bluuebunny/crossref_metadata_2025 huggingface dataset:
Interval-valued (p,q,r)-Spherical Fuzzy Sets and Their Applications in MCGDM and MCDM Based on TOPSIS method and Aggregation Operators
Authors: Karaaslan Faruk , Karamaz Fatih
Published: May 2023

The (p,q,r)-Spherical fuzzy set is a useful generalization of other fuzzy structures such as fuzzy, intuitionistic fuzzy, Pythagorean fuzzy, picture fuzzy, q-rung orthopair fuzzy, spherical fuzzy, and T-spherical fuzzy sets. Also, expressing real-life data as a subinterval of the closed interval [0,1] rather than a crisp number provides better results in fuzzy mathematics. In this paper, we define a more general concept than (p,q,r)-spherical fuzzy sets called interval-valued (p,q,r)-spherical fuzzy set (IVpqr-SFS). Set-theoretical and arithmetic operations between two IVpqr-SFSs are defined. Some results related to these operations are obtained. Two aggregation operators named interval-valued (p,q,r)-spherical fuzzy weighted arithmetic (IVpqr-SFWAA) and interval-valued (p,q,r)-spherical fuzzy weighted geometric (IVpqr-SFWGA) aggregation operators are introduced for IVpqr-SF numbers (IVpqr-SFN) and their properties of them were examined. The proposed operators are explained with examples. Furthermore, the score and accuracy functions of an IVpqr-SFN are introduced. We also define distance measures between two same types IVpqr-SFSs based on Hamming, Euclidean, and Hausdorff distance measures. Moreover, a multi-criteria group decision-making (MCGDM) method is developed based on the TOPSIS method by using the proposed distance measures and score function, and a numerical example is given to show the process of the proposed MCGDM method. In addition, a multi-criteria decision-making (MCDM) method is developed using the proposed IVpqr-SFWAA, IVpqr-SFWGA operators, and an illustrative example is given to show the process of the proposed MCDM method. Finally, a comparative analysis was presented between the proposed methods and the existing methods.
A critical examination of the protection level for primary producers in the first tier of the aquatic risk assessment for plant protection products
Authors: Duquesne Sabine , Brendel Stephan , Hönemann Linda , Konschak Marco , Solé Magali , Wogram Joern , Pieper Silvia
Published: May 2023

Background
The aim of environmental risk assessment (ERA) for pesticides is to protect ecosystems by ensuring that specific protection goals (SPGs) are met. The ERA follows a prospective tiered approach, starting with the most conservative and simple step in risk assessment using the lowest available endpoint. For aquatic primary producers, however, the recommendation to use the lowest endpoint (referring to 50% inhibition in: “biomass” –area under the curve- EbC50, yield EyC50 or growth rate ErC50) and a default assessment factor (AF) of 10 has been changed in 2015, by switching to the sole use of the growth rate inhibition endpoint (ErC50). This study examines the implications of this change on the level of conservatism provided by the tier 1 risk assessment and evaluates whether it ensures a suitable minimum protection level.
Results
Our analysis shows that replacing the lowest endpoint with the growth rate inhibition endpoint while maintaining the AF of 10 significantly reduces the conservatism level of the tier 1 risk assessment. Comparing protection levels achieved with different endpoints reveals that the current assessment is less protective than the previously agreed assessment. To ensure a similar level of protection, we recommend to increase the AF to a minimum of 24 in the tier 1 risk assessment based on ErC50.
Independently of the endpoint selected for the tier 1 risk assessment, several issues in the general risk assessment of pesticides for aquatic primary producers contribute to uncertainties when assessing the protection levels, e.g. a lack of appropriate comparison of the surrogate reference tier with field conditions, the suitability of ErC50 for certain macrophytes species, and the regulatory framework's failure to consider realistic conditions in agricultural landscapes with multiple stressors and pesticide mixtures.
Conclusions
We advise to consider adjusting the risk assessment in order to reach at least the previously agreed protection level for aquatic primary producers. In view of multiple uncertainties pointing at a higher risk in the field as assumed in the ERA, continuing using an endpoint with a higher value and without adjustment of the assessment factor jeopardize the aim of halting biodiversity loss in surface waters.
Seasonal Variations of Arrhythmias and Their Impact on Mortality in Cancer Patients with Health Disparities: A Propensity Score Adjusted Machine Learning Analysis of Over 100 Million Hospitalizations Across 3 Years
Authors: Park Jong Kun , Monlezun Dominique , Kim Jin Wan , Going James , Khalaf Shaden , Honan Kevin , Badalamenti Andrew , Liu Victor , Barout Ahmad , Boone David , Safavi-Naeini Payam , Koutroumpakis Efstratios , Cilingiroglu Mehmet , Marmagkiolis Konstantinos , Iliescu Cezar , Karimzad Kaveh , Madjid Mohammad
Published: May 2023

Background
Arrhythmias are observed to increase during high influenza activity seasons (HIA, December to February) with significant clinical impact among high-risk patients, so their outcomes may be optimized through closer monitoring of these populations. It is unknown if cancer is such a risk factor.
Methods
This is a retrospective analysis of arrhythmia-related mortality and the effect of health disparities in patients with cancer during HIA and non-HIA seasons in a nationally representative database. Machine Learning-augmented Propensity Score adjusted multivariable regression (ML-PSr) was performed using the 2016–2018 National Inpatient Sample (NIS), the United States’ largest all-payer hospitalized dataset.
Results
16,795,379 (18.48%) patients presented with arrhythmia of whom 3,214,914 (19.14%) were during HIA. In ML-PSr, HIA did not significantly increase the odds of arrhythmia for cancer patients (OR 1.01, 95%CI 0.99–1.03, p = 0.37), but the odds of arrhythmia-related mortality were higher during HIA seasons (OR 1.19, 95%CI 1.12–1.27, p < 0.001) compared to non-HIA seasons (OR 1.17, 95%CI 1.13–1.22, p < 0.001). Primary malignancies with the highest prevalence of arrhythmias during HIA were lung (19.60%), leukemia (11.49%), non-Hodgkin lymphoma (NHL) (8.24%), prostate (8.15%), and multiple myeloma (MM) (6.21%) (p < 0.001). HIA increased arrhythmia-related mortality most for the following primary malignancies by year: gastrointestinal in 2016 (OR 1.15, 95%CI 1.01–1.32, p = 0.039), leukemia in 2017 (OR 1.31, 95%CI 1.10–1.54, p = 0.002), GI in 2018 (OR 1.14, 95%CI 1.01–1.29, p = 0.029), and renal in 2018 (OR 1.54, 95%CI 1.06–2.23, p = 0.025). Among patients with active cancer and arrhythmia, African Americans had significantly greater mortality than Caucasians (OR 1.13, 95%CI 1.03–1.23, p = 0.013) independent of socio-economic and clinical confounders.
Conclusion
This study suggests arrhythmia-related mortality was higher during HIA seasons compared to non-HIA seasons in cancer patients and showed notable disparities by race and worse outcomes by primary malignancy.
Invasions and symbioses: multidimensional variability of the microbiome of an introduced ascidian species
Authors: Galià-Camps Carles , Baños Elena , Pascual Marta , Carreras Carlos , Turon Xavier
Published: May 2023

Background Animals should be viewed as holobionts, complex entities composed of an animal host and their associated symbionts. This integrated perspective recognizes that the interaction between these two components is vital for the survival of the host. This synergy can be particularly relevant in the case of invasive species, as they constantly face habitat changes, and thus play a crucial role in their introduction and adaptation success. However, our understanding on the microbiome changes of invasive species from juveniles to adults associated with different tissues remains limited.Results We reveal that the introduced ascidian Styela plicata has a highly variable microbiome, which undergoes significant changes from juvenile to adult individuals and is highly specialised for each compartment analysed (tunic, gill, and gut) in different localities. This is the first time that a distinct gill microbiome is identified in an ascidian species. The variability observed is attributed to S. plicata’s ability to acquire its resident bacteria from the surrounding water, with a subsequent differential proliferation leading to the development of clearly differentiated microbiomes in each tissue. We also observe that the microbiome varies across harbours, suggesting adaptation to local environmental conditions. Furthermore, we find that each tissue’s microbiome is strongly correlated with environmental trace element concentrations, especially in adults, where trace element levels are higher. This fact suggests that the microbiome of S. plicata can play a role by either taking advantage or disposing of trace elements, many of which are toxic. Finally, we examine the metabolic pathways attributable to each microbiome, revealing that adult microbiomes have specific metabolic pathways that might enhance tissue functionality, conferring a high adaptive potential to S. plicata to withstand new conditions during the introduction process, turning this species into one of the most successful invasive holobionts worldwide.Conclusions Our findings emphasise the need for integrative approaches to investigate animal microbiomes, considering multiple variables to fully comprehend the relationship between host and microbiome, as well as their implications for host integrity. Thus, this work confirms the complex interplay between S. plicata and its microbiomes, and how it has significant implications for the invasive success of this species.
Increased cerebrospinal fluid levels of neuroinflammatory biomarkers in athletes with persistent symptoms following sports-related concussion
Authors: Gard Anna , Vedung Fredrik , Piehl Fredrik , Khademi Mohsen , Wernersson Maria Portonova , Rorsman Ia , Tegner Yelverton , Pessah-Rasmussen Hélène , Ruscher Karsten , Marklund Niklas
Published: May 2023

A sports-related concussion (SRC) is often caused by rapid head rotation at impact, leading to shearing and stretching of axons in the white matter and initiation of secondary inflammatory processes that may exacerbate the initial injury. We hypothesized that athletes with persistent post-concussive symptoms (PPCS) display signs of ongoing neuroinflammation, as reflected by altered profiles of cerebrospinal fluid (CSF) biomarkers, in turn relating to symptom severity. We recruited athletes with PPCS for ≥ 6 months for symptom rating using the Sport Concussion Assessment Tool, version 5 (SCAT-5) and for cognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). We analysed 27 CSF inflammatory biomarkers (pro-inflammatory chemokines and cytokine panels) by a multiplex immunoassay using antibodies as electrochemiluminescent labels to quantify concentrations in PPCS athletes, and in healthy age-, sex- and athletically matched controls. Thirty-six subjects were included, 24 athletes with PPCS and 12 controls. The SRC athletes had sustained a median of five concussions, the most recent at a median of 17 months prior to the investigation. When comparing CSF cytokines and chemokines levels in SRC athletes and controls, we found a significant increase in eight (IL-2, TNF-α, IL-15, TNF-β, VEGF, Eotaxin, IP-10, and TARC), a significant decrease in one (Eotaxin-3), and unaltered levels of 16, and two were un-detectable. The SRC athletes reported many and severe post-concussive symptoms on SCAT5, and 10 out of 24 athletes performed in the impaired range (Z<-1.5) on cognitive testing. Individual biomarker concentrations did not correlate with cognitive function. In conclusion, based on CSF inflammatory marker profiling we find signs of ongoing neuroinflammation persisting months to years after the last sport-related concussion in athletes with prolonged and persistent post-concussive symptoms. Since an ongoing inflammatory response may exacerbate the brain injury these results encourage studies of treatments targeting the post-injury inflammatory response in sports-related concussion.
Targeting UNC-51-like kinase 1 can inhibit esophageal cancer cell proliferation and regulate autophagy
Authors: Mao Yazhen , Chen Hongquan , Chen Yong , Qian Hongyun , Chen Qing , Lin Wei , Qi Yuanlin
Published: May 2023

The purpose of this study was to investigate the expression of UNC-51-like kinase 1 (ULK1) in esophageal cancer(ESCA) and its prognostic value, its effect on esophageal cancer cell growth and proliferation, and the synergistic effect of its inhibitor and cisplatin on esophageal cancer cells. Methods: 1. The expression and prognosis of ULK1 in pancancer and ESCA were analyzed with the TCGA database. 2. The effect of ULK1 knockdown on the proliferation of esophageal cancer ECA109 cells was observed in the plate colony formation assay. 3. CCK-8 assay, flow cytometry and Western blotting were used to explore the synergistic effect of cisplatin and a ULK1 inhibitor on the apoptosis of esophageal cancer cells. 4. Bioinformatics and Western blotting were used to analyze the possible mechanism by which ULK1 regulates ESCA. Results: 1. ULK1 was highly expressed in esophageal squamous cell carcinoma (ESCC) and was negatively correlated with the prognosis of patients. 2. Knockdown of ULK1 reduced the proliferation ability of esophageal cancer cells; 3. The combination of a ULK1 inhibitor and cisplatin enhanced the toxicity to ESCC cells and induced apoptosis. 4. ULK1 may be related to autophagy in ECA cells, and the combination of a ULK1 inhibitor and cisplatin can enhance the toxicity of cisplatin by inhibiting autophagy. Conclusion: Knockdown of ULK1 or the use of small molecule inhibitors can inhibit the proliferation of esophageal cancer cells, induce apoptosis, and enhance the toxicity of chemotherapeutic drugs on esophageal cancer cells, which may be related to the regulation of autophagy.
Exploring the Influence of Climatic Variables on Mycobiome Composition and Community Diversity in Lichens: Insights from Structural Equation Modeling Analysis
Authors: Yang Ji Ho , Woo Jung-Jae , Kim Wonyong , Oh Seung-Yoon , Hur Jae-Seoun
Published: May 2023

BackgroundLichens are symbiotic organisms composed of a fungus and a photosynthetic partner, which are key ecological bioindicators due to their sensitivity to environmental changes. The endolichenic fungi (ELF) living inside lichen thalli, are an important but understudied component of playing crucial ecological roles such as nutrient cycling and protection against environmental stressors. Therefore ELF community investigation is vital for fostering sustainable ecosystems and leveraging their ecological benefits. Deciphering the intricate relationships between ELF and their lichen hosts, alongside the influence of environmental factors on these communities, presents a significant challenge in pinpointing the underlying drivers of community structure and diversity.ResultsOur research demonstrated that locational factors were the main drivers of the ELF community structure, rather than host haplotype. Several climatic factors affected the diversity of the ELF community and contributed to the prevalence of different types of fungal residents within the ELF community. A decrease in isothermality was associated with a greater prevalence of pathotrophic and saprotrophic fungi within the ELF community, resulting in an overall increase in community diversity. By conducting a structural equation modeling analysis, we identified a robust link between climatic variables, fungal trophic mode abundance, and the species diversity of the ELF community.ConclusionThis study's discoveries emphasize the significance of examining climate-related factors when investigating ELF's structure and function. The connection between fungi and climate is intricate and complex, and can be influenced by various other factors. Investigating the potential for ELF to adapt to changing climatic conditions, as well as the potential effects of changes in ELF communities on lichen function, would be valuable research areas. We anticipate that our research results will establish a basis for numerous future ELF research projects and have a significant impact on the field.
RETRACTED: Self Learning and Context based approach of Slot Label Creation and Slot Filling for Interactive Systems
Authors: Magoo Chandni , Singh Manjeet
Published: May 2023

The authors have requested that this preprint be removed from Research Square.
Young People’s Sense of Agency and Responsibility towards Mental Health in Brazil: A Reflexive Thematic Analysis
Authors: Mendes Josimar Antônio Alcântara , Murta Sheila Giardini , Siston Felipe Rodrigues , Cunha Rafaela Oliveira da , Seabra Brenda Thallys Rocha , Ferreira Julyana Alves , Souza Rafael Ribeiro Alves , Santos Victor Hugo Lima , Singh Ilina , Pavarini Gabriela
Published: May 2023

Background: Young people have the potential to be effective agents within their communities, and can play a critical role in promoting their peers’ mental health and well-being. But do young people feel a sense of agency and responsibility towards promoting their peers’ mental health and well-being? This co-produced study mapped how Brazilian young people perceived their role in promoting their peers’ mental health and well-being, as well as perceived barriers to their engagement.
Methods: Participants were 46 Brazilian adolescents aged between 15 and 18 years old, recruited primarily via social media. Data were collected via focus groups and individual interviews conducted by a youth collaborator and a senior researcher. Anonymised transcripts were analysed through a reflexive thematic analysis that generated four themes.
Results: Two themes report on young people’s sense of agency and responsibility and the strategies they use to promote their peers’ mental health and well-being. Most participants felt motivated to promote mental health and many seemed very committed to providing such support; yet, others felt it was a burden or did not think it was their duty. Examples of strategies included peer-to-peer support such as listening to each other without judgement, but also collective actions such as organising support groups in the school. The other two themes report on contextual and intrapersonal issues that can impair young people’s potential to support their peers’ mental health and well-being, and included: feeling unheard or not trusted by adults, fearing judgement due to mental health stigma, and lacking skills and self-efficacy.
Conclusions: These results help advance our understanding of adolescents’ potential for taking action to promote mental health and well-being. However, their potential will not be realised unless identified barriers are addressed, for instance by providing young people with peer support training, and tackling adultism and mental health stigma.
You just want a break from the hatred of failure: The lived experience of being a student physiotherapist perfectionist and considerations for educators
Authors: McKay Jane , Williams Kim , Stewart Jennie
Published: May 2023

Perfectionism is a personality orientation associated with mental health and adjustment problems. Recent evidence demonstrates that perfectionism is widespread among students and on the rise, with recent generations of students placing increasingly more importance on perfection. Whilst the extant literature is vast, it tends to focus on psychopathology and identification of perfectionism correlates rather than the experience of student perfectionism. Furthermore, the education literature, is scant and there is a need to understand the deeper processes and nuances of perfectionism, particularly within health professions education where high study demands, competition to gain entry to educational programmes, and professional cultures may nurture the problem. This phenomenological study explored the lived experiences of physiotherapy students as they wrestled with perfectionism in the various facets of their studies. Participants were ten physiotherapy students with elevated perfectionism. Semi-structured interviews were undertaken and participants completed log sheets to document perfectionism-related experiences. Idiographic profiles were composed and interview transcripts were analysed, drawing upon features of both phenomenological and thematic analysis. Perfectionism was found to have toxic consequences for the learning experience. Harmful phenomenological experiences included perpetual and excessive achievement striving, punitive self-criticism and health and wellbeing difficulties. A range of sabotaging learning behaviours such as self-handicapping and feedback avoidance was also illuminated, and cultural and organisational influences perceived to foster perfectionism emerged. Findings are discussed in relation to underlying processes and implications for educators. The prospect of findings transferring to other educational contexts is highlighted.
Persistent endothelial dysfunction in post-COVID-19 syndrome and its associations with symptom severity and chronic inflammation
Authors: Kuchler Timon , Günthner Roman , Ribeiro Andrea , Hausinger Renate , Streese Lukas , Wöhnl Anna , Kesseler Veronika , Negele Johanna , Assali Tarek , Carbajo-Lozoya Javier , Lech Maciej , Adorjan Kristina , Stubbe Hans Christian , Hanssen Henner , Kotilar Konstantin , Haller Berhard , Heemann Uwe , Schmaderer Christoph
Published: May 2023

Background
Post-COVID-19 syndrome (PCS) is a lingering disease with ongoing symptoms such as fatigue and cognitive impairment resulting in a high impact on the daily life of patients. Understanding the pathophysiology of PCS is a public health priority, as it still poses a diagnostic and treatment challenge for physicians.
Methods
In this prospective observational cohort study, we analyzed the retinal microcirculation using Retinal Vessel Analysis (RVA) in a cohort of patients with PCS and compared it to an age- and gender-matched healthy cohort (n=41, matched out of n = 204).
Measurements and main results
PCS patients exhibit persistent endothelial dysfunction (ED), as indicated by significantly lower venular flicker-induced dilation (vmax; 3.42% ± 1.77% vs. 4.64 % ± 2.59%; p = 0.02), narrower central retinal artery equivalent (CRAE; 178.1 [167.5 - 190.2] vs. 189.1 [179.4 - 197.2], p = 0.01) and lower arteriolar-venular ratio (AVR; (0.84 [0.8 - 0.9] vs. 0.88 [0.8 - 0.9], p = 0.007). When combining AVR and vmax, predicted scores reached good ability to discriminate groups (area under the curve: 0.75). Higher PCS severity scores correlated with lower AVR (R= -0.37 p = 0.017). The association of microvascular changes with PCS severity were amplified in PCS patients exhibiting higher levels of inflammatory parameters.
Conclusion
Our results demonstrate that prolonged endothelial dysfunction is a hallmark of PCS, and impairments of the microcirculation seem to explain ongoing symptoms in patients. As potential therapies for PCS emerge, RVA parameters may become relevant as clinical biomarkers for diagnosis and therapy management.
Trial Registration
This study was previously registered at ClinicalTrials (“All Eyes on PCS - Analysis of the Retinal Microvasculature in Patients With Post-COVID-19 Syndrome”. NCT05635552. https://clinicaltrials.gov/ct2/show/NCT05635552).
TMEM147 aggravates the progression of HCC by modulating cholesterol homeostasis, suppressing ferroptosis, and promoting M2 polarization of TAMs
Authors: Huang Jingjing , Pan Huayang , Sun Jing , Wu Jiaming , Xuan Qiyue , Wang Jinge , Ke Shanjia , Lu Shounan , Li Zihao , Feng Zhigang , Hua Yongliang , Yu Qingan , Yin Bing , Qian Baolin , Zhou Menghua , Xu Yanan , Bai Miaoyu , Zhang Yingmei , Wu Yaohua , Ma Yong , Jiang Hongchi , Dai Wenjie
Published: May 2023

Background: The endoplasmic reticulum (ER) regulates critical processes, including lipid synthesis, which can be affected by transmembrane proteins localized in the ER membrane. One of them, the transmembrane protein 147 (TMEM147) has been recently implicated for its role in hepatocellular carcinoma (HCC) tumorigenesis, though the mechanisms remain unclear. Here, we investigated the role of TMEM147 in HCC and its underlying mechanisms.
Methods: Expression of TMEM147 was examined in human HCC and adjacent non-tumorous tissues using quantitative real-time polymerase chain reaction (qRT-PCR), western blotting, and immunohistochemistry. The effects of TMEM147 on HCC progression were investigated both in vitro and in vivo. Proteins interacting with TMEM147 were identified using RNAseq analysis, immunoprecipitation, and mass spectrometry analyses. Lipidomic analysis and enzyme-linked immunosorbent assay (ELISA) were employed to identify and analyze cholesterol and 27-hydroxycholesterol (27HC) contents. Comprehensive experimental methods were used to demonstrate ferroptosis in HCC cells. The fatty acid content of macrophages affected by TMEM147 was quantified using ELISA. Macrophage phenotypes were determined using various assays, such as immunofluorescence assay and flow cytometry analysis.
Results: TMEM147 mRNA and protein levels were upregulated in HCC, and increased TMEM147 expression was associated with poor survival. TMEM147 promoted tumor cell proliferation and metastasis in vitro and in vivo. It was found to interact with the key sterol reductase DHCR7, which affected cellular cholesterol homeostasis and increased extracellular 27HC levels in HCC. TMEM147 promoted the expression of DHCR7 by enhancing the activity of the transcription factor, STAT2. 27HC upregulated the expression of glutathione peroxidase 4 in HCC, leading to ferroptosis resistance and promotion of HCC proliferation. HCC cell-derived 27HC activated PPARγ signaling and enhanced lipid metabolism in macrophages, thereby activating M2 polarization, and then promoted the invasion and migration of HCC.
Conclusions: Our results indicated that TMEM147 confers ferroptosis resistance and M2 macrophage polarization, which are mainly dependent on the upregulation of cellular cholesterol homeostasis and 27HC secretion, leading to cancer growth and metastasis. Our findings suggest that the TMEM147/STAT2/DHCR7/27HC axis in the tumor microenvironment may serve as a promising therapeutic target for HCC.
Spin Injection Efficiency in the Topological Insulator and Diluted Magnetic Semiconductor Structure
Authors: Pak Myong Chol , Ri Un Chol , Jong Yong Gwang
Published: May 2023

We discuss spin transport in topological insulator (TI) and diluted magnetic semiconductor (DMS) heterogeneous structures. In DMS / FM (Ferromagnetic Metal) heterogeneous structure, the spin injection efficiency changes according to the electric field and Fermi energy were investigated. Thehigher electric field, the stronger spin injection efficiency, and its velocity of increase gets lower and approaches to the equilibrium state. Additionally, the higher interface conductivity, the weaker spin injection efficiency, and the transmission due to Fermi energy of spin up and spin down is different from each other. In the same structure, the spin injection efficiency changes depending on the magnetic field, and the spin injection efficiency vibrates sensitively according to the magnetic field. In TI / DMS heterogeneous structure, the spin current changes according to magnetic field were investigated. Here, when the magnetic field is low, the spin current oscillates, and as the magnetic field increases, the vibration is attenuated. It also decreases with increasing temperature and weakens vibrations. This is due to the competitive effect of the chiral properties of Dirac type quasiparticles in the topological insulator and the unique properties of exchange interaction between electrons and ions in DMS. This result allows us to expect the possibility of spintronic devices with high sensitivity to magnetic field.
Evaluation of Areca Quality Based on Principal Component and Hierarchical Cluster Analyses in Hainan, China
Authors: Wang Shiping , Kang Xiaoning , Dai Jiahui , Dai Wenting , Zhang Jing , Ji Jianbang
Published: May 2023

Areca (Areca catechu L.) is one of the most important cash crops in China and is considered the fourth most widely used addictive substance. In addition, areca is widely used in traditional and herbal medicines. The major characteristics of the fruit are affected by its genetic background and growth environment. The growing environment in different regions will impact the quality of agricultural products and the processing quality. The quality of areca is not only the basis of its commercialization development and processing quality, but also is an important basis for the scientific planting of areca. Therefore, determining the quality of areca will provide evidence for scientific planting and more optimal applications. We evaluated the quality of areca by comparing the differences in physicochemical characteristics using principal component analysis (PCA) and hierarchical cluster analysis. A total of 165 arecas, in the same growth period, were collected from 11 main producing regions in Hainan Province. Our results illustrate that the physicochemical characteristics of areca in different regions were significantly different. The PCA was conducted using 10 quality indexes, and three principal components were extracted to reflect 80% of the original variables. The first principal component mainly reflected the fruit shape quality, the second principal component mainly reflected the hardness quality, and the third principal component mainly reflected the functional component quality. The relationship between each producing region and the principal component could be obtained intuitively from the principal component score plots. The arecas in Wanning and Wenchang were larger and their cellulose content was greater than in other areas, indicating that they were more suitable for processing. In contrast, the arecas in Baoting, Wuzhishan, Danzhou, Tunchang, and Dongfang had a greater arecoline content than the other areas, making them more suitable for use as medicinal materials. Hierarchical cluster analysis classified the 11 producing regions into five categories based on the measured parameters, which was consistent with the results of the PCA score plots. These results could provide information to improve the use of areca in China.
Pseudogap metal and magnetization plateau from doping moiré Mott insulator
Authors: Zhang Yang , Fu Liang
Published: May 2023

The problem of doping Mott insulators is of fundamental importance and long-standing interest in the study of strongly correlated electron systems. The advent of semiconductor based moiré materials opens a new ground for simulating the Hubbard model on the triangular lattice and exploring its rich phase diagram as a function of doping and external magnetic field. Based on our recent identification of spin polaron quasiparticle in Mott insulator, in this work we predict the emergence of a pseudogap metal phase at small doping below half filling and an intermediate range of fields, which exhibits a single-particle gap and a doping-dependent magnetization plateau.
GENEL SAĞLIK SİGORTASI KAPSAMINDA YURT DIŞINDA SUNULAN SAĞLIK HİZMETLERİNDEN YARARLANMA
Authors: DEMİRKAYA Seher
Published: May 2023

Kişilerin sağlık hakkı kapsamında tedavi, tanı ve tetkik gibi hizmetleri yurt içinde alması ve bunlara ulaşımın öncelikle hükümetler tarafından ücretsiz/karşılıksız olarak sağlanması gerekir. Ancak bazen ülke içinde sunulan sağlık hizmetleri yeterli olmamakta, kişiler gerekli tedavi hizmetlerini almak için vatandaşı olunan ülke dışına yönelmek zorunda kalmaktadırlar. Bu durum da yurt dışında alınacak tedavi hizmetlerinin sigorta kapsamında yer alıp almayacağı sorununu ortaya çıkarmaktadır. Türkiye açısından konu değerlendirildiğinde, yurt dışı tedavi hizmetlerinden yararlanmanın genel sağlık sigortası kapsamına dâhil edildiği, sigorta kapsamındaki kişilerin faydalanabildiği, ancak söz konusu hizmetlerden yararlanabilmenin bazı koşullara ve işlemlere tabi tutulduğu görülmektedir. Sigorta kapsamında yurt dışı tedavi hizmetlerinden yararlanabilmenin ön koşulu Türkiye’de tedavi ve tetkik hizmetlerinin gerçekleştirilemediğinin ispat edilmesidir. Sonrasında ise ilgili raporların ve diğer prosedürlerin tamamlanması gerekir. Gerekli işlemler konusunda genel sağlık sigortası hükümleri yol göstericidir. Sosyal güvenlik sisteminin parçalı ve dağınık yapısı, genel sağlık sigortasına ilişkin işlemlerin düzenlendiği hukuki kaynaklara da yansımaktadır. Bu çalışmada, yurt dışında tedavi ve tetkik hizmeti alınabilmesinin genel sağlık sigortası kapsamındaki yerine, 5510 sayılı Kanun’daki genel hükümlere ve bunların uygulamasını açıklayan ilgili yönetmelik, tebliğ ve genelgelere dayalı olarak yapılacak işlemlere ve gerekli prosedürlere değinilerek, dağınık durumdaki mevzuat hükümleri bir araya getirilmeye çalışılmıştır. Böylelikle, yurt dışında genel sağlık sigortası kapsamında sağlık hizmeti alacak Türk vatandaşlarına ilişkin tüm hükümlerin bir arada yer aldığı bir başvuru kaynağı oluşturulmaya çaba gösterilmiştir.
Contribution to the study of ammonium leaching and its influencing factors in the soils of Al-Sin Lake Catchment, Banias, Syria
Authors: Mahalla Dia , Shahin Haytham , Ghaffar Muhammad , Dais Maher , Ibrahim Kinan
Published: May 2023

In this study, the sites of Beit Aana, Al-Qutailbiya, Quorfase and Al-Waha Spring were characterized by high levels of leaching whereas the highest concentrations of ammonium leaching were measured in December 2019 and March 2020, ranging between 5.74 and 5.81 mg/L. However, the lowest concentration (0.97 mg/L) was recorded in February 2020 in the sites of Bestwair, Beit Al-Alouni, Geiboul and Al-Rahbeyia with lower levels of leaching. The highest concentrations of ammonium leaching were obtained during November 2019 and April 2020, ranging between 3.51 and 4.31 mg/L whilst the lowest concentration of ammonium (0.59 mg/L) was determined in January 2020. It was found that the levels of ammonium leaching decreased with depth. The statistical study showed a correlation between ammonium leaching and the following variables: organic matter (OM), the saturated hydraulic conductivity (SHC) and pH. Regression equations representing ammonium leaching in soil horizons and their role were also obtained.
Quantitative study of biofilm yield and biomass distribution of a multi-stage moving-bed biofilm system
Authors: Chen Ning , Wang Xiaodong , Huang Mei , Maletskyi Zakhar , Ratnaweera Harsha , Bi Xuejun
Published: May 2023

A multi-stage anoxic/oxic (A/O) moving-bed biofilm reactor (MBBR) system with multiple chambers was established for municipal wastewater treatment. The active biomass quantity, bioactivity, and biomass yield of a pilot-scale multi-stage MBBR were investigated in this study. The microbial activity and heterotrophic yield coefficients (YH) were measured using respirometric techniques in each chamber at different temperature conditions. Meanwhile, the growth, nitrification, and denitrification rates of functional biomass were also quantified as specific respiration rate (SOUR). The total active biomass in the multi-stage A/O-MBBR system was 0.71–1.68 g COD/m2 for the aerobic reactor and 0.39–1.44 g COD/m2 for the anoxic reactor at 10–19 °C. The YH values for the anoxic reactors were 0.61–0.69, which were comparable to the recommended value of the activated sludge model (ASM1). The correlation coefficient between Nitrospira and the autotrophic specific respiration rate (SOURA) was 0.82. Meanwhile, denitrifying genera showed a significant correlation with the heterotrophic specific respiration rate (SOURH) and the active heterotrophic biomass (XH). This study provided insights into biomass distribution and the corresponding kinetic parameters for the multi-stage MBBR systems, which may serve as a reference for process design and trouble shooting.
Screening and Activity Evaluation of Novel BCR-ABL/T315I Tyrosine
Kinase Inhibitors
Authors: Su Jie , Fu Chenggong , Wang Shuo , Chen Xuelian , Wang Runan , Shi Huaihuai , Li Jiazhong , Wang Xin
Published: May 2023

Introduction:

Chronic myeloid leukemia (CML) is a kind of malignant tumor
formed by the clonal proliferation of bone marrow hematopoietic stem cells. BCR-ABL
fusion protein, found in more than 90% of patients, is a vital target for discovering anti-
CML drugs. Up to date, imatinib is the first BCR-ABL tyrosine kinase inhibitor (TKI) approved
by the FDA for treating CML. However, the drug resistance problems appeared
for many reasons, especially the T135I mutation, a "gatekeeper" of BCR-ABL. Currently,
there is no long-term effective and low side effect drug in clinical.

Methods:

This study intends to find novel TKIs targeting BCR-ABL with high inhibitory
activity against T315I mutant protein by combining artificial intelligence technology and
cell growth curve, cytotoxicity, flow cytometry and Western blot experiments.

Results:

The obtained compound was found to kill leukemia cells, which had good inhibitory
efficacy in BaF3/T315I cells. Compound no 4 could induce cell cycle arrest, cause
autophagy and apoptosis, and inhibit the phosphorylation of BCR-ABL tyrosine kinase,
STAT5 and Crkl proteins.

Conclusion:

The results indicated that the screened compound could be used as a lead compound
for further research to discover ideal chronic myeloid leukemia therapeutic drugs.
Discovery of Novel Cysteine Protease Inhibitors for the Treatment of
Coronavirus (COVID-19)
Authors: De Surya K.
Published: May 2023

The application describes compounds, such as compounds of general Formula,
with warheads and their use in treating medical diseases or disorders, such as viral infections.
Pharmaceutical compositions and synthetic methods of various compounds with
warheads are included. The compounds are inhibitors of proteases, such as the 3C, CL- or
3CL-like protease.
Synthesis and Biological Activity of 2,6-Naphthyridine Derivatives: A Mini Review
Authors: Wójcicka Anna
Published: May 2023

The broad spectrum of biological activity of 2,6-naphthyridine, one of the six
structural isomers of pyridopyridine, is the main reason for the development of new compounds
containing this scaffold. This review paper aims to present various methods for obtaining
2,6-naphthyridine analogues and their biological activity, which have been reported
in the scientific literature. Compounds containing the 2,6-naphthyridine moiety can be isolated
from plants or obtained synthetically from various substrates: pyridine derivatives,
other heterocyclic derivatives, or acyclic compounds. Biological investigations have shown
that these compounds exhibit various biological activity; among others, they have an effect
on the central nervous system or anticancer or antimicrobial activity.
LncRNA CAI2 Contributes to Poor Prognosis of Glioma through the
PI3K-Akt Signaling Pathway
Authors: Jiang Yu , Zhang Jinhui , Yu Shengjin , Zheng Linlin , Shen Yue , Ju Weiwei , Lin Lijuan
Published: May 2023

Aims:

We aim to explore new potential therapeutic targets and markers in human glioma

Background:

Gliomas are the most common malignant primary tumor in the brain.

Objective:

In the present research, we evaluated the effect of CAI2, a long non-coding RNA, on
the biological behaviors of glioma and explored the related molecular mechanism.

Methods:

The expression of CAI2 was analyzed using qRT-PCR in 65 cases of glioma patients. The
cell proliferation was determined with MTT and colony formation assays, and the PI3K-AKt signaling
pathway was analyzed using western blot.

Results:

CAI2 was upregulated in human glioma tissue compared with the matched, adjacent nontumor
tissue and was correlated with WHO grade. Survival analyses proved that the overall survival
of patients with high CAI2 expression was poor compared to that of patients with low CAI2 expression.
High CAI2 expression was an independent prognostic factor in glioma. The absorbance
values in the MTT assay after 96 h were .712 ± .031 for the si-control and .465 ± .018 for the si-
CAI2-transfected cells, and si-CAI2 inhibited colony formation in U251 cells by approximately
80%. The levels of PI3K, p-AKt, and AKt in si-CAI2-treated cells were decreased.

Conclusion:

CAI2 may promote glioma growth through the PI3K-AKt signaling pathway. This
research provided a novel potential diagnostic marker for human glioma.
Intrinsic Apoptotic Pathway Genes of Circulating Blood Neutrophils Triggered
during HIV Infection and Remained Stimulated in ART Patients
Authors: Munshi Saif Ullah , Muraduzzaman A K M , Islam Nabeela Mahboob , Tabassum Shahina
Published: May 2023

Background:

The intrinsic apoptotic pathway of neutrophils in Human Immunodeficiency
Virus (HIV) infection results in spontaneous neutrophil death. There is a scarcity of data regarding
the gene expression of an intrinsic apoptotic pathway of neutrophils in HIV patients.

Objective:

The objective of this study was to observe the differential expression of some important
genes involved in the intrinsic apoptotic pathway of HIV patients, including those who were receiving
antiretroviral therapy (ART).

Methods:

Blood samples were collected from asymptomatic, symptomatic, ART receiver HIV patients,
and healthy individuals. Total RNA was extracted from neutrophils and subjected to quantitative
real-time PCR assay. CD4+T cells and an automated complete blood count were performed.

Results:

Among the asymptomatic, symptomatic, and ART receiver HIV patients (n=20 in each
group), median CD4+T counts were 633, 98, and 565 cells/ml, and the length of HIV infection in
months (± SD) was 24.06 ± 21.36, 62.05 ± 25.51, and 69.2 ± 39.67, respectively. Compared with
healthy controls, intrinsic apoptotic pathway genes, i.e., BAX, BIM, Caspase-3, Caspase-9, MCL-1,
and Calpain-1, were upregulated to 1.21 ± 0.33, 1.8 ± 0.25, 1.24 ± 0.46, 1.54 ± 0.21, 1.88 ± 0.30,
and 5.85 ± 1.34 fold in the asymptomatic group, and even more significantly, i.e., 1.51 ± 0.43, 2.09
± 1.13, 1.85 ± 1.22, 1.72 ± 0.85, 2.26 ± 1.34, and 7.88 ± 3.31 fold in symptomatic patients, respectively.
Despite CD4+ T-cell levels increased in the ART receiver group, these genes did not approach
the level of healthy or asymptomatic and remained significantly upregulated.

Conclusion:

The genes involved in the intrinsic apoptotic pathway in circulating neutrophils during
HIV infection were stimulated in vivo, and ART reduced the expression of those upregulated genes
but did not return to the level of asymptomatic or healthy individuals.
Scaffold-hopping of Linifanib to Design 6-phenylisoxazolo[3,4-b]pyridin-3-amine
Derivatives as FLT3 Inhibitors for Treating Acute Myeloid Leukemia
Authors: Wu Shi-Han , Ma Yi-Yuan , Yang Li-Jin , Cao Yu-Hao , Tong Zhen-Jiang , Wu Jia-Zhen , Wang Yi-Bo , Sha Jiu-Kai , Ding Ning , Liang Qiao-Li , Chang Liang , Wang Xiao-Long , Duan Jin-Ao , Yu Yan-Cheng , Dai Wei-Chen , Xie Ke , Leng Xue-Jiao , Xue Xin , Sun Shan-Liang , Li Nian-Guang , Shi Zhi-Hao
Published: May 2023

Background:

Acute myeloid leukemia (AML) is the most common type of blood cancer. Fmslike
tyrosine kinase 3 (FLT3) is a member of the class III receptor tyrosine kinase family. Overexpression
of FLT3 was found in 70-100% of patients with acute myeloid leukaemia. FLT3 internal tandem duplication
alteration (ITD) and the tyrosine kinase domain (TKD) are the most common molecular alteration in
AML, and FLT3 has become a promising drug target for AML.

Objective:

A series of 6-phenylisoxazolo[3,4-b]pyridin-3-amine derivatives F1–F15 with amide bonds as
FLT3 inhibitors were designed and synthesized in order to find a new lead compound to treat AML.

Methods:

We designed an original scaffold-hopping protocol by combing the RECAP tool with the
Gilde-Based Core-Hopping tool to design novel FLT3 inhibitors based on Linifanib. Inhibitors assembled
were ranked by the docking scores generated by Glide. Compounds undisclosed among the top 10 were
selected to design a series of 6-phenylisoxazolo[3,4-b]pyridin-3-amine derivatives as FLT3 inhibitors.
The kinase inhibitory activities of the fifteen compounds were assayed on FLT3 and FLT3-ITD. The antitumor
activities of the structurally modified compounds F1–F15 were evaluated against MOLM-13 and
MV4-11, typical FLT3-dependent human AML cells carrying FLT3-ITD mutants and the FLT3-
independent human cervical carcinoma cell line HL-60 (harboring wide-type FLT3).

Results:

Structure–activity relationship (SAR) analysis showed that F14 could inhibit FLT3 and FLT3-
ITD by 52% and 45.55%, respectively, at the concentration of 1 mΜ. F14 exhibited potent activity
against FLT3-dependent human acute myeloid leukemia (AML) cell lines, MOLM-13, and MV4-11 (harboring
FLT3-ITD mutant) with IC50 values of 2.558 μM and 1.785 μM, respectively.

Conclusion:

F14 could be used as a novel lead compound to further develop FLT3 inhibitors against
AML with FLT3-ITD mutant.
Berberine Contents as a Quality Marker in Medicinal Plants and
Amounts of Berberine Passing into Serum
Authors: Cansu  Aydın Sabire , Kalaycıoğlu Zeynep , Erim F. Bedia
Published: May 2023

Background:

Berberine is an alkaloid found in some medicinal plants. Berberine-containing plants have traditionally been used in the treatment of diseases since ancient times. Berberine is a natural compound that has an important place in traditional Chinese medicine. Currently, berberine is being evaluated extensively in clinical trials and is one of the natural products on which most scientific research studies have been published. Numerous clinical and pharmacological research results have been published on the therapeutic effect of berberine against cancer, diabetes, and heart disease

Objective:

The first purpose of this review is to display the berberine content of plants found in different regions of the world, and the second purpose is to provide the amount of berberine passing into the serum.

Methods:

Herbal supplements and extracts prepared from plants containing berberine are commercially marketed. The content of berberine in plants varies widely, and berberine is a quality indicator for many medicinal plants.

Results:

Different analytical methods have been developed for reliable berberine analysis. Plant and serum berberine levels reported between the years 2013 and 2022 in journals covered by SCI are collected in this review article.

Conclusion:

We hope that this overview of berberine amounts will be useful in future pharmaceutical and pharmacokinetic studies.
Optimization of RST Controller for Speed Control of Linear Induction
Motor Using Genetic Algorithm
Authors: Laid Khettache , Djalal Djarah , Ghania Zidani , Rachid Abdessemed
Published: May 2023

Background:

In this study, a new model of linear induction motor, along with the impact
of end-effect on motor performance, is proposed. Moreover, a new strategy of control approach
based on the polynomial RST controller is suggested and investigated.

Objective:

The proposed approach can provide a robust control strategy and overcome the limitations
imposed by the proportional-integral (PI) regulator in the FOC technique. RST controller has a
two-degree of freedom structure and consists of three polynomials, namely R, S and T, which are
determined by the pole placement method and resolving of a Diophantine equation. Despite this, the
implementation of this method is usually difficult and becomes more complicated with the complexity
of the controlled plants.

Methods:

This study proposes the genetic algorithm (GA) optimization strategy for tuning RST controller
parameters (adjust the controller coefficients) in order to achieve an adequate response time
by minimizing the different objective functions, such as steady-state error, settling time, and rise
time.

Results:

The accuracy and control performance of the proposed technique are checked and validated
using Matlab /Simulink environment software tool. Simulation results reported that the proposed
method (RST-GA) could provide robust solutions with perfect reference tracking and efficient disturbance
rejection.

Conclusion:

These significant results make the proposed approach a promising technique for the
design of a high-performance controller, which is highly suitable for industrial and electrical applications.