bluuebunny/crossref_metadata_2025 huggingface dataset:
Flint Type Analysis at Late Acheulian Jaljulia (Israel), and Implications for the Origins of Prepared Core Technologies
Authors: Agam Aviad , Rosenberg-Yefet Tamar , Wilson Lucy , Shemer Maayan , Barkai Ran
Published: June 2022

Prepared Core Technologies, often considered a hallmark of the Middle Paleolithic Mousterian, have recently been observed, to some extent, in many late Lower Paleolithic Acheulian sites. This may indicate a Lower Paleolithic origin of the Levallois method, although the circumstances leading to its emergence, spread and assimilation are still debated. We aim at contributing towards this intriguing issue by studying patterns of flint procurement and exploitation at Late Acheulian Jaljulia (Israel; ∼500–300 kya). We classified artifacts into flint types, using four samples: a general sample, bifaces, “regular” cores with one/two striking platforms, and prepared cores, divided into proto-Levallois, prepared (general) and discoid cores. A geologic survey located potential flint sources, and a petrographic analysis was used to assign flint types to sources. Our results show that while local Turonian flint of the Bi’na Formation dominates the general sample, selectivity in using specific flint types was observed, including among local materials. While brecciated flint types are especially common among handaxes and discoid cores, among proto-Levallois and prepared cores (general), fine-textured homogenous flint types are more common, suggesting that such flint types are better-suited when improved control over the end-product was desired. Based on our results, and following previous suggestions, we support the hypothesis that prepared core technologies in the Levant did not originate from one single technological trajectory. We support the idea that the production of predetermined blanks was based on knowledge gathered from several technological trajectories, including mainly biface shaping and the production of flakes from regular cores. This novel method was most likely transmitted time and again between individuals, gradually adjusting it to produce improved end-products. We see these conclusions as additional support for the view of prepared core technologies at the Late Acheulian as a demonstration of cumulative culture, and the existence of high-fidelity social learning mechanisms in practice already during the late Lower Paleolithic of the Levant.
FC-ZSM: Spatiotemporal Downscaling of Rain Radar Data Using a Feature Constrained Zooming Slow-Mo Network
Authors: Chen Haoran , Qin Huawang , Dai Yuewei
Published: June 2022

This work studies the application of deep learning methods in the spatiotemporal downscaling of meteorological elements. Aiming at solving the problems of the single network structure, single input data feature type, and single fusion mode in the existing downscaling problem’s deep learning methods, a Feature Constrained Zooming Slow-Mo network is proposed. In this method, a feature fuser based on the deformable convolution is added to fully fuse dynamic and static data. Tested on the public rain radar dataset, we found that the benchmark network without feature fusion is better than the mainstream U-Net series networks and traditional interpolation methods in various performance indexes. After fully integrating various data features, the performance can be further improved.
The Utility and Development of the Competencies of Professional Psychology Rating Scales (COPPR)
Authors: Rice Kylie , Schutte Nicola S. , Cosh Suzanne M. , Rock Adam J. , Banner Stephanie E. , Sheen Jade
Published: June 2022

Competency-based professional psychology training is now common practice in many countries. An implication of competency-based training is the need to assess practitioner competence across multiple domains of practice; however, standardized measures of competence are limited. In Australia, currently there is no standardized, quantitative measure of professional competencies at registered psychologist level. The absence of a measure has implications for education, training, practice, and research in professional psychology. To address this gap, this article provides a conceptual overview of the utility and development of the Competencies of Professional Psychology Rating scales (COPPR), including the process of initial pre-test, pilot, and review. This developmental process resulted in the thematic identification of competencies within 11 domains of practice, and the creation of both COPPR-Self report and COPPR-Observer report versions. The pre-test provided content validity for the COPPR, and the initial results of the pilot test suggest strong convergent and divergent validity. The measure differentiated between novice and experienced practitioners, suggesting the scale is appropriate for use across career stages. The COPPR scales address the need for a standardized and quantitative measure across multiple domains of practice at registered psychologist level in Australia. The COPPR scales are intended to have utility across professional psychology student and supervisee performance evaluation, self-reflection for psychologists in practice, educational evaluation at professional psychology level, and various research contexts.
Case Report: High-Calorie Glucose Infusion and Tight Glycemic Control in Ameliorating Refractory Acidosis of Empagliflozin-Induced Euglycemic Diabetic Ketoacidosis
Authors: Wan Azman Siti Sanaa , Sukor Norlela , Abu Shamsi Muhammad Yusuf , Ismail Ilham , Kamaruddin Nor Azmi
Published: June 2022

The current widespread use of sodium-glucose co-transporter 2 (SGLT2) inhibitors has triggered an increase in reported cases of euglycemic diabetic ketoacidosis (EDKA), often characterized by a protracted metabolic acidosis that is resistant to conventional DKA treatment. We report a case of empagliflozin-induced EDKA with severe metabolic acidosis intractable to aggressive fluid resuscitation and boluses of bicarbonate infusion. Following the introduction of high-calorie glucose infusion coupled with tight glycemic control, the recalcitrant acidosis was successfully corrected. This is the first case report that adopts the above approach, representing a paradigm shift in the management of SGLT2 inhibitor-induced EDKA.
Early Thyroid Volume Reduction in Subacute Thyroiditis Can be a Potential Indicator for Hypothyroidism
Authors: Park Ji Yong , Choi Wonsuk , Hong A Ram , Yoon Jee Hee , Kim Hee Kyung , Kang Ho-Cheol
Published: June 2022

Background

Thyroid volume has been reported to decrease significantly after episodes of subacute thyroiditis (SAT); however, the relationship between thyroid volume and hypothyroidism remains unclear. This study assessed the association between thyroid volume changes and the hypothyroid phase in patients with SAT, a condition that can progress to persistent hypothyroidism.

Methods

This retrospective study evaluated 37 patients diagnosed with SAT at the Department of Endocrinology and Metabolism of Chonnam National University Hwasun Hospital (CNUHH) between 2016 and 2021. Since we could not determine the clinical characteristics of patients with SAT before their episodes, 120 healthy individuals who underwent thyroid ultrasonography during regular check-ups from 2019 to 2021 at CNUHH were selected for comparison. Subgroup analyses were performed on patients with SAT with and without the hypothyroid phase during their clinical course.

Results

Thyroid volume was significantly greater in SAT patients at the first visit than in controls (p<0.05), and it decreased constantly throughout the follow-up period. Subgroup analysis showed that the initial thyroid volumes were similar in patients with SAT with and without the hypothyroid phase. However, SAT patients with the hypothyroid phase had significantly smaller thyroid volumes at the 1 month (p=0.025) and 3 month (p=0.006) follow-up visits. The reduction rate of the thyroid volume was significantly different within the first month (p=0.009).

Conclusion

A greater reduction in thyroid volume in SAT patients within 1 month of episode had a higher chance of developing a subsequent hypothyroid phase, which can lead to persistent hypothyroidism. Serial thyroid ultrasonography in patients with SAT, especially within the first month, may help in predicting the disease course of SAT.
Study on the Production Decline Characteristics of Shale Oil: Case Study of Jimusar Field
Authors: Luo Shuanghan , Su Hao
Published: June 2022

The productivity of horizontal shale oil wells is low. To achieve cost-effective development, hydraulic fracturing techniques are often used. After hydraulic fracturing, wells have a high initial production rate. After a period of production, the production rate will decline rapidly and then remain low for an extended period of time. The study of the decline characteristics of horizontal wells is of great importance. We have collected development data from 94 horizontal wells in the Jimusar field. Some classical decline curve methods, such as the “power law–loss ratio” rate decline model, the stretch exponential equation, and the Duong decline curve, can be used to fit the production history. For example, Wells JHW018, JI172_H, and JI36_H were analyzed for production variations at different stages after the onset of production decline. On the basis of the performance of the parameters in typical wells, it was found that only Valko extended decline curves could be used to obtain satisfactory prediction results. A controlled fracture decline rate is proposed to describe the extent of the initial decline. The findings of this study can help for better predict of shale reservoir production after volume fracturing.
Two-Step Thermochemical CO2 Splitting Using Partially-Substituted Perovskite Oxides of La0.7Sr0.3Mn0.9X0.1O3 for Solar Fuel Production
Authors: Sawaguri Hiroki , Gokon Nobuyuki , Hayashi Kosuke , Iwamura Yoshikazu , Yasuhara Daichi
Published: June 2022

We investigated, herein, the redox activity of partial substitution of the B-site in a series of lanthanum/strontium-manganese-based (LSM) perovskite oxide, La0.7Sr0.3Mn0.9X0.1O3 for solar two-step thermochemical fuel production using concentrated solar radiation as an energy source. We systematically investigated the effects of partial substitution in LaSrMnO3 in terms of their kinetics behavior, oxygen/CO productivity, thermal reduction/oxidation temperatures. Furthermore, repeatability was evaluated and compared among the samples prepared using the same procedure and studied using the same test method. We observed and evaluated the long-term thermal stability of the redox activity and valence variation of the constituting ionic species of the perovskite in the two-step thermochemical CO2 splitting. From the perspectives of superior activity and long-term repeatability, Ni-, Co-, and Mg-substituted LSM perovskites are promising for thermochemical two-step CO2/H2O splitting to produce synthetic gas.
Energy and Exergy Based Thermal Analysis of a Solar Assisted Yogurt Processing Unit
Authors: Husnain Syed Nabeel , Amjad Waseem , Munir Anjum , Hensel Oliver
Published: June 2022

Energy and exergy based thermal analysis was conducted for a solar assisted yogurt processing unit capable of performing required heating and cooling processes in a single container. The system consisted of a round-shaped fermentation chamber connected with a hot water storage tank coupled with an evacuated tube collector and a pillow plate at the bottom of the chamber for cooling through a PV-operated refrigeration unit. Experiments were conducted using three different volumes of cow’s raw milk (30, 40, and 50 L). Energy analysis showed that 40% of the total energy was consumed during the heating process of raw milk in all cases, with an overall heat transfer efficiency of more than 80%. The specific product energy was calculated to be lower (485 kJ/kg) for the higher volume of milk (50 L). The exergy losses in the compressor of the refrigeration unit were calculated almost constant (1.0037 kW), while the exergy recovered during the refrigeration process was found in the range of 0.48–4.54 kJ/kg, 1.35–3.96 kJ/kg, and 0.84–6.18 kJ/kg for 50, 40, and 30 L of batches, respectively. Out of the total available power (2218 W) at the evacuated tube collector, 69.70% of energy was available for milk heating. The study is useful for designing optimization based on the distribution of energy and losses at various system components.
Study on Thermal Shock Failure Characteristics of RPV During IVR System Start-Up for Typical Advanced PWR
Authors: Zhu Dahuan , Sun Hongping , Zheng Bin , Huang Tao , Deng Jian , Xu Youyou , Luo Yuejian
Published: June 2022

When the large pressurized water reactor in-vessel retention (IVR) system is put into operation, the outer wall of the reactor pressure vessel (RPV) will experience severe temperature fluctuations and be subjected to high internal pressure loads at the same time. In order to ensure the structural integrity of the RPV under such conditions, first, through the severe accident system program, the case that has the greatest impact on the pressure-bearing thermal shock of the outer wall of the reactor pressure vessel was selected under the station blackout (SBO) accident. Then, based on this case, the fracture mechanics finite element method was used to calculate and evaluate the pressure thermal shock (PTS) of the RPV, and the final crack size at the end of the life of the core barrel and the lower head was obtained by fatigue crack expansion calculation. The maximum ratio of the stress intensity factor correction value and corresponding limit value under the PTS transient load is about 0.874, which meets the requirements of RCC-M specification. The results of the study indicate that the RPV will not experience fracture failure when the IVR system is put into service during the station blackout accident for the HPR1000 nuclear power plant.
An Analysis of Trends and Policies Promoting Alternative Fuel Vessels and Their Refueling Infrastructure in Europe
Authors: Gómez Vilchez Jonatan J. , Julea Andreea , Lodi Chiara , Marotta Alessandro
Published: June 2022

In recognition of the contribution of navigation activities to greenhouse gas emissions, there are ongoing efforts in Europe to deploy zero- and low-emission vessel technologies. The main objective of this paper is to present an assessment of waterborne transport decarbonization in Europe by analyzing key policies and trends. In particular, the policy actions put forward by the European Union Member States and the United Kingdom between 2016 and 2018, including refueling infrastructure, the market evolution of alternatively-powered vessels and their techno-economic barriers are investigated. Our work focuses on electricity, hydrogen and natural gas. Our findings suggest that the policy and market responses to promote alternative fuel and electric vessels in Europe so far have been rather weak and lag behind the efforts exerted on road transport. Our conclusion is that, besides further research and development, more ambitious policy measures are needed to keep the prospect of waterborne transport decarbonization within reach in Europe.
Condition Monitoring of Substation Equipment Based on Machine Vision
Authors: Wang Yiyao
Published: June 2022

This article aims to reach a global level by selecting a Harr-like function with the participation of bubbles and light and shadow on a digital display, improving the fitness function of the genetic algorithm and the crossover change function. The classifier support vector machine parameters were optimized by an improved genetic algorithm. Finally, compared to other identification algorithms, basic component analysis reduces the number of characters through support vector machines and recognizes the target character. The results of the experiment showed that eight sets of experiments were performed on each character. Experiments have shown that character recognition is best achieved using Harr-like software and then SVM classification based on improved gene algorithms. For small samples, the sorting speed is also fast, which can meet the time requirement. In addition, the historical state data of the transformer are analyzed, which is consistent with the manual monitoring results, but the time is shorter; machine vision has been shown to be effective in monitoring the condition of substation equipment.
Multi-Energy Acquisition Modeling and Control Strategy of Underwater Vehicles
Authors: Shen Shijun , Wang Chaofan , Qiu Zhiqiang , Ke Zhiwu , Gong Dawei
Published: June 2022

An autonomous underwater vehicle (AUV) can only carry limited energy for improved flexibility, but this brings the problem of working endurance. The acquisition of environmental energy by an underwater robot is a positive way to supplement energy and increase endurance. However, the instability and difference in power output capacity of different environmental energies will lead to low utilization of environmental energy. In this study, a multi-energy acquisition model is established to manage the AUV’s energy, which includes a heart rate sampling system, a mixed-energy circuit topology, and a maximum power output algorithm of environmental energy based on power trajectory tracking. The simulating results show that the power output control strategy can effectively improve the multi-energy acquisition and utilization efficiency of underwater vehicles, which has a positive significance and could improve endurance time.
Whole-Genome Resequencing of Xiangxi Cattle Identifies Genomic Diversity and Selection Signatures
Authors: Luo Xiaoyu , Li Jianbo , Xiao Chentong , Sun Luyang , Xiang Weixuan , Chen Ningbo , Lei Chuzhao , Lei Hong , Long Yun , Long Ting , Suolang Quji , Yi Kangle
Published: June 2022

Understanding the genetic diversity in Xiangxi cattle may facilitate our efforts toward further breeding programs. Here we compared 23 Xiangxi cattle with 78 published genomes of 6 worldwide representative breeds to characterize the genomic variations of Xiangxi cattle. Based on clustering models in population structure analysis, we displayed that Xiangxi cattle had a mutual genome ancestor with Chinese indicine, Indian indicine, and East Asian taurine. Population genetic diversity was analyzed by four methods (nucleotide diversity, inbreeding coefficient, linkage disequilibrium decay and runs of homozygosity), and we found that Xiangxi cattle had higher genomic diversity and weaker artificial selection than commercial breed cattle. Using four testing methods (θπ, CLR, FST, and XP-EHH), we explored positive selection regions harboring genes in Xiangxi cattle, which were related to reproduction, growth, meat quality, heat tolerance, and immune response. Our findings revealed the extent of sequence variation in Xiangxi cattle at the genome-wide level. All of our fruitful results can bring about a valuable genomic resource for genetic studies and breed protection in the future.
Evaluation of ABCA1 and FNDC3B Gene Polymorphisms Associated With Pseudoexfoliation Glaucoma and Primary Angle-Closure Glaucoma in a Saudi Cohort
Authors: Kondkar Altaf A. , Sultan Tahira , Azad Taif A. , Osman Essam A. , Almobarak Faisal A. , Lobo Glenn P. , Al-Obeidan Saleh A.
Published: June 2022

Objective: It is plausible that common disease mechanisms exist in glaucoma pathophysiology. Accordingly, we investigated the genetic association of two previously reported primary open-angle glaucoma (POAG)-related gene polymorphisms, rs2472493 (A > G) in ABCA1 and rs7636836 (C > T) in FNDC3B, in primary angle-closure glaucoma (PACG) and pseudoexfoliation glaucoma (PXG).

Methods: TaqMan genotyping was performed in a total of 442 subjects consisting of 246 healthy controls, 102 PACG patients, and 94 PXG patients. Statistical evaluations were performed to detect allelic and genotype association of the variants with the disease and clinical variables such as intraocular pressure (IOP) and cup/disc ratio.

Results: Overall, there was no allelic or genotype association of these variants in PACG and PXG. However, rs7636836[T] allele significantly increased the risk of PXG among men (p = 0.029, odds ratio [OR] = 2.69, 95% confidence interval = 1.11–6.51). Similarly, rs2472493 and rs7636836 genotypes also showed significant association with PXG among men in over-dominant model (p = 0.031, OR = 1.98, 95% CI = 1.06–3.71) and co-dominant model (p = 0.029, OR = 2.69, 95% CI = 1.11–6.51), respectively. However, none survived Bonferroni’s correction. Besides, the synergic presence of rs2472493[G] and rs7636836[T] alleles (G-T) was found to significantly increase the risk of PACG (p = 0.026, OR = 2.85, 95% CI = 1.09–7.46). No significant genotype influence was observed on IOP and cup/disc ratio.

Conclusion: Our results suggest that the polymorphisms rs2472493 in ABCA1 and rs7636836 in FNDC3B genes may be associated with PXG among men, and a G-T allelic combination may confer an increased risk of PACG in the middle-eastern Saudi cohort. Further research in a larger population-based sample is needed to validate these findings.
Long Noncoding RNA LINC00467: Role in Various Human Cancers
Authors: Wu Di , Li Rongfei , Liu Jingyu , Zhou Changcheng , Jia Ruipeng
Published: June 2022

Intricate genetic mutations promote the progression of different cancer types. Long noncoding RNAs (lncRNAs) have been widely demonstrated to participate in the genomic activities of various human cancers. Long intergenic non-coding RNA 467 (LINC00467) is an upregulated lncRNA in diverse diseases, especially in several types of cancers. Functional experiments of LINC00467 revealed that LINC00467 overexpression enhanced cell chemoresistance, proliferation, migration, and invasion in several types of cancers. Moreover, overexpressed LINC00467 was associated with a poor clinical prognosis. The present evidence suggests that LINC00467 may serve as a promising prognostic indicator and become a novel cancer therapeutic target. In this review, we introduce the biologic functions of lncRNAs and describe the molecular mechanism and clinical significance of LINC00467 in detail.
Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer
Authors: Dai Longfei , Wang Xu , Bai Tao , Liu Jianjun , Chen Bo , Yang Wenqi
Published: June 2022

Our study aimed to explore the effect of cellular senescence and to find potential therapeutic strategies for gastric cancer. Cellular senescence-related genes were acquired from the CellAge database, while gastric cancer data were obtained from GEO and TCGA databases. SMARCA4 had the highest mutation frequency (6%), and it was linked to higher overall survival (OS) and progression-free survival (PFS). The gastric cancer data in TCGA database served as a training set to construct a prognostic risk score signature, and GEO data were used as a testing set to validate the accuracy of the signature. Patients with the low-risk score group had a longer survival time, while the high-risk score group is the opposite. Patients with low-risk scores had higher immune infiltration and active immune-related pathways. The results of drug sensitivity analysis and the TIDE algorithm showed that the low-risk score group was more susceptible to chemotherapy and immunotherapy. Most patients with mutation genes had a lower risk score than the wild type. Therefore, the risk score signature with cellular senescence-related genes can predict gastric cancer prognosis and identify gastric cancer patients who are sensitive to chemotherapy and immunotherapy.
Cryptococcus neoformans Infection Induces IL-17 Production by Promoting STAT3 Phosphorylation in CD4+ T Cells
Authors: Guo Xiaoman , Mao Xinru , Tian Di , Liao Yixin , Su Bintao , Ye Chaoliang , Shi Dongling , Liu Tie Fu , Ling Yun , Hao Yi
Published: June 2022

Cryptococcus neoformansinfection in the central nervous system is a severe infectious disease with poor outcomes and high mortality. It has been estimated that there are 220,000 new cases each year. Over 90% ofC. neoformansmeningitis cases were diagnosed in AIDS patients with CD4+T cell count <100 cells/μl; however, the mechanism of cryptococcal meningitis in patients with normal immune functions remains unclear. IL-17 is a pro-inflammatory cytokine and plays an important role in anti-fungal immunity. Here we report that significantly high levels of IL-17 were predominantly detected in the cerebrospinal fluid of patients with either AIDS- or non-AIDS-associatedC. neoformansmeningitis but not in patients with tuberculous meningitis or non-neurosyphilis. Antifungal therapy minimized the IL-17 level in the cerebrospinal fluid. Anin vitromechanistic study showed thatC. neoformansstimulation of healthy peripheral blood mononuclear cells prompted IL-17 production, and CD4+T cells were the predominant IL-17-producing cells. IL-17 production byC. neoformansstimulation was STAT3 signaling dependent. Inhibition of STAT3 phosphorylation attenuated theC. neoformans-mediated IL-17 expression. Our data highlighted the significance of CD4+T cells in antifungal immunity and suggested IL-17 as a diagnostic biomarker ofC. neoformansinfection and STAT3 as a checkpoint for antifungal targeted therapies.
Clinical Significance of Serum Albumin and Implications of FcRn Inhibitor Treatment in IgG-Mediated Autoimmune Disorders
Authors: Ward E. Sally , Gelinas Deborah , Dreesen Erwin , Van Santbergen Jolien , Andersen Jan Terje , Silvestri Nicholas J. , Kiss Joseph E. , Sleep Darrell , Rader Daniel J. , Kastelein John J. P. , Louagie Els , Vidarsson Gestur , Spriet Isabel
Published: June 2022

Serum albumin (SA), the most abundant soluble protein in the body, maintains plasma oncotic pressure and regulates the distribution of vascular fluid and has a range of other important functions. The goals of this review are to expand clinical knowledge regarding the functions of SA, elucidate effects of dysregulated SA concentration, and discuss the clinical relevance of hypoalbuminemia resulting from various diseases. We discuss potential repercussions of SA dysregulation on cholesterol levels, liver function, and other processes that rely on its homeostasis, as decreased SA concentration has been shown to be associated with increased risk for cardiovascular disease, hyperlipidemia, and mortality. We describe the anti-inflammatory and antioxidant properties of SA, as well as its ability to bind and transport a plethora of endogenous and exogenous molecules. SA is the primary serum protein involved in binding and transport of drugs and as such has the potential to affect, or be affected by, certain medications. Of current relevance are antibody-based inhibitors of the neonatal Fc receptor (FcRn), several of which are under clinical development to treat immunoglobulin G (IgG)-mediated autoimmune disorders; some have been shown to decrease SA concentration. FcRn acts as a homeostatic regulator of SA by rescuing it, as well as IgG, from intracellular degradationviaa common cellular recycling mechanism. Greater clinical understanding of the multifunctional nature of SA and the potential clinical impact of decreased SA are needed; in particular, the potential for certain treatments to reduce SA concentration, which may affect efficacy and toxicity of medications and disease progression.
Vaccination Against SARS-CoV-2 in Lung Transplant Recipients: Immunogenicity, Efficacy and Safety
Authors: Svorcova Monika , Novysedlak Rene , Lischke Robert , Vachtenheim Jiri , Strizova Zuzana
Published: June 2022

Lung transplant (LuTx) recipients are considered to be at higher risk of developing serious illness from COVID-19. COVID-19 vaccines were shown in randomized clinical trials to substantially reduce the severity of COVID-19, however, patients receiving immunosuppressants were excluded from these trials. Observational studies report a proportion of solid organ transplant (SOT) recipients being able to mount sufficient titers of SARS-CoV-2 specific IgG antibodies, however, other studies demonstrate that more than 90% of the SOT recipients elicit neither humoral nor cellular immune response after vaccination. Currently, the third booster dose of the COVID-19 vaccines was shown to elicit strong immune responses and may, thus, represent a potent tool in the prevention of severe COVID-19 infection in SOT recipients, including patients after lung transplantation. To address the main challenges of SARS-CoV-2 vaccination in LuTx recipients in the era of COVID-19, we have closely collected all available data on the immunogenicity, efficacy and safety of COVID-19 vaccines in LuTx recipients.
CRISPR-Cas9 Targeting of the eIF4E1 Gene Extends the Potato Virus Y Resistance Spectrum of the Solanum tuberosum L. cv. Desirée
Authors: Lucioli Alessandra , Tavazza Raffaela , Baima Simona , Fatyol Karoly , Burgyan Jozsef , Tavazza Mario
Published: June 2022

Translation initiation factors and, in particular, the eIF4E family are the primary source of recessive resistance to potyviruses in many plant species. However, no eIF4E-mediated resistance to this virus genus has been identified in potato (Solanum tuberosum L.) germplasm. As in tomato, the potato eIF4E gene family consists of eIF4E1, its paralog eIF4E2, eIF(iso)4E, and nCBP. In tomato, eIF4E1 knockout (KO) confers resistance to a subset of potyviruses, while the eIF4E1/2 double KO, although conferring a broader spectrum of resistance, leads to plant developmental defects. Here, the tetraploid potato cv. Desirée owning the dominant Ny gene conferring resistance to potato virus Y (PVY) strain O but not NTN was used to evaluate the possibility to expand its PVY resistance spectrum by CRISPR-Cas9-mediated KO of the eIF4E1 susceptibility gene. After a double process of plant protoplast transfection-regeneration, eIF4E1 KO potatoes were obtained. The knockout was specific for the eIF4E1, and no mutations were identified in its eIF4E2 paralog. Expression analysis of the eIF4E family shows that the disruption of the eIF4E1 does not alter the RNA steady-state level of the other family members. The eIF4E1 KO lines challenged with a PVYNTN isolate showed a reduced viral accumulation and amelioration of virus-induced symptoms suggesting that the eIF4E1 gene was required but not essential for its multiplication. Our data show that eIF4E1 editing can be usefully exploited to broaden the PVY resistance spectrum of elite potato cultivars, such as Desirée, by pyramiding eIF4E-mediated recessive resistance.
The Effects of Carbon Source and Growth Temperature on the Fatty Acid Profiles of Thermobifida fusca
Authors: Winkelman Dirk C. , Nikolau Basil J.
Published: June 2022

The aerobic, thermophilic Actinobacterium, Thermobifida fusca has been proposed as an organism to be used for the efficient conversion of plant biomass to fatty acid-derived precursors of biofuels or biorenewable chemicals. Despite the potential of T. fusca to catabolize plant biomass, there is remarkably little data available concerning the natural ability of this organism to produce fatty acids. Therefore, we determined the fatty acids that T. fusca produces when it is grown on different carbon sources (i.e., glucose, cellobiose, cellulose and avicel) and at two different growth temperatures, namely at the optimal growth temperature of 50°C and at a suboptimal temperature of 37°C. These analyses establish that T. fusca produces a combination of linear and branched chain fatty acids (BCFAs), including iso-, anteiso-, and 10-methyl BCFAs that range between 14- and 18-carbons in length. Although different carbon sources and growth temperatures both quantitatively and qualitatively affect the fatty acid profiles produced by T. fusca, growth temperature is the greater modifier of these traits. Additionally, genome scanning enabled the identification of many of the fatty acid biosynthetic genes encoded by T. fusca.
Nanotechnology and Matrix Metalloproteinases in Cancer Diagnosis and Treatment
Authors: Gonzalez-Avila Georgina , Sommer Bettina , García-Hernandez A. Armando , Ramos Carlos , Flores-Soto Edgar
Published: June 2022

Cancer is still one of the leading causes of death worldwide. This great mortality is due to its late diagnosis when the disease is already at advanced stages. Although the efforts made to develop more effective treatments, around 90% of cancer deaths are due to metastasis that confers a systemic character to the disease. Likewise, matrix metalloproteinases (MMPs) are endopeptidases that participate in all the events of the metastatic process. MMPs’ augmented concentrations and an increased enzymatic activity have been considered bad prognosis markers of the disease. Therefore, synthetic inhibitors have been created to block MMPs’ enzymatic activity. However, they have been ineffective in addition to causing considerable side effects. On the other hand, nanotechnology offers the opportunity to formulate therapeutic agents that can act directly on a target cell, avoiding side effects and improving the diagnosis, follow-up, and treatment of cancer. The goal of the present review is to discuss novel nanotechnological strategies in which MMPs are used with theranostic purposes and as therapeutic targets to control cancer progression.
Potential Markers of Neurocognitive Disorders After Cardiac Surgery: A Bibliometric and Visual Analysis
Authors: Ji Linna , Li Fang
Published: June 2022

Background

Identifying useful markers is essential for diagnosis and prevention of perioperative neurocognitive disorders (PNDs). Here, we attempt to understand the research basis and status, potential hotspots and trends of predictive markers associated with PNDs after cardiac surgery via bibliometric analysis.

Methods

A total of 4,609 original research articles and reviews that cited 290 articles between 2001 and 2021 were obtained from the Web of Science Core Collection (WoSCC) as the data source. We used the software CiteSpace to generate and analyze visual networks of bibliographic information, including published years and journals, collaborating institutions, co-cited references, and co-occurring keywords.

Results

The number of annual and cumulative publications from 2001 to 2021 has been increasing on the whole. The Harvard Medical School was a very prolific and important institution in this field. The journal of Ann Thorac Surg (IF 4.33) had the most publications, while New Engl J Med was the most cited journal. Neuron-specific enolase (NSE), S100b and kynurenic acid (KYNA) were frequently discussed as possible markers of PNDs in many references. Cardiopulmonary bypass (CPB) was a keyword with high frequency (430) and sigma (6.26), and inflammation was the most recent burst keyword.

Conclusion

Potential markers of PNDs has received growing attention across various disciplines for many years. The research basis mainly focuses on three classic biomarkers of S100b, NSE, and KYNA. The most active frontiers are the inflammation-related biomarkers (e.g., inflammatory cells, cytokines, or mediators) and surgery-related monitoring parameters (e.g., perfusion, oxygen saturation, and the depth of anesthesia).
The Curved Openspace Algorithm and a Spike-Latency Model for Sonar-Based Obstacle Avoidance
Authors: Wen Chenxi , Horiuchi Timothy K.
Published: June 2022

The rapid control of a sonar-guided vehicle to pursue a goal while avoiding obstacles has been a persistent research topic for decades. Taking into account the limited field-of-view of practical sonar systems and vehicle kinematics, we propose a neural model for obstacle avoidance that maps the 2-D sensory space into a 1-D motor space and evaluates motor actions while combining obstacles and goal information. A two-stage winner-take-all (WTA) mechanism is used to select the final steering action. To avoid excessive scanning of the environment, an attentional system is proposed to control the directions of sonar pings for efficient, task-driven, sensory data collection. A mobile robot was used to test the proposed model navigating through a cluttered environment using a narrow field-of-view sonar system. We further propose a spiking neural model using spike-timing representations, a spike-latency memory, and a “race-to-first-spike” WTA circuit.
Treatment Response Prediction for Major Depressive Disorder Patients via Multivariate Pattern Analysis of Thalamic Features
Authors: Li Hanxiaoran , Song Sutao , Wang Donglin , Zhang Danning , Tan Zhonglin , Lian Zhenzhen , Wang Yan , Zhou Xin , Pan Chenyuan , Wu Yue
Published: June 2022

Antidepressant treatment, as an important method in clinical practice, is not suitable for all major depressive disorder (MDD) patients. Although magnetic resonance imaging (MRI) studies have found thalamic abnormalities in MDD patients, it is not clear whether the features of the thalamus are suitable to serve as predictive aids for treatment responses at the individual level. Here, we tested the predictive value of gray matter density (GMD), gray matter volume (GMV), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) of the thalamus using multivariate pattern analysis (MVPA). A total of 74 MDD patients and 44 healthy control (HC) subjects were recruited. Thirty-nine MDD patients and 35 HC subjects underwent scanning twice. Between the two scanning sessions, patients in the MDD group received selective serotonin reuptake inhibitor (SSRI) treatment for 3-month, and HC group did not receive any treatment. Gaussian process regression (GPR) was trained to predict the percentage decrease in the Hamilton Depression Scale (HAMD) score after treatment. The percentage decrease in HAMD score after SSRI treatment was predicted by building GPRs trained with baseline thalamic data. The results showed significant correlations between the true percentage of HAMD score decreases and predictions (p < 0.01, r2 = 0.11) in GPRs trained with GMD. We did not find significant correlations between the true percentage of HAMD score decreases and predictions in GMV (p = 0.16, r2 = 0.00), ALFF (p = 0.125, r2 = 0.00), and fALFF (p = 0.485, r2 = 0.10). Our results suggest that GMD of the thalamus has good potential as an aid in individualized treatment response predictions of MDD patients.
Computed Tomography and Magnetic Resonance Imaging in the Diagnosis of Cerebral Paragonimiasis in Children
Authors: Du Jinhui , Liu Likun , Fan Haiqing , Yu Yue , Luo Yilin , Yu Hui , Liao Xin
Published: June 2022

Objective

To investigate the computed tomography (CT) and magnetic resonance image (MRI) manifestations of cerebral paragonimiasis (CP) in children and to improve the understanding of the disease.

Methods

The cranial CT and MRI data of 12 children with positive intradermal tests for Paragonimus-specific antigens were retrospectively analyzed. Additionally, the lesion locations, morphology, and imaging characteristics were analyzed.

Results

The lesions were located in the cerebral parenchyma in 12 cases, with 10 in the supratentorial area and two in the subtentorial area, among which three cases included involvement of the meninges. The morphology of the lesions was mainly nodular and striated, with clear or indistinct borders and varying degrees of surrounding edema. The lesions showed isodense or slightly hyperdense opacities on the CT scans, heterogeneous equal or slightly decreased signal intensities on the T1-weighted images (T1WI), heterogeneous equal or slightly increased signal intensities on the T2-weighted images (T2WI), and equal or slightly increased signal intensities on the diffusion-weighted images (DWI) in MRIs. In four cases, the cyst wall showed equal T1 and short T2 signals, and in six cases, the characteristic “tunnel sign” and “worm-eaten sign” were visible. The contrast-enhanced MRI showed strip-shaped enhancement in five cases, nodular or ring-shaped enhancement in three cases, linear enhancement in two cases, and uneven enhancement in two cases. The meninges adjacent to the lesions were thickened with significant enhancement in four cases.

Conclusion

CP was mostly located in the cerebral parenchyma with involvement of the adjacent meninges. CT and MRI scans had certain imaging characteristics, and the MRI may particularly be of great value for the diagnosis of CP.
The Gain-of-Function R222S Variant in Scn11a Contributes to Visceral Hyperalgesia and Intestinal Dysmotility in Scn11aR222S/R222S Mice
Authors: Zhao Chenyu , Jin Jishuo , Hu Haoye , Zhou Xi , Shi Xiaoliu
Published: June 2022

Background

The SCN11A gene encodes the α-subunit of the Nav1. 9 channel, which is a regulator of primary sensory neuron excitability. Nav1.9 channels play a key role in somatalgia. Humans with the gain-of-function mutation R222S in SCN11A exhibit familial episodic pain. As already known, R222S knock-in mice carrying a mutation orthologous to the human R222S variant demonstrate somatic hyperalgesia. This study investigated whether Scn11aR222S/R222S mice developed visceral hyperalgesia and intestinal dysmotility.

Methods

We generated Scn11aR222S/R222S mice using the CRISPR/Cas9 system. The somatic pain threshold in Scn11aR222S/R222S mice was assessed by Hargreaves' test and formalin test. The excitability of dorsal root ganglia (DRG) neurons was assessed by whole-cell patch-clamp recording. Visceralgia was tested using the abdominal withdrawal reflex (AWR), acetic acid-induced writhing, and formalin-induced visceral nociception tests. Intestinal motility was detected by a mechanical recording of the intestinal segment and a carbon powder propelling test. The excitability of the enteric nervous system (ENS) could influence gut neurotransmitters. Gut neurotransmitters participate in regulating intestinal motility and secretory function. Therefore, vasoactive intestinal peptide (VIP) and substance P (SP) were measured in intestinal tissues.

Results

The R222S mutation induced hyperexcitability of dorsal root ganglion neurons in Scn11aR222S/R222S mice. Scn11aR222S/R222S mice exhibited somatic hyperalgesia. In addition, Scn11aR222S/R222S mice showed lower visceralgia thresholds and slowed intestinal movements when compared with wild-type controls. Moreover, Scn11aR222S/R222S mice had lower SP and VIP concentrations in intestinal tissues.

Conclusions

These results indicated that Scn11aR222S/R222S mice showed visceral hyperalgesia and intestinal dysmotility.
CONN-NLM: A Novel CONNectome-Based Non-local Means Filter for PET-MRI Denoising
Authors: Sun Zhuopin , Meikle Steven , Calamante Fernando
Published: June 2022

Background

Advancements in hybrid positron emission tomography-magnetic resonance (PET-MR) systems allow for combining the advantages of each modality. Integrating information from MRI and PET can be valuable for diagnosing and treating neurological disorders. However, combining diffusion MRI (dMRI) and PET data, which provide highly complementary information, has rarely been exploited in image post-processing. dMRI has the ability to investigate the white matter pathways of the brain through fibre tractography, which enables comprehensive mapping of the brain connection networks (the “connectome”). Novel methods are required to combine information present in the connectome and PET to increase the full potential of PET-MRI.

Methods

We developed a CONNectome-based Non-Local Means (CONN-NLM) filter to exploit synergies between dMRI-derived structural connectivity and PET intensity information to denoise PET images. PET-MR data are parcelled into a number of regions based on a brain atlas, and the inter-regional structural connectivity is calculated based on dMRI fibre-tracking. The CONN-NLM filter is then implemented as a post-reconstruction filter by combining the nonlocal means filter and a connectivity-based cortical smoothing. The effect of this approach is to weight voxels with similar PET intensity and highly connected voxels higher when computing the weighted-average to perform more informative denoising. The proposed method was first evaluated using a novel computer phantom framework to simulate realistic hybrid PET-MR images with different lesion scenarios. CONN-NLM was further assessed with clinical dMRI and tau PET examples.

Results

The results showed that CONN-NLM has the capacity to improve the overall PET image quality by reducing noise while preserving lesion contrasts, and it outperformed a range of filters that did not use dMRI information. The simulations demonstrate that CONN-NLM can handle various lesion contrasts consistently, as well as lesions with different levels of inter-connectivity.

Conclusion

CONN-NLM has unique advantages of providing more informative and accurate PET smoothing by adding complementary structural connectivity information from dMRI, representing a new avenue to exploit synergies between MRI and PET.
Molecular Signatures of Response to Mecasermin in Children With Rett Syndrome
Authors: Shovlin Stephen , Delepine Chloe , Swanson Lindsay , Bach Snow , Sahin Mustafa , Sur Mriganka , Kaufmann Walter E. , Tropea Daniela
Published: June 2022

Rett syndrome (RTT) is a devastating neurodevelopmental disorder without effective treatments. Attempts at developing targetted therapies have been relatively unsuccessful, at least in part, because the genotypical and phenotypical variability of the disorder. Therefore, identification of biomarkers of response and patients’ stratification are high priorities. Administration of Insulin-like Growth Factor 1 (IGF-1) and related compounds leads to significant reversal of RTT-like symptoms in preclinical mouse models. However, improvements in corresponding clinical trials have not been consistent. A 20-weeks phase I open label trial of mecasermin (recombinant human IGF-1) in children with RTT demonstrated significant improvements in breathing phenotypes. However, a subsequent randomised controlled phase II trial did not show significant improvements in primary outcomes although two secondary clinical endpoints showed positive changes. To identify molecular biomarkers of response and surrogate endpoints, we used RNA sequencing to measure differential gene expression in whole blood samples of participants in the abovementioned phase I mecasermin trial. When all participants (n = 9) were analysed, gene expression was unchanged during the study (baseline vs. end of treatment, T0–T3). However, when participants were subclassified in terms of breathing phenotype improvement, specifically by their plethysmography-based apnoea index, individuals with moderate-severe apnoea and breathing improvement (Responder group) displayed significantly different transcript profiles compared to the other participants in the study (Mecasermin Study Reference group, MSR). Many of the differentially expressed genes are involved in the regulation of cell cycle processes and immune responses, as well as in IGF-1 signalling and breathing regulation. While the Responder group showed limited gene expression changes in response to mecasermin, the MSR group displayed marked differences in the expression of genes associated with inflammatory processes (e.g., neutrophil activation, complement activation) throughout the trial. Our analyses revealed gene expression profiles associated with severe breathing phenotype and its improvement after mecasermin administration in RTT, and suggest that inflammatory/immune pathways and IGF-1 signalling contribute to treatment response. Overall, these data support the notion that transcript profiles have potential as biomarkers of response to IGF-1 and related compounds.