bluuebunny/crossref_metadata_2025 huggingface dataset:
Photomodulation Alleviates the Senescence of Adipose-Derived Stem Cells Aging in Vitro
Authors: Shu Xin , Wu Jiaqi , Zhang Tao , Ma Xiaoyu , Du Zuoqin , Wang Liqun , Chen Ni , Zheng Youkun , Luo Mao , Wu Jianbo
Published: March 2022

Adipose-derived stem cells (ASCs) therapies are emerging as a promising approach to therapeutic regeneration. Therapeutic persistence and reduced functional stem cell following cell delivery remain a critical hurdle for the clinical investigation due to the senescence of freshly isolated ASCs, extensive in-vitro passage. Cultured ASCs were derived from subcutaneous white adipose tissue isolated from mice fed a normal diet (NFD) or high-fat fed (HFD). ASCs were passaged in vitro and prepared for subculture up to passage 9, after light and non-light-treated ASCs. We performed senescence-associated-β-galactosidase (SA-β-gal) staining and real-time PCR to evaluate the time-dependent changes in expression levels of mRNA related to cell cycle, cellular senescence markers, and senescence-associated secretory phenotype (SASP). The mRNA expression levels of senescence and SASP markers were significantly increased at passages 7 and 9 of ASCs-NFD. At the same passage number, ASCs-HFD showed a markedly higher mRNA level of senescence and SASP than that in ASCs-NFD. At different passages (Passages 3, 5, 7, and 9), these cells were performed by light treatment. Photomodulation reduced the expression of senescence, SASP, and SA-β-Gal in all cells at passage. Moreover, the light-treated ASCs-derived exosomes decrease the expression of senescence, SASP, and SA-β-Gal in the later passage cells. Furthermore, Light treatment significantly increased the Ca 2 + influx compared to the non-light-treated ASCs. Collectively, ASCs can undergo cellular senescence in-vitro passage. Photomodulation may be better preserved over senescence in aged ASCs. Light-treated ASCs-derived exosomes could be served as e a new protective paradigm for the cellular senescence in-vitro passage.
The Novel P330L Pathogenic Variant of Aromatic Amino Acid Decarboxylase Maps on the Catalytic Flexible Loop Underlying its Crucial Role
Authors: Bisello Giovanni , Kusmierska Katarzyna , Verbeek Marcel M. , Sykut-Cegielska Jolanta , Willemsen Michèl A.A.P. , Wevers Ron A. , Szymańska Krystyna , Poznanski Jarosław , Drozak Jakub , Wertheim–Tysarowska Katarzyna , Rygiel Agnieszka Magdalena , Bertoldi Mariarita
Published: March 2022

Aromatic amino acid decarboxylase (AADC) deficiency is a rare monogenic disease, often fatal in the first decade, causing severe intellectual disability, movement disorders and autonomic disfunction. It is due to mutations in the gene coding for the AADC enzyme responsible for the synthesis of the important neurotransmitters dopamine, norepinephrine, epinephrine and serotonin. Using whole exome sequencing, we have identified a novel homozygous c989C>T (Pro330Leu) variant of AADC causing AADC deficiency. Pro330 is part of an essential structural and functional element: the flexible catalytic loop suggested to cover the active site crevice as a lid and properly position the catalytic residues. Our investigations provide evidence that Pro330 concurs in the achievement of an optimal catalytic competence. Through a combination of bioinformatic approaches, dynamic light scattering measurements, limited proteolysis experiments, spectroscopic and in solution analyses, we demonstrate that the substitution of Pro330 with Leu, although not determining gross conformational changes, results in an enzymatic species that is highly affected in catalysis. This defect does not lead to active site structural disassembling, nor to the inability to bind the pyridoxal 5’-phosphate (PLP) cofactor. The molecular basis for the pathogenic effect of this variant is rather due to a mispositioning of the catalytically competent external aldimine intermediate, as corroborated by spectroscopic analyses and pH dependence of the kinetic parameters. Altogether, we determined the structural basis for the severity of the manifestation of AADC deficiency in this patient and discussed the rationale for a precision therapy.
A Physics-based Neural Network for Flight Dynamics Modelling and Simulation
Authors: Stachiw Terrin , Crain Alexander David , Ricciardi Joseph
Published: March 2022

The authors have developed a novel physics-based nonlinear autoregressive exogeneous neural network model architecture for flight modelling across the entire flight envelope, called FlyNet. When using traditional parameter estimation and output-error methods, aircraft models are captured about a single point in the flight envelope using a first-order Taylor series to approximate forces and moments. To enable analysis throughout the entire flight envelope, the traditional models can be extended across the entire flight envelope by interpolating or stitching between a number of these single-condition models. This paper completes the evolutionary next step in aircraft modelling to consider all second-order Taylor series terms instead of a subset of those and by exploiting the ability of neural networks to capture more complex and nonlinear behaviour for the efficient development of a continuous flight simulation model valid across the entire flight envelope. This method is valid for fixed- and rotary-wing aircraft. The behaviour of a conventional model is compared to FlyNet using flight test data collected from the National Research Council of Canada’s Bell 412HP in forward flight.
Parents’ Experiences Caring for Children with Acute Otitis Media: A Qualitative Analysis
Authors: Lee Matthew , Kavalieratos Dio , Alberty Anastasia , Groff Destin , Haralam Mary Ann , Shaikh Nader
Published: March 2022

Background
Little is known regarding parents’ experiences caring for children with acute otitis media (AOM). The goal of this study was to explore parents’ experiences caring for their child with AOM, identifying symptoms they observed, their thoughts and feelings about those symptoms, how they managed the episode, and what factors caused them to seek medical evaluation.
Methods
We conducted semi-structured in-depth interviews with parents of children 3–36 months old with AOM regarding (1) symptoms and behaviors that led parents to believe their child might have AOM; (2) symptoms that were most bothersome to parent and child; (3) what parents did in response to these symptoms; (4) motivations for seeking clinical care; and (5) parents’ expectations regarding AOM resolution.
Results
We interviewed 24 parents within 72 hours of diagnosis of AOM. Ear tugging was the symptom parents believed was most indicative of AOM, despite its presence in only half of the children in this sample. Parents consistently sought medical care when their child had fever or lack of sleep, or when symptoms worsened or were unresponsive to home remedies. Parents of children with history of recurrent AOM had less difficulty identifying symptoms of AOM than parents of children with their first ear infection.
Conclusions
Our findings provide insight into symptoms of AOM that cause parents concern and motivate the use of healthcare services.
Influence of Adsorption Characteristics of Surfactants Sodium Dodecyl Sulfate and Aerosol-OT on Transition Phase of Water-Based Lubrication
Authors: Fang Jingbo , Bai Pengpeng , Ouyang Chuke , Liu Chenxu , Wen Xiangli , Li Yuanzhe , Meng Yonggang , Ma Liran , Tian Yu
Published: March 2022

Previous studies of surfactants as water-based lubrication additives have mainly focused on their steady-state behavior, but the “transition phase” between two steady states has been rarely studied, which is more or at least equally important for actual lubrication conditions. In this study, the lubrication behaviors of sodium dodecyl sulfate (SDS) and sodium bis (2-ethylhexyl) sulfosuccinate (Aerosol-OT, AOT) solutions were comparatively investigated under step-changed working conditions. It was found that the duration of the transition phase of AOT solution as lubricant was significantly shorter than that of SDS. During the transition phase, the contact zone experienced a slight running-in and fresh surfaces were created. Compared with SDS, the adsorption rate of AOT was higher, and its adsorption amount was lower due to the larger steric hindrance of the molecular structure. Therefore, the adsorption state of AOT in the contact zone could reach a new dynamic equilibrium faster, so that the friction coefficient would reach a stable value faster. Different from the common opinion that running-in is the cause of the transition phase of lubrication, this study indicates that the dynamic adsorption behavior of surfactant molecules mainly contributes to this process, which should be paid more attention to guide their industrial applications.
Changes in Homocysteine and Non-Mercaptoalbumin Levels After Acute Exercise: A Crossover Study
Authors: Shinagawa Akiho , Yamazaki Tomoki , Minematsu Ayako , Serizawa Naho , Hosoi Yuri , Ninomiya Yusuke , Miyakoshi Yuichi , Yano Tomohiro , Ota Masako
Published: March 2022

Background
Acute exercise is one factor that increases blood homocysteine levels, and elevated homocysteine levels cause oxidative stress. Albumin, which is abundant in blood, is an antioxidant, and the redox state of albumin is used as an index of oxidative stress in blood. This study aimed to assess the effect of acute exercise on plasma homocysteine levels and the blood non-mercaptoalbumin/mercaptoalbumin ratio as an oxidative stress marker.
Methods
This study used a crossover design with exercise and control conditions. Under exercise conditions, a bicycle ergometer was used to perform 40 min of transient constant-load exercise at 65% heart rate reserve. Under control conditions, participants rested for 40 min. Blood was collected before, 30 min after, and 90 min after exercise, and at the same time points under control conditions. Samples were analyzed for the homocysteine concentration and non-mercaptoalbumin/mercaptoalbumin ratio.
Results
The results revealed that a 65% heart rate reserve and 40 min of acute exercise increased plasma homocysteine concentration and non-mercaptoalbumin ratio. In the intra-condition comparison, the plasma Hcy concentration was significantly increased at Post 30 min (་0.83 ± 0.70 µmol/L, P = 0.003) compared with that at Pre in the exercise condition. Furthermore, 90 min after exercise, the blood non-mercaptoalbumin ratio was significantly increased (་0.35 ± 0.71%, P = 0.030) compared to Pre.
Conclusion
These results indicate that the plasma Hcy concentration first increased, and then the non-mercaptoalbumin/mercaptoalbumin ratio increased as the elevated state was maintained. This study revealed that 65% HRR, 40 min of acute exercise increased plasma Hcy concentraion and non-mercaptoalbumin ratio.
Saponin Protects Against Cyclophosphamide- Induced Kidney and Liver Damage via Antioxidant and Anti-Inflammatory Actions
Authors: Golmohammadi Mohammad Ghasem , Banaei Shokofeh , Abedi Ali
Published: March 2022

Purpose
The liver and kidney are organs affected by chemotherapy drugs such as cyclophosphamide (CP). This study examined the protective effects of treatment with saponin (SP) against CP-induced nephrotoxicity and hepatotoxicity.
Methods
24 adult male mice were divided into four groups (N = 6): Control group, CP (15mg/kg), SP (2.5 mg/kg) and CP + SP. After treatment, the blood samples were collected for the determination of biochemical parameters and liver and kidney samples were taken for histological analysis and the assessment of oxidative stress and inflammatory markers.
Results
Cyclophosphamide decreased renal and liver functions and antioxidant enzymes, which significantly increased blood urea nitrogen- creatinine (BUN- Cr), liver enzyme levels, malondialdehyde, Nuclear factor kappa β (NF-kB) and Interleukin 1 beta (IL-1B) concentrations. Moreover, histopathological findings of the CP group showed that there were acute tubular necrosis and glomerular atrophy in the renal tissues and lymphocyte infiltration in the liver samples. Treatment with saponin improved hepatic and nephric functions, the pathological changes and antioxidant capacity, also, decreased lipid peroxidation and inflammation.
Conclusion
It seems that saponin could exert a hepato-nephropretective effect against cyclophosphamide toxicity.
Effects Of Different Host-Plant Components On Physiological Indices In Spodoptera Frugiperda
Authors: Fang Min , Lu Si-Han , Yao Ling , Li Gui-ting , Zheng Ren-Wen , Tang Qing-Feng
Published: March 2022

Spodoptera frugiperda (J.E.Smith) (Lepidoptera: Noctuidae) is an invasive pest that ravaging crops in many provinces of China. In order to specifically control this invasive pest, understanding of the relationship between the insect and the hosts is necessary. In this study, we have compared the biological and nutritional indices of S. frugiperda by feeding it with five different host-plants (Zea mays, Triticum aestivum, Digitaria sanguinalis, Glycine max and Eleusine indica) under laboratory conditions. The biological and nutritional indices of Z. mays feeding S. frugiperda were the best. However, the pupa weight and fecundity of S. frugiperda fed with G. max and E. indica were significantly lower than those fed with other hosts, efficiency of conversion of digested food (ECD) and efficiency of conversion of ingested food (ECI) were also lower than others. The total phenol content of hosts was negatively correlated with the growth and nutrient accumulation of S. frugiperda, while the C/N content was positively correlated. When fed on different host plants, the biological and nutritional indices of S. frugiperda were different, but all of them could complete the life cycle. Therefore, S. frugiperda also has a tendency to feed on other hosts, especially plants with high C/N content, when Z. mays is insufficient.
Learning Path Optimization Based On Multi-Attribute Matching And Variable Length Continuous Representation
Authors: Xiao Qin , Zhang Yong-Wei , Song Ying-Lei , Chen Mi-Mi
Published: March 2022

Personalized learning path considers both learner and resource attributes. The evolutionary algorithm approach usually forms the learning path generation problem into a problem that optimizes the matching degree of the learner and the generated learning path. The proposed work considers the learner attributes as ability level, learning objective, learning style, and expected learning time. The learning path attributes include difficulty level, covered concept, supported learning styles, required learning time, and prerequisites. A variable-length representation of the learning path is adopted based on floating numbers, which significantly reduces the encoding length and simplifies the learning path generating process. An improved differential evolution algorithm is applied to optimize the matching degree of learning path and learner. The quantitative experiments on different problem scales show the proposed system outperforms the binary-based representation approaches in scaling ability and outperforms the comparative algorithms in efficiency.
Retrosynthetic Planning with Experience-Guided Monte Carlo Tree Search
Authors: Hong Siqi , Zhuo Hankz Hankui , Jin Kebing , Shao Guang , Zhou Zhanwen
Published: March 2022

Retrosynthetic planning problem is to analyze a complex molecule and give a synthetic route using simple building blocks. The huge number of chemical reactions leads to a combinatorial explosion of possibilities, and even the experienced chemists often have difficulty to select the most promising transformations. The current approaches rely on human-defined or machine-trained score functions which have limited chemical knowledge or use expensive estimation methods such as rollout to guide the search. In this paper, we propose EG-MCTS, a novel MCTS-based retrosynthetic planning approach, to deal with retrosynthetic planning problem. Instead of exploiting rollout, we build an Experience Guidance Network to learn knowledge from synthetic experiences during the search. Experiments on benchmark USPTO datasets show that, our EG-MCTS gains significant improvement over state-of-the-art approaches both in efficiency and effectiveness. Routes designed by EG-MCTS for real drugs or compounds exhibit the effectiveness of our approach on assisting chemists performing retrosynthetic analysis.
Our EG-MCTS system solves almost a quarter more and twice times faster than the traditional computer-aided MCTS search method. In a comparative experiment with the literature, our computer-generated routes were generally viewed to be equivalent to reported literature routes by chemists.
Pando’s Pulse: Vital Signs Signal Course Correction at World-Renowned Aspen Forest
Authors: Rogers Paul C.
Published: March 2022

Upland aspen (Populus spp.) forests contribute significantly to biodiversity in their circumboreal role as keystone species. As aspen ecosystems flourish or diminish, myriad dependent species follow suit. The 43-hectare Pando aspen (Populus tremuloides Michx.) clone in Utah, USA, is thought to be the largest living organism on earth, but is faltering due to chronic herbivory. Long-term resilience in aspen communities, including Pando, rests on successful recruitment of vegetative suckers that are nutritiously desirable to browsing ungulates. Here, I evaluate aspen reproduction alongside numerous vital indicators of Pando’s status in the first trend assessment of this embattled iconic forest. I measured 64 plots using 19 indicators to determine current conditions. Findings show that the genetically uniform Pando is “breaking up” because of herbivory and fencing. Initial successes within fenced zones are tempered by nearly half of Pando that remains unprotected from chronic wild and domestic herbivory. I propose a strategy of process-based stewardship informed by adaptive monitoring to restore this famed ‘one-tree forest.’ Lessons from Pando include linkages to struggling, often species rich, aspen systems facing similar challenges globally.
LncRNA260 siRNA promotes M2 macrophage polarization by reducing IL28RA alternative splicing
Authors: Yang Xin-Xing , Li Yan-Yan , Gong Ge , Geng Hong-Yu
Published: March 2022

Background and: Regulating the macrophages toward M2 polarization has become a therapeutic target for promoting cardiac repair after acute myocardial infarction (AMI). Macrophages can promote the transformation from inflammatory M1 type to anti-inflammatory M2 type by activating PI3K/AKT signaling pathway. In our previous study, we found that down-regulation of lncRNA260 could ameliorate hypoxic cardiomyocytes injury by regulating IL28RA through the activation of PI3K/AKT signaling pathways. It was suggested that lncRNA260 siRNA could promote the macrophages toward M2 polarization by regulating IL28RA. In this study, lncRNA260 siRNA was used to observe the polarization of mouse bone marrow macrophages and investigate its related mechanisms.Objective and methods: LncRNA 260 specific siRNA were designed and synthesized which were transfected into murine bone marrow-derived macrophages (BMDM)with liposomes. The experiment was divided into three groups: hypoxia group, hypoxia + lncRNA 260 specific siRNA transfection group, Normoxia group. The CD206-FITC/CD107b (Mac-3) or CD206-APC/CD11b-FITC double positive proportions were used to compare the M2 polarization ratio in the hypoxia process by using the immunofluorescence staining method. The p-AKT, Arginase 1, PI3KCG, IL28RAV1, IL28RAV2 proteins expression changes were observed by using the western blot method.Results: Compared with the Normoxia group, the double positive ratio of CD206-FITC/ Mac-3 and CD206-APC/CD11b-FITC were both significantly decreased in Hypoxia group (P<0.05). Compared with the hypoxia group, the double positive ratio of CD206-FITC/ Mac-3 and CD206/CD11b were both significantly increased in the Hypoxia + lncRNA260 siRNA transfection group (P<0.05). In the Hypoxia group, the ratios of Arg 1/β-Actin, p-AKT/β-Actin, PI3KCG/β-Actin, IL28RAV1/β-Actin were significantly lower than those in the Normoxia group (1.00±0.01) (P<0.05). After transfection with lncRNA260 siRNA, the ratios of Arg1/β-Actin, p-AKT/β-Actin , PI3KCG/β-Actin, IL28RAV1/β-Actin were significantly higher than those in the Hypoxia group (P<0.05) .Compared with the Normoxia group, the IL28RAV2/β-Actin in the Hypoxia group was significantly increased. After transfection with lncRNA260 siRNA, the ratio of IL28RAV2/β-Actin was significantly decreased than that in the Hypoxia group (P<0.05).Conclusion: LncRNA260 siRNA could promote the M2 polarization of the hypoxia macrophages by reducing the IL28RAV2 alternative splicing variant, which might be related to the activation of the JAK-STAT and PI3K/AKT signaling pathways.
Chest dual energy CT to assess the effects of steroids on lung function in severe COVID-19 patients
Authors: Perchiazzi Gaetano , Larina Aleksandra , Hansen Tomas , Frithiof Robert , Hultström Michael , Lipcsey Miklos , Pellegrini Mariangela
Published: March 2022

Background. Steroids have been shown to reduce inflammation, hypoxic pulmonary vasoconstriction (HPV) and lung oedema. Based on evidences from clinical trials, steroids are widely used in severe COVID-19. However, the effect on lung aeration and perfusion in this group of patients are unexplored.Objective. Profiting by dual energy computed tomography (DECT), we investigated whether steroids affect HPV in severe COVID-19 and whether they reduce lung oedema and improve gas distribution.Methods. Severe COVID-19 patients included in a single-center prospective observational study at the intensive care unit at Uppsala University Hospital who had undergone DECT were enrolled in the current study. Patients’ cohort was divided in two groups depending on the administration of steroids. From each patient’s DECT, 20 inflation maps and 20 perfusion maps, evenly distributed along the cranial-caudal axis, were analyzed. To estimate HPV, perfusion distribution was analyzed in both the whole lung and the hypoinflated areas. Total lung weight, index of lung oedema, was estimated.Results. Sixty patients were analyzed, whereof 43 received steroids. Patients exposed to steroids showed a better (non-perfused area 10% vs 15%, p < 0.01) and more homogeneous (kurtosis: 2.51 vs 1.85, p < 0.01) perfusion of hypoinflated areas, indicating reduced HPV. Moreover, they showed a significantly lower lung weight (853gr vs 1005gr, p = 0.01).Conclusions. The use of steroids was associated with impaired HPV and reduced lung oedema in severe COVID-19. This is consistent with previous findings in other diseases. Moreover, reduced lung weight and a more homogeneous distribution of gas within the lung were shown in patients treated with steroids.Trial registration: Clinical Trials ID: NCT04316884, Registered March 13, 2020
Flood susceptibility computation using state-of-the-art machine learning and optimization algorithms
Authors: Costache Romulus-Dumitru , Arabameri Alireza , I Abu Reza Md. Towfiqul , Abba S.I. , Pandey Manish , Ajin R.S. , Pham Binh Thai
Published: March 2022

The present study aims to estimate the flood susceptibility degree over the Prahova River basin located in the central-southern part of Romania. To obtain the proposed outcomes, the next 10 flood predictors were used as independent variable in the machine learning models: slope angle, convergence index, distance from river, elevation, plan curvature, hydrological soil group, lithology, topographic wetness index, rainfall and land use. The factors along with 158 flood locations, that represent the dependent variables, were involved in the training procedure of the following four ensemble models: Deep Learning Neural Network –Statistical Index (DLNN-SI), Particle Swarm Optimization-Deep Learning Neural Network–Statistical Index (PSO-DLNN-SI), Support Vector Machine–Statistical Index (SVM-SI) and Particle Swarm Optimization-Support Vector Machine–Statistical Index (PSO-SVM-SI). Through the Statistical Index method, the coefficients of each flood predictor class/category were calculated. The best performance was achieved by PSO-DLNN-SI model for which an AUC-ROC Curve of 0.952 was calculated. It is worth to note the application of PSO algorithm manage to increase the models performance. Also, it is important to note that around 25% of the study area has a high and very high exposure to flood phenomena.
Genome-wide identification and expression analysis of bZIP transcription factors under abiotic stress in alfalfa (Medicago sativa L.)
Authors: Parajuli Atit , Sanguinet Karen A. , Zhang Zhiwu
Published: March 2022

Background Alfalfa (Medicago sativa L.) is the most cultivated forage legume around the world. Under a variety of growing conditions, forage yield in alfalfa is stymied by biotic and abiotic stresses including heat, salt, drought, and disease. Given the sessile nature of plants, they use strategies such as differential gene expression to respond to environmental cues. Transcription factors control the expression of genes that contribute to or enable tolerance and survival during periods of stress. Basic-leucine zipper (bZIP) transcription factors have been demonstrated to play a critical role in regulating plant growth and development as well as mediate the responses to abiotic stress in several species, including Arabidopsis thaliana, Oryza sativa, Lotus japonicus and Medicago truncatula. However, there is little information about bZIP transcription factors in cultivated alfalfa. ResultIn the present study, 237 bZIP genes were identified in alfalfa from publicly available sequencing data. Multiple sequence alignments showed the presence of intact bZIP motifs in the identified sequences. Based on previous phylogenetic analyses in Arabidopsis thaliana, alfalfa bZIPs were similarly divided and fell into 10 groups. The physico-chemical properties, motif analysis and phylogenetic study of the alfalfa bZIPs revealed high specificity within groups. The differential expression of alfalfa bZIPs in a suite of tissues indicates that bZIP genes are specifically expressed at different developmental stages in alfalfa. Similarly, expression analysis in response to ABA, cold, drought and salt stresses, indicates that a subset of bZIP genes are also differentially expressed and likely play a role in abiotic stress signaling and/or tolerance.ConclusionsTaken together, this work provides a framework for the future study of bZIPs in alfalfa and presents candidate bZIPs involved in stress-response signaling.
First report of Culex quinquefasciatus Say (Diptera: Culicidae) larvae susceptible to temephos, malathion, cypermethrin, and Deltamethrin in Jakarta, Indonesia: Detoxification enzyme activity and the midgut cell damage
Authors: Subahar Rizal , Aulia Annisa Putri , Yulhasri Yulhasri , Yazid Fatmawati , Felim Ris Raihan , Susanto Lisawati , Winita Rawina , Adugna Tilahun
Published: March 2022

Background: Insecticide-resistant Culex quinquefasciatus mosquitoes have been reported worldwide but the susceptibility status of Cx.quinquefasciatus larvae to insecticides has not been determined in Jakarta, Indonesia. This study aimed to evaluate the susceptibility status of Cx. quinquefasciatus larvae to temephos, malathion, cypermethrin, and deltamethrin in Jakarta, Indonesia, through the mode of action detoxification enzyme activity and digestive system damage.Methods: Cx. quinquefasciatus larvae were collected from five sites in Jakarta. The larval susceptibility test to temephos used the WHO standard kits (1.25, 6.25, 31.25, and 156.25 ppm) and to malathion (0.5 ppm), cypermethrin (.25 ppm), and deltamethrin (0.35 ppm). The activity of acetylcholinesterase (AChE), glutathione S-transferase (GST), and oxidase were measured by the biochemical method. The larval midgut cell damage was examined using the routine histopathological method and transmission electron microscopy (TEM).Results: At 24 h, temephos and deltamethrin caused 100% larval death of Cx.quinquefasciatus in five sites of Jakarta. Temephos and malathion significantly inhibited AChE activity, while cypermethrin and deltamethrin significantly inhibited oxidase activity. All tested insecticides significantly damaged the larval midgut. The TEM findings showed the damaged parts of the midgut epithelial cells included the cell membrane, nuclei, nucleoli, mitochondria, and other organelles cells.Conclusion: This study is the first to report that Cx.quinquefasciatus larvae in Jakarta were completely susceptible to temephos and deltamethrin through metabolic enzymes and midgut cell damage. This study provides baseline data to improve mosquito control programs.
Automated classification of time-activity-location patterns for improved estimation of personal exposure to air pollution
Authors: Chatzidiakou Lia , Krause Anika , Kellaway Mike , Han Yiqun , Li Yilin , Martin Elizabeth , Kelly Frank J , Zhu Tong , Barratt Benjamin , Jones Roderic L
Published: March 2022

Background: Air pollution epidemiology has primarily relied on measurements from fixed outdoor air quality monitoring stations to derive population-scale exposure. Characterisation of individual time-activity-location patterns is critical for accurate estimations of personal exposure and dose because pollutant concentrations and inhalation rates vary significantly by location and activity. Methods: We developed and evaluated an automated model to classify major exposure-related microenvironments (home, work, other static, in-transit) and separated them into indoor and outdoor locations, sleeping activity and five modes of transport (walking, cycling, car, bus, metro/train) with multidisciplinary methods from the fields of movement ecology and artificial intelligence. As input parameters, we used GPS coordinates, accelerometry, and noise, collected at 1 min intervals with a validated Personal Air quality Monitor (PAM) carried by 35 volunteers for one week each. The model classifications were then evaluated against manual time-activity logs kept by participants. Results: Overall, the model performed reliably in classifying home, work, and other indoor microenvironments (F1-score>0.70) but only moderately well for sleeping and visits to outdoor microenvironments (F1-score=0.57 and 0.3 respectively). Random forest approaches performed very well in classifying modes of transport (F1-score>0.91). We found that the performance of the automated methods significantly surpassed those of manual logs. Conclusions: Automated models for time-activity classification can markedly improve exposure metrics. Such models can be developed in many programming languages, and if well formulated can have general applicability in large-scale health studies, providing a comprehensive picture of environmental health risks during daily life with readily gathered parameters from smartphone technologies.
Heterogeneity of Tick Abundance and Infection with Zoonotic Pathogenic Bacteria in a Belgian Peri-Urban Forest
Authors: Rousseau Raphael , Mori Marcella , Kabamba Benoît , Vanwambeke Sophie O.
Published: March 2022

Background
Forests are the primary habitats for Ixodes ricinus and harbor high tick populations, vectors of various pathogens. As such, they are often considered as a homogenous land cover harboring abundant tick populations. However, little is known about the heterogeneity in tick density within a peri-urban forest, where human exposure is high. The study aims to assess the micro-environmental factors that favor tick abundance and their infection with three pathogens, in a peri-urban forest.
Methods
Ticks were sampled 17 times in 2016 in seven locations of a peri-urban forest during the period of tick activity. Three zoonotic pathogens were screened, Borrelia burgdorferi s.l., Coxiella burnetii, and Francisella tularensis. The influences of micro-environmental factors on tick abundance and infected tick abundance were tested with multiple negative binomial generalized linear models.
Results
787 nymphs and 81 adult ticks were collected., resulting in densities of 6.61 nymphs and 0.68 adults per 10 km². These densities were variable between the sites, ranging from 2.12 to 14.59 nymphs per 10m² and 0.24 to 1.29 adults per 10m². The prevalence of B. burgdorferi s.l. was estimated at 3.37%. Coxiella burnetii was detected three times (1.36%) and F. tularensis was not detected. Tick abundances were highest in deciduous forests, located in sandy and loamy-sand soils covered by dense vegetation not easily accessible to forest visitors. The temperature during the sampling also positively affected tick abundance. No variables were significant for the models for infected ticks.
Conclusions
Tick abundance was in the upper range of other estimated tick densities in Belgian forests. Borrelia infection prevalence was lower but the genospecies composition was similar to previous studies in Belgium. The assumption that forests are a homogenously suitable tick habitat is questioned and we underline the necessity to account for micro-environmental conditions and human exposure.
Geospatial Modeling of Socio-Economic and Environmental Determinants of Typhoid Fever in Kano State, Nigeria
Authors: Abdulkarim Ishaq A. , Salisu Hassana Sulaiman , Ahmed Mohammed , Mohammed Murtala Uba
Published: March 2022

Typhoid is a significant health problem, particularly in developing countries like Nigeria where access to sanitation is still a challenge. This study modeled the socio-economic and environmental determinants of typhoid fever in Kano State, the most populated state located in the northwestern part of Nigeria. Data was collected from the State Hospital Management Board after submitting the requirement for ethical approval. Landsat 8 image was downloaded from an open-source website USGS earth explorer and Kano state administrative boundaries from GRID3 websites. Land use/land cover maps and Kano priority data were collected from the Department of Geography, Bayero University Kano. The study used 6 variables: literacy rate, population density, housing density, urbanization, NDVI, and LST to model typhoid fever. Based on the study’s findings the Kano Municipal, Gaya, Gezewa and Bebeji recorded the highest prevalence per 10,000 persons of above 300. That there is a significant association between 5 of the 6 factors (with exception of land surface temperature (LST)). Out of the 5 factors, 4 showed positive significance (literacy rate, Population Density, Household density, and Percentage Urban) while the mean NDVI is the only one that showed a negative significance. The coefficient of determination (R square) is < 0.5 (0.374488) which showed the variable poorly described the prevalence rate. The model was also found to be biased because the Jarque-Bera Statistic is statistically significant which means the study is missing one or more key explanatory variables. It was recommended that the government should invest more in Data acquisition to help improve the quality of research in the study area.
Long noncoding RNA KB-1980E6.3 promotes breast cancer progression through the PI3K/AKT signalling pathway
Authors: He Lin , Tang Lingfeng , Wang Rui , Li Liu , Zhu Pengpeng , Jiang Kunwei , Tu Gang
Published: March 2022

The authors have requested that this preprint be removed from Research Square.
Development of Artificial Sebum-containing Leeming and Notman Agar Medium to Enhance the Growth of Malassezia
Authors: Suzuki Kazuhiro , Inoue Mizuna , Takayama Kodai , Nagahama Tohru , Cho Otomi , Kurakado Sanae , Sugita Takashi
Published: March 2022

Modified Leeming and Notman agar medium (mLNA) has been widely utilized to grow lipophilic fungi belonging to the genus Malassezia. We developed a new artificial sebum-containing mLNA to obtain higher yields of Malassezia spp. The olive oil in mLNA was replaced with artificial sebum composed of triglyceride (triolein), diglyceride (glyceryl distearate), fatty acids (palmitic acid, myristic acid, pentadecanoic acid, and oleic acid), and squalene, and the Tween 60 was replaced with glyceryl stearate. Nine human-associated Malassezia species grew well on the artificial sebum-containing mLNA, and the yield of the most predominant fungus on human skin, Malassezia restricta, in artificial sebum-containing mLNA was double that in standard mLNA.
A content analysis for Children’s Chinese Reader and its implications
Authors: Cai Qiao-Yu , Chao Feng-Mei
Published: March 2022

Chinese learning materials for children has yet to be explored. This study revises the assessment form in Chinese Learning Materials Design Prerequisites, developed by Wang in 2008, to evaluate Chinese learning materials for Children, with a focus on a book series entitled Children’s Chinese Reader published by the Overseas Community Affairs Council in Taipei, Taiwan. The purpose of this study is two-fold. The first attempt is to find out the potential merits and the drawbacks that need addressing urgently. The second attempt is to see the potentiality of using the same materials on different groups of children leaners such as children learning Chinese as a second language, instead of the target learners that the book series has set on. The finding from the initial evaluation indicated a low score of 91 in individually evaluated categories except one, which is being systematic. Categories in being specific, being practical, being scientific, and being intriguing all received a low score. The current surmise is that the then Children’s Chinese Reader is a synchronic product of its time that now calls for advancement in latest theoretical research and contemporary teaching principles if materials for children’s learning can play an appropriate role in modern-day teaching.
Evaluation of the association between coronary artery aneurysm and concomitant infection in patients with Kawasaki disease
Authors: Liu Jie , Qin SuYuan , Su DanYan , Ye BingBing , Wang BaoFeng , Pang Yusheng
Published: March 2022

Purpose: Multisystem inflammatory syndrome in children, which has overlapping clinical features with Kawasaki disease (KD), has generated considerable interest in the relationship between KD and infectious diseases during the ongoing global outbreak of coronavirus disease 2019. However, few studies have focused on the relationship between KD and concomitant infection, and reports on the relationship between infections and recovery from coronary artery aneurysms (CAA) are even rarer.Methods: Patients were classified into case and control groups according to the results of their pathogen examinations, and the baseline characteristics of the two groups were compared. The Kaplan–Meier survival analysis was used to compare the medium-term recovery time of CAA between patients with and without infections, and multivariable analyses were performed to evaluate potential risk factors associated with CAA without recovery between 1 and 2 years of follow-up.Results: A total of 353 pediatric patients with KD were included, of whom 83 (23.5%) had confirmed co-infection. There were no significant differences in patients’ response to treatment and coronary artery outcome when compared between patients with and without infections. Among the 90 patients diagnosed with CAA, 20 (22.2%) had confirmed co-infection, and no significant differences were observed in coronary artery changes from baseline at 2 weeks, 4 weeks, and 3 months in patients with CAA with and without infections. The estimated median time (6 months, 95%CI:1.920–10.080) was higher in the CAA co-infected group than in the CAA non-infected group (3 months, 95%CI:2.366–3.634), with no significant difference. Multivariate analysis revealed that a high Z-score of the coronary artery internal diameter at 1 month after onset was significantly associated with CAA without recovery. The Z score of the left main coronary artery was ≥3.215 with an 89% sensitivity and 77% specificity in predicting CAA without recovery within 1 year of onset. The Z score of the right coronary artery was ≥3.845 with a 64% sensitivity and 98% specificity in predicting CAA without recovery within 1 year of onset and with an 83% sensitivity and 88% specificity within 2 years of onset.Conclusions: Concomitant infection with KD diagnosis did not affect the patients’ response to IVIG treatment and coronary artery outcome when compared with patients without infections; however, the time to coronary artery normalization was not notably prolonged in CAA patients with infections, but a larger maximum Z score at 1 month after onset was a risk factor significantly associated with coronary artery dilatation without recovery within 2 years of onset.
First in-human trial protocol investigating a scaffold-free Bio 3D conduit developed from autologous dermal fibroblasts for peripheral nerve regeneration: a safety and feasibility study
Authors: Nagai-Tanima Momoko , Ikeguchi Ryosuke , Ushimaru Mika , Amino Yoko , Aoi Ishikawa , Akieda Shizuka , Noguchi Takashi , Ito Hiromu , Aoyama Tomoki , Matsuda Shuichi
Published: March 2022

Background
Autologous nerve grafting is considered to be the gold standard treatment for severe and/or wide-ranging damage resulting in neurotmesis. However, the technique has several disadvantages including donor site morbidity and the limited supply of donor nerves. B3CON-01 is a scaffold-free three-dimensional conduit composed entirely of autologous dermal fibroblasts and is designed to overcome these disadvantages. Herein, the authors propose a protocol to evaluate the safety and utility of B3CON-01 in humans with peripheral nerve injury as the first step before randomized clinical trial test.
Methods
Individuals with a severed peripheral nerve cutting or defect, measuring ≤ 20 mm in length and diameter ≤ 2 mm, will be recruited. After participants provide informed consent, autologous dermal fibroblasts will be collected from each via skin biopsy. B3CON-01 is produced using the fibroblasts and transplanted into each subject. To avoid contamination among tissues, the protocol will be performed separately in each subject. Outcomes will be assessed at baseline and post-intervention at each time point. Participants will be assessed at 12 months’ follow-up. The primary outcome measure is the safety of the intervention. The safety endpoint will be the incidence of adverse events and defects. As a secondary assessment, efficacy will be assessed using nerve system and functional analyses.
Conclusion
The protocol of this study will be the first to assess the safety and efficacy of B3CON-01 in humans, and will contribute to not only the development of a treatment for peripheral nerve injury, but also to “made-to-order” personalized therapies in regenerative medicine.
A Study of a Fractional-order Model of Coronavius Disease 2019(COVID-19) after Mass Caccination
Authors: Wang Chunhua , Ma Xiaojuan
Published: March 2022

New coronavirus (COVID-19) broke out at the end of 2019. Today, the epidemic has spread all over the world. The number of confirmed cases is 250 million and the number of deaths has reached about 5000000, which undoubtedly caused serious public health disasters all over the world. In the face of the problem that the virus continues to mutate and the virus spreads faster and survives for a longer time after mutation, as well as the situation of asymptomatic infected persons, the study of the transmission law and epidemic trend of COVID-19 provides theoretical support for how to effectively prevent epidemics, which is of great research value. Most of the previous studies on COVID-19 adopt SIR model and variants of SIR model, and there are few theoretical studies on the impact of asymptomatic infection on the transmission, prevention and control of infectious diseases.Because the time of large-scale vaccination of COVID-19 vaccine in China is about the middle of 2021, so far, no scholars have studied the transmission law and prevention and control of COVID-19 virus after large-scale vaccination. In addition,most researchers use the integer-order models.Generally speaking, integer-order may not capture satisfactory model attributes. Based on this, this paper proposes a SEQIR model with quarantine item, sets up seven fractional order equations, studies and compares the epidemic prevention measures taken by the two places in the face of the re outbreak of the epidemic before mass vaccination (Beijing) and after vaccination (Hunan), calculates the size of the basic regeneration number $R_{0}$ in the two places and reports according to the real data of the two places, different numerical simulations are carried out.Studies have shown that mass vaccination and nucleic acid detection can effectively reduce the transmission of the virus. In addition, in the area where the epidemic situation is concentrated, a large number of nucleic acid tests in time can enable asymptomatic infected persons to be detected in time. After isolating asymptomatic infected people, asymptomatic infected people will infect fewer susceptible people.
Biological and behavioral predictors of compensatory energy intake after exercise
Authors: Höchsmann Christoph , Beckford Safiya E , French Jeffrey A , Boron Julie B , Stevens Jeffrey R , Koehler Karsten
Published: March 2022

Energy intake in the post-exercise state is highly variable and compensatory eating – i.e., (over‑) compensation of the expended energy via increased post-exercise energy intake – occurs in some individuals but not others. We aimed to identify predictors of post-exercise energy intake and compensation. In a randomized crossover design, 57 healthy participants (21.7 [SD=2.5] years; 23.7 [SD=2.3] kg/m2, 75% White, 54% female) completed two laboratory-based test-meals following (1) 45-min exercise and (2) 45-min rest (control). We assessed associations between biological (sex, body composition, appetite hormones) and behavioral (habitual exercise via prospective exercise log, appetitive traits) characteristics at baseline and total energy intake, compensatory energy intake (intake – exercise expenditure), and the difference between post-exercise and post-rest intake. We found a differential impact of biological and behavioral characteristics on total post-exercise energy intake in men and women. In men, only fasting (baseline) concentrations of appetite-regulating hormones (peptide YY [PYY, β=0.88, P<0.001] and adiponectin [β=0.66, P=0.005] predicted total post-exercise energy intake, while in women, only habitual exercise (β=−0.44, P=0.017) predicted total post-exercise energy intake. Predictors of compensatory intake (intake – exercise expenditure) were almost identical to those of total intake. The difference in energy intake between exercise and rest was associated with VO2peak (β=−0.45, P=0.020), fasting PYY (β=0.53, P=0.036), and fasting adiponectin (β=0.57, P=0.021) in men but not women (all P>0.51). Our results show that biological and behavioral characteristics differentially affect total and compensatory post-exercise energy intake in men and women. This may help identify individuals who are more likely to compensate for the energy expended in exercise. Targeted countermeasures to prevent compensatory energy intake after exercise should take the demonstrated sex differences into account.