bluuebunny/crossref_metadata_2025 huggingface dataset:
DRpred: A Novel Deep Learning-Based Predictor for Multi-Label mRNA Subcellular Localization Prediction by Incorporating Bayesian Inferred Prior Label Relationships
Authors: Wang Xiao , Yang Lixiang , Wang Rong
Published: August 2024

The subcellular localization of messenger RNA (mRNA) not only helps us to understand the localization regulation of gene expression but also helps to understand the relationship between RNA localization pattern and human disease mechanism, which has profound biological and medical significance. Several predictors have been proposed for predicting the subcellular localization of mRNA. However, there is still considerable room for improvement in their predictive performance, especially regarding multi-label prediction. This study proposes a novel multi-label predictor, DRpred, for mRNA subcellular localization prediction. This predictor first utilizes Bayesian networks to capture the dependencies among labels. Subsequently, it combines these dependencies with features extracted from mRNA sequences using Word2vec, forming the input for the predictor. Finally, it employs a neural network combining BiLSTM and an attention mechanism to capture the internal relationships of the input features for mRNA subcellular localization. The experimental validation on an independent test set demonstrated that DRpred obtained a competitive predictive performance in multi-label prediction and outperformed state-of-the-art predictors in predicting single subcellular localizations, obtaining accuracies of 82.14%, 93.02%, 80.37%, 94.00%, 90.58%, 84.53%, 82.01%, 79.71%, and 85.67% for the chromatin, cytoplasm, cytosol, exosome, membrane, nucleolus, nucleoplasm, nucleus, and ribosome, respectively. It is anticipated to offer profound insights for biological and medical research.
CRISPR/Cas9-Based Genome Editing of Fall Armyworm (Spodoptera frugiperda): Progress and Prospects
Authors: Salum Yussuf Mohamed , Yin Anyuan , Zaheer Uroosa , Liu Yuanyuan , Guo Yi , He Weiyi
Published: August 2024

The fall armyworm (Spodoptera frugiperda) poses a substantial threat to many important crops worldwide, emphasizing the need to develop and implement advanced technologies for effective pest control. CRISPR/Cas9, derived from the bacterial adaptive immune system, is a prominent tool used for genome editing in living organisms. Due to its high specificity and adaptability, the CRISPR/Cas9 system has been used in various functional gene studies through gene knockout and applied in research to engineer phenotypes that may cause economical losses. The practical application of CRISPR/Cas9 in diverse insect orders has also provided opportunities for developing strategies for genetic pest control, such as gene drive and the precision-guided sterile insect technique (pgSIT). In this review, a comprehensive overview of the recent progress in the application of the CRISPR/Cas9 system for functional gene studies in S. frugiperda is presented. We outline the fundamental principles of applying CRISPR/Cas9 in S. frugiperda through embryonic microinjection and highlight the application of CRISPR/Cas9 in the study of genes associated with diverse biological aspects, including body color, insecticide resistance, olfactory behavior, sex determination, development, and RNAi. The ability of CRISPR/Cas9 technology to induce sterility, disrupt developmental stages, and influence mating behaviors illustrates its comprehensive roles in pest management strategies. Furthermore, this review addresses the limitations of the CRISPR/Cas9 system in studying gene function in S. frugiperda and explores its future potential as a promising tool for controlling this insect pest.
Eosinophilia as Monitoring Parameter for Chronic Graft-versus-Host Disease and Vitamin D Metabolism as Monitoring Parameter for Increased Infection Rates in Very Long-Term Survivors of Allogeneic Stem Cell Transplantation—A Prospective Clinical Study
Authors: Neumann Thomas , Peters Nadette , Schneidewind Laila , Krüger William
Published: August 2024

Background: Our aim is to investigate cardiovascular risk factors, chronic graft-versus-host disease (CGvHD), and vitamin D metabolism in very long-term survivors of adult allogeneic stem cell transplantation (alloSCT). Methods: This study is a prospective unicentric, non-interventional trial. The detailed study protocol is available via the WHO Clinical Trial Registry. Results: We were able to include 33 patients with a mean age of 60.5 years (SD 11.1). Acute myeloid leukemia (AML) was the most frequent underlying disease (n = 12; 36.4%). The median survival time was 9.0 years (IQR 8.5–13.0). Relevant cardiovascular risk factors in the study population are the body mass index, cholesterol, LDL cholesterol, and lipoprotein(a). Cardiovascular risk factors have no significant impact on HRQoL. CGvHD of the skin as a limited disease was present in six patients (18.2%), and it has no impact on HRQoL. CGvHD was significantly associated with eosinophilia in peripheral blood (p = 0.003). Three patients (9.1%) had a shortage of calcitriol, and one patient (3.0%) took calcium substitution. The shortage is significantly associated with increased infection rates (p = 0.038). Conclusions: Cardiovascular risk factors and CGvHD need to be closely monitored. Eosinophilia might be a good and convenient monitoring parameter for CGvHD.
Association of Endothelial Cell Activation with Acute Kidney Injury during Coronary Angiography and the Influence of Recombinant Human C1 Inhibitor—A Secondary Analysis of a Randomized, Placebo-Controlled, Double-Blind Trial
Authors: Moser Stephan , Araschmid Laura , Panagiotou Anneza , Bonati Leo H. , Breidthardt Tobias , Fahrni Gregor , Kaiser Christoph , Jeger Raban , Trendelenburg Marten , Osthoff Michael
Published: August 2024

Background: Acute kidney injury (AKI) as a result of iodinated contrast media (CM) has been linked to CM-induced renal ischemia and toxic effects on endothelial cells (EC). The recombinant human C1 inhibitor (rhC1INH) has been shown to influence EC activation. Methods: Secondary analysis of 74/77 (96%) participants of a double-blind, randomized, and placebo-controlled study that assessed the effect of rhC1INH on AKI. E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule (VCAM-1), and CC-chemokin-ligand-5 (CCL5) were determined in frozen blood samples over 48 h and analyzed according to the treatment group and renal outcomes. Results: The mean age was 76.7 years, and 37 patients each received rhC1INH and placebo, respectively. In the entire study population, minor differences in median EC activation markers/CCL5 concentrations during the first 48 h compared to baseline were observed (e.g., E-selectin 27.5 ng/mL at baseline vs. 29.7 ng/mL on day 1, CCL5: 17.7 ng/mL at baseline vs. 32.2 ng/mL on day 2). Absolute changes in ICAM-1/E-selectin concentrations correlated with a higher peak change in urinary NGAL concentrations. However, AKI was not associated with significant changes in EC markers/CCL5. Last, no significant differences in serum concentrations of EC activation markers/CCL5 were evident between the placebo and the rhC1INH group. Conclusions: CM administration during coronary angiography only mildly activated ECs within the first 48 h, which does not explain subsequent AKI. The administration of rhC1INH was not associated with a reduction of EC activation or CCL5.
A Self-Learning Hyper-Heuristic Algorithm Based on a Genetic Algorithm: A Case Study on Prefabricated Modular Cabin Unit Logistics Scheduling in a Cruise Ship Manufacturer
Authors: Li Jinghua , Dong Ruipu , Wu Xiaoyuan , Huang Wenhao , Lin Pengfei
Published: August 2024

Hyper-heuristic algorithms are known for their flexibility and efficiency, making them suitable for solving engineering optimization problems with complex constraints. This paper introduces a self-learning hyper-heuristic algorithm based on a genetic algorithm (GA-SLHH) designed to tackle the logistics scheduling problem of prefabricated modular cabin units (PMCUs) in cruise ships. This problem can be regarded as a multi-objective fuzzy logistics collaborative scheduling problem. Hyper-heuristic algorithms effectively avoid the extensive evaluation and repair of infeasible solutions during the iterative process, which is a common issue in meta-heuristic algorithms. The GA-SLHH employs a genetic algorithm combined with a self-learning strategy as its high-level strategy (HLS), optimizing low-level heuristics (LLHs) while uncovering potential relationships between adjacent decision-making stages. LLHs utilize classic scheduling rules as solution support. Multiple sets of numerical experiments demonstrate that the GA-SLHH exhibits a stronger comprehensive optimization ability and stability when solving this problem. Finally, the validity of the GA-SLHH in addressing real-world decision-making issues in cruise ship manufacturing companies is validated through practical enterprise cases. The results of a practical enterprise case show that the scheme solved using the proposed GA-SLHH can reduce the transportation time by up to 37%.
Recent Developments in Personal Glucose Meters as Point-of-Care Testing Devices (2020–2024)
Authors: Yang Dan-Ni , Geng Shan , Jing Rong , Zhang Hao
Published: August 2024

Point-of-care testing (POCT) is a contemporary diagnostic approach characterized by its user-friendly nature, cost efficiency, environmental compatibility, and lack of reliance on professional experts. Therefore, it is widely used in clinical diagnosis and other analytical testing fields to meet the demand for rapid and convenient testing. The application of POCT technology not only improves testing efficiency, but also brings convenience and benefits to the healthcare industry. The personal glucose meter (PGM) is a highly successful commercial POCT tool that has been widely used not only for glucose analysis, but also for non-glucose target detection. In this review, the recent advances from 2020 to 2024 in non-glucose target analysis for PGMs as POCT devices are summarized. The signal transduction strategies for non-glucose target analysis based on PGMs, including enzymatic transduction, nanocarrier transduction (enzyme or glucose), and glucose consumption transduction are briefly introduced. Meanwhile, the applications of PGMs in non-glucose target analysis are outlined, encompassing biomedical, environmental, and food analysis, along with other diverse applications. Finally, the prospects of and obstacles to employing PGMs as POCT tools for non-glucose target analysis are discussed.
Understanding Perceptions of Tourism Impact on Quality of Life in Traditional Earthen–Wooden Villages: Insights from Residents and Tourists in Meishan
Authors: Zhang Shuang , Li Zhirong , Liu Shaobo
Published: August 2024

This study focuses on four traditional earthen–wooden villages in Hunan Province, exploring the multifaceted impacts of tourism development on the quality of life from the perspectives of both residents and tourists. Utilizing structural equation modeling, this research examines how macro-level cultural resources, meso-level spatial characteristics, and micro-level traditional architecture influence the development of cultural tourism and its subsequent effects on quality of life. The findings indicate that while cultural resources and spatial characteristics positively contribute to the quality of cultural tourism development, traditional architecture presents a complex challenge. Specifically, traditional architecture negatively impacts quality of life due to maintenance demands and modernization pressures, yet it also enhances cultural tourism through its intrinsic heritage value. Spatial characteristics are identified as the most significant positive factor, indirectly enhancing both tourism quality and overall life satisfaction by enriching the cultural landscape. Additionally, the study uncovers significant differences in how residents and tourists perceive the impacts of tourism. Tourists generally seek enriching and authentic experiences, while residents are more directly affected by the socio-economic and environmental changes brought by tourism. This divergence highlights the need for balanced and targeted management strategies that address the distinct needs and perceptions of both groups at various stages of tourism development. By addressing these dynamic factors, this study offers valuable insights for policymakers and administrators aiming to balance heritage preservation with sustainable economic growth in traditional earthen–wooden villages. The research also underscores the critical role of community engagement and adaptive strategies in fostering resilient and thriving rural communities in the 21st century.
FE-YOLO: A Lightweight Model for Construction Waste Detection Based on Improved YOLOv8 Model
Authors: Yang Yizhong , Li Yexue , Tao Maohu
Published: August 2024

Construction waste detection under complex scenarios poses significant challenges due to low detection accuracy, high computational complexity, and large parameter volume in existing models. These challenges are critical as accurate and efficient detection is essential for effective waste management in the construction industry, which is increasingly focused on sustainability and resource optimization. This paper aims to address the low accuracy of detection, high computational complexity, and large parameter volume in the models of construction waste detection under complex scenarios. For this purpose, an improved YOLOv8-based algorithm called FE-YOLO is proposed in this paper. This algorithm replaces the C2f module in the backbone with the Faster_C2f module and integrates the ECA attention mechanism into the bottleneck layer. Also, a custom multi-class construction waste dataset is created for evaluation. FE-YOLO achieves an mAP@50 of 92.7% on this dataset, up by 3% compared to YOLOv8n. Meanwhile, the parameter count and floating-point operations are scaled down by 12% and 13%, respectively. Finally, a test is conducted on a publicly available construction waste dataset. The test results demonstrate the excellent performance of this algorithm in generalization and robustness.
The FLARE Score and Circulating Neutrophils in Patients with Cancer and COVID-19 Disease
Authors: Seguí Elia , Torres Juan Manuel , Auclin Edouard , Casadevall David , Peiro Carmona Sara , Aguilar-Company Juan , García de Herreros Marta , Gorría Teresa , Laguna Juan Carlos , Rodríguez Marta , González Azucena , Epaillard Nicolas , Gavira Javier , Bolaño Victor , Tapia Jose C. , Tagliamento Marco , Teixidó Cristina , Arasanz Hugo , Pilotto Sara , Lopez-Castro Rafael , Mielgo-Rubio Xabier , Urbano Cristina , Recondo Gonzalo , Diaz Pavon Mar , Bluthgen Maria Virginia , Minatta José Nicolas , Lupinacci Lorena , Brasó-Maristany Fara , Prat Aleix , Vlagea Alexandru , Mezquita Laura
Published: August 2024

Purpose: Inflammation and neutrophils play a central role in both COVID-19 disease and cancer. We aimed to assess the impact of pre-existing tumor-related inflammation on COVID-19 outcomes in patients with cancer and to elucidate the role of circulating neutrophil subpopulations. Methods: We conducted a multicenter retrospective analysis of 524 patients with cancer and SARS-CoV-2 infection, assessing the relationship between clinical outcomes and circulating inflammatory biomarkers collected before and during COVID-19 infection. Additionally, a single-center prospective cohort study provided data for an exploratory analysis, assessing the immunophenotype of circulating neutrophils and inflammatory cytokines. The primary endpoints were 30-day mortality and the severity of COVID-19 disease. Results: Prior to COVID-19, 25% of patients with cancer exhibited elevated dNLR, which increased to 55% at the time of COVID-19 diagnosis. We developed the FLARE score, incorporating both tumor- and infection-induced inflammation, which categorized patients into four prognostic groups. The poor prognostic group had a 30-day mortality rate of 68%, significantly higher than the 23% in the favorable group (p < 0.0001). This score proved to be an independent predictor of early mortality. This prospective analysis revealed a shift towards immature forms of neutrophils and higher IL-6 levels in patients with cancer and severe COVID-19 infection. Conclusions: A pre-existing tumor-induced pro-inflammatory state significantly impacts COVID-19 outcomes in patients with cancer. The FLARE score, derived from circulating inflammatory markers, emerges as an easy-to-use, globally accessible, effective tool for clinicians to identify patients with cancer at heightened risk of severe COVID-19 complications and early mortality who might benefit most from immediate and intensive treatment strategies. Furthermore, our findings underscore the significance of immature neutrophils in the progression of COVID-19 in patients with cancer, advocating for further investigation into how these cells contribute to both cancer and COVID-19 disease.
Antimigratory Effect of Lipophilic Cations Derived from Gallic and Gentisic Acid and Synergistic Effect with 5-Fluorouracil on Metastatic Colorectal Cancer Cells: A New Synthesis Route
Authors: Suárez-Rozas Cristian , Jara José Antonio , Cortés Gonzalo , Rojas Diego , Araya-Valdés Gabriel , Molina-Berrios Alfredo , González-Herrera Fabiola , Fuentes-Retamal Sebastián , Aránguiz-Urroz Pablo , Campodónico Paola Rossana , Maya Juan Diego , Vivar Raúl , Catalán Mabel
Published: August 2024

Colorectal cancer (CRC) is the third leading cause of cancer deaths in the world. Standard drugs currently used for the treatment of advanced CRC—such as 5-fluorouracil (5FU)—remain unsatisfactory in their results due to their high toxicity, high resistance, and adverse effects. In recent years, mitochondria have become an attractive target for cancer therapy due to higher transmembrane mitochondrial potential. We synthesized gallic acid derivatives linked to a ten-carbon aliphatic chain associated with triphenylphosphonium (TPP+C10), a lipophilic cationic molecule that induces the uncoupling of the electron transport chain (ETC). Other derivatives, such as gentisic acid (GA-TPP+C10), have the same effects on colorectal cancer cells. Although part of our group had previously reported preparing these structures by a convergent synthesis route, including their application via flow chemistry, there was no precedent for a new methodology for preparing these compounds. In this scenario, this study aims to develop a new linear synthesis strategy involving an essential step of Steglich esterification under mild conditions (open flask) and a high degree of reproducibility. Moreover, the study seeks to associate GA-TPP+C10 with 5FU to evaluate synergistic antineoplastic effects. In addition, we assess the antimigratory effect of GA-TPP+C10 and TPP+C10 using human and mouse metastatic CRC cell lines. The results show a new and efficient synthesis route of these compounds, having synergistic effects in combination with 5FU, increasing apoptosis and enhancing cytotoxic properties. Additionally, the results show a robust antimigratory effect of GATPP+C10 and TPP+C10, reducing the activation pathways linked to tumor progression and reducing the expression of VEGF and MMP-2 and MMP-9, common biomarkers of advanced CRC. Moreover, TPP+C10 and GA-TPP+C10 increase the activity of metabolic signaling pathways through AMPK activation. The data allow us to conclude that these compounds can be used for in vivo evaluations and are a promising alternative associated with conventional therapies for advanced colorectal cancer. Additionally, the reported intermediates of the new synthesis route could give rise to analog compounds with improved therapeutic activity.
Using mHealth Technology to Evaluate Daily Symptom Burden among Adult Survivors of Childhood Cancer: A Feasibility Study
Authors: Howell Kristen E. , Baedke Jessica L. , Bagherzadeh Farideh , McDonald Aaron , Nathan Paul C. , Ness Kirsten K. , Hudson Melissa M. , Armstrong Gregory T. , Yasui Yutaka , Huang I-Chan
Published: August 2024

Background: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer to evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). Methods: This prospective study used an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after the symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. These surveys comprised a PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models were used to analyze total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression was used to analyze the association between daily symptom burden in the first month and HRQOL in the third month, adjusted for covariates. Results: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL in each study week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95% CI: 4.10–9.02), depression (6.32; 95% CI: 3.18–9.47), fatigue (7.93; 95% CI: 5.11–10.80), sleep (6.07; 95% CI: 3.43–8.70), pain (5.16; 95% CI: 2.11–8.22), and cognitive function (–6.89; 95% CI: –10.00 to –3.79) in the third month. Conclusions: Daily assessment revealed fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability.
Prevalence of Germline Pathogenic Variants in Renal Cancer Predisposition Genes in a Population-Based Study of Renal Cell Carcinoma
Authors: Bruinsma Fiona , Harraka Philip , Jordan Susan , Park Daniel , Pope Bernard , Steen Jason , Milne Roger , Giles Graham , Winship Ingrid , Tucker Katherine , Southey Melissa , Nguyen-Dumont Tu
Published: August 2024

Renal cell carcinoma (RCC) has been associated with germline pathogenic or likely pathogenic (PLP) variants in recognised cancer susceptibility genes. Studies of RCC using gene panel sequencing have been highly variable in terms of study design, genes included, and reported prevalence of PLP variant carriers (4–26%). Studies that restricted their analysis to established RCC predisposition genes identified variants in 1–6% of cases. This work assessed the prevalence of clinically actionable PLP variants in renal cancer predisposition genes in an Australian population-based sample of RCC cases. Germline DNA from 1029 individuals diagnosed with RCC who were recruited through the Victoria and Queensland cancer registries were screened using a custom amplicon-based panel of 21 genes. Mean age at cancer diagnosis was 60 ± 10 years, and two-thirds (690, 67%) of the participants were men. Eighteen participants (1.7%) were found to carry a PLP variant. Genes with PLP variants included BAP1, FH, FLCN, MITF, MSH6, SDHB, TSC1, and VHL. Most carriers of PLP variants did not report a family history of the disease. Further exploration of the clinical utility of gene panel susceptibility testing for all RCCs is warranted.
Bond Strength of Composite Resin to Bioceramic Cements: An In Vitro Study
Authors: Alvarado-Orozco Alejandra , Hardan Louis , Bourgi Rim , Monjarás-Ávila Ana Josefina , Cuevas-Suárez Carlos Enrique , Rodríguez-Vilchis Laura Emma , Farrayeh Antoun , Flores-Ferreyra Blanca Irma , Contreras-Bulnes Rosalía , Haikel Youssef , Kharouf Naji
Published: August 2024

Bioceramic endodontic cements, known for their antibacterial properties, calcium ion release, and alkaline pH, may come into contact with various irrigants after furcal perforation repair. This study aimed to evaluate the effect of different irrigating solutions and setting times on the shear bond strength (SBS) of Biodentine® (Septodont, Saint-Maur-des-Fosses Cedex, France) to a self-adhering flowable composite. Sixty Biodentine® (Septodont, Saint-Maur-des-Fosses Cedex, France) blocks were prepared and divided into two groups based on the setting time: 72 h and 7 days. These were further subdivided into five subgroups based on the irrigation solution applied: distilled water, sodium hypochlorite, ethylenediaminetetraacetic acid, chlorhexidine, and phosphoric acid. They were then restored with Dyad FlowTM (KerrTM, Orange, CA, USA). SBS and failure modes were assessed at 24 h and 6 months. A two-way analysis of variance (ANOVA) test was performed to analyze the effect of the different irrigating solutions and setting times on the SBS of Biodentine® (Septodont, Saint-Maur-des-Fosses Cedex, France) and Dyad FlowTM (KerrTM, Orange, CA, USA). The level of significance was set at a ≤0.05. At 24 h, SBS was significantly influenced by both the irrigant solution (p = 0.029) and setting time (p = 0.018); at 6 months, SBS was influenced only by the irrigating solutions (p < 0.001). The predominant mode of bond failure was adhesive across all groups. In conclusion, while the setting time did not affect the bond strength, certain irrigating solutions reduced it. Thus, careful consideration of surface treatments applied to Biodentine® is crucial for successful endodontic and restorative outcomes.
Effects of Heat-Induced Oxidative Stress and Astaxanthin on the NF-kB, NFE2L2 and PPARα Transcription Factors and Cytoprotective Capacity in the Thymus of Broilers
Authors: Kuehu Donna Lee , Fu Yuanyuan , Nasu Masaki , Yang Hua , Khadka Vedbar S. , Deng Youping
Published: August 2024

The thymus, a central lymphoid organ in animals, serves as the site for T cell development, differentiation and maturation, vital to adaptive immunity. The thymus is critical for maintaining tissue homeostasis to protect against tumors and tissue damage. An overactive or prolonged immune response can lead to oxidative stress from increased production of reactive oxygen species. Heat stress induces oxidative stress and overwhelms the natural antioxidant defense mechanisms. This study’s objectives were to investigate the protective properties of astaxanthin against heat-induced oxidative stress and apoptosis in the chicken thymus, by comparing the growth performance and gene signaling pathways among three groups: thermal neutral, heat stress, and heat stress with astaxanthin. The thermal neutral temperature was 21–22 °C, and the heat stress temperature was 32–35 °C. Both heat stress groups experienced reduced growth performance, while the astaxanthin-treated group showed a slightly lesser decline. The inflammatory response and antioxidant defense system were activated by the upregulation of the NF-kB, NFE2L2, PPARα, cytoprotective capacity, and apoptotic gene pathways during heat stress compared to the thermal neutral group. However, expression levels showed no significant differences between the thermal neutral and heat stress with antioxidant groups, suggesting that astaxanthin may mitigate inflammation and oxidative stress damage.
The Impact of Modern Bone Markers in Multiple Myeloma: Prospective Analyses Pre and Post-First Line Treatment
Authors: Pop Vlad Stefan , Iancu Mihaela , Țigu Adrian Bogdan , Adam Anda , Tomoaia Gheorghe , Farcas Anca Daniela , Bojan Anca Simona , Parvu Andrada
Published: August 2024

Multiple myeloma, the disease characterized by the malignant proliferation of plasma cells that invades the bone marrow, produces osteolytic lesions and secretes monoclonal proteins. Several biomarkers have been shown to represent important tools in the pathogenesis of myeloma and offer insights into bone degradation and formation. The objectives of this current study were to assess the associations of modern biomarkers (TNF-α: tumor necrosis factor; IFN: Interferon; FreeRANKL: Free Receptor Activator for Nuclear Factor kappa B Ligand; RANKL: Receptor Activator for Nuclear Factor kappa B Ligand, Beta crosslaps, IL-6: Interleukin 6) with osteolytic lesions status after first-line treatment and to evaluate the correlations between modern and classical biomarkers (LDH: Lactate Dehydrogenase; VSH: Erythrocyte Sedimentation Rate; Hgb: Hemoglobin, Calcium, Albumin, B2microglobulin) stratified by osteolytic lesions status. A total of 35 patients diagnosed with multiple myeloma divided into two groups according to the osteolytic bone lesions, were studied: (1) unchanged status of osteolytic lesions and (2) changed status of osteolytic lesions. After fist-line treatment, we found a significant difference in Albumin (p = 0.0029) and Calcium levels (p = 0.0304), patients with a changed status in osteolytic lesions having higher values of Albumin and Calcium compared to those without changes in status of osteolytic lesions. After first-line treatment, decreased IL-6 values were significantly correlated with elevated values of Albumin (ρ = −0.96, p = 0.0005) in the patients with changed status of osteolytic lesions. Post-treatment values of IFN showed a significant positive correlation with Hemoglobin (ρ = 0.47, p = 0.0124), IL-6 (ρ = 0.55, p = 0.0026) and TNF-alpha values (ρ = 0.54, p = 0.0029). The results obtained from patients with unmodified lytic lesions identified a significant correlation between the biomarkers IL-6, Free RANKL, and IFN-beta with the classical marker LDH. This association highlights the involvement of these markers in promoting bone destruction and the development of osteolytic lesions.
The ER Stress Induced in Human Neuroblastoma Cells Can Be Reverted by Lumacaftor, a CFTR Corrector
Authors: Pecoraro Michela , Serra Adele , Pascale Maria , Franceschelli Silvia
Published: August 2024

Most neurodegenerative diseases share a common etiopathogenesis, the accumulation of protein aggregates. An imbalance in homeostasis brought on by the buildup of misfolded proteins within the endoplasmic reticulum (ER) results in ER stress in the cell. Three distinct proteins found in the ER membrane—IRE1α, PERK, and ATF6—control the unfolded protein response (UPR), a signal transduction pathway that is triggered to restore normal physiological conditions. Buildup of misfolded proteins in ER lumen leads to a shunting of GRP78/BiP, thus triggering the UPR. PERK autophosphorylation leads to activation of ATF4, the transcription factor; finally, ATF6 activates the UPR’s target genes, including GRP78/Bip. Accordingly, the UPR is a cellular reaction to an ER stress state that, if left unchecked for an extended period, results in apoptosis and irreversible damage. The identification of caspase 4, which is in the ER and is selectively activated by apoptotic stimuli caused by reticular stress, further demonstrated the connection between reticular stress and programed cell death. Moreover, oxidative stress and ER stress are linked. Oxidative stress is brought on by elevated quantities of radical oxygen species, both mitochondrial and cytosolic, that are not under the enzymatic regulation of superoxide dismutases, whose levels fall with increasing stress. Here, we evaluated the activity of Vx-809 (Lumacaftor), a drug used in cystic fibrosis, in SH-SY5Y neuronal cells, in which an ER stress condition was induced by Thapsigargin, to verify whether the drug could improve protein folding, suggesting its possible therapeutic use in proteinopathies, such as neurodegenerative diseases (NDs). Our data show that Vx-809 is involved in the significant reduction in protein produced under ER stress, particularly in the levels of Bip, ATF4, and ATF6 by Western blotting analysis, the reduction in ROS in the cytosol and mitochondria, and the reduction in the activation of the apoptotic pathway, measured by flow cytofluorimetry analysis and in restoring calcium homeostasis.
Genomic Exploration of a Chitinolytic Streptomyces albogriseolus PMB5 Strain from European mantis (Mantis religiosa)
Authors: Baev Vesselin , Iliev Ivan , Apostolova Elena , Gozmanova Mariyana , Hristova Yana , Ilieva Yanitsa , Yahubyan Galina , Gochev Velizar
Published: August 2024

The genus Streptomyces is renowned not only for its natural antibiotic production but also for its abundant chitinolytic enzymes, which break down stubborn chitin into chitooligosaccharides. Despite this, there have been limited studies utilizing whole-genome sequencing to explore the repertoire of chitin degradation and utilization genes in Streptomyces. A particularly compelling source of novel antimicrobials and enzymes lies in the microbiota of insects, where bacterial symbionts produce antimicrobials to protect against opportunistic pathogens and enzymes to adapt to the environment. In this study, we present the chitinolytic strain Streptomyces albogriseolus PMB5, isolated from the insectivorous Mantis religiosa (European mantis). Whole-genome sequencing revealed that PMB5 harbors a linear chromosome of 7,211,961 bp and a linear plasmid of 327,989 bp. The genome comprises 6683 genes, including 6592 protein-coding sequences and 91 RNA genes. Furthermore, genome analysis revealed 19 biosynthetic gene clusters covering polyketides, terpenes, and RiPPs, with 10 clusters showing significant gene similarity (>80%) to known clusters like antimycin, hopene, and geosmin. In the genome of S. albogriseolus PMB5, we were able to identify several antibiotic resistance genes; these included cml (resistance to phenicol), gimA (resistance to macrolides), parY (resistance to aminocoumarin), oleC/oleD (resistance to macrolides), novA (resistance to aminocoumarin) and bla/blc (resistance to beta-lactams). Additionally, three clusters displayed no similarity to known sequences, suggesting novel bioactive compound discovery potential. Remarkably, strain PMB5 is the first reported S. albogriseolus capable of thriving on a medium utilizing chitin as a carbon source, with over 50 chitin-utilizing genes identified, including five AA10 family LPMOs, five GH18 chitinases, and one GH19 chitinase. This study significantly enhances the genomic understanding of S. albogriseolus, a species previously underrepresented in research, paving the way to further exploration of the biotechnological potential of the species.
Extracellular Vesicle-Derived Non-Coding RNAs: Key Mediators in Remodelling Heart Failure
Authors: Zhao Jiayi , Huang Huang
Published: August 2024

Heart failure (HF), a syndrome of persistent development of cardiac insufficiency due to various heart diseases, is a serious and lethal disease for which specific curative therapies are lacking and poses a severe burden on all aspects of global public health. Extracellular vesicles (EVs) are essential mediators of intercellular and interorgan communication, and are enclosed nanoscale vesicles carrying biomolecules such as RNA, DNA, and proteins. Recent studies have showed, among other things, that non-coding RNAs (ncRNAs), especially microRNAs (miRNAs), long ncRNAs (lncRNA), and circular RNAs (circRNAs) can be selectively sorted into EVs and modulate the pathophysiological processes of HF in recipient cells, acting on both healthy and diseased hearts, which makes them promising targets for the diagnosis and therapy of HF. This review aims to explore the mechanism of action of EV-ncRNAs in heart failure, with emphasis on the potential use of differentially expressed miRNAs and circRNAs as biomarkers of cardiovascular disease, and recent research advances in the diagnosis and treatment of heart failure. Finally, we focus on summarising the latest advances and challenges in engineering EVs for HF, providing novel concepts for the diagnosis and treatment of heart failure.
Comparison between Conventional and Simple Measuring Methods of Mean Nocturnal Baseline Impedance in Pediatric Gastroesophageal Reflux Disease
Authors: Pop Radu Samuel , Chiperi Lăcrămioara Eliza , Nechita Vlad-Ionuț , Man Sorin Claudiu , Dumitrașcu Dan Lucian
Published: August 2024

(1) Background: Multichannel intraluminal impedance–pH (MII-pH) monitoring is commonly used to diagnose gastroesophageal reflux disease (GERD). The mean nocturnal baseline impedance (MNBI) is an important parameter, reflecting the esophageal mucosal integrity and improvement in GERD. This study aims to evaluate the correlation between conventionally measured MNBI and a recently described simple MNBI measurement method in diagnosing pediatric GERD. (2) Methods: This prospective observational study enrolled 64 children aged one month to 18 years who underwent 24 h MII-pH monitoring. Conventional MNBI was measured during stable 10 min intervals at night, while the simple MNBI method averaged impedance throughout the nocturnal supine period. (3) Results: Strong correlations were found between conventional and simple MNBI values across all impedance channels in both infants (r > 0.85) and older children (r > 0.9). Conventional and simple MNBIs in the most distal channel (Z6) effectively differentiated non-erosive reflux disease (NERD) from other phenotypes, with AUCs of 0.864 and 0.860, respectively. The simple MNBI demonstrated good diagnostic performance with similar sensitivity and specificity to the conventional MNBI. (4) Conclusions: Including MNBI measurements into routine MII-pH monitoring may enhance GERD diagnosis and reduce the need for more invasive procedures.
Numerical Investigations of Deckhouse Height to the Self-Righting Moment of the Patrol Boat
Authors: Trimulyono Andi , Tuswan Tuswan , Taqi Haidar Farros Mawarizt , Manik Parlindungan , Rindo Good , Samuel Samuel , Mursid Ocid , Iqbal Muhammad
Published: August 2024

The design of patrol boats, especially in Indonesian waters with extreme sea conditions, requires good stability capabilities and self-righting moments. These conditions require patrol boats to have anti-capsized capabilities where, with these capabilities, the patrol boat can return to an upright position at extreme heeling angles. This study investigates how changing the center of gravity (CoG) due to the deckhouse height factor improves self-righting moment capabilities. Four different deckhouse heights are examined to find the optimal self-righting roll moment, with a deckhouse height in the 2.01–2.31 m range. In addition, the presence of the self-righting roll moment is also validated by the computational fluid dynamics (CFD) method using three different mesh sizes. The height of the deckhouse can significantly influence the ship’s stability. The initial investigation shows ships with minimum deckhouse heights of 2.06 m have positive righting lever arms at 170° and are classified as anti-capsized ships. It has been discovered that buoyancy and the center of gravity are crucial variables in obtaining the self-righting moment. The deckhouse’s height increases the stability of the ship’s righting arm by enhancing the metacenter point. The findings demonstrate that more excellent stability is achieved with a larger deckhouse height.
The Impact of Surgical Telementoring on Reducing the Complication Rate in Endoscopic Endonasal Surgery of the Skull Base
Authors: Ravnik Janez , Rowbottom Hojka , Snyderman Carl H. , Gardner Paul A. , Šmigoc Tomaž , Glavan Matic , Kšela Urška , Kljaić Nenad , Lanišnik Boštjan
Published: August 2024

Background: Pituitary adenomas represent the most common pituitary disorder, with an estimated prevalence as high as 20%, and they can manifest with hormone hypersecretion or deficiency, neurological symptoms from mass effect, or incidental findings on imaging. Transsphenoidal surgery, performed either microscopically or endoscopically, allows for a better extent of resection while minimising the associated risk in comparison to the transcranial approach. Endoscopy allows for better visualisation and improvement in tumour resection with an improved working angle and less nasal morbidity, making it likely to become the preferred surgical treatment for pituitary neoplasms. The learning curve can be aided by telementoring. Methods: We retrospectively analysed the clinical records of 94 patients who underwent an endoscopic endonasal resection of a pituitary neoplasm between the years 2011 and 2023 at Maribor University Medical Centre in Slovenia. Remote surgical telementoring over 3 years assisted with the learning curve. Results: The proportion of complication-free patients significantly increased over the observed period (60% vs. 79%). A gradual but insignificant increase in the percentage of patients with improved endocrine function was observed. Patients’ vision improved significantly over the observed period. By gaining experience, the extent of gross total tumour resection increased insignificantly (67% vs. 79%). Conclusions: Telementoring for the endoscopic endonasal approach to pituitary neoplasms enables low-volume centres to achieve efficiency, decreasing rates of postoperative complications and increasing the extent of tumour resection.
Identifying the Pathogenic Variants in Heart Genes in Vietnamese Sudden Unexplained Death Victims by Next-Generation Sequencing
Authors: Nguyen Tat Tho , Lien Nguyen Thi Kim , Luu Sy Hung , Ta Van To , Dang Viet Duc , Nguyen Thi Hoa , Tung Nguyen Van , Thanh Le Tat , Xuan Nguyen Thi , Hoang Nguyen Huy
Published: August 2024

In forensics, one-third of sudden deaths remain unexplained after a forensic autopsy. A majority of these sudden unexplained deaths (SUDs) are considered to be caused by inherited cardiovascular diseases. In this study, we investigated 40 young SUD cases (<40 years), with non-diagnostic structural cardiac abnormalities, using Targeted NGS (next-generation sequencing) for 167 genes previously associated with inherited cardiomyopathies and channelopathies. Fifteen cases identified 17 variants on related genes including the following: AKAP9, CSRP3, GSN, HTRA1, KCNA5, LAMA4, MYBPC3, MYH6, MYLK, RYR2, SCN5A, SCN10A, SLC4A3, TNNI3, TNNI3K, and TNNT2. Of these, eight variants were novel, and nine variants were reported in the ClinVar database. Five were determined to be pathogenic and four were not evaluated. The novel and unevaluated variants were predicted by using in silico tools, which revealed that four novel variants (c.5187_5188dup, p.Arg1730llefsTer4 in the AKAP9 gene; c.1454A>T, p.Lys485Met in the MYH6 gene; c.2535+1G>A in the SLC4A3 gene; and c.10498G>T, p.Asp3500Tyr in the RYR2 gene) were pathogenic and three variants (c.292C>G, p.Arg98Gly in the TNNI3 gene; c.683C>A, p.Pro228His in the KCN5A gene; and c.2275G>A, p.Glu759Lys in the MYBPC3 gene) still need to be further verified experimentally. The results of our study contributed to the general understanding of the causes of SUDs. They provided a scientific basis for screening the risk of sudden death in family members of victims. They also suggested that the Targeted NGS method may be used to identify the pathogenic variants in SUD victims.
A Lightweight Insulator Defect Detection Model Based on Drone Images
Authors: Lu Yang , Li Dahua , Li Dong , Li Xuan , Gao Qiang , Yu Xiao
Published: August 2024

With the continuous development and construction of new power systems, using drones to inspect the condition of transmission line insulators has become an inevitable trend. To facilitate the deployment of drone hardware equipment, this paper proposes IDD-YOLO (Insulator Defect Detection-YOLO), a lightweight insulator defect detection model. Initially, the backbone network of IDD-YOLO employs GhostNet for feature extraction. However, due to the limited feature extraction capability of GhostNet, we designed a lightweight attention mechanism called LCSA (Lightweight Channel-Spatial Attention), which is combined with GhostNet to capture features more comprehensively. Secondly, the neck network of IDD-YOLO utilizes PANet for feature transformation and introduces GSConv and C3Ghost convolution modules to reduce redundant parameters and lighten the network. The head network employs the YOLO detection head, incorporating the EIOU loss function and Mish activation function to optimize the speed and accuracy of insulator defect detection. Finally, the model is optimized using TensorRT and deployed on the NVIDIA Jetson TX2 NX mobile platform to test the actual inference speed of the model. The experimental results demonstrate that the model exhibits outstanding performance on both the proprietary ID-2024 insulator defect dataset and the public SFID insulator dataset. After optimization with TensorRT, the actual inference speed of the IDD-YOLO model reached 20.83 frames per second (FPS), meeting the demands for accurate and real-time inspection of insulator defects by drones.
Dimma: Semi-Supervised Low-Light Image Enhancement with Adaptive Dimming
Authors: Kozłowski Wojciech , Szachniewicz Michał , Stypułkowski Michał , Zięba Maciej
Published: August 2024

Enhancing low-light images with natural colors poses a challenge due to camera processing variations and limited access to ground-truth lighting conditions. To address this, we propose Dimma, a semi-supervised approach that aligns with any camera using a small set of image pairs captured under extreme lighting conditions. Our method employs a convolutional mixture density network to replicate camera-specific noise present in dark images. We enhance results further by introducing a conditional UNet architecture based on user-provided lightness values. Trained on just a few real image pairs, Dimma achieves competitive results compared to fully supervised state-of-the-art methods trained on large datasets.
Adherence to CPAP Therapy in Obstructive Sleep Apnea: A Prospective Study on Quality of Life and Determinants of Use
Authors: Milinovic Karla , Pavlinac Dodig Ivana , Lusic Kalcina Linda , Pecotic Renata , Ivkovic Natalija , Valic Maja , Dogas Zoran
Published: August 2024

Obstructive sleep apnea (OSA) often goes unrecognized despite common symptoms, such as excessive daytime sleepiness, fatigue, and impaired quality of life (QoL). Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA, but optimal daily usage and time needed for observable effects remain unclear. This study aimed to investigate the short-term effects of CPAP on daytime sleepiness and QoL in patients with severe OSA. Medical records were collected from 87 patients with severe OSA who initiated CPAP therapy. Also, validated questionnaires were used before and after one month of CPAP to analyze QoL—the Calgary Sleep Apnea Quality of Life Index (SAQLI), the Cues to CPAP Use Questionnaire (CCUQ), and daytime sleepiness—the Epworth Sleepiness Scale (ESS). Multiple regression analysis was conducted to identify predictors of CPAP usage. Of the total participants aged 55.6 ± 12.5, 77% were males, and 62% were CPAP adherent. Reductions in daytime sleepiness (ESS) were noted, as well as improvements in both overall QoL (SAQLI) and specifically in the domains of daily functioning, social interactions, emotional well-being, and symptom perception. Important cues for CPAP usage recognized by patients were physicians’ instructions and physicians’ concern regarding their patients’ condition. Furthermore, multiple regression revealed higher SAQLI scores and lower ESS scores as positive predictors of CPAP usage, along with lower AHI after one month of CPAP being associated with sufficient adherence.