can be significantly reduced.
Alkoxyl side‐chain effects of acidic ionic liquids catalysts for the esterification of n‐butyl butyrate
Authors: Feng Xiantao , Wang Qiannan , Wang Mengyang , Liu Liang
Published: February 2021

Three kinds of alkoxy group‐functionalized acidic ionic liquids (ILs) are reported in this work, namely, 1‐(methoxyethyl)‐3‐methylimidazolium hydrogen sulphate [MOE‐MIM]HSO4, 1‐(ethyoxyethyl)‐3‐methylimidazolium hydrogen sulphate [EOE‐MIM]HSO4, and 1‐(propyoxyethyl)‐3‐methylimidazolium hydrogen sulphate [POE‐MIM]HSO4. The short side chain on the cation of [MOE‐MIM]HSO4decreases the solubility of the IL in butanol and butyric acid and facilitates the separation of the IL from a reaction medium. The yield of butyl butyrate is up to 99.5%. After 10 rounds of recycling, the catalytic performance of [MOE‐MIM]HSO4shows no significant changes.
Prediction and analysis of thermal‐hydraulic performance of tubes with teardrop dimples based on artificial neural networks
Authors: Lei Xiang‐shu , Li Jin‐bo , Qi Xin , Liu Ying‐wen
Published: February 2021

In this study, the prediction and analysis of the thermal‐hydraulic performance of tubes with teardrop dimples were carried out. First, a numerical model of dimpled tubes using ANSYS 17.0 was established and verified by comparison with the Nusselt number (Nu) and friction factor (f) in the literature. Second, artificial neural networks (ANNs) were developed with five neurons in the input layer, the hidden layers of various neurons, and one neuron in the output layer. The five neurons are the diameter of the windward sphere (d1), diameter of the leeward sphere (d2), dimple depth (hd), spacing between two axially adjacent dimples (l), and quantity of dimples in a transverse cross‐section (N). After careful comparison, the model with the 5‐2‐6‐1 structure was selected for predicting both f and Nu, while the model with the 5‐6‐1 structure was selected for performance evaluation criteria (PEC). Finally, the influence of d2/d1 on the heat transfer and pressure drop is discussed when l/d1 or N changes. The results showed when N is moderate or l/d1 is large within the scope of the design, the heat transfer performance in the windward part of the teardrop dimples is better than that of the spherical dimples. In addition, as N increases or l/d1 decreases, the influence of dimples on the main flow increases, making the mixture of hot and cold working fluid better but causing a greater pressure drop. This study may provide ideas and guidance for the design, selection, and optimization of dimpled tubes.
Root coverage stability: A systematic overview of controlled clinical trials with at least 5 years of follow‐up
Authors: Bertl Kristina , Spineli Loukia M. , Mohandis Khalid , Stavropoulos Andreas
Published: February 2021

Objectives

To systematically assess the long‐term outcome (≥5 years) of root coverage procedures reported in controlled clinical trials.

Material and Methods

Literature search was performed according to the PRISMA guidelines with the following eligibility criteria: (a) English or German language; (b) controlled (CT) or randomised controlled clinical trials (RCT); (c) root coverage procedure with ≥5 years follow‐up; and (d) clinical treatment effect size and/or patient‐related outcome measures (PROMs) reported.

Results

Four CT and 14 RCT with a follow‐up of 5–20 years fulfilled the eligibility criteria; sample size per study ranged from 8 to 70 patients contributing with 18–149 sites. Coronally advanced flap (CAF) and CAF + connective tissue graft (CTG) were the prevalent treatments (i.e., in 24 and 38% of the groups, respectively), while other flap designs and adjuncts (i.e., enamel matrix derivative, bone graft, collagen membrane) were represented only once. For single Miller class I/II gingival recessions (GR), CAF + CTG appeared advantageous compared to other techniques, and provided low residual recession depths (i.e., ≤0.5 mm), and complete root coverage in ≥2/3 of the patients; similar tendency was observed for multiple GR. No data on Miller class III/IV GR is available. No meta‐analysis was feasible due to lack of similarity in the clinical and methodological characteristics across the trials and observed comparisons of interventions.

Conclusions

CAF + CTG appears to be the ‘gold standard’ technique for the treatment of single and multiple Miller class I/II GR also in regard to long‐term (i.e., ≥5 years of follow‐up) treatment outcomes. There is little information regarding the performance, on the long‐term, of other techniques and adjuncts.
Kernel weight responses to the photothermal environment in maize dent × flint and flint × flint hybrids
Authors: Hisse Ignacio R. , D’Andrea Karina E. , Otegui María E.
Published: February 2021

Maize (Zea mays L.) grain yield is assumed to be source limited during the flowering period but sink limited during grain growth; however, environmental restrictions during active grain filling may strongly affect final kernel weight (KW). In this study, we evaluated the effect of natural changes in photothermal conditions during lag phase (LP) and effective grain‐filling period (EGFP) on KW, its physiological determinants, and the post‐flowering source–sink relationships of flint and semident germplasm. F1 hybrids of flint × flint and dent × flint background were tested during four seasons (Y1, Y2, Y3, and Y4). Across years, the highest KW (286 mg) was obtained under the maximum photothermal quotients during LP (PTQLP = 1.18 MJ m−2 °C−1) and EGFP (PTQEGFP = 1.07 MJ m−2 °C−1) of Y2, whereas the smallest KW (252 mg) and source–sink ratio during grain filling was obtained under the lowest PTQEGFP (.79 MJ m−2 °C−1) of Y3. Supra‐optimum temperatures during LP of Y3 negatively affected potential KW determination, and hence kernel growth rate (P < .001) as a result of reduced assimilate availability per kernel. Hybrids dent × flint exhibited higher grain yield, kernel number, and plant growth around flowering than flint × flint throughout evaluated seasons but had reduced source–sink relationship during grain filling (P < .05) and increased KW sensitivity (P < .001) to changes in the photothermal conditions. Results emphasized the importance of the photothermal environment during grain filling on KW determination (particularly for seasons with great photothermal imbalance between filling subphases) as well as the dependency of KW responses on the genetic background.
Asymmetrical multilevel inverter topology with low total standing voltage and reduced switches count
Authors: Arif M. Saad Bin , Sarwer Zeeshan , Siddique Marif Daula , Md. Ayob Shahrin , Iqbal Atif , Mekhilef Saad
Published: February 2021

This paper presented an improved asymmetrical multilevel inverter module with reduced switches count. The basic module is capable of producing 15 level outputs with four dc sources and 10 switches. The proposed topology has an inherent ability to generate negative voltage levels, made it possible to utilize lower rating switches, and has lower total standing voltage. To have more number of levels, a series‐connected cascade extension of the module has been done. The three different algorithms for selecting the magnitude of dc sources are proposed. The generalized relations for different parameters are based on the number of added basic units and the number of presented levels for each source selection algorithm. Nearest level control (NLC) is used as the modulation technique. A comparative study shows that the developed topology outperformed other selected existing topologies on many parameters. The performance of the module is evaluated through detailed simulation and power loss analysis. Accuracy of the obtained simulation results is validated through proper experimental testing of the circuit in the laboratory.
A quick approach for medetomidine enantiomer determination in dog plasma by chiral liquid chromatography–tandem mass spectrometry and application to a pharmacokinetic study
Authors: Bardhi Anisa , Zaghini Anna , Levionnois Olivier , Barbarossa Andrea
Published: February 2021

In the present study, a rapid, sensitive and high‐throughput liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of medetomidine enantiomers in dog plasma was developed and validated. The separation and individual quantification of chiral compounds can be a tricky task in LC. This is particularly true when target analytes have a relatively small mass, as is the case with medetomidine, a potent and highly specific α2‐adrenoceptor agonist widely used in both human and veterinary medicine. The proposed approach is based on a quick liquid–liquid extraction with ethyl acetate and filtration prior to injection. The optimized mobile phase composition allowed to perfectly separate the two enantiomers of medetomidine in a short chromatographic run time, using a cellulose tris(4‐methylbenzoate)‐based chiral column. A lower limit of quantification of 0.1 ng/mL was reached for both analytes thanks to the high sensitivity and selectivity of MS/MS and the use of racemic medetomidine‐d3 as internal standard prevented potential matrix effect. Linearity was satisfying (R2 > 0.99) over the range 0.1–25 ng/mL, as well as within‐ and between‐session accuracy and precision, both always <15%. This method was also applied with success to a series of samples from a pharmacokinetic (PK) study aimed at comparing dex‐ and levomedetomidine behaviour after administration of the racemic mixture in dogs. The simple extraction procedure, which allows reduced solvent and time consumption without compromising analytical performances, makes this technique a useful tool for this kind of applications even when small animals are involved, due to the small amount of sample required.
First phylogenetic analysis of Dryophthorinae (Coleoptera, Curculionidae) based on structural alignment of ribosomal DNA reveals Cenozoic diversification
Authors: Chamorro Maria Lourdes , de Medeiros Bruno A. S. , Farrell Brian D.
Published: February 2021

Dryophthorinae is an economically important, ecologically distinct, and ubiquitous monophyletic group of pantropical weevils with more than 1,200 species in 153 genera. This study provides the first comprehensive phylogeny of the group with the aim to provide insights into the process and timing of diversification of phytophagous insects, inform classification and facilitate predictions. The taxon sampling is the most extensive to date and includes representatives of all five dryophthorine tribes and all but one subtribe. The phylogeny is based on secondary structural alignment of 18S and 28S rRNA totaling 3,764 nucleotides analyzed under Bayesian and maximum likelihood inference. We used a fossil‐calibrated relaxed clock model with two approaches, node‐dating and fossilized birth‐death models, to estimate divergence times for the subfamily. All tribes except the species‐rich Rhynchophorini were found to be monophyletic, but higher support is required to ascertain the paraphyly of Rhynchophorini with more confidence. Nephius is closely related to Dryophthorini and Stromboscerini, and there is strong evidence for paraphyly of Sphenophorina. We find a large gap between the divergence of Dryophthorinae from their sister group Platypodinae in the Jurassic‐Cretaceous boundary and the diversification of extant species in the Cenozoic, highlighting the role of coevolution with angiosperms in this group.
A geographical perspective on the relationship between Impatiens spur lengths and bill lengths of sunbirds in Afrotropical mountains
Authors: Hořák David , Janeček Štěpán
Published: February 2021

Trait matching—a correlation between the morphology of plants and their pollinators—has been frequently observed in pollination interactions. Different intensities of natural selection in individual regions should cause such correlations to be observable across different local assemblages. In this study, we focused on matching between spur lengths of the genus Impatiens and bill lengths of sunbirds in tropical Africa. For 25 mountain and island locations, we compiled information about the composition and traits of local Impatiens and sunbird assemblages. We found that assemblage mean and maximum values of bill lengths were positively correlated with mean and maximum spur lengths across locations. Moreover, our results suggest that the positive correlations hold only for forest sunbird assemblages sharing the same habitat with Impatiens species. We further show that long‐billed sunbirds seem to locally match the morphology of multiple Impatiens plant species, not vice versa. Our observation implies that trait matching significantly contributes to structuring of Impatiens–sunbird pollination systems. We suggest that special habitat preferences together with spatial isolation of mountain environment might play a role in this case.
Sensitivity of productivity to precipitation amount and pattern varies by topographic position in a semiarid grassland
Authors: Hoover David L. , Lauenroth William K. , Milchunas Daniel G. , Porensky Lauren M. , Augustine David J. , Derner Justin D.
Published: February 2021

Aboveground net primary productivity (ANPP) in grasslands is an important integrator of terrestrial ecosystem function, a key driver of global biogeochemical cycles, and a critical source of food for wild and domesticated herbivores. ANPP exhibits high spatial and temporal variability, driven by a suite of factors including precipitation amount and pattern, biotic and abiotic legacies, and topographic heterogeneity. Global climate models forecast an altered hydrological cycle due to climate change, including higher precipitation variability and more extreme events, which may further increase spatiotemporal variability in ANPP. Therefore, it is essential to understand the sensitivity of this central ecosystem function to various precipitation metrics, legacies, and topographic positions to better inform sustainable grassland management. In this study, we analyzed long‐term (36‐yr) ANPP data collected across a topographic sequence in the semiarid shortgrass steppe of North America to examine patterns and drivers of spatiotemporal variability in ANPP. We observed that (1) ANPP varied substantially by topographic position, with greater divergence during years with high production, (2) ANPP variability was higher temporally (16‐fold maximum difference across years) than spatially (4‐fold maximum difference across topographic positions), (3) warm‐season perennial grasses were the dominant plant functional type across all topographic positions and strongly influenced total ANPP dynamics, and (4) ANPP had strong sensitivities to current year precipitation amount and pattern that varied by plant functional type, as well as weaker sensitivities to precipitation and productivity legacies. Overall, the lowest topographic position had the highest sensitivity to precipitation, likely due to higher resource availability via the downhill movement of water and nutrients during years with high precipitation and large rainfall events. These results suggest that temporal and spatial ANPP variability in shortgrass steppe is primarily driven by the combined effects of precipitation amount and pattern during the current year, with the dominant warm‐season perennial grasses governing these responses.
Resolving trained immunity with systems biology
Authors: Koeken Valerie A.C.M. , van Crevel Reinout , Netea Mihai G. , Li Yang
Published: February 2021

Trained immunity is characterized by long‐term functional reprogramming of innate immune cells following challenge with pathogens or microbial ligands during infection or vaccination. This cellular reprogramming leads to increased responsiveness upon restimulation, and is mediated through epigenetic and metabolic modifications. In this review, we describe how molecular mechanisms underlying trained immunity, for example, induced by β‐glucan or Bacille Calmette‐Guérin (BCG) vaccination, can be investigated by using and integrating different layers of information including genome, epigenome, transcriptome, proteome, metabolome, microbiome, immune cell phenotyping, and function. We also describe the most commonly used experimental and computational techniques. Finally, we provide a number of examples of how a systems biology approach was applied to study trained immunity to understand interindividual variation or the complex interplay between molecular layers. In conclusion, trained immunity represents an opportunity for regulating innate immune function, and understanding the complex interplay of mechanisms that mediate trained immunity might enable us to employ it as a clinical tool in the future.
Mobilization of electroosmotic flow markers in capillary zone electrophoresis
Authors: Martínková Eva , Křížek Tomáš , Kubíčková Anna , Coufal Pavel
Published: February 2021

UV‐absorbing neutral substances are commonly used as markers of mean electroosmotic flow in capillary electrophoresis for their zero electrophoretic mobility in an electric field. However, some of these markers can interact with background electrolyte components and migrate at a different velocity than the electroosmotic flow. Thus, we tested 11 markers primarily varying in their degree of methylation and type of central atom in combination with five background electrolyte cations differing in their ionic radii and surface charge density, measuring the relative electrophoretic mobility using thiourea as a reference marker. Our results from this set of experiments showed some general trends in the mobilization of the markers based on the effects of marker structure and type of background electrolyte cation on the relative electrophoretic mobility. As an example, the effects of an inadequate choice of marker on analyte identification were illustrated in the electrophoretic separation of glucosinolates. Therefore, our findings may help electrophoretists appropriately select electroosmotic flow markers for various electrophoretic systems.
Harnessing Joule heating in microfluidic thermal gel electrophoresis to create reversible barriers for cell enrichment
Authors: Cornejo Mario A. , Linz Thomas H.
Published: February 2021

Gel electrophoresis is a ubiquitous bioanalytical technique used to characterize the components of cell lysates. However, analyses of bulk lysates sacrifice detection sensitivity because intracellular biomolecules become diluted, and the liberation of proteases and nucleases can degrade target analytes. This report describes a method to enrich cells directly within a microfluidic gel as a first step toward online measurement of trace intracellular biomolecules with minimal dilution and degradation. Thermal gels were employed as the gel matrix because they can be reversibly converted between liquid and solid phases as a function of temperature. Rather than fabricate costly heating elements into devices to control temperature—and thus the phase of the gel—Joule heating was used instead. Adjoining regions of liquid‐phase and solid‐phase gel were formed within microfluidic channels by selectively inducing localized Joule heat. Cells migrated through the liquid gel but could not enter the solid gel—accumulating at the liquid–solid gel boundary—whereas small molecule contaminants passed through to waste. Barriers were then liquified on‐demand by removing Joule heat to collect the purified, non‐lysed cells for downstream analyses. Using voltage‐controlled Joule heating to regulate the phase of thermal gels is an innovative approach to facilitate in‐gel cell enrichment in low‐cost microfluidic devices.
Serum N‐glycan fingerprint helps to discriminate intrahepatic cholangiocarcinoma from hepatocellular carcinoma
Authors: Huang Chenjun , Xu Xuewen , Wang Mengmeng , Xiao Xiao , Cheng Cheng , Ji Jun , Fang Meng , Gao Chunfang
Published: February 2021

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are two main types of primary liver cancer, and reliable discrimination is important for optimal treatment. Aberrant glycosylation was detected in HCC and ICC. Both cross‐sectional and follow‐up studies were performed to establish a differential diagnosis model using N‐glycans. A total of 420 participants were enrolled, with 310 patients in training cohort and 110 patients in validation cohort. The follow‐up cohort was used to assess the prognosis of ICC. As the results, the diagnostic efficacy of the model was superior to alpha‐fetoprotein (AFP), carcinoembryonic antigen (CEA) and carbohydrate antigen 19‐9 (CA 19‐9) when identifying ICC from HCC (AUC of the nomogram: 0.845, 95%CI: 0.788–0.902; AFP: 0.793, 95%CI: 0.732–0.854; CEA: 0.592, 95%CI: 0.496–0.687; CA 19‐9: 0.674, 95%CI: 0.582–0.767) in training cohort. In validation cohort, this model (AUC: 0.810, 95% CI: 0.728–0.891) also demonstrated high efficacy in distinguishing ICC from HCC. Furthermore, the nomogram helps to stratify ICC into two subgroups with high or low risk of survival and recurrence. Therefore, a nomogram integrating six N‐glycans [NGA2FB(Peak2), NG1A2F (Peak3), NA2 (Peak5), NA2F (Peak6), NA3 (Peak8) and NA4 (Peak11)] was established for ICC and HCC differentiation, and for prognosis assessment in ICC patients.
Addressing neuropsychological diagnostics in adults with epilepsy: Introducing the International Classification of Cognitive Disorders in Epilepsy: The IC CODE Initiative
Authors: Norman Marc , Wilson Sarah J. , Baxendale Sallie , Barr William , Block Cady , Busch Robyn M. , Fernandez Alberto , Hessen Erik , Loring David W. , McDonald Carrie R. , Hermann Bruce P.
Published: February 2021

This paper addresses the absence of an international diagnostic taxonomy for cognitive disorders in patients with epilepsy. Initiated through the 2020 Memorandum of Understanding between the International League Against Epilepsy and the International Neuropsychological Society, neuropsychological representatives from both organizations met to address the problem and consequences of the absence of an international diagnostic taxonomy for cognitive disorders in epilepsy, overview potential solutions, and propose specific solutions going forward. The group concluded that a classification of cognitive disorders in epilepsy, including an overall taxonomy and associated operational criteria, was clearly lacking and sorely needed. This paper reviews the advantages and shortcomings of four existing cognitive diagnostic approaches, including taxonomies derived from the US National Neuropsychology Network, DSM‐V Neurocognitive Disorders, the Mild Cognitive Impairment classification from the aging/preclinical dementia literature, and the Research Domain Criteria Initiative. We propose a framework to develop a consensus‐based classification system for cognitive disorders in epilepsy that will be international in scope and be applicable for clinical practice and research globally and introduce the International Classification of Cognitive Disorders in Epilepsy (IC‐CODE) project.
A consistent sharp interface fictitious domain method for moving boundary problems with arbitrarily polyhedral mesh
Authors: Chai Guoliang , Wang Le , Gu Zhaolin , Yu Chunlei , Zhang Yigen , Shu Qinglin , Su Junwei
Published: February 2021

A consistent, sharp interface fully Eulerian fictitious domain method is proposed in this article for moving boundary problems. In this method, a collocated finite volume method is used for the continuous phase; a geometry intersection method is employed for numerical integrals over the solid domain and transport of the body force; the pseudo body force defined at “solid centers” ensures the algorithm consists of the body force between the continuous form and its discretization counterpart; an explicit flux correction on cell faces and resulting mass source is introduced into the continuity equation to lower noncontinuity errors in the velocity correction step. This method is valid for stationary and moving boundary problems with arbitrarily polyhedral mesh. Several numerical tests are carried out to validate the proposed method. A second‐order spatial accuracy is found in the flow around a cylinder case, and the spurious force oscillation is well suppressed for the in‐line oscillation of a circular cylinder case. The performances on different meshes are tested, and structured mesh yields the best result, polyhedral next, and tetrahedral worst. A serial of tests is further performed on structured mesh to verify the effect of three different features (i.e., storing the body force at the solid centers, flux correction, and whether including the body force in the momentum equation) on the numerical predictions. Numerical results show that, in the in‐line oscillation of a circular cylinder, “flux correction” can eliminate the large spikes in the drag coefficient, and “including the body force in the momentum equation” helps suppress the small oscillations. For other tests, “storing the body force at the solid centers” has enormous impacts on the final results of moving boundary problems, “flux correction” has little effects and the necessity of “including the body force in the momentum equation” is case dependent.
Biostratigraphic significance and geometric morphometrics of Euestheria gutta (Crustacea: Branchiopoda: Spinicaudata): An index fossil of continental Permian–Triassic transitional beds
Authors: Miao Xue , Chu Daoliang , Tong Jinnan , Benton Michael J. , Yu Jianxin , Luo Liang , Shu Wenchao , Wu Yuyang
Published: February 2021

The Permian–Triassic mass extinction was the largest biotic extinction event in the Phanerozoic and affected both marine and continental life. Marine Permian–Triassic transitional sequences can be correlated in many regions, but this has proved difficult for continental successions. A growing number of studies show that spinicaudatans are some of the most common fossils in continental strata and can be used as index fossils for continental stratigraphic division and correlation. Here we document the morphology and biostratigraphic significance of Euestheria gutta based on well‐preserved fossils from southwestern China. It shows strong intraspecific morphological variation, while the most important feature is the strongly convex larval valve and significant finely pitted to weakly reticulated ornamentation on the growth bands. Evidence from palaeobotany, charcoal, and organic carbon isotopes indicated that the continental mass extinction in southwestern China was marked by the catastrophic loss of tropical rainforest vegetation, enhanced wildfire and a negative carbon isotope excursion (CIE) during the P–Tr transition. Meanwhile, abundant E. gutta first appeared at the onset of the negative CIE and just above the horizon of the loss of macroflora. Based on the global geographic distribution of E. gutta and temporal correlation, we conclude that this species existed from the latest Permian to the earliest Triassic, and the occurrence of E. gutta could be used as an index fossil of the continental mass extinction interval or P–Tr transitional beds.
Rate of use and effectiveness of oseltamivir in the treatment of influenza illness in high‐risk populations: A systematic review and meta‐analysis
Authors: Shim So‐Jung , Chan Mei , Owens Louisa , Jaffe Adam , Prentice Bernadette , Homaira Nusrat
Published: February 2021

Background

Oseltamivir is recommended in the treatment of influenza illness in high‐risk populations, including those with chronic heart and lung diseases.

Objectives

We conducted a systematic review and meta‐analysis to determine the rate of use and effectiveness of oseltamivir in these groups of patients.

Methods

The protocol for the systematic review was registered on PROSPERO (CRD42019125998). Medline, EMBASE, Cochrane CENTRAL, and CINAHL were searched for observational studies and randomized controlled trials published up to 16 February 2020. Quality appraisal of final studies was conducted using GRADE guidelines. Data were extracted using a predeveloped template. Main outcomes measured included the rate of use of oseltamivir for influenza‐like‐illness and its effectiveness in reducing disease severity in patients with cardiopulmonary diseases. Outcomes measured for effectiveness were influenza‐related complications (respiratory infections and asthma exacerbations), hospitalization rates, and time to freedom from illness. Risk of bias was assessed using Cochrane's Risk of Bias 2.0 tool for randomized trials and Cochrane's Risk of Bias in nonrandomized Studies of Interventions tool for nonrandomized trials. Where data were available, pooled analyses were conducted. Dichotomous variables were evaluated using the Mantel‐Hansel method. A random effect model was applied. Summary measures were reported as risk ratios where relevant.

Results

Our systematic review identified nine studies. Oseltamivir use ranged from 25% to 100%. When oseltamivir group was compared to placebo, rates of respiratory tract infections reduced by 28% (RR = 0.72, 95% CI = 0.59‐0.90), hospitalization reduced by 52% (RR = 0.48, 95% CI = 0.28‐0.80) and median time to illness alleviation decreased by 10.4 to 120 hours. There was no significant reduction in asthma exacerbation rates.

Conclusions

Our systematic review suggests that the use of oseltamivir is beneficial in reducing disease severity, however, its use in high‐risk population remains suboptimal.
Bile acids during pregnancy: Trimester variations and associations with glucose homeostasis
Authors: Gagnon Marianne , Trottier Jocelyn , Weisnagel S. John , Gagnon Claudia , Carreau Anne‐Marie , Barbier Olivier , Morisset Anne‐Sophie
Published: February 2021

Background and aims

Bile acids are known to contribute to hepatic glucose and lipid metabolism regulation. Although glucose homeostasis sustains well‐characterized modifications during uncomplicated pregnancies, changes in bile acids concentrations and relative proportions throughout pregnancy remain unknown. Furthermore, literature shows strong associations between bile acids profiles and glucose homeostasis under normal metabolic conditions. We seek, first, to characterize bile acids' metabolic changes across trimesters and, second, to evaluate associations between changes in bile acids and glucose homeostasis indexes in the first and second trimesters.

Methods

A total of 78 women were recruited and followed at each trimester of pregnancy. Fasting serum samples were collected once per trimester in which quantitative measurement of 30 different bile acids' molecules were performed using liquid chromatography with tandem mass spectrometry (LC‐MS/MS). Glucose homeostasis indexes were measured in the first and second trimesters, after a 12‐hour fast and following a 75 g oral glucose tolerance test.

Results

Total bile acids increased from the first trimester to late pregnancy, along with the cholic acid: chenodeoxycholic acid and conjugated: unconjugated bile acids ratios. Changes in bile acids were positively associated with elevated peripheral and hepatic insulin resistance indexes, as well as with trimestral changes in these indexes.

Conclusion

Our findings suggest that modifications occurring in bile acids' profiles during normal pregnancy are associated with changes in glucose homeostasis. Further research is needed to examine the nature of those associations and the possible outcome of bile acids changes on pathological glucose homeostasis alterations during pregnancy.
Owner offspring gender and long‐term resource allocation in Chinese family firms
Authors: Wang Xia , Gao Cencen , Feng Mingming
Published: February 2021

A long‐term orientation helps companies improve business performance and achieve sustainable competitive advantages. We use data for Chinese family firms listed on the Shanghai and Shenzhen A‐share stock markets during the years 2000 and 2018. We examine the influence of owner offspring gender on family firms' long‐term resource allocation. We find a “son effect” in long‐term resource allocation among family firms, that is, owners raising sons tend to have a longer investment horizon and are more willing to increase innovation. This “son effect” is more significant for owners who were born in patriarchal regions where the social system is controlled or governed by men. We also find that son‐raising owners' long‐term resource allocation is mainly motivated by their willingness of intergenerational inheritance. This study fills a research gap regarding the influence of owner offspring gender on corporate long‐term resource allocation, enriches the literature on the heterogeneity of executive behavior and corporate governance of family firms, and provides important implications for understanding the decision making and long‐term investments of Chinese family firms.