bluuebunny/crossref_metadata_2025 huggingface dataset:
Pilocarpine‐Induced Effects on Salivary Secretion as a Pharmacological Biomarker for Cholinergic Parasympathetic Activation
Authors: Treijtel Nicoline , Groenendaal‐van de Meent Dorien , Michon Ingrid , Korstanje Cees , Meijer John , Francke Klaus , Grossmann Matthias , de Vries Michiel
Published: November 2021

Pilocarpine‐induced salivary secretion could serve as a nontherapeutic target engagement biomarker in a clinical setting to test the activity of an M3 positive allosteric modulator (PAM). The potentiating effect on the reactivity of the M3 receptor to the agonistic effect of pilocarpine would support the mechanism of action of an M3 PAM in a variety of therapeutic areas. The aim of this study was to determine the optimal pilocarpine dose needed for evaluation of this potentiating effect. Therefore, the effects of pilocarpine on salivary secretion rate and its pharmacokinetics were explored at single doses of 2.5, 5, and 10 mg of pilocarpine or placebo. The study also explored the test‐retest variability of the pilocarpine‐induced effects on salivary secretion. Pilocarpine caused a reproducible, dose‐related increase in overall and maximum salivary secretion rate, in line with pilocarpine exposure. Oral doses of pilocarpine from 2.5 to 10 mg were safe and well tolerated, consistent with the published safety profile. These results support the use of pilocarpine in single‐dose pharmacological challenge studies. The recommended dose for evaluating M3 PAM activity would be between 2.5 and 5 mg, showing a small increase in salivary secretion rate with room for further increase due to PAM activation.
Comparison of Liu and two parameter principal component estimator to combat multicollinearity
Authors: Kaçıranlar Selahattin , Özbay Nimet , Özkan Ecem , Güler Hüseyin
Published: November 2021

Biased estimation methods like ridge regression, Liu‐type regression, two‐parameter regression and principal component regression have become very popular in the analysis of applied researches for health, economics, chemometrics, and social sciences in recent years. A dataset in such applied fields tends to be characterized by many independent variables on relatively fewer observations. In addition, there is a high degree of near collinearity among the explanatory variables. It is common knowledge that under these conditions, ordinary least squares estimations of regression coefficients may be very unstable, leading to very poor prediction accuracy. The aim of this article is to examine the performance of the combination of principal components regression and some biased regression estimators such as ridge, Liu and two‐parameter estimators. For this reason, a real‐life application is presented in which different selection methods of the biasing parameters are employed.
A cellular census of human peripheral immune cells identifies novel cell states in lung diseases
Authors: Song Dongli , Yan Furong , Fu Huirong , Li Liyang , Hao Jie , Zhu Zhenhua , Ye Ling , Zhang Yong , Jin Meiling , Dai Lihua , Fang Hao , Song Zhenju , Wu Duojiao , Wang Xiangdong
Published: November 2021

Increasing evidence supports a central role of the immune system in lung diseases. Understanding how immunological alterations between lung diseases provide opportunities for immunotherapy. Exhausted T cells play a key role of immune suppression in lung cancer and chronic obstructive pulmonary disease was proved in our previous study. The present study aims to furthermore define molecular landscapes and heterogeneity of systemic immune cell target proteomic and transcriptomic profiles and interactions between circulating immune cells and lung residential cells in various lung diseases. We firstly measured target proteomic profiles of circulating immune cells from healthy volunteers and patients with stable pneumonia, stable asthma, acute asthma, acute exacerbation of chronic obstructive pulmonary disease, chronic obstructive pulmonary disease and lung cancer, using single‐cell analysis by cytometry by time‐of‐flight with 42 antibodies. The nine immune cells landscape was mapped among those respiratory system diseases, including CD4+ T cells, CD8+ T cells, dendritic cells, B cells, eosinophil, γδT cells, monocytes, neutrophil and natural killer cells. The double‐negative T cells and exhausted CD4+ central memory T cells subset were identified in patients with acute pneumonia. This T subset expressed higher levels of T‐cell immunoglobulin and mucin domain‐containing protein 3 (Tim3) and T‐cell immunoreceptor with Ig and ITIM domains (TIGIT) in patients with acute pneumonia and stable pneumonia. Biological processes and pathways of immune cells including immune response activation, regulation of cell cycle and pathways in cancer in peripheral blood immune cells were defined by bulk RNA sequencing (RNA‐seq). The heterogeneity among immune cells including CD4+, CD8+ T cells and NK T cells by single immune cell RNA‐seq with significant difference was found by single‐cell sequencing. The effect of interstitial telocytes on the immune cell types and immune function was finally studied and the expressions of CD8a and chemokine C–C motif receptor 7 (CCR7) were increased significantly in co‐cultured groups. Our data indicate that proteomic and transcriptomic profiles and heterogeneity of circulating immune cells provides new insights for understanding new molecular mechanisms of immune cell function, interaction and modulation as a source to identify and develop biomarkers and targets for lung diseases.
Get up early: Revealing behavioral responses of sandeel to ocean warming using commercial catch data
Authors: Henriksen Ole , Rindorf Anna , Mosegaard Henrik , Payne Mark R. , van Deurs Mikael
Published: November 2021

Warming of the oceans and shifts in the timing of annual key events are likely to cause behavioral changes in species showing a high degree of site fidelity. While this is well studied in terrestrial systems, there are fewer examples from the marine environment. Sandeel (Ammodytes marinus) is a small eel‐shaped teleost fish with strong behavioral attachment to sandy habitats in which they are buried from late summer through winter. When spring arrives, the sandeel emerge to feed during the day for several of months before returning to the sand for overwintering refuge.

Using fisheries data from the North Sea, we investigated whether catch rates reflect the timing of emergence and if seasonal patterns are related to temperature and primary production.

Catch per unit effort (CPUE) was used to describe sandeel emergence. We developed indicators of the relative timing of the emergence from the winter sand refuge and the subsequent growth period. Different modeling approaches were used to investigate the relationship with bottom temperature and primary production.

Variation in emergence behavior was correlated with variation in sea bottom temperature. Warmer years were characterized by earlier emergence. Significant warming over the last three decades was evident in all sandeel habitats in the North Sea throughout most of their adult life history, though no net shift in the phenology of emergence was detected. Minimum temperature during spring was a better predictor of emergence behavior than, for example, degree days.

This study emphasizes how temperature‐induced changes in behavior may have implications for predators and fisheries of sandeel. The method can be applied to other species for which the timing of exploitation (i.e., fisheries) and species life history are well matched.
Measuring Daphnia life history in the wild: The efficacy of individual field cages
Authors: O’Connor Michael , Sadler Daniel E. , Brunner Franziska S. , Reynolds Alan , White Nicola , Price Stephen , Plaistow Stewart J.
Published: November 2021

Life‐history studies are often conducted in a laboratory environment where it is easy to assay individual animals. However, factors such as temperature, photoperiod, and nutrition vary greatly between laboratory and field environments, making it difficult to compare results. Consequently, there is a need to study individual life histories in the field, but this is currently difficult in systems such as Daphnia where it is not possible to mark and track individual animals. Here, we present a proof of principle study showing that field cages are a reliable method for collecting individual‐level life‐history data in Daphnia magna. As a first step, we compared the life history of paired animals reared outside and inside cages to test the hypothesis that cages allow free flow of algal food resources. We then used a seminatural mesocosm setting to compare the performance of individual field cages versus glass jars refilled with mesocosm water each day. We found that cages did not inhibit food flow and that differences in life histories between three clones detected in the jar assays were also detectable using the much less labor‐intensive field cages. We conclude that field cages are a feasible approach for collecting individual‐level life‐history data in systems such as Daphnia where individual animals cannot be marked and tracked.
Adaptive co‐evolution of mitochondria and the Y‐chromosome: A resolution to conflict between evolutionary opponents
Authors: Wade Michael J. , Fogarty Laurel
Published: November 2021

In most species with motile sperm, male fertility depends upon genes located on the Y‐chromosome and in the mitochondrial genome. Coordinated adaptive evolution for the function of male fertility between genes on the Y and the mitochondrion is hampered by their uniparental inheritance in opposing sexes: The Y‐chromosome is inherited uniparentally, father to son, and the mitochondrion is inherited maternally, mother to offspring. Preserving male fertility is problematic, because maternal inheritance permits mitochondrial mutations advantageous to females, but deleterious to male fertility, to accumulate in a population. Although uniparental inheritance with sex‐restricted adaptation also affects genes on the Y‐chromosome, females lack a Y‐chromosome and escape the potential maladaptive consequences of male‐limited selection. Evolutionary models have shown that mitochondrial mutations deleterious to male fertility can be countered by compensatory evolution of Y‐linked mutations that restore it. However, direct adaptive coevolution of Y‐ and mitochondrial gene combinations has not yet been mathematically characterized. We use population genetic models to show that adaptive coevolution of Y and mitochondrial genes are possible when Y‐mt gene combinations have positive effects on male fertility and populations are inbred.
Pollinator individual‐based networks reveal the specialized plant–pollinator mutualism in two biodiverse communities
Authors: Wang Lin‐Lin , Yang Yong‐Ping , Duan Yuan‐Wen
Published: November 2021

Generalization of pollination systems is widely accepted by ecologists in the studies of plant–pollinator interaction networks at the community level, but the degree of generalization of pollination networks remains largely unknown at the individual pollinator level. Using potential legitimate pollinators that were constantly visiting flowers in two alpine meadow communities, we analyzed the differences in the pollination network structure between the pollinator individual level and species level. The results showed that compared to the pollinator species‐based networks, the linkage density, interaction diversity, interaction evenness, the average plant linkage level, and interaction diversity increased, but connectance, degree of nestedness, the average of pollinator linkage level, and interaction diversity decreased in the pollinator individual‐based networks, indicating that pollinator individuals had a narrower food niche than their counterpart species. Pollination networks at the pollinator individual level were more specialized at the network level (H′2) and the plant species node level (d′) than at the pollinator species‐level networks, reducing the chance of underestimating levels of specialization in pollination systems. The results emphasize that research into pollinator individual‐based pollination networks will improve our understanding of the pollination networks at the pollinator species level and the coevolution of flowering plants and pollinators.
Long‐term Pseudogymnoascus destructans surveillance data reveal factors contributing to pathogen presence
Authors: Grider John F. , Russell Robin E. , Ballmann Anne E. , Hefley Trevor J.
Published: November 2021

The disease white‐nose syndrome (WNS) was first recognized in upstate New York in 2006 and has since spread across much of the United States (U.S.), causing severe mortality in several North American bat species. To aid in the identification and monitoring of at‐risk bat populations, we evaluate factors associated with the presence of the causative fungal agent of WNS, Pseudogymnoascus destructans (Pd), in the continental United States. We obtained Pd samples through hibernaculum surveys conducted from 2013 to 2020, with all samples analyzed at the U.S. Geological Survey National Wildlife Health Center. Using generalized additive models, we estimated the likelihood of Pd presence under three different hypotheses: human‐mediated, species‐mediated, and hibernaculum type. In addition to hypothesis‐related predictor variables, a subset of models included a smoothed nonseparable effect of longitude and latitude and a smoothed effect of time since study onset to account for spatial and temporal autocorrelation. Under all hypotheses, models indicated probability of Pd detection is best described by the smoothed nonseparable effect of longitude and latitude and a smoothed effect of time since onset of this study. After accounting for spatial and temporal autocorrelations, only hibernaculum type significantly affected Pd presence, with mines and culverts/tunnels less likely to contain Pd compared with caves. Reduced likelihood of Pd presence in mines and culverts/tunnels bodes well for bats of the western and southern United States, where use of these hibernaculum types is more common. While our findings can help guide monitoring and management efforts, the potential for long‐distance dispersal combined with variation in community composition and hibernation ecology between the western and eastern United States necessitates the continued monitoring of Pd presence.
Targeted next‐generation sequencing of environmental DNA improves detection of invasive European green crab (Carcinus maenas)
Authors: Westfall Kristen Marie , Therriault Thomas W. , Abbott Cathryn L.
Published: November 2021

In the northeast Pacific Ocean, there is high interest in developing eDNA‐based survey methods to aid management of invasive populations of European green crab (Carcinus maenas). Expected benefits are improved sensitivity for early detection of secondary spread and to assess the outcome of eradication efforts. A new eDNA‐based approach we term “targeted next‐generation sequencing (tNGS)” is introduced here and shown to improve detection relative to qPCR at sites with lower green crab CPUE values measured by trapping. DNA standards (gBlock) with starting molecule copies that were 10 to 100 times lower than the qPCR limit of detection returned significant numbers of sequencing reads, which in our field assessments translated to a 7%–10% increase in detection probability from tNGS relative to qPCR at sites with lower CPUE. We also found the number of sequencing reads from tNGS was significantly correlated with green crab CPUE whereas Ct values from qPCR were not. When sources of variation were partitioned for each assay, we found the difference between mean within‐site and mean between‐site variation was much larger and had non‐overlapping confidence intervals for tNGS relative to qPCR, suggesting the former may offer more power for detecting spatial variation in eDNA availability. Results presented here indicate this approach is suitable for species of known low abundances where a positive detection has high economic or environmental consequences, or for labs doing eDNA surveys for whom NGS‐based workflows are operationally more efficient than qPCR given its upward scalability. Any species with an existing qPCR assay can be easily tested with a tNGS assay using the approach presented here. We conclude with a discussion on the fitness for purpose of tNGS vs. qPCR for various applications and on how to best apply molecular surveys in management programs.
A Simple Synthetic Route to Well‐Defined [Pd(NHC)Cl(1‐tBu‐indenyl)] Pre‐catalysts for Cross‐Coupling Reactions
Authors: Liu Yaxu , Scattolin Thomas , Gobbo Alberto , Beliš Marek , Van Hecke Kristof , Nolan Steven P. , Cazin Catherine S. J.
Published: November 2021

The development of robust, more efficient, general, easily accessible Pd(II)–NHC pre‐catalysts remains a key issue in cross‐coupling applications. A selection of well‐defined, air and moisture stable [Pd(NHC)Cl(1‐tBu‐indenyl)] (NHC=IPr, IPrCl, IMes, SIMes, IPr*) pre‐catalysts have been synthesized in good to excellent yields by reacting [Pd(1‐tBu‐indenyl)(μ‐Cl)]2 and various NHC⋅HCl precursors in the presence of the weak base K2CO3 in green acetone. The synthesized Pd(II)‐NHC derivatives displayed excellent catalytic activity in classical Suzuki‐Miyaura and Buchwald–Hartwig reactions, especially when IPrCl is employed as ancillary ligand. Additionally, in the challenging Suzuki‐Miyaura reaction between esters and arylboronic acids, the [Pd(IPr*)Cl(1‐tBu‐indenyl)] complex exhibited the optimum catalytic activity under very mild reaction conditions.
Ionic‐Liquid‐Catalyzed Synthesis of Imines, Benzimidazoles, Benzothiazoles, Quinoxalines and Quinolines through C−N, C−S, and C−C Bond Formation
Authors: Badhani Gaurav , Joshi Abhisek , Adimurthy Subbarayappa
Published: November 2021

We report the tetramethyl ammonium hydroxide catalyzed oxidative coupling of amines and alcohols for the synthesis of imines under metal‐free conditions by utilizing oxygen from air as the terminal oxidant. Under the same conditions, with ortho‐phenylene diamines and 2‐aminobenzenethiols the corresponding benzimidazoles and benzothiazoles were obtained. Quinoxalines were obtained from ortho‐phenylene diamines and 1‐phenylethane‐1,2‐diol, the conditions were then extended to the synthesis of quinoline building blocks by reaction of 2‐amino benzyl alcohols either with 1‐phenylethan‐1‐ol or acetophenone derivatives. The formation of C−N, C−S and C−C bonds was achieved under metal‐free conditions. A broad range of amines (aromatic, aliphatic, cyclic and heteroaromatic) as well as benzylic alcohols including heteroaryl alcohols reacted smoothly and provided the desired products. The mild reaction conditions, commercially available catalyst, metal‐free, good functional‐group tolerance, broad range of products (imines, benzimidazoles, benzothiazoles, quinoxalines and quinolines) and applicability at gram scale reactions are the advantages of the present strategy.
On the Redox Activity of the Solid Electrolyte Interphase in the Reduction/Oxidation of Silicon Nanoparticles in Secondary Lithium Batteries
Authors: Bongiorno Corrado , Mannino Giovanni , D'Alessio Umberto , Monforte Francesca , Condorelli Guglielmo Guido , Spinella Corrado , La Magna Antonino , Brutti Sergio
Published: November 2021

Chemical and structural modifications occurring in homogeneous crystalline Si nanoparticles (NPs) used as anode material in Li cells are investigated. State‐of‐the‐art high‐resolution scanning transmission electron microscopy coupled with electron energy loss spectroscopy resolved at the nanoscale is exploited. It is directly highlighted by electron spectromicroscopy that, above 0.1 V versus Li, the electrochemical activity of Si electrodes involves a complex interplay between Li incorporation, electrolyte degradation, and Si reduction/oxidation. These redox processes occur upon cycling through partially reversible reactions mediated by the solid electrolyte interphase. Overall, a SiO2 amorphous layer forms in the oxidized electrodes at the Si NPs interface with the electrolyte: this oxide shell partially dissolves upon reduction to give Li2CO3 and amorphous Si. Si NPs cores are therefore eroded upon cycling as their outer layers are directly involved in a reversible oxygen shifting mechanism at the interface, whereas unreacted SiO2 accumulates cycle‐by‐cycle. These findings extend the comprehension of the Si pulverization mechanism in Li batteries.
Scalable multiple changepoint detection for functional data sequences
Authors: Harris Trevor , Li Bo , Tucker J. Derek
Published: November 2021

We propose the multiple changepoint isolation (MCI) method for detecting multiple changes in the mean and covariance of a functional process. We first introduce a pair of projections to represent the variability “between” and “within” the functional observations. We then present an augmented fused lasso procedure to split the projections into multiple regions robustly. These regions act to isolate each changepoint away from the others so that the powerful univariate CUSUM statistic can be applied region‐wise to identify the changepoints. Simulations show that our method accurately detects the number and locations of changepoints under many different scenarios. These include light and heavy tailed data, data with symmetric and skewed distributions, sparsely and densely sampled changepoints, and mean and covariance changes. We show that our method outperforms a recent multiple functional changepoint detector and several univariate changepoint detectors applied to our proposed projections. We also show that MCI is more robust than existing approaches and scales linearly with sample size. Finally, we demonstrate our method on a large time series of water vapor mixing ratio profiles from atmospheric emitted radiance interferometer measurements.
Astrocyte reactivity in a mouse model of SCN8A epileptic encephalopathy
Authors: Thompson Jeremy A. , Miralles Raquel M. , Wengert Eric R. , Wagley Pravin K. , Yu Wenxi , Wenker Ian C. , Patel Manoj K.
Published: November 2021

Objective

SCN8A epileptic encephalopathy is caused predominantly by de novo gain‐of‐function mutations in the voltage‐gated sodium channel Nav1.6. The disorder is characterized by early onset of seizures and developmental delay. Most patients with SCN8A epileptic encephalopathy are refractory to current anti‐seizure medications. Previous studies determining the mechanisms of this disease have focused on neuronal dysfunction as Nav1.6 is expressed by neurons and plays a critical role in controlling neuronal excitability. However, glial dysfunction has been implicated in epilepsy and alterations in glial physiology could contribute to the pathology of SCN8A encephalopathy. In the current study, we examined alterations in astrocyte and microglia physiology in the development of seizures in a mouse model of SCN8A epileptic encephalopathy.

Methods

Using immunohistochemistry, we assessed microglia and astrocyte reactivity before and after the onset of spontaneous seizures. Expression of glutamine synthetase and Nav1.6, and Kir4.1 channel currents were assessed in astrocytes in wild‐type (WT) mice and mice carrying the N1768D SCN8A mutation (D/+).

Results

Astrocytes in spontaneously seizing D/+ mice become reactive and increase expression of glial fibrillary acidic protein (GFAP), a marker of astrocyte reactivity. These same astrocytes exhibited reduced barium‐sensitive Kir4.1 currents compared to age‐matched WT mice and decreased expression of glutamine synthetase. These alterations were only observed in spontaneously seizing mice and not before the onset of seizures. In contrast, microglial morphology remained unchanged before and after the onset of seizures.

Significance

Astrocytes, but not microglia, become reactive only after the onset of spontaneous seizures in a mouse model of SCN8A encephalopathy. Reactive astrocytes have reduced Kir4.1‐mediated currents, which would impair their ability to buffer potassium. Reduced expression of glutamine synthetase would modulate the availability of neurotransmitters to excitatory and inhibitory neurons. These deficits in potassium and glutamate handling by astrocytes could exacerbate seizures in SCN8A epileptic encephalopathy. Targeting astrocytes may provide a new therapeutic approach to seizure suppression.
Surrogate probabilistic seismic demand modelling of inelastic single‐degree‐of‐freedom systems for efficient earthquake risk applications
Authors: Gentile Roberto , Galasso Carmine
Published: November 2021

This paper proposes surrogate models (or metamodels) mapping the parameters controlling the dynamic behaviour of inelastic single‐degree‐of‐freedom (SDoF) systems (i.e., force‐displacement capacity curve, hysteretic behaviour) and the parameters of their probabilistic seismic demand model (PSDM, i.e., conditional distribution of an engineering demand parameter [EDP] given a ground‐motion intensity measure [IM]). These metamodels allow the rapid derivation of fragility curves of SDoF representation of structures. Gaussian Process (GP) regression is selected as the metamodelling approach because of their flexibility in implementation, the resulting accuracy and computational efficiency. The metamodel training dataset includes 10,000 SDoF systems analysed via cloud‐based non‐linear time‐history analysis (NLTHA) using recorded ground motions. The proposed GP regressions are tested in predicting the PSDM of both the SDoF database (through ten‐fold cross validation) and eight realistic reinforced concrete (RC) frames, benchmarking the results against NLTHA. An application is conducted to propagate such modelling uncertainty to both fragility and vulnerability/loss estimations. Error levels are deemed satisfactory for practical applications, especially considering the low required modelling effort and analysis time. Regarding single‐building applications enabled by the proposed metamodel, this paper presents a first attempt at a direct loss‐based design procedure, which allows setting a target loss level for the designed structure (shown for a realistic RC frame). An earthquake risk model involving dynamic exposure and vulnerability modules is illustrated as an example of building portfolio applications. Specifically, the proposed application considers a retrofit‐based seismic risk‐reduction policy for a synthetic building portfolio, for which it is possible estimating the loss evolution over time.
Risk Assessment of Gypsum Amendment on Agricultural Fields: Effects of Sulfate on Riverine Biota
Authors: Rantamo Krista , Arola Hanna , Aroviita Jukka , Hämälainen Heikki , Hannula Maija , Laaksonen Rami , Laamanen Tiina , Leppänen Matti T. , Salmelin Johanna , Syrjänen Jukka T. , Taskinen Antti , Turunen Jarno , Ekholm Petri
Published: November 2021

Gypsum (CaSO4∙2H2O) amendment is a promising way of decreasing the phosphorus loading of arable lands, and thus preventing aquatic eutrophication. However, in freshwaters with low sulfate concentrations, gypsum-released sulfate may pose a threat to the biota. To assess such risks, we performed a series of sulfate toxicity tests in the laboratory and conducted field surveys. These field surveys were associated with a large-scale pilot exercise involving spreading gypsum on agricultural fields covering 18% of the Savijoki River (Finland) catchment area. The gypsum amendment in such fields resulted in approximately a four-fold increase in the mean sulfate concentration for a 2-month period, and a transient, early peak reaching approximately 220 mg/L. The sulfate concentration gradually decreased almost to the pregypsum level after 3 years. Laboratory experiments with Unio crassus mussels and gypsum-spiked river water showed significant effects on foot movement activity, which was more intense with the highest sulfate concentration (1100 mg/L) than with the control. Survival of the glochidia after 24 and 48 h of exposure was not significantly affected by sulfate concentrations up to 1000 mg/L, nor was the length growth of the moss Fontinalis antipyretica affected. The field studies on benthic algal biomass accrual, mussel and fish density, and Salmo trutta embryo survival did not show gypsum amendment effects. Gypsum treatment did not raise the sulfate concentrations even to a level just close to critical for the biota studied. However, because the effects of sulfate are dependent on both the spatial and the temporal contexts, we advocate water quality and biota monitoring with proper temporal and spatial control in rivers within gypsum treatment areas. Environ Toxicol Chem 2022;41:108–121. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Analysis of side information impact on the physical layer security performances in wireless wiretap channel
Authors: Pakravan Saeid , Hodtani Ghosheh Abed
Published: November 2021

Information‐theoretic analysis of the communication systems performances is of practical and theoretical importance. In this article, we study side information impact on physical layer security in a Rayleigh fading wiretap channel by deriving closed‐form expressions for the average secrecy capacity (ASC), secrecy outage probability (SOP), secrecy coverage region (SCR), and specifically, the asymptotic behavior of SOP. The results, while including previous works as special cases, show that side information has positive effects over ASC and SOP, and also, it increases the SCR, as expected intuitively. Numerical evaluations have been done to support the claims.
An enhancedLTEhandover scheme for high‐speed railway application
Authors: Amin Sadrabadi Hossein , Ardalani Nahid , Bakhshi Hamidreza
Published: November 2021

High‐speed railway (HSR) is one of the most important modes of passenger transport with many advantages, such as; safety, high capacity, short intervals, and comfort. To provide high speed mobile data to the passengers of HSR for infotainment services, the best option is LTE or LTE‐R. The LTE‐R is a railway specialized network under development. The very high speed of trains in HSR, which are far faster than conventional commuters, counteracts the seamless data service and deteriorates the QoS which is mainly due to handover (HO) failure when the user equipment (UE) is moving very fast. Conventional LTE HO schemes are not designed for very high speed of HSR. Some research studies were done to provide HO schemes with more adaptation with the HSR condition but the desired specifications are not fully satisfied. In this article, we have devised a new S3 scheme for LTE HO based on time‐to‐trigger parameter in which the required ETSI's HO success rate standard at very high speed moving UE is met with a good safety margin. In addition, the presented scheme shows better performance in terms of HO latency, reference signal received power gap and handover operation probability. To do the job, an accurate mathematical analysis was developed for the proposed S3 scheme, conventional A3 and A4 schemes and the H2 scheme that we found to be the best one out of previous research studies. The results obtained have been verified by simulations.
Ultrasonic extraction, structural characterization, and antioxidant activity of oligosaccharides from red yeast rice
Authors: Liu Kai , Xie Long , Gu Huan , Luo Jia , Li Xiaofang
Published: November 2021

Red yeast rice is consumed as a medicinal food to lower blood lipids. Besides, it is used to color food, make wine, etc. In this study, water‐soluble oligosaccharides in red yeast rice were extracted by ultrasonic‐assisted extraction method. The parameters to extract oligosaccharides from red yeast rice were optimized by the Box‐Behnken design under the following optimal extraction conditions: extraction temperature, 60°C; extraction time, 97 min; and liquid/material ratio, 25 ml/g. The structure and the antioxidant activity of the new oligosaccharide were preliminarily investigated. Total carbohydrates extracted from red yeast rice with 80% ethanol–water solution (v/v) were first removed from pigments using D101 macroporous adsorption resin. The total sugar contents were then purified by DE52 resins and Sephadex G‐25 resins to obtain red yeast rice oligosaccharides, coded as RYRO1. Structural characterization experiments indicated that RYRO1 is an oligosaccharide with a weight average molecular weight of 874 Da and a theoretical degree of polymerization of 4.86. RYRO1 is composed of mannose, glucosamine, glucose, and galactose with a molar ratio of 0.248:0.019:1:0.026. The ABTS, DPPH, and hydroxyl free radical

scavenging assays showed antioxidant nature of RYRO1.
Mixed‐diurnal tidal record from a Palaeoproterozoic embayment in the Par Formation, Gwalior Group, Central India
Authors: Paul Pritam Paritosh , Chakraborty Partha Pratim
Published: November 2021

The Palaeoproterozoic Par Formation, Gwalior Group, central India contains a mixed, predominantly diurnal, tidal record in an embayment‐like estuarine setting where flood energy exceeded the ebb energy. From two order differences in set thickness between flood‐ and ebb‐generated bedforms an asymmetry in peak tidal current velocity of flood and ebb is inferred with domination of flood current. From the presence of crossover in successive neap records and 27.75 neap‐spring cycles per year, an unambiguous clue for tidal forcing by lunar declination rather than lunar phase is inferred. Harmonic analysis of foreset‐lamina thickness from tidal sand waves suggests that a tropical month of minimum 26 lunar days was in effect at the Gwalior Sea during the late Palaeoproterozoic (2,000–1,791 Ma).
Connectivity‐based parcellation of normal and anatomically distorted human cerebral cortex
Authors: Doyen Stephane , Nicholas Peter , Poologaindran Anujan , Crawford Lewis , Young Isabella M. , Romero‐Garcia Rafeael , Sughrue Michael E.
Published: November 2021

For over a century, neuroscientists have been working toward parcellating the human cortex into distinct neurobiological regions. Modern technologies offer many parcellation methods for healthy cortices acquired through magnetic resonance imaging. However, these methods are suboptimal for personalized neurosurgical application given that pathology and resection distort the cerebrum. We sought to overcome this problem by developing a novel connectivity‐based parcellation approach that can be applied at the single‐subject level. Utilizing normative diffusion data, we first developed a machine‐learning (ML) classifier to learn the typical structural connectivity patterns of healthy subjects. Specifically, the Glasser HCP atlas was utilized as a prior to calculate the streamline connectivity between each voxel and each parcel of the atlas. Using the resultant feature vector, we determined the parcel identity of each voxel in neurosurgical patients (n = 40) and thereby iteratively adjusted the prior. This approach enabled us to create patient‐specific maps independent of brain shape and pathological distortion. The supervised ML classifier re‐parcellated an average of 2.65% of cortical voxels across a healthy dataset (n = 178) and an average of 5.5% in neurosurgical patients. Our patient dataset consisted of subjects with supratentorial infiltrating gliomas operated on by the senior author who then assessed the validity and practical utility of the re‐parcellated diffusion data. We demonstrate a rapid and effective ML parcellation approach to parcellation of the human cortex during anatomical distortion. Our approach overcomes limitations of indiscriminately applying atlas‐based registration from healthy subjects by employing a voxel‐wise connectivity approach based on individual data.
Acquired Resistance to Antiangiogenic Therapies in Hepatocellular Carcinoma Is Mediated by Yes‐Associated Protein 1 Activation and Transient Expansion of Stem‐Like Cancer Cells
Authors: Castven Darko , Czauderna Carolin , Becker Diana , Pereira Sharon , Schmitt Jennifer , Weinmann Arndt , Shah Viral , Hajduk Jovana , Keggenhoff Friederike , Binder Harald , Keck Tobias , Heilmann‐Heimbach Stefanie , Wörns Marcus A. , Thorgeirsson Snorri S. , Breuhahn Kai , Galle Peter R. , Marquardt Jens U.
Published: November 2021

Induction of neoangiogenesis is a hallmark feature during disease progression of hepatocellular carcinoma (HCC). Antiangiogenetic compounds represent a mainstay of therapeutic approaches; however, development of chemoresistance is observed in the majority of patients. Recent findings suggest that tumor‐initiating cells (TICs) may play a key role in acquisition of resistance, but the exact relevance for HCC in this process remains to be defined. Primary and established hepatoma cell lines were exposed to long‐term sorafenib treatment to model acquisition of resistance. Treatment effects on TICs were estimated by sphere‐forming capacity in vitro, tumorigenicity in vivo, and flow cytometry. Adaptive molecular changes were assessed by whole transcriptome analyses. Compensatory mechanisms of resistance were identified and directly evaluated. Sustained antiproliferative effect following sorafenib treatment was observed in three of six HCC cell lines and was followed by rapid regrowth, thereby mimicking responses observed in patients. Resistant cells showed induction in sphere forming in vitro and tumor‐initiating capacity in vivo as well as increased number of side population and epithelial cell adhesion molecule‐positive cells. Conversely, sensitive cell lines showed consistent reduction of TIC properties. Gene sets associated with resistance and poor prognosis, including Hippo/yes‐associated protein (YAP), were identified. Western blot and immunohistochemistry confirmed increased levels of YAP. Combined treatment of sorafenib and specific YAP inhibitor consistently revealed synergistic antioncogenic effects in resistant cell lines. Conclusion: Resistance to antiangiogenic therapy might be driven by transient expansion of TICs and activation of compensatory pro‐oncogenic signaling pathways, including YAP. Specific targeting of TICs might be an effective therapeutic strategy to overcome resistance in HCC.
Integrating health planning and primary care infrastructure for COVID‐19 and tuberculosis care in India: Challenges and opportunities
Authors: Yadav Prakrati , Vohra Chirag , Gopalakrishnan Maya , Garg Mahendra Kumar
Published: November 2021

Tuberculosis (TB) is the leading cause of death from a single infectious agent worldwide. The COVID‐19 pandemic has overburdened healthcare services around the world especially in resource constrained settings. It has shaken already unstable foundation of TB control programs in India and other high burden states. A 25% decline is expected in TB detection while estimates suggest 13% increase in TB deaths due to the impact of the pandemic. However, the significant intersections between the two diseases perhaps offer potential opportunities for consolidating the efforts to tackle both. The widespread implementation and acceptance of universal masking and social distancing in India has helped limit transmission of both diseases. Integrating the capacity building strategies for the two diseases, optimizing the existing the surveillance and monitoring systems which have been achieved over the years will result in a single vertically integrated national program addressing both, rather than multiple parallel program which utilize the already sparse primary care manpower and infrastructure. In this article, we explore the impact of the COVID‐19 pandemic on tuberculosis in India and offer suggestions on how effective health planning can efficiently integrate infrastructure and manpower at primary level to provide care for both COVID‐19 and tuberculosis.
People living with mental disorder in Nigeria amidst COVID‐19: Challenges, implications, and recommendations
Authors: Aborode Abdullahi Tunde , Corriero Anna Chiara , Mehmood Qasim , Nawaz Arisha , Aayush  , Upadhyay Prashant , Badri Rawa , Hasan Mohammad Mehedi
Published: November 2021

COVID‐19 has become a global public health obstacle. This disease has caused negligence on mental health institutions, decreased trust in the healthcare system and traditional and religious beliefs, and has created a widespread stigma on people living with mental health illness, specifically in Nigeria. The increase of COVID‐19 cases that have exhausted the healthcare system in Nigeria have brought further negligence to people living with mental disorder, thus increasing the burden of the disease on these patients. Overall, this article considerably highlighted the need for equal accessibility to healthcare resources, as well as the requirement of proper attention and care for mental health patients in Nigeria. This article discusses the challenges that surfaced because of the COVID‐19 pandemic on people living with mental illness and their implications, as well as suggesting necessary actions and recommendations.
A regional coupled approach to water cycle prediction during winter 2013/14 in the United Kingdom
Authors: Lewis Huw W. , Dadson Simon J.
Published: November 2021

A regional coupled approach to water cycle prediction is demonstrated for the 4‐month period from November 2013 to February 2014. This provides the first multi‐component analysis of precipitation, soil moisture, river flow and coastal ocean simulations produced by an atmosphere‐land‐ocean coupled system focussed on the United Kingdom (UK), running with horizontal grid spacing of around 1.5 km across all components. The Unified Model atmosphere component, in which convection is explicitly simulated, reproduces the observed UK rainfall accumulation (r2 of 0.95 for water day accumulation), but there is a notable bias in its spatial distribution—too dry over western upland areas and too wet further east. The JULES land surface model soil moisture state is shown to be in broad agreement with a limited number of cosmic‐ray neutron probe observations. A comparison of observed and simulated river flow shows the coupled system is useful for predicting broad scale features, such as distinguishing high and low flow regions and times during the period of interest but are less accurate than optimized hydrological models. The impact of simulated river discharge on NEMO model simulations of coastal ocean state is explored in the coupled modelling framework, with comparisons provided relative to experiments using climatological river input and no river input around the UK coasts. Results show that the freshwater flux around the UK contributes of order 0.2 psu to the mean surface salinity, and comparisons to profile observations give evidence of an improved vertical structure when applying simulated flows. This study represents the first assessment of the coupled system performance from a hydrological perspective, with priorities for future model developments and challenges for evaluation of such systems discussed.
Automatic classification of severity of COVID‐19 patients using texture feature and random forest based on computed tomography images
Authors: Amini Nasrin , Shalbaf Ahmad
Published: November 2021

Severity assessment of the novel Coronavirus (COVID‐19) using chest computed tomography (CT) scan is crucial for the effective administration of the right therapeutic drugs and also for monitoring the progression of the disease. However, determining the severity of COVID‐19 needs a highly expert radiologist by visual assessment, which is time‐consuming, boring, and subjective. This article introduces an advanced machine learning tool to determine the severity of COVID‐19 to mild, moderate, and severe from the lung CT images. We have used a set of quantitative first‐ and second‐order statistical texture features from each image. The first‐order texture features extracted from the image histogram are variance, skewness, and kurtosis. The second‐order texture features extraction methods are gray‐level co‐occurrence matrix, gray‐level run length matrix, and gray‐level size zone matrix. Finally, using the extracted features, CT images of each person are classified using random forest (RF) as an ensemble method based on majority voting of the decision trees outputs to four classes. We have used a dataset of CT scans labeled as being normal (231), mild (563), moderate (120), and severe (42) determined by expert radiologists. The experimental results indicate the combination of all feature extraction methods, and RF achieves the highest result compared with the other strategies in detecting the four classes of severity of COVID‐19 from CT images with an accuracy of 90.95%. This proposed system can work well and can be used as an assistant diagnostic tool for quantification of lung involvement of COVID‐19 to monitor the progression of the disease.
Training behavior analysts to conduct functional analyses using a remote group behavioral skills training package
Authors: Lloveras Lindsay A. , Tate Savannah A. , Vollmer Timothy R. , King Melissa , Jones Hannah , Peters Kerri P.
Published: November 2021

Behavioral skills training (BST) is a well‐established procedure used to train individuals how to perform a variety of complex skills. Previous research has used BST to train parents, teachers, and clinicians how to conduct a variety of clinical procedures, including functional analysis of problem behavior. Although this procedure has been demonstrated to be very effective, it can be time consuming and resource intensive. In the present study, 13 behavior analysts were trained to conduct functional analyses of problem behavior. All participants were employees of a multistate early intervention clinic. This staff training was conducted fully remotely, and trainers acted as child role‐play partners. Participants experienced baseline, an instruction/discussion component, a post‐instruction probe, group BST, and a post‐BST probe. For 5 participants, in‐situ probes were also conducted. All participants achieved mastery and in‐situ errors were low.
Greater Carboxy-Methyl-Lysine Is Associated With Increased Fracture Risk in Type 2 Diabetes
Authors: Dhaliwal Ruban , Ewing Susan K. , Vashishth Deepak , Semba Richard D. , Schwartz Ann V.
Published: November 2021

Accumulation of advanced glycation end-products (AGE) in bone alters collagen structure and function. Fluorescent AGEs are associated with fractures but less is known regarding non-fluorescent AGEs. We examined associations of carboxy-methyl-lysine (CML), with incident clinical and prevalent vertebral fractures by type 2 diabetes (T2D) status, in the Health, Aging, and Body Composition cohort of older adults. Incident clinical fractures and baseline vertebral fractures were assessed. Cox regression was used to analyze the associations between serum CML and clinical fracture incidence, and logistic regression for vertebral fracture prevalence. At baseline, mean ± standard deviation (SD) age was 73.7 ± 2.8 and 73.6 ± 2.9 years in T2D (n = 712) and non-diabetes (n = 2332), respectively. Baseline CML levels were higher in T2D than non-diabetes (893 ± 332 versus 771 ± 270 ng/mL, p < 0.0001). In multivariate models, greater CML was associated with higher risk of incident clinical fracture in T2D (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.24–1.79 per 1-SD increase in log CML) but not in non-diabetes (HR 1.03; 95% CI, 0.94–1.13; p for interaction = 0.001). This association was independent of bone mineral density (BMD), glycated hemoglobin (hemoglobin A1c), weight, weight loss, smoking, cystatin-C, and medication use. CML was not significantly associated with the odds of prevalent vertebral fractures in either group. In conclusion, higher CML levels are associated with increased risk of incident clinical fractures in T2D, independent of BMD. These results implicate CML in the pathogenesis of bone fragility in diabetes. © 2021 American Society for Bone and Mineral Research (ASBMR).