bluuebunny/crossref_metadata_2025 huggingface dataset:
Case Report: Delayed Guillain-Barré syndrome following trauma: A case series and manage considerations
Authors: Zhang Yiliu , Huang Chuxin , Lu Wei , Hu Qing
Published: August 2022

Aim

To analyze clinical associations between Guillain-Barré syndrome (GBS) and trauma.

Material and Methods

We retrospectively reviewed the data of eight patients with post-traumatic GBS between July 2011 and December 2018 at the Second Xiangya Hospital, China, and analyzed the triggers, clinical manifestation, examination results, treatment, prognosis, and potential mechanism related to post-traumatic GBS.

Results

The included patients had GBS preceded by no risk factors other than trauma. Their age ranged from 15 to 60 years (the median age was 52 years), and six patients were males. The potential traumatic triggers included spinal surgery (n = 2), high-intensity exercise (n = 2), traumatic brain injury (n = 1), excessive fatigue (n = 1), ischemic stroke (n = 1), and cardiopulmonary resuscitation (n = 1). The major manifestation was symmetrical limb weakness and/or numbness in all patients. The diagnosis of GBS was based on the results of electromyography, albumino-cytological dissociation, or antiganglioside antibody in cerebrospinal fluid, and other diseases were excluded. Immunotherapy improved symptoms, except in one patient who died.

Conclusions

Trauma is a probable risk factor for GBS that is very easily overlooked, thereby leading to misdiagnosis in clinical practice. We emphasize a new concept of post-traumatic GBS to promote doctors' awareness when they meet people with weakness and sensory deficits after trauma, which benefit early diagnosis, timely treatment, and reduced mortality rate of GBS.
Financial Distress and Psychological Well-Being During the COVID-19 Pandemic
Authors: Borrescio-Higa Florencia , Droller Federico , Valenzuela Patricio
Published: August 2022

Objective: We examine the impact of financial distress caused by the COVID-19 pandemic on mental health and psychological well-being.

Methods: We analyze cross-sectional survey data (n = 2,545) from the Life during Pandemic study in Chile. We estimate linear probability models to analyze the relationship between economic fragility, financial distress, and psychological well-being.

Results: Our findings show unemployment and income loss are highly predictive of experiencing a range of financial problems, such as a lack of savings, as well as difficulties paying bills, consumer debt, and mortgage loans. In turn, financial distress leads to a higher prevalence of poor well-being and mental health deterioration, and sleep problems.

Conclusion: Expansion of mental health assistance services are needed, as new diagnosis of mental health conditions has increased, but treatment has not, pointing to a barrier in the access to some mental health care services during the pandemic. Policies designed with the objective of improving financial education are necessary to increase precautionary savings and financial resilience, and alleviate the psychological burden of debt in the future.
Knowledge Gaps in End-of-Life Care and Planning Options Among Older Adults in Switzerland
Authors: Vilpert Sarah , Borasio Gian Domenico , Maurer Jürgen
Published: August 2022

Objectives: Good knowledge about end-of-life (EOL) care options helps in discussing and planning important aspects of the end of life in advance and contributes to improved well-being among dying patients and their families.

Methods: Our study explores knowledge levels of EOL care and planning options and its sociodemographic and regional patterning using nationally representative data from respondents aged 55+ of wave 6 of the Survey of Health, Ageing and Retirement in Europe in Switzerland (n = 2,199).

Results: Respondents answered correctly on average to just under four out of eight questions regarding EOL care options. Women, individuals with higher education levels, and those living with a partner showed a higher EOL knowledge score, whereas the score is lower among older adults (75+) and individuals living in French- and Italian-speaking Switzerland.

Conclusion: In view of the significant EOL knowledge gaps among older adults in Switzerland, further education efforts on EOL care options are needed, with particular attention to the population groups most affected.
Adherence to Coronavirus Disease 2019 Preventive Measures in a Representative Sample of the Population of the Canton of Vaud, Switzerland
Authors: Butty Audrey , Bühler Nolwenn , Pasquier Jérôme , Dupraz Julien , Faivre Vincent , Estoppey Sandrine , Rawlinson Cloé , Gonseth Nusslé Semira , Bochud Murielle , D’Acremont Valérie
Published: August 2022

Objectives: We quantified adherence to COVID-19 preventive measures and explored associated factors, after the first and during the second Swiss epidemic waves.

Methods: With an observational cohort study in a representative sample of individuals aged 15 years and more, we analysed the association between self-reported adherence to COVID-19 preventive measures (respect of simple hygiene rules; respect of social distancing rules; wearing a mask) and socio-demographic factors, the existence of a chronic disease, and the existence of a previous confirmed COVID-19 episode.

Results: Highest adherence was to simple hygiene rules, followed by social distancing rules and mask wearing, with a slight decrease for simple hygiene rules and a strong increase for mask wearing between visits. Men were significantly less likely to respect simple hygiene rules and wear a mask in public. Participants aged 65 years and more (versus 25–64 years) and those with at least one chronic disease (versus none) were two times more likely to respect social distancing rules and wear a mask.

Conclusion: Adherence to social distancing rules and mask wearing was rather poor, especially compared to other countries.
Exploring the Roles of Dispositional Mindfulness and Cognitive Reappraisal in the Relationship Between Neuroticism and Depression Among Postgraduate Students in China
Authors: Hou Lulu , Chang Lei , Chen Lirong , Fei Junfeng , Zhou Renlai
Published: August 2022

Objectives: Previous studies revealed a positive association between neuroticism and depression. This study further extended the previous findings by exploring the psychological processes underlying this association among Chinese postgraduates. Guided by theoretical models and empirical research, we proposed a multiple mediation and moderated mediation model to investigate the roles of dispositional mindfulness and cognitive reappraisal in the relationship between neuroticism and depression.

Methods: Using the NEO Five-Factor Inventory, Beck Depression Inventory, Mindfulness Attention Awareness Scale, and Emotion Regulation Questionnaire, 1103 first-year postgraduates at a comprehensive university in China were surveyed. Path analysis was adopted to test the models.

Results: The results showed that dispositional mindfulness mediated the association between neuroticism and depression. Further, this mediating effect was moderated by cognitive reappraisal, with this effect being stronger in individuals with low engagement in cognitive reappraisal.

Conclusion: The results support interrelations among neuroticism, depression, dispositional mindfulness, and cognitive reappraisal as moderated mediation rather than multiple mediation. The results enhance our understanding of psychological mechanisms between neuroticism and depression and provide suggestions for interventions to prevent or reduce depression in highly neurotic postgraduates.
Identification and Characterization of Genes Related to the Prognosis of Hepatocellular Carcinoma Based on Single-Cell Sequencing
Authors: Chen Wenbiao , Zhang Feng , Xu Huixuan , Hou Xianliang , Tang Donge , Dai Yong
Published: August 2022

The heterogeneity of hepatocellular carcinoma (HCC) highlights the importance of precision therapy. In recent years, single-cell RNA sequencing has been used to reveal the expression of genes at the single-cell level and comprehensively study cell heterogeneity. This study combined big data analytics and single-cell data mining to study the influence of genes on HCC prognosis. The cells and genes closely related to the HCC were screened through single-cell RNA sequencing (71,915 cells, including 34,414 tumor cells) and big data analysis. Comprehensive bioinformatics analysis of the key genes of HCC was conducted for molecular classification and multi-dimensional correlation analyses, and a prognostic model for HCC was established. Finally, the correlation between the prognostic model and clinicopathological features was analyzed. 16,880 specific cells, screened from the single-cell expression profile matrix, were divided into 20 sub-clusters. Cell typing revealed that 97% of these cells corresponded to HCC cell lines, demonstrating the high specificity of cells derived from single-cell sequencing. 2,038 genes with high variability were obtained. The 371 HCC samples were divided into two molecular clusters. Cluster 1 (C1) was associated with tumorigenesis, high immune score, immunotherapy targets (PD-L1 and CYLA-4), high pathological stage, and poor prognosis. Cluster 2 (C2) was related to metabolic and immune function, low immune score, low pathological stage, and good prognosis. Seven differentially expressed genes (CYP3A4, NR1I2, CYP2C9, TTR, APOC3, CYP1A2, and AFP) identified between the two molecular clusters were used to construct a prognostic model. We further validated the correlation between the seven key genes and clinical features, and the established prognostic model could effectively predict HCC prognosis. Our study identified seven key genes related to HCC that were used to construct a prognostic model through single-cell sequencing and big data analytics. This study provides new insights for further research on clinical targets of HCC and new biomarkers for clinical application.
Fabrication and Actuation Performance of Selective Laser Melting Additive-Manufactured Active Shape-Memory Alloy Honeycomb Arrays
Authors: Xu Yuesheng , Qiu Lei , Yuan Shenfang
Published: August 2022

Shape-memory alloy (SMA) honeycomb arrays have drawn worldwide attention for their potential active applications in smart morphing wings. However, the manufacturing of complex active SMA honeycomb arrays via conventional processes is a difficult task, and the actuation performance of the honeycomb arrays has not yet been well–investigated. In this work, the active SMA honeycomb arrays were fabricated by selective laser melting (SLM) additive manufacturing, and their actuation performance was investigated. The results show that the SLM–fabricated active SMA honeycomb arrays can generate obvious actuation performance during the transformation and exhibit a higher maximum actuation stress of 2.53 MPa at a R/t ratio of 4 and a tensile pre–strain of 35%. This research will contribute to the design and further improvement of active SMA honeycomb arrays based on SLM additive manufacturing, promoting the engineering applications for smart morphing wings.
Design of Cotton Recovery Device and Operation Parameters Optimization
Authors: Wang Hezheng , Cao Silin , Liu Yongrui , Yang Yuxin , Meng Xiangyu , Ji Peng
Published: August 2022

This research aims to optimize the working parameters of the sawtooth-type recovery device for cotton fallen on the ground to enhance cotton’s recovery effect. Firstly, the cotton-picking mechanism and cotton unloading mechanism of the cotton recovery device were designed. The movement trajectory of the serrated tooth end of the designed device, the cotton non-missing picking condition, and the cotton unloading condition were noted. Secondly, virtual simulation technology developed a model of the interaction process between the picking equipment and the soil. To determine the optimal combination of operating parameters for the recovery device, a three-factor, three-level response surface optimization test was conducted using Box–Behnken’s central combination method with operating machine speed, spacing between serrated discs, and serrated disc speed as the test factors, and the picking and impurity rate as the test indexes. In addition, a response surface regression model was developed to analyze the effects of the selected factors on the recovery unit, and each factor was optimized. When the picking and impurity rates were 79.09% and 35.12%, respectively, the optimal operating speed of the machine was 0.96 m/s, the spacing of the serrated discs was 40 mm, and the speed of the serrated discs was 68 rpm. The relative error between the experimental findings and the theoretical optimized values was less than 5%, and the optimized working parameters were reliable. This study can provide a reference for the device used to recover cotton that has fallen to the ground.
A Two-Point Ultrasound-Guided Injection Technique for the Transversus Thoracis Plane Block: A Canine Cadaveric Study
Authors: Alaman Manuel , Bonastre Cristina , González-Marrón Adrián , Maidanskaia Ekaterina Gámez , Laborda Alicia
Published: August 2022

The transversus thoracis plane (TTP) block desensitizes the intercostal nerves that run through this plane, providing analgesia to the ventral thoracic wall. Two canine cadavers were used to assess the feasibility of the transverse approach for the TTP (t-TTP) under ultrasound guidance to inject a solution at the third and sixth intercostal spaces. Eight cadavers were used to compare the spread and number of intercostal nerves that were stained when a low volume (LV) 0.5 mL kg−1 or a high volume (HV) 1 mL kg−1 of a dye-lidocaine solution was injected into the same hemithorax, injecting the volume equally at these intercostal spaces using the transverse approach. Fisher’s exact test and Wilcoxon signed-rank test were used to contrast the spread of the different volume solutions. The injectate spread along the TTP after all injections, dying a median number (range) of 3 (2–5) and 6 (5–6) nerves with LV and HV, respectively (p = 0.011). The two-point injection of HV, using the t-TTP approach, is a feasible technique that provides a consistent staining from T2 to T7 intercostal nerves. The injection of HV instead of LV increases the spread and enhances the number of stained intercostal nerves.
Accuracy Comparison among 3D-Printing Technologies to Produce Dental Models
Authors: Kim Jun , Pinhata-Baptista Otavio , Ayres Ana , da Silva Renan , Lima Jacqueline , Urbano Gabriel , No-Cortes Juliana , Vasques Mayra , Cortes Arthur
Published: August 2022

Background: Little is known on accuracy comparisons among 3D-printing trueness and precision to produce dental models. The purpose of this study was to investigate the accuracy of different 3D-printing technologies (SLA; DLP; LCD poly and monochromatic; and Polyjet). Methods: Fifteen models were manufactured by the five different 3D printers used in this study. The manufactured models were physically measured in the corresponding lengths for trueness and reproducibility. Means and standard deviations were obtained for the five computer-aided manufacturing (CAM) methods and compared. Results: No significant difference was found in the comparison between observers in all measurements performed with the different model algorithms. Pairwise Wilcoxon non-parametric test comparisons of trueness between 3D-printers revealed statistically significant differences between Stratasys versus Anycubic (p = 0.025) and Anycubic versus Form 2 (p = 0.048). Conclusion: The present findings suggest that the 3D-printing methods may have small significant discrepancies when compared to the original digital files, which may not be clinically relevant. In addition, there were no significant discrepancies among median measurements of each printing method (within 3D-printer analysis), which suggests that, for dental casts, all of the studied devices performed similarly.
Using Chatbots as AI Conversational Partners in Language Learning
Authors: Belda-Medina Jose , Calvo-Ferrer José Ramón
Published: August 2022

Recent advances in Artificial Intelligence (AI) and machine learning have paved the way for the increasing adoption of chatbots in language learning. Research published to date has mostly focused on chatbot accuracy and chatbot–human communication from students’ or in-service teachers’ perspectives. This study aims to examine the knowledge, level of satisfaction and perceptions concerning the integration of conversational AI in language learning among future educators. In this mixed method research based on convenience sampling, 176 undergraduates from two educational settings, Spain (n = 115) and Poland (n = 61), interacted autonomously with three conversational agents (Replika, Kuki, Wysa) over a four-week period. A learning module about Artificial Intelligence and language learning was specifically designed for this research, including an ad hoc model named the Chatbot–Human Interaction Satisfaction Model (CHISM), which was used by teacher candidates to evaluate different linguistic and technological features of the three conversational agents. Quantitative and qualitative data were gathered through a pre-post-survey based on the CHISM and the TAM2 (technology acceptance) models and a template analysis (TA), and analyzed through IBM SPSS 22 and QDA Miner software. The analysis yielded positive results regarding perceptions concerning the integration of conversational agents in language learning, particularly in relation to perceived ease of use (PeU) and attitudes (AT), but the scores for behavioral intention (BI) were more moderate. The findings also unveiled some gender-related differences regarding participants’ satisfaction with chatbot design and topics of interaction.
Planning Urban Internal Transport Based on Cell Phone Data
Authors: Xu Hong , Zhao Jin
Published: August 2022

Based on cell phone data, mining residents’ travel characteristics and regional traffic connection characteristics has become an important technology for urban road traffic planning research. Based on cell phone data extracted from Wuxue City, this paper proposes an operability method for mining regional traffic contact intensity information based on cell phone data and an urban road network evaluation method. We analyze the travel characteristics of residents and the current situation of traffic connections between towns by constructing a planning road model of Wuxue city and find that the traffic connection of Wuxue city shows a spatial development pattern with Wuxue street as the intersection, one horizontal and one vertical, and the traffic accessibility gradually decreases from south to north. We analyze the spatial characteristics and problems of the planning of the road network in Wuxue and propose a modification plan. We verify the reasonableness of the modified plan by calculating traffic accessibility and road density. The research provides a new way to obtain spatio-temporal information about passenger flows by applying cell phone data to urban road planning.
The Comparison of the Level of Aggressiveness of Oyama Karate and Mixed Martial Art Fighters
Authors: Rydzik Łukasz
Published: August 2022

Background: Aggressive behavior is inherent in many sports, especially martial arts. It is usually considered undesirable; nevertheless, in some cases, it can be a motivating factor in a competition. It is important to distinguish types of aggression. The aim of this study was to compare the level of aggressiveness between athletes practicing mixed martial arts (MMA) and Oyama Karate. Methods: In total, 30 Oyama Karate and 30 mixed martial art athletes were asked about their aggressive behavior. The Buss–Perry Aggression Questionnaire was used in the study. Results were statistically analyzed. Results: There were statistically significant differences between the performance of Oyama Karate and MMA athletes (p < 0.001), which occurred in all the types of aggression tested (anger, physical aggression, hostility, and verbal aggression). Hence, the results of the study confirmed the accuracy of the research hypothesis that the level of intensity of aggression is higher in MMA fighters than in full-contact Oyama Karate fighters. Conclusions: Physical aggression was dominant in the evaluated fighters. The greatest difference between both groups of fighters was in verbal aggression, whereas the smallest was in hostility.
Short Takeoff and Landing Strategy for Small-Scale Thrust-Vectoring Vertical/Short Takeoff and Landing Vehicles
Authors: Wang Zian , Gong Zheng , Mao Shengchen , Zhou Zan , Chen Yongliang , Zhang Tongren
Published: August 2022

This work provides a feasible solution to the shipborne short landing problem for thrust-vectoring V/STOL vehicles. The short takeoff and shipborne rolling vertical landing strategy was designed in this work. First, the strategy design reference was established by flying performance and mission requirements, including the short takeoff and landing performance, deceleration performance, trajectory stability, velocity stability, and conversion corridor, using attainable equilibrium set methods based on the six dimensions of freedom model of the study object. Then, a piecewise short takeoff landing strategy was designed based on the references, together with a nonlinear dynamic inverse-based control designed frame for strategy execution. Finally, the hardware-in-loop Monte-Carlo simulation was implemented for the strategy feasibility verification. The proposed short takeoff and landing strategy satisfies the shipborne short takeoff and landing mission requirements. The short takeoff shortens the taxiing distance by 40% compared to a normal takeoff. With a 20% perturbance on all model parameters, the touchdown speed can be controlled to 14 ± 1 m/s, and the landing point position can be constrained inside a 5 m radius circle with almost zero lateral displacements.
Safety Assessment of Organic High-Protein Bars during Storage at Ambient and Refrigerated Temperatures
Authors: Trząskowska Monika , Neffe-Skocińska Katarzyna , Okoń Anna , Zielińska Dorota , Szydłowska Aleksandra , Łepecka Anna , Kołożyn-Krajewska Danuta
Published: August 2022

This study aimed to assess the safety characteristics of organic high-protein bars (HPB) during storage at ambient and refrigerated temperatures based on selected microbiological and chemical indicators. After production, the total number of microorganisms ranged from 3.90–4.26 log CFU/g;. The Enterobacteriaceae family was present at 2.81–3.32 log CFU/g, and the count of yeasts and moulds was 2.61–3.99 log CFU/g. No Salmonella sp. was found in 25 g of the product. Bacillus cereus was present in samples B1 and B2. Staphylococcus aureus was presented in samples below the detection limit (<2 log CFU/g). During the storage of products, the number of microorganisms varied. After production and storage, in all samples of HPB, the amount of mycotoxins was below the detection limit. The presence of histamine and tryptamine was not found in the HPB throughout the study period. Regarding TBARS, it can be concluded that the use of prunes and oat flakes (B2 bar composition) in the production of organic bars, and refrigerated storage, reduces the degree of fat oxidation. Among the tested variants, the composition of the B3 bar seemed to be the safest and worth further research, mainly due to the lower frequency of undesirable microorganisms. The protective antioxidative effect of prunes and oat flakes in bars stored at 22 °C indicates the value of the composition of bar B2. The appropriate composition modifications and the use of heat treatment proved to be effective in improving the safety characteristics of HPB. Relying on the results it is possible to store HPB for at least 3 months. Next to standard safety parameters, the unique and effective to increase the safety of HPB is controlling the presence of B. cereus and other low water activity (aw) resistant microorganisms.
Effect of Particle Sizes and Dosages of Rubber Waste on the Mechanical Properties of Rubberized Concrete Composite
Authors: Abbas Safeer , Fatima Ayesha , Kazmi Syed Minhaj Saleem , Munir Muhammad Junaid , Ali Shahid , Rizvi Mujasim Ali
Published: August 2022

The utilization of waste rubber in concrete composites has gained more attention nowadays owing to its enhanced engineering properties and eco-friendly viability. This study explored the effect of waste rubber sizes and its contents on the mechanical properties of developed concrete composites. Rubber waste with various particle sizes (R1, R5 and R10) was replaced with 10%, 20% and 30% of aggregates by volume, and the workability, compressive, splitting tensile and flexural strengths and impact resistance of the developed composite were investigated. An increase in the waste rubber contents decreased the slump of the composite due to the rougher surface of the rubber particles. The reduction in the slump was more pronounced for mixtures with smaller rubber sizes. Similarly, an increase in rubber contents decreased the compressive strength, tensile strength and flexural strength because of the lower stiffness of the used rubber waste and the poor bond between the rubber particles and the matrix. For instance, an approximately 27% decrease in compressive strength was observed for the mixture incorporating 20% of R1 rubber compared to that of the control mixture without rubber. It was observed that the incorporation of rubber waste in the concrete composite led to an enhanced resilience toward impact loading due to the improved energy dissipation mechanism offered by the rubberized concrete composite. For example, 13 blows in the case of 30% of the rubber replacement were required for the final crack as compared to 5 blows for the control mixture without rubber. It can be concluded that the choice of the optimal replacement ratio and the size of the rubber yield the developed rubberized concrete composite with a desirable strength and impact resistance.
Multi-Metal Distribution Patterns in Soils of the Sacramento River Floodplain and Their Controlling Factors
Authors: Lotz Tom , Su Shoubao , Opp Christian
Published: August 2022

Metal contamination, especially in river floodplain soils, can have detrimental effects on human health. Much research has been conducted to describe the distribution patterns of metals and the factors involved in these patterns. However, most studies focus on the distribution of individual metals in soils, not on the co-occurrence of metals, and on a selection of metals associated with anthropogenic sources known to have especially severe effects; this had led to a lack of knowledge about many other metals with potentially harmful effects. Therefore, this study aimed to identify the multi-metal distribution patterns of 38 metals in the Sacramento River floodplain and find their controlling factors. We found 484 significant correlations between metal distributions. Less commonly studied metals, such as gallium, lanthanum, scandium, and vanadium, had more than 25 correlations each. In total, 13 individual metal patterns described the spatial distribution of 22 metals. Three multi-metal patterns were extracted, explaining 86.9% of the spatial variation of the individual patterns. The most important factors were the distance to specific streams due to emission and transport processes in their watersheds, and local soil properties. We conclude that multi-metal distribution patterns hold more information than individual metal patterns, contributing to the gathering of information about less commonly sampled metals and allowing more specific source identification.
Design and Performance of Photon Imaging Detector Based on Cross-Strip Anode with Charge Induction
Authors: Jiang Zhongzhi , Ni Qiliang
Published: August 2022

Imaging detectors based on a microchannel plate (MCP) and charge division anode with charge induction have broad applications in particles (photons, neutrons, ions, and electrons) detection. However, the application of a charge induction readout mode is mostly focused on planar anodes, and there are few reports on double-layer cross-strip (XS) anodes with high spatial resolution and low gain requirements. In this paper, we design the parameters of the resistive layer and XS anode by theoretical derivation and the three-dimensional finite element method, including the sheet resistance, substrate thickness, strip width, and insulation thickness. The performance of the XS detector is characterized with the help of a resolution target and full field illumination using three different centroid algorithms. We conclude that the modified center of gravity (MCoG) has best imaging performance, which achieves a spatial resolution of 44.2 μm with a periodic distortion about 25.8%.
Spatiotemporal Trends and Influencing Factors of PM2.5 Concentration in Eastern China from 2001 to 2018 Using Satellite-Derived High-Resolution Data
Authors: Wang Weihang , He Qingqing , Gao Kai , Zhang Ming , Yuan Yanbin
Published: August 2022

Ambient exposure to fine particulate matter (PM2.5) in eastern China, a densely populated region with very high-level PM2.5 pollution, has attracted great concern from the public, government, and scientific community. By taking advantage of advanced statistical methods and a high-resolution PM2.5 dataset, this study explicitly investigated the spatiotemporal changes in PM2.5 in eastern China from 2001 to 2018 at multiple spatial and temporal scales and examined its links with natural and socioeconomic factors to explore their effects on PM2.5 changes. This study found that the PM2.5 concentration in most of eastern China declined recently, while most of the discernable decreasing trends occurred in the southern and western areas of the study domain, and the statistically significant increasing trends were primarily in the North China Plain. The influencing factors analysis found that, among the selected four natural and five anthropogenic factors, temperature, and population density exerted more potent effects than the other influencing factors, and all the influencing factors were found to impose complex effects on the PM2.5 concentration over space and time. Our study draws a complete picture of the changes in PM2.5 and its possible influences, which could guide future actions to mitigate PM2.5 pollution in eastern China.
During HCV DAA Therapy Plasma Mip1B, IP10, and miRNA Profile Are Distinctly Associated with Subsequent Diagnosis of Hepatocellular Carcinoma: A Pilot Study
Authors: Damjanovska Sofi , Alao Hawwa , Zebrowski Elizabeth , Kowal Corinne , Kostadinova Lenche , Davitkov Perica , Falck-Ytter Yngve , Shive Carey L. , Cartwright Michael , Richardson Brian , Wald David , Cameron Mark , Valadkhan Saba , Anthony Donald D.
Published: August 2022

Background: Hepatitis C virus (HCV) therapy lowers risk of hepatocellular carcinoma (HCC). Little is known about factors driving/preceding HCC in treated persons. MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) regulate host response and pathogenesis of disease. We investigated plasma levels of these RNAs and select serum markers before, during, and after HCV therapy, preceding HCC. Methods: Of 187 DAA treated HCV patients where therapy oriented longitudinal sampling was performed at a time without HCC diagnosis, 9 were subsequently diagnosed with HCC within 2 years of therapy. They were matched with 7 patients not diagnosed with HCC over the same time period. RNASeq was performed on plasma, and serum was assessed for biomarkers of inflammation by ELISA. Results: HCC diagnosis was 19 months (6–28) after therapy start in the HCC group. 73 and 63 miRs were differentially expressed at baseline (before DAA therapy) and 12 weeks after DAA therapy comparing HCC and non-HCC groups. Several lncRNA- showed differential expression as well. Several miRNA suppressors of cancer-related pathways, lncRNA- and mRNA-derived stabilized short RNAs were consistently absent in the plasma of patients who developed HCC. Serum IP10, and MCP-1 level was higher in the HCC group 12 weeks after therapy, and distinct miRNAs correlated with IP10 and MCP-1. Finally, in a focused analysis of 8 miRNAs best associated with HCC we observed expression of mi576 and mi-5189 correlation with expression of a select group of PBMC mRNA. Conclusions: These results are consistent with complex interplay between RNA-mediated host immune regulation and cancer suppression, strikingly skewed 12 weeks following therapy, prior to HCC diagnosis.
Impact of SARS-CoV-2 RBD Mutations on the Production of a Recombinant RBD Fusion Protein in Mammalian Cells
Authors: Gerez Guillaume , Martinez Jerome , Steinbrugger Christophe , Bouanich Sandra , Dimino Johanna , Piegay Corine , Combe Maxime , Berthier Franck , Daniel Soizic
Published: August 2022

SARS-CoV-2 receptor-binding domain (RBD) is a major target for the development of diagnostics, vaccines and therapeutics directed against COVID-19. Important efforts have been dedicated to the rapid and efficient production of recombinant RBD proteins for clinical and diagnostic applications. One of the main challenges is the ongoing emergence of SARS-CoV-2 variants that carry mutations within the RBD, resulting in the constant need to design and optimise the production of new recombinant protein variants. We describe here the impact of naturally occurring RBD mutations on the secretion of a recombinant Fc-tagged RBD protein expressed in HEK 293 cells. We show that mutation E484K of the B.1.351 variant interferes with the proper disulphide bond formation and folding of the recombinant protein, resulting in its retention into the endoplasmic reticulum (ER) and reduced protein secretion. Accumulation of the recombinant B.1.351 RBD-Fc fusion protein in the ER correlated with the upregulation of endogenous ER chaperones, suggestive of the unfolded protein response (UPR). Overexpression of the chaperone and protein disulphide isomerase PDIA2 further impaired protein secretion by altering disulphide bond formation and increasing ER retention. This work contributes to a better understanding of the challenges faced in producing mutant RBD proteins and can assist in the design of optimisation protocols.
A Human Stem Cell-Derived Neurosensory–Epithelial Circuitry on a Chip to Model Herpes Simplex Virus Reactivation
Authors: Mazzara Pietro Giuseppe , Criscuolo Elena , Rasponi Marco , Massimino Luca , Muggeo Sharon , Palma Cecilia , Castelli Matteo , Clementi Massimo , Burioni Roberto , Mancini Nicasio , Broccoli Vania , Clementi Nicola
Published: August 2022

Both emerging viruses and well-known viral pathogens endowed with neurotropism can either directly impair neuronal functions or induce physio-pathological changes by diffusing from the periphery through neurosensory–epithelial connections. However, developing a reliable and reproducible in vitro system modeling the connectivity between the different human sensory neurons and peripheral tissues is still a challenge and precludes the deepest comprehension of viral latency and reactivation at the cellular and molecular levels. This study shows a stable topographic neurosensory–epithelial connection on a chip using human stem cell-derived dorsal root ganglia (DRG) organoids. Bulk and single-cell transcriptomics showed that different combinations of key receptors for herpes simplex virus 1 (HSV-1) are expressed by each sensory neuronal cell type. This neuronal–epithelial circuitry enabled a detailed analysis of HSV infectivity, faithfully modeling its dynamics and cell type specificity. The reconstitution of an organized connectivity between human sensory neurons and keratinocytes into microfluidic chips provides a powerful in vitro platform for modeling viral latency and reactivation of human viral pathogens.
Molecularly Imprinted Nanoparticles towards MMP9 for Controlling Cardiac ECM after Myocardial Infarction: A Predictive Experimental-Computational Chemistry Investigation
Authors: Villano Anthea , Barcaro Giovanni , Monti Susanna , Barbani Niccoletta , Rizzo Antonio , Rossin Daniela , Rastaldo Raffaella , Giachino Claudia , Cristallini Caterina
Published: August 2022

The recent advances in nanotechnology are revolutionizing preventive and therapeutic approaches to treating cardiovascular diseases. Controlling the extracellular matrix metalloproteinase (MMP) activation and expression in the failing human left ventricular myocardium represents a significant therapeutic target for heart disease. In this study, we used molecularly imprinting polymers (MIPs) to restore the correct balance between MMPs and their tissue inhibitors (TIMPs), and explored the potential of this technique exhaustively through chemical synthesis, physicochemical and biological characterizations, and computational chemistry methods. By molecular dynamics simulations based on classical force fields, we simulated the early stages of the imprinting process in solution disclosing the pivotal interaction established between the monomers and the MMP9 protein template. The average interaction energies of methacrylic acid (MAA) and poly (ethylene glycol) ethyl ether methacrylate (PEG) units were in the ranges 17–22 and 30–37 kcal/mol, respectively. At low coverage, the PEG monomers seemed firmly anchored to the protein surface and were not displaced by water, while only about 20% of MAA was replaced by water. The synthesis of MIPs was successfully with a monomer conversion higher than 99% and the production of spherical particles with average diameter of 344 ± 33 nm. HPLC analysis showed a specific recognition factor of MMP9 on MIPs of about 1.3. FT-IR Chemical Imaging confirmed the mechanisms necessary to generate a “selective memory” of the MIPs towards the enzyme. HPLC results indicated that the rebound amount of both TIMP1 and MMP2 to MIPs is lower than that of the template, showing a selectivity factor of 2.1 and 2.3, respectively. Preliminary tests on the effect of MIPs on H9C2 cells revealed that this treatment has no cytotoxic effects.
Membranolytic Mechanism of Amphiphilic Antimicrobial β-Stranded [KL]n Peptides
Authors: Schweigardt Fabian , Strandberg Erik , Wadhwani Parvesh , Reichert Johannes , Bürck Jochen , Cravo Haroldo L. P. , Burger Luisa , Ulrich Anne S.
Published: August 2022

Amphipathic peptides can act as antibiotics due to membrane permeabilization. KL peptides with the repetitive sequence [Lys-Leu]n-NH2 form amphipathic β-strands in the presence of lipid bilayers. As they are known to kill bacteria in a peculiar length-dependent manner, we suggest here several different functional models, all of which seem plausible, including a carpet mechanism, a β-barrel pore, a toroidal wormhole, and a β-helix. To resolve their genuine mechanism, the activity of KL peptides with lengths from 6–26 amino acids (plus some inverted LK analogues) was systematically tested against bacteria and erythrocytes. Vesicle leakage assays served to correlate bilayer thickness and peptide length and to examine the role of membrane curvature and putative pore diameter. KL peptides with 10–12 amino acids showed the best therapeutic potential, i.e., high antimicrobial activity and low hemolytic side effects. Mechanistically, this particular window of an optimum β-strand length around 4 nm (11 amino acids × 3.7 Å) would match the typical thickness of a lipid bilayer, implying the formation of a transmembrane pore. Solid-state 15N- and 19F-NMR structure analysis, however, showed that the KL backbone lies flat on the membrane surface under all conditions. We can thus refute any of the pore models and conclude that the KL peptides rather disrupt membranes by a carpet mechanism. The intriguing length-dependent optimum in activity can be fully explained by two counteracting effects, i.e., membrane binding versus amyloid formation. Very short KL peptides are inactive, because they are unable to bind to the lipid bilayer as flexible β-strands, whereas very long peptides are inactive due to vigorous pre-aggregation into β-sheets in solution.
Associations of Texture Features of Proton Density Fat Fraction Maps between Lumbar Vertebral Bone Marrow and Paraspinal Musculature
Authors: Leonhardt Yannik , Dieckmeyer Michael , Zoffl Florian , Feuerriegel Georg C. , Sollmann Nico , Junker Daniela , Greve Tobias , Holzapfel Christina , Hauner Hans , Subburaj Karupppasamy , Kirschke Jan S. , Karampinos Dimitrios C. , Zimmer Claus , Makowski Marcus R. , Baum Thomas , Burian Egon
Published: August 2022

Chemical shift encoding-based water–fat MRI (CSE-MRI)-derived proton density fat fraction (PDFF) has been used for non-invasive assessment of regional body fat distributions. More recently, texture analysis (TA) has been proposed to reveal even more detailed information about the vertebral or muscular composition beyond PDFF. The aim of this study was to investigate associations between vertebral bone marrow and paraspinal muscle texture features derived from CSE-MRI-based PDFF maps in a cohort of healthy subjects. In this study, 44 healthy subjects (13 males, 55 ± 30 years; 31 females, 39 ± 17 years) underwent 3T MRI including a six-echo three-dimensional (3D) spoiled gradient echo sequence used for CSE-MRI at the lumbar spine and the paraspinal musculature. The erector spinae muscles (ES), the psoas muscles (PS), and the vertebral bodies L1-4 (LS) were manually segmented. Mean PDFF values and texture features were extracted for each compartment. Features were compared between males and females using logistic regression analysis adjusted for age and body mass index (BMI). All texture features of ES except for Sum Average were significantly (p < 0.05) different between men and women. The three global texture features (Variance, Skewness, Kurtosis) for PS as well as LS showed a significant difference between male and female subjects (p < 0.05). Mean PDFF measured in PS and ES was significantly higher in females, but no difference was found for the vertebral bone marrow’s PDFF. Partial correlation analysis between the texture features of the spine and the paraspinal muscles revealed a highly significant correlation for Variance(global) (r = 0.61 for ES, r = 0.62 for PS; p < 0.001 respectively). Texture analysis using PDFF maps based on CSE-MRI revealed differences between healthy male and female subjects. Global texture features in the lumbar vertebral bone marrow allowed for differentiation between men and women, when the overall PDFF was not significantly different, indicating that PDFF maps may contain detailed and subtle textural information beyond fat fraction. The observed significant correlation of Variance(global) suggests a metabolic interrelationship between vertebral bone marrow and the paraspinal muscles.
Altered Regional Homogeneity and Amplitude of Low-Frequency Fluctuations Induced by Electroconvulsive Therapy for Adolescents with Depression and Suicidal Ideation
Authors: Li Xiao , Chen Xiaolu , Zhou Yi , Dai Linqi , Cui Long-Biao , Yu Renqiang , Ai Ming , Huang Qian , Tian Yu , Ming Mei , Kuang Li
Published: August 2022

Resting-state functional magnetic resonance imaging (rs-fMRI) was used to investigate the effects of electroconvulsive therapy (ECT) causing brain function changes in adolescents who suffered from depression and suicidal ideation (SI). A total of 30 patients (MDDs) and 25 healthy controls (HCs) matched by gender, age, and education level were enrolled. The amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (ReHo) were used to compare differences between HCs and MDDs at baseline, and differences in ALFF and ReHo pre/post ECT in MDDs. Pearson correlation analysis was used to evaluate the relationship between altered brain function and clinical symptoms. At baseline, MDDs showed decreased ALFF in the left inferior temporal gyrus and right amygdala, decreased ReHo in left inferior temporal gyrus, and increased ReHo in the right inferior frontal gyrus, opercular part and left middle occipital gyrus. After ECT, MDDs showed increased ALFF in the right middle occipital gyrus, decreased ALFF in left temporal pole, left inferior frontal gyrus, opercular part, and right frontal middle gyrus, increased ReHo in the right middle occipital gyrus, and left inferior temporal gyrus. Pearson correlation found HAMD scores at baseline were negatively correlated with ALFF in the left inferior temporal gyrus, and HAMD and BSSI scores after ECT were negatively correlated with ALFF in the right middle occipital gyrus. The abnormal activities of amygdala, inferior temporal gyrus and middle occipital gyrus might be related to depressive and suicidal symptoms in adolescents.
The Remapping of Peripersonal Space in a Real but Not in a Virtual Environment
Authors: Ferroni Francesca , Gallese Vittorio , Soccini Agata Marta , Langiulli Nunzio , Rastelli Francesca , Ferri Donato , Bianchi Francesco , Ardizzi Martina
Published: August 2022

One of the most surprising features of our brain is the fact that it is extremely plastic. Among the various plastic processes supported by our brain, there is the neural representation of the space surrounding our body, the peripersonal space (PPS). The effects of real-world tool use on the PPS are well known in cognitive neuroscience, but little is still known whether similar mechanisms also govern virtual tool use. To this purpose, the present study investigated the plasticity of the PPS before and after a real (Experiment 1) or virtual motor training with a tool (Experiment 2). The results show the expansion of the PPS only following real-world tool use but not virtual use, highlighting how the two types of training potentially rely on different processes. This study enriches the current state of the art on the plasticity of PPS in real and virtual environments. We discuss our data with respect to the relevance for the development of effective immersive environment for trainings, learning and rehabilitation.
MHC Class II Expression Influences the Composition and Distribution of Immune Cells in the Metastatic Colorectal Cancer Microenvironment
Authors: Griffith Brian D. , Turcotte Simon , Lazarus Jenny , Lima Fatima , Bell Samantha , Delrosario Lawrence , McGue Jake , Krishnan Santhoshi , Oneka Morgan D. , Nathan Hari , Smith J. Joshua , D’Angelica Michael I. , Shia Jinru , Di Magliano Marina Pasca , Rao Arvind , Frankel Timothy L.
Published: August 2022

Despite advances in therapy over the past decades, metastatic colorectal cancer (mCRC) remains a highly morbid disease. While the impact of MHC-I on immune infiltration in mCRC has been well studied, data on the consequences of MHC-II loss are lacking. Multiplex fluorescent immunohistochemistry (mfIHC) was performed on 149 patients undergoing curative intent resection for mCRC and stratified into high and low human leukocyte antigen isotype DR (HLA-DR) expressing tumors. Intratumoral HLA-DR expression was found in stromal bands, and its expression level was associated with different infiltrating immune cell makeup and distribution. Low HLA-DR expression was associated with increased intercellular distances and decreased population mixing of T helper cells and antigen-presenting cells (APC), suggestive of decreased interactions. This was associated with less co-localization of tumor cells and cytotoxic T lymphocytes (CTLs), which tended to be in a less activated state as determined by Ki67 and granzyme B expression. These findings suggest that low HLA-DR in the tumor microenvironment of mCRC may reflect a state of poor helper T-cell interactions with APCs and CTL-mediated anti-tumor activity. Efforts to restore/enhance MHC-II presentation may be a useful strategy to enhance checkpoint inhibition therapy in the future.