bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

AbstractAbnormal 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

AbstractI 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

AbstractBackground and AimsIt 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.MethodsArticles 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.ResultsResults 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.ConclusionWith 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

AbstractThe 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

AbstractThere 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

AbstractSynthetic 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

AbstractTemozolomide (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

AbstractClinically, 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

AbstractA 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

AbstractCeftaroline 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

AbstractPer 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

AbstractBrexpiprazole 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.