bluuebunny/crossref_metadata_2025 huggingface dataset:
Malignant Melanoma: Insights into Cancer Stem Cells, Tumor Microenvironment, and the Renin-Angiotensin System
Authors: Kilmister Ethan J , Tan Swee T
Published: June 2024

Malignant melanoma (MM) is the most fatal form of skin cancer, accounting for 90% of all skin cancer deaths. Multiple dysregulated cellular pathways are involved in MM, including the MAPK/ERK and PI3K/PTEN/AKT pathways, which can be targeted with novel targeted inhibitors. However, these blockades can be overcome through the activation of alternative pathways, leading to treatment resistance. The high immunogenicity of MM has been exploited using checkpoint inhibitors resulting in improved survival outcomes of patients with advanced MM. However, their side effect profile and prohibitive cost remain a challenge and the survival outcomes for patients with metastatic MM remain poor. Treatment resistance has been attributed to the presence of cancer stem cells (CSCs), a small subpopulation of pluripotent, highly tumorigenic cells proposed to drive cancer progression, metastasis, and treatment resistance. CSCs reside within the MM tumor microenvironment (TME) regulated by the immune system, and the paracrine renin-angiotensin system (RAS), expressed in many cancer types, including MM. This article reviews the current treatment of advanced MM with targeted therapy and immune checkpoint blockers, highlights the emergence of mRNA vaccine. It also discusses the MM TME and its relationship with CSCs, and the local immune system and the paracrine RAS. It highlights the regulation of the MAPK/ERK and PI3K/AKT/mTOR pathways by the RAS via prorenin receptor and angiotensin II receptor 1, and how this relates to the CSCs and treatment resistance. This underscores the potential multi-modal therapeutic strategy by concurrent targeting of multiple components of the TME.
Novel Treatment Modalities of Type 1 Diabetes Mellitus: Opportunities and Challenges
Authors: Salama Rasha Aziz Attia , Patni MohamedAnas MohamedFaruk , Ba-Hutair Shadha Nasser Mohammed , Wadid Nihal Amir , Akikwala Mushirabanu Sharifmiyan
Published: June 2024

Despite the effectiveness of insulin injections in managing hyperglycemia in Type 1 Diabetes, they fall short in addressing autoimmunity and regenerating damaged islets. This review aims to explore the potential of various treatment modalities for T1DM, including mesenchymal stem cells (MSCs), MSC-derived exosomes, gene therapy, islet allotransplantation, and pancreatic islet cell transplantation. Results: MSCs demonstrate efficacy in T1DM treatment through immunomodulation and tissue regeneration, although further research is warranted to optimize their therapeutic potential. Gene therapy presents a promising approach despite challenges such as donor shortage and immune rejection. Pancreatic islet cell transplantation emerges as a viable option, albeit with associated risks including graft rejection and the need for immunosuppression. Teplizumab, an FDA-approved humanized monoclonal antibody, revolutionizes the treatment landscape of Type 1 Diabetes by significantly delaying its onset, offering a paradigm shift since the discovery of insulin Conclusion: Ongoing studies and technological advancements in T1DM management offer a promising outlook for improved treatments and possibly even eradication on a global scale. MSCs, MSC-derived exosomes, gene therapy, and pancreatic islet transplantation hold considerable potential.
Seroepidemiology of Hepatitis B and C in a Medically Vulnerable Area: An Experience from the Ulleung Liver Cancer Prevention and Management Project
Authors: Ryu Dong-Hee , Lee Eun-Young , Ha Soo-Jung , Hong Namsoo
Published: June 2024

Ulleung County, one of the most medically vulnerable areas in South Korea, requires public attention because of the high incidence of liver cancer. This study was conducted as a part of the Ulleung Liver Cancer Prevention and Management Project. The purpose of this study was to estimate the community prevalence of hepatitis B and C viruses and to identify the associated risk factors. The Project’s interagency workgroup established a procedure for conducting blood sampling and health behavior surveys at the Ulleung Public Community Health Center. A total of 1,792 residents aged 40 years and older voluntarily participated in the study between 2019 and 2022. The hepatitis B surface antigen (HBs Ag) and hepatitis C virus antibody (anti-HCV) positive rates in Ulleung were 7.19% and 1.37%, respectively. Low education level and lifetime smoking were associated with HBsAg positivity, whereas cupping therapy at non-medical institutions was associated with anti-HCV positivity. The odds of HBs Ag positivity were lower among those with tattoos than among those without. There was a difference in the risk factors associated with hepatitis B and C viral infection. While a high HBs Ag positivity rate alone may not fully explain the high incidence of liver cancer in Ulleung, it may be a contributing factor.
Associations between Body Segment Masses and Punches, Front Kick, or the Countermovement Jump Performance in Military Personnel
Authors: Vagner Michal , Malecek Jan , Olah Vladan , Stastny Petr
Published: June 2024

Despite the recognized influence of body mass on combat techniques, the relationship between body segment mass (BSM) and combat moves remains unexplored. This study aimed to examine the relationship between striking arm mass (SAM), kicking leg mass (KLM), and body mass (BM) with the dynamic forces of the direct punches (DP), palm strikes (PS), elbow strikes (ES), front kicks (FK), and countermovement jumps (CMJ) performance. Sixteen male military cadets (22.3 ± 1.8 years, 181.4 ± 7.0 cm, 82.1 ± 8.5 kg) performed combat techniques, with performance measured by using a force plate and body segment mass assessed by Dual-energy X-ray absorptiometry. Spearman's correlation analysis, the Wilcoxon test, and Cohen's d were applied. Results indicated the relationship between KLM or BM and FK impulse (r = 0.64, p = 0.01; r = 0.52, p = 0.04, respectively) and CMJ impact force (r = 0.80, p ≤ 0.01; r = 0.70, p ≤ 0.01, respectively). Moreover, FK peak and impact forces were moderately correlated with CMJ jump height (r = 0.74, p ≤ 0.01; r = 0.77, p ≤ 0.01). The highest relationship was found between KLM and FK impulse; however, the difference in variability explained by KLM versus body mass is only 12%. This suggests that knowledge of BSM did not provide a significantly better estimate of the dynamic forces of the punches and FK than BM.
Determination of Atmospheric Pollen Grains by Volumetric Method in Sarıkamış District (Kars-Türkiye)
Authors: Akpınar Salih , Altunoğlu Mustafa Kemal
Published: June 2024

Atmospheric pollens were investigated using the Lanzoni VPSS 2000 device for 2 years between 2012 and 2013 in the Sarıkamış district of Kars province, one of the highest regions of Türkiye. A total of 37909 pollen grains were collected; 15,298 pollen grains in 2012 and 22611 pollen grains in 2013. Out of 43 identified taxa, 21 were arboreal and 22 were non arboreal. Pollen from arboreal plants accounted for 36.34% (13778 pollen) of the total, while pollen from non arboreal plants accounted for 63.56% (24095 pollen). The most frequent arboreal plants pollen in the Sarıkamış atmosphere were Pinaceae (29.79%), Cupressaceae/Taxaceae (2.54%), and Morus (1.30%). The main non arboreal plants pollen in the atmosphere of Sarıkamış were Poaceae (44.60%), Artemisia (2.98%), Amaranthaceae (2.79%), Rumex (2.41%), Urticaceae (2.33%), Plantago (2.19%), and Boraginaceae (1.40%). The maximum pollen concentration was observed in June.
Resolving Relationships of Bolbitis sinensis Species Complex Using RAD Sequencing
Authors: Nie Liyun , Fang Yuhan , Xia Zengqiang , Wei Xueying , Wu Zhiqiang , Yan Yuehong , Wang Faguo
Published: June 2024

Species identification and phylogenetic relationships clarification are fundamental goals in species delimitation. Yet these tasks pose challenges when based on morphologies, geographic distribution, and genomic data. Previously, two new species of fern genus Bolbitis, B. × multipinna and B. longiaurita, were described based on morphological traits, are phylogenetically intertwined with B. sinensis and fail to form monophyletic groups. To address the unclear phylogenetic relationships within the B. sinensis species complex, RAD sequencing was performed on 65 individuals from five populations. Our integrated analysis of phylogenetic tree, neighbor net, and genetic structure, indicate that the B. sinensis species complex should not be considered as separate species. Moreover, our findings reveal differences in the degree of genetic differentiation among five populations, ranged from low to moderate, which might be influenced by geographical distance and gene flow. The Fst values also confirmed that genetic differentiation intensifies with increasing geographic distance. Collectively, this study clarifies the complex phylogenetic relationships within the B. sinensis species complex, elucidates the genetic diversity and differentiation across the studied populations, and offers valuable genetic insights that contribute to the broader study of evolutionary relationships and population genetics within the Bolbitis species.
SwinDefNet: A Novel Surface Water Mapping Model in Mountain and Cloudy Regions Based on Sentinel-2 Imagery
Authors: Chen Xinyue , Pan Haiyan , Liu Jun
Published: June 2024

Surface water plays a crucial role in climate change, human production, and life, making accurate monitoring and observation of surface water particularly important. However, due to the significant diversity and complexity of water distribution in surface space, accurate mapping of surface water faces considerable challenges. When extracting water bodies from medium-resolution satellite remote sensing images, CNN methods may suffer from limitations in receptive fields and insufficient context modeling capabilities, leading to the loss of water body boundary details and poor fusion of multiscale features. Currently, there is relatively little research on this issue; therefore, it is necessary to explore new combinations of deep learning networks to address these challenges. The purpose of this study is to address the above issues. We propose a new combination of deep learning networks that fully utilize multiscale information to enhance water features. Specifically, we first combine deformable convolutions with the Swin Transformer to increase effective receptive fields while better integrating global semantic information. This combination can capture features of water bodies at different scales, improve the accuracy and integrity of water extraction, and provide reliable technical support for detailed water body extraction. We tested the newly constructed model using Sentinel-2 satellite images. Our model achieved results of over 90%, with an average accuracy of 97.89%, average precision of 94.98%, average recall of 90.05%, and an average F1 score of 92.33%. In addition, our model achieved an accuracy of 98.03% in mountainous areas. Our experiments and results validate the potential of combining the Swin Transformer and deformable convolutions in detailed water body extraction.
Characteristics and Driving Mechanisms of Coastal Wind Speed During Typhoon Season: A Case Study of Typhoon Lekima
Authors: Wang Lingzi , Fu Aodi , Bashir Bashar , Gu Jinjun , Sheng Haibo , Deng Liyuan , Deng Weisi , Alsafadi Karam
Published: June 2024

The development and utilization of wind energy is of great significance to the sustainable development of China's economy and the realization of the goal of "dual carbon". Under the typhoon system, the randomness and volatility of wind speed become an important basis for affecting the energy efficiency utilization and design of wind turbines. Therefore, based on wind speed and wind direction data at 10m, 30m, 50m and 70m heights of a wind power tower in Yancheng, Jiangsu Province, this paper analyzes the change characteristics of wind speed and wind direction by using BFAST method and Hurst index. Based on typhoon body data, topographic data and mesoscale system wind direction data, the causes of the occurrence and development of wind speed and wind direction of wind tower are further analyzed, and a conclusion is drawn: (1) In BEAST method, there are 5, 5, 6 and 6 change points at the height of 10m, 30m, 50m and 70m respectively. Among them, the change points at the height of 10m, 30m and 50m all change before and after node 325, and the change time point at the height of 70m is inconsistent with other heights. Hurst index results show that the inconsistency at 70m altitude is stronger than that at other altitudes. (2) The wind direction sequence at 10m, 30m, 50m and 70m altitude is fitted by stages, and the direction of wind direction is SE-E-SE-SW-W-NW, where, At the height of 70m, the deviation of the fitting trend line from other altitudes is larger in the wind speed strengthening stage and weakening stage. (3) The wind speed at the height of 10m and 70m has different response degrees to the typhoon body. The correlation between the wind speed and the distance between the wind measurement tower and the typhoon near the center is stronger at the height of 10m than at the height of 70m. The surface type and the wind direction of the mesoscale system also have certain effects on the wind speed and direction. In this paper, the change characteristics and influencing factors of wind speed and direction of wind tower are studied, which provides methods and theoretical support for the study of short-term wind speed when typhoon passes through, and provides reliable support for the selection of wind power forecast indicators and the selection and design of wind turbines under extreme gale weather systems.
Synthesis and Characterization of Novel Silylated Sm3+ and Eu3+ Complexes Incorporated into Mesoporous and Dense Silica Nanoparticles
Authors: Jorge Juliana , Silva Jaqueline Rodrigues da , Boldo Diego , Santos Kristiane Fanti Del Pino , Duarte Adriana Pereira , Castro Gustavo Rocha de , Azevedo Ricardo Bentes de , Prada Ariadna Lafourcade , Amado Jesús Rafael Rodríguez , Verelst Marc , Martines Marco Antonio Utrera
Published: June 2024

The aim of this manuscript is to synthesize and characterize novel silylated Sm3+ and Eu3+ complexes and incorporate them into mesoporous silica nanoparticles (MSNs) and dense silica nanoparticles (DSNs). Sm3+ and Eu3+ ion complexes were chosen for their strong UV-visible emission, deep-red luminescence, and effective interaction with bidentate organic ligands, such as 2-thenoyltrifluoroacetone (tta) and 1,10-phenanthroline (phen). Silylated ligands were employed as coupling agents to form covalent bonds between the complexes and an oxide matrix via a conventional sol-gel process. This approach aims to enhance the thermal stability and photophysical properties of the resulting hybrid material compared to free complexes. The new silylated-bidentate ligand complexes, using tta and phen as organic ligands and 3-chloropropyltriethoxysilane as the silylating agent, were characterized by FTIR, luminescence spectroscopy, and luminescence decay. After incorporation into silica nanoparticles, the hybrid materials were characterized by SEM, TEM, DLS, zeta potential, SAXS, porosity, surface area measurements, luminescence spectroscopy, and MTT assay. The results confirm the successful synthesis of new luminescent silylated complexes with high luminescence intensity and their incorporation into silica nanoparticles.
Persistent Illegal Hunting of Wildlife in an African Landscape: Insights from a Study in the Luangwa Valley, Zambia
Authors: Zyambo Paul , Mwitwa Jacob , Kalaba Felix Kanungwe , Kazonga Eustarckio
Published: June 2024

Decades of illegal hunting (poaching) have adversely affected wildlife populations and thereby limited sustainable wildlife conservation in the Luangwa Valley, Zambia. Despite intervention efforts to address the problem, illegal hunting of wildlife has persisted. Therefore, this study was conducted to understand the persistence of illegal hunting by investigating drivers of poaching and intervention measures using mixed-methods approach. Stratified random sampling was used to collect data from 346 respondents through structured questionnaires. Purposive sampling was used to collect data through nine (9) focus group discussions and three (3) in-depth interviews with experts. The study revealed that persistent illegal hunting was mainly driven by people’s critical needs for survival and sustaining livelihoods and not by inadequate law enforcement as presumed by resource managers. Although law enforcement was the most prevalent intervention measure, it did not deter local illegal hunters because the main motivations for poaching were not effectively addressed. The key implication of findings is that where illegal harvesting of natural resources in protected areas by local resource users is driven by people’s critical needs for survival and livelihoods which are ineffectively addressed, illegal harvesting may persist even with increased law enforcement. The study provides empirical evidence, novel conceptual knowledge and understanding on how prevalent drivers of poaching and other factors may have influenced persistent illegal hunting in the Luangwa Valley.
Nano-indentation Response of Structural Self-Healing Epoxy Resin: A Hybrid Experimental-Simulation Approach
Authors: Spinelli Giovanni , Guarini Rosella , Ivanov Evgeni , Calabrese Elisa , Raimondo Marialuigia , Longo Raffaele , Guadagno Liberata , Vertuccio Luigi
Published: June 2024

In these last years, self-healing polymers have emerged as a topic of considerable interest owing to their capability to partially restore material properties and thereby extend the product's lifespan. The main purpose of this study is to investigate the nano-indentation response in terms of hardness, reduced modulus, contact depth and coefficient of friction of a self-healing resin developed for use in aeronautical and aerospace contexts. To achieve this, the bifunctional epoxy precursor underwent tailored functionalization to improve its toughness, facilitating effective compatibilization with a rubber phase dispersed within the host epoxy resin. This approach aimed to highlight the significant impact of the quantity and distribution of rubber domains within the resin on enhancing its mechanical properties. The main results are that pure resin exhibits a higher hardness (about 36.7% more) and reduced modulus (about 7% more), consequently leading to a lower contact depth and coefficient of friction (11.4% less) compared to other formulations that, conversely, are well-suited for preserving damage from mechanical stresses due to their capabilities in absorbing mechanical energy. Furthermore, finite element method (FEM) simulations of the nanoindentation process were conducted. The numerical results were meticulously compared with experimental data, demonstrating a good agreement. This validation of the FEM model underscores its efficacy in predicting the mechanical behavior of nanocomposite materials under nanoindentation. The proposed investigation aims to contribute knowledge and optimization tips about self-healing resins.
Regulation of Plant Metabolism by Melatonin Signaling
Authors: Shi Dawei , Zhao Lejia , Zhang Ruijia , Song Qiaofeng
Published: June 2024

Melatonin, a naturally occurring chemical, has pleiotropic effects across various species. It plays a vital role in animals by regulating the body clock, while in plants, it is known to resist aging. Melatonin is associated with various plant physiological processes, including stress response, plant growth, and flowering time. It has prospects in enhancing and promoting plant growth and development, as well as in strengthening crop yield and increasing sustainability in agriculture. This review summarized the potential roles of melatonin in several plant species, as well as its biosynthetic modes. In addition, we described the recently uncovered melatonin features in plants, summarized the issues and challenges facing plant melatonin research and some feasible solution ideas are proposed.
Amylolytic Capability and Performance of Probiotic Strains in a Controlled Sorghum Fermentation System
Authors: Rapoo Seth Molamu , Thaoge-Zwane Mathoto- Lydia
Published: June 2024

This study aimed to explore the fermentation behavior of selected potential probiotic strains during sorghum fermentation, considering their microbial counts, pH levels, and antibacterial activity, their ability to break down starch. The fermentation processes were conducted in the presence and absence of glucose, and the lactic acid bacterial strains underwent controlled fermentation to assess microbial counts, amylase activity, pH, and lactic acid levels in the presence and absence of glucose. In addition, the inhibitory activity of these potential probiotic strains against pathogenic bacteria (Salmonella typhimurium, Escherichia coli, and Staph-ylococcus aureus) was examined through co-culturing. The results demonstrated that all nine Lactobacillus strains exhibited robust growth in both sugar and sugar-free fermentation experiments. Glucose supple-mentation significantly enhanced lactic acid yield which was in a range of 0.19-0.52 % compared to fer-mentation without glucose with a range of 0.03-0.29 %. The selected Lactobacillus strains effectively lowered the pH to less than 4 after 24 hours, producing substantial lactic acid. Notably, in the absence of glucose, only Lb. helveticus D7 and Lb. amylolyticus D12 achieved pH levels below 4 after 8 hours, producing the highest lactic acid amounts of 0.27 and 0.29 % after 24 hours, respectively. Amylase activity was detected on two strains D7 and D12. Furthermore, most of the tested Lactobacillus strains demonstrated complete inhibition of pathogen growth after 24 hours of co-culturing, suggesting their potential for enhancing the safety quality of sorghum-based fermented products.
Sympathetic Activation Promotes Sodium Glucose Co-Transporter-1 Protein Expression in Rodent Skeletal Muscle
Authors: Matthews Jennifer R , Herat Lakshini Y , Schlaich Markus P , Matthews Vance B
Published: June 2024

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.
Impact of Fibrin Gel Architecture on Hepatocyte Growth Factor Release and Its Role in Modulating Cell Behavior for Tissue Regeneration
Authors: Wein Svenja , Jung Shannon Anna , Al Enezy-Ulbrich Miriam Aischa , Reicher Luca , Rütten Stephan , Kühnel Mark , Jonigk Danny , Jahnen-Dechent Wilhelm , Pich Andrij , Neuss Sabine
Published: June 2024

A novel scaffold design has been created to enhance tissue engineering and regenerative medicine by optimizing the controlled, prolonged release of hepatocyte growth factor (HGF), a powerful chemoattractant for endogenous mesenchymal stem cells. We present a new stacked scaffold that is made up of three different fibrin gel layers, each of which has HGF integrated into the matrix. The design attempts to preserve HGF's regenerative properties for long periods of time, which is necessary for complex tissue regeneration. These multi-layered fibrin gels have been mechanically evaluated using rheometry, and their degradation behavior has been studied using D-Dimer ELISA. Understanding the kinetics of HGF release from this novel scaffold configuration is essential for understanding HGF's long-term sustained bioactivity. A range of cell-based tests were carried out to verify the functionality of HGF following extended incorporation. These tests included 2-photon microscopy using phalloidin staining to examine cellular morphology, SEM analysis for scaffold-cell interactions, and scratch and scatter assays to assess migration and motility. The analyses show that the novel stacking scaffold promotes vital cellular processes for tissue regeneration in addition to supporting HGF's bioactivity. This scaffold design was developed for in situ tissue engineering. Using the body as a bioreactor, the scaffold should recruit mesenchymal stem cells from their niche thus combining the regenerative abilities of HGF and MSCs to promote tissue remodeling and wound repair.
Application of Audio-Magnetotelluric and Dual-Frequency Induced Polarization Joint Inversion in a Pb-Zn Deposit Exploration in Inner Mongolia, China
Authors: Arnone Massimo , Angelillis Barbara , Costantiello Alberto , Leogrande Angelo
Published: June 2024

In this article, we analyze the relationships that connect graduates from high school, the training system and employment rates and conditions in the Italian regions between 2004 and 2022. The data used refer to the Istat Bes database. The results show that the growth in the number of high school graduates is positively associated with higher university education and employment with the exception of job satisfaction. Subsequently we also present a clusterization with k-Means algorithm confronting the Silhouette Coefficient with the Elbow Method. Finally, we confront seven different machine-learning algorithms for the prediction of the level of graduated from high school. We also present economic policy suggestions to increase schooling in the Italian regions. The results are critically discussed.
The Depression, Anxiety, and Stress of Student-athletes’ from a Pre- to Post-COVID-19 World
Authors: Bird Georgia A , Cumming Jennifer , Quinton Mary L
Published: June 2024

This study explored differences in student-athletes’ symptoms of depression, anxiety, and stress pre- to post-COVID-19 pandemic. The WHO reported a 25% increase in depression and anxiety rates worldwide with young people disproportionately affected. Student-athletes face many stressors related to their sporting and academic feats but what is not known is how the COVID-19 pandemic affected their experiences of mental illness. A multiple cohort cross-sectional study design was employed, and data collected using physical and online surveys. Participants (M age = 19.98 years, SD = 1.50) were recruited from UK universities (N = 807; 427 pre-pandemic cohort, 380 post-pandemic cohort). Results revealed statistically significant differences in mean depression, anxiety, and stress scores between cohorts. Scores for the post-pandemic cohort were significantly higher than pre-pandemic, suggesting a worsening of symptom severity. Distributions of student-athletes across categories of symptom severity also worsened for depressive and anxiety symptoms post-pandemic and were skewed towards more severe categories. Symptoms of de-pression, anxiety, and stress were a concern pre-pandemic. Rates are higher in the post-pandemic cohort, suggesting a worsening of symptoms. This data adds to evidence on student-athletes’ symptoms of mental illness by exploring a UK sample and comparing scores pre- and post-pandemic.
Target-Driven Tissue-Agnostic Drug Approvals; a New Path of Drug Development
Authors: Thein Kyaw Z , Myat Yin M , Park Byung S , Panigrahi Kalpana , Kummar Shivaani
Published: June 2024

The regulatory approvals of tumor agnostic therapies have led to reevaluation of the drug development process. Conventional models of drug development are histology-based. On the other hand, tumor agnostic drug development of a new drug (or combination) focuses on targeting a common genomic biomarker in multiple cancers, regardless of histology. Basket-like clinical trials with multiple cohorts allow clinicians to evaluate pan-cancer efficacy and toxicity. There are currently 8 tumor agnostic approvals granted by the Food and Drug Administration (FDA). This includes two immune checkpoint inhibitors, and 5 targeted therapy agents. Pembrolizumab is an anti-PD-1 antibody that was the first FDA approved tumor agnostic treatment for unresectable or metastatic microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) solid tumors in 2017. It was later approved for tumor mutational burden-high (TMB-H) solid tumors, although the TMB cut-off used is still debated. Subsequently, in 2021, another anti-PD-1 antibody, Dostarlimab was also approved for dMMR solid tumors in the refractory setting. Patients with fusion-positive cancers are typically difficult to treat due to their rare prevalence and distribution. Gene rearrangements or fusions are present in a variety of tumors. neurotrophic tyrosine kinase (NTRK) fusions are present in a range of pediatric and adult solid tumors in varying frequency. Larotrectinib and entrectinib were approved for neurotrophic tyrosine kinase (NTRK) fusion-positive cancers. Similarly, selpercatinib was approved for Rearranged During Transfection (RET) fusion-positive solid tumors. FDA approved the first combination therapy of dabrafenib, a B-Raf Proto-Oncogene Serine/Threonine Kinase (BRAF) inhibitor, plus trametinib, a mitogen-activated protein kinase (MEK) inhibitor for patients 6 months or older with unresectable or metastatic tumors (except colorectal cancer) carrying BRAFV600E mutation. The most recent FDA tumor agnostic approval is of fam-trastuzumab deruxtecan-nxki (T-Dxd) for HER2-positive solid tumors. It is important to identify and expeditiously develop drugs that have the potential to provide clinical benefit across tumor types.
Manual Dexterity and Hand Grip Strength Modifications After Application of Transcranial Static Magnetic Field Stimulation (tSMS) Over the Primary Motor Cortex (M1) in Healthy Subjects: A Triple-Blind, Randomized Clinical Trial
Authors: Navarro-López Víctor , Carratalá-Tejada María , Oliviero Antonio , Vázquez Diego Fernández , Del-Valle-Gratacós Manuel , Jiménez Jiménez Samuel , Molina-Rueda Francisco
Published: June 2024

: Objective. To test the hypothesis that a session of unilateral tSMS over the dominant primary motor cortex (M1) in healthy subjects produces a transient decrease in manual dexterity. Methods. A triple-blinded randomized control trial was conducted in 40 healthy participants who were allocated to real- or sham-tSMS group. Each participant underwent one session of tSMS and were assessed before, immediately after, 15 minutes, and 40 minutes after stimulation. Outcome measures were Finger Tapping Test (FTT), 5-seconds FTT, nine Hole Peg Test, and the hand grip assessment. Results: Significant differences were found between groups 15 minutes after stimulation in favor of the tSMS group in the FTT (2.2 ± 0.99; CI= .18-4.22; d= .84p=.034), and 5-second FTT (4.2 ± 1.98; CI= .199-8.2, d= .68; p=.04). In the intragroup analysis, a significantly lower number of taps 15 minutes after stimulation was observed in sham group (3.3 ± 1.01; CI= .47-6.13; d= .42; p=.015), but not in the real stimulation group. Conclusion: A unilateral session of tSMS in the M1 of the dominant hemisphere of healthy individuals does not reduce manual dexterity or grip strength. This technique could have benefits on the motor performance of the arm contralateral to the stimulated motor cortex
Homogeneous Projective Coordinates for the Bondi-Metzner-Sachs Group
Authors: Esposito Giampiero , Vitale Giuseppe Filiberto
Published: June 2024

This paper studies the Bondi-Metzner-Sachs group in homogeneous
projective coordinates, because it is then possible to write all
transformations of such a group in a manifestly linear way.
The 2-sphere metric, Bondi-Metzner-Sachs metric, asymptotic Killing
vectors, generators of supertranslations,
as well as boosts and rotations of Minkowski spacetime, are
all re-expressed in homogeneous projective coordinates.
Last, the integral curves of vector fields which generate supertranslations
are evaluated in detail. This work prepares the ground for more advanced
applications of the differential geometry of asymptotically flat
spacetimes in projective coordinates.
A Fair Contribution Measurement Method for Federated
Learning
Authors: Guo Peng , Yang Yanqing , Guo Wei , Shen Yanping
Published: June 2024

Federated learning is an effective approach for preserving data privacy and security, enabling machine learning to occur in a distributed environment and promoting its development. However, an urgent problem that needs to be addressed is how to encourage active client participation in federated learning. The Shapley Value, a classical concept in cooperative game theory, has been utilized for data valuation in machine learning services. Nevertheless, existing numerical evaluation schemes based on the Shapley Value are impractical as they necessitate additional model training, leading to increased communication overhead. Moreover, participants’ data may exhibit Non-IID characteristics, posing a significant challenge to evaluating participant contributions. Non-IID data weakens the marginal effects of participants, which in turn affects model accuracy and leads to underestimated contribution measurements. Current works often overlook the impact of heterogeneity on model aggregation. This paper presents a fair federated learning contribution measurement scheme that addresses the need for additional model computations. By introducing a noval aggregation weight, it enhances the accuracy of contribution measurement. Experiments on the MNIST dataset show that the proposed method can accurately compute the contributions of participants. Compared to existing baseline algorithms, the model accuracy is significantly improved, with a similar time cost.
Solar Radiation Forecasting — State of Art and Methodological Discussion
Authors: Chodakowska Ewa , Nazarko Joanicjusz , Nazarko Łukasz , Rabayah Hesham S.
Published: June 2024

Effective solar forecasting has become a critical topic in the scholarly literature in recent years due to the rapid growth of photovoltaic energy production worldwide and the inherent variability of this source of energy. Due to the technological and econonomic limitations of energy storage solutions, using other, mosty conventional, sources to cover energy shortfalls and at the same time utilising solar surpluses production becomes necessary. The need to optimize energy systems, ensuring power continuity, and balancing energy supply and demand has led to the development of various forecasting methods and approaches based on meteorological data or photovoltaic plant characteristics. This article presents the results of a meta-review of the solar forecasting literature, including the current state of knowledge and methodological discussion. It presents a comprehensive set of forecasting methods, evaluates current classifications, and proposes a new synthetic typology. The article emphasizes the increasing role of artificial intelligence (AI) and machine learning (ML) techniques in improving forecast accuracy, alongside traditional statistical and physical models. It explores the challenges of hybrid and ensemble models, which combine multiple forecasting approaches to enhance performance. The paper addresses the emerging trends in solar forecasting research, such as the integration of big data and advanced computational tools. Additionally, from a methodological perspective, the article outlines a rigorous approach to the meta-review research procedure, addresses the scientific challenges associated with conducting bibliometric research, and highlights best practices and principles. This includes defining research questions, selecting eligibility criteria, literature search, data extraction, synthesis, and assessing bias and quality. The article contributes to the solar forecasting field by providing up-to-date knowledge, along with insights on the emerging trends, future research directions, and anticipating implications for the theory and practicce.
Investigation of the Clinical Value of Four Visualization Modalities for Congenital Heart Disease
Authors: Lee Shen-Yuan , Squelch Andrew , Sun Zhonghua
Published: June 2024

Diagnosing congenital heart disease (CHD) remains challenging because of its complex morphology. Representing the intricate structures of CHD on conventional two-dimensional flat screens is difficult owing to wide variations in the pathologies. Technological advancements, such as three-dimensional printed heart models (3DPHM) and virtual reality (VR), could potentially address the limitations of viewing complex structures using conventional methods. This study aimed to investigate the usefulness and clinical value of four visualization modalities across three different cases of CHD, including ventricular septal defect, double outlet right ventricle, and tetralogy of fallot. Seventeen cardiac specialists were invited to participate in this study, which was aimed at assessing the usefulness and clinical value of four visualization modalities, namely, DICOM images, 3DPHM, VR, and 3D PDF. Of these modalities, 76.4% of the specialists ranked VR as the best for understanding the spatial associations among cardiac structures and for presurgical planning. Meanwhile, 94.1% ranked 3DPHM as the best modality for communicating with patients and their families. Of the various visualization modalities, VR was the best tool for assessing anatomical locations and vessels, comprehending the spatial relationships among cardiac structures, and for presurgical planning. The 3DPHM models were the best tool for medical education as well as communication. In summary, both 3DPHM and VR have their own advantages and outperform the other two modalities, i.e., DICOM images and 3D PDF, in terms of visualizing and managing CHD.
Environmental Impact Assessment of Volatile Organic Compound Emissions during Trenchless Cured-in-Place Pipe Installation
Authors: Bavilinezhad Salar , Najafi Mohammad , Kaushal Vinayak , Elledge William , Kaynak Burak
Published: June 2024

Cured-in-place pipe (CIPP) lining is a widely adopted method for pipeline renewal, offering advantages such as rapid installation and cost-effectiveness. However, concerns regarding the environmental impacts of volatile organic compound (VOC) emissions during the installation process have raised issues regarding the CIPP method. The literature review conducted in this paper indicated the need for stringent monitoring and management practices to mitigate adverse effects, emphasizing the importance of safe installation protocols. This paper presents the initial results of a case study focusing on VOC emissions, specifically investigating non-styrene polyester resins and water curing. To capture emissions from CIPP activities, the methodology involved air sampling using various equipment, including photoionization detectors (PID), summa canisters, passive worker sampler sorbent tubes, and method 13 cartridges. The preliminary findings indicate that non-styrene polyester resins do not exceed the exposure limits set out by the OSHA and USEPA. The future phases of this project will explore different resins and curing methods.
Regional Variations in Urban Trash: Connections between Litter Communities and Place
Authors: Kachef Randa L , Chadwick Michael
Published: June 2024

In this study, data analysis methods from ecology were applied to litter surveys to evaluate patterns among urban litter items found in two types of streets in England (High Streets and Central Business Districts). Results indicate that sites characterised as a High Street (predominantly leisure activities such as shopping and dining) contained lower densities, less variety, yet featured items with higher potential for environmental contamination than sites categorised as Central Business District (identified by high numbers of professional workers and transport links). Although litter were significantly different between sites, the litter community structure was not. Our results suggest that litter typologies and associated activities can lead to specific knowledge of key influential items in a site and inform future evidence based and sustainable mitigation systems.
Adsorption of Co2+ by Graphene Oxide based on DFT
Authors: Bao Ping , Wang Xiao-wei , Men Jin-feng , Xie Yu-dong
Published: June 2024

Aiming at the removal of radioactive cobalt ions from water by graphene oxide (GO), the adsorption mechanism of Co2+ on graphene oxide was analyzed using the quantum chemical calculation software Gaussian 16 based on the density functional theory. The influence of material structure factors such as carboxyl group, hydroxyl group, epoxy group and graphene sheet as well as external environmental factors such as pH, temperature and interfering ions on the adsorption effect was determined, and the influence of external environment was verified through experiments. Through calculation and experiment, it was found that the existence of oxygen-containing functional groups on graphene oxide can improve the adsorption efficiency of the materialappropriately,and increasing pH under acidic conditions was also helpful to improve the adsorption effect, and the material had certain selectivity for Co2+, the adsorption capacity and selectivity could be further improved when it was modified by increasing hydroxyl group.
Deficient Gap Junction Coupling in Two Common Hearing Loss-Related Variants of GJB2
Authors: Chen Kaitian , Jiang Hongyan
Published: June 2024

Objectives. The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2.Methods. Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling.Results. The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells’ sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT.Conclusion. The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.
The influence of Myoinositol to improve biochemical manifestations of the serum and follicular fluid and ICSI outcomes in patients with PCOS: A prospective randomized research
Authors: Yazdanpanah Zeynab , Cheraghi Ebrahim , Nasrabadi Mitra Heydari , Salehipour Masoud
Published: June 2024

Purpose
The research investigated the capacity of Myo-inositol (MI) in order that it improves biochemical markers in serum and follicular fluid, and ultimately, intracytoplasmic sperm injection (ICSI) outcomes of women with PCOS.
Methods
Sixty infertile patients with PCOS who were undergoing ovulation induction for ICSI, were randomly divided to two groups. The MI group received 2000 mg Myo-inositol + 1 mg folic acid twice a day for 6 weeks with starting the ICSI cycle. For the same period, the control group received a placebo containing only folic acid (1 mg). Levels of hormonal profiles in serum and follicular fluid, as well as oxidative stress markers (MDA, TAC, GPx, and SOD) were estimated using an ELISA assay. Primary end points were ICSI cycle outcomes.
Results
Compared to the placebo group, the MI group demonstrated significant reduction in serum and follicular fluid levels of LH, LH/FSH ratio, total testosterone, AMH, and Androstenedione. Furthermore, the MI group exhibited meaningful increases in TAC, GPx, and SOD, but MDA significantly decreased. While the number of recovered and mature oocytes is not similar statistically among the groups, the MI group showed significant improvements in the percentage of immature oocytes, cleavage rate, and good embryo quality. A meaningful correlation was checked between follicular fluid AMH level and LH, FSH, total testosterone, Androstenedione, insulin, MDA, the number of recovered oocytes, and immature oocytes.
Conclusion
Our outcomes indicate that Myo-inositol administration in women with PCOS undergoing ART helps to improve their hormonal profiles, and the quality of oocytes and embryos. (Trial registration: IRCT202220921056008N1)
Badminton player ranking model based on dynamic ELO model
Authors: Yang Rong , Kai Yue
Published: June 2024

In this paper, the ELO scoring method is applied to rank the badminton players. By analyzing the ranking results, we find that the basic ELO model can only see the rank of the players at the top level, while other players are unable due to the reason that they have the same ELO score. Because the basic ELO model only considers the result of the competition, without taking into account the past performance of players, physical condition , and other factors, it cannot fully reflect the true level. Therefore, improving the basic model is necessary. Firstly, the initial score is rese-lected based on the past performance of players. Then, different weights are assigned to each stage of the competition, and a streak mechanism is introduced to establish a more comprehensive dynamic system. In particular , for players who are unable to participate in the competition due to unexpected factors, we also establish different scoring methods. Finally , a new badminton player ranking is obtained based on the improved model. In the final, the classical Goodman−Kruskal correlation coefficient in statistics is selected for numerical analysis, and the comparison results are highly consistent. In particular, we can measure the winning rate of different players through the model, which can also help us better predict the performance of players in the game.