bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymmetric coplanar strip‐fed electrically small reconfigurable 5G mid‐band antenna
Authors: Gunamony Shine Let , Bala G. Josemin , Raj S. Merlin Gilbert , Pratap C. Benin
Published: July 2021

This work aims to provide an electrically small reconfigurable antenna with modification in the radiating strip length to switch between 5G mid‐band and 4G band‐40 application. Initially, the length of the radiating strip is designed to operate at 3.5 GHz for 5G mid‐band applications. Using switch configuration, the length of the radiating strip is modified so that the antenna's resonant frequency shifts from 3.5 GHz to 2.32 GHz, which can be operated at 4G band‐40. The effective radiation remains the same at two resonant modes. In terms of size, the proposed antenna geometry is (16.5 × 10.5 × 1.6) mm3. The designed antenna with an electrical length of 0.7014 mm is electrically small in size in comparison with the works of literature. Antenna structure provides a gain of 0.69 dBi and 1.35 dBi at resonant frequencies 2.32 GHz and 3.5 GHz, respectively. The geometry of the antenna is straightforward, and the prototype is fabricated on a low‐profile FR4 substrate. The simulated results are validated experimentally.
Burrow webs: Clawing the surface of interactions with burrows excavated by American badgers
Authors: Andersen Megan L. , Bennett Drew E. , Holbrook Joseph D.
Published: July 2021

Ecosystem engineers are organisms that influence their environment, which includes alterations leading to habitat provisioning for other species. Perhaps the most well‐examined guild of species provisioning habitat for other species is tree cavity excavators or woodpeckers (Picidae). Many studies have examined the suite of secondary cavity users that rely on woodpeckers, and how the ecological network of secondary users, collectively referred to as the nest web, changes across communities. Despite similar habitat provisioning processes, fewer studies have assessed the suite of species associated with burrowers providing access to subterranean habitat. Here, we begin to characterize the burrow web provisioned by American badgers (Taxidea taxus) and evaluate the diversity and frequency of species interactions we detected at abandoned badger burrows in Wyoming, USA. We deployed camera traps at 23 badger burrows and identified interactions with the burrow by birds, mammals, and reptiles. Overall, we discovered 31 other species utilizing badger burrows, consisting of 12 mammals, 18 birds, and 1 reptile. Mammals, other than American badgers themselves and other fossorial species such as ground squirrels (Urocitellus sp.), frequently using burrows included mice (Peromyscus sp.), long‐tailed weasel (Mustela frenata), pygmy rabbit (Brachylagus idahoensis), and desert cottontail (Sylvilagus audubonii). Of the 18 bird species detected, most accounted for <5% of overall detections, besides chipping sparrows (Spizella passerina) at 7.2%–11.5% of detections. The most common category of detection by bird species was foraging, contrary to mammals, which used the burrow frequently and were commonly observed entering and exiting the burrow. This work provides additional context on the ecological role of American badgers within their environment. More broadly, this work scratches the surface of many remaining questions to explore with the aim of advancing our understandings about burrow webs across the diversity of burrowing species and the communities in which they occur.
Layer‐specific global longitudinal strain and the risk of heart failure and cardiovascular mortality in the general population: the Copenhagen City Heart Study
Authors: Skaarup Kristoffer Grundtvig , Lassen Mats C.H. , Johansen Niklas D. , Sengeløv Morten , Marott Jacob L. , Jørgensen Peter G. , Jensen Gorm , Schnohr Peter , Prescott Eva , Søgaard Peter , Gislason Gunnar , Møgelvang Rasmus , Biering‐Sørensen Tor
Published: July 2021

Aims

Layer‐specific global longitudinal strain (GLS) has been demonstrated to predict outcome in various patient cohorts. However, little is known regarding the prognostic value of layer‐specific GLS in the general population and whether different layers entail differential prognostic information. The aim of the present study was to investigate the prognostic value of whole wall (GLSWW), endomyocardial (GLSEndo), and epimyocardial (GLSEpi) GLS in the general population.

Methods and results

A total of 4013 citizens were included in the present study. All 4013 had two‐dimensional speckle tracking echocardiography performed and analysed. Outcome was a composite endpoint of incident heart failure and/or cardiovascular death. Mean age was 56 years and 57% were female. During a median follow‐up time of 3.5 years, 133 participants (3.3%) reached the composite outcome. Sex modified the relationship between all GLS parameters and outcome. In sex‐stratified analysis, no GLS parameter remained significant predictors of outcome in females. In contrast, GLSWW [hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.02–1.31, per 1% decrease] and GLSEpi (HR 1.19, 95% CI 1.04–1.38, per 1% decrease) remained as significant predictors of outcome in males after multivariable adjustment (including demographic, clinical, biochemistry, and echocardiographic parameters). Lastly, only in males did GLS parameters provide incremental prognostic information to general population risk models.

Conclusions

In the general population, sex modifies the prognostic value of GLS resulting in GLSEpi being the only layer‐specific prognosticator in males, while no GLS parameter provides independent prognostic information in females.
Improvement of Photoelectrocatalytic Activity and Stability of WO3 for Oxygen Photoevolution Reaction by Loading of Brownmillerite‐Type Ca2FeCoO5 as a Cocatalyst
Authors: Tsuji Etsushi , Degami Yoshiki , Okada Hiroyuki , Suganuma Satoshi , Katada Naonobu
Published: July 2021

Brownmillerite‐type Ca2FeCoO5 (CFCO), whose crystal structure is categorized into an oxygen‐deficiency‐ordered perovskite, is one of the most effective catalysts for the oxygen evolution reaction (OER). Herein, CFCO is applied as a cocatalyst of WO3 for the oxygen photoevolution reaction under visible light illumination. CFCO is synthesized by a sol−gel method and calcination at 873 K and loaded on a WO3 electrode by an electrophoretic deposition method. The photocatalytic activity of WO3 for the oxygen photoevolution reaction is improved by loading an appropriate amount of CFCO to reach a close level of RuO2/WO3 and Co−Pi/WO3. Furthermore, photocorrosion of WO3 is suppressed by CFCO loading, leading to high stability. Because both the lower edge of the conduction band and the upper edge of the valence band of CFCO are higher than those of WO3, only photoexcited holes at WO3 move to CFCO and easily react with water on the CFCO surface, leading to acceleration of the OER and suppressing of photocorrosion of WO3.
The epileptogenic zone in children with tuberous sclerosis complex is characterized by prominent features of focal cortical dysplasia
Authors: Hulshof Hanna M. , Benova Barbora , Krsek Pavel , Kyncl Martin , Lequin Maarten H. , Belohlavkova Anezka , Jezdik Petr , Braun Kees P. J. , Jansen Floor E.
Published: July 2021

Objective

Patients with tuberous sclerosis complex (TSC) present with drug‐resistant epilepsy in about 60% of cases, and evaluation for epilepsy surgery may be warranted. Correct delineation of the epileptogenic zone (EZ) among multiple dysplastic lesions on MRI represents a challenging step in pre‐surgical evaluation.

Methods

Two experienced neuroradiologists evaluated pre‐ and post‐surgical MRIs of 28 epilepsy surgery patients with TSC, assessing characteristics of tubers, cysts, calcifications, and focal cortical dysplasia (FCD)—resembling lesions. Utilizing multiple metrics, we compared MRI features of the EZ—defined as the resected area in TSC patients who achieved seizure‐freedom 2 years after epilepsy surgery—with features of other brain areas. Using combinatorial analysis, we identified combinations of dysplastic features that are most frequently observed in the epileptogenic zone in TSC patients.

Results

All TSC‐associated dysplastic features were more frequently observed in the EZ than in other brain areas (increased cortical thickness, gray‐white matter blurring, transmantle sign, calcifications, and tubers; Kendal's tau 0.35, 0.25, 0.27, 0.26, and 0.23, respectively; P value <.001 in all). No single feature could reliably and independently indicate the EZ in all patients. Conversely, the EZ was indicated by the presence of the combination of three of the following features: tubers, transmantle sign, increased cortical thickness, calcifications, and the largest FCD‐affected area. Out of these, the largest FCD‐affected area emerged as the most reliable indicator of the EZ, combined either with calcifications or tubers.

Significance

The epileptogenic zone in TSC patients harbors multiple dysplastic features, consistent with focal cortical dysplasia. A specific combination of these features can indicate the EZ and aid in pre‐surgical MRI evaluation in epilepsy surgery candidates with TSC.
P2‐K0.76Fe0.2Mg0.1Mn0.7O2made from earth‐abundant elements for rechargeable potassium ion battery
Authors: Feng Jie , Luo Shao‐hua , Yang Liu , Cai Kexing , Dou Yuxin , Wang Qing , Zhang Yahui , Liu Xin
Published: July 2021

Due to the large volume change, limited energy density, large safety problems, and other factors restricting the development of potassium ion battery in the process of charge and discharge, the research on the cathode materials of potassium ion battery is an indispensable part. In this article, we designed and predicted P2‐type structures by introducing “cationic potential” that captures the key interactions of the layered materials. The precursors of the designed potassium ion battery cathode materials were obtained by co‐precipitation method. Through component analysis, the experimental conditions most in line with the theoretical content of precursors were found. The cathode material was synthesized by solid phase method. This material has a highly reversible K+insertion/deinsertion effect. The initial discharge specific capacity of the battery appears at about 47 mAh/g. After 30 charge‐discharge cycle tests, the discharge specific capacity of the battery drops to about 33 mAh/g, and the retention rate is about 70%.
Subchronic Exposure to Environmental Concentrations of Chlorpyrifos Affects Swimming Activity of Rainbow Trout Larvae
Authors: Weeks Santos Shannon , Gonzalez Patrice , Cormier Bettie , Mazzella Nicolas , Moreira Aurélie , Clérandeau Christelle , Morin Bénédicte , Cachot Jérôme
Published: July 2021

Chlorpyrifos (CPF), an organophosphorous pesticide, can be found in aquatic ecosystems at concentrations of up to several hundred nanograms per liter because of water runoff from treated crops. While some studies have shown that low concentrations of CPF may have adverse effects on aquatic species, comparatively little is known about its effect on fish embryos and larvae. To investigate the developmental effects of CPF, rainbow trout (Oncorhynchus mykiss) eyed-stage embryos were exposed in semistatic conditions to 0.3 and 3 µg/L of CPF up to the end of the sac-fry stage, 3 weeks, at 12 °C. Several endpoints were analyzed including survival, hatching delay, hatching success, biometry, swimming activity, DNA damage, lipid peroxidation, protein carbonyl content, acetylcholinesterase (AChE) activity, and gene expression. At the end of the 3-week exposure, larvae exposed to the highest concentration of CPF were less mobile compared to the control and the lowest CPF conditions. No significant differences in AChE activity were observed in either set of CPF conditions compared to control, but it was significantly reduced for larvae exposed to 3 µg/L compared to those exposed to 0.3 µg/L of CPF. Expression of genes that encoded estrogen receptor beta was downregulated for larvae exposed to both CPF concentrations. Expression of cytochrome P450 family 19 subfamily A member 1 was also significantly repressed but only on larvae exposed to the highest concentration of CPF. Our results indicated that subchronic exposure to environmental concentrations of CPF could lead to sublethal effects on early-life stages of rainbow trout, especially effects on swimming activity that could affect foraging activity and escaping from predators. Environ Toxicol Chem 2021;40:3092–3102. © 2021 SETAC
Increased functional interaction within frontoparietal network during working memory task in major depressive disorder
Authors: Cao Wanyi , Liao Haiyan , Cai Sainan , Peng Wanrong , Liu Zhaoxia , Zheng Kaili , Liu Jinyu , Zhong Mingtian , Tan Changlian , Yi Jinyao
Published: July 2021

Abnormal fronto‐parietal activation has been suggested as a neural underpinning of the working memory (WM) deficits in major depressive disorder (MDD). However, the potential interaction within the frontoparietal network during WM processing in MDD remains unclear. This study aimed to examine the role of abnormal functional interactions within frontoparietal network in the neuropathological mechanisms of WM deficits in MDD. A total of 40 MDD patients and 47 demographic matched healthy controls (HCs) were included. Functional magnetic resonance imaging and behavioral data were collected during numeric n‐back tasks. The psychophysiological interaction and dynamic causal modelling methods were applied to investigate the connectivity within the frontoparietal network in MDD during n‐back tasks. The psychophysiological interaction analysis revealed that MDD patients showed increased functional connectivity between the right inferior parietal lobule (IPL) and the right dorsolateral prefrontal cortex (dlPFC) compared with HCs during the 2‐back task. The dynamic causal modelling analysis revealed that MDD patients had significantly increased forward modulation connectivity from the right IPL to the right dlPFC than HCs during the 2‐back task. Partial correlation was used to calculate the relationship between connective parameters and psychological variables in the MDD group, which showed that the effective connectivity from right IPL to right dlPFC was correlated negatively with the sensitivity index d’ of WM performances and positively with the depressive severity in MDD group. In conclusion, the abnormal functional and effective connectivity between frontal and parietal regions might contribute to explain the neuropathological mechanism of working memory deficits in major depressive disorder.
New(spaper) evidence of a reduction in suicide mentions during the 19th century US gold rush
Authors: Kronenberg Christoph
Published: July 2021

I analyze the relationship between state‐level economic shocks and suicides using gold mined in the United States (US) between 1840 and 1860 as a large unexpected economic shock. Mined gold was an unexpected and large economic shock of up to 3.5% of GDP. This provides as good as random variation to the local economy that I use to estimate the effect of economic changes on suicides. Comprehensive mortality data by state and year does not exist for the US for 1840–1860. Thus, I use web‐scraped data from a newspaper archive and use suicide mentions per 100,000 pages to proxy for suicides. Overall, results show that mined gold is linked with an apparent reduction in newspaper suicide mentions in line with previous research.
HIV‐1 molecular epidemiology in Bangladesh: A systematic review
Authors: Molla Md. Maruf Ahmed , Yeasmin Mahmuda , Ghosh Asish Kumar , Nafisa Tasnim , Islam Md. Khairul , Saif‐Ur‐Rahman K.M.
Published: July 2021

Background and Aims

It is postulated that molecular methods along with mathematical modeling can provide critical inference regarding epidemiological parameters, transmission dynamics, spatiotemporal characteristics, and intervention efficacy. Hence, studying molecular epidemiology of human immunodeficiency virus (HIV)‐1 infection, especially in resource‐limited settings and with a large diaspora of the migrant population such as that of Bangladesh, is of paramount importance. The purpose of this systematic review was to concisely present and discuss the findings from previous studies conducted in Bangladesh regarding HIV‐1 subtype prevalence.

Methods

Articles were retrieved from six publicly available databases regarding HIV‐1 molecular epidemiology using keywords HIV, HIV‐1, subtype(s), Bangladesh, and any combination of aforementioned keywords using Boolean operators. A total of 14 articles were downloaded and screened for suitability. Finally, five studies, containing pooled sequences from 317 individuals, were included in this systematic review.

Results

Results revealed a preponderance of subtype C among HIV‐1 infected population (51.10%), followed by circulating recombinant form (CRF)_07BC (15.46%), CRF_01AE (5.68%), A1 (4.73%), CRF_02AG (3.47%), G (3.15%), CRF_62BC (2.84%), B (2.21%), and other subtypes and recombinant forms in small percentages. Subtype C was largely predominant in intravenous drug users as well as female sex workers, whereas the migrant population exhibited a diverse subtype including rare recombinant forms, largely due to their travel in the Middle East and other South East Asian countries.

Conclusion

With the number of HIV‐1 infections increasing among the general population and a steady increase in the migrant population, molecular epidemiological data are required to curb the progression of the HIV‐1 epidemic in Bangladesh.
Entropy generation and curvature effect on peristaltic thrusting of (Cu–Al2O3) hybrid nanofluid in resilient channel: Nonlinear analysis
Authors: Mekheimer Khaled S. , Abo‐Elkhair Rabea E. , Ali Khalid K. , Keshta Moustafa G.
Published: July 2021

The pharyngeal stage of bolus transport or blood motion in the arteries cannot ignore the effect of curvature and inertial forces in peristaltic channels. Thus, the nonlinear curvature of peristaltic pumping becomes significant when the moving wall induces a curvilinear fluid motion at infinite Reynolds numbers, also the intrauterine fluid flow in the case of curvature nonpregnant uterus is an application of it. Hybrid nanofluids are new types of nanofluids, which can be produced by the suspension of multiple kinds of nanoparticles in base fluids. A hybrid nanomaterial is a substance that contains chemical and physical features of multiple materials together and gives these features in a homogeneous phase. The synthetic hybrid nanomaterial reveals significant physio‐chemical features that do not present in the individual components. In this investigation, the flow of an incompressible viscous fluid driven by sinusoidal waves moves on boundaries of the symmetric channel is studied when inertia and streamline curvature effects are not negligible, where the flow of nanofluid and hybrid nanofluid has been utilized to investigate the axial and normal behavior of velocities and heat transfer. An approximate solution to the second‐order in the wavenumber (giving the curvature effect) is obtained. To transform the variable cross‐section of the channel to a uniform cross‐section, we used a domain transformation, and this facilitates an easy way of getting a closed‐form of solutions to higher orders. Also, the pressure gradient and time flow rate relations are obtained. The influence of various biophysical parameters has been demonstrated through the graphs. All flow properties, temperature profile, and rate of heat transfer at the walls are greatly influenced by the presence of copper nanofluid. Furthermore, we observed that the case of spherical‐shaped nanoparticles provides a better heat transfer ability as compared to the case of cylindrically shaped nanoparticles. The effects of inertia and curvature are discussed and compared with some previous results in the literature.
Quantification of perfusion and metabolism in an autism mouse model assessed by diffuse correlation spectroscopy andnear‐infraredspectroscopy
Authors: Rinehart Benjamin , Poon Chien‐Sing , Sunar Ulas
Published: July 2021

There is a need for quantitative biomarkers for early diagnosis of autism. Cerebral blood flow and oxidative metabolism parameters may show superior contrasts for improved characterization. Diffuse correlation spectroscopy (DCS) has been shown to be reliable method to obtain cerebral blood flow contrast in animals and humans. Thus, in this study, we evaluated the combination of DCS and fNIRS in an established autism mouse model. Our results indicate that autistic group had significantly (P = .001) lower (~40%) blood flow (1.16 ± 0.26) × 10−8 cm2/s), and significantly (P = .015) lower (~70%) oxidative metabolism (52.4 ± 16.6 μmol/100 g/min) compared to control group ([1.93 ± 0.74] × 10−8 cm2/s, 177.2 ± 45.8 μmol/100 g/min, respectively). These results suggest that the combination of DCS and fNIRS can provide hemodynamic and metabolic contrasts for in vivo assessment of autism pathological conditions noninvasively.
Biocompatibility of polyvinyl alcohol/trisodium trimetaphosphate as vitreous substitute in experimental vitrectomy model in rabbits
Authors: de Oliveira Ramon Antunes , Muralha Felipe Picanço , Grupenmacher Alex Treiger , de Araújo Morandim‐Giannetti Andreia , Bersanetti Patrícia Alessandra , Maia Maurício , Magalhães Junior Octaviano
Published: July 2021

Synthetic hydrogels have been proposed as vitreous substitutes recently. This study aims to evaluate the biocompatibility of polyvinyl alcohol (PVA) crosslinked with trisodium trimetaphosphate (SMTP) hydrogel in rabbit vitrectomized eyes. Seven animals were submitted to pars plana vitrectomy and the vitreous was replaced by PVA/SMTP hydrogel. Optical coherence tomography, fluorescein angiogram, clinical, and electrophysiological (ERG) examinations were analyzed at baseline, on postoperative days 7 and 30. The fellow eye was used as the control group. Hydrogel opacification was observed and ERG recordings were reduced in the hydrogel group in rod response, b‐wave cone response and flicker. A histological analysis showed retinal disorganization, presence of multinucleated cells, and intraretinal hydrogel particles. The PVA/SMTP hydrogel showed poor biocompatibility. Novel biomaterials compounds should be analyzed in vivo.
LINC00511 facilitates Temozolomide resistance of glioblastoma cells via sponging miR‐126‐5p and activating Wnt/β‐catenin signaling
Authors: Lu Yan , Tian Meng , Liu Jiongbo , Wang Kuanhong
Published: July 2021

Temozolomide (TMZ) is the first‐line chemotherapy drug for glioblastoma (GBM) but acquired TMZ resistance is frequently observed. Thus, a TMZ resistant GBM cell line U87‐R was established to search for potential long noncoding RNAs (lncRNAs) used in TMZ resistance. In our study, LINC00511 was identified as a TMZ resistance‐associated lncRNA in U87‐R cells by transcriptome RNA sequencing. The potential functions of LINC00511 were evaluated by quantitative real‐time polymerase chain reaction, cell viability assay, colony formation assay, western blot, soft agar assay, flow cytometry, tumor xenograft model, immunofluorescence, sphere formation assay, fluorescent in situ hybridization, luciferase reporter assay, and RNA pull‐down assay. We found that LINC00511 was upregulated in U87‐R cells and GBM samples, and correlated with poor prognosis of GBM patients. Silencing LINC00511 impaired TMZ tolerance of U87‐R cells, while LINC00511 overexpression increased TMZ resistance of sensitive GBM cells. Wnt/β‐catenin signaling was activated in U87‐R cells, and inhibiting Wnt/β‐catenin signaling enhanced TMZ sensitivity. Furthermore, LINC00511 was mainly distributed in the cytoplasm of GBM cells and regulated Wnt/β‐catenin activation by acting as a molecular sponge for miR‐126‐5p. Multiple genes of Wnt/β‐catenin signaling such as DVL3, WISP1, and WISP2 were targeted by miR‐126‐5p. MiR‐126‐5p restoration impaired TMZ resistance of GBM cells. In conclusion, our results provided a novel insight into acquired TMZ resistance of GBM cells and suggested LINC00511 as a potential biomarker or therapeutic target for GBM patients.
Trehalose alleviates doxorubicin‐induced cardiotoxicity in female Swiss albino mice by suppression of oxidative stress and autophagy
Authors: Abu‐Khudir Rasha , Ibrahim Wafaa M. , Shams Mohammed E. , Salama Afrah F.
Published: July 2021

Clinically, the use of doxorubicin (DOX) is limited due to DOX‐induced cardiotoxicity (DIC). The current study aimed to evaluate the cardioprotective effect of trehalose (TRE) against DIC in a female Swiss albino mouse model. Mice were divided into five experimental groups: Gp. I: saline control group (200 μl/mouse saline three times per week for 3 weeks day after day), Gp. II: DOX‐treated group (2 mg/kg body weight three times per week for 3 weeks day after day), Gp. III: TRE group (200 μg/mouse three times per week for 3 weeks day after day), Gp. IV: DOX + TRE cotreatment group (animals were coadministered with DOX and TRE as in Gp. II and III, respectively), and Gp. V: DOX + TRE posttreatment group (animals were treated with DOX as in Gp. II followed by treatment with TRE as in Gp. III). DOX‐treated mice showed significant elevation in cardiac injury biomarkers (lactate dehydrogenase, creatine kinase isoenzyme‐MB, and cardiac troponin I), cardiac oxidative stress (OS) markers (malondialdehyde and myeloperoxidase), and cardiac levels of autophagy‐related protein 5. Moreover, DOX significantly reduced the levels of total antioxidant capacity and activities of catalase and glutathione S‐transferase. In contrast, TRE treatment of DOX‐administered mice significantly improved almost all of the above‐mentioned assessed parameters. Furthermore, histopathological changes of cardiac tissues observed in mice treated with TRE in combination with DOX were significantly improved as compared to DOX‐treated animals. Taken together, the present study provides evidence that TRE has cardioprotective effects against DIC, which is likely mediated via suppression of OS and autophagy.
Resonance hyper‐Raman spectroscopy of deoxythymidine monophosphate
Authors: Yu Chi‐Nan , Hiramatsu Hirotsugu
Published: July 2021

A 532 nm‐excited resonance hyper‐Raman (HR) spectrum of deoxythymidine is reported. The 532 nm excitation satisfies the two‐photon resonance condition to the ππ* absorption band of the pyrimidine ring at 250–280 nm, and hence we recorded the resonance HR spectrum with high signal‐to‐noise ratio. The resonance HR spectrum of deoxythymidine is compared with its 266 nm‐excited resonance Raman spectrum. The remarkable similarity between these spectra indicates that the single electronic structure contributes to the resonance effect in each case. The peak assignment is given for the RHR bands by analogy with that for the resonance Raman spectrum. This study offers the fundamental information to study DNA using the HR spectroscopy.
Ceftaroline Dosage Optimized for Pediatric Patients With Renal Impairment Using Physiologically Based Pharmacokinetic Modeling
Authors: Zhou Jie , You Xiang , Guo Guimu , Ke Meng , Xu Jianwen , Ye Lingling , Wu Wanhong , Huang Pinfang , Lin Cuihong
Published: July 2021

Ceftaroline fosamil is a fifth‐generation cephalosporin approved as a treatment for adults and children with community‐acquired bacterial pneumonia and acute bacterial skin and skin structure infections. However, its pharmacokinetics have not been fully evaluated in children with renal impairment. This study aimed to propose proper ceftaroline dosages optimized for the renally impaired pediatric population using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of ceftaroline was established and verified to simulate its disposition in the healthy population and renally impaired adults and to predict the exposure in renally impaired pediatric patients. Consistency was confirmed between simulated and observed data after intravenous administration of various ceftaroline regimens; fold errors were within the 2‐fold error range. Among 6‐year‐old children, healthy subjects had 1.5‐fold, 2‐fold, and 2.6‐fold lower areas under the plasma concentration–time curve (AUCs) than the moderate, severe, and end‐stage renally impaired patient groups, respectively; among 1‐year‐old children, healthy subjects had 1.5‐fold, 2.1‐fold, and 2.5‐fold lower AUCs than the respective renally impaired patient groups; among 1‐month‐old children, healthy subjects had 1.5‐fold, 1.8‐fold, and 2.2‐fold lower AUCs than the respective renally impaired patient groups. The proposed dosage should be adjusted to 8, 6, and 5 mg/kg every 8 hours for patients aged ≥2 years to <18 years (≤33 kg) with moderate, severe, and end‐stage renal impairment, respectively; 5, 4, and 3 mg/kg every 8 hours for patients aged 2 months to <2 years with moderate, severe, and end‐stage renal impairment, respectively; 4, 3.5, and 2.5 mg/kg every 8 hours for patients 0 to <2 months of age with moderate, severe, and end‐stage renal impairment, respectively. Furthermore, pharmacodynamic investigations demonstrated that adequate antimicrobial effects were attained at the proposed doses in 3 age groups. Hence, our PBPK model can be an effective tool to support ceftaroline dosage proposals for renally impaired pediatric patients.
Influence of Renal Function on the Single‐Dose Pharmacokinetics of Besifovir, a Novel Antiviral Agent for theTreatment of Hepatitis B Virus Infection
Authors: Hwang Jun Gi , Kim Yu Kyong , Choi Young‐sim , Kwon Soon Kil , Han Joung‐Ho , Park Min Kyu
Published: July 2021

Per the well‐known resistance of hepatitis B virus to nucleoside/nucleotide analogs, alternative treatment options with higher resistance barriers have been approved for use in both treatment‐naïve and lamivudine‐resistant hepatitis B virus infections. This phase I study was conducted in adults with normal and impaired renal function to evaluate the effect of renal impairment on the pharmacokinetics of besifovir, a prodrug of an acyclic nucleotide phosphonate, that is mainly cleared via renal excretion. An open‐label, single‐dose parallel‐group clinical study was conducted in subjects with normal renal function and mild, moderate, and severe renal impairment. Subjects received a single oral dose of besifovir dipivoxil 150 mg, and serial blood and urine samples were collected for up to 72 hours after dosing to assess the pharmacokinetic characteristics of besifovir. The extent of plasma exposure of besifovir, detected as its major and active metabolites, LB80331 and LB80317, respectively, increased with worsening renal function. Compared to the subjects with normal renal function, the mean areas under the concentration‐time curves of LB80331 increased by 1.5‐, 2.5‐, and 4.5‐fold in subjects with mild, moderate, and severe impairment, respectively. LB80317 showed a 1.8‐, 3.2‐, and 6.2‐fold increase in subjects with mild, moderate, and severe renal impairment compared to those with normal function. The ratios of LB80331 renal clearance and the average estimated glomerular filtration rate of each renal impairment group with respect to the normal group were similar. The increase in plasma exposure and decrease in renal clearance suggest the need to adjust dosage regimens in patients with moderate to severe renal impairment.
Brexpiprazole Pharmacokinetics in CYP2D6 Poor Metabolizers: Using Physiologically Based Pharmacokinetic Modeling to Optimize Time to Effective Concentrations
Authors: Elmokadem Ahmed , Bruno Christopher D. , Housand Conrad , Jordie Eric Burroughs , Chow Christina R. , Lesko Lawrence J. , Greenblatt David J.
Published: July 2021

Brexpiprazole is an oral antipsychotic agent indicated for use in patients with schizophrenia, or as adjunctive treatment for major depressive disorder. As cytochrome P450 (CYP) 2D6 contributes significantly to brexpiprazole metabolism, there is a label‐recommended 50% reduction in dose among patients with the CYP2D6 poor metabolizer phenotype. This study uses a whole‐body physiologically based pharmacokinetic (PBPK) model to compare the pharmacokinetics of brexpiprazole in patients known to be extensive metabolizers (EMs) and poor metabolizers (PMs). A PBPK model was constructed, verified, and validated against brexpiprazole clinical data, and simulations of 500 subjects were performed to establish the median time to effective concentrations in EMs and PMs. The PBPK simulations captured brexpiprazole PK well and demonstrated significant differences in the time to effective concentrations between EMs and PMs according to the label‐recommended titration. Additionally, these simulations suggest that CYP2D6 PMs consistently achieve lower minimum concentrations during the dosing interval than CYP2D6 EMs. Simulations using an alternative dosing strategy of twice‐daily dosing (as opposed to once daily) in PMs during the first week of brexpiprazole dosing yielded more consistent plasma concentrations between EMs and PMs, without exceeding the area under the plasma concentration–time curve observed in the EMs. Taken together, the results of these PBPK simulations suggest that product labeling for brexpiprazole titration in CYP2D6 PMs likely overcompensates for the decreased clearance seen in this population. We propose an alternative dosing strategy that decreases the time to effective concentrations and recommend a reevaluation of steady‐state PK in this population to potentially allow for higher daily doses in CYP2D6 PMs.
Safety and efficacy of endoscopic cyanoacrylate injection in the management of gastric varices: A systematic review and meta‐analysis
Authors: Chirapongsathorn Sakkarin , Manatsathit Wuttiporn , Farrell Ann , Suksamai Anuchit
Published: July 2021

Background and Aim

Bleeding from gastric varices is a catastrophic event and poses difficulty in management. The efficacy and safety of cyanoacrylate injection remain unclear. We performed a systematic review and meta‐analysis to evaluate the effect of endoscopic cyanoacrylate injection in the management of gastric varices.

Methods

We conducted a comprehensive search of MEDLINE, Embase, Web of Science, Scopus databases, and Cochrane Database of Systematic Reviews through November 2020 and manually reviewed the literature. Trial‐specific risk ratios (RRs) were estimated and pooled using random‐effect model meta‐analysis.

Results

We included seven randomized controlled trials (six for secondary prophylaxis and one for primary prophylaxis) at low risk of bias in which 126 deaths were reported among 583 patients with gastric varices. All studies reported the use of N‐butyl‐2‐cyanoacrylate glue. Cyanoacrylate use was associated with significantly lower all‐cause mortality (RR, 0.59; 95% confidence interval [CI], 0.36–0.98; I2 = 41%) and rebleeding rate after hemostasis (RR, 0.49; 95% CI, 0.35–0.68, I2 = 0%) compared with any other treatment approach not involving cyanoacrylate. When cyanoacrylate was compared with each individual treatment approach (propranolol only, band ligation, sclerotherapy with alcohol or ethanolamine), data comprised sparse limited comparative conclusions. The use of cyanoacrylate injection was not associated with an increase in serious adverse events. The quality of evidence is moderate, graded down due to the small number of events and wide CIs.

Conclusion

The use of endoscopic cyanoacrylate injection therapy for gastric varices may be associated with lower all‐cause mortality and better hemostasis compared with other therapies.
Regulatory effect of m6A modification on different viruses
Authors: Yu Pei‐Lun , Cao San‐Jie , Wu Rui , Zhao Qin , Yan Qi‐Gui
Published: July 2021

N6‐methyladenosine (m6A) modification is the most common and reversible posttranscriptional modification of RNA in eukaryotes, which is mainly regulated by methyltransferase, demethylase, and specific binding protein. The replication of the virus and host immune response to the virus are affected by m6A modification. In different kinds of viruses, m6A modification has two completely opposite regulatory functions. This paper reviews the regulatory effects of m6A modification on different viruses and provides a reference for studying the regulatory effects of RNA epitranscriptomic modification.
Lineage and sublineage analysis of human papillomavirus type 56 in cervical samples of Iranian women
Authors: Jalali‐Alhosseini Parvin , Shoja Zabihollah , Soleimani‐Jelodar Rahim , Shokrallahnia‐Roshan Hadi , Jalilvand Somayeh
Published: July 2021

Understanding the regional lineages and sublineages of human papillomavirus type 56 (HPV 56) would be of great importance for further evolutionary, epidemiological, and biological investigations. To identify the distribution of lineages and sublineages of HPV 56 in Iran, the sequence variations of the E6 gene were analyzed in normal, premalignant, and malignant samples obtained from the cervix. In total, 58 HPV 56‐positive samples were investigated by nested‐PCR and followed by bidirectional direct nucleotide sequencing analysis. Both lineages A and B were identified in the studied samples. Lineage B was dominant as it was detected in 88.4% of all samples and the remaining samples belonged to lineage A (11.6%). Sublineages A1 and A2 were detected in 3.3% and 8.3% of all samples, respectively. With regard to the pathological stages of cervical specimens, no statistically significant differences were found in the three studied groups (p > 0.05). In conclusion, our findings showed that lineage B of HPV 56 was prevalent in Iran. However, further studies with a larger sample size are warranted to estimate the pathogenicity risk of HPV 56 lineages/sublineages to the progression of cervical cancer among Iranian women.
Gait function improvements, using Cardiff Classifier, are related to patient‐reported function and pain following hip arthroplasty
Authors: Biggs Paul , Holsgaard‐Larsen Anders , Holt Cathy A. , Naili Josefine E.
Published: July 2021

Summarizing results of three‐dimensional (3D) gait analysis into a comprehensive measure of overall gait function is valuable to discern to what extent gait function is affected, and later recovered after surgery and rehabilitation. This study aimed to investigate whether preoperative gait function, quantified and summarized using the Cardiff Classifier, can predict improvements in postoperative patient‐reported activities of daily living, and overall gait function 1 year after total hip arthroplasty (THA). Secondly, to explore relationships between pre‐to‐post surgical change in gait function versus changes in patient‐reported and performance‐based function. Thirty‐two patients scheduled for THA and 25 nonpathological individuals were included in this prospective cohort study. Patients were evaluated before THA and 1 year postoperatively using 3D gait analysis, patient‐reported outcomes, and performance‐based tests. Kinematic and kinetic gait parameters, derived from 3D gait analysis, were quantified using the Cardiff Classifier. Linear regressions investigated the predictive value of preoperative gait function on postoperative outcomes of function, and univariate correlations explored relationships between pre‐to‐post surgical changes in outcome measures. Preoperative gait function, by means of Cardiff Classifier, explained 35% and 30% of the total variance in change in patient‐reported activities of daily living, and in gait function, respectively. Moderate‐to‐strong correlations were found between change in gait function and change in patient‐reported function and pain, while no correlations were found between change in gait function and performance‐based function. Clinical significance: Preoperative gait function predicts postsurgical function to a moderate degree, while improvements in gait function after surgery are more closely related to how patients perceive function than their maximal performance of functional tests.
Rapid climate changes during the Lateglacial and the early Holocene as seen from plant community dynamics in the Polar Urals, Russia
Authors: Bjune Anne E. , Greve Alsos Inger , Brendryen Jo , Edwards Mary E. , Haflidason Haflidi , Johansen Maren S. , Mangerud Jan , Paus Aage , Regnéll Carl , Svendsen John‐Inge , Clarke Charlotte L.
Published: July 2021

A detailed, well‐dated record of pollen and sedimentary ancient DNA (sedaDNA) for the period 15 000–9500 cal a
bp describes changes at Lake Bolshoye Shchuchye in the Polar Ural Mountains, located far east of the classical Lateglacial sites in western Europe. Arctic tundra rapidly changed to lusher vegetation, possibly including both dwarf (Betula nana) and tree birch (B. pubescens), dated in our record to take place 14 565 cal a
bp, coincident with the onset of the Bølling in western Europe; this was paralleled by increased summer temperatures. A striking feature is an early decline in Betula pollen and sedaDNA reads 300 years before the onset of the Younger Dryas (YD) in western Europe. Given the solid site chronology, this could indicate that the YD cooling started in Siberia and propagated westwards, or that the vegetation reacted to the inter‐Allerød cooling at 13 100 cal a
bp and did not recover during the late Allerød. During the YD, increases in steppe taxa such as Artemisia and Chenopodiaceae suggest drier conditions. At the onset of the Holocene, the vegetation around the lake reacted fast to the warmer conditions, as seen in the increase of arboreal taxa, especially Betula, and a decrease in herbs such as Artemisia and Cyperaceae.
Relationship of soil pH value and soil Pb bio‐availability and Pb enrichment in tea leaves
Authors: Ye Jianghua , Zhang Qi , Liu Guoying , Lin Liwen , Wang Haibin , Lin Shunxian , Wang Yuchao , Wang Yuhua , Zhang Qingxu , Jia Xiaoli , He Haibin
Published: July 2021

BACKGROUND

Lead (Pb) is not an essential element for the growth of tea trees, but it is an important index for evaluating the quality and safety of tea. Lead is a sensitive metal to pH. Exploring the changing trend of soil Pb and enrichment coefficient of Pb in tea leaves affected by soil acidification is significant for tea planting and tea quality safety control.

RESULTS

A percent of 37.57% of the 364 tea plantations in Anxi county of China showed soil acidification that is a soil pH value < 4.5. However, the total Pb content in the soil and Pb content of tea leaves met the requirements stipulated in China. The soil available Pb content and Pb content in tea leaves were both significantly negatively correlated with soil pH value, and increased with the decrease of soil pH value. The soil available Pb content had a significant positive correlation with soil total Pb content. However, the soil total Pb content had no significant correlation with soil pH value. Moreover, the soil Pb bio‐availability coefficient and the Pb enrichment coefficient of tea leaves decreased with the increase of soil pH value.

CONCLUSION

More than a third of tea plantations in Anxi county had been acidified. The decrease of pH value leads to an increase in the bio‐availability coefficient of soil Pb content and the enrichment coefficient of Pb content in tea leaves. The lower soil pH value resulted in the increase of the absorption and accumulation of Pb by tea trees, thus an increase of Pb content in tea leaves. © 2021 Society of Chemical Industry.
Triazine‐based covalent organic polymer: A promising coating for solid‐phase microextraction
Authors: Wang Zhuo , Zhang Ying , Chang Guifen , Li Jinqiu , Yang Xiumin , Zhang Shuaihua , Zang Xiaohuan , Wang Chun , Wang Zhi
Published: July 2021

Advancement of novel coating materials for solid‐phase microextraction is highly needed for sample pretreatment. Herein, a triazine‐based covalent organic polymer was constructed from the monomers of cyanuric chloride and trans‐stilbene via the Friedel‐Crafts reaction and thereafter used as a solid‐phase microextraction fiber coating for the extraction of polycyclic aromatic hydrocarbons and their nitrated and oxygenated derivatives. The newly‐developed solid‐phase microextraction method coupled with gas chromatography/flame ionization detection gives enhancement factors of 548–1236 and limits of detection of 0.40–2.81 ng/L for the determination of polycyclic aromatic hydrocarbons and their derivatives. The one fiber precision for five replicate determinations of the analytes and the fiber‐to‐fiber precision with three parallel prepared fibers, expressed as relative standard deviations, was in the range of 4.6–9.4% and 6.2–10.9%, respectively. The relative recoveries of the analytes for environmental water samples were in the range of 88.6–106.4% with the relative standard deviations ranging from 4.0 to 11.7% (n = 5).
Inverse Design of Ultra‐Compact Multimode Waveguide Bends Based on the Free‐Form Curves
Authors: Sun Shangsen , Dong Penghui , Zhang Fengchun , Wang Juanli , Zhu Ning , Shi Yaocheng
Published: July 2021

On‐chip mode‐division multiplexing (MDM) can increase the transmission capacity of a single optical bus waveguide. It is of great significance for the MDM systems to design the multimode waveguide bends (MWBs) with compact sizes. A method of designing the MWB using the inverse design algorithm is presented in this paper. Ultra‐compact MWBs with high performances are realized by changing the curvature radius of the waveguide curve, and the fabrication process only requires a single step photo‐lithography and plasma etching. The three‐mode bent waveguide with an effective radius of only 9.35 µm is designed and tested. The theoretical excess losses of TE0, TE1, and TE2 mode are less than 0.04 dB in a wide spectral range of 1500 to 1600 nm, and the crosstalks between all guided modes are all less than −29 dB. For the fabricated 90° waveguide bend the measured excess losses are 0.17, 0.04, and 0.16 dB at the central wavelength of 1550 nm, respectively, and the crosstalks between all three modes are less than −21 dB in the wavelength range from 1520 to 1600 nm. The proposed design method can be also extended to more mode‐channels.
Cognitive Impairments in Spinocerebellar Ataxia Type 10 and Their Relation to Cortical Thickness
Authors: Chirino‐Pérez Amanda , Vaca‐Palomares Israel , Torres Diana L. , Hernandez‐Castillo Carlos R. , Diaz Rosalinda , Ramirez‐Garcia Gabriel , Fernandez‐Ruiz Juan
Published: July 2021

Background

Spinocerebellar ataxia type 10 is a neurodegenerative disorder caused by the expansion of an ATTCT pentanucleotide repeat. Its clinical features include ataxia and, in some cases, epileptic seizures. There is, however, a dearth of information about its cognitive deficits and the neural bases underpinning them.

Objectives

The objectives of this study were to characterize the performance of spinocerebellar ataxia type 10 patients in 2 cognitive domains typically affected in spinocerebellar ataxias, memory and executive function, and to correlate the identified cognitive impairments with ataxia severity and cerebral/cerebellar cortical thickness, as quantified by MRI.

Methods

Memory and executive function tests were administered to 17 genetically confirmed Mexican spinocerebellar ataxia type 10 patients, and their results were compared with 17 healthy matched volunteers. MRI was performed in 16 patients.

Results

Patients showed deficits in visual and visuospatial short‐term memory, reduced storage capacity for verbal memory, and impaired monitoring, planning, and cognitive flexibility, which were ataxia independent. Patients with seizures (n = 9) and without seizures (n = 8) did not differ significantly in cognitive performance. There were significant correlations between short‐term visuospatial memory impairment and posterior cerebellar lobe cortical thickness (bilateral lobule VI, IX, and right X). Cognitive flexibility deficiencies correlated with cerebral cortical thickness in the left middle frontal, cingulate, opercular, and temporal gyri. Cerebellar cortical thickness in several bilateral regions was correlated with motor impairment.

Conclusions

Patients with spinocerebellar ataxia type 10 show significant memory and executive dysfunction that can be correlated with deterioration in the posterior lobe of the cerebellum and prefrontal, cingulate, and middle temporal cortices. © 2021 International Parkinson and Movement Disorder Society