bluuebunny/crossref_metadata_2025 huggingface dataset:
Wireless Sensor Network Based Real-Time Pedestrian Detection and Classification for Intelligent Transportation System
Authors: Kumar Saureng , Sharma S. C. , Kumar Ram
Published: January 2023

Pedestrian safety has become a critical consideration in developing society especially road traffic, an intelligent transportation need of the hour is the solution left. India tops the world with 11% of global road accidents. With this data, we have moved in the direction of computer vision applications for efficient and accurate pedestrian detection for intelligent transportation systems (ITS). The important application of this research is robot development, traffic management and control, unmanned vehicle driving (UVD), intelligent monitoring and surveillance system, and automatic pedestrian detection system. Much research has focused on pedestrian detection, but sustainable solution-driven research must still be required to overcome road accidents. We have proposed a wireless sensor network-based pedestrian detection system that classifies the real-time set of pedestrian activity and samples the reciprocally received signal strength (RSS) from the sensor node. We applied a histogram of oriented gradient (HOG) descriptor algorithm K-nearest neighbor, decision tree and linear support vector machine to measure the performance and prediction of the target. Also, these algorithms have performed a comparative analysis under different aspects. The linear support vector machine algorithm was trained with 481 samples. The performance achieves the accuracy of 98.90%and has accomplished superior results with a maximum precision of 0.99, recall of 0.98, and F-score of 0.95 with 2% error rate. The model’s prediction indicates that it can be used in the intelligent transportation system. Finally, the limitation and the challenges discussed to provide an outlook for future research direction to perform effective pedestrian detection.
Resource Allocation Modeling Framework to Refactor Software Design Smells
Authors: Gupta Priyanka , Anand Adarsh , Mellal Mohamed Arezki
Published: January 2023

The domain to study design flaws in the software environment has created enough opportunity for the researchers. These design flaws i.e., code smells, were seen hindering the quality aspects of the software in many ways. Once detected, the segment of the software which was found to be infected with such a flaw has to be passed through some refactoring steps in order to remove it. To know about their working phenomenon in a better way, authors have innovatively talked about the smell detection mechanism using the NHPP modeling framework. Further the authors have also chosen to investigate about the amount of resources/efforts which should be allotted to various code smell categories. The authors have developed an optimization problem for the said purpose which is being validated on the real-life smell data set belonging to an open-source software system. The obtained results are in acceptable range and are justifying the applicability of the model.
A Chaotic System and Count Tracking Mechanism-based Dynamic S-Box and Secret Key Generation
Authors: Pal Sagnik , Selvanambi Ramani , Malik Preeti , Karuppiah Marimuthu
Published: January 2023

In cryptography, Block ciphers use S-Boxes to perform substitution and permutation operations on a data block. S-Boxes provide non-linearity and confusion of bits to the cryptographic algorithms. In addition, secret keys are critical security aspects for encrypting and decrypting messages. The uncertainty and randomness of the secret key and S-boxes used in the algorithm determine the extent of security against any cryptanalysis attack. This paper proposes a new mechanism to dynamically generate a secret key and S-Box each time while sending and receiving the message. These dynamically generated S-Boxes and keys depend on mutually decided security parameters and message transfer history. Furthermore, a new counter-based mechanism is introduced in this paper. These enhancement techniques are applied to the serpent cipher algorithm, and a data transfer simulation is performed to validate the efficacy of the proposed method. We observe that the dynamically generated S-box follows the strict avalanche criteria. We further validate that the encrypted message shows higher sensitivity to the S-box and the secret key in enhanced serpent cipher than the original version. However, to validate our proposed method, we test and analyze the improvements in the Serpent Cipher Algorithm.
Trajectory Control of Robotic Manipulator using Metaheuristic Algorithms
Authors: Rawat Devendra , Gupta Mukul Kumar , Sharma Abhinav
Published: January 2023

Robotic manipulators are extremely nonlinear complex and, uncertain systems. They have multi-input multi-output (MIMO) dynamics, which makes controlling manipulators difficult. Robotic manipulators have wide applications in many industries like processes, medicine, and space. Effective control of these manipulators is extremely important to perform these industrial tasks. Researchers are working on the control of robotic manipulators using conventional and intelligent control methods. Conventional control methods are proportional integral and derivative (PID), Fractional order proportional integral and derivative (FOPID), sliding mode control (SMC), and optimal & robust control while intelligent control method includes Artificial Neural network (ANN), Fuzzy logic control (FLC) and metaheuristic optimization algorithms based control schemes. This paper presents the trajectory control of a robotic manipulator using a PID controller. Four different meta-heuristic algorithms namely Sooty tern optimization (STO), Spotted Hyena optimizer (SHO), Atom Search optimization (ASO), and Arithmetic Optimization algorithm (AOA) are used to optimize the gains of PID controller for trajectory control of a two-link robotic manipulator and a novel hybrid sooty tern and particle swarm optimization (STOPSO) has been designed. These optimization techniques are nature-inspired algorithms that give the optimal gain values while minimizing the performance indices. A performance index comprising Integral time absolute error (ITAE) having weights for both links has been considered to achieve the desired trajectory. These optimization techniques are stochastic in nature so statistical analysis and Freidman’s ranking test has been performed to evaluate the effectiveness of these algorithms. The proposed hybrid STOPSO provided a fitness value of 0.04541 and showed a standard deviation of 0.0002. A comparative study of these optimization techniques is presented and as a result, hybrid STOPSO provides the best results with minimum fitness value followed by STO, AOA, ASO, and SHO algorithms.
Software Test Case Generation Tools and Techniques: A Review
Authors: Verma Abhishek Singh , Choudhary Ankur , Tiwari Shailesh
Published: January 2023

Software Industry is evolving at a very fast pace since last two decades. Many software developments, testing and test case generation approaches have evolved in last two decades to deliver quality products and services. Testing plays a vital role to ensure the quality and reliability of software products. In this paper authors attempted to conduct a systematic study of testing tools and techniques. Six most popular e-resources called IEEE, Springer, Association for Computing Machinery (ACM), Elsevier, Wiley and Google Scholar to download 738 manuscripts out of which 125 were selected to conduct the study. Out of 125 manuscripts selected, a good number approx. 79% are from reputed journals and around 21% are from good conference of repute. Testing tools discussed in this paper have broadly been divided into five different categories: open source, academic and research, commercial, academic and open source, and commercial & open source. The paper also discusses several benchmarked datasets viz. Evosuite 10, SF100 Corpus, Defects4J repository, Neo4j, JSON, Mocha JS, and Node JS to name a few. Aim of this paper is to make the researchers aware of the various test case generation tools and techniques introduced in the last 11 years with their salient features.
Strategies for promoting tendon-bone healing: Current status and prospects
Authors: Yang Chenhui , Teng Yuanjun , Geng Bin , Xiao Hefang , Chen Changshun , Chen Rongjin , Yang Fei , Xia Yayi
Published: January 2023

Tendon-bone insertion (TBI) injuries are common, primarily involving the rotator cuff (RC) and anterior cruciate ligament (ACL). At present, repair surgery and reconstructive surgery are the main treatments, and the main factor determining the curative effect of surgery is postoperative tendon-bone healing, which requires the stable combination of the transplanted tendon and the bone tunnel to ensure the stability of the joint. Fibrocartilage and bone formation are the main physiological processes in the bone marrow tract. Therefore, therapeutic measures conducive to these processes are likely to be applied clinically to promote tendon-bone healing. In recent years, biomaterials and compounds, stem cells, cell factors, platelet-rich plasma, exosomes, physical therapy, and other technologies have been widely used in the study of promoting tendon-bone healing. This review provides a comprehensive summary of strategies used to promote tendon-bone healing and analyses relevant preclinical and clinical studies. The potential application value of these strategies in promoting tendon-bone healing was also discussed.
Periodic health checkups reduce the risk of hospitalization in patients with type 2 diabetes
Authors: Hamasaki Hidetaka , Yanai Hidekatsu
Published: January 2023

Introduction

Periodic health checkups (PHCs) represent a unique system in Japan that is useful for the early detection of lifestyle-related diseases and cardiovascular diseases (CVDs). This study aims to investigate the association of PHCs with the hospitalization risk of patients with type 2 diabetes mellitus (T2DM).

Methods

A retrospective cohort study was conducted from April 2013 to December 2015 and included participant information such as CVD history, lifestyle, and whether PHC was conducted in addition to regular medical examinations. Difference in clinical data between patients with and without PHC was examined. Furthermore, Cox regression analysis was performed to investigate the independent association of PHCs with hospitalization.

Results

Herein, 1,256 patients were selected and followed up for 2.35 ± 0.73 years. In the PHC group, body mass index, waist circumference, proportion of patients with a history of CVD, and number of hospitalizations were lower than those in the non-PHC group. Furthermore, the PHC group exhibited a significant association with lower hospitalization risk (hazard ratio = 0.825; 95% confidence interval, 0.684 to 0.997; p = 0.046) in the Cox model.

Conclusion

This study revealed that PHCs minimized the risk of hospitalization in patients with T2DM. Furthermore, we discussed the effectiveness of PHCs in enhancing health outcomes and reducing health care costs in such patients.
Endothelial ADAM10 controls cellular response to oxLDL and its deficiency exacerbates atherosclerosis with intraplaque hemorrhage and neovascularization in mice
Authors: van der Vorst Emiel P. C. , Maas Sanne L. , Theodorou Kosta , Peters Linsey J. F. , Jin Han , Rademakers Timo , Gijbels Marion J. , Rousch Mat , Jansen Yvonne , Weber Christian , Lehrke Michael , Lebherz Corinna , Yildiz Daniela , Ludwig Andreas , Bentzon Jacob F. , Biessen Erik A. L. , Donners Marjo M. P. C.
Published: January 2023

Introduction

The transmembrane protease A Disintegrin And Metalloproteinase 10 (ADAM10) displays a “pattern regulatory function,” by cleaving a range of membrane-bound proteins. In endothelium, it regulates barrier function, leukocyte recruitment and angiogenesis. Previously, we showed that ADAM10 is expressed in human atherosclerotic plaques and associated with neovascularization. In this study, we aimed to determine the causal relevance of endothelial ADAM10 in murine atherosclerosis development in vivo.

Methods and results

Endothelial Adam10 deficiency (Adam10ecko) in Western-type diet (WTD) fed mice rendered atherogenic by adeno-associated virus-mediated PCSK9 overexpression showed markedly increased atherosclerotic lesion formation. Additionally, Adam10 deficiency was associated with an increased necrotic core and concomitant reduction in plaque macrophage content. Strikingly, while intraplaque hemorrhage and neovascularization are rarely observed in aortic roots of atherosclerotic mice after 12 weeks of WTD feeding, a majority of plaques in both brachiocephalic artery and aortic root of Adam10ecko mice contained these features, suggestive of major plaque destabilization. In vitro, ADAM10 knockdown in human coronary artery endothelial cells (HCAECs) blunted the shedding of lectin-like oxidized LDL (oxLDL) receptor-1 (LOX-1) and increased endothelial inflammatory responses to oxLDL as witnessed by upregulated ICAM-1, VCAM-1, CCL5, and CXCL1 expression (which was diminished when LOX-1 was silenced) as well as activation of pro-inflammatory signaling pathways. LOX-1 shedding appeared also reduced in vivo, as soluble LOX-1 levels in plasma of Adam10ecko mice was significantly reduced compared to wildtypes.

Discussion

Collectively, these results demonstrate that endothelial ADAM10 is atheroprotective, most likely by limiting oxLDL-induced inflammation besides its known role in pathological neovascularization. Our findings create novel opportunities to develop therapeutics targeting atherosclerotic plaque progression and stability, but at the same time warrant caution when considering to use ADAM10 inhibitors for therapy in other diseases.
The visualization of Orphadata neurology phenotypes
Authors: Hier Daniel B. , Yelugam Raghu , Carrithers Michael D. , Wunsch Donald C.
Published: January 2023

Disease phenotypes are characterized by signs (what a physician observes during the examination of a patient) and symptoms (the complaints of a patient to a physician). Large repositories of disease phenotypes are accessible through the Online Mendelian Inheritance of Man, Human Phenotype Ontology, and Orphadata initiatives. Many of the diseases in these datasets are neurologic. For each repository, the phenotype of neurologic disease is represented as a list of concepts of variable length where the concepts are selected from a restricted ontology. Visualizations of these concept lists are not provided. We address this limitation by using subsumption to reduce the number of descriptive features from 2,946 classes into thirty superclasses. Phenotype feature lists of variable lengths were converted into fixed-length vectors. Phenotype vectors were aggregated into matrices and visualized as heat maps that allowed side-by-side disease comparisons. Individual diseases (representing a row in the matrix) were visualized as word clouds. We illustrate the utility of this approach by visualizing the neuro-phenotypes of 32 dystonic diseases from Orphadata. Subsumption can collapse phenotype features into superclasses, phenotype lists can be vectorized, and phenotypes vectors can be visualized as heat maps and word clouds.
Effect of supercritical CO2 extraction on pore characteristics of coal and its mechanism
Authors: Chen Run , Hu Kunpeng , Lv Fengrong , Zhang Yajun
Published: January 2023

Abundant pore space in coal is not only the place for the accumulation of coalbed methane (CBM), but also the tunnel for gas migration. In this study, five sets of coal samples before and after the second coalification were selected from the eastern margin of Ordos Basin to simulate supercritical CO2 (Sc-CO2) extraction in supercritical extraction equipment. The evolutions of pore structure and porosity were tested by mercury intrusion porosimetry and nuclear magnetic resonance spectroscopy to compare the changes of pore structure and porosity due to the Sc-CO2 extraction, and to explain the related mechanism. The results show that: (1) Pore volume, pore specific surface area, and connectivity characteristics changed significantly due to Sc-CO2 extraction, and the increment of pore volume and pore specific surface area presented a law of increase–decrease–increase with the increase in the coal rank, and the turning point was near the second coalification. (2) The porosity increment change trend due to Sc-CO2 extraction was increase–decrease–increase with increasing coal rank, and the turning point was again near the second coalification, which supports the mercury intrusion porosimetry results. (3) The changes were observed in the porosity characteristics due to Sc-CO2 extraction through pore-increasing and expanding effects. Before the second coalification, the pore-increasing and expanding effects co-existed in the micropores, and after the second coalification, the pore-expanding effect mainly existed in the transitional pores and above. (4) The variation model for the pore structure of coal due to Sc-CO2 extraction was established. The conclusions offer not only important theoretical significance for the CO2-enhanced CBM (CO2-ECBM) mechanism but also important significance for CO2-ECBM engineering.
The management correlation between metabolic index, cardiovascular health, and diabetes combined with cardiovascular disease
Authors: Zhang Yi , Liu Chao , Xu Yijing , Wang Yanlei , Dai Fang , Hu Honglin , Jiang Tian , Lu Yunxia , Zhang Qiu
Published: January 2023

Background

Cardiovascular disease (CVD) has become a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Although there is also evidence that multifactorial interventions to control blood glucose, blood pressure, and lipid profiles can reduce macrovascular complications and mortality in patients with T2DM, the link between these risk factors has not been established.

Methods

On 10 December 2018, 1,920 people in four cities in Anhui Province were included. Latent category analysis (LCA) was used to explore the clustering mode of HRBs (health risk behaviors). The primary exposure was HRBs and exercise and diet interventions, and the primary outcome was CVD and other variables, including zMS, triglyceride-glucose index (TyG), TyG-WC (waist circumference), TyG-BMI, TG/HDL, and cardiovascular health (CVH). A multivariable logistic regression model was used to establish the relationship between HRBs, exercise, diet interventions, and CVD. Moderate analysis and mediation moderation analysis were employed by the PROCESS method to explore the relationship between these variables. Sensitivity analysis explored the robustness of the model.

Results

The mean age was 57.10 ± 10.0 years old. Overall, CVD affects approximately 19.9% of all persons with T2DM. Macrovascular complications of T2DM include coronary heart disease, myocardial infarction (MI), cardiac insufficiency, and cerebrovascular disease. Elderly age (χ2 = 22.70), no occupation (χ2 = 20.97), medium and high socioeconomic status (SES) (χ2 = 19.92), higher level of TyG-WC (χ2 = 6.60), and higher zMS (χ2 = 7.59) were correlated with high CVD. Many metabolic indices have shown a connection with T2DM combined with CVD, and there was a dose−response relationship between HRB co-occurrence and clustering of HRBs and zMS; there was a dose−response relationship between multifactorial intervention and CVH. In the mediation moderation analysis, there was an association between HRB, gender, TyG, TyG-BMI, and CVD. From an intervention management perspective, exercise and no diet intervention were more significant with CVD; moreover, there was an association between intervention management, gender, zMS, TyG-WC, TyG-BMI, TG/HDL, and CVD. Finally, there was an association between sex, CVH, and CVD. Sensitivity analysis demonstrated that our results were robust.

Conclusions

CVD is one of the common complications in patients with type 2 diabetes, and its long-term outcome will have more or less impact on patients. Our findings suggest the potential benefits of scaling up multifactorial and multifaceted interventions to prevent CVD in patients with T2DM.
Investigation of He’s Yang Chao recipe against oxidative stress-related mitophagy and pyroptosis to improve ovarian function
Authors: Miao Chenyun , Zhao Ying , Chen Yun , Wang Ruye , Ren Ning , Chen Bixia , Dong Pingpei , Zhang Qin
Published: January 2023

Background

Primary ovarian insufficiency (POI) is a common gynecological disease with serious ramifications including low pregnancy rate and low estrogen symptoms. Traditional Chinese medicine is regarded as an effective treatment for POI. However, the therapeutic mechanism of it is unclear.

Methods

In this study, a mouse model of primary ovarian insufficiency was established by intraperitoneal injection of cyclophosphamide (CTX) and He’s Yang Chao Recipe (HSYC) concentrate was used for intragastric administration. Serum hormone levels (Anti-Müllerian Hormone, Estradiol, Progesterone, Luteinizing Hormone and Follicle Stimulating Hormone) and Oxidative Stress (OS) related products, superoxide dismutase (SOD), GSH-Px, and malondialdehyde (MDA) were measured by enzyme-linked immunosorbent assay. Pathological changes in ovarian tissue were evaluated by hematoxylin and eosin staining, and flow cytometry was used to determine reactive oxygen species content and mitochondrial membrane potential levels in granulosa cells. Mitochondrial distribution and morphology were investigated using immunofluorescence staining. The level of mitophagy was evaluated by LC3 immunofluorescence staining and autophagosome counts using electron microscopy. Western blotting and qPCR were used to detect the expression of proteins and genes related to mitophagy and the NLRP3 inflammasome.

Results

After HSYC treatment, the ovarian damage was milder than in the CTX group. Compared with the CTX group; SOD, GSH-Px, and the total antioxidant capacity were significantly increased, while MDA and ROS were decreased in the HSYC treatment groups. Furthermore, mitochondrial distribution and membrane potential levels were improved after HSYC treatment compared to the CTX group. After the HSYC treatment, the LC3 fluorescent intensity and autophagosome counts were decreased. Similarly, mitophagy related markers PINK1, Parkin, LC3, and Beclin1 were decreased, while p62 was significantly increased, compared with the CTX groups. The mRNA and protein expression of NLRP3 inflammasome, NLRP3, caspase-1, GSDMD, IL-18, and IL-1β were significantly decreased in the HSYC treatment groups.

Conclusion

This is the first study in molecular mechanisms underlying HSYC against granulosa cell injury in POI. HSYC protects ovaries from CTX-induced ovarian damage and oxidative stress. HSYC enhanced ovarian function in mice with primary ovarian insufficiency by inhibiting PINK1-Parkin mitophagy and NLRP3 inflammasome activation.
Psychological factors in functional hypothalamic amenorrhea: A systematic review and meta-analysis
Authors: Bonazza Federica , Politi Giuliana , Leone Daniela , Vegni Elena , Borghi Lidia
Published: January 2023

Background

Psychological factors have been found to be associated with functional hypothalamic amenorrhea (FHA); however, their role in the onset or persistence of FHA is still understudied. The study aims to assess the associations of psychological factors with the presence vs the absence of FHA.

Methods

A systematic literature search has been conducted across the major databases (PubMed, PsycINFO, Scopus, and Embase) to explore the psychological factors associated with FHA. The search was limited to English-written articles published from 2000 onwards. Articles were selected based on stringent inclusion/exclusion criteria. After data extraction, meta-analysis and meta-synthesis were conducted.

Results

Of 349 retrieved articles, eight studies were included. Findings indicate that the main psychological factors associated to FHA seem to be depression and eating attitudes, especially drive for thinness. FHA women present higher levels of anxiety, sleep disorders, dysfunctional attitudes, and alexithymia. The meta-analysis on drive for thinness revealed that the pooled MD across the studies was statistically significant both in the fixed 0.63 (95% CI: 0.31–0.95) and random model 0.70 (95% CI: 0.13–1.26). Likewise, as for depression, the pooled MD across the studies was statistically significant both in the fixed 0.60 (95% CI: 0.36–0.84) and random model 0.61 (95% CI: 0.20–1.01).

Discussion

Findings showed the association of psychological factors and FHA and recognized their involvement in the persistence of the disorder. A multidisciplinary approach should involve a collaborative process between gynecologists, clinical psychologists, and psychiatrists, from diagnosis to treatment. Longitudinal studies should be implemented with a comparison/control group or by including clinical psychologists in the psychological assessment and study design.
Optimal allocation of a wind turbine and battery energy storage systems in distribution networks based on the modified BES-optimizer
Authors: Kamel Salah , Abdel-Mawgoud Hussein , Alrashed Mohammed M. , Nasrat Loai , Elnaggar Mohamed F.
Published: January 2023

Recently, incorporating renewable energy resources (RERs) like wind turbines (WTs) in a distribution network is rapidly increased to meet the load growth. However, distribution networks have been facing many challenges to withstand the intermittent output power of RERs. Battery energy storage (BES) is used with RERs to smoothly inject the output power to the grid by RERs. Therefore, this paper proposes an effective strategy for optimal allocation of WT and BES in RDS to decrease the total system losses. In addition, a modified bald eagle search (BES-optimizer) is proposed to obtain the preferable allocations of WT and BES simultaneously in the radial distribution system (RDS) considering the probabilistic distribution of the WT and load demand. IEEE 69-bus RDS is utilized as a test system. Based on the obtained results, installing WTs with BES gives better results than installing WTs alone in the RDS. However, the proposed algorithm proved its efficiency to obtain the best global results compared with other well-known techniques.
Tween 20 Stabilized Conventional Heavy Crude Oil-In-Water Emulsions Formed by Mechanical Homogenization
Authors: Shen Wanhua , Koirala Narayan , Mukherjee Debjani , Lee Kenneth , Zhao Min , Li Jianbing
Published: January 2023

This study investigated the preparation of stable conventional heavy crude oil-in-water (O/W) emulsions by mechanical homogenization with the addition of a non-ionic surfactant, Tween-20. A four-factor, five-level central composite design was carried out to investigate the effects of four independent variables, including mixing intensity (4,000–10,000 rpm), mixing duration (5–45 min), water salinity (0–40 g/L), and the concentration of emulsifier (0.1–2.1 wt%) on the emulsion stability. Emulsion stability was determined by quantification of creaming index, turbidity change rate, and average oil droplet size. The results demonstrated that the salinity of 30 g/L, mixing intensity of 8,500 rpm, mixing duration of 35 min, and emulsifier concentration of 1.6 wt% led to the formation of the most stable emulsion.
Spatial distribution characteristics of splashing rainfall caused by nappe flow impingement on a plunge pool
Authors: Sun Qian , Yuan Hao , Wei Wangru , Hu Liangliang , Xie Chunhang
Published: January 2023

Splashing is the main atomization source for a jet impinging on a liquid layer. Increased understanding of splashing rainfall characteristics can help to reduce the hazard of flood discharge atomization in hydraulic engineering. In this study, the spatial distribution of splashing rainfall caused by a nappe flow impinging on a downstream water cushion was experimentally investigated. Effects of the main hydraulic factors of impingement velocity, unit discharge, and water-cushion depth on splashing were investigated. The shape of splashing rainfall contours was approximately elliptical in horizontal planes. Maximum rainfall intensity was in the surrounding impingement region, and rainfall intensity decreased with an increase in the distance between the impingement center point and measurement points. Splashing rainfall intensity increased with increases in impingement velocity and unit discharge, whereas the opposite was observed with an increase in plunge pool depth. A gamma distribution described rainfall intensity distribution in the longitudinal and vertical direction, whereas a Gaussian distribution described intensity in the transverse direction. A series of empirical relations were proposed.
System dynamics simulation and regulation of human-water system coevolution in Northwest China
Authors: Wei Li , Liu Xiaopeng , Li Xinyan , Gao Haiyan
Published: January 2023

The human-water system synergy in Northwest China has become more significant as the ecological civilization construction continues and the implementation of the 2030 Agenda for Sustainable Development in China proceeds. In this study, taking the Ningxia Hui Autonomous Region as a typical research region, the human–water system coevolution model was established by coupling SD (System Dynamics) model and coevolution model from the theoretical perspective of complex system synergies, to simulate the human-water system’s coevolution trends from 2010 to 2030 in this region. Five regulation schemes were then designed to enhance the synergy of the human-water system by adjusting sensitive decision variables. The results revealed that the supply to demand ratio of water and the synergy index of the human-water system obtained by the status continuation scheme would decline from 1.02 and 0.39 in 2020 to 0.81 and 0.35 in 2030, respectively, indicating the growing gap between water supply and demand and revealing the worsening human-water relationship. Under the comprehensive optimization scheme, the supply to demand ratio of water and the synergy index of the human-water system would be higher than under the other schemes, demonstrating a substantially improved human-water relationship. Hence, a comprehensive optimization regulation scheme is proposed. This scheme combines improving pro-environmental water consumption, adapting industrial structures, and carrying out water conservation and pollution prevention. This research renders a decision-making basis for regulating regional water resources and finding paths to developing a harmonious relationship between humans and water.
Structurally rich dry grasslands – Potential stepping stones for bats in open farmland
Authors: Ewert Sophie P. , Knörnschild Mirjam , Jung Kirsten , Frommolt Karl-Heinz
Published: January 2023

Agricultural intensification has caused decrease and fragmentation of European semi-natural dry grasslands. While a high biodiversity value of dry grasslands is acknowledged for plants and insects, locally and on landscape level, their relevance for mobile species, such as bats, is unknown. Here we investigate the use of dry grassland fragments by bats in an agriculturally intensified region in Germany and evaluate local and landscape factors influencing bat activity and assemblages. Specifically, we predicted that a combination of local dry grassland structural richness and landscape features as well as their interactions affect bat activity and foraging above dry grasslands. We also expected that these features influence compositions of local bat assemblages. We repeatedly sampled at 12 dry grassland plots with acoustic monitoring and assessed activity and foraging of bat species/sonotypes, which we grouped into guilds known for foraging in open land, at vegetation edges and in narrow spaces. We determined structural richness of the dry grassland plots in field and derived landscape features from digital landscape data. A relatively high proportion of bat species/sonotypes used dry grasslands regularly. The edge space foragers responded positively to higher local structural richness. Their dry grassland use increased when surrounding forests and woody features were less available, but they foraged more on dry grasslands closer to water bodies. Narrow space bat activity on dry grasslands decreased with less landscape connectivity. Open and narrow space foragers responded to local structural richness only in landscape context. For all bat guilds we found increased use of structurally richer dry grasslands when there was more open farmland in the surroundings. This was also the case for edge space foragers, when landscapes were more homogeneous. Lastly, with increasing structural richness, bat assemblages were more dominated by edge space foragers. We show the importance of European dry grassland fragments for the highly mobile group of bats under certain local structural and landscape compositional conditions. Our results underline the value of heterogeneous dry grassland fragments as potential stepping stones in intensively used farmland areas and contribute to evidence based decision making in dry grassland management and bat conservation.
Old forest structural development drives complexity of nest webs in a naturally disturbed boreal mixedwood forest landscape
Authors: Cadieux Philippe , Drapeau Pierre , Ouellet-Lapointe Ugo , Leduc Alain , Imbeau Louis , Deschênes Réjean , Nappi Antoine
Published: January 2023

Structural complexity generated by forest development processes and tree species compositional changes provide key habitat features for vertebrate communities that rely upon tree size and decay processes for foraging, denning or nesting. Complexity of forest structure in old stands could not only be key for harboring increased taxonomic species diversity but also greater functional diversity through more complexity in networks of tree cavity dependent species. Using a nest web approach that hierarchically links cavity-bearing trees with cavity formation agents (natural decay processes and avian excavators) and cavity users (non-excavator species), we compared network characteristics of nest webs along a time since fire gradient in a naturally disturbed boreal mixedwood forest landscape in eastern North America. Since 2003, twelve 24 to 40 ha plots ranging from 61 to more than 245 years after fire were surveyed at the Lake Duparquet Research and Teaching Forest in Abitibi, Quebec, Canada to detect active nesting, and denning cavities. We found that network complexity both in terms of number of vertebrate species and number of interactions among species, increased along the age gradient and was significantly higher in the older stands than predicted by chance. Whereas cavity-nesting communities in old forests used a higher diversity of tree species over a wide range of decay stages, trembling aspen remained a key cavity-bearing tree throughout the age gradient. Woodpeckers were the main cavity formation agents whereas less than 1% of cavities originated from natural decay. The structural development of older forests is thus a driver for functional diversity in cavity-using vertebrate communities through higher interaction richness in nest webs, among cavity-bearing trees, excavators and non-excavating users. The pivotal contribution of the entire gradient of old forest cover types to the overall complexity of nest webs in the boreal mixedwood zone is also a key for the resilience of the cavity-using vertebrate community to natural disturbances. We discuss how such resilience may be compromised by even-aged industrial timber harvesting with short rotations that shifts the age structure of boreal landscapes toward regenerating and young pole forests whereas old forest cover types become below their historical range of variability.
Systematic genetic analysis of pediatric patients with autoinflammatory diseases
Authors: Poker Yvonne , von Hardenberg Sandra , Hofmann Winfried , Tang Ming , Baumann Ulrich , Schwerk Nicolaus , Wetzke Martin , Lindenthal Viola , Auber Bernd , Schlegelberger Brigitte , Ott Hagen , von Bismarck Philipp , Viemann Dorothee , Dressler Frank , Klemann Christian , Bergmann Anke Katharina
Published: January 2023

Monogenic autoinflammatory diseases (AID) encompass a growing group of inborn errors of the innate immune system causing unprovoked or exaggerated systemic inflammation. Diagnosis of monogenic AID requires an accurate description of the patients’ phenotype, and the identification of highly penetrant genetic variants in single genes is pivotal. We performed whole exome sequencing (WES) of 125 pediatric patients with suspected monogenic AID in a routine genetic diagnostic setting. Datasets were analyzed in a step-wise approach to identify the most feasible diagnostic strategy. First, we analyzed a virtual gene panel including 13 genes associated with known AID and, if no genetic diagnosis was established, we then analyzed a virtual panel including 542 genes published by the International Union of Immunological Societies associated including all known inborn error of immunity (IEI). Subsequently, WES data was analyzed without pre-filtering for known AID/IEI genes. Analyzing 13 genes yielded a definite diagnosis in 16.0% (n = 20). The diagnostic yield was increased by analyzing 542 genes to 20.8% (n = 26). Importantly, expanding the analysis to WES data did not increase the diagnostic yield in our cohort, neither in single WES analysis, nor in trio-WES analysis. The study highlights that the cost- and time-saving analysis of virtual gene panels is sufficient to rapidly confirm the differential diagnosis in pediatric patients with AID. WES data or trio-WES data analysis as a first-tier diagnostic analysis in patients with suspected monogenic AID is of limited benefit.
Clinical and genetic features of luscan-lumish syndrome associated with a novel de novo variant of SETD2 gene: Case report and literature review
Authors: Zhang Yanqing , Zhang Haozheng , Wu Wei , Wang Dong , Lv Yuqiang , Zhao Dongmei , Wang Lingxiao , Liu Yi , Zhang Kaihui
Published: January 2023

Introduction: Luscan-Lumish syndrome (LLS) is currently recognized as a rarely-observed condition featured with overgrowth, macrocephaly, obesity, type I Chiari malformation, and linguistic retardation. So far, there have been only a few LLS cases registered worldwide, but with none of them reported from China. To acquire a deeper understanding on the clinical and genetic features of this disease, a Chinese boy with LLS caused by a heterozygous variant in SETD2 gene was investigated in the present study.

Methods: The patient was clinically examined and the medical history of his family was collected. Genetic testing was performed to determine the genetic etiology.

Results: The proband was a boy aged 5-year-7-month-old, who was referred to our hospital due to “being a slow learner in kindergarten”. The child had a history of delayed motor and language development in comparison to his peers. After admission, physical examination revealed tall stature and macrocephaly as the major manifestation, in addition to a relatively lower rating in intelligence assessment as well as abnormal MRI images showing a slightly shorter corpus callosum accompanied by a mildly thinner corpus callosum body. Whole exome sequencing (WES) revealed a heterozygous c.2514_2516delTAG (p.Ser838del) variant in SETD2 gene, which was subsequently identified as a novel de novo variant. According to the standardized genetic variant classification published by the American College of Medical Genetics and Genomics (ACMG), the variant, with a pathogenicity analysis result indicating PS2 + PM2_Supporting + PM4, was determined to be likely pathogenic. Through literature review, the clinical phenotypes of the 15 LLS cases were summarized, including 8 cases of overgrowth (53%), 13 cases of macrocephaly (87%), 11 cases of developmental delay (73%), 8 cases of autism (53%), and 7 cases of special facial features (47%). Besides, abnormal craniocerebral MRI findings were noticed in 7 cases. Despite that the mutation sites of the 15 patients varied from case to case, they showed a uniformly distributed pattern throughout the whole SETD2 gene, including 5 missense mutations, 5 frameshift mutations and 5 non-sense mutations.

Conclusion: LLS, not having been recognized till recent years, is identified as an autosomal dominant syndrome triggered by SETD2 gene mutation. As the first report of LLS in China, the case in our study was proved to be associated with a unique type of SETD2 gene mutation that has never been reported previously, which is believed to enrich the mutation spectrum of SETD2 gene and also, deepening the clinicians’ understanding on the disease.
SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure
Authors: Gandhirajan Anugraha , Roychowdhury Sanjoy , Kibler Christopher , Cross Emily , Abraham Susamma , Bellar Annett , Nagy Laura E. , Scheraga Rachel Greenberg , Vachharajani Vidula
Published: January 2023

Alcohol abuse, reported by 1/8th critically ill patients, is an independent risk factor for death in sepsis. Sepsis kills over 270,000 patients/year in the US. We reported that the ethanol-exposure suppresses innate-immune response, pathogen clearance, and decreases survival in sepsis-mice via sirtuin 2 (SIRT2). SIRT2 is an NAD+-dependent histone-deacetylase with anti-inflammatory properties. We hypothesized that in ethanol-exposed macrophages, SIRT2 suppresses phagocytosis and pathogen clearance by regulating glycolysis. Immune cells use glycolysis to fuel increased metabolic and energy demand of phagocytosis. Using ethanol-exposed mouse bone marrow- and human blood monocyte-derived macrophages, we found that SIRT2 mutes glycolysis via deacetylating key glycolysis regulating enzyme phosphofructokinase-platelet isoform (PFKP), at mouse lysine 394 (mK394, human: hK395). Acetylation of PFKP at mK394 (hK395) is crucial for PFKP function as a glycolysis regulating enzyme. The PFKP also facilitates phosphorylation and activation of autophagy related protein 4B (Atg4B). Atg4B activates microtubule associated protein 1 light chain-3B (LC3). LC3 is a driver of a subset of phagocytosis, the LC3-associated phagocytosis (LAP), which is crucial for segregation and enhanced clearance of pathogens, in sepsis. We found that in ethanol-exposed cells, the SIRT2-PFKP interaction leads to decreased Atg4B-phosphorylation, decreased LC3 activation, repressed phagocytosis and LAP. Genetic deficiency or pharmacological inhibition of SIRT2 reverse PFKP-deacetylation, suppressed LC3-activation and phagocytosis including LAP, in ethanol-exposed macrophages to improve bacterial clearance and survival in ethanol with sepsis mice.
Immunogenicity, Effectiveness, and Safety of Inactivated Virus (CoronaVac) Vaccine in a Two-Dose Primary Protocol and BNT162b2 Heterologous Booster in Brazil (Immunita-001): A One Year Period Follow Up Phase 4 Study
Authors: Grenfell Rafaella F. Q. , Almeida Nathalie B. F. , Filgueiras Priscilla S. , Corsini Camila A. , Gomes Sarah V. C. , de Miranda Daniel A. P. , Lourenço Adelina J. , Martins-Filho Olindo A. , de Oliveira Jaquelline G. , Teixeira-Carvalho Andrea , Campos Guilherme R. F. , Nogueira Mauricio L. , Alves Pedro Augusto , Fernandes Gabriel R. , Castilho Leda R. , Lima Tulio M. , de Abreu Daniel P. B. , Alvim Renata G. F. , Silva Thaís Bárbara de S. , Jeremias Wander de J. , Otta Dayane A. , Campi-Azevedo Ana Carolina ,   Immunita-001 Team
Published: January 2023

Background

Effective and safe vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are critical to controlling the COVID-19 pandemic and will remain the most important tool in limiting the spread of the virus long after the pandemic is over.

Methods

We bring pioneering contributions on the maintenance of the immune response over a year on a real-life basis study in 1,587 individuals (18-90 yrs, median 39 yrs; 1,208 female/379 male) who underwent vaccination with two doses of CoronaVac and BNT162b2 booster after 6-months of primary protocol.

Findings

Elevated levels of anti-spike IgG antibodies were detected after CoronaVac vaccination, which significantly decreased after 80 days and remained stable until the introduction of the booster dose. Heterologous booster restored antibody titers up to-1·7-fold, changing overall seropositivity to 96%. Titers of neutralising antibodies to the Omicron variant were lower in all timepoints than those against Delta variant. Individuals presenting neutralising antibodies against Omicron also presented the highest titers against Delta and anti-Spike IgG. Cellular immune response measurement pointed out a mixed immune profile with a robust release of chemokines, cytokines, and growth factors on the first month after CoronaVac vaccination followed by a gradual reduction over time and no increase after the booster dose. A stronger interaction between those mediators was noted over time. Prior exposure to the virus leaded to a more robust cellular immune response and a rise in antibody levels 60 days post CoronaVac than in individuals with no previous COVID-19. Both vaccines were safe and well tolerated among individuals.

Interpretation

Our data approach the effectiveness of CoronaVac association with BNT162b2 from the clinical and biological perspectives, aspects that have important implications for informing decisions about vaccine boosters.

Funding

Fiocruz, Brazil.
Caspase-11 contributes to site-1 protease cleavage and SREBP1 activation in the inflammatory response of macrophages
Authors: Cheng Yinglan , Manabe Ichiro , Hayakawa Sumio , Endo Yusuke , Oishi Yumiko
Published: January 2023

Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that control fatty acid and cholesterol metabolism. As the major SREBP isoform in macrophages, SREBP1a is also required for inflammatory and phagocytotic functions. However, it is insufficiently understood how SREBP1a is activated by the innate immune response in macrophages. Here, we show that mouse caspase-11 is a novel inflammatory activator of SREBP1a in macrophages. Upon LPS treatment, caspase-11 was found to promote the processing of site-1 protease (S1P), an enzyme that mediates the cleavage and activation of SREBP1. We also determined that caspase-11 directly associates with S1P and cleaves it at a specific site. Furthermore, deletion of the Casp4 gene, which encodes caspase-11, impaired the activation of S1P and SREBP1 as well as altered the expression of genes regulated by SREBP1 in macrophages. These results demonstrate that the caspase-11/S1P pathway activates SREBP1 in response to LPS, thus regulating subsequent macrophage activation.