bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Tumor-Suppressive miR-139-3p-Regulated Genes: TRIP13 as a Therapeutic Target in Lung Adenocarcinoma
Authors: Hagihara Yoko , Tomioka Yuya , Suetsugu Takayuki , Shinmura Masahiro , Misono Shunsuke , Goto Yusuke , Kikkawa Naoko , Kato Mayuko , Inoue Hiromasa , Mizuno Keiko , Seki Naohiko
Published: November 2023

Analyses of our microRNA (miRNA) expression signature combined with The Cancer Genome Atlas (TCGA) data revealed that both strands of pre-miR-139 (miR-139-5p, the guide strand, and miR-139-3p, the passenger strand) are significantly downregulated in lung adenocarcinoma (LUAD) clinical specimens. Functional analyses of LUAD cells ectopically expressing miR-139-3p showed significant suppression of their aggressiveness (e.g., cancer cell proliferation, migration, and invasion). The involvement of the passenger strand, miR-139-3p, in LUAD pathogenesis, is an interesting finding contributing to the elucidation of unknown molecular networks in LUAD. Of 1108 genes identified as miR-139-3p targets in LUAD cells, 21 were significantly upregulated in LUAD tissues according to TCGA analysis, and their high expression negatively affected the prognosis of LUAD patients. We focused on thyroid hormone receptor interactor 13 (TRIP13) and investigated its cancer-promoting functions in LUAD cells. Luciferase assays showed that miR-139-3p directly regulated TRIP13. siRNA-mediated TRIP13 knockdown and TRIP13 inhibition by a specific inhibitor (DCZ0415) attenuated the malignant transformation of LUAD cells. Interestingly, when used in combination with anticancer drugs (cisplatin and carboplatin), DCZ0415 exerted synergistic effects on cell proliferation suppression. Identifying the molecular pathways regulated by tumor-suppressive miRNAs (including passenger strands) may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.
Understanding the Role of Radio-Sensitizing Nanoparticles in Enhancing Pathologic Response in Soft Tissue Sarcomas
Authors: Stergioula Anastasia , Pantelis Evaggelos , Kontogeorgakos Vasileios , Lazaris Andreas C. , Agrogiannis Georgios
Published: November 2023

High-atomic-number (Z) nanoparticles produce a cascade of low-energy secondary electrons and characteristic X-rays when ionized by X-ray irradiation. These secondary particles deposit their energy in the vicinity of the nanoparticles and, provided that the latter are selectively accumulated within tumor cells, this results in increased DNA damage and tumor cell deaths. This study reviews the utilization of high-Z nanoparticles in the treatment of soft tissue sarcomas (STS). Both in vitro and in vivo experiments demonstrated that the dose is enhanced by approximately 1.2 when polyethelyne glycol (PEG)-modified gold nanoparticles, and from 1.4 to 1.8 when hafnium oxide nanoparticles (NBTXR3, Nanobiotix SA, France) are introduced into tumor cells and activated by X-ray beams. In a phase 2/3 clinical trial investigating the therapeutic benefit of using nanoparticles in preoperative external beam radiotherapy for locally advanced STS, the proportion of patients with a pathological complete response in their resected tumor was doubled when NBTXR3 nanoparticles were used. Additionally, a higher percentage of patients with complete tumor resection was observed in the NBTXR3 plus radiotherapy group. Similar toxicity profiles were found for both the NBTXR3 plus radiotherapy and the radiotherapy alone patient groups. The incorporation of radio-sensitizing nanoparticles in the preoperative radiotherapy of STS could enhance treatment outcomes.
Is System xc− a Suitable Target for Tumour Detection and Response Assessment with Imaging?
Authors: Sharkey Amy R. , Witney Timothy H. , Cook Gary J. R.
Published: November 2023

System xc− is upregulated in cancer cells and can be imaged using novel radiotracers, most commonly with (4S)-4-(3-[18F]fluoropropyl)-L-glutamic acid (18F-FSPG). The aim of this review was to summarise the use of 18F-FSPG in humans, explore the benefits and limitations of 18F-FSPG, and assess the potential for further use of 18F-FSPG in cancer patients. To date, ten papers have described the use of 18F-FSPG in human cancers. These studies involved small numbers of patients (range 1–26) and assessed the use of 18F-FSPG as a general oncological diagnostic agent across different cancer types. These clinical trials were contrasting in their findings, limiting the scope of 18F-FSPG PET/CT as a purely diagnostic agent, primarily due to heterogeneity of 18F-FSPG retention both between cancer types and patients. Despite these limitations, a potential further application for 18F-FSPG is in the assessment of early treatment response and prediction of treatment resistance. Animal models of cancer have shown that changes in 18F-FSPG retention following effective therapy precede glycolytic changes, as indicated by 18F-FDG, and changes in tumour volume, as measured by CT. If these results could be replicated in human clinical trials, imaging with 18F-FSPG PET/CT would offer an exciting route towards addressing the currently unmet clinical needs of treatment resistance prediction and early imaging assessment of therapy response.
Effects of Dickkopf-1 (DKK-1) on Prostate Cancer Growth and Bone Metastasis
Authors: Yuan Shiyu , Hoggard Nathan K. , Kantake Noriko , Hildreth Blake E. , Rosol Thomas J.
Published: November 2023

Osteoblastic bone metastases are commonly detected in patients with advanced prostate cancer (PCa) and are associated with an increased mortality rate. Dickkopf-1 (DKK-1) antagonizes canonical WNT/β-catenin signaling and plays a complex role in bone metastases. We explored the function of cancer cell-specific DKK-1 in PCa growth, metastasis, and cancer–bone interactions using the osteoblastic canine PCa cell line, Probasco. Probasco or Probasco + DKK-1 (cells transduced with human DKK-1) were injected into the tibia or left cardiac ventricle of athymic nude mice. Bone metastases were detected by bioluminescent imaging in vivo and evaluated by micro-computed tomography and histopathology. Cancer cell proliferation, migration, gene/protein expression, and their impact on primary murine osteoblasts and osteoclasts, were evaluated in vitro. DKK-1 increased cancer growth and stimulated cell migration independent of canonical WNT signaling. Enhanced cancer progression by DKK-1 was associated with increased cell proliferation, up-regulation of NF-kB/p65 signaling, inhibition of caspase-dependent apoptosis by down-regulation of non-canonical WNT/JNK signaling, and increased expression of epithelial-to-mesenchymal transition genes. In addition, DKK-1 attenuated the osteoblastic activity of Probasco cells, and bone metastases had decreased cancer-induced intramedullary woven bone formation. Decreased bone formation might be due to the inhibition of osteoblast differentiation and stimulation of osteoclast activity through a decrease in the OPG/RANKL ratio in the bone microenvironment. The present study indicated that the cancer-promoting role of DKK-1 in PCa bone metastases was associated with increased growth of bone metastases, reduced bone induction, and altered signaling through the canonical WNT-independent pathway. DKK-1 could be a promising therapeutic target for PCa.
ATP/IL-33-Co-Sensing by Mast Cells (MCs) Requires Activated c-Kit to Ensure Effective Cytokine Responses
Authors: Seifert Johanna , Küchler Claudia , Drube Sebastian
Published: November 2023

Mast cells (MCs) are sentinel cells which represent an important part of the first line of defense of the immune system. MCs highly express receptors for danger-associated molecular patterns (DAMPs) such as the IL-33R and P2X7, making MCs to potentially effective sensors for IL-33 and adenosine-triphosphate (ATP), two alarmins which are released upon necrosis-induced cell damage in peripheral tissues. Besides receptors for alarmins, MCs also express the stem cell factor (SCF) receptor c-Kit, which typically mediates MC differentiation, proliferation and survival. By using bone marrow-derived MCs (BMMCs), ELISA and flow cytometry experiments, as well as p65/RelA and NFAT reporter MCs, we aimed to investigate the influence of SCF on alarmin-induced signaling pathways and the resulting cytokine production and degranulation. We found that the presence of SCF boosted the cytokine production but not degranulation in MCs which simultaneously sense ATP and IL-33 (ATP/IL-33 co-sensing). Therefore, we conclude that SCF maintains the functionality of MCs in peripheral tissues to ensure appropriate MC reactions upon cell damage, induced by pathogens or allergens.
Bitcoin and Its Energy, Environmental, and Social Impacts: An Assessment of Key Research Needs in the Mining Sector
Authors: Rudd Murray A. , Bratcher Lee , Collins Simon , Branscum David , Carson Matthew , Connell Shaun , David Elliot , Gronowska Magdalena , Hess Sebastien , Mitchell Austin , Prusak Matt , Schneps Kyle , Serezhin Maxim , Wolfe Scott A. , Porter Dennis
Published: November 2023

In this study, we used a combination of AI-assisted analysis of social media discourse and collaboration with industry experts to delve into the key research needs associated with the Bitcoin mining industry. We identified primary threats, opportunities, and research questions related to the Bitcoin mining industry and its wider impacts, focusing on its energy use and environmental footprint. Our findings spotlight the industry’s move towards increasingly greater energy efficiency and an emerging commitment to renewable energy, highlighting its potential to contribute to the coming energy transition. We underscore the transformative potential of emerging applications in the Bitcoin mining sector, especially regarding demand response, grid flexibility, and methane mitigation. We suggest that targeted research on Bitcoin can serve policymakers, private sector decision-makers, research funding agencies, environmental scientists, and the Bitcoin industry itself. We propose that filling key information gaps could help clarify the risks and benefits of Bitcoin mining by encouraging collaboration among researchers, policymakers, and industry stakeholders and conducting research that provides baseline peer-reviewed evidence surrounding Bitcoin’s production and impacts. A collaborative approach could help mitigate the risks and realize the benefits of Bitcoin mining, including potentially positive and substantive contributions in alignment with the Sustainable Development Goals.
Comparative Analysis of the GH/IGF-1 Axis during the First Sixth Months in Children with Low Birth Weight
Authors: Diniz Luciana Pessoa Maciel , Cavalcante Taisy Cinthia Ferro , da Silva Amanda Alves Marcelino
Published: November 2023

Objective: To analyze the relation between alterations in the growth hormone (GH)/insulin-like growth factor 1 (IGF-1) axis during the first 6 months of life and weight in children born in the lower-middle São Francisco region. Methods: This is an analytical cohort and exploratory. Thirty children, were formed two groups, one of low birth weight children (LBW, n = 15) and another of normal weight (NBW = 15) were initially identified in a hospital and reapproached at 3 and 6 months of age. Birth weight and alterations in GH/IGF-1 curves were measured at birth and the third and sixth months of life. Results: Weight gain during the 6 months of follow-up in newborns with a low birth weight was greater compared to newborns with a normal birth weight. All children who were born with a low birth weight had an altered GH/IGF-1 curve at birth (p = 0.002). Most newborns with a low birth weight maintained the alteration in the GH/IGF-1 curve at the third month of life (p = 0.027). Regarding the GH/IGF-1 curve at the sixth month, alteration persisted in greater proportion among children with a low birth weight. Conclusions: Alterations in insulin resistance markers, demonstrated by increased GH without a proportional increase in IGF-1, were observed to be significant in children with a low birth weight with greater adiposity in this group which may increase the risk of metabolic diseases in later life.
Psychiatric Hospitalization for Psychopathological Disorders and Self-Injurious Behaviors in Italian Children and Adolescents during COVID-19
Authors: Pontillo Maria , Menghini Deny , Averna Roberto , Labonia Milena , Lazzaro Giulia , Tata Maria Cristina , Vicari Stefano
Published: November 2023

The evidence shows that the COVID-19 pandemic dramatically increased the number of urgent psychiatric consultations for children and adolescents in hospital emergency departments (EDs). However, what needs to be further investigated are the characteristics of psychiatric hospitalization in children and adolescents admitted to the Child and Adolescent Neuropsychiatry Unit wards in EDs. Specifically, this retrospective study aimed to examine changes in (i) the number of inpatients and (ii) the distribution of psychopathological disorders and self-injurious behaviors in our Child and Adolescent Neuropsychiatry Unit ward during the COVID-19 lockdown in Italy (March–June 2020; October 2020–January 2021) compared with the same months of previous years. We found a significantly lower number of inpatients during the first four quarantine months than the first four reference months and a higher number of inpatients during the second four quarantine months than the second four reference months. Additionally, we found an increased frequency of mood disorders, non-suicidal self-injurious behavior, and suicidal ideation during the COVID-19 lockdown compared to the reference periods. Our findings underline the need to develop psychological healthcare services for future emergency periods in order to identify and treat psychological distress in children and adolescents early, reducing the risk of psychiatric hospitalization.
In Silico Evaluation of Coding and Non-Coding nsSNPs in the Thrombopoietin Receptor (MPL) Proto-Oncogene: Assessing Their Influence on Protein Stability, Structure, and Function
Authors: Al-nakhle Hakeemah H. , Yagoub Hind S. , Anbarkhan Sadin H. , Alamri Ghadah A. , Alsubaie Norah M.
Published: November 2023

The thrombopoietin receptor (MPL) gene is a critical regulator of hematopoiesis, and any alterations in its structure or function can result in a range of hematological disorders. Non-synonymous single nucleotide polymorphisms (nsSNPs) in MPL have the potential to disrupt normal protein function, prompting our investigation into the most deleterious MPL SNPs and the associated structural changes affecting protein–protein interactions. We employed a comprehensive suite of bioinformatics tools, including PredictSNP, InterPro, ConSurf, I-Mutant2.0, MUpro, Musitedeep, Project HOPE, STRING, RegulomeDB, Mutpred2, CScape, and CScape Somatic, to analyze 635 nsSNPs within the MPL gene. Among the analyzed nsSNPs, PredictSNP identified 28 as significantly pathogenic, revealing three critical functional domains within MPL. Ten of these nsSNPs exhibited high conservation scores, indicating potential effects on protein structure and function, while 14 were found to compromise MPL protein stability. Although the most harmful nsSNPs did not directly impact post-translational modification sites, 13 had the capacity to substantially alter the protein’s physicochemical properties. Some mutations posed a risk to vital protein–protein interactions crucial for hematological functions, and three non-coding region nsSNPs displayed significant regulatory potential with potential implications for hematopoiesis. Furthermore, 13 out of 21 nsSNPs evaluated were classified as high-risk pathogenic variants by Mutpred2. Notably, amino acid alterations such as C291S, T293N, D295G, and W435C, while impactful on protein stability and function, were deemed non-oncogenic “passenger” mutations. Our study underscores the substantial impact of missense nsSNPs on MPL protein structure and function. Given MPL’s central role in hematopoiesis, these mutations can significantly disrupt hematological processes, potentially leading to a variety of disorders. The identified high-risk pathogenic nsSNPs may hold promise as potential biomarkers or therapeutic targets for hematological diseases. This research lays the foundation for future investigations into the MPL gene’s role in the realm of hematological health and diseases.
Effect of the Solvent Type on the Colloidal Stability and the Degree of Condensation of Silica Sols Stabilized by Amphiphilic Urethane Acrylate and the Properties of Their Coating Films
Authors: Le Hong Nhung , Lee Choonho , Jung Woochul , Kim Juyoung
Published: November 2023

The colloidal stability of silica O-I hybrid sols that have a high degree of condensation could result in the formation of a hard coating film on a substrate, which could depend on the properties of solvents used in the sol-gel reaction. In this study, the effect of the solvent type on the colloidal stability and degree of condensation of the silica sols was investigated by preparing various silica O-I hybrid sols using different solvent mixtures composed of various aprotic and protic solvents in the presence of amphiphilic urethane acrylate. Silica sols prepared using the appropriate aprotic-protic solvent mixture showed a higher degree of condensation and long-term colloidal stability, which was confirmed using 29Si-NMR and DLS. Furthermore, the coating film formed from these silica sols showed a remarkable hardness of 0.97 GPa, with a thickness of 4.76 µm confirmed using nanoindentation measurements.
A Comprehensive Update on Helminth Parasite Biodiversity and Richness in Peruvian Amphibians
Authors: Chero Jhon D. , Cruces Celso L. , Cacique Edson R. , Ponce Jodie A. , Iannacone José , Alvariño Lorena , Sanchez Lidia , Sáez Gloria , Lopez Jorge , Da Silva Reinaldo José
Published: November 2023

This study aimed to comprehensively update and expand the knowledge on the diversity and richness of helminth parasites found in Peruvian amphibians. A systematic search was conducted across primary databases, encompassing both indexed and non-indexed articles, to compile the most recent data. As of the present study, a total of 83 distinct helminth taxa have been documented in association with 78 anuran species of the order Anura, marking a 176.7% increase from previously recorded figures. Nematodes exhibited the highest species richness, totalling 52 taxa (62.65%), followed by trematodes (21 taxa, 25.3%), acanthocephalans and cestodes (4 taxa each, 4.8%), and monogeneans (2 taxa, 2.4%). The overwhelming majority (85.5%) of the collected parasites (71 taxa) were identified as mature helminths, with the remaining 14.5% (12 taxa) in their larval stages. Notably, Cosmocerca brasiliense Travassos, 1925 (Cosmocercidae), and Physaloptera sp. (Physalopteridae) were the most prevalent nematodes, having infected the broadest range of host species. Rhinella marina Linnaeus, 1758 (Bufonidae), emerged as the anuran host with the highest diversity, harboring 17 distinct helminth species. These findings underscore the crucial role of helminth parasites in shaping amphibian ecosystems and their significance as bioindicators of environmental health. Protecting both amphibian hosts and their associated helminth parasites is paramount, as it is intrinsically linked to the preservation of ecological equilibrium within these ecosystems.
How Much Do We Know about Oral Cancer?—An Online Survey
Authors: Horvat Iva , Lončar-Brzak Božana , Andabak Rogulj Ana , Cigić Livia , Pezelj Ribarić Sonja , Sikora Miroslav , Vidović-Juras Danica
Published: November 2023

Introduction: Oral cancer (OC) is a disease with a high mortality rate due to its late recognition. Since the oral cavity is easily accessible for visual inspection, enabling early diagnosis, the education of healthcare workers about preventive oral examinations is critical. This research aimed to assess the level of participants’ OC knowledge, as well as to raise awareness about this diagnosis. Materials and methods: The research was conducted as an online survey among students of dental medicine, students of medicine, doctors of dental medicine and doctors of medicine. The questionnaire was designed solely for the purpose of this study and consisted of 29 questions. The first part of the questionnaire consisted of general questions about the participants, whereas the questions in the second part addressed their knowledge and attitudes towards OC. Results: The surveyed population comprised of 140 dental students, 105 medical students, 159 doctors of dental medicine and 100 medical doctors. The level of knowledge about OC among the participants is not yet satisfactory. The group of dental medicine students scored highest, while medical doctors showed the weakest knowledge. Conclusion: Additional education about OC for doctors of dental medicine and medical doctors is needed. This step will improve prevention and increase chances for early detection.
Expression and Functional Analysis of the PaPIP1-2 Gene during Dormancy and Germination Periods of Kernel-Using Apricot (Prunus armeniaca L.)
Authors: Li Shaofeng , Zheng Guangshun , Wang Fei , Yu Hai , Wang Shaoli , Guan Haohui , Lv Fenni , Xia Yongxiu
Published: November 2023

Aquaporins play a crucial role in helping water molecules move across cell membranes. While some studies have examined the role of AQPs in model plants like Arabidopsis, their impact on the ability of non-model plants to withstand environmental stress is largely unknown. In this study, we have explored the functions of the PaPIP1-2 gene, which encodes a protein called PIP, in apricot kernels (Prunus armeniaca L.). Our findings reveal how the PaPIP1-2 gene behaves during both dormancy and sprouting phases. Using a network analysis, we identified its interaction with six genes related to cold resistance. The mRNA levels of PaAQP genes, which co-express with cold resistance genes, remain consistent throughout different stages of P. armeniaca flower bud development, including physiological dormancy (PD), ecological dormancy (ED), sprouting period (SP), and germination stage (GS). Furthermore, our investigation of the location of the GFP-tagged PaPIP1-2 protein showed that it is mainly found in the cell membrane. Yeast strains with overexpressed PaPIP1-2 exhibited improved cold resistance and higher protein content. Similarly, when we overexpressed PaPIP1-2 in Arabidopsis, it enhanced the growth of these transgenic plants under cold stress. This improvement was associated with reduced levels of MDA (malondialdehyde); decreased ion leakage; increased proline accumulation; superoxide dismutase (SOD) activity; and the expression of cold resistance genes like AtPUB26, AtBTF3L, AtEBF1-1, and AtRAV1, compared with the wild-type plants. In summary, our results highlight the role of the P. armeniaca PaPIP1-2 gene in enhancing cold resistance and its importance in the dormancy and germination stages.
Milk Protein Hydrolysis by Actinidin—Kinetic and Thermodynamic Characterisation and Comparison to Bromelain and Papain
Authors: Kaur Surjit , Vasiljevic Todor , Huppertz Thom
Published: November 2023

Plant proteases, including actinidin, papain and bromelain, have been widely used in the food industry but with limited application in dairy systems. This research aimed to establish and compare operational parameters (kinetics, temperature, enzyme type, time and thermodynamics) relevant to the applications of these enzymes in the hydrolysis of whey protein isolates (WPI), whey protein concentrates (WPC) or milk protein concentrates (MPC). The degree of hydrolysis (DH) increased with the rise in temperature, and the maximum DH was achieved at 60 °C for all three dairy systems. The addition of papain resulted in a greater %DH of whey proteins in comparison to bromelain. The cleavage of proteins was clearly time-dependent (p < 0.05), while the pH did not change significantly (p > 0.05) during this time. PAGE analysis revealed that all three enzymes mainly acted on α-lactalbumin and αs-casein in WPI and MPC, respectively. Kinetic parameters from the Lineweaver–Burk plot at 60 °C using WPC and MPC as a substrate varied widely, establishing that WPC hydrolysis was characterised by a lower KM, higher kcat, kcat/KM and Vmax compared to MPC in the case of all three enzymes. The difference in kcat/KM values amongst all enzymes (actinidin > papain > bromelain) indicated the difference in the strength of substrate binding sites. The thermodynamic parameters of these enzymes with MPC and WPC were also determined at a temperature range of 15–60 °C, and the results indicate the potential application of papain and actinidin in the dairy industry.
Antioxidant Activity, Formulation, Optimization and Characterization of an Oil-in-Water Nanoemulsion Loaded with Lingonberry (Vaccinium vitis-idaea L.) Leaves Polyphenol Extract
Authors: Wang Siyu , Cheng Yuan , Wang Jingyi , Ding Miao , Fan Ziluan
Published: November 2023

The active ingredients in lingonberry leaves and their beneficial properties to the human body have been well confirmed. In order to improve the stability and antioxidant activity of the active ingredients in lingonberry leaves, the response surface optimization method was used to prepare an oil-in-water nanoemulsion of polyphenol extract from lingonberry leaves. The active components in the extract were analyzed by ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UPLC-TQ-MS), and bioactive compounds such as apigenin, sorbitol, and hesperidin were mainly found. Nanoemulsion droplets of 120 nm in diameter were prepared using ultrasonic emulsification. The optimal nanoemulsion formulation was determined through rigorous testing, and it was determined to be 10% (w/w) lingonberry extract and 20% (w/w) medium chain triglyceride (MCT). Additionally, a surfactant mixture was used, which combined soy protein isolate (SPI) and whey protein isolate (WPI) at 4% (w/w). The preparation method utilized ultrasonic emulsification, applying an ultrasonic power of 360 W for a duration of 300 s. The antioxidant activity (DPPH inhibition rate, ABTS inhibition rate and total reducing power) of the lingonberry nanoemulsion was significantly higher than that of the lingonberry polyphenol (LBP) extract. The nanoemulsion prepared using the optimal formulation had an entrapping efficiency of 73.25% ± 0.73% and a diameter of 114.52 ± 0.015 nm, with a satisfactory particle size of nanoscale and a PDI of 0.119 ± 0.065, demonstrating good stability of the emulsion.
Imidazolopiperazine (IPZ)-Induced Differential Transcriptomic Responses on Plasmodium falciparum Wild-Type and IPZ-Resistant Mutant Parasites
Authors: Dembele Laurent , Dara Antoine , Maiga Mohamed , Maiga Fatoumata O. , Cissoko Djeneba , Djimde Abdoulaye A.
Published: November 2023

Imidazolopiperazine (IPZ), KAF156, a close analogue of GNF179, is a promising antimalarial candidate. IPZ is effective against Plasmodium falciparum and Plasmodium vivax clinical malaria in human with transmission blocking property in animal models and effective against liver stage parasites. Despite these excellent drug efficacy properties, in vitro parasites have shown resistance to IPZ. However, the mechanism of action and resistance of IPZ remained not fully understood. Here, we used transcriptomic analysis to elucidate mode of action of IPZs. We report, in wild-type parasites GNF179 treatment down regulated lipase enzymes, two metabolic pathways: the hydrolysis of Phosphoinositol 4,5-bipohosphate (PIP2) that produce diacyglycerol (DAG) and the cytosolic calcium Ca2+ homeostasis which are known to be essential for P. falciparum survival and proliferation, as well for membrane permeability and protein trafficking. Furthermore, in wild-type parasites, GNF179 repressed expression of Acyl CoA Synthetase, export lipase 1 and esterase enzymes. Thus, in wild-type parasites only, GNF179 treatment affected enzymes leading lipid metabolism, transport, and synthesis. Lastly, our data revealed that IPZs did not perturb known IPZ resistance genes markers pfcarl, pfact, and pfugt regulations, which are all instead possibly involved in the drug resistance that disturb membrane transport targeted by IPZ.
Development of a Set of Assessment Tools for Health Professionals to Design a Tailored Rehabilitation Exercise and Sports Program for People with Stroke in South Korea: A Delphi Study
Authors: Lee Minyoung , Park Yoon , Eun Seon-Deok , Ho Seung Hee
Published: November 2023

We developed a set of assessment tools for health professionals to evaluate the physical functions, mental functions, and social abilities of people with stroke (PWS) from 6 months to 3 years after stroke onset, to design a tailored “Rehabilitation Exercise and Sports” (RES) program, which the South Korean government was required to provide by the Act on Guarantee of Right to Health and Access to Health Services for people with disabilities. Since previous studies mainly dealt with the chronic stage of PWS, it would not be appropriate to apply assessment tools used in previous studies, as they are not compatible with the time window (6 months to 3 years) used to define the target population of the RES program. We reviewed the literature to identify evaluation factors and assessment tools applied in previous studies, and developed a Delphi questionnaire with closed-ended questions based on the literature review’s results and supplementary open-ended questions. A 20-expert panel conducted four rounds of the Delphi survey, including two rounds to determine evaluation factors and two rounds to determine assessment tools. The Delphi survey revealed that 22 evaluation factors and 24 corresponding assessment tools reached consensus among the experts. However, no assessment tools reached consensus for three evaluation factors: muscle endurance, flexibility, and dynamic balance. A comprehensive set of assessment tools would be useful for health professionals to understand the health status of PWS from 6 months to 3 years after stroke onset, and help the design of tailored RES programs.
Socioeconomic Inequalities as a Cause of Health Inequities in Spain: A Scoping Review
Authors: Blasco-Palau Guillem , Prades-Serrano Jara , González-Chordá Víctor M.
Published: November 2023

The objectives of this review were to identify the population groups most frequently studied, to determine the methods and techniques most commonly used to show health inequities, and to identify the most frequent socioeconomic and health indicators used in the studies on health inequities due to socioeconomic inequalities that have been carried out on the Spanish healthcare system. A scoping review was carried out of the studies conducted in the Spanish State and published in literature since 2004, after the publication of the Law of Cohesion and Quality of the National Health System. The PRISMA extension for scoping reviews was followed. The methodological quality of the studies was assessed using the critical reading guides of the Joanna Briggs Institute and an adaptation of the STROBE guide for ecological studies. A total of 58 articles out of 811 articles were included. Most of the articles were (77.59%, n = 45) cross-sectional studies, followed by ecological studies (13.8%, n = 8). The population group used was uneven, while the main geographical area under investigation was the whole state (51.7%, n = 30) compared to other territorial distributions (48.3%, n = 28). The studies used a multitude of health and socioeconomic indicators, highlighting self-perception of health (31.03%, n = 19) and social class (50%, n = 29). The relationship between better health and better socioeconomic status is evident. However, there is variability in the populations, methods, and indicators used to study health equity in Spain. Future health research and policies require greater systematization by public institutions and greater cooperation among researchers from disciplines such as sociology, economics, and health.
Effectiveness of Virtual Reality and Feedback to Improve Gait and Balance in Patients with Diabetic Peripheral Neuropathies: Systematic Review and Meta-Analysis
Authors: Alonso-Enríquez Laura , Gómez-Cuaresma Laura , Billot Maxime , Garcia-Bernal Maria Isabel , Benitez-Lugo Maria Luisa , Casuso-Holgado María Jesús , Luque-Moreno Carlos
Published: November 2023

Diabetic peripheral neuropathy (DPN) is the primary complication in patients with diabetes mellitus, characterized by loss of sensation and function in the lower limbs. Virtual reality (VR) and/or sensory feedback (FB) therapy has shown positive effects in other neurologic conditions such as stroke. However, consensus regarding their effectiveness in the DPN population is lacking. This study aims to analyze existing scientific evidence about the effects of VR and/or FB on improving gait and balance and reducing the risk of falls in patients with DPN (pwDPN). A thorough search was conducted in scientific databases including PubMed, Scopus, and EMBASE, up until November 2023. CMSQ, the PEDro scale, and the Cochrane Collaboration’s tool were used to assess the methodological quality and risk of bias of the studies. A total of 10 studies were selected for qualitative analysis, with three contributing information to the meta-analysis. The combined results suggest a positive trend in favor of VR and FB rehabilitation; however, significant differences were not observed in balance (SMD = −0.81, 95% CI = −1.90, 0.29; p = 0.15; I2 = 86%) or gait speed improvements (MD = −1.05, 95% CI = −2.96, 0.85; p = 0.28; I2 = 89%). Therefore, further randomized controlled studies are still needed to achieve stronger conclusions regarding the benefits of VR and/or FB in pwDPN.
Turning a Pest into a Natural Enemy: Removing Earwigs from Stone Fruit and Releasing Them in Pome Fruit Enhances Pest Control
Authors: Hanel Aldo , Orpet Robert J. , Hilton Richard , Nottingham Louis , Northfield Tobin D. , Schmidt-Jeffris Rebecca
Published: November 2023

The European earwig Forficula auricularia (L.) (Dermaptera: Forficulidae) is an omnivorous insect that is considered a minor pest of stone fruit and a key predator of pests in pome fruit orchards. In many pome fruit orchards, earwigs are absent or in low abundance due to broad-spectrum spray programs and the slow recolonization rate of earwigs. Orchards in transition to organic or “selective” conventional programs often struggle to achieve effective levels of biological control, and thus, may benefit from inoculating earwigs to expedite their re-establishment. In a two-year study, we evaluated the potential for mass trapping earwigs from stone fruit using rolled cardboard traps to reduce fruit damage and provide earwigs for augmentation in pome fruit. We also tested whether a single mass release or five releases (on alternating weeks) of the same total number of earwigs in apples and pears reduced pests relative to plots where no releases occurred. Mass trapping did not decrease earwig abundance or substantially reduce fruit damage in stone fruit orchards. However, trapping was an efficient method for providing earwigs for augmentation. Earwig abundances were only increased in orchards where earwigs were previously low or absent; however, multiple orchards with varying prior levels of earwigs exhibited reductions in key pests (woolly apple aphid and pear psylla). For some other pests evaluated, plots with mass releases of earwigs had a slight trend in overall lower pest density when compared with control plots. A strategy for moving earwigs out of stone fruit orchards and into pome fruit orchards could be an effective method for augmenting orchard predator populations.
Sex-Specific Cut-Offs of Seven Adiposity Indicators and Their Performance in Predicting Metabolic Syndrome in Arab Adults
Authors: Alfawaz Hanan A. , Khan Nasiruddin , Ansari Mohammed G. A. , Khattak Malak N. K. , Saadawy Gamal M. , Al-Daghri Nasser M.
Published: November 2023

This study aimed to assess several indicators of adiposity and their effectiveness in predicting metabolic syndrome (MetS) and identify their cut-off values among general Saudi adults. Consequently, 833 participants (49% male and 51% female) aged 42.2 ± 11.9 years (408 MetS and 425 as controls) were enrolled into this cross-sectional study. Information on demographics, anthropometrics and biochemical results was retrieved from a registry. MetS was defined according to the National Cholesterol Education Program’s (NCEP III) criteria. Overall, the lipid accumulation product (LAP) and waist–TG index (WTI) had the highest discriminatory ability for MetS (area under the curve (AUC): 0.857 and 0.831), respectively, followed by the visceral adiposity index (VAI) and dysfunctional adiposity index (DAI) (AUC: 0.819 and 0.804), respectively. Based on gender, the LAP and WTI were the best indicators for discriminating MetS and presented the highest Youden index values, with cut-off values of 49.8 (sensitivity 68.5%, specificity 82.4%), and 8.7 (sensitivity 70.7%, specificity 81.9%), respectively, in females and 46.2 (sensitivity 85.6%, specificity 76.3%) and 8.9 (sensitivity 73.9%, specificity 84.8%), respectively, in males. The LAP and WTI performed well in both genders with a superior ability to identify MetS in males and could be used to predict MetS in Saudi adults.
Exploring Social Bonds and Well-Being in Young Adults during and beyond the COVID-19 Pandemic
Authors: Mari Emanuela , Quaglieri Alessandro , Di Consiglio Micaela , Couyoumdjian Alessandro , Cricenti Clarissa , Lausi Giulia , Pizzo Alessandra , D’Amato Vincenzo , D’Amato Sabina , Vozzella Emilia Anna , Ferrara Antonietta , Giannini Anna Maria , Burrai Jessica
Published: November 2023

Background: Young adults, aged between 17 and 25 years, experienced a strong impact on both their mental health and well-being due to COVID-19. Indeed, they were simultaneously faced with the normative tasks of their age and stressors associated with the long-lasting COVID-19 pandemic. This study offers further insights into the perceptions of the well-being (stress, anxiety, and depression) and social bonds in young Italian adults during and after the COVID-19 pandemic. Methods: The first survey was conducted between December and February 2021 (i.e., during the second wave in Italy) and included a total sample of 347 participants. The second survey took place between April and May 2022 (i.e., at the end of the health emergency in Italy) and consisted of a total sample of 313 participants. Results: T-tests, correlations, and linear regressions were performed. Overall, our findings showed an increased mood disturbance was positively correlated with having contracted COVID-19 and negatively associated with social connectedness. Furthermore, social assurance was found to negatively predict mood disorders during COVID-19. Conclusion: While numerous studies have focused on mental health, there has been limited exploration of protective factors, which could represent a different perspective that emphasizes individuals’ resources rather than their vulnerabilities.
Impact of ISP Tuning on Object Detection
Authors: Molloy Dara , Deegan Brian , Mullins Darragh , Ward Enda , Horgan Jonathan , Eising Ciaran , Denny Patrick , Jones Edward , Glavin Martin
Published: November 2023

In advanced driver assistance systems (ADAS) or autonomous vehicle research, acquiring semantic information about the surrounding environment generally relies heavily on camera-based object detection. Image signal processors (ISPs) in cameras are generally tuned for human perception. In most cases, ISP parameters are selected subjectively and the resulting image differs depending on the individual who tuned it. While the installation of cameras on cars started as a means of providing a view of the vehicle’s environment to the driver, cameras are increasingly becoming part of safety-critical object detection systems for ADAS. Deep learning-based object detection has become prominent, but the effect of varying the ISP parameters has an unknown performance impact. In this study, we analyze the performance of 14 popular object detection models in the context of changes in the ISP parameters. We consider eight ISP blocks: demosaicing, gamma, denoising, edge enhancement, local tone mapping, saturation, contrast, and hue angle. We investigate two raw datasets, PASCALRAW and a custom raw dataset collected from an advanced driver assistance system (ADAS) perspective. We found that varying from a default ISP degrades the object detection performance and that the models differ in sensitivity to varying ISP parameters. Finally, we propose a novel methodology that increases object detection model robustness via ISP variation data augmentation.
Impacts of Lithology and Slope Position on Arbuscular Mycorrhizal Fungi Communities in a Karst Forest Soil
Authors: Zhao Jin , He Xunyang , Xiao Dan , Chen Meifeng , Cheng Ming , Wang Zhongcheng
Published: November 2023

The influence of lithology and slope position on arbuscular mycorrhizal fungi (AMF) communities has been explored in various ecosystems, but there is a limited understanding of these mechanisms in karst regions. This study focused on typical karst hills with contrasting lithologies, specifically dolomite and limestone. Additionally, three slope positions (upper, middle, and lower) were investigated within each hill in karst forest ecosystems. Total phosphorus (TP) content in the soil was higher in dolomite compared to limestone. Conversely, exchangeable calcium (Ca) was lower in dolomite than in limestone. Notably, the lithology, rather than the slope position, exerted a significant impact on AMF diversity and abundance and the presence of specific AMF taxa. Dolomite exhibited greater AMF richness and a higher Shannon index in comparison to limestone when not accounting for slope position. The AMF community composition differed between dolomite and limestone. For instance, without considering slope position, the relative abundance of Acaulospora, Diversispora, and Paraglomus was higher in dolomite than in limestone, while the relative abundance of Claroideoglomus displayed an opposing trend. Furthermore, a more complex interaction among AMF taxa was observed in dolomite as compared to limestone, as evidenced by an increase in the number of nodes and edges in the co-occurrence networks within the dolomite. The genera Glomus, Claroideoglomus, and Diversispora exhibited a higher number of links with each other and with other AMF taxa. The study identified TP and Ca as the primary factors determining variations in AMF diversity between dolomite and limestone. Consequently, it is imperative to consider the underlying lithology and soil conditions when addressing the restoration of degraded karst hilly areas.
Isolation and Characterization of Novel Huperzine-Producing Endophytic Fungi from Lycopodiaceae Species
Authors: Le Thanh Thi Minh , Pham Ha Thanh , Trinh Ha Thi Thu , Tran Hoa Thi , Chu Ha Hoang
Published: November 2023

Huperzine A (HupA) is an important drug for treating Alzheimer’s disease (AD) and is primarily extracted from the Huperzia serrata (Lycopodiaceae). Failures in the chemical synthesis of Hup and in vitro culture have put H. serrata in danger of extinction, and there is a need for an extensive investigation of Hup from alternative perspectives. The aim of this study is to identify endophytic fungi that produce high Hup or simultaneously produce many types of Hup and have high genetic stability derived from other Lycopodiaceae species as a source of materials for natural Hup production. In this work, Hup-producing endophytic fungi were isolated from three species: Lycopodium clavatum, Phlegmariurus squarrosus, and P. phlegmaria. Of these, L. clavatum and P. squarrosus were confirmed as novel sources of Hup-producing fungi. Based on morphological characteristics and nuclear ribosomal DNA ITS sequences, four endophytic fungi Colletotrichum siamense THG1-17, Epicoccum sorghinum THG01-18, Phoma sp. TKH3-2, and Phyllosticta sp. THG2-27 were firstly isolated from these Lycopodiaceae plants, which were capable of simultaneously producing both HupA and HupB, as evidenced by high-performance liquid chromatography analysis. The four strains showed stability in Hup yield over 50 generations of culture with an in vitro storage period of 3 months. These isolated fungi will provide a new source of materials for further research to develop drugs containing HupA as well as HupB for AD treatment in the future.
Volatile Fingerprint Mediates Yeast-to-Mycelial Conversion in Two Strains of Beauveria bassiana Exhibiting Varied Virulence
Authors: Ramírez-Ordorica Arturo , Patiño-Medina José Alberto , Meza-Carmen Víctor , Macías-Rodríguez Lourdes
Published: November 2023

Beauveria bassiana is a dimorphic and entomopathogenic fungus with different ecological roles in nature. In pathogenic fungi, yeast-to-mycelial conversion, which is controlled by environmental factors, is required for virulence. Here, we studied the effects of different stimuli on the morphology of two B. bassiana strains and compared the toxicities of culture filtrates. In addition, we explored the role of volatiles as quorum sensing-like signals during dimorphic transition. The killing assays in Caenorhabditis elegans (Nematoda: Rhabditidae) showed that strain AI2 isolated from a mycosed insect cadaver had higher toxicity than strain AS5 isolated from soil. Furthermore, AI2 showed earlier yeast-to-mycelial switching than AS5. However, an increase in inoculum size induced faster yeast-to-mycelium conversion in AS5 cells, suggesting a cell-density-dependent phenomenon. Gas chromatography-mass spectrometry (GC-MS) analyses showed that the fingerprint of the volatiles was strain-specific; however, during the morphological switching, an inverse relationship between the abundance of total terpenes and 3-methylbutanol was observed in both strains. Fungal exposure to 3-methylbutanol retarded the yeast-to-mycelium transition. Hence, this study provides evidence that volatile compounds are associated with critical events in the life cycle of B. bassiana.
A Three-Party Decision Evolution Game Analysis of Coal Companies and Miners under China’s Government Safety Special Rectification Action
Authors: Xie Can , Li Hongxia , Chen Lei
Published: November 2023

Research on the behavior of coal companies and miners under the government’s safety special rectification action is significant for maintaining social stability. In this paper, we constructed a dynamic evolutionary game model involving the government, coal companies, and miners. We analyzed the asymptotic stability conditions of the behavioral strategies of the participants in the game through phase diagrams and conducted a simulation analysis using Matlab R2021b to explore the impact of the key parameters in the model on the strategic choices of the game participants. The research findings indicated: (1) intricate interactive dynamics exist among the three stakeholders in safety rectification endeavors, with diverse intervention strategies manifesting varying impacts on participants’ conduct and outcomes; (2) setting reasonable reward and punishment mechanisms for safety behaviors by the government toward coal companies and miners helps to increase the probability of both choosing proactive safety behaviors. Coal companies that set reasonable reward and punishment mechanisms for the safety behaviors of miners can promote miners’ willingness to cooperate. Additionally, reducing safety rectification costs and enhancing the social reputation benefits of safety rectification can facilitate the optimal strategic choices of the three parties; and (3) the simulation analysis results corroborate the conclusions on the stability of strategies across all stakeholders, affirming the validity of the research outcomes and furnishing pertinent recommendations for enhancing the safety rectification framework.
Stability of Stochastic Networks with Proportional Delays and the Unsupervised Hebbian-Type Learning Algorithm
Authors: Zheng Famei , Wang Xiaojing , Cheng Xiwang
Published: November 2023

The stability problem of stochastic networks with proportional delays and unsupervised Hebbian-type learning algorithms is studied. Applying the Lyapunov functional method, a stochastic analysis technique and the Ito^ formula, we obtain some sufficient conditions for global asymptotic stability. We also discuss the estimation of the second moment. The correctness of the main results is verified by two numerical examples.