bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition mechanism and antiviral activity of an α-ketoamide based SARS-CoV-2 main protease inhibitor
Authors: Chen Xiaoxin , Huang Xiaodong , Ma Qinhai , Kuzmič Petr , Zhou Biao , Xu Jinxin , Liu Bin , Jiang Haiming , Zhang Wenjie , Yang Chunguang , Wu Shiguan , Huang Jianzhou , Li Haijun , Long Chaofeng , Zhao Xin , Xu Hongrui , Sheng Yanan , Guo Yaoting , Niu Chuanying , Xue Lu , Xu Yong , Liu Jinsong , Zhang Tianyu , Spencer James , Deng Wenbin , Chen Shu-Hui , Xiong Xiaoli , Yang Zifeng , Zhong Nanshan
Published: March 2023

SARS-CoV-2 has demonstrated extraordinary ability to evade antibody immunity by antigenic drift. Small molecule drugs may provide effective therapy while being part of a solution to circumvent SARS-CoV-2 immune escape. In this study we report an α-ketoamide based peptidomimetic inhibitor of SARS-CoV-2 main protease (Mpro), RAY1216. Enzyme inhibition kinetic analysis established that RAY1216 is a slow-tight inhibitor with a Ki of 8.6 nM; RAY1216 has a drug-target residence time of 104 min compared to 9 min of PF-07321332 (nirmatrelvir), the antiviral component in Paxlovid, suggesting that RAY1216 is approximately 12 times slower to dissociate from the protease:inhibitor complex compared to PF-07321332. Crystal structure of SARS-CoV-2 Mpro:RAY1216 complex demonstrates that RAY1216 is covalently attached to the catalytic Cys145 through the α-ketoamide warhead; more extensive interactions are identified between bound RAY1216 and Mpro active site compared to PF-07321332, consistent with a more stable acyl-enzyme inhibition complex for RAY1216. In cell culture and human ACE2 transgenic mouse models, RAY1216 demonstrates comparable antiviral activities towards different SARS-CoV-2 virus variants compared to PF-07321332. Improvement in pharmacokinetics has been observed for RAY1216 over PF-07321332 in various animal models, which may allow RAY1216 to be used without ritonavir. RAY1216 is currently undergoing phase III clinical trials to test real-world therapeutic efficacy against COVID-19.
Light and temperature induced shedding, encystment and excystment of avian fluke Philophthalmu sp. under laboratory conditions
Authors: Jayawardena U. A , Amerasinghe P. H , Rajakaruna R. S
Published: March 2023

Objective: Cercarial shedding, encystment and excystment of digeneans are complex processes, dependent on intrinsic and extrinsic factors. We reportsequential events occur during shedding, encystment and excystment of cercariae of Philophthalmus sp.,released by freshwater snail, Thiara scabra. Snails were exposed to direct sunlight in petri dishes containing dechlorinated tap water (pH~ 6.5, 27° C) under laboratory conditions and the shedding, encystment and excystment of cercariae were observed under dissecting microscope.
Results:Megarulous cercariae actively emerged from the snail exhibited vigorous movement prior to encystment. They attached to the petri dish with the adhesive gland at the tip of the tail,immobilized the body, shed the tail and formed a flask shapedcyst within 10−15 min. After 30−40 min, excystment started with sequential events; activation, breaching and final release of the metacercaria from the cyst, completed in another 10−15 min. The excessive heat emanating from the microscope light bulb may have induced this behaviour. This is the first report of Philophthalmus sp, infecting T.scabrain Sri Lanka.Experimental induction of the life cycle stages of digeneans may provide valuable insight to explore their life history and provide models for testing the efficacy of antihelmintics against trematodes of medical and veterinary importance.
Data-driven methodology for optimal Lithium-ion battery RUL prediction
Authors: Puente Daniel , Amelibia Jon , Cumplido Iker , Hernandez Aitor , Ugarte Iñigo , Duo Aitor
Published: March 2023

Lithium-ion batteries have emerged as a prevalent power source in a variety of industries, including the electric vehicle sector due to their higher energy density and low self-discharge. With the use and passage of time, batteries degrade and eventually die, endangering the integrity of the objects they power. The ability to accurately predict the Remaining Useful Life (RUL) of lithium-ion batteries is crucial for optimizing their utilization and ensuring their safe operation. For this purpose, a deep learning-based approach trained on the widely used Oxford battery degradation dataset with the help of Generative Adversarial Networks (GANs) has been implemented. The designed network consists of a Long-Short-Term Memory (LSTM) architecture with the implementation of a stratification strategy and a custom loss function. The illustrative results show that the suggested approach can produce adaptable and reliable predictions of the RUL.
InSAR monitoring and evaluation study on the safety and stability of high-altitude limestone dumps
Authors: DONG Jianjun , Mei Yuan , JIANG Hao , GAO Ke
Published: March 2023

The conventional method of monitoring the stability and safety of slopes at high-altitude dumps is associated with a high financial investment and poses a risk for personnel involved in the deployment of monitoring instruments. In order to mitigate the challenges posed by conventional monitoring methods, including high investment and potential risks to personnel, we employed Synthetic Aperture Radar Interferometry (InSAR) technology for the evaluation of slope stability at a high-altitude dumps in Sangri County, Shannan, Tibet. The utilization of Synthetic Aperture Radar Differential Interferometry (D-InSAR) technology was employed to observe the deformation of the dumps over the course of the rainy season, spanning from 2019 to 2022. A four-year (Nov 2018 to Oct 2022) deformation rate assessment of the dumps was performed utilizing the Small Baseline Subset⁃Interferometric Synthetic Aperture Radar (SBAS-InSAR) technology. The accuracy of InSAR monitoring in high-altitude slope areas was verified through correction with the results obtained from GNSS RTK monitoring. The state of stability and safety of the slope at the dumps was evaluated based on the results obtained from deformation monitoring. The D-InSAR monitoring results indicated that when the rainfall surpassed 300 mm, the slope deformation of the dumps exhibited a maximum displacement of 20 mm, necessitating intervention. The results of SBAS-InSAR monitoring indicate that the slope of the dumps underwent substantial deformation changes during the rainy season, yet remained stable during the dry periods. However, the results of our SBAS-InSAR monitoring indicate that the deformation and displacement curves of the dumps did not correspond entirely with changes in rainfall, and exhibited a hysteresis phenomenon in terms of deformation magnitude. The application of InSAR technology allows for the comprehensive and dynamic monitoring of the slopes at high-altitude dumps, offering reliable long-term assessments of safety and stability and ensuring secure and stable operations.
CRitical Assessment of genomic COntamination detection at several Taxonomic ranks (CRACOT)
Authors: Cornet Luc , Lupo Valerian , Declerck Stéphane , Baurain Denis
Published: March 2023

Background Genome contamination is a well-known issue in (meta)genomics. Although it has received a lot of attention, with an increasing number of detection tools made available over the years, no comparison between these tools exists in the literature.
Results Here, we report the benchmarking of six of the most popular tools using a simulated framework. Our simulations were conducted on six different taxonomic ranks, from phylum to species. The analysis of the estimated contamination levels indicates that the precision of the tools is not good, often due to large overdetection but also underdetection, especially at the genus and species ranks. Furthermore, our results show that only redundant contamination is accurately estimated.
Conclusion Our results indicate that using a combination of tools, including Kraken2, is necessary to estimate the contamination level accurately. We also provide a freely available contamination simulation framework, CRACOT, which may be useful for estimating the accuracy of future algorithms.
Neurodesk: An accessible, flexible, and portable data analysis environment for reproducible neuroimaging
Authors: Bollmann Steffen , Renton Angela , Dao Thuy , Johnstone Tom , Civier Oren , Sullivan Ryan , White David , Lyons Paris , Slade Benjamin , Abbott David , Amos Toluwani , Bollmann Saskia , Botting Andy , Campbell Megan , Chang Jeryn , Close Thomas , Eckstein Korbinian , Egan Gary , Evas Stefanie , Flandin Guillaume , Garner Kelly , Garrido Marta , Ghosh Satrajit , Grignard Martin , Hannan Anthony , Huber Laurentius (Renzo) , Kaczmarzyk Jakub , Kasper Lars , Kuhlmann Levin , Lou Kexin , Mantilla-Ramos Yorguin-Jose , Mattingley Jason , Morris Jo , Narayanan Akshaiy , Pestilli Franco , Puce Aina , Ribeiro Fernanda , Rogasch Nigel , Rorden Chris , Schira Mark , Shaw Thomas , Sowman Paul , Spitz Gershon , Stewart Ashley , Ye Xincheng , Zhu Judy , Hughes Matthew , Narayanan Aswin
Published: March 2023

Neuroimaging data analysis often requires purpose-built software, which can be challenging to install and may produce different results across computing environments. Beyond being a roadblock to neuroscientists, these issues of accessibility and portability can hamper the reproducibility of neuroimaging data analysis pipelines. Here, we introduce the Neurodesk platform, which harnesses software containers to support a comprehensive and growing suite of neuroimaging software (https://www.neurodesk.org/). Neurodesk includes a browser-accessible virtual desktop environment and a command line interface, mediating access to containerized neuroimaging software libraries on various computing platforms, including personal and high-performance computers, cloud computing and Jupyter Notebooks. This community-oriented, open-source platform enables a paradigm shift for neuroimaging data analysis, allowing for accessible, flexible, fully reproducible, and portable data analysis pipelines.
Antipsychotic Polypharmacy and Associated Factors among Patients with Schizophrenia at Comprehensive Specialized Hospitals in the Northwest Ethiopia: a Multicenter Cross-sectional Study, 2022
Authors: Tamene Fasil Bayafers , Sema Faisel Dula , Sendeke Ashenafi Kibret
Published: March 2023

Background: Antipsychotic polypharmacy refers to the co-prescription of more than one antipsychotic drug for a particular patient. Despite recommendations by guidelines to minimize combinations of antipsychotics except after repeated trial of antipsychotic monotherapy, it is quite a frequent practice to utilize combinations.
Objective: This study aimed to assess antipsychotic polypharmacy and its associated factors among patients with schizophrenia at Comprehensive Specialized Hospitals in Northwest Ethiopia.
Method: A cross sectional study was conducted among 422 patients with schizophrenia using systematic random sampling. The Alcohol, Smoking and Substance Involvement Screening Test, were used to measure substance use. Data entry and analysis were done using Epi-data version 4.6.1 and SPSS version 24 respectively. Binary logistic regression was applied to identify factors associated with antipsychotic polypharmacy. Variables with a p-value < 0.05 at a 95% confidence interval were considered as statistically significant.
Result: The overall prevalence of antipsychotic polypharmacy was 22.7% (CI: 19 - 27). Duration of illness (AOR: 2.88; CI: 1.49, 5.59), duration of treatment (AOR: 3.79; CI: 1.05, 13.62), number of admission (AOR: 4.93; CI: 2.52, 9.64) and substance use (AOR: 2.58; CI: 1.49, 4.47) were significantly associated with antipsychotic polypharmacy.
Conclusion and recommendation: In this study, antipsychotic polypharmacy was recorded in considerable amount of patients. Duration of illness, duration of treatment, number of admissions, and substance use were significantly associated with antipsychotic polypharmacy. Therefore, clinicians and other responsible stakeholder groups should identify interventions that need to be implemented to improve antipsychotic utilization.
Multiple-Response Optimization by using Neural Networks and Metaheuristic Algorithms
Authors: Abbasi Hossein , Noorossana Rassoul , Tavakkoli-Moghaddam Reza
Published: March 2023

An important problem in manufacturing or product and process design is optimization of several responses simultaneously. Common approaches for multiple response optimization problems often begin with estimating the relationship between responses as outputs and control factors as inputs. Among these methods, response surface methodology (RSM), has attracted more attention in recent years, but in certain cases, relationship between responses and control factors are far too complex to be efficiently estimated by regression models and RSM method especially when we want optimize several responses simultaneously. An alternative approach proposed in this paper is to use artificial neural network (ANN) to estimate the response functions, Because of high mean square error (MSE) in neural network training step we use heuristic algorithms instead of Descent Gradient based algorithms. In the optimization phase a particle swarm optimization (PSO) and desirability function are considered to determine the optimal settings for the control factors. Two case study from literature are prepared to illustrate the strength of proposed approach in optimization of multiple response problems.
Microbial diversity and activity of biofilms from geothermal springs in Croatia
Authors: Kostešić Ema , Mitrović Maja , Kajan Katarina , Marković Tamara , Haumann Bela , Orlić Sandi , Pjevac Petra
Published: March 2023

Hot spring biofilms are stable, highly complex microbial structures. They form at dynamic redox and light gradients and are composed of microorganisms adapted to the extreme temperatures and fluctuating geochemical conditions of geothermal environments. In Croatia, a large number of poorly investigated geothermal springs hosts biofilm communities. Here, we investigated the microbial community composition of biofilms collected over several seasons at 12 geothermal springs and wells. We found biofilm microbial communities to be temporally stable and highly dominated by Cyanobacteria in all but one high-temperature sampling site (Bizovac well). Of the physiochemical parameters recorded, temperature was found to have the strongest influence on biofilm microbial community composition. Besides Cyanobacteria, the biofilms were mainly inhabited by Chloroflexi, Gammaproteobacteria and Bacteroides. In a series of incubations with Cyanobacteria-dominated biofilms from Tuhelj spring, and Chloroflexi- and Proteobacteria-dominated biofilms from Bizovac well, we stimulated either chemoorganotrophic or chemolithotrophic community members, to determine the fraction of microorganisms in biofilms dependent on organic carbon (in situ predominantly produced via photosynthesis) versus energy derived from geochemical redox gradients (here simulated by addition of thiosulfate). We found a surprisingly similar level of activity in response to all substrates in these two distinct biofilm communities and observed microbial community composition and hot spring geochemistry to be poor predictors of microbial activity in the studies systems.
Cell proliferation and apoptosis immunolocalisation suggest an association between aggressiveness and the preferred location of mural unicystic ameloblastomas: A multicentricStudy
Authors: Costa Rebeca Vieira , Balbinot Karolyny Martins , Silveira Gabriela Cristina Avertano Rocha da , Kataoka Maria Sueli da Silva , Menezes Silvio Augusto Fernandes , Freitas Vanessa Morais , Vasconcelos Ana Carolina Uchoa , Etges Adriana , Santos Fabricio Passador , Júnior Sérgio Melo Alves , Jaeger Ruy Gastaldoni , Pinheiro João de Jesus Viana
Published: March 2023

Objectives
This study aimed to assess whether the different biological behaviour between subtypes of unicystic ameloblastoma (UA) are related to the expression of proteins that modulate cell proliferation and apoptosis.
Materials and methods
Immunohistochemical study with a sample of 32 cases of UA, 11 cases of conventional ameloblastoma (CAM) and 10 dental follicles (DF) cases was performed. Cell proliferation was assessed using Ki-67 status and apoptosis by expression of Caspase-3. Positive cells were quantified in each sample and the difference among groups was compared.
Results
Mural UA (MUA) showed a higher immunostaining of Ki-67 (p < 0.05) and a lower immunostaining of Caspase-3 (p < 0.05) compared to luminal and intraluminal subtypes of UA (LIUA) and CAM. For both proteins, the LIUA and CAM groups showed no statistical difference. The neoplastic cells of the cystic capsule of the MUA showed a higher expression of Ki-67 protein (p < 0.0001) and a lower expression of Caspase-3 (p < 0.0001) compared to the lumen. DF showed lower Ki-67 and Caspase-3 immunostaining (p < 0.05) than neoplasms, except when comparing Caspase-3 expression between DF and MUA, as there was no statistical difference.
Conclusions
The higher immunoexpression of Ki-67 and lower of Caspase-3 in MUA, in the parenchyma cells inside the cystic capsule, suggests an association between the biological behaviour and the location of neoplastic cells in the tumour.
Cheese whey permeate as a precursor of lactose-free, galactose-rich bioproducts: an approach for optimization and application
Authors: Flores Viviana K. Rivera , DeMarsh Timothy A. , Fan Xingrui , Alcaine Samuel D.
Published: March 2023

Under specific conditions, the fermentation of whey permeate (WP) by Brettanomyces claussenii can create bioproducts with high galactose concentrations and potential functionalities. The aims of this research are to optimize the fermentation of WP by B. claussenii using response surface methodology to maximize the production of ethanol and galactose, and to characterize various products obtained with this approach. For this purpose, five fermentation factors were studied to determine their impacts on ethanol and galactose: temperature (20 - 40°C), substrate concentration (5 - 15%TS), lactase enzyme/substrate ratio (0 - 40 IU/ g lactose), inoculation level (6 - 8 log cfu/mL), and time (6 - 30 days). Linear models, containing quadratic and interaction effects, were built for the optimization of both responses. Optimal levels were predicted for the maximum obtainment of ethanol and galactose simultaneously, which utilized the following parameters: 15%TS, 37 IU / g lactose, 28°C, 7.5 log cfu/mL, and 30 days, which together were predicted to produce 4.0%v/v ethanol and 51 g/L galactose in the final product. These parameters were then applied to 18-L fermentations, and the resulting fermentates were processed via distillation and freeze-drying. As a result, four product streams were obtained: a fermented product with 3.4%v/v ethanol and 56 g/L galactose; a 45%v/v ethanol distillate; a galactose-rich drink base (63 g/L); and a galactose-rich powder (55%w/w). These results demonstrate that it is possible to maximize the production of ethanol and galactose from the fermentation of WP and to design manufacturing processes based on these optimization models, to develop novel, potentially functional bioproducts from this stream.
Unveiling the anti-glioma potential of a marine derivative, Fucoidan: its synergistic cytotoxicity with Temozolomide-an in vitro and in silico experimental study
Authors: Biswas Indrani , Precilla Daisy S , Kuduvalli Shreyas S , Ramachandran Muralidharan Arumugam , Akshaya S , Raman Venkat , Prabhu Dhamodharan , T.S Anitha , T.S Anitha
Published: March 2023

IntroductionGlioma, coined as a “butterfly” tumor associated with a dismal prognosis. Marine algal compounds with the richest sources of bioactive components, act as significant anti-tumor therapeutics. However, there is a paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. Therefore, the present study aimed to evaluate the synergistic anti-proliferative, anti-inflammatory and pro-apoptotic effects of Fucoidan with Temozolomide inin vitroandin silicoexperimental setup.MethodologyThe anti-proliferative effects of Temozolomide and Fucoidan was evaluated on C6 glioma cells by MTT and migration assay. Modulation of inflammatory markers and apoptosis induction was affirmed at the morphological and transcriptional level, by dual staining and gene expression. Molecular docking (MD) and molecular dynamics simulation (MDS) studies were performed against the targets to rationalize the inhibitory effect.ResultsThe dual-drug combination significantly reduced the cell viability and migration of glioma cells in a synergistic dose-dependent manner. At the molecular level, the dual-drug combination significantly down-regulated inflammatory genes with a concomitant upregulation of pro-apoptotic marker. In consensus with our in vitro findings, molecular docking and simulation studies revealed that the anti-tumor ligands: Temozolomide, Fucoidan with 5-(3-Methy1-trizeno)-imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) had the potency to bind to the inflammatory proteins at their active sites, mediated by H-bonds and other non-covalent interactions.ConclusionThe dual-drug cocktail of TMZ and FU may act as a potential therapeutic adjuvant for patients with glioma. However, rigorous pre-clinical experimental evidence is warranted for the possible translation of this combination from bench to bedside
Determinants of delay in treatment seeking among malaria patients in public health facilities of Dambi Dollo and Sayyo district, Western Ethiopia: A facility based case control study
Authors: Goshu Chimdesa Jabesa , Tafasa Sagni Mulugeta
Published: March 2023

Background: To prevent malaria from progressing to the more severe types and from increasing mortality, early and prompt treatment seeking is essential. However other investigations have shown that malaria medications were not received in the necessary amount of time. Determinants of treatment seeking delay among malaria patients must therefore be understood in order to create interventions and strategies.
Objective: The main objective of this study is to identify the determinants treatment seeking delay among malaria patients in public health facilities of Dambi Dollo and Sayyo district, Kellem Wallaga zone, Western Ethiopia, 2022.
Methods: From March 25, 2022, through May 15, 2022, a facility-based case-control research involving a sample of 322 confirmed malaria patients, 161 cases, and 161 controls was done. The study was carried out in six randomly chosen public health facilities, with a proportionate distribution of the total sample among them. Face-to-face interviews with structured and tested questionnaires were used to gather the data. EpiData version 4.4.2.1 was used to import the data, which was then exported to SPSS version 25.0 for cleaning and analysis. The causes of treatment seeking delay were determined using multivariable logistic regression analysis after bivariable analysis had been used to identify candidate factors. A p-value of 0.05 with a 95% confidence interval has been judged statistically significant. The Institutional Review Board of Dambi Dollo University's college of medicine and health sciences granted ethical approval.
Result: Patients of age <15 years of age[AOR=3.7(1.34-10.32)], Farmers in occupation [AOR=3.59(1.17-11.01)], Expensive health care costs[AOR=5.45(1.22-24.23)], Having practice of self-medication[AOR=2.01(1.10-3.67)], Previous malaria infection[AOR=1.82(1.04-3.17)], Decision made by household head[AOR=0.51(0.28-0.91)]and Waiting time at the health facility[AOR=1.91(1.19-3.24)] were found to be important determinants of treatment seeking delay among malaria patients. Conclusion and recommendations: It was discovered that factors such as age, occupation, health care costs, prior malaria infection, waiting period, use of self-medication, and decision-making were factors in treatment seeking delay. The two separate health offices and facilities should collaborate to provide regular health education, appropriate healthcare, and private drug shop inspections.
Impact of preoperative biliary drainage on pancreaticoduodenectomy complications in periampullary tumors: A case-control study
Authors: Tasar Pinar , Kilicturgay Sadik , Bakar Burak , Sen Murat , Sigirli Deniz
Published: March 2023

Purpose This study aimed to investigate the effects of preoperative biliary drainage and different preoperative biliary drainage methods in patients with mechanical jaundice who underwent pancreaticoduodenectomy for periampullary tumors. Methods Patients with periampullary tumor with mechanical jaundice who were operated on at the U.U. General Surgery Department between October 2015 and August 2021 were included in this study. The patients were divided into endoscopic biliary drainage, percutaneous transhepatic biliary drainage, and nonpreoperative biliary drainage groups. Patients’ demographic and clinical characteristics were analyzed. Results Of the 173 patients included in the study, 121 underwent preoperative biliary drainage. Of these 121 patients, 32.2% underwent endoscopic biliary drainage. Age, sex, comorbidities, and weight loss were similar in all groups. Cholangitis was the most common complication in the endoscopic biliary drainage and percutaneous transhepatic biliary drainage groups. Postoperative surgical site infection and Clavien‒Dindo ≥ 3b complications were significantly higher in the endoscopic biliary drainage group (P < .001;P = .031, respectively). The length of stay was significantly higher in the endoscopic biliary drainage group (P = .044). Mortality and readmission were similar in all groups. Conclusions Routine preoperative biliary drainage in periampullary tumor with mechanical jaundice does not reduce complications. Percutaneous transhepatic biliary drainage results in a faster decrease in bilirubin and lower infectious complication rates, but it may cause serious technique-related problems.
Does Surveillance Capitalism Trigger the Financial Performance of Information Technology Firms? A Reflection from FAANG Business Models
Authors: Biju A V , Aparna A S , Treesa Jency , Nikhil N K
Published: March 2023

This paper maps the idea of surveillance capitalism of FAANG (Facebook, Apple, Amazon, Netflix, and Google), which have capitalised on the behavioural surplus accumulated in their databases and how they utilise this data for future business models. The fundamental research question is how the data-driven models trigger these companies’ future financial performance and ensure sustainable growth. A triangulation approach was used to observe the world of surveillance capitalism through multiple lenses. The relative valuation models were used to substantiate the exponential growth of FAANG companies from 2006 to 2020. Financial indicators like the EPS, ROE, Market Capitalization and ROA were used to capture the growth of FAANG. Our undertaking shows that FAANG earns substantial revenue through data-driven business models catalysing the present companies' growth. This paper also illuminates the nudging effect created by behaviour-centric advertisements, which results in the brand value appreciation of FAANG. The article can be seen as a novel attempt as it empirically proves that FAANG has grown faster due to the power of surveillance capitalism.
JEL Code: A130; O330: O380: K420
Colored-Sticky paper trapability of periurban population of sand flies (Diptera: Psychodidae)
Authors: Ahmed Tasneem , Ali Mayada , Ismail Ibrahim , Ahmed Khalid , Karamalla Lubna , Mohamed Yassir
Published: March 2023

Background: Sand flies are the natural vectors of humans leishmaniasis a neglected disease, yet universally endemic in 98 countries with 350 million people at risk. Though significant advancements have been made in developing therapeutics attack on the vectors is anticipated to be a promising approach for controlling the vectors and the disease. Hence the current study was carried out to provide accurate data required for execution of successful control of local sand flies population.
Mehtods: The randomized Latin square technique was used to determine the aparnt effeicency and performance of colored sticky paper traps in order to establish an effective sampling and controling system.
Results: The white, yellow and green colored sticky paper traps were found to be significantly more attractive and effective than red and blue colored ones to the local sand flies population.
Conclusion: The trap color was the source of captured variation observed. White and yellow sampling system was suggested for clarifying sand fly population under quantitative studies to generate information necessary for carrying out successful control as they captured the efficient leishmaniasis vectors P. papatasi and P. orientalis though prevalent in low densities.
The Molecular Mechanism of Scutellaria Barbata Flavonoids in Promoting Neurogenesis and Improving Memory Impairment Mediated by CREB Phosphorylation in Rats
Authors: Liu Xinyang , Liu Yuling , Cheng Jianjun , Gao Yang , Zhao Chunying , Ma Shuai , Li Caixia , Shang Yazhen
Published: March 2023

Background
The present study was aimed to investigate the effect and molecular mechanism of Scutellaria barbata flavonoids (SBFs) in promoting neurogenesis and improving memory impairment mediated by CREB phosphorylation in rats.
Methods
Alzheimer’s disease (AD) model was established by intracerebroventricular injection of amyloid beta-peptide 25–35 (Aβ25−35) in combination with aluminum trichloride (AlCl3) and recombinant human transforming growth factor-β1 (RHTGF-β1) (composited Aβ) in rats. The Morris water maze was used to screen the successful AD model of rats. The screened successful AD model rats were randomly divided into three groups including a model group and two drug groups of 140 mg/kg SBFs and 0.5 mg/kg Rolipram (Positive control drug). After administration for 38 days, the Morris water maze test was used to measure the learning and memory ability of the rats. HE staining was used to observe the morphology of neurons in the hippocampus and cerebral cortex regionsof the rats' brains. Immunohistochemistry was used to detect the expression of NeuN in the hippocampal gyrus of rats. The mRNA expression of TrkB, RSK,CREB, and BDNF and the protein expression of NeuN, TrkB, RSK, P-CREB-Ser133, and BDNF in the hippocampus and cerebral cortex of the rats were assayed by quantitative real-time PCR (qPCR) and Western blotting methods.
Results
Intracerebroventricular injection of composited Aβ induced memory impairment, impaired neurons, decreased the protein expression of NeuN in the hippocampal gyrus, increased the mRNA expression levels of TrkB, RSK and BDNF, decreased the mRNA expression level of CREB and the protein expression levels of NeuN, TrkB, RSK, P-CREB-Ser133 and BDNF in the hippocampus and cerebral cortex of rats. However, SBFs attenuated memory impairment which was induced by composited Aβ in rats and ameliorated neuropathological changes in the brain, increased the expression of NeuN protein in the hippocampal gyrus, and regulated mRNA and protein expressions in composited Aβ treated rats. Rolipram ameliorated learning and memory disorder induced by composited Aβ, increased the protein expression of P-CREB-Ser133, increased the expression of NeuN protein in the hippocampal gyrus, promoted neurogenesis, and improved the neuropathological changes in the brain. The effect of SBFs was also similar to Rolipram.
Conclusion
The effect of SBFs was consistent with the positive control drug Rolipram. SBFs could promote neurogenesis and improve learning and memory impairment in AD rats, and its mechanism was mediated by CREB phosphorylation.
Combined of favorite cartoon stickers and fruit juices to reduce premedication anxiety in preschool children in the absence of parents
Authors: Liu Ting , Wang Dan , Wang Yanting , Tao Yingying , Zhu Ming , Zhang Mazhong , Sun Ying , Peng Zhezhe
Published: March 2023

Background

Several initiatives had been promoted to largely reduce transmission during the new coronavirus disease 2019 (COVID-19) World Pandemic. However, children's preoperative anxiety was more prominent when parents were advised not to stay with their children in the preoperative holding area. This study aimed to determine whether combined of favorite carton stickers and fruit juices could reduce premedication anxiety in preschool children who lacked parental presence and were scheduled for elective surgery.

Methods

One hundred and fourteen healthy children, aged 3–6 years, assigned to elective surgery were randomized to one of three groups: Group A (a cartoon noggin), Group B (a cartoon noggin and cartoon stickers), Group C (a cartoon noggin, cartoon stickers, and fruit juices). All groups routinely received sedative premedication (oral midazolam, 0.5mg/kg) before anesthesia induction. The modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF) was used to evaluate the anxiety of each child in the following time points: T0 (baseline anxiety: immediately after arriving in the preoperative holding area), T1 (3 min after the interventions), T2 (at the time of midazolam oral administration).

Results

There was no significant difference in mYPAS-SF scores among the three groups at T0 (P = 0.174). Children in Group C manifested significantly lower mYPAS-SF scores at T1 compared with Group A and Group B (P < 0.001 and P = 0.012), and T2 (P < 0.001 vs both groups). Subjects in Group B showed lower mYPAS-SF scores than that in Group A at T1 (P = 0.008) and T2 (P = 0.009).

Conclusions

Cartoon stickers for reducing premedication anxiety were effective, besides, the combination of cartoon stickers and fruit juices was found to be a profitable tool to reduce premedication anxiety in preschool children undergoing elective surgery.
Clinical Trial Registry: A one-month, open-label study to evaluate the effect of the combination of favorite carton stickers and fruit juices on preschool children who suffer premedication anxiety.
(https://www.chictr.org.cn/showproj.aspx?proj=185586) Registration number: ChiCTR2200066644.
The site of origin of medulloblastoma: Does the neurosurgical perspective support the current concept from molecular data?
Authors: Ciobanu-Caraus Olga , Kasprian Gregor , Furtner Julia , Kool Marcel , Sill Martin , Frischer Josa M. , Cho Anna , Peyrl Andreas , Haberler Christine , Slavc Irene , Czech Thomas , Rössler Karl , Gojo Johannes , Dorfer Christian
Published: March 2023

Purpose Developmental gene expression data from medulloblastoma (MB) supported by retrospective MR imaging studies suggest that WNT-MB originate from the region of the embryonic lower rhombic lip (LRL), whereas SHH-MB and non-WNT/non-SHH-activated MB arise from cerebellar precursor matrix regions. This study aims to analyze detailed intraoperative data with regard to the site of origin (STO) and compare these findings with the hypothesized regions of origin associated with the molecular group.
Methods A review of the institutional database identified 58 pediatric patients who were operated on a MB at our department between 1996 and 2020 and had a detailed operative report, surgical video as well as clinical and genetic classification data available for analysis. The STO was assessed based on intraoperative findings of an expert neurosurgeon blinded to the molecular group information.
Results Using the intraoperatively defined STO, “correct” prediction of molecular groups was feasible in 20% of WNT-MB, 60% of SHH-MB and 71% of non-WNT/non-SHH activated MB. The positive predictive values of the neurosurgical inspection to detect the molecular group were 0.21 (95% CI 0.08–0.48) for WNT-MB, 0.86 (95% CI 0.49–0.97) for SHH-MB and 0.73 (95% CI 0.57–0.85) for non-WNT/non-SHH activated MB.
Conclusions The present study demonstrated a limited predictive value of the intraoperatively observed STO for the prediction of the molecular group of MB. Thus, our findings challenge the current concept of the molecular group-specific origins based on developmental gene expression data and neuroradiological STO definitions.
Using Personalized Next Session to Improve Session-Based Recommender Systems
Authors: Chen Yen-Liang , Wu Chia-Chi , Shih Po-Cheng
Published: March 2023

In e-commerce, session-based personalized recommendation is still a challenging task due to the limited information of users in a session. Therefore, it is not enough to include only the user's local information. Instead, we should consider global information, i.e., extract information from all users' sessions to explore more collaborative information. However, using all session information will waste computing resources, and there will be a lot of information in the global information that is not relevant to the current user, which will damage the correctness of the prediction. Therefore, instead of referencing all global information, we select only those sessions that are useful to users, the so-called Personalized Next Session (PNS), as global information to improve the lack of local information. This work is the first to adopt a deep network architecture study incorporating the concept of PNS to recommend the next item of the current session to the user. We have conducted experiments on several real-world datasets. Extensive experimental results show that our proposed deep network architecture outperforms state-of-the-art recommendation methods.
WITHDRAWN: Bortezomib in PTEN-deficient patients with advanced intrahepatic cholangiocarcinoma: an open-label, prospective, phase II trial
Authors: zeng tianmei , Jiang Tian-yi , Yang Guang , Cheng Zhuo , Lou Cheng , Wei Wei , Tao Chen-jie , Hu Shouzi , Wang Hui , Cui Xiao-wen , Tan Ye-xiong , Dong Li-wei , Wang Hong-yang , Yuan Zhen-gang
Published: March 2023

Background: Intrahepatic cholangiocarcinoma (ICC) is characterized by a dismal prognosis with limited therapeutic options. To explore phosphatase and tension homology deleted on chromosome ten (PTEN) as a biomarker for proteasome inhibition in ICC, we conducted a phase II trial to assess the second line efficacy of bortezomib in PTEN-deficient advanced ICC patients.
Methods: Between July 1, 2017, and June 30, 2021, a total of 130 patients with advanced ICC were screened by PTEN immunohistochemical staining and 16 patients were enrolled. Patients with PTEN deficiency who had progressed after gemcitabine combined cisplatin received single-agent bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. The primary endpoint was objective response rate (ORR) according to Response Evaluation Criteria in Solid Tumors v1.1.
Results: The median time of follow up was 4.63 months (95% CI: 0.7~17.2 months). Among the 16 enrolled patients, 13 of them had completed treatment with bortezomib at least 2 cycles and been evaluated. The ORR was 23% (3/13) and disease control rate was 54% (7/13). The median progress-free survival (mPFS) was 2.95 months (95% CI: 2.1~5.1 months) and the median overall survival (mOS) was 7.2 (95% CI: 0.7~21.6 months) months in the intent-to-treat patients. Treatment-related adverse events of any grade were reported in 16 patients, with thrombopenia being the most common toxicity. Patients with PTEN staining score of 0 were more likely to benefit from bortezomib than those with staining score > 0.
Conclusions: Bortezomib yielded encouraging objective response and a favorable overall survival as a second-line therapy in PTEN-deficient ICC patients. Our findings suggest bortezomib as a promising treatment option in selected ICC patients with PTEN deficiency.
Trial Registration: ClinicalTrials.gov (NCT03345303).
TLR1-N248S polymorphism Reduces the Therapeutic Efficacy of Chemotherapy by Attenuating Antitumor Immunity in Locally Advanced Colorectal Cancer
Authors: Huang Kevin Chih-Yang , Ke Tao-Wei , Chen Chia-Yi , Chiang Shu-Fen , Hong Wei-Ze , Lai Chia-Ying , Chen Tsung-Wei , Yang Pei-Chen , Liang Ji-An , Chen William Tzu-Liang , Chao K. S. Clifford
Published: March 2023

Regional lymph nodes metastasis is an important predictor for survival outcome and the indicator for postoperative adjuvant chemotherapy in patients with colorectal cancer (CRC) patient. Even the advance in the adjuvant chemotherapeutic regimen, the 5-year distant metastasis and survival are still unsatisfied. Here, we evaluate the clinical significance of single-nucleotide polymorphisms on TLR1 and TLR2, which are the receptors for HMGB1 that is the hallmark for immunogenic cell death (ICD), in patients with stage II-III colon carcinoma (COAD). We found patients with high cytosolic HMGB1 are associated with survival outcome in stage III COAD patients who received adjuvant chemotherapy. Moreover, patients with TLR1-N248S polymorphism (rs4833095) may influence the therapeutic efficacy of adjuvant chemotherapy, suggesting TLR1-N248S is an independent prognostic factor for locally advanced colon carcinoma patients. Moreover, patient bearing TLR1-N248S polymorphism had high risk of distant metastasis after first-line adjuvant chemotherapeutic regimen with 5 year by multivariate COX analysis [HR=1.694, 95%CI=1.063-2.698, p=0.027]. We found that defective TLR1 impaired TLR1/2 signaling on dendritic cells (DCs) maturation for antitumor immune response under immunogenic chemotherapy oxaliplatin (OXP) treatment. Defective TLR1 on DCs impaired its maturation ability by HMGB1 and reduced the secretion of IFN from T cells to eradicate the residual tumor cells in vitro. Moreover, systemic inhibition of TLR1/2 dramatically reduced the tumor-infiltrating immune cells by OXP treatment, leading to poor therapeutic response to OXP. On the contrary, administration with TLR1/2 agonist synergistically increased the benefit of OXP treatment and triggered high density of tumor-infiltrating immune cells. We also observed that less tumor-infiltrating cytotoxic T lymphocyte was located within tumor microenvironment in patients bearing TLR1-N248S polymorphism. Taken together, these results showed that patients bearing TLR1-N248S polymorphism might reduce the therapeutic response to adjuvant chemotherapy by attenuating antitumor immune response via impairing HMGB1-mediated DC maturation in locally advanced colon carcinoma patients.
How different is different? Systematically identifying distribution shifts and their impacts in NER datasets
Authors: Li Xue , Groth Paul
Published: March 2023

When processing natural language, we are frequently confronted with the problem of distribution shift. For example, using a model trained on a news corpus to subsequently process legal text exhibits reduced performance. While this problem is well-known, to this point, there has not been a systematic study of detecting shifts and investigating the impact shifts have on model performance for NLP tasks. Therefore, in this paper, we detect and measure two types of distribution shift, across three different representations, for 12 benchmark Named Entity Recognition datasets. We show that both input shift and label shift can lead to dramatic performance degradation. For example, fine-tuning on a wide spectrum dataset (Ontonotes) and testing on an email dataset (Cerec) that shares labels leads to a 63-points drop in F1 performance. Overall, our results indicate that the measurement of distribution shift can provide guidance to the amount of data needed for fine-tuning and whether or not a model can be used "off-the-shelf" without subsequent fine-tuning. Finally, our results show that shift measurement can play an important role in NLP model pipeline definition.
An exploration into the causal relationships between educational attainment, intelligence, and wellbeing: an observational and two-sample Mendelian randomisation study
Authors: Armitage J. M , Wootton R.E , Haworth C.M.A , Davis O.S.P.
Published: March 2023

Educational attainment is associated with a range of positive outcomes, yet its impact on wellbeing is unclear, and complicated by high correlations with intelligence. We use genetic and observational data to investigate for the first time, whether educational attainment and intelligence are causally and independently related to wellbeing. Results from our multivariable Mendelian randomisation demonstrated a positive causal impact of educational attainment on wellbeing that remained after accounting for intelligence, and a negative impact of intelligence that was independent of educational attainment. Observational analyses suggested that these associations may be subject to sex differences, with benefits to wellbeing greater for females who attend higher education compared to males. For intelligence, males scoring more highly on measures related to happiness were those with lower intelligence. Our findings demonstrate a unique benefit for wellbeing of staying in school, over and above improving cognitive abilities, with benefits likely to be greater for females compared to males.
Protective Effects of Grape Seed Procyanidin Extract on Fluoride-Induced nephrotoxicity and the possible role of Nrf2 signaling pathway
Authors: Wang Er Hui , Ping Guan Fang , Bu Yong Jun
Published: March 2023

To investigate effects of fluoride-induced renal damage and possible role of the Nrf2 signaling pathway and explore the protective activity of Grape Seed Procyanidin Extract (GSPE). A fluoride-exposed rat model was established through drinking water. Oxidative stress parameters and serum markers that reflect renal function were analyzed. Pathological changes were assessed using HE and TUNEL methods. Nrf2 signaling pathway-related and apoptosis-related cleaved Caspase-3 proteins were detected by Western blot. Fluoride exposure caused a significant increase in serum markers of renal function, renal histopathological alterations, oxidative stress, and apoptosis. The protein expression levels of Nrf2, HO-1, and NQO-1 along the Nrf2 signaling pathway were depressed, while the cleaved Caspase-3 protein were upregulated after fluoride exposure. HE and TUNEL examination showed that the renal tissue of fluoride rats was repaired by GSPE. The level of MDA was decreased; while the level of GSH, activities of CAT, and SOD of the kidney were promoted by GSPE. Decreased serum markers such as BUN, UA, and Cr indicate a marked improvement in renal function. GSPE therapy up-regulated the expression levels of Nrf2, HO-1, NQO-1 and down-regulated cleaved Caspase-3 proteins in the kidney. Supplementary GSPE with fluoride significantly alleviated its nephrotoxicity. The results above mentioned indicated that fluoride induced nephrotoxicity possibly through activate the Nrf2 signaling pathway and the presence of GSPE mitigate its nephrotoxicity.
Design and Realization of Void-centric Zone Plate Ultrasonic Transducer: Considering Structural Vibration of Piezoelectric Metamaterials
Authors: Sim Min-Jung , Elmina Bernadette , Kim Sung Mok , Baik Kyungmin , Kim Yong
Published: March 2023

We developed and experimentally realized a novel type of focal transducer called a void-centric zone plate ultrasonic transducer (VZPUT). Although VZPUT is a planar transducer, it can focus ultrasound and control the focal length using a single-channel electric network. Further, unlike a classical Fresnel zone plate, the VZPUT has space for an imaging probe at the center, making it useful for therapeutic focused ultrasound (FUS). To realize VZPUT, we develop a novel void-centric zone plate (VZP) that allows design freedom for the radius of the space at the center. Then, we fabricate the piezoelectric VZP, an acoustic metamaterial, considering its structural vibration modes that appear within the operating frequency range. The VZPUT demonstrated applicability to therapeutic FUS in that it could control the focal point by the operating frequency with real-time monitoring images from the imaging probe mounted at the center.