bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting loop3 of sclerostin preserves its cardiovascular protective action and promotes bone formation
Authors: Yu Yuanyuan , Wang Luyao , Ni Shuaijian , Li Dijie , Liu Jin , Chu Hang Yin , Zhang Ning , Sun Meiheng , Li Nanxi , Ren Qing , Zhuo Zhenjian , Zhong Chuanxin , Xie Duoli , Li Yongshu , Zhang Zong-Kang , Zhang Huarui , Li Mei , Zhang Zhenlin , Chen Lin , Pan Xiaohua , Xia Weibo , Zhang Shu , Lu Aiping , Zhang Bao-Ting , Zhang Ge
Published: July 2022

Sclerostin negatively regulates bone formation by antagonizing Wnt signalling. An antibody targeting sclerostin for the treatment of postmenopausal osteoporosis was approved by the U.S. Food and Drug Administration, with a boxed warning for cardiovascular risk. Here we demonstrate that sclerostin participates in protecting cardiovascular system and inhibiting bone formation via different loops. Loop3 deficiency by genetic truncation could maintain sclerostin’s protective effect on the cardiovascular system while attenuating its inhibitory effect on bone formation. We identify an aptamer, named aptscl56, which specifically targets sclerostin loop3 and use a modified aptscl56 version, called Apc001PE, as specific in vivo pharmacologic tool to validate the above effect of loop3. Apc001PE has no effect on aortic aneurysm and atherosclerotic development in ApoE−/− mice and hSOSTki.ApoE−/− mice with angiotensin II infusion. Apc001PE can promote bone formation in hSOSTki mice and ovariectomy-induced osteoporotic rats. In summary, sclerostin loop3 cannot participate in protecting the cardiovascular system, but participates in inhibiting bone formation.
Effect of exchange-correlation functionals on the estimation of migration barriers in battery materials
Authors: Devi Reshma , Singh Baltej , Canepa Pieremanuele , Sai Gautam Gopalakrishnan
Published: July 2022

Facile ionic mobility within host frameworks is crucial to the design of high-energy-density batteries with high-power-densities, where the migration barrier (Em) is the governing factor. Here, we assess the accuracy and computational performance of generalized gradient approximation (GGA), the strongly constrained and appropriately normed (SCAN), and their HubbardUcorrections, GGA+Uand SCAN+U, within the density functional theory-nudged elastic band framework, in the prediction of Emas benchmarked against experimental data. Importantly, we observe SCAN to be more accurate than other frameworks, on average, albeit with higher computational costs and convergence difficulties, while GGA is a feasible choice for “quick” and “qualitative” Empredictions. Further, we quantify the sensitivity of Emwith adding uniform background charge and/or the climbing image approximation in solid electrolytes, and the HubbardUcorrection in electrodes. Our findings will improve the quality of Empredictions which will enable identifying better materials for energy storage applications.
A dominant negative ADIPOQ mutation in a diabetic family with renal disease, hypoadiponectinemia, and hyperceramidemia
Authors: Simeone Christopher A. , Wilkerson Joseph L. , Poss Annelise M. , Banks James A. , Varre Joseph V. , Guevara Jose Lazaro , Hernandez Edgar Javier , Gorsi Bushra , Atkinson Donald L. , Turapov Tursun , Frodsham Scott G. , Morales Julio C. Fierro , O’Neil Kristina , Moore Barry , Yandell Mark , Summers Scott A. , Krolewski Andrzej S. , Holland William L. , Pezzolesi Marcus G.
Published: July 2022

Adiponectin, encoded by ADIPOQ, is an insulin-sensitizing, anti-inflammatory, and renoprotective adipokine that activates receptors with intrinsic ceramidase activity. We identified a family harboring a 10-nucleotide deletion mutation in ADIPOQ that cosegregates with diabetes and end-stage renal disease. This mutation introduces a frameshift in exon 3, resulting in a premature termination codon that disrupts translation of adiponectin’s globular domain. Subjects with the mutation had dramatically reduced circulating adiponectin and increased long-chain ceramides levels. Functional studies suggest that the mutated protein acts as a dominant negative through its interaction with non-mutated adiponectin, decreasing circulating adiponectin levels, and correlating with metabolic disease.
Quantum computational phase transition in combinatorial problems
Authors: Zhang Bingzhi , Sone Akira , Zhuang Quntao
Published: July 2022

Quantum Approximate Optimization algorithm (QAOA) aims to search for approximate solutions to discrete optimization problems with near-term quantum computers. As there are no algorithmic guarantee possible for QAOA to outperform classical computers, without a proof that bounded-error quantum polynomial time (BQP) ≠ nondeterministic polynomial time (NP), it is necessary to investigate the empirical advantages of QAOA. We identify a computational phase transition of QAOA when solving hard problems such as SAT—random instances are most difficult to train at a critical problem density. We connect the transition to the controllability and the complexity of QAOA circuits. Moreover, we find that the critical problem density in general deviates from the SAT-UNSAT phase transition, where the hardest instances for classical algorithms lies. Then, we show that the high problem density region, which limits QAOA’s performance in hard optimization problems (reachability deficits), is actually a good place to utilize QAOA: its approximation ratio has a much slower decay with the problem density, compared to classical approximate algorithms. Indeed, it is exactly in this region that quantum advantages of QAOA over classical approximate algorithms can be identified.
Dataset of Speech Production in intracranial Electroencephalography
Authors: Verwoert Maxime , Ottenhoff Maarten C. , Goulis Sophocles , Colon Albert J. , Wagner Louis , Tousseyn Simon , van Dijk Johannes P. , Kubben Pieter L. , Herff Christian
Published: July 2022

Speech production is an intricate process involving a large number of muscles and cognitive processes. The neural processes underlying speech production are not completely understood. As speech is a uniquely human ability, it can not be investigated in animal models. High-fidelity human data can only be obtained in clinical settings and is therefore not easily available to all researchers. Here, we provide a dataset of 10 participants reading out individual words while we measured intracranial EEG from a total of 1103 electrodes. The data, with its high temporal resolution and coverage of a large variety of cortical and sub-cortical brain regions, can help in understanding the speech production process better. Simultaneously, the data can be used to test speech decoding and synthesis approaches from neural data to develop speech Brain-Computer Interfaces and speech neuroprostheses.
The near-global ocean mesoscale eddy atmospheric-oceanic-biological interaction observational dataset
Authors: Dong Changming , Liu Lingxiao , Nencioli Francesco , Bethel Brandon J. , Liu Yu , Xu Guangjun , Ma Jing , Ji Jinlin , Sun Wenjin , Shan Haixia , Lin Xiayan , Zou Bin
Published: July 2022

Amongst the variety of oceanic processes running the gamut of spatiotemporal scales, mesoscale eddies are the most common and often have region-specific characteristics. The large kinetic energy inherent to eddies themselves is a strong modulator of the global climate, ocean circulation, productivity, and freshwater transport. This study uses multi-source satellite remote sensing observation data to construct a multi-parameter eddy dataset for the 1993–2019 period, which differs significantly from a few of previous published eddy datasets that include only basic sea surface eddy physical features. Eddies within the dataset have life cycles of greater than four weeks, and their corresponding sea surface chlorophyll, sea surface temperature, and wind fields are provided. Atmospheric and oceanic variables are used to present a comprehensive picture of a given mesoscale eddy’s impact on the local physical, but also biological environment. The dataset would find immense value in research on mesoscale eddies, their impact on the atmosphere, and related biological processes.
Improvisation is a novel tool to study musicality
Authors: Weiss Michael W. , Peretz Isabelle
Published: July 2022

Humans spontaneously invent songs from an early age. Here, we exploit this natural inclination to probe implicit musical knowledge in 33 untrained and poor singers (amusia). Each sang 28 long improvisations as a response to a verbal prompt or a continuation of a melodic stem. To assess the extent to which each improvisation reflects tonality, which has been proposed to be a core organizational principle of musicality and which is present within most music traditions, we developed a new algorithm that compares a sung excerpt to a probability density function representing the tonal hierarchy of Western music. The results show signatures of tonality in both nonmusicians and individuals with congenital amusia, who have notorious difficulty performing musical tasks that require explicit responses and memory. The findings are a proof of concept that improvisation can serve as a novel, even enjoyable method for systematically measuring hidden aspects of musicality across the spectrum of musical ability.
Short-term forecasting of Mmax during hydraulic fracturing
Authors: Li Ziyan , Eaton David , Davidsen Jörn
Published: July 2022

Previous studies of injection-induced earthquake sequences have shown that the maximum magnitude (Mmax) of injection-induced seismicity increases with the net injected volume (V); however, different proposed seismic-hazard paradigms predict significantly different values of Mmax. Using injection and seismicity data from two project areas in northeastern British Columbia, Canada, where hydraulic fracturing induced seismicity was observed, we test the predictive power and robustness of three existing and one novel method to estimate Mmax. Due to their vastly different values of seismogenic index (Σ), these two project areas represent end-member cases of seismogenic response. Our novel method progressively adjusts the Mmax forecast under the assumption that each recorded event embodies an incremental release of fluid-induced stress. The results indicate that our method typically provides the lowest upper bound of the tested methods and it is less sensitive to site-specific calibration parameters such as Σ. This makes the novel method appealing for operational earthquake forecasting schemes as a real-time mitigation strategy to manage the risks of induced seismicity.
Wear resistance of an additively manufactured high-carbon martensitic stainless steel
Authors: Iakovakis Eleftherios , Avcu Egemen , Roy Matthew J. , Gee Mark , Matthews Allan
Published: July 2022

The dry sliding wear behaviour of a high carbon martensitic stainless steel (HCMSS) consisting of ~ 22.5 vol% of chromium (Cr)- and vanadium (V)-rich carbides processed by electron beam melting (EBM) has been captured. The microstructure consisted of martensite and retained austenite phases with a homogeneous distribution of sub-micron-sized V-rich and micron-sized Cr-rich carbides, leading to relatively high hardness. The CoF decreased ~ 14.1% with increasing load in the steady-state, due to the material transferred from the wear track over the counterbody. The wear rate of the HCMSS compared to martensitic tool steel processed in the same manner, and it was nearly identical under low applied load. The dominant wear mechanism was removal of the steel matrix through abrasion, followed by the oxidation of the wear track, while three-body abrasive wear occurred with increasing load. A plastically deformed zone beneath the wear track was revealed through cross-sectional hardness mapping. Specific phenomena occurred with increasingly aggressive wear conditions were described with carbide cracking, pull-out of V-rich carbides and matrix cracking. This study revealed the wear performance of the additively manufactured HCMSS, which could pave the way for producing components for wear-related applications ranging from shafts to plastic injection moulds via EBM.
An innovative dual recognition aptasensor for specific detection of Staphylococcus aureus based on Au/Fe3O4 binary hybrid
Authors: El-Wekil Mohamed M. , Halby Hamada Mohamed , Darweesh Mahmoud , Ali Mohamed E. , Ali Ramadan
Published: July 2022

Pathogenic bacteria cause disease outbreaks and threaten human health, prompting the research on advanced detection assays. Herein, we developed a selective molecular imprinted aptasensor for sensitive and prompt quantitation of Staphylococcus aureus (S. aureus) bacteria. The aptasensor was constructed by immobilization of aptamer on gold nanoparticles modified magnetic nanoparticles (apt-AuNPs@ Fe3O4). A functional monomer (o-phenylenediamine, o-phen) was electro-polymerized on the surface of the as-synthesized nanocomposite in the presence of a template (S. aureus). After removing S. aureus, the formed imprinted sites were available to extract pathogenic bacteria from complicated matrices. The surface morphology of the as-fabricated nanocomposites was characterized using different spectroscopic and electrochemical methods. Moreover, we thoroughly evaluated factors affecting the synthesis and determination procedures. The molecular imprinted aptasensor exhibited a wide linear range of 101–107 CFU mL−1 with a Limit of Detection, LOD (signal to noise = 3) of 1 CFU mL−1. The aptasensor detected S. aureus in milk, conduit water, and apple juice samples with good recoveries % and satisfactory relative standard deviations (RSDs %) values.
The role of demographic and academic features in a student performance prediction
Authors: Bilal Muhammad , Omar Muhammad , Anwar Waheed , Bokhari Rahat H. , Choi Gyu Sang
Published: July 2022

Educational Data Mining is widely used for predicting student's performance. It’s a challenging task because a plethora of features related to demographics, personality traits, socio-economic, and environmental may affect students' performance. Such varying features may depend on the level of study, program offered, nature of subject, and geographical location. This study attempted to predict the final semester’s results of students studying Doctor of Veterinary Medicine (DVM) based on their pre-admission academic achievements, demographics, and first semester performance. The imbalanced data led to non-generic prediction models, so it was addressed through synthetic minority oversampling technique. Among five prediction models, the Support Vector Machine led the best with 92% accuracy. The decision tree model identified key features affecting students’ performance. The analysis led to the conclusion that marks obtained in Biology, Islamiat, and Urdu at Matric and English at Intermediate level affected the students’ performance in their final semester. The findings provide useful information to predict students’ performance and guidelines for academic institutes’ management regarding improving students’ achievement. It is speculated that adoption of digital transformation may help reduce difficulty faced in data collection and analysis.
Process optimization and technoeconomic environmental assessment of biofuel produced by solar powered microwave pyrolysis
Authors: Fodah Ahmed Elsayed Mahmoud , Abdelwahab Taha Abdelfattah Mohammed
Published: July 2022

Microwave pyrolysis of corn stover has been optimized by Response surface methodology under different microwave power (500, 700, and 900 W) and three ratios of activated carbon additive (10, 15, and 20%) for obtaining maximum bio-oil yield followed by biochar. The optimal result has been evaluated and the environmental and techno-economic impacts of using solar-powered microwave heating have been tested. The optimal pyrolysis condition found to be 700 W microwave power and 10% of activated carbon. The yields of both bio-oil and biochar were about 74 wt% under optimal condition. The higher heat values of 26 MJ/kg and 16 MJ/kg were respectively achieved for biochar and bio-oil. The major components of bio-oil were hydrocarbons (36%) and phenols (28%) with low oxygen-containing compounds (2%) and acids (2%). Using the solar-powered system, 20,549 tonnes of CO2 can be mitigated over the lifetime of the set-up, resulting in USD 51,373 in carbon credit earnings, compared to 16,875 tonnes of CO2 mitigation and USD 42,167 in carbon credit earnings from a grid electricity system. The payback periods for solar-powered and grid-connected electrical systems are estimated to be 1.6 and 0.5 years, respectively, based on biochar and bio-oil income of USD 39,700 and USD 45,400.
End-to-end deep learning framework for printed circuit board manufacturing defect classification
Authors: Bhattacharya Abhiroop , Cloutier Sylvain G.
Published: July 2022

We report a complete deep-learning framework using a single-step object detection model in order to quickly and accurately detect and classify the types of manufacturing defects present on Printed Circuit Board (PCBs). We describe the complete model architecture and compare with the current state-of-the-art using the same PCB defect dataset. These benchmark methods include the Faster Region Based Convolutional Neural Network (FRCNN) with ResNet50, RetinaNet, and You-Only-Look-Once (YOLO) for defect detection and identification. Results show that our method achieves a 98.1% mean average precision(mAP[IoU = 0.5]) on the test samples using low-resolution images. This is 3.2% better than the state-of-the-art using low-resolution images (YOLO V5m) and 1.4% better than the state-of-the-art using high-resolution images (FRCNN-ResNet FPN). While achieving better accuracies, our model also requires roughly 3× fewer model parameters (7.02M) compared with the state-of-the-art FRCNN-ResNet FPN (23.59M) and YOLO V5m (20.08M). In most cases, the major bottleneck of the PCB manufacturing chain is quality control, reliability testing and manual rework of defective PCBs. Based on the initial results, we firmly believe that implementing this model on a PCB manufacturing line could significantly increase the production yield and throughput, while dramatically reducing manufacturing costs.
Dry preserved multilayered fibroblast cell sheets are a new manageable tool for regenerative medicine to promote wound healing
Authors: Matsuno Yutaro , Yanagihara Masashi , Ueno Koji , Saito Toshiro , Kurazumi Hiroshi , Suzuki Ryo , Katsura Shunsaku , Oga Atsunori , Hamano Kimikazu
Published: July 2022

This study investigated the therapeutic effects of dry-preserved multi-layered fibroblast cell sheets (dry sheets) on cutaneous ulcers. Dry sheets were prepared by air-drying multi-layered fibroblast cell sheets (living sheets) to cease their life activities. Before in vivo application, we tested the release of growth factors into the medium to examine the mechanisms of dry sheets in wound healing. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were released from both dry and living sheets, while high levels of fibroblast growth factor-2 (FGF-2) and high mobility group box 1 (HMGB1) protein were only from dry sheets. An in vitro fibroblast proliferation assay revealed that the dry sheet eluate significantly enhanced cell proliferation and VEGF and HGF production compared with living sheet eluate. FGF-2-neutralizing antibodies significantly blocked this proliferative response. In wounds created on diabetic mice, the dry sheet-treatment groups using autologous or allogeneic cells showed significantly accelerated wound closure compared with that in the no-treatment group. The storage stability of the dry sheet was better at refrigeration temperature than at room temperature and remained stable for at least 4 weeks. Our data indicated that allogeneic dry sheets represent a promising new tool for regenerative medicine that promotes wound healing.
Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study
Authors: Suárez José Francisco , Zamora Víctor , Garin Olatz , Gutiérrez Cristina , Pont Àngels , Pardo Yolanda , Goñi Alai , Mariño Alfonso , Hervás Asunción , Herruzo Ismael , Cabrera Patricia , Sancho Gemma , Ponce de León Javier , Macías Víctor , Guedea Ferran , Vigués Francesc , Castells Manuel , Ferrer Montse ,   Multicentric Spanish Group of Clinically Localized Prostate Cancer, Ferrer Montse , Garin Olatz , Pont Àngels , Pardo Yolanda , Alonso Jordi , Zamora Víctor , Guedea Ferran , Ventura Montse , Gutiérrez Cristina , Ferrer Ferran , Boladeras Ana , Suárez José Francisco , Castells Manel , Bonet Xavier , Ávila Mónica , Pastor Sergi , Bonet Carmen , Sancho Gemma , Ponce de León Javier , Palou Joan , de Paula Belén , Goñi Alai , Fernández Pablo , Herruzo Ismael , Hervás Asunción , Ramos Alfredo , Macías Víctor , Solé Josep , Bonet Marta , Mariño Alfonso , Cabrera Patricia , Ortiz María José
Published: July 2022

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan–Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.

Study identifier at ClinicalTrials.gov: NCT01492751.
An in silico approach to study the role of epitope order in the multi-epitope-based peptide (MEBP) vaccine design
Authors: Salaikumaran Muthu Raj , Kasamuthu Prasanna Sudharson , Aathmanathan Veeranarayanan Surya , Burra V. L. S. Prasad
Published: July 2022

With different countries facing multiple waves, with some SARS-CoV-2 variants more deadly and virulent, the COVID-19 pandemic is becoming more dangerous by the day and the world is facing an even more dreadful extended pandemic with exponential positive cases and increasing death rates. There is an urgent need for more efficient and faster methods of vaccine development against SARS-CoV-2. Compared to experimental protocols, the opportunities to innovate are very high in immunoinformatics/in silico approaches, especially with the recent adoption of structural bioinformatics in peptide vaccine design. In recent times, multi-epitope-based peptide vaccine candidates (MEBPVCs) have shown extraordinarily high humoral and cellular responses to immunization. Most of the publications claim that respective reported MEBPVC(s) assembled using a set of in silico predicted epitopes, to be the computationally validated potent vaccine candidate(s) ready for experimental validation. However, in this article, for a given set of predicted epitopes, it is shown that the published MEBPVC is one among the many possible variants and there is high likelihood of finding more potent MEBPVCs than the published candidates. To test the same, a methodology is developed where novel MEBP variants are derived by changing the epitope order of the published MEBPVC. Further, to overcome the limitations of current qualitative methods of assessment of MEBPVC, to enable quantitative comparison and ranking for the discovery of more potent MEBPVCs, novel predictors, Percent Epitope Accessibility (PEA), Receptor specific MEBP vaccine potency (RMVP), MEBP vaccine potency (MVP) are introduced. The MEBP variants indeed showed varied MVP scores indicating varied immunogenicity. Further, the MEBP variants with IDs, SPVC_446 and SPVC_537, had the highest MVP scores indicating these variants to be more potent MEBPVCs than the published MEBPVC and hence should be preferred candidates for immediate experimental testing and validation. The method enables quicker selection and high throughput experimental validation of vaccine candidates. This study also opens the opportunity to develop new software tools for designing more potent MEBPVCs in less time.
A comparison of high-throughput SARS-CoV-2 sequencing methods from nasopharyngeal samples
Authors: Gerber Zuzana , Daviaud Christian , Delafoy Damien , Sandron Florian , Alidjinou Enagnon Kazali , Mercier Jonathan , Gerber Sylvain , Meyer Vincent , Boland Anne , Bocket Laurence , Olaso Robert , Deleuze Jean-François
Published: July 2022

The COVID-19 pandemic caused by the new Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to threaten public health and burden healthcare systems worldwide. Whole SARS-CoV-2 genome sequencing has become essential for epidemiological monitoring and identification of new variants, which could represent a risk of increased transmissibility, virulence, or resistance to vaccines or treatment. Different next-generation sequencing approaches are used in SARS-CoV-2 sequencing, although with different ability to provide whole genome coverage without gaps and to reliably detect new variants. In this study, we compared the performance of three target enrichment methods (two multiplex amplification methods and one hybridization capture) using nasopharyngeal swabs from infected individuals. We applied these target enrichment methods to the same set of nasopharyngeal samples (N = 93) in high-throughput mode. SARS-CoV-2 genome was obtained using short-read next-generation sequencing. We observed that each method has some advantages, such as high mapping rate (CleanPlex and COVIDSeq) or absence of systematic variant calling error (SureSelect) as well as their limitations such as suboptimal uniformity of coverage (CleanPlex), high cost (SureSelect) or supply shortages (COVIDSeq). Nevertheless, each of the three target enrichment kits tested in this study yielded acceptable results of whole SARS-CoV-2 genome sequencing and either of them can therefore be used in prospective programs of genomic surveillance of SARS-CoV-2. Genomic surveillance will be crucial to overcoming the ongoing pandemic of COVID-19, despite its successive waves and continually emerging variants.
The screening for anticoagulant rodenticide gene VKORC1 polymorphism in the rat Rattus norvegicus, Rattus tanezumi and Rattus losea in Hong Kong
Authors: Huang Elaine Y. Y. , Law Sean T. S. , Nong Wenyan , Yip Ho Yin , Uea-Anuwong Theethawat , Magouras Ioannis , Hui Jerome H. L.
Published: July 2022

Anticoagulants are a major component of rodenticides used worldwide, which function by effectively blocking the vitamin K cycle in rodents. The rat Vitamin K epoxide Reductase Complex (VKORC) subunit 1 is the enzyme responsible for recycling vitamin K, and five substitution mutations (Tyr139Cys, Tyr139Ser, Tyr139Phe and Leu128Gln and Leu120Gln) located in the VKORC1 could result in resistance to anticoagulant rodenticides. This study carried out a VKORC1-based survey to estimate the anticoagulant rodenticide resistance in three Rattus species (R. losea, R. norvegicus, and R. tanezumi) collected in Hong Kong. A total of 202 rats captured in Hong Kong between 2017 and 2021 were analysed. Sequencing of molecular marker cytochrome c oxidase subunit 1 (COX1) was carried out to assist the species identification, and the identities of 52 lesser ricefield rats (R. losea), 81 common rats (R. norvegicus) and 69 house rats (R. tanezumi) were confirmed. Three VKORC1 exons were amplified from individuals by PCR followed by Sanger sequencing. A total of 47 R. tanezumi (68.1%) contained Tyr139Cys mutation in VKORC1 gene, and half of them were homozygous. None of the collected R. losea and R. norvegicus were detected with the five known substitutions leading to anticoagulant rodenticides resistance, and previously undescribed missense mutations were revealed in each species. Whole genome sequencing was further carried out on some individuals, and single nucleotide polymorphisms (SNPs) were also identified in the introns. This is the first study investigating the situation of anticoagulant rodenticide resistance in the rats collected in Hong Kong. Given that the efficacy of rodenticides is crucial for effective rodent management, regular genetic testing as well as population genomic analyses will be required to both monitor the situation and understand the adaption of different rat haplotypes for integrated pest management. Susceptibility tests for individual rodenticides should also be conducted regularly to assess their effectiveness on local species.
Development of microbial communities in biofilm and activated sludge in a hybrid reactor
Authors: Godzieba Martyna , Zubrowska-Sudol Monika , Walczak Justyna , Ciesielski Slawomir
Published: July 2022

Microorganisms play a key role in biological wastewater treatment. The form in which biomass develops determines the efficiency and mechanisms of organic compound conversion, due to different conditions in various microbial structures. However, the results of studies comparing the microbial communities in biofilm and activated sludge have often conflicted. Therefore, this study compared the composition and development of the bacterial communities in biofilm and activated sludge in a hybrid reactor, employing 16S rRNA sequencing. Statistical analysis of the sequencing data included the identification of taxa characteristic to the biofilm and activated sludge, alpha and beta diversity analysis, and network analysis. These analyses indicated that the biofilm bacterial community was richer and more diverse than the activated sludge community. The mean numbers of OTU were 1614 in the biofilm and 993 in the activated sludge, and the mean values of the Chao1 (1735 vs. 1105) and Shannon (5.3 vs. 4.3) biodiversity indices were significantly higher for the biofilm. The biofilm was a better environment for development of nitrifiers (e.g., Nitrosomonas, Nitrospira) and phosphorus accumulating organisms (Candidatus Accumulibacter). Bacteria in the biofilm co-occurrence network had more connections (based on Spearman's rank correlation coefficient) with each other, indicating that they interact more than those in the activated sludge.
The French EVAL-PLH cohort of persons with polyhandicap
Authors: Hamouda Ilyes , Rousseau Marie-Christine , Beltran Anzola Any , Aim Marie-Anastasie , de Villemeur Thierry Billette , Auquier Pascal , Baumstarck Karine ,   the EVAL-PLH group, de Villemeur Thierry Billette , Rousseau Marie-Christine , Khaldi-Cherif Sherezad , Maincent Kim , Felce Agnès , Baumstarck Karine , Auquier Pascal , Dany Lionel , Beltran Any , Hamouda Ilyes , Aim Marie-Anastasie , Boutalbi Narjess , Kemlin Isabelle , Roger Julie , Julien Patrick , Heng Ponha , Willocq Daniel , Valkov Maria , Pietra Stéphane , Lenormand Stéphane , Lind Katia
Published: July 2022

Polyhandicap is characterized by a combination of profound intellectual disability and serious motor deficit, resulting in the extreme restriction of autonomy and communication. The aim of the EVAL-PLH (EVALuation PoLyHandicap) study is to identify the impact of socioeconomic, environmental, and epidemiological determinants on the health status of the persons with polyhandicap and the daily lives of their caregivers. EVAL-PLH is a prospective cohort study. The study involved persons with severe polyhandicap (who were cared for at reeducation centers, residential facilities, and one specialized pediatric/neurological department of a university hospital), their familial caregivers and the institutional caregivers. Data collection included sociodemographics, heath status, and psychocomportemental information. Data have been collected at 2 points (2015-2016 and 2020-2021). The French EVAL-PLH cohort is the first cohort study focusing on persons with polyhandicap, their families, and the health care workers caring for them. The sustainability of the device is essential to assist patients, families, clinicians, and health decision-making authorities in the optimization of care management.
Fractional quantum oscillator and disorder in the vibrational spectra
Authors: Stephanovich V. A. , Kirichenko E. V. , Dugaev V. K. , Sauco Jackie Harjani , Brito Belén López
Published: July 2022

We study the role of disorder in the vibration spectra of molecules and atoms in solids. This disorder may be described phenomenologically by a fractional generalization of ordinary quantum-mechanical oscillator problem. To be specific, this is accomplished by the introduction of a so-called fractional Laplacian (Riesz fractional derivative) to the Scrödinger equation with three-dimensional (3D) quadratic potential. To solve the obtained 3D spectral problem, we pass to the momentum space, where the problem simplifies greatly as fractional Laplacian becomes simply$$k^\mu $$kμ,kis a modulus of the momentum vector and$$\mu $$μis Lévy index, characterizing the degree of disorder. In this case,$$\mu \rightarrow 0$$μ→0corresponds to the strongest disorder, while$$\mu \rightarrow 2$$μ→2to the weakest so that the case$$\mu =2$$μ=2corresponds to “ordinary” (i.e. that without fractional derivatives) 3D quantum harmonic oscillator. Combining analytical (variational) and numerical methods, we have shown that in the fractional (disordered) 3D oscillator problem, the famous orbital momentum degeneracy is lifted so that its energy starts to depend on orbital quantum numberl. These features can have a strong impact on the physical properties of many solids, ranging from multiferroics to oxide heterostructures, which, in turn, are usable in modern microelectronic devices.
Maternal stress induced endoplasmic reticulum stress and impaired pancreatic islets’ insulin secretion via glucocorticoid receptor upregulation in adult male rat offspring
Authors: Salimi Mina , Eskandari Farzaneh , Binayi Fateme , Eliassi Afsaneh , Ghanbarian Hossein , Hedayati Mehdi , Fahanik-babaei Javad , Eftekhary Mohamad , Keyhanmanesh ‬Rana , Zardooz Homeira
Published: July 2022

Exposure to perinatal (prenatal and/or postnatal) stress is considered as a risk factor for metabolic disorders in later life. Accordingly, this study aimed to investigate the perinatal stress effects on the pancreatic endoplasmic reticulum (ER) stress induction, insulin secretion impairment and WFS1 (wolframin ER transmembrane Glycoprotein, which is involved in ER homeostasis and insulin secretion) expression changes, in rat offspring. According to the dams’ period of exposure to variable stress, their male offspring were divided into, control (CTRL); pre-pregnancy, pregnancy, lactation stress (PPPLS); pre-pregnancy stress (PPS); pregnancy stress (PS); lactation stress (LS); pre-pregnancy, pregnancy stress (PPPS); pregnancy, lactation stress (PLS); pre-pregnancy, lactation stress (PPLS) groups. Offspring pancreases were removed for ER extraction and the assessment of ER stress biomarkers, WFS1 gene DNA methylation, and isolated islets’ insulin secretion. Glucose tolerance was also tested. In the stressed groups, maternal stress significantly increased plasma corticosterone levels. In PPS, PS, and PPPS groups, maternal stress increased Bip (Hsp70; heat shock protein family A member 4), Chop (Ddit3; DNA- damage inducible transcript3), and WFS1 protein levels in pancreatic extracted ER. Moreover, the islets’ insulin secretion and content along with glucose tolerance were impaired in these groups. In PPS, PS, LS and PPPS groups, the pancreatic glucocorticoid receptor (GR) expression increased. Maternal stress did not affect pancreatic WFS1 DNA methylation. Thus, maternal stress, during prenatal period, impaired the islets’ insulin secretion and glucose homeostasis in adult male offspring, possibly through the induction of ER stress and GR expression in the pancreas, in this regard the role of WFS1 protein alteration in pancreatic ER should also be considered.
Face mediated human–robot interaction for remote medical examination
Authors: Lalitharatne Thilina D. , Costi Leone , Hashem Ryman , Nisky Ilana , Jack Rachael E. , Nanayakkara Thrishantha , Iida Fumiya
Published: July 2022

Realtime visual feedback from consequences of actions is useful for future safety-critical human–robot interaction applications such as remote physical examination of patients. Given multiple formats to present visual feedback, using face as feedback for mediating human–robot interaction in remote examination remains understudied. Here we describe a face mediated human–robot interaction approach for remote palpation. It builds upon a robodoctor–robopatient platform where user can palpate on the robopatient to remotely control the robodoctor to diagnose a patient. A tactile sensor array mounted on the end effector of the robodoctor measures the haptic response of the patient under diagnosis and transfers it to the robopatient to render pain facial expressions in response to palpation forces. We compare this approach against a direct presentation of tactile sensor data in a visual tactile map. As feedback, the former has the advantage of recruiting advanced human capabilities to decode expressions on a human face whereas the later has the advantage of being able to present details such as intensity and spatial information of palpation. In a user study, we compare these two approaches in a teleoperated palpation task to find the hard nodule embedded in the remote abdominal phantom. We show that the face mediated human–robot interaction approach leads to statistically significant improvements in localizing the hard nodule without compromising the nodule position estimation time. We highlight the inherent power of facial expressions as communicative signals to enhance the utility and effectiveness of human–robot interaction in remote medical examinations.
Quantum coherence of a circularly accelerated atom in a spacetime with a reflecting boundary
Authors: Zhang Wanhe , Liu Xiaobao , Yang Tingli
Published: July 2022

We investigate, in the paradigm of open quantum systems, the dynamics of quantum coherence of a circularly accelerated atom coupled to a bath of vacuum fluctuating massless scalar field in a spacetime with a reflecting boundary. The master equation that governs the system evolution is derived. Our results show that in the case without a boundary, the vacuum fluctuations and centripetal acceleration will always cause the quantum coherence to decrease. However, with the presence of a boundary, the quantum fluctuations of the scalar field are modified, which makes that quantum coherence could be enhanced as compared to that in the case without a boundary. Particularly, when the atom is very close to the boundary, although the atom still interacts with the environment, it behaves as if it were a closed system and quantum coherence can be shielded from the effect of the vacuum fluctuating scalar field.
Glycometabolism change during Burkholderia pseudomallei infection in RAW264.7 cells by proteomic analysis
Authors: Li Xuexia , Zeng Yingfei , Guo Shengnan , Chen Chen , Liu Lin , Xia Qianfeng
Published: July 2022

Burkholderia pseudomallei is a Gram-negative intracellular bacterium that causes melioidosis, a life-threatening disease. The interaction of B. pseudomallei with its host is complicated, and cellular response to B. pseudomallei infection is still largely unknown. In this study, we aimed to determine host-cell responses to B. pseudomallei at the proteomics level. We performed proteomic profiling of B. pseudomallei HNBP001-infected mouse macrophage RAW264.7 cells to characterize the cellular response dynamics during infection. Western blot analysis was utilized for the validation of changes in protein expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the clusterProfiler R package. Compared with the negative control (NC) group, 811 common proteins varied over time, with a cut-off level of two fold change and an adjusted P-value less than 0.05. The bioinformatics analysis revealed that the proteins significantly changed in the B. pseudomallei HNBP001 infection group (Bp group) were enriched in glycometabolism pathways, including glycolysis, fructose and mannose metabolism, pentose phosphate pathway, galactose metabolism, and carbon metabolism. Western blot analysis verified three selected proteins involved in glycometabolism pathways, namely PGM1, PKM, and PGK1 were increase over time post the infection. Furthermore, in vitro functional analysis revealed an increased glucose uptake and decreased ATP production and O-GlcNAcylation in the Bp group compared with control group, suggesting that B. pseudomallei HNBP001 infection induces changes in glycometabolism in RAW264.7 cells. These results indicate that glycometabolism pathways change in RAW264.7 cells post B. pseudomallei HNBP001 infection, providing important insights into the intimate interaction between B. pseudomallei and macrophages.
A comprehensive analysis of meloxicam particles produced by nanosecond laser ablation as a wet milling technique
Authors: Nagy Eszter , Homik Zsolt , Smausz Tamás , Kopniczky Judit , Náfrádi Máté , Alapi Tünde , Kokai David , Burián Katalin , Szabó-Révész Piroska , Ambrus Rita , Hopp Béla
Published: July 2022

Recently, the number of water insoluble and poorly soluble drug compounds has increased significantly. Therefore, growing interest has been witnessed in different particle size reduction techniques to improve the dissolution rates, transport characteristics and bioavailability of drugs. Laser ablation has proven to be an alternative method to the production of nano- and micrometre-sized drug particles without considerable chemical damage. We present the nanosecond laser ablation of drug pastilles in distilled water, targeting meloxicam, a poorly water soluble nonsteroidal anti-inflammatory drug, at different laser wavelengths (248 nm, 532 nm and 1064 nm). Besides chemical characterization, crystallinity, morphology and particle size studies, the mechanism of the particle generation process was examined. The applicability of ablated particles in drug formulation was investigated by solubility, cytotoxicity and anti-inflammatory effect measurements. We showed that laser ablation is a clean, efficient and chemically non-damaging method to reduce the size of meloxicam particles to the sub-micrometre–few micrometre size range, which is optimal for pulmonary drug delivery. Complemented by the excellent solubility (four to nine times higher) and anti-inflammatory (four to five times better) properties of the particles compared to the initial drug, laser ablation is predicted to have wider applications in the development of drug formulations.
Behavioral and neurophysiological aspects of working memory impairment in children with dyslexia
Authors: Wang Jie , Huo Shuting , Wu Ka Chun , Mo Jianhong , Wong Wai Leung , Maurer Urs
Published: July 2022

The present study aimed to identify behavioral and neurophysiological correlates of dyslexia which could potentially predict reading difficulty. One hundred and three Chinese children with and without dyslexia (Grade 2 or 3, 7- to 11-year-old) completed both verbal and visual working memory (n-back) tasks with concurrent EEG recording. Data of 74 children with sufficient usable EEG data are reported here. Overall, the typically developing control group (N = 28) responded significantly faster and more accurately than the group with dyslexia (N = 46), in both types of tasks. Group differences were also found in EEG band power in the retention phase of the tasks. Moreover, forward stepwise logistic regression demonstrated that both behavioral and neurophysiological measures predicted reading difficulty uniquely. Dyslexia was associated with higher frontal midline theta activity and reduced upper-alpha power in the posterior region. This finding is discussed in relation to the neural efficiency hypothesis. Whether these behavioral and neurophysiological patterns can longitudinally predict later reading development among preliterate children requires further investigation.
Smooth muscle cell specific NEMO deficiency inhibits atherosclerosis in ApoE−/− mice
Authors: Imai Takashi , Van Trieu-My , Pasparakis Manolis , Polykratis Apostolos
Published: July 2022

The development of atherosclerotic plaques is the result of a chronic inflammatory response coordinated by stromal and immune cellular components of the vascular wall. While endothelial cells and leukocytes are well-recognised mediators of inflammation in atherosclerosis, the role of smooth muscle cells (SMCs) remains incompletely understood. Here we aimed to address the role of canonical NF-κB signalling in SMCs in the development of atherosclerosis. We investigated the role of NF-κB signalling in SMCs in atherosclerosis by employing SMC-specific ablation of NEMO, an IKK complex subunit that is essential for canonical NF-κB activation, in ApoE−/− mice. We show that SMC-specific ablation of NEMO (NEMOSMCiKO) inhibited high fat diet induced atherosclerosis in ApoE−/− mice. NEMOSMCiKO/ApoE−/− mice developed less and smaller atherosclerotic plaques, which contained fewer macrophages, decreased numbers of apoptotic cells and smaller necrotic areas and showed reduced inflammation compared to the plaques of ApoE−/− mice. In addition, the plaques of NEMOSMCiKO/ApoE−/− mice showed higher expression of α-SMA and lower expression of the transcriptional factor KLF4 compared to those of ApoE−/− mice. Consistently, in vitro, NEMO-deficient SMCs exhibited reduced proliferation and migration, as well as decreased KLF4 expression and lower production of IL-6 and MCP-1 upon inflammatory stimulus (TNF or LPS) compared to NEMO-expressing SMCs. In conclusion, NEMO-dependent activation of NF-κB signalling in SMCs critically contributes to the pathogenesis of atherosclerosis by regulating SMC proliferation, migration and phenotype switching in response to inflammatory stimuli.
Production of kidney organoids arranged around single ureteric bud trees, and containing endogenous blood vessels, solely from embryonic stem cells
Authors: Palakkan Anwar A. , Tarnick Julia , Waterfall Martin , Sallam May , Glykofrydis Fokion , Elhendawi Mona , Davies Jamie A.
Published: July 2022

There is intense worldwide effort in generating kidney organoids from pluripotent stem cells, for research, for disease modelling and, perhaps, for making transplantable organs. Organoids generated from pluripotent stem cells (PSC) possess accurate micro-anatomy, but they lack higher-organization. This is a problem, especially for transplantation, as such organoids will not be able to perform their physiological functions. In this study, we develop a method for generating murine kidney organoids with improved higher-order structure, through stages using chimaeras of ex-fetu and PSC-derived cells to a system that works entirely from embryonic stem cells. These organoids have nephrons organised around a single ureteric bud tree and also make vessels, with the endothelial network approaching podocytes.