bluuebunny/crossref_metadata_2025 huggingface dataset:
Design for Six Sigma and TRIZ for Inventive Design Applied to Recycle Cigarette Butts
Authors: Donnici Giampiero , Frizziero Leonardo , Liverani Alfredo , Leon-Cardenas Christian
Published: December 2022

A deep research and analysis of a “critical waste” object has been carried out, understood as a subject that does not fare high on the separate collection and recycling system yet: the cigarette butt. This acknowledged social waste is the first among all the garbage detected everywhere around neighborhoods worldwide, and is therefore the epicenter of a situation so worrying that it is necessary to find a solution concerning the environmental pollution. The present exercise was developed, by means of proper product design methods like TRIZ and QFD driven by DFSS rulings, to conceive of new products and services in order to create incentive for the smokers to lessen the environmental pollution problem. The social implications are about the possibility of modifying the bad habits of the smokers and making the user act consciously towards the environment. Throwing the cigarette-stub in the new collection device, rather than on the ground, enables users to enjoy both moral and economic returns. The “Buttalo” service is aimed to incentivize the population to fight against environmental pollution whilst helping smokers to be conscious about it.
Electric Double Layer: The Good, the Bad, and the Beauty
Authors: Dourado André H. B.
Published: December 2022

The electric double layer (EDL) is the most important region for electrochemical and heterogeneous catalysis. Because of it, its modeling and investigation are something that can be found in the literature for a long time. However, nowadays, it is still a hot topic of investigation, mainly because of the improvement in simulation and experimental techniques. The present review aims to present the classical models for the EDL, as well as presenting how this region affects electrochemical data in everyday experimentation, how to obtain and interpret information about EDL, and, finally, how to obtain some molecular point of view insights on it.
Effects of Different Soybean and Maize Mixed Proportions in a Strip Intercropping System on Silage Fermentation Quality
Authors: Meng He , Jiang Yan , Wang Lin , Wang Sui , Zhang Zicheng , Tong Xiaohong , Wang Shaodong
Published: December 2022

Soybean (Glycine max Merr.), with a high nutritional value, is an important oil crop and a good protein feed crop. Due to the shortage of high-protein feed and the high import pressure on soybean, scarce high-protein feed is the main research target for improving feed quality. High-quality soybean (Qihuang 34) and high-yield silage maize (Zea mays L.) (Jingling silage 386) varieties were used as the experimental materials in this study. The silage quality and the microbial community of the mixed silage of soybean and maize were analyzed, and the compatible intercropping ratios of maize–soybean mixed silage were evaluated. This experiment designed five strip intercropping systems (SIS) in a randomized block. The intercropping row ratios of maize and soybean were 0:1 (pure soybean, S), 1:0 (pure maize, M), 1:1 (MS1), 1:3 (MS2), and 1:5 (MS3). Dry matter yield and fresh matter yield were improved in the treatments of MS1 and MS2. In the mixed silage systems of maize and soybean, with an increase in soybean proportion, crude protein (CP), neutral detergent fiber (NDF), and acid detergent fiber (ADF) contents gradually increased, but the contents of water-soluble carbohydrates (WSC) and dry matter (DM) reduced to different degrees (p < 0.05). Moreover, the soybean silage alone had a poor fermentation performance, as indicated by high pH, high acetic acid (AA), propionic acid (PA), butyric acid (BA), and ammonia-N (NH3-N) concentrations, and low lactic acid (LA) concentration. By contrast, the mixed silage materials were conducive to reducing the pH, PA, BA, and NH3-N, and increasing the LA content. The relative abundance of Lactobacillus and Weissella in the MS were higher, and the abundance of undesirable bacteria were lower than in the S. The MS2 materials had the lowest pH, the highest LA concentration, and the highest relative abundance of Lactobacillus and Weissella among the three mixed silage groups. Therefore, the mixed silage in the SIS modified the microbial communities and improved the feed fermentation quality while increasing yields. The better intercropping ratio of maize–soybean mixed silage was 1:3. These results could provide a theoretical basis for the wide application and popularization of soybean as a high-protein silage forage source.
Ensiled Mixed Vegetables Enriched Carbohydrate Metabolism in Heterofermentative Lactic Acid Bacteria
Authors: Forwood Daniel L. , Holman Devin B. , Meale Sarah J. , Chaves Alex V.
Published: December 2022

This study evaluated the fermentation quality, nutritive profile, in vitro fermentation, and microbial communities colonising sorghum ensiled with an unsalable vegetable mixture (chopped beans, carrot, and onion (1:1:1) ) including: (1)−100% sorghum; (2)−80% sorghum + 20% vegetable mix or (3)−60% sorghum + 40% vegetable mix, on a dry matter (DM) basis, with or without a probiotic inoculant. Samples were obtained across 0, 1, 3, 5,7, and 101 days ensiling and after 14 d aerobic exposure. The V4 region of the 16S rRNA gene and the ITS1 region were sequenced to profile bacterial, archaeal, and fungal communities. Compared to the 0% DM, ethanol increased (p < 0.01) from 8.42 to 20.4 ± 1.32 mM with 40% DM vegetable mix inclusion, while lactate decreased from 5.93 to 2.24 ± 0.26 mM. Linear discriminant analysis revealed that relative abundances of 12 bacterial taxa were influenced by silage treatments (log LDA score ≥ 4.02; p ≤ 0.03), while predicted functional pathways of alternative carbohydrate metabolism (hexitol, sulfoquinovose and glycerol degradation; N-acetyl glucosamine biosynthesis; log LDA score ≥ 2.04; p ≤ 0.02) were similarly enriched. This study indicated that carbohydrate metabolism by heterofermentative lactic acid bacteria can increase the feed value of sorghum when ensiled with an unsalable vegetable mixture at 40%DM, without requiring a high quantity of lactate.
The Sum of Two Halves May Be Different from the Whole—Effects of Splitting Sequencing Samples Across Lanes
Authors: Williams Eleanor C. , Chazarra-Gil Ruben , Shahsavari Arash , Mohorianu Irina
Published: December 2022

The advances in high-throughput sequencing (HTS) have enabled the characterisation of biological processes at an unprecedented level of detail; most hypotheses in molecular biology rely on analyses of HTS data. However, achieving increased robustness and reproducibility of results remains a main challenge. Although variability in results may be introduced at various stages, e.g., alignment, summarisation or detection of differential expression, one source of variability was systematically omitted: the sequencing design, which propagates through analyses and may introduce an additional layer of technical variation. We illustrate qualitative and quantitative differences arising from splitting samples across lanes on bulk and single-cell sequencing. For bulk mRNAseq data, we focus on differential expression and enrichment analyses; for bulk ChIPseq data, we investigate the effect on peak calling and the peaks’ properties. At the single-cell level, we concentrate on identifying cell subpopulations. We rely on markers used for assigning cell identities; both smartSeq and 10× data are presented. The observed reduction in the number of unique sequenced fragments limits the level of detail on which the different prediction approaches depend. Furthermore, the sequencing stochasticity adds in a weighting bias corroborated with variable sequencing depths and (yet unexplained) sequencing bias. Subsequently, we observe an overall reduction in sequencing complexity and a distortion in the biological signal across technologies, experimental contexts, organisms and tissues.
Effect of the Melanocortin 4-Receptor Ile269Asn Mutation on Weight Loss Response to Dietary, Phentermine and Bariatric Surgery Interventions
Authors: Salazar-Valencia Itzel G. , Villamil-Ramírez Hugo , Barajas-Olmos Francisco , Guevara-Cruz Martha , Macias-Kauffer Luis R. , García-Ortiz Humberto , Hernández-Vergara Omar , Díaz de Sandy-Galán David Alberto , León-Mimila Paola , Centeno-Cruz Federico , González-Salazar Luis E. , Guizar-Heredia Rocío , Pichardo-Ontiveros Edgar , Jacobo-Albavera Leonor , Posadas-Sánchez Rosalinda , Vargas-Alarcón Gilberto , Velazquez-Cruz Rafael , Gutiérrez-Aguilar Ruth , Zerrweck Carlos , Rocha-González Héctor Isaac , Reyes-García Juan Gerardo , Carrasco-Portugal Miriam del C. , Flores-Murrieta Francisco Javier , Tovar Armando R. , Orozco Lorena , Villarreal-Molina Teresa , Canizales-Quinteros Samuel
Published: December 2022

The loss of function melanocortin 4-receptor (MC4R) Ile269Asn mutation has been proposed as one of the most important genetic contributors to obesity in the Mexican population. However, whether patients bearing this mutation respond differently to weight loss treatments is unknown. We tested the association of this mutation with obesity in 1683 Mexican adults, and compared the response of mutation carriers and non-carriers to three different weight loss interventions: dietary restriction intervention, phentermine 30 mg/day treatment, and Roux-en-Y gastric bypass (RYGB) surgery. The Ile269Asn mutation was associated with obesity [OR = 3.8, 95% CI (1.5–9.7), p = 0.005]. Regarding interventions, in the dietary restriction group only two patients were MC4R Ile269Asn mutation carriers. After 1 month of treatment, both mutation carriers lost weight: −4.0 kg (−2.9%) in patient 1, and −1.8 kg (−1.5%) in patient 2; similar to the mean weight loss observed in six non-carrier subjects (−2.9 kg; −2.8%). Phentermine treatment produced similar weight loss in six carriers (−12.7 kg; 15.5%) and 18 non-carriers (−11.3 kg; 13.6%) after 6 months of pharmacological treatment. RYGB also caused similar weight loss in seven carriers (29.9%) and 24 non-carriers (27.8%), 6 months after surgery. Our findings suggest that while the presence of a single MC4R loss of function Ile269Asn allele significantly increases obesity risk, the presence of at least one functional MC4R allele seems sufficient to allow short-term weight loss in response to dietary restriction, phentermine and RYGB. Thus, these three different interventions may be useful for the short-term treatment of obesity in MC4R Ile269Asn mutation carriers.
No Evidence to Support a Causal Relationship between Circulating Adiponectin Levels and Ankylosing Spondylitis: A Bidirectional Two-Sample Mendelian Randomization Study
Authors: Xie Jiale , Yang Mingyi , Yu Hui , Xu Ke , Wan Xianjie , Wang Jiachen , Wang Guoqiang , Xu Peng
Published: December 2022

Based on previous observational studies, the causal association between circulating adiponectin (CA) levels and ankylosing spondylitis (AS) risk remains unclear. Therefore, this study aims to investigate whether CA levels are related to the risk of AS. We carried out a bidirectional two-sample Mendelian randomization (MR) analysis to examine the causal correlation between CA levels and AS via published genome-wide association study (GWAS) datasets. Single-nucleotide polymorphisms (SNPs) related to CA levels were derived from a large GWAS that included 39,883 individuals of European descent. SNPs related to AS were obtained from the FinnGen consortium (2252 cases and 227,338 controls). The random-effects inverse variance weighted (IVW) method was the primary method utilized in our research. We also used four complementary approaches to improve the dependability of this study (MR–Egger regression, Weighted median, Weighted mode, and Simple mode). Random-effects IVW (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.79–1.27, p = 0.984) and four complementary methods all indicated that genetically predicted CA levels were not causally related to the risk of AS. In reverse MR analysis, there is little evidence to support the genetic causality between the risk of AS and CA levels.
How Effective Is a Buddhist Pilgrimage Circuit as a Product and Strategy for Heritage Tourism in India?
Authors: Shinde Kiran A.
Published: December 2022

Buddhist heritage in India is receiving reasonable attention for tourism development with a particular emphasis on promoting Buddhist circuits. One Buddhist pilgrimage circuit covering eight locations including four most sacred places, namely, Bodhgaya, Sarnath, Kushinagar, and Lumbini, is popular for spiritual and religious reasons. Fieldwork conducted in these four sites reveals complex patterns of visitation that question the idea of a circuit as a tourism product. The primary circuit-goers are foreign Buddhist followers, but the magnitude of their visitation is very low. They constitute less than 10 percent of visitors and are far outnumbered by domestic visitors. Domestic visitors driven by recreational purposes hardly complete the entire circuit; their visits are directed to two popular sites while other sites are used as “middle-of-the-trip centers” or places for daytrips. The interviews with various stakeholders including religious institutions, private tour operators, and relevant government agencies, show that the itineraries of circuit-goers depend on several factors including the convenience of travel, accommodation facilities, the ability to perform pilgrimage rituals, and institutional governance for tourism. This paper argues that Buddhist pilgrimage circuits operate more as a cultural landscape at a cognitive level rather than as a distinct physical route and a product that can be effectively translated into as strategy for tourism development in Buddhist sites.
Biological Control of Downy Mildew and Yield Enhancement of Cucumber Plants by Trichoderma harzianum and Bacillus subtilis (Ehrenberg) under Greenhouse Conditions
Authors: Núñez-Palenius Héctor G. , Orosco-Alcalá Blanca E. , Espitia-Vázquez Isidro , Olalde-Portugal Víctor , Hoflack-Culebro Mariana , Ramírez-Santoyo Luis F. , Ruiz-Aguilar Graciela M. L. , Cruz-Huerta Nicacio , Valiente-Banuet Juan I.
Published: December 2022

The downy mildew disease of cucurbits is considered the most economically damaging disease of Cucurbitaceae worldwide. The causal agent, Pseudoperonospora cubensis (Berkeley & Curtis), may cause complete crop losses of cucurbits. Few commercial cucurbit cultivars are resistant to this disease. Commercially, P. cubensis is controlled primarily with synthetic fungicides that inhibit or eliminate the pathogen. Several biological agents have also been identified that provide some level of control. In our study, foliar applications of three strains of Trichoderma harzianum and two native strains of Bacillus subtilis were evaluated for the control of the disease on cucumber plants grown under commercial greenhouse conditions. The study was conducted using a completely randomized design with six individual treatments during two production cycles: fall 2015 and spring 2016. The response variables included disease incidence and severity, plant height, total yield, fruit quality, and weight. B. subtilis provided the best control over the incidence and severity of the disease in both production cycles. Interestingly, while T. harzianum was less effective at controlling the disease, it enhanced plant growth and productivity, and produced a higher number of better-quality fruits per plot. This increased yield with higher quality fruits may result in higher profit for the growers.
Systematic Identification of Long Non-Coding RNAs under Allelopathic Interference of Para-Hydroxybenzoic Acid in S. lycopersicum
Authors: Liang Guoting , Niu Yajie , Guo Jing
Published: December 2022

The importance of long noncoding RNAs (lncRNAs) in plant development has been established, but a systematic analysis of the lncRNAs expressed during plant allelopathy has not been carried out. We performed RNA-seq experiments on S. lycopersicum subjected to different levels of para-hydroxybenzoic acid (PHBA) stress during plant allelopathy and identified 61,729 putative lncRNAs. Of these, 7765 lncRNAs cis-regulated 5314 protein-coding genes (PGs). Among these genes, 1116 lncRNAs and 2239 PGs were involved in a complex web of transcriptome regulation, and we divided these genes into 12 modules. Within these modules, 458 lncRNAs and 975 target genes were found to be highly correlated. Additionally, 989 lncRNAs trans-regulated 1765 PGs, and we classified them into 11 modules, within which 335 lncRNAs were highly correlated with their 633 corresponding target genes. Only 98 lncRNAs in S. lycopersicum had homologs in the lncRNA database of Arabidopsis thaliana, all of which were affected by the PHBA treatments. MiRNAs that interacted with both mRNAs and lncRNAs were selected on the basis of weighted correlation network analysis (WGCNA) results to make lncRNA-miRNA-mRNA triplets. Our study presents a systematic identification of lncRNAs involved in plant allelopathy in S. lycopersicum and provides research references for future studies.
Aluminum Cation Doping in Ruddlesden-Popper Sr2TiO4 Enables High-Performance Photocatalytic Hydrogen Evolution
Authors: He Jingsheng , Han Xiao , Xiang Huimin , Ran Ran , Wang Wei , Zhou Wei , Shao Zongping
Published: December 2022

Hydrogen (H2) is regarded as a promising and renewable energy carrier to achieve a sustainable future. Among the various H2 production routes, photocatalytic water splitting has received particular interest; it strongly relies on the optical and structural properties of photocatalysts such as their sunlight absorption capabilities, carrier transport properties, and amount of oxygen vacancy. Perovskite oxides have been widely investigated as photocatalysts for photocatalytic water splitting to produce H2 because of their distinct optical properties, tunable band gaps and excellent compositional/structural flexibility. Herein, an aluminum cation (Al3+) doping strategy is developed to enhance the photocatalytic performance of Ruddlesden-Popper (RP) Sr2TiO4 perovskite oxides for photocatalytic H2 production. After optimizing the Al3+ substitution concentration, Sr2Ti0.9Al0.1O4 exhibits a superior H2 evolution rate of 331 μmol h−1 g−1, which is ~3 times better than that of Sr2TiO4 under full-range light illumination, due to its enhanced light harvesting capabilities, facilitated charge transfer, and tailored band structure. This work presents a simple and useful Al3+ cation doping strategy to boost the photocatalytic performance of RP-phase perovskites for solar water splitting.
Disease Activity Is Associated with Obesity in Newly Diagnosed Pediatric Patients with Ulcerative Colitis
Authors: Kadenczki Orsolya , Dezsofi Antal , Cseh Aron , Szucs Daniel , Vass Noemi , Nemes Eva , Tarnok Andras , Szakos Erzsebet , Guthy Ildiko , Kovacs Marta , Karoliny Anna , Czelecz Judit , Kiss Csongor , Müller Katalin Eszter
Published: December 2022

Malnutrition and inflammatory bowel disease (IBD) are interrelated conditions. Our aim was to assess the prevalence of malnutrition, to compare anthropometric parameters in the evaluation of nutritional status in pediatric IBD, and to investigate the association between anthropometric parameters and disease activity indices (AI). Pediatric patients with newly diagnosed IBD recorded between 2010 and 2016 in the Hungarian Pediatric IBD Registry were included in this cross-sectional study. Body weight, body mass index (BMI), weight-for-height, and ideal body weight percent (IBW%) were analyzed. Pearson linear and non-linear correlations and polynomial regression analyses were performed to assess correlation between nutritional status and AI. p-values < 0.05 were considered significant. Anthropometric data of 1027 children with IBD (Crohn’s disease (CD): 699; ulcerative colitis (UC): 328; mean age 13.7 years) were analyzed. IBW% identified more obese patients than BMI both in CD (7.02% vs. 2.28%) and UC (12.17% vs. 5.48%). Significant negative correlation was found among anthropometric parameters and AI in CD. In contrast, polynomial regression analysis revealed a U-shaped correlation curve between IBW% and AI in UC. Our findings show that obesity has a bimodal association with disease activity in pediatric UC. Furthermore, IBW% was more useful to identify obese pediatric patients with IBD.
Transcriptome Analysis of Acinetobacter baumannii in Rapid Response to Subinhibitory Concentration of Minocycline
Authors: Gao Lili , Ma Xiaochun
Published: December 2022

The increasing emergence of multidrug-resistant Acinetobacter baumannii brings great threats to public health. Minocycline is a kind of semisynthetic derivative of the antibacterial drug tetracycline and is often used to treat infections caused by multidrug-resistant A. baumannii with other antibiotics. However, minocycline-resistant A. baumannii appears constantly. To rapidly explore the response of A. baumannii to minocycline stress, RNA-seq was carried out to compare the difference in the transcriptome of A. baumannii ATCC19606 in the presence or absence of minocycline. The results showed that 25 genes were differentially expressed, including 10 downregulated genes and 15 upregulated genes, and 24 sRNA were upregulated and 24 were downregulated based on the filter criteria (Log2FC > 1 or <−1 and FDR < 0.05). RtcB family protein and ABC transporter ATP-binding protein were upregulated by 2.6- and 11.3-fold, and molecular chaperone GroES, chaperonin GroL, class C beta-lactamase ADC-158, amino acid ABC transporter permease, and APC family permease were downregulated by at least two-fold in the presence of half-MIC minocycline. The differentially expressed genes are mainly involved in the stress response, the GroES/GroEL chaperonin system, and transport metabolic pathways. sRNA 1248 was significantly upregulated, and sRNA 1767, 5182, and 6984 were downregulated in a rapid response to minocycline. These results provide insights into the adaptive mechanism of A. baumannii to minocycline.
Construction Land Expansion of Resource-Based Cities in China: Spatiotemporal Characteristics and Driving Factors
Authors: Li Jiangsu , Li Weihua , Li Bo , Duan Liangrong , Zhang Tianjiao , Jia Qi
Published: December 2022

Studying construction land expansion (CLE) characteristics and driving factors in resource-based cities (RBCs) is important to promote efficient land use and maintain ecological equilibrium in RBCs. This study explores the CLE and its driving factors in RBCs. The results indicated that (1) the CLE in RBCs became increasingly obvious, and the number of cities with expansion areas exceeding 20 km2 increased from 29 to 86. In RBCs in different regions, CLE in eastern, central, and western regions was obvious, while CLE in the northeast region decelerated. The order of CLE degree at different stages of RBCs was mature, growing, regenerative, and declining. (2) Single factors such as gross domestic product, fixed-asset investment, and secondary industry added value, playing a major role. This differs from the dominant role of population and urbanization in existing research. This occurred because population growth is slow, the urbanization rate is low, population contraction prominently occurs, and economic development exhibits notable path dependence in RBCs. (3) Interaction-factor detection demonstrated that the force of two-factor interaction was greater than that of a single factor, and the interactions of total population with fixed-asset investment and economic development level strongly drove CLE in RBCs.
Salivary Diagnostic for Monitoring Strenuous Exercise—A Pilot Study in a Cohort of Male Ultramarathon Runners
Authors: Borchers Josephin , Merle Cordula Leonie , Schöneborn Deborah Diana , Lyko Lea Ronja , Thouet Thomas , Wolfarth Bernd , Kottmann Tanja , Scheibenbogen Carmen , Zimmer Jeannot , Diederich Sven , Bauer Katrin , Sack Ulrich , Schmalz Gerhard , Ziebolz Dirk , Wüstenfeld Jan
Published: December 2022

Intense physical stress, such as that in ultramarathon running, affects the immune system. For monitoring in sports medicine, non-invasive methods, e.g., salivary analysis, are of interest. This pilot cohort study aimed to assess changes in salivary parameters in response to an ultramarathon. The results were compared to blood parameters. Male, healthy finishers (n = 9, mean age: 48 ± 8.8 years, mean height: 1.8 ± 0.1 m, mean weight: 72.5 ± 7.2 kg, mean BMI: 23.5 ± 1.9 kg/cm²) of a 160 km ultramarathon were included. Saliva and blood samples were collected at three time points: T1 (baseline), T2 (shortly after the ultramarathon) and T3 (after recovery). In saliva, cortisol, testosterone, IL-1β, IL-6, IL-8, IL-10, TNF-α, albumin, IgA, α-amylase, aMMP-8, and neopterin were assessed via ELISA. In blood, cortisol, testosterone, IL-1β, IL-6, IL-8, IL-10, TNF-α, blood cell counts, procalcitonin, CRP, osmolality, albumin, and α-amylase were analyzed. The statistical evaluation comprised longitudinal testing and cross-sectional testing between saliva and blood using ratios of T2 and T3 to baseline values. Various parameters in saliva and blood changed in response to the ultramarathon. Comparing blood and saliva, the longitudinal changes of testosterone (p = 0.02) and α-amylase (p = 0.03) differed significantly. Despite the limitations of the study, it underlines that saliva is an interesting option for comprehensive monitoring in sports medicine and necessitates further studies.
Spatial Differentiation of Digital Rural Development and Influencing Factors in the Yellow River Basin, China
Authors: Ren Jiamin , Zheng Chenrouyu , Guo Fuyou , Zhao Hongbo , Ma Shuang , Cheng Yu
Published: December 2022

The new development mode represented by the digital economy has provided new ideas for sustainable rural development. To comprehensively understand the status of digital rural development and propose scientific measures of rural revitalization in the Yellow River Basin (YRB), this study used counties as the research unit and data from 2020 to analyze the spatial differentiation characteristics and influencing factors by employing the Theil index, spatial autocorrelation analysis, and a geodetector model. The results showed that the digital rural development index in the YRB is slightly higher than it is in China overall, but the sub-index for the digital economy is lagging. The levels of digital rural development in the different reaches were lower reaches > middle reaches > upper reaches. Additionally, municipal districts and county-level cities have higher statuses than t general counties. Moreover, the decomposition of the Theil index shows that the intra-group differences in the upper reaches and general counties are the most important cause of the total differences. Moreover, the levels of digital rural development demonstrate spatial differences, with high and low levels in the east and west, respectively. An obvious reliable spatial correlation exists, and the spatial agglomeration featured with a similar level is significant. Finally, the influencing factors of spatial heterogeneity of digital rural development in the YRB and different reaches were different, with government expenditure being the main leading factor in the YRB and its upper reaches, while educational attainment and industrial structure are the leading factors in the middle reaches and lower reaches, respectively. The explanatory power of the interactions between the factors far exceeds that of a single factor, as shown through double-factor and nonlinear enhancement. This study provides a scientific reference for facilitating more targeted policy measures to achieving the goal of digital China and rural revitalization.
Examining Coroners’ Recommendations for Health and Safety Management of Ageing Heavy Vehicle Drivers: A STAMP Analysis
Authors: Batson Angela , Newnam Sharon , Koppel Sjaan
Published: December 2022

Recommendations were analysed from coronial cases involving ageing heavy vehicle drivers (≥55 years) and mapped onto a Systems Theoretic Accident Model and Processes (STAMP) control structure to identify the controllers and control actions influential in the heavy vehicle industry with regard to health and safety. A National Coronial Information System (NCIS) database search revealed 38 coroners’ recommendations arising from 14 unique cases of ageing driver involvement. There were no ageing themes identified in the analysis of coroners’ findings and recommendations. An examination of the STAMP control structure identified that the highest concentration of recommendations was in the level of regulation, the second most senior level of control, although safety constraints were advised for all five levels of the system. In regard to identifying themes of control flaws in the recommendations, the study found that “unidentified hazards” were the most common type of safety failure in the analysis of cases of ageing drivers, concentrated at the regulatory level, which indicates that additional risk identification methods by upper levels of control are needed. Therefore, a recommendation arising from the current study is that additional controls in safety intervention are necessitated in the upper and middle levels of the road freight transportation system; in particular, formalising health and safety education for organisational managers, with a focus on identifying ageing issues, would fill a gap in the system for managing ageing heavy vehicle drivers. In conclusion, this study has found that improving the health and safety of ageing heavy vehicle drivers necessitates additional safety constraints with a focus on formalised safety education for organisational managers, in addition to a means to detect emerging and unforeseen hazards in the road freight transportation industry.
Evaluation of Complexity Measurement Tools for Correlations with Health-Related Outcomes, Health Care Costs and Impacts on Healthcare Providers: A Scoping Review
Authors: Kaneko Hiromitsu , Hanamoto Akiko , Yamamoto-Kataoka Sachiko , Kataoka Yuki , Aoki Takuya , Shirai Kokoro , Iso Hiroyasu
Published: December 2022

Various tools to measure patient complexity have been developed. Primary care physicians often deal with patient complexity. However, their usefulness in primary care settings is unclear. This study explored complexity measurement tools in general adult and patient populations to investigate the correlations between patient complexity and outcomes, including health-related patient outcomes, healthcare costs, and impacts on healthcare providers. We used a five-stage scoping review framework, searching MEDLINE and CINAHL, including reference lists of identified studies. A total of 21 patient complexity management tools were found. Twenty-five studies examined the correlation between patient complexity and health-related patient outcomes, two examined healthcare costs, and one assessed impacts on healthcare providers. No studies have considered sharing information or action plans with multidisciplinary teams while measuring outcomes for complex patients. Of the tools, eleven used face-to-face interviews, seven extracted data from medical records, and three used self-assessments. The evidence of correlations between patient complexity and outcomes was insufficient for clinical implementation. Self-assessment tools might be convenient for conducting further studies. A multidisciplinary approach is essential to develop effective intervention protocols. Further research is required to determine these correlations in primary care settings.
Changes in Air Quality during the Period of COVID-19 in China
Authors: Xu Xin , Huang Shupei , An Feng , Wang Ze
Published: December 2022

This paper revisits the heterogeneous impacts of COVID-19 on air quality. For different types of Chinese cities, we analyzed the different degrees of improvement in the concentrations of six air pollutants (PM2.5, PM10, SO2, NO2, CO, and O3) during COVID-19 by analyzing the predictivity of air quality. Specifically, we divided the sample into three groups: cities with severe outbreaks, cities with a few confirmed cases, and cities with secondary outbreaks. Ensemble empirical mode decomposition (EEMD), recursive plots (RPs), and recursive quantitative analysis (RQA) were used to analyze these heterogeneous impacts and the predictivity of air quality. The empirical results indicated the following: (1) COVID-19 did not necessarily improve air quality due to factors such as the rebound effect of consumption, and its impacts on air quality were short-lived. After the initial outbreak, NO2, CO, and PM2.5 emissions declined for the first 1–3 months. (2) For the cities with severe epidemics, air quality was improved, but for the cities with second outbreaks, air quality was first enhanced and then deteriorated. For the cities with few confirmed cases, air quality first deteriorated and then improved. (3) COVID-19 changed the stability of the air quality sequence. The predictability of the air quality index (AQI) declined in cities with serious epidemic situations and secondary outbreaks, but for the cities with a few confirmed cases, the AQI achieved a stable state sooner. The conclusions may facilitate the analysis of differences in air quality evolution characteristics and fluctuations before and after outbreaks from a quantitative perspective.
Methotrexate-Induced Liver Injury Is Associated with Oxidative Stress, Impaired Mitochondrial Respiration, and Endoplasmic Reticulum Stress In Vitro
Authors: Schmidt Saskia , Messner Catherine Jane , Gaiser Carine , Hämmerli Carina , Suter-Dick Laura
Published: December 2022

Low-dose methotrexate (MTX) is a standard therapy for rheumatoid arthritis due to its low cost and efficacy. Despite these benefits, MTX has been reported to cause chronic drug-induced liver injury, namely liver fibrosis. The hallmark of liver fibrosis is excessive scarring of liver tissue, triggered by hepatocellular injury and subsequent activation of hepatic stellate cells (HSCs). However, little is known about the precise mechanisms through which MTX causes hepatocellular damage and activates HSCs. Here, we investigated the mechanisms leading to hepatocyte injury in HepaRG and used immortalized stellate cells (hTERT-HSC) to elucidate the mechanisms leading to HSC activation by exposing mono- and co-cultures of HepaRG and hTERT-HSC to MTX. The results showed that at least two mechanisms are involved in MTX-induced toxicity in HepaRG: (i) oxidative stress through depletion of glutathione (GSH) and (ii) impairment of cellular respiration in a GSH-independent manner. Furthermore, we measured increased levels of endoplasmic reticulum (ER) stress in activated HSC following MTX treatment. In conclusion, we established a human-relevant in vitro model to gain mechanistical insights into MTX-induced hepatotoxicity, linked oxidative stress in HepaRG to a GSH-dependent and -independent pathway, and hypothesize that not only oxidative stress in hepatocytes but also ER stress in HSCs contribute to MTX-induced activation of HSCs.
Evolution of Treatment in Advanced Cholangiocarcinoma: Old and New towards Precision Oncology
Authors: Capuozzo Maurizio , Santorsola Mariachiara , Landi Loris , Granata Vincenza , Perri Francesco , Celotto Venere , Gualillo Oreste , Nasti Guglielmo , Ottaiano Alessandro
Published: December 2022

Cholangiocarcinoma (CCA) is a malignant neoplasm arising in the epithelium of the biliary tract. It represents the second most common primary liver cancer in the world, after hepatocellular carcinoma, and it constitutes 10–15% of hepatobiliary neoplasms and 3% of all gastrointestinal tumors. As in other types of cancers, recent studies have revealed genetic alterations underlying the establishment and progression of CCA. The most frequently involved genes are APC, ARID1A, AXIN1, BAP1, EGFR, FGFRs, IDH1/2, RAS, SMAD4, and TP53. Actionable targets include alterations of FGFRs, IDH1/2, BRAF, NTRK, and HER2. “Precision oncology” is emerging as a promising approach for CCA, and it is possible to inhibit the altered function of these genes with molecularly oriented drugs (pemigatinib, ivosidenib, vemurafenib, larotrectinib, and trastuzumab). In this review, we provide an overview of new biologic drugs (their structures, mechanisms of action, and toxicities) to treat metastatic CCA, providing readers with panoramic information on the trajectory from “old” chemotherapies to “new” target-oriented drugs.
Focus on Marine Animal Safety and Marine Bioresources in Response to the SARS-CoV-2 Crisis
Authors: Yang Yao , Li Jiacheng , Han Fang
Published: December 2022

SARS-CoV-2 as a zoonotic virus has significantly affected daily life and social behavior since its outbreak in late 2019. The concerns over its transmission through different media directly or indirectly have evoked great attention about the survival of SARS-CoV-2 virions in the environment and its potential infection of other animals. To evaluate the risk of infection by SARS-CoV-2 and to counteract the COVID-19 disease, extensive studies have been performed to understand SARS-CoV-2 biogenesis and its pathogenesis. This review mainly focuses on the molecular architecture of SARS-CoV-2, its potential for infecting marine animals, and the prospect of drug discovery using marine natural products to combat SARS-CoV-2. The main purposes of this review are to piece together progress in SARS-CoV-2 functional genomic studies and antiviral drug development, and to raise our awareness of marine animal safety on exposure to SARS-CoV-2.
Excess BAFF Alters NR4As Expression Levels and Breg Function of Human Precursor-like Marginal Zone B-Cells in the Context of HIV-1 Infection
Authors: Doyon-Laliberté Kim , Aranguren Matheus , Byrns Michelle , Chagnon-Choquet Josiane , Paniconi Matteo , Routy Jean-Pierre , Tremblay Cécile , Quintal Marie-Claude , Brassard Nathalie , Kaufmann Daniel E. , Poudrier Johanne , Roger Michel
Published: December 2022

We have reported excess B-cell activating factor (BAFF) in the blood of HIV-infected progressors, which was concomitant with increased frequencies of precursor-like marginal zone (MZp) B-cells, early on and despite antiretroviral therapy (ART). In controls, MZp possess a strong B-cell regulatory (Breg) potential. They highly express IL-10, the orphan nuclear receptors (NR)4A1, NR4A2 and NR4A3, as well as the ectonucleotidases CD39 and CD73, all of which are associated with the regulation of inflammation. Furthermore, we have shown MZp regulatory function to involve CD83 signaling. To address the impact of HIV infection and excessive BAFF on MZp Breg capacities, we have performed transcriptomic analyses by RNA-seq of sorted MZp B-cells from the blood of HIV-infected progressors. The Breg profile and function of blood MZp B-cells from HIV-infected progressors were assessed by flow-cytometry and light microscopy high-content screening (HCS) analyses, respectively. We report significant downregulation of NR4A1, NR4A2, NR4A3 and CD83 gene transcripts in blood MZp B-cells from HIV-infected progressors when compared to controls. NR4A1, NR4A3 and CD83 protein expression levels and Breg function were also downregulated in blood MZp B-cells from HIV-infected progressors and not restored by ART. Moreover, we observe decreased expression levels of NR4A1, NR4A3, CD83 and IL-10 by blood and tonsillar MZp B-cells from controls following culture with excess BAFF, which significantly diminished their regulatory function. These findings, made on a limited number of individuals, suggest that excess BAFF contributes to the alteration of the Breg potential of MZp B-cells during HIV infection and possibly in other situations where BAFF is found in excess.
Understanding Life at High Temperatures: Relationships of Molecular Channels in Enzymes of Methanogenic Archaea and Their Growth Temperatures
Authors: Ginsbach Laura F. , Gonzalez Juan M.
Published: December 2022

Analyses of protein structures have shown the existence of molecular channels in enzymes from Prokaryotes. Those molecular channels suggest a critical role of spatial voids in proteins, above all, in those enzymes functioning under high temperature. It is expected that these spaces within the protein structure are required to access the active site and to maximize availability and thermal stability of their substrates and cofactors. Interestingly, numerous substrates and cofactors have been reported to be highly temperature-sensitive biomolecules. Methanogens represent a singular phylogenetic group of Archaea that performs anaerobic respiration producing methane during growth. Methanogens inhabit a variety of environments including the full range of temperatures for the known living forms. Herein, we carry out a dimensional analysis of molecular tunnels in key enzymes of the methanogenic pathway from methanogenic Archaea growing optimally over a broad temperature range. We aim to determine whether the dimensions of the molecular tunnels are critical for those enzymes from thermophiles. Results showed that at increasing growth temperature the dimensions of molecular tunnels in the enzymes methyl-coenzyme M reductase and heterodisulfide reductase become increasingly restrictive and present strict limits at the highest growth temperatures, i.e., for hyperthermophilic methanogens. However, growth at lower temperature allows a wide dimensional range for the molecular spaces in these enzymes. This is in agreement with previous suggestions on a potential major role of molecular tunnels to maintain biomolecule stability and activity of some enzymes in microorganisms growing at high temperatures. These results contribute to better understand archaeal growth at high temperatures. Furthermore, an optimization of the dimensions of molecular tunnels would represent an important adaptation required to maintain the activity of key enzymes of the methanogenic pathway for those methanogens growing optimally at high temperatures.
Evaluation of Circulating Platelet Extracellular Vesicles and Hypertension Mediated Organ Damage
Authors: Lugo-Gavidia Leslie Marisol , Burger Dylan , Nolde Janis M. , Matthews Vance B. , Schlaich Markus P.
Published: December 2022

Elevated circulating platelet-derived extracellular vesicles (pEVs) have been associated with arterial hypertension. The role of hypertension-mediated organ damage (HMOD) to induce EV release is still unknown. We studied the micro- and macro-vascular changes (retinal vascular density and pulse wave velocity), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), and assessed the psychosocial status (anxiety and depression) in hypertensive patients to determine their relationship with EV release. Pulse wave velocity showed a significant positive correlation with pEVs (r = 0.33; p = 0.01). Systolic blood pressure (SBP) negatively correlated with retinal vascularity. The superficial retinal vascular plexus density in the whole image showed a significant negative correlation with 24 h SBP (r = −0.38, p < 0.01), day-SBP (r = −0.35, p = 0.01), and night-SBP (r = −0.27, p = 0.04). pEVs did not show significant associations with microvascular damage (retinal vascular density), endothelial function (flow-mediated vasodilation of brachial artery and finger plethysmography), or psychosocial status (anxiety and depression). Our results indicate that the pEV levels were associated with macrovascular damage measured by PWV, whereas no significant association between pEVs and microvascular damage, endothelial function, or emotional status could be detected. The potential utility of pEV in clinical practice in the context of HMOD may be limited to macrovascular changes.
Promitotic Action of Oenothera biennis on Senescent Human Dermal Fibroblasts
Authors: Ceccacci Sara , Roger Kévin , Metatla Ines , Chhuon Cerina , Tighanimine Khaled , Fumagalli Stefano , De Lucia Adriana , Pranke Iwona , Cordier Corinne , Monti Maria Chiara , Guerrera Ida Chiara
Published: December 2022

Accumulation of senescent dermal fibroblasts drives skin aging. The reactivation of proliferation is one strategy to modulate cell senescence. Recently, we reported the exact chemical composition of the hydrophilic extract of Oenothera biennis cell cultures (ObHEx) and we showed its skin anti-aging properties. The aim of this work is to assess its biological effect specifically on cell senescence. ObHEx action has been evaluated on normal human dermal fibroblasts subjected to stress-induced premature senescence (SIPS) through an ultra-deep proteomic analysis, leading to the most global senescence-associated proteome so far. Mass spectrometry data show that the treatment with ObHEx re-establishes levels of crucial mitotic proteins, strongly downregulated in senescent cells. To validate our proteomics findings, we proved that ObHEx can, in part, restore the activity of ‘senescence-associated-ß-galactosidase’, the most common hallmark of senescent cells. Furthermore, to assess if the upregulation of mitotic protein levels translates into a cell cycle re-entry, FACS experiments have been carried out, demonstrating a small but significative reactivation of senescent cell proliferation by ObHEx. In conclusion, the deep senescence-associated global proteome profiling published here provides a panel of hundreds of proteins deregulated by SIPS that can be used by the community to further understand senescence and the effect of new potential modulators. Moreover, proteomics analysis pointed to a specific promitotic effect of ObHEx on senescent cells. Thus, we suggest ObHEx as a powerful adjuvant against senescence associated with skin aging.
Atherosclerosis: From Molecular Biology to Therapeutic Perspective 2.0
Authors: Perrotta Ida
Published: December 2022

Atherosclerosis is a chronic inflammatory disease of large- and medium-sized arteries involving aberrant immune–inflammatory responses, dysfunctional molecular pathways, and impaired tissue repair mechanisms [...]
An Overview of Recent Advancements in Conducting Polymer–Metal Oxide Nanocomposites for Supercapacitor Application
Authors: Patil Pranoti H. , Kulkarni Vidya V. , Jadhav Sushilkumar A.
Published: December 2022

Supercapacitors have gained significant attention as energy storage devices due to their high specific power, fast charge–discharge rate and extended cycling stability. Recent research focuses on the search for new electrode materials to enhance the specific capacitance of supercapacitors. Conducting polymers (CPs) and metal oxides (MOs) are being extensively tested as electrode materials in supercapacitors. CPs have poor cycling stability and low mechanical strength but are easy to process, while MOs exhibit easy availability, variable oxidation states and possess high specific capacitance, but they are somewhat difficult to process. Therefore, combining both (CP) and (MO) in a composite offers better results for the electrochemical performance of supercapacitors. This review mainly focuses on the discussion of CP/MO based nanocomposites recently reported for supercapacitor applications. The collective information presented in this report will provide researchers a view into the latest developments in this field. The continued research on this topic will reveal further potential applications of CP/MO composites.