bluuebunny/crossref_metadata_2025 huggingface dataset:
CEO Information Ability, Absorptive Capacity, and E-Commerce Adoption among Small, Medium, and Micro Enterprises in China
Authors: Gu Jiafeng
Published: January 2022

The purpose of this study was to explore the relationship between chief executive officer (CEO) characteristics, absorptive capacity, and e-commerce adoption in SMMEs. To achieve this objective, the study analyzed primary data gathered from 2675 small, medium, and micro enterprises (SMMEs) in China. A logistic regression model was employed to estimate how the CEO characteristics and absorptive capacity of SMMEs influenced their e-commerce adoption. The study revealed a significant positive relationship between CEO information ability, confidence, and e-commerce adoption. Additionally, this study confirmed a positive relationship between absorptive capacity and the adoption of e-commerce.
Efficiency Analysis of Graduate Alumni Insertion into the Labor Market as a Sustainable Development Goal
Authors: Blanco Miguel , Bares Lydia , Ferasso Marcos
Published: January 2022

The assumption that greater education levels of a given population leads to better employability levels thanks to higher education institutions (HEI) is widely known. However, most of the research related to HEI is focused on the determination of efficiency levels from an eminently academic perspective. The objective of this research is to carry out a comparative analysis of the efficiency degree of Latin American universities in terms of labor insertion for their graduate alumni, in order to evaluate the Sustainable Development Goal 8 related to decent work and economic growth. The data enveloping analysis (DEA) methodology was implemented. Main results showed different levels of labor efficiency among the studied institutions that were classified into eight groups of universities. Likewise, it was noted that Latin American university students showed employment levels above those of workers with lower levels of education and training.
Developmental Brain Asymmetry. The Good and the Bad Sides
Authors: Cara Monica Laura , Streata Ioana , Buga Ana Maria , Iliescu Dominic Gabriel
Published: January 2022

Brain asymmetry is a hallmark of the human brain. Recent studies report a certain degree of abnormal asymmetry of brain lateralization between left and right brain hemispheres can be associated with many neuropsychiatric conditions. In this regard, some questions need answers. First, the accelerated brain asymmetry is programmed during the pre-natal period that can be called “accelerated brain decline clock”. Second, can we find the right biomarkers to predict these changes? Moreover, can we establish the dynamics of these changes in order to identify the right time window for proper interventions that can reverse or limit the neurological decline? To find answers to these questions, we performed a systematic online search for the last 10 years in databases using keywords. Conclusion: we need to establish the right in vitro model that meets human conditions as much as possible. New biomarkers are necessary to establish the “good” or the “bad” borders of brain asymmetry at the epigenetic and functional level as early as possible.
Seismic Mitigation of Curved Continuous Girder Bridge Considering Collision Effect
Authors: Li Zhengying , Kang Shaobo , You Chuan
Published: January 2022

Due to structural irregularity, curved bridgesaremore likely to cause non-uniform collisions and unseating between adjacent components when subjected to earthquakes. Based on the analysis of the collision response of curved bridges duringearthquakes, and according to the seismic characteristics of curved bridges, research was carried out on pounding mitigation and unseating prevention measures. A curved bridge with double column piers was taken as an engineering example, and a finite element model of curved bridges thatcould consider the non-uniform contact collision between adjacent components was built with ABAQUS software. Viscoelastic dampers, viscous dampers, and a lead rubber bearing were selected as the damping devices, and a steel wire rope-rubber mat was used as the pounding mitigation device to form the combinatorial seismic mitigation system. Based on the principle of energy dissipation combined with constraints, three kinds of combined seismic mitigation case were determined; a seismic response analysis was then performed. The results indicated that the three kinds of combined seismic case were effective atreducing the response topounding force, stress, damage, girder torsion and displacement, and achieved the goals of seismic mitigation and unseating prevention.
A Hybrid Shuffled Frog Leaping Algorithm and Its Performance Assessment in Multi-Dimensional Symmetric Function
Authors: Li Fei , Guo Wentai , Deng Xiaotong , Wang Jiamei , Ge Liangquan , Guan Xiaotong
Published: January 2022

Ensemble learning of swarm intelligence evolutionary algorithm of artificial neural network (ANN) is one of the core research directions in the field of artificial intelligence (AI). As a representative member of swarm intelligence evolutionary algorithm, shuffled frog leaping algorithm (SFLA) has the advantages of simple structure, easy implementation, short operation time, and strong global optimization ability. However, SFLA is susceptible to fall into local optimas in the face of complex and multi-dimensional symmetric function optimization, which leads to the decline of convergence accuracy. This paper proposes an improved shuffled frog leaping algorithm of threshold oscillation based on simulated annealing (SA-TO-SFLA). In this algorithm, the threshold oscillation strategy and simulated annealing strategy are introduced into the SFLA, which makes the local search behavior more diversified and the ability to escape from the local optimas stronger. By using multi-dimensional symmetric function such as drop-wave function, Schaffer function N.2, Rastrigin function, and Griewank function, two groups (i: SFLA, SA-SFLA, TO-SFLA, and SA-TO-SFLA; ii: SFLA, ISFLA, MSFLA, DSFLA, and SA-TO-SFLA) of comparative experiments are designed to analyze the convergence accuracy and convergence time. The results show that the threshold oscillation strategy has strong robustness. Moreover, compared with SFLA, the convergence accuracy of SA-TO-SFLA algorithm is significantly improved, and the median of convergence time is greatly reduced as a whole. The convergence accuracy of SFLA algorithm on these four test functions are 90%, 100%, 78%, and 92.5%, respectively, and the median of convergence time is 63.67 s, 59.71 s, 12.93 s, and 8.74 s, respectively; The convergence accuracy of SA-TO-SFLA algorithm on these four test functions is 99%, 100%, 100%, and 97.5%, respectively, and the median of convergence time is 48.64 s, 32.07 s, 24.06 s, and 3.04 s, respectively.
Effect of Pulsatility on the Transport of Thrombin in an Idealized Cerebral Aneurysm Geometry
Authors: Hume Struan , Tshimanga Jean-Marc Ilunga , Geoghegan Patrick , Malan Arnaud G. , Ho Wei Hua , Ngoepe Malebogo N.
Published: January 2022

Computational models of cerebral aneurysm thrombosis are designed for use in research and clinical applications. A steady flow assumption is applied in many of these models. To explore the accuracy of this assumption a pulsatile-flow thrombin-transport computational fluid dynamics (CFD) model, which uses a symmetrical idealized aneurysm geometry, was developed. First, a steady-flow computational model was developed and validated using data from an in vitro experiment, based on particle image velocimetry (PIV). The experimental data revealed an asymmetric flow pattern in the aneurysm. The validated computational model was subsequently altered to incorporate pulsatility, by applying a data-derived flow function at the inlet boundary. For both the steady and pulsatile computational models, a scalar function simulating thrombin generation was applied at the aneurysm wall. To determine the influence of pulsatility on thrombin transport, the outputs of the steady model were compared to the outputs of the pulsatile model. The comparison revealed that in the pulsatile case, an average of 10.2% less thrombin accumulates within the aneurysm than the steady case for any given time, due to periodic losses of a significant amount of thrombin-concentrated blood from the aneurysm into the parent vessel’s bloodstream. These findings demonstrate that pulsatility may change clotting outcomes in cerebral aneurysms.
A Novel Approach for Multiplicative Linguistic Group Decision Making Based on Symmetrical Linguistic Chi-Square Deviation and VIKOR Method
Authors: Gong Zhiwei , Lin Jian , Weng Ling
Published: January 2022

Most linguistic-based approaches to multi-attribute group decision making (MAGDM) use symmetric, uniformly distributed sets of additive linguistic terms to express the opinions of decision makers. However, in reality, there are also some problems that require the use of asymmetric, uneven, i.e., non-equilibrium, multiplicative linguistic term sets to express the evaluation. The purpose of this paper is to propose a new approach to MAGDM under multiplicative linguistic information. The aggregation of linguistic data is an important component in MAGDM. To solve this problem, we define a chi-square for measuring the difference between multiplicative linguistic term sets. Furthermore, the linguistic generalized weighted logarithm multiple averaging (LGWLMA) operator and linguistic generalized ordered weighted logarithm multiple averaging (LGOWLMA) operator are proposed based on chi-square deviation. On the basis of the proposed two operators, we develop a novel approach to GDM with multiplicative linguistic term sets. Finally, the evaluation of transport logistics enterprises is developed to illustrate the validity and practicality of the proposed approach.
SCRnet: A Spatial Consistency Guided Network Using Contrastive Learning for Point Cloud Registration
Authors: Shao Huixiang , Zhang Zhijiang , Feng Xiaoyu , Zeng Dan
Published: January 2022

Point cloud registration is used to find a rigid transformation from the source point cloud to the target point cloud. The main challenge in the point cloud registration is in finding correct correspondences in complex scenes that may contain many noise and repetitive structures. At present, many existing methods use outlier rejections to help the network obtain more accurate correspondences, but they often ignore the spatial consistency between keypoints. Therefore, to address this issue, we propose a spatial consistency guided network using contrastive learning for point cloud registration (SCRnet), in which its overall stage is symmetrical. SCRnet consists of four blocks, namely feature extraction block, confidence estimation block, contrastive learning block and registration block. Firstly, we use mini-PointNet to extract coarse local and global features. Secondly, we propose confidence estimation block, which formulate outlier rejection as confidence estimation problem of keypoint correspondences. In addition, the local spatial features are encoded into the confidence estimation block, which makes the correspondence possess local spatial consistency. Moreover, we propose contrastive learning block by constructing positive point pairs and hard negative point pairs and using Point-Pair-INfoNCE contrastive loss, which can further remove hard outliers through global spatial consistency. Finally, the proposed registration block selects a set of matching points with high spatial consistency and uses these matching sets to calculate multiple transformations, then the best transformation can be identified by initial alignment and Iterative Closest Point (ICP) algorithm. Extensive experiments are conducted on KITTI and nuScenes dataset, which demonstrate the high accuracy and strong robustness of SCRnet on point cloud registration task.
Experimental Review of ΛΛ¯ Production
Authors: Zhou Xiaorong , Yan Liang , Ferroli Rinaldo Baldini , Huang Guangshun
Published: January 2022

Exclusive hyperon-antihyperon production provides a unique insight for understanding of the intrinsic dynamics when strangeness is involved. In this paper, we review the results of ΛΛ¯ production via different reactions from various experiments, e.g., via p¯p annihilation from the LEAR experiment PS185, via electron-positron annihilation using the energy scan method at the CLEO-c and BESIII experiments and the initial-state-radiation approach utilized at the BaBar experiment. The production cross section of ΛΛ¯ near the threshold is sensitive to QCD based prediction. Experimental high precision data for p¯p→Λ¯Λ close to the threshold region is obtained. The cross section of e+e−→ΛΛ¯ is measured from its production threshold to high energy. A non-zero cross section for e+e−→ΛΛ¯ near threshold is observed at BaBar and BESIII, which is in disagreement with the pQCD prediction. However, more precise data is needed to confirm this observation. Future experiments, utilizing p¯p reaction such as PANDA experiment or electron-positron annihilation such as the BESIII and BelleII experiments, are needed to extend the experimental data and to understand the ΛΛ¯ production.
Twisted Waves near a Plasma Cutoff
Authors: Mendonça José Tito , Willim Camilla , Vieira Jorge
Published: January 2022

This work considers twisted wave propagation in inhomogeneous and unmagnetised plasma, and discusses the wave properties in the cutoff region. The qualitative differences between twisted waves described by a single Laguerre–Gauss (LG) mode, and light springs resulting from the superposition of two or more LG modes with different frequency and helicity are studied. The peculiar properties displayed by these waves in the nonuniform plasma are discussed. The pulse envelope of a light-spring shows a contraction at reflection, which resembles that of a compressed mechanical spring. The case of normal incidence is examined, and nonlinear ponderomotive effects are discussed, using theory and simulations.
Sub-Chronic Difenoconazole Exposure Induced Gut Microbiota Dysbiosis in Mice
Authors: Bao Zhiwei , Wang Weitao , Wang Xiaofang , Qian Mingrong , Jin Yuanxiang
Published: January 2022

Difenoconazole (DIF) is a widely separated triazole fungicide in many countries. The excessive usage of DIF increases the high volume of residues in agriculture production and water bodies. Some previous studies demonstrated the toxic effects of DIF on non-target animals, however, there were still some gaps in the knowledge of the potential hazards of DIF to mammals and human health. Herein, 7-week-old male mice were exposed to 30 and 100 mg/kg/day DIF for 14 and 56 days. We observed that 56 days of DIF exposure decreased the colonic mucus expression of alcin blue-periodic acid-schiff (AB-PAS) stain and the immunochemical stain of muc2 protein. The transcript levels of mucin protein (muc1, muc2 and muc3) decreased significantly in the gut of mice followed 56 days of 100 mg/kg/day DIF exposure. In addition, the gut microbiota composition was also affected after 14 or 56 days of DIF exposure. Although the mucus expression after 14 days of DIF exposure only decreased slightly, the gut microbiota composition compared with the control group was changed significantly. Moreover, the DIF-30 and DIF-100 caused respectively different changes on the gut microbiota. The relative abundance of Bacteroidetes decreased significantly after 14 days and 56 days of DIF exposure. After 14 days of DIF exposure, there were 35 and 18 differential genera in the DIF-30 and DIF-100 group, respectively. There were 25 and 32 differential genera in the DIF-30 and DIF-100 group after 56 days of exposure, respectively. Meanwhile, the alpha diversity indexes, including observed species, Shannon, Simpson, Chao1 and ACE, in gut microbiota decreased significantly after 56 days of DIF exposure. Interestingly, the relative abundance of Akkermansia increased significantly after 56 days of 100 mg/kg/d DIF exposure. Although Akkermansia was considered as one probiotic, the phenomenon of dramatic Akkermansia increase with the decrease in gut microbiota diversity needed further discussion. These results provided some new insights on how DIF exposure impacts the mucus barrier and induces gut microbiota dysbiosis.
Dynamics and Merger Rate of Primordial Black Holes in a Cluster
Authors: Stasenko Viktor D. , Kirillov Alexander A. , Belotsky Konstantin M.
Published: January 2022

The PBH clusters can be sources of gravitational waves, and the merger rate depends on the spatial distribution of PBHs in the cluster which changes over time. It is well known that gravitational collisional systems experience the core collapse that leads to significant increase of the central density and shrinking of the core. After core collapse, the cluster expands almost self-similarly (i.e., density profile extends in size without changing its shape). These dynamic processes affect the merger rate of PBHs. In this paper, the dynamics of the PBH cluster is considered using the Fokker–Planck equation. We calculate the merger rate of PBHs on cosmic time scales and show that its time dependence has a unique signature. Namely, it grows by about an order of magnitude at the moment of core collapse which depends on the characteristics of the cluster, and then decreases according to the dependence R∝t−1.48. It was obtained for monochromatic and power-law PBH mass distributions with some fixed parameters. Obtained results can be used to test the model of the PBH clusters via observation of gravitational waves at high redshift.
Nucleosynthesis, Mixing Processes, and Gas Pollution from AGB Stars
Authors: Ventura Paolo , Dell’Agli Flavia , Tailo Marco , Castellani Marco , Marini Ester , Tosi Silvia , Di Criscienzo Marcella
Published: January 2022

We discuss the evolution of stars through the asymptotic giant branch, focusing on the physical mechanisms potentially able to alter the surface chemical composition and on how changes in the chemistry of the external regions affect the physical properties of the star and the duration of this evolutionary phase. We focus on the differences between the evolution of low-mass stars, driven by the growth of the core mass and by the surface carbon enrichment, and that of their higher mass counterparts, which experience hot bottom burning. In the latter sources, the variation of the surface chemical composition reflects the equilibria of the proton capture nucleosynthesis experienced at the base of the convective envelope. The pollution expected from this class of stars is discussed, outlining the role of mass and metallicity on the chemical composition of the ejecta. To this aim, we considered evolutionary models of 0.7–8 M⊙ stars in a wide range of metallicities, extending from the ultra-metal-poor domain to super-solar chemistries.
Concomitant Radical Cystectomy and Infrarenal Aortic Aneurysm Repair with Cryopreserved Aortic Allograft: A Case Report
Authors: Cianflone Francesco , Bianchi Alberto , Novella Giovanni , Tafuri Alessandro , Cerruto Maria Angela , Zivi Andrea , Veraldi Gian Franco , Antonelli Alessandro
Published: January 2022

In localized muscle invasive bladder cancer (MIBC), the gold standard treatment is radical cystectomy (RC) with bilateral pelvic lymph node dissection (PLND), associated with cisplatin-based neoadjuvant chemotherapy, whereas first-line treatment for metastatic patients is cisplatin-based chemotherapy. In men with an abdominal aortic aneurysm (AAA), elective repair is recommended when its diameter is >5.5 cm, while cryopreserved arterial allografts (CAA) offer resistance to infection. A patient with simultaneous metastatic MIBC, associated with left hydronephrosis, and infrarenal AAA of 49 mm diameter was evaluated in an interdisciplinary study. Concomitant surgery was opted for; first, the AAA repair with CAA implantation was practiced, followed by retroperitoneal and common iliac lymphadenectomy. Thereafter, RC and PLND were conducted, and a Wallace-1 ileal conduit and a stoma were constructed. Chest and abdomen contrast-enhanced CT at 2 months showed the onset of two osteolytic lesions on the left ilium. At oncological re-evaluation the patient was deemed cisplatin-fit.
SARS-CoV-2 Reverse Zoonoses to Pumas and Lions, South Africa
Authors: Koeppel Katja Natalie , Mendes Adriano , Strydom Amy , Rotherham Lia , Mulumba Misheck , Venter Marietjie
Published: January 2022

Reverse-zoonotic infections of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) from humans to wildlife species internationally raise concern over the emergence of new variants in animals. A better understanding of the transmission dynamics and pathogenesis in susceptible species will mitigate the risk to humans and wildlife occurring in Africa. Here we report infection of an exotic puma (July 2020) and three African lions (July 2021) in the same private zoo in Johannesburg, South Africa. One Health genomic surveillance identified transmission of a Delta variant from a zookeeper to the three lions, similar to those circulating in humans in South Africa. One lion developed pneumonia while the other cases had mild infection. Both the puma and lions remained positive for SARS-CoV-2 RNA for up to 7 weeks.
Discriminatory Weight of SNPs in Spike SARS-CoV-2 Variants: A Technically Rapid, Unambiguous, and Bioinformatically Validated Laboratory Approach
Authors: Musso Nicolò , Bonacci Paolo Giuseppe , Bongiorno Dafne , Stracquadanio Stefano , Bivona Dalida Angela , Palermo Concetta Ilenia , Scalia Guido , Fichera Marco , Stefani Stefania
Published: January 2022

Background: The SARS-CoV-2 virus has assumed considerable importance during the COVID-19 pandemic. Its mutation rate is high, involving the spike (S) gene and thus there has been a rapid spread of new variants. Herein, we describe a rapid, easy, adaptable, and affordable workflow to uniquely identify all currently known variants through as few analyses. Our method only requires two conventional PCRs of the S gene and two Sanger sequencing reactions, and possibly another PCR/sequencing assay on a N gene portion to identify the B.1.160 lineage. Methods: We selected an S gene 1312 bp portion containing a set of SNPs useful for discriminating all variants. Mathematical, statistical, and bioinformatic analyses demonstrated that our choice allowed us to identify all variants even without looking for all related mutations, as some of them are shared by different variants (e.g., N501Y is found in the Alpha, Beta, and Gamma variants) whereas others, that are more informative, are unique (e.g., A57 distinctive to the Alpha variant). Results: A “weight” could be assigned to each mutation that may be present in the selected portion of the S gene. The method’s robustness was confirmed by analyzing 80 SARS-CoV-2-positive samples. Conclusions: Our workflow identified the variants without the need for whole-genome sequencing and with greater reliability than with commercial kits.
Obesity and Metabolic Dysregulation in Children Provide Protective Influenza Vaccine Responses
Authors: Kainth Mundeep K. , Fishbein Joanna S. , Aydillo Teresa , Escalera Alba , Odusanya Rachael , Grammatikopoulos Kalliopi , Scotto Tiffany , Sethna Christine B. , García-Sastre Adolfo , Deutschman Clifford S.
Published: January 2022

The most effective intervention for influenza prevention is vaccination. However, there are conflicting data on influenza vaccine antibody responses in obese children. Cardio-metabolic parameters such as waist circumference, cholesterol, insulin sensitivity, and blood pressure are used to subdivide individuals with overweight or obese BMI into ‘healthy’ (MHOO) or ‘unhealthy’ (MUOO) metabolic phenotypes. The ever-evolving metabolic phenotypes in children may be elucidated by using vaccine stimulation to characterize cytokine responses. We conducted a prospective cohort study evaluating influenza vaccine responses in children. Participants were identified as either normal-weight children (NWC) or overweight/obese using BMI. Children with obesity were then characterized using metabolic health metrics. These metrics consisted of changes in serum cytokine and chemokine concentrations measured via multiplex assay at baseline and repeated at one month following vaccination. Changes in NWC, MHOO and MUOO were compared using Chi-square/Fisher’s exact test for antibody responses and Kruskal–Wallis test for cytokines. Differences in influenza antibody responses in normal, MHOO and MUOO children were statistically indistinguishable. IL-13 was decreased in MUOO children compared to NWC and MHOO children (p = 0.04). IL-10 approached a statistically significant decrease in MUOO compared to MHOO and NWC (p = 0.07). Influenza vaccination does not provoke different responses in NCW, MHOO, or MUOO children, suggesting that obesity, whether metabolically healthy or unhealthy, does not alter the efficacy of vaccination. IL-13 levels in MUO children were significantly different from levels in normal and MHOO children, indicating that the metabolically unhealthy phenotypes may be associated with an altered inflammatory response. A larger sample size with greater numbers of metabolically unhealthy children may lend more insight into the relationship of chronic inflammation secondary to obesity with vaccine immunity.
miR-541-3p Promoted Porcine Reproductive and Respiratory Syndrome Virus 2 (PRRSV-2) Replication by Targeting Interferon Regulatory Factor 7
Authors: Shi Xibao , Yang Yuanhao , Zhang Xiaozhuan , Chang Xiaobo , Chen Jing , Wang Chao , Wang Aiping , Wang Jianhua , Qin Jianru , Ye Xianlong , Jin Wei , Zhang Gaiping
Published: January 2022

Porcine reproductive and respiratory syndrome (PRRS) is a disease caused by PRRS virus (PRRSV), which seriously harms the pig industry. Revealing the mechanism by which PRRSV inhibits immune response will help prevent and control PRRS. Here, we found that PRRSV-2 may hijack host miR-541-3p to inhibit host innate immune response. Firstly, this work showed that miR-541-3p mimics could facilitate the replication of PRRSV-2 and the results of the quantitative real time polymerase chain reaction (qRT-PCR) showed that PRRSV-2 could up-regulate the expression of miR-541-3p in MARC-145 cells. Since previous studies have shown that type I interferon could effectively inhibit the replication of PRRSV-2, the present work explored whether miR-541-3p regulated the expression of type I interferon and found that miR-541-3p could negatively regulate the transcription of type I interferon by targeting interferon regulatory factor 7 (IRF7). More importantly, PRRSV-2 infection could down-regulate the expression of IRF7 and over-expression of IRF7 could down-regulate the replication of PRRSV-2 in MARC-145 cells. In conclusion, PRRSV-2 infection up-regulated the expression of miR-541-3p to promote its replication in MARC-145 cells, since miR-541-3p can negatively regulate the transcription of type I interferon by targeting IRF7.
Prolonged Viability of Senecavirus A in Exposed House Flies (Musca domestica)
Authors: Turner Justin Heath , Paim Willian Pinto , Maggioli Mayara Fernanda , Peter Cristina Mendes , Miknis Robert , Talley Justin , Bauermann Fernando Vicosa
Published: January 2022

House flies (Musca domestica) are often present in swine farms worldwide. These flies utilize animal secretions and waste as a food source. House flies may harbor and transport microbes and pathogens acting as mechanical vectors for diseases. Senecavirus A (SVA) infection in pigs occurs via oronasal route, and animals shed high virus titers to the environment. Additionally, SVA possesses increased environmental resistance. Due to these reasons, we investigated the tenacity of SVA in house flies. Five groups of flies, each composed of ten females and ten males, were exposed to SVA, titer of 109.3 tissue culture infectious dose (TCID50/mL). Groups of male and female flies were collected at 0, 6, 12, 24, and 48 h post-exposure. For comparison purposes, groups of flies were exposed to Swinepox virus (SwPV). Infectious SVA was identified in all tested groups. Successful isolation of SVA demonstrated the titers varied between 106.8 and 102.8 TCID50/mL in female groups and varied from 105.85 to 103.8 TCID50/mL in male groups. In contrast, infectious SwPV was only detected in the female group at 6 h. The significant SVA infectious titer for prolonged periods of time, up to 48 h, indicates a potential role of flies in SVA transmission.
A Conserved Tryptophan in the Envelope Cytoplasmic Tail Regulates HIV-1 Assembly and Spread
Authors: Snetkov Xenia , Haider Tafhima , Mesner Dejan , Groves Nicholas , van Engelenburg Schuyler B. , Jolly Clare
Published: January 2022

The HIV-1 envelope (Env) is an essential determinant of viral infectivity, tropism and spread between T cells. Lentiviral Env contain an unusually long 150 amino acid cytoplasmic tail (EnvCT), but the function of the EnvCT and many conserved domains within it remain largely uncharacterised. Here, we identified a highly conserved tryptophan motif at position 757 (W757) in the LLP-2 alpha helix of the EnvCT as a key determinant for HIV-1 replication and spread between T cells. Alanine substitution at this position potently inhibited HIV-1 cell–cell spread (the dominant mode of HIV-1 dissemination) by preventing recruitment of Env and Gag to sites of cell–cell contact, inhibiting virological synapse (VS) formation and spreading infection. Single-molecule tracking and super-resolution imaging showed that mutation of W757 dysregulates Env diffusion in the plasma membrane and increases Env mobility. Further analysis of Env function revealed that W757 is also required for Env fusion and infectivity, which together with reduced VS formation, result in a potent defect in viral spread. Notably, W757 lies within a region of the EnvCT recently shown to act as a supporting baseplate for Env. Our data support a model in which W757 plays a key role in regulating Env biology, modulating its temporal and spatial recruitment to virus assembly sites and regulating the inherent fusogenicity of the Env ectodomain, thereby supporting efficient HIV-1 replication and spread.
In Acute Dengue Infection, High TIM-3 Expression May Contribute to the Impairment of IFNγ Production by Circulating Vδ2 T Cells
Authors: Cimini Eleonora , Grassi Germana , Beccacece Alessia , Casetti Rita , Castilletti Concetta , Capobianchi Maria , Nicastri Emanuele , Agrati Chiara
Published: January 2022

γδ T cells are innate cells able to quickly eliminate pathogens or infected/tumoral cells by their antiviral and adjuvancy activities. The role of γδ T cells during Dengue Viral Infection (DENV) infection is not fully elucidated. Nevertheless, human primary γδ T cells have been shown to kill in vitro DENV-infected cells, thus highlighting their possible antiviral function. The aim of this work was to characterize the phenotype and function of Vδ2 T cells in DENV patients. Fifteen DENV patients were enrolled for this study and peripheral blood mononuclear cells (PBMC) were used to analyze Vδ2-T-cell frequency, differentiation profile, activation/exhaustion status, and functionality by multiparametric flow cytometry. Our data demonstrated that DENV infection was able to significantly reduce Vδ2-T-cell frequency and to increase their activation (CD38 and HLA-DR) and exhaustion markers (PD-1 and TIM-3). Furthermore, Vδ2 T cells showed a reduced capability to produce IFN-γ after phosphoantigenic stimulation that can be associated to TIM-3 expression. Several studies are needed to depict the possible clinical impact of γδ-T-cell impairment on disease severity and to define the antiviral and immunoregulatory activities of γδ T cells in the first phases of infection.
Investigation of Biological Factors Contributing to Individual Variation in Viral Titer after Oral Infection of Aedes aegypti Mosquitoes by Sindbis Virus
Authors: Hodoameda Peter , Addae Linus , Clem Rollie J.
Published: January 2022

The mechanisms involved in determining arbovirus vector competence, or the ability of an arbovirus to infect and be transmitted by an arthropod vector, are still incompletely understood. It is well known that vector competence for a particular arbovirus can vary widely among different populations of a mosquito species, which is generally attributed to genetic differences between populations. What is less understood is the considerable variability (up to several logs) that is routinely observed in the virus titer between individual mosquitoes in a single experiment, even in mosquitoes from highly inbred lines. This extreme degree of variation in the virus titer between individual mosquitoes has been largely ignored in past studies. We investigated which biological factors can affect titer variation between individual mosquitoes of a laboratory strain of Aedes aegypti, the Orlando strain, after Sindbis virus infection. Greater titer variation was observed after oral versus intrathoracic infection, suggesting that the midgut barrier contributes to titer variability. Among the other factors tested, only the length of the incubation period affected the degree of titer variability, while virus strain, mosquito strain, mosquito age, mosquito weight, amount of blood ingested, and virus concentration in the blood meal had no discernible effect. We also observed differences in culture adaptability and in the ability to orally infect mosquitoes between virus populations obtained from low and high titer mosquitoes, suggesting that founder effects may affect the virus titer in individual mosquitoes, although other explanations also remain possible.
GNS561 Exhibits Potent Antiviral Activity against SARS-CoV-2 through Autophagy Inhibition
Authors: Bestion Eloïne , Zandi Keivan , Belouzard Sandrine , Andreani Julien , Lepidi Hubert , Novello Marie , Rouquairol Clara , Baudoin Jean-Pierre , Rachid Madani , La Scola Bernard , Mege Jean-Louis , Dubuisson Jean , Schinazi Raymond F. , Mezouar Soraya , Halfon Philippe
Published: January 2022

Since December 2019, SARS-CoV-2 has spread quickly worldwide, leading to more than 280 million confirmed cases, including over 5,000,000 deaths. Interestingly, coronaviruses were found to subvert and hijack autophagic process to allow their viral replication. Autophagy-modulating compounds thus rapidly emerged as an attractive strategy to fight SARS-CoV-2 infection, including the well-known chloroquine (CQ). Here, we investigated the antiviral activity and associated mechanism of GNS561/Ezurpimtrostat, a small lysosomotropic molecule inhibitor of late-stage autophagy. Interestingly, GNS561 exhibited antiviral activity of 6–40 nM depending on the viral strain considered, currently positioning it as the most powerful molecule investigated in SARS-CoV-2 infection. We then showed that GNS561 was located in lysosome-associated-membrane-protein-2-positive (LAMP2-positive) lysosomes, together with SARS-CoV-2. Moreover, GNS561 increased LC3-II spot size and caused the accumulation of autophagic vacuoles and the presence of multilamellar bodies, suggesting that GNS561 disrupted the autophagy mechanism. To confirm our findings, we used the K18-hACE2 mouse model and highlighted that GNS561 treatment led to a decline in SARS-CoV-2 virions in the lungs associated with a disruption of the autophagy pathway. Overall, our study highlights GNS561 as a powerful drug in the treatment of SARS-CoV-2 infection and supports the hypothesis that autophagy blockers could be an alternative strategy for COVID-19.
Molecular Epidemiology of Rotavirus Strains in Symptomatic and Asymptomatic Children in Manhiça District, Southern Mozambique 2008–2019
Authors: Manjate Filomena , João Eva D. , Chirinda Percina , Garrine Marcelino , Vubil Delfino , Nobela Nélio , Kotloff Karen , Nataro James P. , Nhampossa Tacilta , Acácio Sozinho , Tate Jacqueline E. , Parashar Umesh , Mwenda Jason M. , Alonso Pedro L. , Nyaga Martin , Cunha Celso , Mandomando Inácio
Published: January 2022

Group A rotaviruses remain the leading cause of diarrhoea in children aged <5 years. Mozambique introduced rotavirus vaccine (Rotarix®) in September 2015. We report rotavirus genotypes circulating among symptomatic and asymptomatic children in Manhiça District, Mozambique, pre- and post-vaccine introduction. Stool was collected from enrolled children and screened for rotavirus by enzyme-immuno-sorbent assay. Positive specimens were genotyped for VP7 (G genotypes) and VP4 (P genotypes) by the conventional reverse transcriptase polymerase chain reaction. The combination G12P[8] was more frequently observed in pre-vaccine than in post-vaccine introduction, in moderate to severe diarrhoea (34%, 61/177 vs. 0, p < 0.0001) and controls (23%, 26/113 vs. 0, p = 0.0013) and mixed genotypes (36%, 24/67 vs. 7% 4/58, p = 0.0003) in less severe diarrhoea. We observed changes in post-vaccine compared to pre-vaccine introduction, where G3P[4] and G3P[8] were prevalent in moderate to severe diarrhoea (10%, 5/49 vs. 0, p = 0.0002; and 14%, 7/49 vs. 1%, 1/177, p < 0.0001; respectively), and in less severe diarrhoea (21%, 12/58 vs. 0, p = 0.003; and 24%, 14/58 vs. 0, p < 0.0001; respectively). Our surveillance demonstrated the circulation of similar genotypes contemporaneously among cases and controls, as well as switching from pre- to post-vaccine introduction. Continuous surveillance is needed to evaluate the dynamics of the changes in genotypes following vaccine introduction.
So Pathogenic or So What?—A Brief Overview of SIV Pathogenesis with an Emphasis on Cure Research
Authors: Kleinman Adam J. , Pandrea Ivona , Apetrei Cristian
Published: January 2022

HIV infection requires lifelong antiretroviral therapy (ART) to control disease progression. Although ART has greatly extended the life expectancy of persons living with HIV (PWH), PWH nonetheless suffer from an increase in AIDS-related and non-AIDS related comorbidities resulting from HIV pathogenesis. Thus, an HIV cure is imperative to improve the quality of life of PWH. In this review, we discuss the origins of various SIV strains utilized in cure and comorbidity research as well as their respective animal species used. We briefly detail the life cycle of HIV and describe the pathogenesis of HIV/SIV and the integral role of chronic immune activation and inflammation on disease progression and comorbidities, with comparisons between pathogenic infections and nonpathogenic infections that occur in natural hosts of SIVs. We further discuss the various HIV cure strategies being explored with an emphasis on immunological therapies and “shock and kill”.
Efficacy of Corticosteroid Therapy for HTLV-1-Associated Myelopathy: A Randomized Controlled Trial (HAMLET-P)
Authors: Yamauchi Junji , Tanabe Kenichiro , Sato Tomoo , Nakagawa Masanori , Matsuura Eiji , Tsuboi Yoshio , Tamaki Keiko , Sakima Hirokuni , Ishihara Satoshi , Ohta Yuki , Matsumoto Naoki , Kono Kenichi , Yagishita Naoko , Araya Natsumi , Takahashi Katsunori , Kunitomo Yasuo , Nagasaka Misako , Coler-Reilly Ariella , Hasegawa Yasuhiro , Araujo Abelardo , Jacobson Steven , Grassi Maria Fernanda Rios , Galvão-Castro Bernardo , Bland Martin , Taylor Graham P. , Martin Fabiola , Yamano Yoshihisa
Published: January 2022

Corticosteroids are most commonly used to treat HTLV-1-associated myelopathy (HAM); however, their clinical efficacy has not been tested in randomized clinical trials. This randomized controlled trial included 8 and 30 HAM patients with rapidly and slowly progressing walking disabilities, respectively. Rapid progressors were assigned (1:1) to receive or not receive a 3-day course of intravenous methylprednisolone in addition to oral prednisolone therapy. Meanwhile, slow progressors were assigned (1:1) to receive oral prednisolone or placebo. The primary outcomes were a composite of ≥1-grade improvement in the Osame Motor Disability Score or ≥30% improvement in the 10 m walking time (10 mWT) at week 2 for rapid progressors and changes from baseline in 10 mWT at week 24 for slow progressors. In the rapid progressor trial, all four patients with but only one of four without intravenous methylprednisolone achieved the primary outcome (p = 0.14). In the slow progressor trial, the median changes in 10 mWT were −13.8% (95% CI: −20.1–−7.1; p < 0.001) and −6.0% (95% CI: −12.8–1.3; p = 0.10) with prednisolone and placebo, respectively (p for between-group difference = 0.12). Whereas statistical significance was not reached for the primary endpoints, the overall data indicated the benefit of corticosteroid therapy. (Registration number: UMIN000023798, UMIN000024085)
Immunogenicity and Protective Capacity of a Virus-like Particle Vaccine against Chlamydia trachomatis Type 3 Secretion System Tip Protein, CT584
Authors: Webster Everett , Seiger Kyra W. , Core Susan B. , Collar Amanda L. , Knapp-Broas Hannah , Graham June , Shrestha Muskan , Afzaal Sarah , Geisler William M. , Wheeler Cosette M. , Chackerian Bryce , Frietze Kathryn M. , Lijek Rebeccah S.
Published: January 2022

An effective vaccine against Chlamydia trachomatis is urgently needed as infection rates continue to rise and C. trachomatis causes reproductive morbidity. An obligate intracellular pathogen, C. trachomatis employs a type 3 secretion system (T3SS) for host cell entry. The tip of the injectosome is composed of the protein CT584, which represents a potential target for neutralization with vaccine-induced antibody. Here, we investigate the immunogenicity and efficacy of a vaccine made of CT584 epitopes coupled to a bacteriophage virus-like particle (VLP), a novel platform for Chlamydia vaccines modeled on the success of HPV vaccines. Female mice were immunized intramuscularly, challenged transcervically with C. trachomatis, and assessed for systemic and local antibody responses and bacterial burden in the upper genital tract. Immunization resulted in a 3-log increase in epitope-specific IgG in serum and uterine homogenates and in the detection of epitope-specific IgG in uterine lavage at low levels. By contrast, sera from women infected with C. trachomatis and virgin controls had similarly low titers to CT584 epitopes, suggesting these epitopes are not systemically immunogenic during natural infection but can be rendered immunogenic by the VLP platform. C. trachomatis burden in the upper genital tract of mice varied after active immunization, yet passive protection was achieved when immune sera were pre-incubated with C. trachomatis prior to inoculation into the genital tract. These data demonstrate the potential for antibody against the T3SS to contribute to protection against C. trachomatis and the value of VLPs as a novel platform for C. trachomatis vaccines.
Using Adaptive Capacity to Shift Absorptive Capacity: A Framework of Water Reallocation in Highly Modified Rivers
Authors: Rudberg Peter M. , Karpouzoglou Timos
Published: January 2022

Damming and water regulation creates highly modified rivers with limited ecosystem integrity and resilience. This, coupled with an ongoing global biodiversity crisis, makes river restoration a priority, which requires water reallocation. Coupled human–natural systems research provides a suitable lens for integrated systems’ analysis but offers limited insight into the governance processes of water reallocation. Therefore, we propose an analytical framework, which combines insight from social–hydrological resilience and water reallocation research, and identifies the adaptive capacity in highly modified rivers as the capacity for water reallocation. We test the framework by conducting an analysis of Sweden, pre- and post-2019, a critical juncture in the governance of the country’s hydropower producing rivers. We identify a relative increase in adaptive capacity post- 2019 since water reallocation is set to occur in smaller rivers and tributaries, while leaving large-scaled rivers to enjoy limited water reallocation, or even increased allocation to hydropower. We contend that the proposed framework is broad enough to be of general interest, yet sufficiently specific to contribute to the construction of middle-range theories, which could further our understanding of why and how governance processes function, change, and lead to outcomes in terms of modified natural resource management and resilience shifts.
Topography Impacts Hydrology in the Sub-Humid Ethiopian Highlands
Authors: Mhiret Demesew A. , Dersseh Minychl G. , Guzman Christian D. , Dagnew Dessalegn C. , Abebe Wubneh B. , Zimale Fasikaw A. , Zaitchik Benjamin F. , Tilahun Seifu A. , Walraevens Kristine , Steenhuis Tammo S.
Published: January 2022

Understanding the relationship between topography, hydrological processes, and runoff source areas is essential in engineering design, such as predicting floods and implementing effective watershed management practices. This relationship is not well defined in the highlands with a monsoon climate and needs further study. The objective of this study is to relate topographic position and hydrological response in tropical highlands. The research was conducted in the Debre Mawi watershed in the northwest sub-humid Ethiopian highlands. In the monsoon rain phase of 2017 and 2018, groundwater depth, infiltration rate, and surface runoff were monitored at the upslope, midslope, and downslope positions. Surface runoff rates were measured in farmer fields through distributed V-notch weirs as estimates of positional runoff. Average water table depths were 30 cm deep in the downslope regions and 95 cm in the upslope position. The water table depth affected the steady-state infiltration rate in the rain phase. It was high upslope (350 mm h−1), low midslope (49 mm h−1), and zero downslope. In 2017, the average runoff coefficients were 0.29 for the upslope and midslope and 0.73 downslope. Thus, topographic position affects all aspects of the watershed hydrology in the humid highlands and is critical in determining runoff response.
Integration of Numerical Models and InSAR Techniques to Assess Land Subsidence Due to Excessive Groundwater Abstraction in the Coastal and Lowland Regions of Semarang City
Authors: Lo Weicheng , Purnomo Sanidhya Nika , Dewanto Bondan Galih , Sarah Dwi , Sumiyanto
Published: January 2022

This study was carried out to assess land subsidence due to excessive groundwater abstraction in the northern region of Semarang City by integrating the application of both numerical models and geodetic measurements, particularly those based on the synthetic aperture radar interferometry (InSAR) technique. Since 1695, alluvial deposits caused by sedimentations have accumulated in the northern part of Semarang City, in turn resulting in changes in the coastline and land use up to the present. Commencing in 1900, excessive groundwater withdrawal from deep wells in the northern section of Semarang City has exacerbated natural compaction and aggravated the problem of land subsidence. In the current study, a groundwater model equivalent to the hydrogeological system in this area was developed using MODFLOW to simulate the hydromechanical coupling of groundwater flow and land subsidence. The numerical computation was performed starting with the steady-state flow model from the period of 1970 to 1990, followed by the model of transient flow and land subsidence from the period of 1990 to 2010. Our models were calibrated with deformation data from field measurements collected from various sources (e.g., leveling, GPS, and InSAR) for simulation of land subsidence, as well as with the hydraulic heads from observation wells for simulation of groundwater flow. Comparison of the results of our numerical calculations with recorded observations led to low RMSEs, yet high R2 values, mathematically indicating that the simulation outcomes are in good agreement with monitoring data. The findings in the present study also revealed that land subsidence arising from groundwater pumping poses a serious threat to the northern part of Semarang City. Two groundwater management measures are proposed and the future development of land subsidence is accordingly projected until 2050. Our study shows quantitatively that the greatest land subsidence occurs in Genuk District, with a magnitude of 36.8 mm/year. However, if the suggested groundwater management can be implemented, the rate and affected area of land subsidence can be reduced by up to 59% and 76%, respectively.