bluuebunny/crossref_metadata_2025 huggingface dataset:
Cochlear implantation in advanced otosclerosis: utility of pre-operative radiological assessment in predicting intra-operative difficulty and final electrode position
Authors: Wong D , Copson B , Gerard J-M , Hill F , Leigh J , Dowell R
Published: April 2023

Objective

This study aimed to determine if pre-operative radiological scoring can reliably predict intra-operative difficulty and final cochlear electrode position in patients with advanced otosclerosis.

Method

A retrospective cohort study of advanced otosclerosis patients who underwent cochlear implantation (n = 48, 52 ears) was compared with a larger cohort of post-lingually deaf adult patients (n = 1414) with bilateral hearing loss and normal cochlear anatomy. Pre-operative imaging for advanced otosclerosis patients and final electrode position were scored and correlated with intra-operative difficulty and speech outcomes.

Results

Advanced otosclerosis patients benefit significantly from cochlear implantation. Mean duration of deafness was longer in the advanced otosclerosis group (19.5 vs 14.3 years; p < 0.05).

Conclusion

Anatomical changes in advanced otosclerosis can result in increased difficulty of surgery. Evidence of pre-operative cochlear luminal changes was associated with intra-operative difficult insertion and final non-scala tympani position. Nearly all electrodes implanted in the advanced otosclerosis cohort were peri-modiolar. No reports of facial nerve stimulation were observed.
Autonomous social robots are real in the mind's eye of many
Authors: Caruana Nathan , Cross Emily S.
Published: April 2023

Clark and Fischer's dismissal of extant human–robot interaction research approaches limits opportunities to understand major variables shaping people's engagement with social robots. Instead, this endeavour categorically requires multidisciplinary approaches. We refute the assumption that people cannot (correctly or incorrectly) represent robots as autonomous social agents. This contradicts available empirical evidence, and will become increasingly tenuous as robot automation improves.
Increase of Simultaneous Soybean Failures Due To Climate Change
Authors: Goulart Henrique M. D. , van der Wiel Karin , Folberth Christian , Boere Esther , van den Hurk Bart
Published: April 2023

While soybeans are among the most consumed crops in the world, most of its production lies in the US, Brazil, and Argentina. The concentration of soybean growing regions in the Americas renders the supply chain vulnerable to regional disruptions. In 2012, anomalous hot and dry conditions occurring simultaneously in these regions led to low soybean yields, which drove global soybean prices to all‐time records. In this study, we explore climate change impacts on simultaneous extreme crop failures as the one from 2012. We develop a hybrid model, coupling a process‐based crop model with a machine learning model, to improve the simulation of soybean production. We assess the frequency and magnitude of events with similar or higher impacts than 2012 under different future scenarios, evaluating anomalies both with respect to present day and future conditions to disentangle the impacts of (changing) climate variability from the long‐term mean trends. We find long‐term trends in mean climate increase the frequency of 2012 analogs by 11–16 times and the magnitude by 4–15% compared to changes in climate variability only depending on the global climate scenario. Conversely, anomalies like the 2012 event due to changes in climate variability show an increase in frequency in each country individually, but not simultaneously across the Americas. We deduce that adaptation of the crop production practice to the long‐term mean trends of climate change may considerably reduce the future risk of simultaneous soybean losses across the Americas.
GOLD Observations of Longitudinal Variations in the Nighttime Equatorial Ionization Anomaly (EIA) Crests' Latitudes
Authors: Eastes R. W. , Karan D. K. , Martinis C. , Daniell R. E. , Gan Q. , Burns A. G. , McClintock W. E.
Published: April 2023

Each day the Global‐scale Observations of the Limb and Disk imager observes the equatorial ionization anomaly (EIA) near sunset from ∼10°E to ∼80°W geographic longitude. Most images cover ∼45° of longitude (∼3 hr), and most longitudes are observed multiple times. Monthly averages of EIA crests' latitude (EIA lats) versus longitude during March, September, and December 2020 have been analyzed. The EIA lats reflect the combined influence of winds, solar radiation, and fields (electric and magnetic) in the equatorial region. Winter solstice differs significantly from the equinoxes, which are similar, but there are notable similarities between all three. The similarities in the EIA lats during the seasons examined indicates that the magnetic equator to subsolar point separation influences them in all three seasons and that it has a more distinct, possibly more significant, influence than winds on the average latitudes.
The Role of Equatorially Forced Waves in Triggering Benguela Niño/Niña as Investigated by an Energy Flux Diagnosis
Authors: Song Qingyang , Aiki Hidenori , Tang Youmin
Published: April 2023

The Benguela Niño/Niña events manifest the anomalous signals of sea surface temperature (SST) in the coastal region of the tropical Atlantic Ocean. These events are triggered by the interannual modulation of either equatorial waves or local atmospheric forcing. In the present study, the mechanism that equatorial waves induce the coastal SST anomaly is investigated in terms of the transfer episodes of wave energy. The analysis suggests that most of the coastal events can be reproduced by subseasonal wind forcing with an interannual modulation that excites oceanic waves of the first three baroclinic modes. The transfer routes of wave energy illustrate the role of wave dynamics that explains how the interannual variability of SST in the equatorial Atlantic is connected with that in coastal regions. The linearly superposed sign‐indefinite potential energy flux owing to waves manifests its capability of sufficiently displacing the thermocline so as to trigger the coastal events. The results suggest that the equatorial wave signal is able to provide credible predictions for remotely forced Benguela Niño/Niña events if a proper transection in central equatorial Atlantic with an appropriate threshold is selected for observing.
The Climatology of Elevated Stratopause Events in the UA‐ICON Model and the Contribution of Gravity Waves
Authors: Karami Khalil , Borchert Sebastian , Eichinger Roland , Jacobi Christoph , Kuchar Ales , Mehrdad Sina , Pisoft Petr , Sacha Petr
Published: April 2023

The climatologies of the stratopause height and temperature in the UA‐ICON model are examined by comparing them to 17‐years (2005–2021) of Microwave Limb Sounder (MLS) observations. In addition, the elevated stratopause (ES) event occurrence, their main characteristics, and driving mechanisms in the UA‐ICON model are examined using three 30‐year time‐slice experiments. While UA‐ICON reasonably simulates the large‐scale stratopause properties similar to MLS observations, at polar latitudes in the Southern Hemisphere the stratopause is ∼8 K warmer and ∼3 km higher than observed. A time lag of about two months also exists in the occurrence of the tropical semiannual oscillation of the stratopause compared to the observations. ES events occur in ∼20% of the boreal winters, after major sudden stratospheric warmings (SSWs). Compared to the SSWs not followed by ES events (SSW‐only), the ES events are associated with the persistent tropospheric forcing and prolonged anomalies of the stratospheric jet. Our modeling results suggest that the contributions of both gravity waves (GW)s and resolved waves are important in explaining the enhanced residual circulation following ES events compared to the SSW‐only events but their contributions vary through the lifetime of ES events. We emphasize the role of the resolved wave drag in the ES formation as in the sensitivity test when the non‐orographic GW drag is absent, the anomalously enhanced resolved wave forcing in the mesosphere gives rise to the formation of the elevated stratopause at about 85 km.
110 μm thin endo-microscope for deep-brain in vivo observations of neuronal connectivity, activity and blood flow dynamics
Authors: Stibůrek Miroslav , Ondráčková Petra , Tučková Tereza , Turtaev Sergey , Šiler Martin , Pikálek Tomáš , Jákl Petr , Gomes André , Krejčí Jana , Kolbábková Petra , Uhlířová Hana , Čižmár Tomáš
Published: April 2023

Light-based in-vivo brain imaging relies on light transport over large distances of highly scattering tissues. Scattering gradually reduces imaging contrast and resolution, making it difficult to reach structures at greater depths even with the use of multiphoton techniques. To reach deeper, minimally invasive endo-microscopy techniques have been established. These most commonly exploit graded-index rod lenses and enable a variety of modalities in head-fixed and freely moving animals. A recently proposed alternative is the use of holographic control of light transport through multimode optical fibres promising much less traumatic application and superior imaging performance. We present a 110 μm thin laser-scanning endo-microscope based on this prospect, enabling in-vivo volumetric imaging throughout the whole depth of the mouse brain. The instrument is equipped with multi-wavelength detection and three-dimensional random access options, and it performs at lateral resolution below 1 μm. We showcase various modes of its application through the observations of fluorescently labelled neurones, their processes and blood vessels. Finally, we demonstrate how to exploit the instrument to monitor calcium signalling of neurones and to measure blood flow velocity in individual vessels at high speeds.
Oncogenic CALR mutant C-terminus mediates dual binding to the thrombopoietin receptor triggering complex dimerization and activation
Authors: Papadopoulos Nicolas , Nédélec Audrey , Derenne Allison , Şulea Teodor Asvadur , Pecquet Christian , Chachoua Ilyas , Vertenoeil Gaëlle , Tilmant Thomas , Petrescu Andrei-Jose , Mazzucchelli Gabriel , Iorga Bogdan I. , Vertommen Didier , Constantinescu Stefan N.
Published: April 2023

Calreticulin (CALR) frameshift mutations represent the second cause of myeloproliferative neoplasms (MPN). In healthy cells, CALR transiently and non-specifically interacts with immature N-glycosylated proteins through its N-terminal domain. Conversely, CALR frameshift mutants turn into rogue cytokines by stably and specifically interacting with the Thrombopoietin Receptor (TpoR), inducing its constitutive activation. Here, we identify the basis of the acquired specificity of CALR mutants for TpoR and define the mechanisms by which complex formation triggers TpoR dimerization and activation. Our work reveals that CALR mutant C-terminus unmasks CALR N-terminal domain, rendering it more accessible to bind immature N-glycans on TpoR. We further find that the basic mutant C-terminus is partially α-helical and define how its α-helical segment concomitantly binds acidic patches of TpoR extracellular domain and induces dimerization of both CALR mutant and TpoR. Finally, we propose a model of the tetrameric TpoR-CALR mutant complex and identify potentially targetable sites.
An α-chloroaldehyde-based formal synthesis of eribulin
Authors: Kaghad Anissa , Panagopoulos Dimitrios , Caballero-García Guillermo , Zhai Huimin , Britton Robert
Published: April 2023

Eribulin (Halaven) is the most structurally complex non-peptidic drug made by total synthesis and has challenged preconceptions of synthetic feasibility in drug discovery and development. However, despite decades of research, the synthesis and manufacture of eribulin remains a daunting task. Here, we report syntheses of the most complex fragment of eribulin (C14–C35) used in two distinct industrial routes to this important anticancer drug. Our convergent strategy relies on a doubly diastereoselective Corey–Chaykovsky reaction to affect the union of two tetrahydrofuran-containing subunits. Notably, this process relies exclusively on enantiomerically enriched α-chloroaldehydes as building blocks for constructing the three densely functionalized oxygen heterocycles found in the C14–C35 fragment and all associated stereocenters. Overall, eribulin can now be produced in a total of 52 steps, which is a significant reduction from that reported in both academic and industrial syntheses.
Astrocytic chloride is brain state dependent and modulates inhibitory neurotransmission in mice
Authors: Untiet Verena , Beinlich Felix R. M. , Kusk Peter , Kang Ning , Ladrón-de-Guevara Antonio , Song Wei , Kjaerby Celia , Andersen Mie , Hauglund Natalie , Bojarowska Zuzanna , Sigurdsson Björn , Deng Saiyue , Hirase Hajime , Petersen Nicolas C. , Verkhratsky Alexei , Nedergaard Maiken
Published: April 2023

Information transfer within neuronal circuits depends on the balance and recurrent activity of excitatory and inhibitory neurotransmission. Chloride (Cl−) is the major central nervous system (CNS) anion mediating inhibitory neurotransmission. Astrocytes are key homoeostatic glial cells populating the CNS, although the role of these cells in regulating excitatory-inhibitory balance remains unexplored. Here we show that astrocytes act as a dynamic Cl− reservoir regulating Cl− homoeostasis in the CNS. We found that intracellular chloride concentration ([Cl−]i) in astrocytes is high and stable during sleep. In awake mice astrocytic [Cl−]i is lower and exhibits large fluctuation in response to both sensory input and motor activity. Optogenetic manipulation of astrocytic [Cl−]i directly modulates neuronal activity during locomotion or whisker stimulation. Astrocytes thus serve as a dynamic source of extracellular Cl− available for GABAergic transmission in awake mice, which represents a mechanism for modulation of the inhibitory tone during sustained neuronal activity.
The F-pilus biomechanical adaptability accelerates conjugative dissemination of antimicrobial resistance and biofilm formation
Authors: Patkowski Jonasz B. , Dahlberg Tobias , Amin Himani , Gahlot Dharmender K. , Vijayrajratnam Sukhithasri , Vogel Joseph P. , Francis Matthew S. , Baker Joseph L. , Andersson Magnus , Costa Tiago R. D.
Published: April 2023

Conjugation is used by bacteria to propagate antimicrobial resistance (AMR) in the environment. Central to this process are widespread conjugative F-pili that establish the connection between donor and recipient cells, thereby facilitating the spread of IncF plasmids among enteropathogenic bacteria. Here, we show that the F-pilus is highly flexible but robust at the same time, properties that increase its resistance to thermochemical and mechanical stresses. By a combination of biophysical and molecular dynamics methods, we establish that the presence of phosphatidylglycerol molecules in the F-pilus contributes to the structural stability of the polymer. Moreover, this structural stability is important for successful delivery of DNA during conjugation and facilitates rapid formation of biofilms in harsh environmental conditions. Thus, our work highlights the importance of F-pilus structural adaptations for the efficient spread of AMR genes in a bacterial population and for the formation of biofilms that protect against the action of antibiotics.
Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula
Authors: Wang Muran , Li Peijun , Li Zewen , da Silva Beatriz S. , Zheng Wu , Xiang Zhenghua , He Yan , Xu Tao , Cordeiro Cristina , Deng Lu , Dai Yuwei , Ye Mengqian , Lin Zhiqing , Zhou Jianhong , Zhou Xuzhao , Ye Fenfen , Cunha Rodrigo A. , Chen Jiangfan , Guo Wei
Published: April 2023

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.
Switchable biomimetic nanochannels for on-demand SO2 detection by light-controlled photochromism
Authors: Zhang Dan , Sun Yongjie , Wang Zhichao , Liu Fang , Zhang Xuanjun
Published: April 2023

In contrast to the conventional passive reaction to analytes, here, we create a proof-of-concept nanochannel system capable of on-demand recognition of the target to achieve an unbiased response. Inspired by light-activatable biological channelrhodopsin-2, photochromic spiropyran/anodic aluminium oxide nanochannel sensors are constructed to realize a light-controlled inert/active-switchable response to SO2 by ionic transport behaviour. We find that light can finely regulate the reactivity of the nanochannels for the on-demand detection of SO2. Pristine spiropyran/anodic aluminium oxide nanochannels are not reactive to SO2. After ultraviolet irradiation of the nanochannels, spiropyran isomerizes to merocyanine with a carbon‒carbon double bond nucleophilic site, which can react with SO2 to generate a new hydrophilic adduct. Benefiting from increasing asymmetric wettability, the proposed device exhibits a robust photoactivated detection performance in SO2 detection in the range from 10 nM to 1 mM achieved by monitoring the rectified current.
A severe neurodegenerative disease with Lewy bodies and a mutation in the glucocerebrosidase gene
Authors: Sipilä Jussi O. T. , Kytövuori Laura , Rauramaa Tuomas , Rauhamaa Hugo , Kaasinen Valtteri , Majamaa Kari
Published: April 2023

Several heterozygous variants of the glucocerebrosidase gene (GBA1) have been reported to increase the risk of Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). GBA1-associated PD has been reported to be more severe than idiopathic PD, and more deleterious variants are associated with more severe clinical phenotypes. We report a family with a heterozygous p.Pro454Leu variant in GBA1. The variant was associated with a severe and rapidly progressive neurodegenerative disease with Lewy bodies that were clinically and pathologically diverse. Pathogenicity prediction algorithms and evolutionary analyses suggested that p.Pro454Leu is deleterious.
Experimental analysis on cyanide removal of gold tailings under medium-temperature roasting
Authors: Hai Long , Fang Xianglong , Zhao Xin , Xu Bo , Cheng Tongjun
Published: April 2023

The cyanide content of gold tailings exceeds the standard seriously due to the cyanide extraction process. In order to improve the resource utilization efficiency of gold tailings, a medium-temperature roasting experiment was carried out on the stock tailings of Paishanlou gold mine after washing and pressing filtration treatment. The thermal decomposition rule of cyanide in gold tailings was analyzed, and the effects of different roasting temperatures and roasting durations on cyanide removal efficiency were compared. The results show that when the roasting temperature reaches 150 °C, the weak cyanide compound and free cyanide in the tailings begin to decompose. When the calcination temperature reached 300 °C, the complex cyanide compound began to decompose. When the roasting temperature reaches the initial temperature of cyanide decomposition, the cyanide removal efficiency can be improved by prolonging the roasting time. After roasting at 250–300 °C for 30–40 min, the total cyanide content in the toxic leachate decreased from 3.27 to 0.01 mg/L, which met the water quality standard of III class in China. The research results provide a low-cost and efficient way for cyanide treatment, which is of great significance for promoting the resource utilization of gold tailings and other cyanide-containing wastes.
Single-blind validation of space-based point-source detection and quantification of onshore methane emissions
Authors: Sherwin Evan D. , Rutherford Jeffrey S. , Chen Yuanlei , Aminfard Sam , Kort Eric A. , Jackson Robert B. , Brandt Adam R.
Published: April 2023

Satellites are increasingly seen as a tool for identifying large greenhouse gas point sources for mitigation, but independent verification of satellite performance is needed for acceptance and use by policy makers and stakeholders. We conduct to our knowledge the first single-blind controlled methane release testing of satellite-based methane emissions detection and quantification, with five independent teams analyzing data from one to five satellites each for this desert-based test. Teams correctly identified 71% of all emissions, ranging from 0.20 [0.19, 0.21] metric tons per hour (t/h) to 7.2 [6.8, 7.6] t/h. Three-quarters (75%) of quantified estimates fell within ± 50% of the metered value, comparable to airplane-based remote sensing technologies. The relatively wide-area Sentinel-2 and Landsat 8 satellites detected emissions as low as 1.4 [1.3, 1.5, 95% confidence interval] t/h, while GHGSat’s targeted system quantified a 0.20 [0.19, 0.21] t/h emission to within 13%. While the fraction of global methane emissions detectable by satellite remains unknown, we estimate that satellite networks could see 19–89% of total oil and natural gas system emissions detected in a recent survey of a high-emitting region.
KLB and NOX4 expression levels as potential blood-based transcriptional biomarkers of physical activity in children
Authors: Galmés Sebastià , Rupérez Azahara I. , Sánchez Juana , Moreno Luis A. , Foraita Ronja , Hebestreit Antje , Molnár Dénes , Palou Andreu , Picó Catalina
Published: April 2023

Insufficient physical activity (PA) in children is considered one of the major contributors to obesity and cardiometabolic complications later in life. Although regular exercise may contribute to disease prevention and health promotion, reliable early biomarkers are required to objectively discern people performing low PA from those who exercise enough. Here, we aimed to identify potential transcript-based biomarkers through the analysis of a whole-genome microarray in peripheral blood cells (PBC) from physically less active (n = 10) comparing with more active (n = 10) children. A set of genes differentially expressed (p < 0.01, Limma test) in less physically active children were identified, including the down-regulation of genes related to cardiometabolic benefits and improved skeletal function (KLB,NOX4, andSYPL2), and the up-regulation of genes whose elevated expression levels are associated with metabolic complications (IRX5,UBD, andMGP). The analysis of the enriched pathways significantly affected by PA levels were those associated with protein catabolism, skeletal morphogenesis, and wound healing, among others, which may suggest a differential impact of low PA on these processes. Microarray analysis comparing children according to their usual PA has revealed potential PBC transcript-based biomarkers that may be useful in early discerning children expending high sedentary time and its associated negative consequences.
Setback zones can effectively reduce exposure to sea-level rise in Europe
Authors: Wolff Claudia , Bonatz Hedda , Vafeidis Athanasios T.
Published: April 2023

Coastal space is one of the most valuable assets of the EU coastal member states, as the coast is highly urbanized. Hard engineering has traditionally been employed to protect communities in coastal lowlands, but as this alternative becomes less sustainable and more costly, coastal managers are increasingly turning to landuse planning strategies, such as setback zones or managed retreat. To explore the efficiency of these planning tools in reducing future urban exposure to sea-level rise and associated hazards, we developed spatially explicit projections of urban extent that account for different socio-economic futures and various types of setback zones. We find that the establishment of coastal setback zones can reduce the exposure of new urban development by at least 50% in the majority of EU countries by 2100. Our results emphasize that future urban exposure to sea-level rise will be significantly influenced by the ways in which we plan, design, and develop urban space in the EU coastal lowlands.
CRISPR-resolved virus-host interactions in a municipal landfill include non-specific viruses, hyper-targeted viral populations, and interviral conflicts
Authors: George Nikhil A. , Hug Laura A.
Published: April 2023

Viruses are the most abundant microbial guild on the planet, impacting microbial community structure and ecosystem services. Viruses are specifically understudied in engineered environments, including examinations of their host interactions. We examined host-virus interactions via host CRISPR spacer to viral protospacer mapping in a municipal landfill across two years. Viruses comprised ~ 4% of both the unassembled reads and assembled basepairs. A total of 458 unique virus-host connections captured hyper-targeted viral populations and host CRISPR array adaptation over time. Four viruses were predicted to infect across multiple phyla, suggesting that some viruses are far less host-specific than is currently understood. We detected 161 viral elements that encode CRISPR arrays, including one with 187 spacers, the longest virally-encoded CRISPR array described to date. Virally-encoded CRISPR arrays targeted other viral elements in interviral conflicts. CRISPR-encoding proviruses integrated into host chromosomes were latent examples of CRISPR-immunity-based superinfection exclusion. The bulk of the observed virus-host interactions fit the one-virus-one-host paradigm, but with limited geographic specificity. Our networks highlight rare and previously undescribed complex interactions influencing the ecology of this dynamic engineered system. Our observations indicate landfills, as heterogeneous contaminated sites with unique selective pressures, are key locations for atypical virus-host dynamics.
A comprehensive analysis of gene expression profiling data in COVID-19 patients for discovery of specific and differential blood biomarker signatures
Authors: Momeni Maryam , Rashidifar Maryam , Balam Farinaz Hosseini , Roointan Amir , Gholaminejad Alieh
Published: April 2023

COVID-19 is a newly recognized illness with a predominantly respiratory presentation. Although initial analyses have identified groups of candidate gene biomarkers for the diagnosis of COVID-19, they have yet to identify clinically applicable biomarkers, so we need disease-specific diagnostic biomarkers in biofluid and differential diagnosis in comparison with other infectious diseases. This can further increase knowledge of pathogenesis and help guide treatment. Eight transcriptomic profiles of COVID-19 infected versus control samples from peripheral blood (PB), lung tissue, nasopharyngeal swab and bronchoalveolar lavage fluid (BALF) were considered. In order to find COVID-19 potential Specific Blood Differentially expressed genes (SpeBDs), we implemented a strategy based on finding shared pathways of peripheral blood and the most involved tissues in COVID-19 patients. This step was performed to filter blood DEGs with a role in the shared pathways. Furthermore, nine datasets of the three types of Influenza (H1N1, H3N2, and B) were used for the second step. Potential Differential Blood DEGs of COVID-19 versus Influenza (DifBDs) were found by extracting DEGs involved in only enriched pathways by SpeBDs and not by Influenza DEGs. Then in the third step, a machine learning method (a wrapper feature selection approach supervised by four classifiers of k-NN, Random Forest, SVM, Naïve Bayes) was utilized to narrow down the number of SpeBDs and DifBDs and find the most predictive combination of them to select COVID-19 potential Specific Blood Biomarker Signatures (SpeBBSs) and COVID-19 versus influenza Differential Blood Biomarker Signatures (DifBBSs), respectively. After that, models based on SpeBBSs and DifBBSs and the corresponding algorithms were built to assess their performance on an external dataset. Among all the extracted DEGs from the PB dataset (from common PB pathways with BALF, Lung and Swab), 108 unique SpeBD were obtained. Feature selection using Random Forest outperformed its counterparts and selected IGKC, IGLV3-16 and SRP9 among SpeBDs as SpeBBSs. Validation of the constructed model based on these genes and Random Forest on an external dataset resulted in 93.09% Accuracy. Eighty-three pathways enriched by SpeBDs and not by any of the influenza strains were identified, including 87 DifBDs. Using feature selection by Naive Bayes classifier on DifBDs, FMNL2, IGHV3-23, IGLV2-11 and RPL31 were selected as the most predictable DifBBSs. The constructed model based on these genes and Naive Bayes on an external dataset was validated with 87.2% accuracy. Our study identified several candidate blood biomarkers for a potential specific and differential diagnosis of COVID-19. The proposed biomarkers could be valuable targets for practical investigations to validate their potential.
Identification of two insecticide resistance markers in Ethiopian Anopheles stephensi mosquitoes using a multiplex amplicon sequencing assay
Authors: Acford-Palmer Holly , Phelan Jody E. , Tadesse Fitsum G. , Kristan Mojca , Collins Emma , Spadar Anton , Walker Thomas , Bousema Teun , Messenger Louisa A. , Clark Taane G. , Campino Susana
Published: April 2023

Since its first detection in 2012 in Djibouti, Anopheles stephensi has invaded and established in the Horn of Africa, and more recently Nigeria. The expansion of this vector poses a significant threat to malaria control and elimination efforts. Integrated vector management is the primary strategy used to interrupt disease transmission; however, growing insecticide resistance is threatening to reverse gains in global malaria control. We present a next-generation amplicon-sequencing approach, for high-throughput monitoring of insecticide resistance genes (ace1, GSTe2, vgsc and rdl), species identification and characterization of genetic diversity (its2 and cox1) in An. stephensi. Ninety-five An. stephensi mosquitoes, collected in Ethiopia, were screened, identifying 104 SNPs, including the knock-down mutation L958F (L1014F in Musca domestica), and for the first time in this vector species, the A296S substitution (A301S in Drosophila melanogaster) in the rdl locus. Two other amino acid substitutions (ace1-N177D, GSTe2-V189L) were also identified but have not been previously implicated in insecticide resistance. Genetic diversity in the mitochondrial cox1 gene revealed shared haplotypes between Ethiopian An. stephensi with samples from Pakistan, Sudan, and Djibouti. Overall, we present a reliable, cost-effective strategy using amplicon-sequencing to monitor known insecticide resistance mutations, with the potential to identify new genetic variants, to assist in the high-throughput surveillance of insecticide resistance in An. stephensi populations.
Synthesis of pyrido-annelated [1,2,4,5]tetrazines, [1,2,4]triazepine, and [1,2,4,5]tetrazepines for anticancer, DFT, and molecular docking studies
Authors: Hassan Aisha Y. , Shabaan Sara N. , El-Sebaey Samiha A. , Abou-Amra Eman S.
Published: April 2023

In this strategy, we attempt to design various novel nitrogen-rich heterocycles in one molecule. Green, simple, and efficient aza-annulations of an active, versatile building block, 1-amino-4-methyl-2-oxo-6-phenyl-1,2-dihydropyridine-3-carbonitrile (1), with different bifunctional reagents were developed under solvent-free conditions, resulting in the bridgehead tetrazines and azepines (triazepine and tetrazepines). Pyrido[1,2,4,5]tetrazines have been synthesized through two pathways; [3 + 3]- and [5 + 1]-annulations. In addition, pyrido-azepines have been developed by applying [4 + 3]-and [5 + 2]-annulations. This protocol establishes an efficient technique for synthesizing essential biological derivatives of 1,2,4,5-tetrazines, 1,2,4-triazepines, and 1,2,4,5-tetrazepine, tolerating a diverse variety of functionalities without the need for catalysis and fast reaction rates in high yields. The National Cancer Institute (NCI, Bethesda, USA) examined twelve compounds produced at a single high dosage (10−5 M). Compounds4,8, and9were discovered to have potent anticancer action against certain cancer cell types. To explain NCI results, the density of states was calculated to conduct a better description of the FMOs. The molecular electrostatic potential maps were created to explain a molecule's chemical reactivity. In silico ADME experiments were performed to better understand their pharmacokinetic characteristics. Finally, the molecular docking investigations on Janus Kinase-2 (PDB ID:4P7E) were carried out to study the binding mechanism, binding affinity, and non-bonding contacts.
Persistence of Toscana virus in sugar and blood meals of phlebotomine sand flies: epidemiological and experimental consequences
Authors: Laroche Lison , Ayhan Nazli , Charrel Rémi , Bañuls Anne-Laure , Prudhomme Jorian
Published: April 2023

Many virological studies have tested the persistence of enveloped RNA viruses in various environmental and laboratory conditions and shown their short-term persistence. In this article, we analyzed Toscana virus (TOSV) infectivity, a pathogenic sandfly-borne phlebovirus, in two different conditions: in the sugar meal and blood meal of sand flies. Our results showed that TOSV RNA was detectable up to 15 days in sugar solution at 26 °C and up to 6 h in blood at 37 °C. Moreover, TOSV remains infective for 7 days in sugar solution and for minimum 6 h in rabbit blood. TOSV has shown persistent infectivity/viability under different conditions, which may have important epidemiological consequences. These results strengthen new hypotheses about the TOSV natural cycle, such as the possibility of horizontal transmission between sand flies through infected sugar meal.
Eco-morphodynamic carbon pumping by the largest rivers in the Neotropics
Authors: Salerno Luca , Vezza Paolo , Perona Paolo , Camporeale Carlo
Published: April 2023

The eco-morphodynamic activity of large tropical rivers in South and Central America is analyzed to quantify the carbon flux from riparian vegetation to inland waters. We carried out a multi-temporal analysis of satellite data for all the largest rivers in the Neotropics (i.e, width > 200 m) in the period 2000–2019, at 30 m spatial resolution. We developed a quantification of a highly efficient Carbon Pump mechanism. River morphodynamics is shown to drive carbon export from the riparian zone and to promote net primary production by an integrated process through floodplain rejuvenation and colonization. This pumping mechanism alone is shown to account for 8.9 million tons/year of carbon mobilization in these tropical rivers. We identify signatures of the fluvial eco-morphological activity that provide proxies for the carbon mobilization capability associated with river activity. We discuss river migration—carbon mobilization nexus and effects on the carbon intensity of planned hydroelectric dams in the Neotropics. We recommend that future carbon-oriented water policies on these rivers include a similar analysis.
2-[18F]FDG-PET/CT is a better predictor of survival than conventional CT: a prospective study of response monitoring in metastatic breast cancer
Authors: Vogsen Marianne , Naghavi-Behzad Mohammad , Harbo Frederik Graae , Jakobsen Nick Møldrup , Gerke Oke , Asmussen Jon Thor , Nissen Henriette Juel , Dahlsgaard-Wallenius Sara Elisabeth , Braad Poul-Erik , Jensen Jeanette Dupont , Ewertz Marianne , Hildebrandt Malene Grubbe
Published: April 2023

This study aimed to compare CE-CT and 2-[18F]FDG-PET/CT for response monitoring metastatic breast cancer (MBC). The primary objective was to predict progression-free and disease-specific survival for responders vs. non-responders on CE-CT and 2-[18F]FDG-PET/CT. The secondary objective was to assess agreement between response categorization for the two modalities. Treatment response in women with MBC was monitored prospectively by simultaneous CE-CT and 2-[18F]FDG-PET/CT, allowing participants to serve as their own controls. The standardized response evaluation criteria in solid tumors (RECIST 1.1) and PET response criteria in solid tumors (PERCIST) were used for response categorization. For prediction of progression-free and disease-specific survival, treatment response was dichotomized into responders (partial and complete response) and non-responders (stable and progressive disease) at the first follow-up scan. Progression-free survival was defined as the time from baseline until disease progression or death from any cause. Disease-specific survival was defined as the time from baseline until breast cancer-specific death. Agreement between response categorization for both modalities was analyzed for all response categories and responders vs. non-responders. At the first follow-up, tumor response was reported more often by 2-[18F]FDG-PET/CT than CE-CT, with only fair agreement on response categorization between the two modalities (weighted Kappa 0.28). Two-year progression-free survival for responders vs. non-responders by CE-CT was 54.2% vs. 46.0%, compared with 59.1% vs. 14.3% by 2-[18F]FDG-PET/CT. Correspondingly, 2-year disease-specific survival were 83.3% vs. 77.8% for CE-CT and 84.6% vs. 61.9% for 2-[18F]FDG-PET/CT. Tumor response on 2-[18F]FDG-PET/CT was significantly associated with progression-free (HR: 3.49, P < 0.001) and disease-specific survival (HR 2.35, P = 0.008), while no association was found for tumor response on CE-CT. In conclusion, 2-[18F]FDG-PET/CT appears a better predictor of progression-free and disease-specific survival than CE-CT when used to monitor metastatic breast cancer. In addition, we found low concordance between response categorization between the two modalities.

Trial registration: Clinical.Trials.gov. NCT03358589. Registered 30/11/2017-Retrospectively registered, http://www.ClinicalTrials.gov.
Effects of COVID-19 pandemic on structural brain development in early adolescence
Authors: van Drunen L. , Toenders Y. J. , Wierenga L. M. , Crone E. A.
Published: April 2023

The COVID-19 pandemic caused a global health crisis with large behavioral effects and serious stress and social consequences. Particularly, teenagers suffered pandemic-related social restrictions including school closures. This study examined whether and how structural brain development was influenced by the COVID-19 pandemic and whether pandemic length was associated with accumulating or resilience effects of brain development. We investigated structural changes in social brain regions (medial prefrontal cortex: mPFC; temporoparietal junction: TPJ) as well as the stress-related hippocampus and amygdala, using a longitudinal design of 2 MRI waves. We selected two age-matched subgroups (9–13 years old), one was tested before (n = 114) and the other during (peri-pandemic group, n = 204) the COVID-19 pandemic. Results indicated that teenagers in the peri-pandemic group showed accelerated development in the mPFC and hippocampus compared to the before-pandemic group. Furthermore, TPJ growth showed immediate effects followed by possibly subsequent recovery effects that returned to a typical developmental pattern. No effects were observed for the amygdala. The findings of this region-of-interest study suggest that experiencing the COVID-19 pandemic measures had accelerating effects on hippocampus and mPFC development but the TPJ showed resilience to negative effects. Follow-up MRI assessments are needed to test acceleration and recovery effects over longer periods.
Spatial correlation between producer services agglomeration and carbon emissions in the Yangtze River Economic Belt based on point-of-interest
Authors: Zeng Peng , Shang Lingjie , Xing Mengkun
Published: April 2023

Agglomeration of the industry significantly impacts economic performance and environmental sustainability. In line with its strategic context of striving to achieve carbon reduction targets, China is making efforts to optimize the producer services landscape to reduce carbon emissions. Understanding the spatial correlation between industrial agglomeration and carbon emissions is particularly crucial against this background. Based on POI and remote sensing data of China’s Yangtze River Economic Belt (YREB), the paper adopts the mean nearest neighbor analysis, kernel density analysis, and standard deviation ellipse to portray the agglomeration of producer services. Then uses Moran's I to present the spatial distribution characteristics of carbon emissions. Accordingly, the spatial heterogeneity of producer services agglomeration and carbon emissions is showed using the Geographic detector so as to provide strong support for industrial structure optimization and sustainable development. Here are some of the conclusions drawn from the study: (1) Producer services are a significant state of agglomeration in the provincial capitals and some central cities, with similar agglomeration patterns. (2) Carbon emissions exhibits significant spatial aggregation characteristics, with the spatial distribution pattern of "High west–Low east". (3) Wholesale and retail services industry is the primary risk factor that causes spatial differentiation of carbon emission intensity, "leasing and business services industry-wholesale and retail services industry" is the key interaction factor of the spatial differentiation. (4) Carbon emissions shows a downward trend followed by an upward trend as producer services agglomeration increases.
Integrating the norm activation model and theory of planned behaviour to investigate farmer pro-environmental behavioural intention
Authors: Savari Moslem , Damaneh Hamed Eskandari , Damaneh Hadi Eskandari , Cotton Matthew
Published: April 2023

Sustainable agriculture requires cooperative and coordinated action across multiple sectors and policy domains. However, farmer-stakeholder behaviors and action remain pivotal to sustainable food system management in many rural development contexts. We assess farmer pro-environmental behavioral intention through the development and application of a novel integrated approach combining two dominant psychological theories of behavior change: the Norm Activation Model (NAM) and Theory of Planned Behavior (TPB). We apply this framework to targeted research with potato growers of Kerman Province in southeastern Iran, using survey data (sample n = 381) analyzed through structural equation modeling (SEM). The integrated NAM-TPB model provides insight into both pro-social and self-interested motivations for farmer pro-environmental behavioral intention, with the model explaining 77% of total variance. We found that three variables, Awareness of Consequence (AC), Perceived Behavioral Control (PBC), and Subjective Norms (SN) were the strongest indicators of pro-environmental behavioral intention. We recommend therefore that agricultural extension and state-led farmer education should first emphasize awareness-raising of negative environmental impacts of current farming practices within training programs, and second, improve social learning amongst farmer communities through sustained farmer community engagement, thus “stabilizing” a social norm of environmental protection amongst peer networks of agricultural workers.
LkARF7 and LkARF19 overexpression promote adventitious root formation in a heterologous poplar model by positively regulating LkBBM1
Authors: Tao Gui-Yun , Xie Yun-Hui , Li Wan-Feng , Li Kui-Peng , Sun Chao , Wang Hong-Ming , Sun Xiao-Mei
Published: April 2023

Cuttage propagation involves adventitious root formation induced by auxin. In our previous study, Larix kaempferi BABY BOOM 1 (LkBBM1), which is known to regulate adventitious root formation, was affected by auxin. However, the relationship between LkBBM1 and auxin remains unclear. Auxin response factors (ARFs) are a class of important transcription factors in the auxin signaling pathway and modulate the expression of early auxin-responsive genes by binding to auxin response elements. In the present study, we identified 14 L. kaempferi ARFs (LkARFs), and found LkARF7 and LkARF19 bound to LkBBM1 promoter and enhanced its transcription using yeast one-hybrid, ChIP-qPCR, and dual-luciferase assays. In addition, the treatment with naphthalene acetic acid promoted the expression of LkARF7 and LkARF19. We also found that overexpression of these two genes in poplar promoted adventitious root formation. Furthermore, LkARF19 interacted with the DEAD-box ATP-dependent RNA helicase 53-like protein to form a heterodimer to regulate adventitious root formation. Altogether, our results reveal an additional regulatory mechanism underlying the control of adventitious root formation by auxin.
Gold nanoparticle doped Cuhemin nanosheets with a remodeling tumor microenvironment for multiple radiotherapy sensitization
Authors: Qiao Kun , Mo Jianlan , Pan You , Zhang Shiyuan , Jiang Cong , Lyu Meng , Cui Ying , Huang Yuanxi , Ning Shipeng
Published: April 2023

We created an integrated nano-system (Cuhemin–Au) for sensitizing radiotherapy. Cuhemin–Au upsets redox equilibrium and destroys mitochondria, leading to radiation sensitivity.
Inorganic anion recognition in aqueous solution by coupling nearby highly hydrophilic and hydrophobic moieties in a macrocyclic receptor
Authors: Romano Giammarco M. , Savastano Matteo , Bazzicalupi Carla , Chelli Riccardo , Lippolis Vito , Bencini Andrea
Published: April 2023

A fluorescent acridine-containing polyamine receptor assumes upon protonation a folded conformation featuring a cleft of appropriate size for preferential binding and optical sensing of Cl−and Br−over oxo anions and I−.
Medium-entropy state quinary keplerate clusters as a remarkable electrocatalyst for small molecule electrooxidation
Authors: Cao Mengyang , Ye Hongfang , Liu Yingying , Wang Jianwen , Zhou Yin , Wang Xianwen , Wu Shining , Xu Feng , Wu Yingpeng
Published: April 2023

We fabricate a library of binary to quinary element Keplerate clusters stabilized in a medium entropy state. Different ions follow the Irving–Williams series to be incorporated in the clusters.
A stable nanotubular metal–organic framework as heterogeneous catalyst for efficient chemical fixation of CO2
Authors: Tian Xueqin , Hu Xuefu , Zhao Wenjing , Wu Pengyan , Wu Yan , Xie Xin , Huang Fangmin , Cheng Jinwen , Wang Jian
Published: April 2023

The incorporation of high-density and easily accessible Lewis acid sites is of great significance to obtain high catalytic activity in the CO2cycloaddition reaction of epoxides.
Production of aromatic hydrocarbons from lignin derivatives by catalytic cracking over a SiO2–Al2O3 catalyst
Authors: Zhang Dequan , Zhang Xinghua , Yin Han , Zheng Qingqi , Ma Longlong , Li Song , Zhang Yuchun , Fu Peng
Published: April 2023

Catalytic cracking of phenolic compounds to aromatic hydrocarbons is vital to the utilization of lignin.
Hybrid core–shell nanoparticles for cell-specific magnetic separation and photothermal heating
Authors: de la Encarnación Cristina , Jungwirth Felix , Vila-Liarte David , Renero-Lecuna Carlos , Kavak Safiyye , Orue Iñaki , Wilhelm Claire , Bals Sara , Henriksen-Lacey Malou , Jimenez de Aberasturi Dorleta , Liz-Marzán Luis M.
Published: April 2023

Hybrid nanoparticles comprising a plasmonic gold nanorod core, silica spacer and outer iron oxide shell were prepared and used for antibody-driven cell separation and selective photo-induced hyperthermia.