bluuebunny/crossref_metadata_2025 huggingface dataset:
Orthogonal Control of Gene Expression in Plants Using Synthetic Promoters and CRISPR-Based Transcription Factors
Authors: Kar Shaunak , Bordiya Yogendra , Rodriguez Nestor , Kim Junghyun , Gardner Elizabeth C , Gollihar Jimmy D , Sung Sibum , Ellington Andrew D
Published: January 2022

Background: The construction and application of synthetic genetic circuits is frequently improved if gene expression can be orthogonally controlled, relative to the host. In plants, orthogonality can be achieved via the use of CRISPR-based transcription factors that are programmed to act on natural or synthetic promoters. The construction of complex gene circuits can require multiple, orthogonal regulatory interactions, and this in turn requires that the full programmability of CRISPR elements be adapted to non-natural and non-standard promoters that have few constraints on their design. Therefore, we have developed synthetic promoter elements in which regions upstream of the minimal 35S CaMV promoter are designed from scratch to interact via programmed gRNAs with dCas9 fusions that allow activation of gene expression. Results: A panel of three, mutually orthogonal promoters that can be acted on by artificial gRNAs bound by CRISPR regulators were designed. Guide RNA expression targeting these promoters was in turn controlled by either Pol III (U6) or ethylene-inducible Pol II promoters, implementing for the first time a fully artificial Orthogonal Control System (OCS). Following demonstration of the complete orthogonality of the designs, the OCS was tied to cellular metabolism by putting gRNA expression under the control of an endogenous plant signaling molecule, ethylene. The ability to form complex circuitry was demonstrated via the ethylene-driven, ratiometric expression of fluorescent proteins in single plants. Conclusions: The design of synthetic promoters is highly generalizable to large tracts of sequence space, allowing Orthogonal Control Systems of increasing complexity to potentially be generated at will. The ability to tie in several different basal features of plant molecular biology (Pol II and Pol III promoters, ethylene regulation) to the OCS demonstrates multiple opportunities for engineering at the system level. Moreover, given the fungibility of the core 35S CaMV promoter elements, the derived synthetic promoters can potentially be utilized across a variety of plant species.
Restricted Feeding Regimens Improve White Striping Associated Muscular Defects In Broiler Chickens
Authors: Ayansola Hammed , Yu Xiaoxiao , Lei Jiaqi , Liao Chaoyong , Guo Yuming , Zhang Bingkun , Wang Bo
Published: January 2022

Background: Ad libitum (AD) feeding is crucial to profitable commercial broiler chicken production. However, it partly disrupts muscle development, causing myopathies like white striping in broilers’ breast meat. For this reason, this study investigated the impacts of intermittent feeding (IF) and fasting strategies as potential alternatives to AD feeding. A total of 384 one-day-old broilers were randomly allotted into 4 groups - ad libitum, 1h-IF group (4 times/day, 1 hour each time), 1.5h-IF (4 times/day, 1.5hrs each time), and acute fasting (1-day acute fasting, 6-days free access to feed). Feed intake, weight gain, muscle structure, differential genes, and protein expressions were assessed in the broiler breast muscles. Results: IF and fasting significantly reduced ectopic fat deposit and muscle fiber size (p < 0.05). Notably, 1.5h-IF promoted PAX7+ satellite cell proliferation supporting muscle growth and repair activities in fast-growth broiler chickens. Consistently, the restricted regimens downregulated the collagen protein synthesis of skeletal muscle-specific E3 ubiquitin ligases (TRIM63 and MAFBX) in 42 – days old breast muscle samples (p < 0.05), especially in the 1.5h-IF group. Compared to AD-fed birds, 1.5h-IF and fasting feeding significantly decreased white striping scores in the breast meat muscle (p < 0.05). ConclusionChronic IF or acute fasting improved muscle health of broiler chickens without significant compromise on growth rate and feed efficiency compared to AD feeding. Therefore, this study presents potential feeding frequencies relevant for optimal growth pace while alleviating the occurrence of myopathic pathophysiology in broiler chickens.
The Importance of Routine Quality Control For Reproducible Pulmonary Measurements By in Vivo Micro-CT
Authors: Mambrini Martina , Mecozzi Laura , Ferrini Erica , Leo Ludovica , Bernardi Davide , Andrea Grandi , Sverzellati Nicola , Ruffini Livia , Silva Mario , Stellari Franco
Published: January 2022

Micro-Computed Tomography (CT) imaging provides densitometric and functional assessment of lung diseases in animal models, playing a key role either in understanding disease progression or in drug discovery studies.The generation of reliable and reproducible experimental data is strictly dependent on a system’s stability. Quality Controls (QC) are essential to monitor micro-CT performance but, although QC procedures are standardized and routinely employed in clinical practice, detailed guidelines for preclinical imaging are lacking. In this work, we propose a routine QC protocol for in vivo micro-CT, based on three commercial phantoms. To investigate the impact of a detected scanner drift on image post-processing, a retrospective analysis using twenty-two healthy mice was performed and lung density histograms used to compare the Area Under Curve (AUC), the skewness and the kurtosis before and after the drift. As expected, statistically significant differences were found for all the selected parameters [AUC: 532 ± 31 vs. 420 ± 38 (p < 0.001); skewness: 2.3 ± 0.1 vs. 2.5 ± 0.1 (p < 0.001) and kurtosis: 4.2 ± 0.3 vs. 5.1 ± 0.5 (p < 0.001)], confirming the importance of the designed QC procedure to obtain a reliable longitudinal quantification of disease progression and drug efficacy evaluation.
Energy Efficiency Strategies For Future Educational Buildings: A Case Study in Madrid
Authors: Ruano Paloma Campo , Montoya José María De Lapuerta , García-Germán Javier , Amigo Jesús M. Menéndez , Ruiz Irene Cámara
Published: January 2022

The authors have requested that this preprint be removed from Research Square.
Thermo-Electrochemical Redox Flow Battery for Continuous Conversion of Low-Grade Waste Heat to Power
Authors: Bleeker Jorrit , Reichert Stijn , Veerman Joost , Vermaas David
Published: January 2022

Here we assess the route to convert low grade waste heat (<100°C) into electricity by leveraging the temperature dependency of redox potentials (Seebeck effect). We use fluid-based redox-active species, which can be easily heated and cooled using heat exchangers. By using a first principles approach, we designed a redox flow battery system with Fe(CN)63−/Fe(CN)64− and I−/I3− chemistry. We evaluate the continuous operation with one flow cell at high temperature and one at low temperature. We show that the most sensitive parameter, the Seebeck coefficient, can be controlled via the redox chemistry, the reaction quotient and solvent additives, and we present the highest Seebeck coefficient for this RFB chemistry. A power density of 0.6 W/m2 and stable operation for 2 hours are achieved experimentally. We predict high (close to Carnot) heat-to-power efficiencies if challenges in the heat recuperation and Ohmic resistance are overcome, and the Seebeck coefficient is further increased.
Slow Firing Single Units Are Essential for Optimal Decoding of Silent Speech
Authors: Kennedy Philip , Ganesh A. , Cervantes A.J.
Published: January 2022

Summary The motivation of someone who is locked-in, that is, paralyzed and mute, is to find relief for their loss of function. The data presented in this report is part of an attempt to restore one of those lost functions, namely, speech. An essential feature of the development of a speech prosthetic is optimal decoding of patterns of recorded neural signals during silent or covert speech, that is, speaking ‘inside the head’ with no audible output due to the paralysis of the articulators. The aim of this paper is to illustrate the importance of both fast and slow single unit firings recorded from an individual with locked-in syndrome and from an intact participant speaking silently. Long duration electrodes were implanted in the motor speech cortex for up to 13 years in the locked-in participant. The data herein provide evidence that slow firing single units are essential for optimal decoding accuracy. Additional evidence indicates that slow firing single units can be conditioned in the locked-in participant five years after implantation, further supporting their role in decoding.
Structure Based Innovative Approach to Analyze Aptaprobe-GPC3 Complexes in Hepatocellular Carcinoma
Authors: Shin Woo-Ri , Park Dae-Young , Kim Ji Hun , Lee Jin-Pyo , Thai Nguyen Quang , Oh In-Hwan , Sekhon Simranjeet Singh , Choi Wooil , Kim Sung Yeon , Cho Byung-Kwan , Kim Sun Chang , Min Jiho , Ahn Ji-Young , Kim Yang-Hoon
Published: January 2022

Background Glypican-3 (GPC3), a membrane-bound heparan sulfate proteoglycan, is a biomarker of hepatocellular carcinoma (HCC) progression. Aptamers specifically binding to target biomolecules have recently emerged as clinical disease diagnosis targets. Here, we describe 3D structure-based aptaprobe platforms for detecting GPC3, such as aptablotting, aptaprobe-based sandwich assay (ALISA), and aptaoptical imaging analysis. Results For preparing the aptaprobe–GPC3 platforms, we obtained 12 high affinity aptamer candidates (GPC3_1 to GPC3_12) that specifically bind to target GPC3 molecules. Structure-based molecular interactions identified distinct aptatopic residues responsible for binding to the paratopic nucleotide sequences (nt-paratope) of GPC3 aptaprobes. Sandwichable and overlapped aptaprobes were selected through structural analysis. The aptaprobe specificity for using in HCC diagnostics were verified through Aptablotting and ALISA. Moreover, Aptaoptical imaging showed that the binding property of GPC3_3 and their GPC3 specificity were maintained in HCC xenograft models, which may indicate a new HCC imaging diagnosis.Conclusion Aptaprobe has the potential to be used as an affinity reagent to detect the target in vivo and in vitro diagnosing system.
The Top 5 Causes of Death In China From 2000 To 2017
Authors: Zou Haiyin , Tian Xinjie , Ren Yongcheng
Published: January 2022

Background: Limited information is available on the epidemiological characteristics of major causes of death in the last 18 years. In this study, we investigated the epidemiological characteristics of the top 5 causes of death in China from 2000 to 2017. Methods: Data were obtained from the 18-year reports of Ministry of Health and analyzed by Grid Search Method, Permutation test, and log-linear regression model. Results: The top 5 consistent causes of death, malignant tumor, cerebrovascular disease, heart trouble, respiratory disease, trauma and toxicosis accounted for 82.6% in 2000, 86.49% in 2017 in urban areas and 83.31% in 2000, 88.34% in 2017 in rural areas. The increasing trends (P<0.05) of proportions of death of malignant tumor, cerebrovascular disease, and heart trouble have average annual percent change (AAPC) = 0.5%, 0.3%, 2.4% in urban areas and 1.7%, 1.5%, 4.3% in rural areas. The AAPCs of respiratory disease are -1.4% in urban areas and -3.6% in rural areas. Cardio-cerebrovascular disease increased (Urban: 39.02% to 43.56%, AAPC=1.3%, P<0.05; Rural: 32.03% to 45.91%, AAPC=2.7%, P<0.05) steeply from 2000 to 2017 which are higher than that of malignant tumor (P<0.05). Conclusion: The top 5 causes of death in China accounted for more than 85% of all deaths in 2017, in which cardio-cerebrovascular disease accounted for the largest proportion with the steepest increasing trend.
Based on Bioinformatics Studies on the Effect of a lpha1H on Key Genes, Pathways in Bladder Cancer and lncRNA on Patient Prognosis
Authors: Wang Xing , Yu Jiandi , peng Kun , Wen Huali , Wang Renjie , Zhou Haiyong
Published: January 2022

Objective: To analyze the differential genes, lncRNA, signaling pathway and patient prognosis of bladder cancer after alpha1H treatment.Methods: Sequencing data GSE172112 for patients in clinical trials with a new bladder cancer drug were downloaded from the GEO database, The bladder cancer tissues using the new drug alpha1H (alpha1-oleate) and placebo were analyzed in the R language, The differentially expressed genes were selected; Differential genes were analyzed for KEGG pathway enrichment using the DAVID database, To explore the effect of a lpha1H treatment on pathways in patients with bladder cancer; at the same time, lncRNA expression data from the Bladder Cancer (BLCA) dataset were also downloaded through the TCGA database, First, screening for differential lncRNA expression, The screening results were then analyzed by univariate Cox regression to initially screen for lncRNA associated with prognosis, The key lncRNA affecting the prognosis were further screened out, The prognostic model was also constructed using multivariate Cox regression analysis. Results: There yielded 394 significantly upregulated genes and 385 significantly downregulated genes in bladder cancer tissue after a lpha1H treatment. Through gene signaling pathway enrichment analysis, the upregulated genes were mainly enriched in the signaling pathways regulating the pluripotent line of stem cell cells, the TGF-signaling pathways, and the cell cycle. The downregulated genes were mainly enriched in the MAPK signaling pathway, phagosomes, and the TNF signaling pathway. After a lpha1H treatment, of 119 differentially expressed lncRNA, from the lnc2cancer database, two genes were found to be potentially associated with bladder cancer prognosis, and the final analysis confirmed the key lncRNA affecting prognosis. The results of survival analysis showed that high expression of LINC00152 unfavorable unfavorable patient prognosis and the new drug alpha1H reduces LINC00152 favors patient prognosis. Conclusion: Alpha1H can cure bladder cancer by regulating hallmark signaling, TGF-beta signaling, and LINC00152.
Sociality of Future Outcomes Moderates The Effects Of Warmth And Competence On Social Optimism Bias - A Pre-Registered Study
Authors: Dricu Mihai , Jossen Sina Ladina , Aue Tatjana
Published: January 2022

People are overoptimistic about the future of those they like or admire (social optimism bias), expecting significantly more desirable than undesirable outcomes. By contrast, they are pessimistic about those they don’t like. To operationalize the (dis)like of social targets, warmth and competence are used as two universal dimensions of social perception. In this pre-registered study, we replicate previous findings while adding two new levels of complexity. First, we make the distinction between the sociality of future outcomes: “alone” outcomes (e.g., enjoying a quiet afternoon by oneself) and “social” outcomes (e.g., enjoying a vacation with the significant other). Second, we investigate the effect of attachment styles on one’s expectations for alone and social outcomes towards the social targets. In line with our hypotheses, the sociality of outcomes moderates both the additive and the multiplicative effects of the warmth and competence of social targets on social optimism bias. Diverging from our hypotheses, we find that attachment anxiety and avoidance do not influence the effects of warmth and competence on social optimism bias. However, exploratory analyses revealed that attachment dimensions buffer the magnitude of social optimism bias for highly self-relevant social targets but do not impact a social pessimism bias for irrelevant targets.
Developing Deep Learning Models for the Classification of Pediatric Elbow Radiographic Abnormalities of Comparable Performance to Physicians: Strategies for Model Optimization With Small Sized Development Sets
Authors: TAN Mark B. , CHUA Russ Y. , FAN Qiao , FORTIER Marielle V. , CHANG Pearlly P.
Published: January 2022

BackgroundTo compare the performance of an AI model based on strategies designed to overcome small sized development sets to pediatric ER physicians at a classification triage task of pediatric elbow radiographs. Methods1,314 pediatric elbow lateral radiographs (mean age: 8.2 years) were retrospectively retrieved, binomially classified based on their annotation as normal or abnormal (with pathology), and randomly partitioned into a development set (993 images), tuning set (109 images), second tuning set (100 images) and test set (112 images). The AI model was trained on the development set and utilized the EfficientNet B1 compound scaling network architecture and online augmentations. Its performance on the test set was compared to a group of five physicians (inter-rater agreement: fair). Statistical analysis: AUC of AI model - DeLong method. Performance of AI model and physician groups - McNemar test. ResultsAccuracy of the model on the test set - 0.804 (95% CI, 0.718 - 0.873), AUROC - 0.872 (95% CI, 0.831 - 0.947). AI model performance compared to the physician group on the test set - sensitivity 0.790 (95% CI 0.684 to 0.895) vs 0.649 (95% CI 0.525 to 0.773), p value 0.088; specificity 0.818 (95% CI 0.716 to 0.920) vs 0.873 (95% CI 0.785 to 0.961), p value 0.439.ConclusionsThe AI model for elbow radiograph triage designed with strategies to optimize performance for a small sized development set showed comparable performance to physicians.
Lumboperitoneal Shunt Surgery Under Rachianesthesia
Authors: Goto Yukihiro , Nozuchi Shinji , Inoue Takuro
Published: January 2022

Purpose: In the very elderly, complications such as postoperative pneumonia or delirium, which are directly associated with longer hospitalization, are more frequent. In order to overcome these drawbacks, we switched from general anesthesia to rachianesthesia for the lumboperitoneal shunt (LPS) procedure in idiopathic normal pressure hydrocephalus (iNPH) patients. This is because iNPH suffers particularly elderly patients, and neuraxial anesthesia techniques such as rachianesthesia reportedly decrease postoperative complications in patients of very advanced age as compared with general anesthesia. Methods: We retrospectively analyzed 45 patients who underwent LPS in our institution, and divided them into two groups based on the anesthetic approach; 1) general anesthesia, 2) rachianesthesia. We analyzed these two groups with regard to postoperative delirium score and the hospital stay.Results: In the general anesthesia group, two patients had respiratory complications after the surgery. The mean postoperative delirium score using the intensive care delirium screening checklist (ICDSC) was 1.3 (1.4) and the length of hospital stay was 13.9 (4.7) days. In the rachianesthesia group, no patients had respiratory complications. The postoperative mean ICDSC was 1.3 (1.4), and the length of hospital stay was 10.8 (2.1) days. The statistical analysis showed the rachianesthesia group to have significantly shorter hospital stays.Conclusions: LPS under rachianesthesia is an alternative to performing this procedure under general anesthesia in elderly patients.
Global Growth in Offshore Wind Turbine Technology
Authors: Bilgili Mehmet , Alphan Hakan
Published: January 2022

Due to the commissioning of floating wind units, the latest technological developments, significant growth, and improvements in turbines, developments in offshore wind power capacity are estimated to increase faster than in the last two decades. The total installed offshore wind power capacity, which is currently 35 GW, is predicted to be approximately 382 GW by 2030 and approximately 2,002 GW by 2050. For this reason, attempts are proposed to lower levelised cost of electricity (LCOE) for offshore wind power generation more than for other energy sources. In this study firstly, the global growth in the nominal capacity and size of offshore wind turbines over the last twenty years is examined. Then, the effects of this increase in nominal capacity and size on the LOCE, total installation cost (TIC), and turbine capacity factor are investigated. In parallel with this development, the changes in distance to shore and water depth for installation offshore wind power plants are reviewed according to the years. In addition, the effects of this global growth on wind farm capacity, turbine-specific power capacity, number of turbines per GW, and area needed per GW are investigated and discussed in detail.
A web-based survey on factors for unvaccination and adverse reactions of SARS-CoV-2 vaccines in Chinese postoperative patients with breast cancer
Authors: Liao Liqiu
Published: January 2022

Background
Vaccination against SARS-COV-2 has been the most important strategy for preventing infection of Coronavirus disease 2019 (COVID-19). Breast cancer is the most common malignancy in women, but there is a lack of research on the pandemics in postoperative patients with breast cancer.
Objective
To investigate the rate and factors for SARS-CoV-2 vaccination and adverse reactions after vaccination in postoperative patients with breast cancer.
Methods
A web-based questionnaire survey on SARS-CoV-2 vaccination in postoperative patients with breast cancer among women.
Results
A total of 947 online questionnaires were collected. Of these, 341 accepted SARS-CoV-2 vaccination, while 606 were not vaccinated. There were significant differences in age, current treatment, the time since surgery, and the symptoms of anxiety and depression between the two groups. We identified current treatment (OR=0.51 for endocrine therapy; 95% CI: 0.29-0.89), the time since surgery (OR=22.49 for 1-2 years; 95% CI: 12.31-41.10; OR=8.49 for 2-5 years ; 95% CI: 4.98-14.46; OR=1.79 for >5 years ; 95% CI: 1.11-2.89), and the symptoms of depression (OR=2.48; 95% CI: 1.19-5.15) as significant factors for unvaccination. The overall incidence of adverse reactions was 43.1%. The most common local and systemic adverse reactions were pain at the injection site (28.4%) and fatigue (8.8%), respectively.
Conclusion
Postoperative patients with breast cancer have a relatively lower rate of vaccination for SARS-CoV-2 than the general population. Receiving treatment, a shorter time since surgery and symptom of depression were associated with unvaccination. More importantly, a favorable safety profile of the vaccines is indicated.
Mental Health Consequences from COVID-19 Pandemic and Strategies for Community Level Recovery
Authors: Somasundaram Daya , Rajeshkannan Nadarajah , Kumarendran Balachandran , Kumanan Thirunavukarasu , Sugirthan Nalayini , Aloysius Ivan Dinesh , Sasikumar Sivanandan , Jegathesan Nalayini
Published: January 2022

Background: The COVID-19 pandemic has spread across the globe from 2019 affecting millions of people physically, mentally, and socio-economically. The purpose of the study was to map out the mental health consequences of the COVID-19 Pandemic and suggest recovery strategies.Methods: A qualitative inquiry into the mental health aspects of the COVID-19 pandemic using observations from working in busy health clinics, general practices, primary and community care setting, and dedicated COVID acute care wards during the pandemic in Australia, United Kingdom and Sri Lanka; discussions with colleagues worldwide; analyzing social and news media comments; literature survey and experience of dealing with past disasters were used to map out mental health consequences and put forward recovery strategies.Results: In covid sufferers, neuropsychiatric symptoms lasting months, unrelated to respiratory insufficiency suggested brain damage due to vascular endothelial injury and/or cerebral venous thrombosis (CVT). A third went onto develop or have a relapse of a psychological or neurological conditions. In the general population, common consequences included common mental health disorders; changing patterns of substance abuse including alcohol; increased domestic violence and child abuse. Family relationships, interactions and understanding improved in many but minority had strained dynamics. Vulnerable groups included the elderly, women, youth; children; disabled; frontline and health workers; minorities and severely mentally ill. At the community level, there were signs of collective (mass) hysteria from panic buying to conspiracy theories, public shaming, fake news and disinformation spreading on social media and mass protests. There were also positive effects such as better understanding of bio-knowledge; interventions (rapid vaccine production, contact tracing methods) and discoveries (mRNA Vaccines), health systems improvements (tele-health), online learning, gratitude toward heath care workers, increased social/community/family cohesion, closer international networking, reduction in suicide rates and drop in interstate and civil conflicts, road accidents, crime and communicable diseases with their resultant morbidity, mortality and mental health consequences. Conclusions: In view of the widespread mental health and psychosocial consequences from the COVID-19 pandemic, a community-based approach is suggested while treating more severe mental disorders at the primary care or specialist level.
Vision-based Pakistani Sign Language Recognition Using Bag-of-Words and Support Vector Machines
Authors: Mirza Muhammad Shaheer , Munaf Sheikh Muhammad , Ali Shahid , Azim Fahad , Khan Saad Jawaid
Published: January 2022

In order to perform their daily activities, a person is required to communicating with others. This can be a major obstacle for the deaf population of the world, who communicate using sign languages (SL). Pakistani Sign Language (PSL) is used by more than 250,000 deaf Pakistanis. Developing a SL recognition system would greatly facilitate these people. This study aimed to collect data of static and dynamic PSL alphabets and to develop a vision-based system for their recognition using Bag-of-Words (BoW) and Support Vector Machine (SVM) techniques. A total of 5,120 images for 36 static PSL alphabet signs and 353 videos with 45,224 frames for 3 dynamic PSL alphabet signs were collected from 10 native signers of PSL. The developed system used the collected data as input, resized the data to various scales and converted the RGB images into grayscale. The resized grayscale images were segmented using Thresholding technique and features were extracted using Speeded Up Robust Feature (SURF). The obtained SURF descriptors were clustered using K-means clustering. A BoW was obtained by computing the Euclidean distance between the SURF descriptors and the clustered data. The codebooks were divided into training and testing using 5-fold cross validation. The highest overall classification accuracy for static PSL signs was 97.80% at 750×750 image dimensions and 500 Bags. For dynamic PSL signs a 96.53% accuracy was obtained at 480×270 video resolution and 200 Bags.
WITHDRAWN: Determination of the Effect of Two Different Methods of Dental Anaesthesia on Pain Level in Pediatric Patients: A Cross-Over, Randomised Trial
Authors: Yilmaz Nagehan , Baygin Ozgul , Tüzüner Tamer , Menteşe Ahmet , Demir Selim
Published: January 2022

ObjectiveTo compare intraosseous (IOA) and needle-free dental anaesthesia (NFA) methods that painless anaesthesia.Materials and MethodsTwenty patients aged 8–10 years were included in this cross-over study. To determine the anxiety levels and pain experienced by the patients, Face, Legs, Activity, Cry, Consolability (FLACC) and Frankl Behavioural scales were used. The pulse rate (PR) and salivary opiorphin levels (SOL) determined. The Friedman and Wilcoxon signed-rank tests were used. p<0.01 was considered significant.ResultsAccording to FLACC scores, IOA and NFA exhibited significantly pain alteration patterns in during local and topical anaesthesia, respectively (p=0.004,0.001; p<0.01). Also, only NFA showed significantly decreased SOL values in 5- and 10- minutes after local anaesthesia periods compared to the before levels (p=0.004, p=0.001; p<0.01).ConclusionsPatients feel similar pain perceptions during local anaesthesia application in both injection systems. According to the SOL values, NFA may provide more higher anaesthetic efficiency than IOA.Clinical RelevanceThis study provides to compare two different new anaesthetic systems for pain reduction during local anesthesia for pediatric population.
Importance of Eosinophilic Infiltration of the Colonic Mucosa in Ulcerative Colitis Patients who are Refractory to Maintenance Therapy
Authors: Miyazu Takahiro , Ishida Natsuki , Asai Yusuke , Tamura Satoshi , Tani Shinya , Yamade Mihoko , Hamaya Yasushi , Iwaizumi Moriya , Osawa Satoshi , Furuta Takahisa , baba satoshi , Sugimoto Ken
Published: January 2022

Eosinophilic infiltration is sometimes observed histologically in ulcerative colitis (UC), but the effect of the degree of infiltration on the treatment course for UC is not completely studied. We investigated whether short-term steroid administration in UC patients refractory to maintenance therapy, with high eosinophilic infiltration in the colonic mucosa, contributed to clinical and endoscopic improvement. Ten patients with endoscopically active and pathologically high eosinophilic infiltration, based on pathological examination using endoscopic biopsy, were examined for clinical background when starting steroid treatment; clinical and endoscopic improvement before and after steroid use were assessed prospectively. The average initial steroid dosage and duration of use were 21.0 mg and 102.7 days, respectively. The mean values before and after steroid use of clinical activity index, Mayo endoscopic subscore, and UC endoscopic index of severity were 2.4 and 1.0, 1.8 and 0.7, and 3.9 and 1.1, respectively. All these scores improved significantly after steroid use (P=0.04, P<0.01, P<0.01, respectively). Steroids were discontinued in all patients; no patients required steroid re-administration. There may be cases of UC with eosinophilic infiltration into the colonic mucosa and resistant to maintenance treatment, suggesting that short-term steroid administration may contribute to clinical and endoscopic improvements.
Neuromorphic Chip Integrated with an LSI and Amorphous-metal-oxide Semiconductor Thin-film Synapse Devices
Authors: Kimura Mutsumi , Shibayama Yuki , Nakashima Yasuhiko
Published: January 2022

Artificial intelligences are promising in future societies, and neural networks are typical technologies with the advantages such as self-organization, self-learning, parallel distributed computing, and fault tolerance, but their size and power consumption are large. Neuromorphic systems are biomimetic systems from the hardware level, with the same advantages as living brains, especially compact size, low power, and robust operation, but some well-known ones are non-optimized systems, so the above benefits are only partially gained, for example, machine learning is processed elsewhere to download fixed parameters. To solve these problems, we are researching neuromorphic systems from various viewpoints. In this study, a neuromorphic chip integrated with an LSI and amorphous-metal-oxide semiconductor (AOS) thin-film synapse devices has been developed. The neuron elements are digital circuit, which are made in an LSI, and the synapse devices are analog devices, which are made of the AOS thin film and directly integrated on the LSI. This is the world's first hybrid chip where neuron elements and synapse devices of different functional semiconductors are integrated, and local autonomous learning is utilized, which becomes possible because the AOS thin film can be deposited without heat treatment and there is no damage to the underneath layer, and has all advantages of neuromorphic systems.
Improvement of Dispersibility of Graphene Oxide by Surface Modification with Rare Earths
Authors: Li Yong , Jiang Zhou , Yu Haidong , Zhou Xuebin , Yi Peng
Published: January 2022

Rare earth-modified graphene oxide (RE-M-GO) materials were successfully prepared by infiltration and heating modifier method. The morphology and phase structure of RE-M-GO were characterized by scanning electron microscopy(SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and energy dispersive spectrometer(EDS). The changes of the chemical structure were indicated by Fourier transform infrared (FTIR). X-ray photoelectron spectroscopy(XPS) was used to study the chemical state of the surface elements of graphene oxide which showed that the rare earth elements were added to the graphene oxide functional groups through the coordination reaction. Additionally, the findings concluded that the effect of modification by Ce is more obvious than La elements and the RE-M-GO materials prepared by the heating modifier method had better dispersibility than infiltration. With activating effect, the rare earth elements grafting to graphene oxide will contribute to its combination with other materials.
Angio-Associated Migratory Cell Protein (AAMP) Regulates the Hippo/YAP Pathway and Mitochondrial Functionality to Drive Osteosarcoma Metastasis
Authors: Zhan Fangbiao , Chen Zhiyu , Xie Chaozheng , Xiang Shuang , Deng Qianrong , Li Huanhuan , Tian Lin , Jian Changchun , Xiang Jiangxia , Ou Yunsheng , Chen Jian , Xu Lixin
Published: January 2022

Background: Osteosarcoma (OS) is the prevalent form of primary bone cancer among adolescents, but the 5-year overall survival rate for patients with a metastatic or recurrent OS is under 20%. Angio-associated migratory cell protein (AAMP) is known to be a key regulator of cellular migration, yet its role in the context of OS metastasis has yet to be firmly established.Methods: Bioinformatics analyses were used to explore the association between AAMP and YAP expression and the prognosis of OS patients, and to evaluate differences in AAMP expression in patients with primary OS, recurrent OS, and pulmonary metastatic OS. Immunohistochemical (IHC) staining was additionally performed to compare AAMP levels in primary OS and pulmonary metastatic OS patient samples. Lentiviral transduction was further used to establish OS cell lines in which AAMP or YAP had been stably knocked down or overexpressed. OS cell migration and invasion were assessed using wound healing and Transwell assays. Proteins associated with the mitochondria, the epithelial-mesenchymal transition (EMT), YAP, and its target proteins were assessed in OS cell lines via Western blotting. OS cell lamellipodia were detected via phalloidin staining. Mitochondrial morphological characteristics were assessed via transmission electron microscopy following the knockdown of AAMP. An ATP kit was employed to measure ATP levels in OS cells in which AAMP had been knocked down. Animal model studies were used to confirm indices associated with OS cell lung metastasis following AAMP knockdown. Results: Patients with metastatic OS exhibit higher levels of AAMP expression that are correlated with poorer patient prognosis. Knocking down AAMP suppressed the migratory, invasive, and EMT activity of analyzed OS cell lines. AAMP was found to regulate CFL1 and thereby control OS cell protrusion. AAMP knockdown was further found to promote OS cell mitochondrial dysfunction and decreased intracellular ATP production, with these AAMP knockdown cells exhibiting impaired migratory and invasive activity as a consequence of YAP inhibition. Consistently, the knockdown of AAMP suppressed the in vivo metastasis of OS cells. Conclusions: Together, these data highlight a model wherein AAMP can promote OS cell migratory and invasive activity by regulating YAP and mitochondrial functionality. The AAMP/CFL1/YAP signaling pathway may thus represent a viable therapeutic target for efforts aimed at suppressing the metastatic progression of OS.
Ectonucleotide Pyrophosphatase Phosphodiesterase 1 Is Correlated With Insulin Resistance and Lipid Metabolism Disorders in the Rat Model of Polycystic Ovary Syndrome
Authors: Xia Jing , Yang Yiqing , Yang Zhe , Wu Gengxiang , Yang Jing
Published: January 2022

Previous studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovary syndrome (PCOS). This study was aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS. Eighteen 23-day-old Sprague-Dawley rats were divided into PCOS and control groups (n= 9/group). Samples were collected after 20 days. Pathological examination and immunofluorescence were performed. Western blotting results of ENPP1 in the ovaries were analysed. Serum levels of ENPP1, hormones, fasting blood glucose (FBG), serum lipids were measured. Levels of ENPP1, testosterone (T), FBG, fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), free fatty acids (FFAs), leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in PCOS group, while adiponectin (ADP) and high-density lipoprotein cholesterol (HDL-C) were significantly lower. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, HOMA-IR, FFAs, leptin, serum lipids and ADP. MRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. Our results revealed that ENPP1 is highly associated with IR and lipid metabolism-related molecules, which may have play important roles in PCOS pathophysiological changes.
Genomic Machine Learning Model Predicts Radiation Therapy Benefit in Early-Stage Breast Cancer Patients with High Accuracy
Authors: Badal Kimberly , Foster Jerome E. , Haraksingh Rajini , John Melford
Published: January 2022

BackgroundRadiation therapy (RT) is frequently recommended for post-surgery treatment of early-stage breast cancer (BC) patients, though not all benefit. Clinical factors currently guide RT treatment decisions. At present, models to predict RT-benefit predominantly use statistical methods with modest performance. In this paper we present a high-accuracy genomic Machine Learning (ML) model to predict RT-benefit in early-stage BC patients. We also present a novel method for selecting genomic features for training ML algorithms. MethodsGene expression data from 463 early-stage BC patients treated with surgery and RT from the METABRIC cohort were obtained. Wilcoxon Rank Sum (Wilcoxon RS) test and Cox Proportional Hazards (Cox PH) were used to reduce the number of genes used to train eight ML algorithms. ML algorithms were trained on 80% of data using 10-fold cross validation and tested on 20% of data to assess performance in predicting relapse status. Results Genome-wide gene expression data was reduced by 96% using Wilcoxon RS and Cox PH to a 1,596 gene set and a 977 gene set. These gene sets were used to train eight ML algorithms resulting in models that ranged in performance accuracies from 54.01% to 95.6%. Highest accuracies were obtained using Support Vector Machine (SVM977–93.41%, SVM1596–95.6%) and Neural Networks algorithms (NN977 – 92.31%, NN1596 – 93.41%). In RT-untreated patients, accuracies of all models were 30% to 40% lower compared to RT-treated patients. SVM977 had the highest sensitivity of 91.09%. Members of the 977 set were enriched with genes involved in cell cycle and differentiation as well as genes associated with radiosensitivity and radioresistance. Conclusion This study presents a novel genomic feature selection approach that used Wilcoxon RS followed by Cox PH to reduce the number of genes from genome-wide gene expression data used for training ML algorithms by 96%. This approach led to an SVM model that used the expression values of 977 genes to predict RT-benefit in early-stage BC patients with 93.41% accuracy. This work demonstrates that ML models can be clinically useful for predicting cancer patient outcomes.
Einstein-Roscoe Regression for the Slag Viscosity Prediction Problem in Steelmaking
Authors: Saigo Hiroto , Bahadur K.C. Dukka , Saito Noritaka
Published: January 2022

In classical machine learning, regressors are trained without attempting to gain insight into the mechanism connecting inputs and outputs. Natural sciences, however, are interested in finding a robust interpretable function for the target phenomenon, that can return predictions even outside of the training domains. This paper focuses on viscosity prediction problem in steelmaking, and proposes Einstein-Roscoe regression (ERR), which learns the coefficients of the Einstein-Roscoe equation, and is able to extrapolate to unseen domains. Besides, it is often the case in the natural sciences that some measurements are much more expensive than the others due to physical constraints. To this end, we employ a transfer learning framework based on Gaussian process, which allows us to estimate the regression parameters using the auxiliary measurements available in a reasonable cost. In experiments using the viscosity measurements in high temperature slag system, ERR is compared favorably with various machine learning approaches in interpolation settings, while outperformed all of them in extrapolation settings. Furthermore, after estimating parameters using the auxiliary dataset obtained at room temperature, increase in accuracy is observed in the high temperature dataset, which corroborates the effectiveness of the proposed approach.
The Combined Effects of Animal Products Intake and Physical Activity With Cause-specific and All-cause Mortality Among Patients With Type 2 Diabetes Mellitus in China: A Prospective Cohort Study
Authors: He Chenlu , Hou Hao , Pei Yifei , Chen Qian , Zhang Ying , Wang Jingjing , Tang Jie , Yan Na , Pan Enchun , Sun Zhongming , Lou Peian , Zhang Xunbao , Wang Wei
Published: January 2022

BackgroundTo determine the associations of animal products intake and physical activity and their combined effects with cause-specific and all-cause mortality among type 2 diabetes mellitus (T2DM) patients in China.MethodsBaseline data of 7311 type 2 diabetes mellitus (T2DM) patients recruited with a stratified random cluster sampling method were collected from December 2013 to January 2014. Participants were followed up until the date of their death or December 2019 for survivors, whichever came first. Nonlinear trends of cause-specific and all-cause mortality were assessed using restricted cubic splines with three knots placed at centiles 10, 50, and 90 of diet intake. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the combined relationship of physical activity and animal products with cause-specific and all-cause mortality.ResultsDuring a median follow-up of 6.1 years, 692 (9.5%) T2DM patients died. The main cause of death was cardiovascular disease (CVD) (35.8%), followed by cancer (20.6%). After multivariable adjustment, a higher level of physical activity was nonlinearly associated with lower all-cause and CVD mortality in a J-shaped pattern, with the protective effect observed >8 MET-h/d. Higher consumption of red meat, poultry, and aquatic products was associated with a lower risk of all-cause mortality (HR = 0.75, 0.64, 0.75, respectively, all P<0.05). In the highest tertiles of physical activity, a higher intake of red meat, poultry, and aquatic products was associated with a lower risk for all-cause mortality than in the lowest tertiles (red meat, HR = 0.80, 0.62, 0.51, and 0.48; poultry, HR = 0.85, 0.51, 0.48, and 0.45; aquatic products, HR = 0.80, 0.57, 0.55, and 0.40, respectively). Similarly, the protective effect of moderate to high intake of poultry, aquatic products, and eggs on CVD mortality in high physical activity was found. ConclusionsOur study highlights that in T2DM patients, better adherence to moderate to high consumption of animal products, including red meat, poultry, and aquatic products, together with engaging in moderate to high levels of physical activity exerts a beneficial effect in lowering cause-specific and all-cause mortality in China.
Practical Quinone-Based Organic Supercapacitor > 6 V
Authors: Katsuyama Yuto , Takehi Takayuki , Sokabe Shu , Tanaka Mai , Ishizawa Mizuki , Abe Hiroya , Watanabe Masaru , Honma Itaru , Nakayasu Yuta
Published: January 2022

Inexpensive, high-performing, and environmentally friendly energy storage devices are required for smart grids that efficiently utilize renewable energy. Energy storage devices consisting of organic active materials are promising because organic materials, especially quinones, are ubiquitous and usually do not require harsh conditions for synthesis, releasing less CO2 during mass production. Although fundamental research-scale aqueous quinone-based organic supercapacitors have shown excellent energy storage performance, no practical research has been conducted. We aimed to develop a practical-scale aqueous-quinone-based organic supercapacitor. By connecting 12 cells of size 10 cm × 10 cm × 0.5 cm each in series, we fabricated a high-voltage (> 6 V) aqueous organic supercapacitor that can charge a smartphone at a 1 C rate. This is the first step in commercializing aqueous organic supercapacitors that could solve environmental problems, such as high CO2 emissions, air pollution by toxic metals, and limited electricity generation by renewable resources.
The Influence of the Geometrical Features on the Seismic Response of Historical Churches Reinforced by Different Cross Lam Roof-Solutions
Authors: Longarini Nicola , Crespi Pietro Giuseppe , Zucca Marco
Published: January 2022

Recent Italian earthquakes have shown the seismic vulnerability of many typical historical masonry churches characterized by one nave and wooden roofs. Under transverse earthquake the nave transverse response of this kind of churches can be influenced by the geometrical and material features. To increase the seismic performance, strengthening interventions aimed to pursue the global box-behavior by the realization of dissipative roof-structure represent a valid strategy especially for avoiding out-of-plane mechanisms. In this way, the roof structure must be able to represent a tool for the damped rocking of the perimeter walls. Cross-laminated timber panels (CLT) have been recently adopted as roof-diaphragm having shown valid ductile behavior in experimental tests, satisfying the conservative restoration criteria at the same time. In this paper, after a description of the numerical approach for the damped rocking mechanism for one nave configuration church, the effectiveness of different CLT based roof-diaphragms in the nave transverse response is investigated for four historical churches. The seismic responses are performed by comparative dynamic nonlinear analyses and the results are shown in terms of displacements and shear actions transferred to the façade. The influence of the geometrical features of the churches on the nave transversal response is deepened by sensitivity analyses with the aim to predict the displacements and shear variations under the same earthquake excitation.