bluuebunny/crossref_metadata_2025 huggingface dataset:
The bioequivalence study design recommendations for immediate-release solid oral dosage forms in the international pharmaceutical regulators programme participating regulators and organisations: differences and commonalities
Authors: Fernandes Eduardo Agostinho Freitas , Oudtshoorn Joy van , Tam Andrew , González Liliana Carolina Arévalo , Aurela Erwin Guzmán , Potthast Henrike , Mettke Katalina , Kuribayashi Ryosuke , Shimojo Kohei , Kasuga Miho , Morales Lázaro , Rodríguez Zulema , Jones Ben , Ahn Choongyul , Yun Eunju , Kim So Hee , Rodrigues Clare , Tiong Toh , Crane Christopher , Walther Chantal , Roost Matthias S. , Chen Tzu-Ling , Hsu Li-feng , Braddy April C. , García-Arieta Alfredo , Abalos Ivana , Divinsky Milly , Alsuwyeh Abdulaziz , Alzenaidy Bader , Alharf Adel
Published: March 2024

Bioequivalence (BE) studies are considered the standard for demonstrating that the performance of a generic drug product in the human body is sufficiently similar to that of its comparator product. The objective of this article is to describe the recommendations from participating Bioequivalence Working Group for Generics (BEWGG) members of the International Pharmaceutical Regulators Programme (IPRP) regarding the conduct and acceptance criteria for BE studies of immediate release solid oral dosage forms. A survey was conducted among BEWGG members regarding their BE recommendations and requirements related to study subjects, study design, sample size, single or multiple dose administration, study conditions (fasting or fed), analyte to be measured, selection of product strength, drug content, handling of endogenous substances, BE acceptance criteria, and additional design aspects. All members prefer conducting single dose cross-over designed studies in healthy subjects with a minimum of 12 subjects and utilizing the parent drug data to assess BE. However, differences emerged among the members when the drug’s pharmacokinetics and pharmacodynamics become more complex, such that the study design (e.g., fasting versus fed conditions) and BE acceptance criteria (e.g., highly variable drugs, narrow therapeutic index drugs) may be affected. The survey results and discussions were shared with the ICH M13 Expert Working Group (EWG) and played an important role in identifying and analyzing gaps during the harmonization process. The draft ICH M13A guideline developed by the M13 EWG was endorsed by ICH on 20 December 2022, under Step 2.
A Comprehensive Brain MRI Image Segmentation System Based on Contourlet Transform and Deep Neural Networks
Authors: Khalili Dizaji Navid , Doğan Mustafa
Published: March 2024

Brain tumors are one of the deadliest types of cancer. Rapid and accurate identification of brain tumors, followed by appropriate surgical intervention or chemotherapy, increases the probability of survival. Accurate determination of brain tumors in MRI scans determines the exact location of surgical intervention or chemotherapy. However, this accurate segmentation of brain tumors, due to their diverse morphologies in MRI scans, poses challenges that require significant expertise and accuracy in image interpretation. Despite significant advances in this field, there are several barriers to proper data collection, particularly in the medical sciences, due to concerns about the confidentiality of patient information. However, research papers for learning systems and proposed networks often rely on standardized datasets because a specific approach is unavailable. This system combines unsupervised learning in the adversarial generative network component with supervised learning in segmentation networks. The system is fully automated and can be applied to tumor segmentation on various datasets, including those with sparse data. In order to improve the learning process, the brain MRI segmentation network is trained using a generative adversarial network to increase the number of images. The U-Net model was employed during the segmentation step to combine the remaining blocks efficiently. Contourlet transform produces the ground truth for each MRI image obtained from the adversarial generator network and the original images in the processing and mask preparation phase. On the part of the adversarial generator network, high-quality images are produced, the results of which are similar to the histogram of the original images. Finally, this system improves the image segmentation performance by combining the remaining blocks with the U-net network. Segmentation is evaluated using brain magnetic resonance images obtained from Istanbul Medipol Hospital. The results show that the proposed method and image segmentation network, which incorporates several criteria, such as the DICE criterion of 0.9434, can be effectively used in any dataset as a fully automatic system for segmenting different brain MRI images.
Study on the Movement of Overlying Rock Strata and Surface Movement in Mine Goaf under Different Treatment Methods Based on PS-InSAR Technology
Authors: Huang Xuxing , Li Xuefeng , Li Hequn , Duan Shanda , Yang Yihao , Du Han , Xiao Wuning
Published: March 2024

The goaf treatment of underground metal mines is an important link in mining, and it is particularly important to master the laws of overlying rock strata and surface movement of goaf. In this paper, Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) technology is used to monitor the surface subsidence of the Taibao lead-zinc mine, and the surface subsidence laws of goaf-closure, partial-filling, and full-filling treatments are analyzed by the time-series method. The findings indicate that the surface subsidence of the closed goaf is solely governed by the pillars, with the quality of these pillars playing a pivotal role in controlling such subsidence. Factors like stope span also influence the surface subsidence of partially filled goaf. Prior to compaction, it is primarily the pillars that control surface subsidence; however, after compaction, filling and pillars jointly regulate this phenomenon. Notably, in filled goaf, the quality of both roof and pillars significantly impacts surface subsidence. Before compaction occurs, control over surface subsidence is not evident, yet post-compaction, the filling is effective and tends to stabilize this process. The research findings are significant in enhancing goaf’s treatment efficacy, mitigating surface damage and minimizing ecological environmental impact.
Near-Future Projection of Sea Surface Winds in Northwest Pacific Ocean Based on a CMIP6 Multi-Model Ensemble
Authors: Bayhaqi Ahmad , Yoo Jeseon , Jang Chan Joo , Kwon Minho , Kang Hyoun-Woo
Published: March 2024

Information about wind variations and future wind conditions is essential for a monsoon domain such as the Northwest Pacific (NWP) region. This study utilizes 10 Generalized Circulation Models (GCM) from CMIP6 to evaluate near-future wind changes in the NWP under various climate warming scenarios. Evaluation against the ERA5 reanalysis dataset for the historical period 1985–2014 reveals a relatively small error with an average of no more than 1 m/s, particularly in the East Asian Marginal Seas (EAMS). Future projections (2026–2050) indicate intensified winds, with a 5–8% increase in the summer season in the EAMS, such as the Yellow Sea, East Sea, and East China Sea, while slight decreases are observed in the winter period. Climate mode influences show that winter El Niño tends to decrease wind speeds in the southern study domain, while intensifying winds are observed in the northern part, particularly under SSP5-8.5. Conversely, summer El Niño induces higher positive anomalous wind speeds in the EAMS, observed in SSP2-4.5. These conditions are likely linked to El Niño-induced SST anomalies. For the application of CMIP6 surface winds, the findings are essential for further investigations focusing on the oceanic consequences of anticipated wind changes such as the ocean wave climate, which can be studied through model simulations.
An Appraisal of the Progress in Utilizing Radiosondes and Satellites for Monitoring Upper Air Temperature Profiles
Authors: Mashao Frederick M. , Demoz Belay , Kifle Yehenew , Klopper Danitza , Chikoore Hector , Sakai Ricardo K. , Ayisi Kingsley K.
Published: March 2024

Upper air temperature measurements are critical for understanding weather patterns, boundary-layer processes, climate change, and the validation of space-based observations. However, there have been growing concerns over data discrepancies, the lack of homogeneity, biases, and discontinuities associated with historical climate data records obtained using these technologies. Consequently, this article reviews the progress of utilizing radiosondes and space-based instruments for obtaining upper air temperature records. A systematic review process was performed and focused on papers published between 2000 and 2023. A total of 74,899 publications were retrieved from the Google Scholar, Scopus, and Web of Science databases using a title/abstract/keyword search query. After rigorous screening processes using relevant keywords and the elimination of duplicates, only 599 papers were considered. The papers were subjected to thematic and bibliometric analysis to comprehensively outline the progress, gaps, challenges, and opportunities related to the utilization of radiosonde and space-based instruments for monitoring upper air temperature. The results show that in situ radiosonde measurements and satellite sensors have improved significantly over the past few decades. Recent advances in the bias, uncertainty, and homogeneity correction algorithms (e.g., machine learning approaches) for enhancing upper air temperature observations present great potential in improving numerical weather forecasting, atmospheric boundary studies, satellite data validation, and climate change research.
Optimization of Aqueous Extraction of Polyphenols from Cuminum cyminum Seeds Using Response Surface Methodology and Assessment of Biological Activity
Authors: El Tannir Hana , Houhou Diana , Debs Espérance , Koubaa Mohamed , Jammoul Adla , Azakir Bilal , Khalil Mahmoud I. , El Darra Nada , Louka Nicolas
Published: March 2024

(1) Background: Cumin seeds, extracted from the plant Cuminum cyminum, are abundant in phenolic compounds and have been extensively researched for their chemical makeup and biological effects. The objective of this research is to enhance the water extraction of polyphenols through the water bath (WB) technique and to evaluate the antiradical, antibacterial, and anticancer effects of the extract. (2) Methods: Response Surface Methodology was used to find the best parameters to extract polyphenols. Three experimental parameters, time, temperature, and solid-liquid ratio, were tested. The disc diffusion method has been used to determine the antimicrobial activities against Salmonella Typhimurium, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Candida albicans. The antiradical activity was performed using the DPPH method, while total phenolic content was performed using Folin–Ciocalteu. High-Performance Liquid Chromatography (HPLC) was conducted to analyze the phytochemical profile of WB extracts. The anticancer activity of the lyophilized extract was assessed against three cancer cell lines (colon (HT29), lung (A549), and breast (MCF7) cancer cell lines).; (3) Results: The optimal conditions for water extraction were 130 min at 72 °C. The total phenolic compounds yield (14.7 mg GAE/g DM) and antioxidant activity (0.52 mg trolox eq./mL) were obtained using a 1:40 solid–liquid ratio. The primary polyphenols identified were the flavonoids rutin (0.1 ppm) and ellagic acid (3.78 ppm). The extract had no antibacterial or antifungal activities against the microorganisms tested. The extract showed anticancer activity of about 98% against MCF7 (breast cancer cell line), about 81% against HT29 (colon cancer cell line), and 85% against A549 (lung cancer cell line) at high doses. (4) Conclusions: Extraction time and a high solid–liquid ratio had a positive impact on polyphenol recovery and in maintaining their quantity and quality. Furthermore, the optimal aqueous extract exhibited strong antiradical activity reflected by the inhibition of free radicals in addition to a significant specificity against the tested cancer cell lines.
Clinical Outcomes in Adenoid Cystic Carcinoma of the Nasal Cavity and Paranasal Sinus: A Comparative Analysis of Treatment Modalities
Authors: Lee Tae Hoon , Kim Kangpyo , Oh Dongryul , Yang Kyungmi , Jeong Han-Sin , Chung Man Ki , Ahn Yong Chan
Published: March 2024

This study aimed to present the treatment patterns and outcomes for adenoid cystic carcinoma (ACC) arising in the nasal cavity and paranasal sinus. Sixty-one sinonasal ACC patients were retrospectively reviewed: 31 (50.8%) underwent surgery followed by postoperative radiation therapy (S+PORT), and 30 (49.2%) received definitive radiation therapy (D(C)RT). T4 disease was significantly more frequent in the D(C)RT group (25.8% vs. 80.0%, p < 0.001), where all T4b disease patients underwent D(C)RT. The 5-year local failure-free survival (LFFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), and overall survival were 61.8% versus 37.8% (p = 0.003), 64.8% versus 38.1% (p = 0.036), 52.6% versus 19.3% (p = 0.010), and 93.2% versus 73.4% (p = 0.001) in the S+PORT and D(C)RT groups, respectively. The absolute differences in 5-year rates of LFFS, DMFS, and PFS between the two groups were smaller in the T3–4 subgroup. The univariate analysis showed that T4b disease, neurologic symptoms, longest diameter of tumor, radiological evidence of nerve involvement, and undergoing D(C)RT were associated with worse clinical outcomes, but the significance disappeared in the multivariate analysis, except for in the case of radiological evidence of nerve involvement. In conclusion, most patients with extensive disease underwent upfront D(C)RT and generally exhibited inferior clinical outcomes when compared to those with less extensive disease and who underwent S+PORT.
Lung Cancer Proteogenomics: Shaping the Future of Clinical Investigation
Authors: Vavilis Theofanis , Petre Maria Louiza , Vatsellas Giannis , Ainatzoglou Alexandra , Stamoula Eleni , Sachinidis Athanasios , Lamprinou Malamatenia , Dardalas Ioannis , Vamvakaris Ioannis N. , Gkiozos Ioannis , Syrigos Konstantinos N. , Anagnostopoulos Athanasios K.
Published: March 2024

Background: Lung cancer is associated with a high incidence of mortality worldwide. Molecular mechanisms governing the disease have been explored by genomic studies; however, several aspects remain elusive. The integration of genomic profiling with in-depth proteomic profiling has introduced a new dimension to lung cancer research, termed proteogenomics. The aim of this review article was to investigate proteogenomic approaches in lung cancer, focusing on how elucidation of proteogenomic features can evoke tangible clinical outcomes. Methods: A strict methodological approach was adopted for study selection and key article features included molecular attributes, tumor biomarkers, and major hallmarks involved in oncogenesis. Results: As a consensus, in all studies it becomes evident that proteogenomics is anticipated to fill significant knowledge gaps and assist in the discovery of novel treatment options. Genomic profiling unravels patient driver mutations, and exploration of downstream effects uncovers great variability in transcript and protein correlation. Also, emphasis is placed on defining proteogenomic traits of tumors of major histological classes, generating a diverse portrait of predictive markers and druggable targets. Conclusions: An up-to-date synthesis of landmark lung cancer proteogenomic studies is herein provided, underpinning the importance of proteogenomics in the landscape of personalized medicine for combating lung cancer.
Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of Mucopolysaccharidosis: A Comparison with Other Neurodegenerative Diseases
Authors: Wiśniewska Karolina , Gaffke Lidia , Żabińska Magdalena , Węgrzyn Grzegorz , Pierzynowska Karolina
Published: March 2024

Mucopolysaccharidoses (MPS) are a group of diseases caused by mutations in genes encoding lysosomal enzymes that catalyze reactions of glycosaminoglycan (GAG) degradation. As a result, GAGs accumulate in lysosomes, impairing the proper functioning of entire cells and tissues. There are 14 types/subtypes of MPS, which are differentiated by the kind(s) of accumulated GAG(s) and the type of a non-functional lysosomal enzyme. Some of these types (severe forms of MPS types I and II, MPS III, and MPS VII) are characterized by extensive central nervous system disorders. The aim of this work was to identify, using transcriptomic methods, organelle-related genes whose expression levels are changed in neuronopathic types of MPS compared to healthy cells while remaining unchanged in non-neuronopathic types of MPS. The study was conducted with fibroblast lines derived from patients with neuronopathic and non-neuronopathic types of MPS and control (healthy) fibroblasts. Transcriptomic analysis has identified genes related to cellular organelles whose expression is altered. Then, using fluorescence and electron microscopy, we assessed the morphology of selected structures. Our analyses indicated that the genes whose expression is affected in neuronopathic MPS are often associated with the structures or functions of the cell nucleus, endoplasmic reticulum, or Golgi apparatus. Electron microscopic studies confirmed disruptions in the structures of these organelles. Special attention was paid to up-regulated genes, such as PDIA3 and MFGE8, and down-regulated genes, such as ARL6IP6, ABHD5, PDE4DIP, YIPF5, and CLDN11. Of particular interest is also the GM130 (GOLGA2) gene, which encodes golgin A2, which revealed an increased expression in neuronopathic MPS types. We propose to consider the levels of mRNAs of these genes as candidates for biomarkers of neurodegeneration in MPS. These genes may also become potential targets for therapies under development for neurological disorders associated with MPS and candidates for markers of the effectiveness of these therapies. Although fibroblasts rather than nerve cells were used in this study, it is worth noting that potential genetic markers characteristic solely of neurons would be impractical in testing patients, contrary to somatic cells that can be relatively easily obtained from assessed persons.
Comparative Effectiveness and Safety of Trastuzumab Biosimilars to Herceptin for Adjuvant Treatment of HER2+ Breast Cancer
Authors: Muñoz Caroline , Tai Xiaochen , Arias Jessica , Eisen Andrea , Chaudhry Munaza , Gavura Scott , Chan Kelvin K. W.
Published: March 2024

Background: Ontario publicly funds reference trastuzumab (Herceptin) and four biosimilar trastuzumab products for adjuvant treatment of HER2+ breast cancer. We assessed the real-world safety and effectiveness of biosimilar trastuzumab compared to Herceptin for adjuvant treatment of patients with HER2+ breast cancer. Methods: This was a population-based, retrospective study comparing the safety and effectiveness of biosimilar trastuzumab and Herceptin for neoadjuvant/adjuvant treatment of HER2+ breast cancer from 2016 to 2021. Treatment patients started biosimilar trastuzumab from November 2019 to June 2021; historical comparator patients started Herceptin from June 2016 to October 2019. Safety outcomes death within 30 days of last dose of trastuzumab, direct hospitalization, emergency department visit leading to hospitalization, early treatment discontinuation, and in-patient admission for congestive heart failure were measured using logistic/negative binomial regression. Overall survival (OS) was measured using Kaplan–Meier methods and Cox proportional hazards regression. Propensity score matching was applied. Results: From June 2016 to 2021, 5071 patients with breast cancer were treated with neoadjuvant/adjuvant trastuzumab. The rate of direct hospitalization (RR: 0.85, 95% CI: 0.74–0.98, p-value: 0.032) was significantly lower in biosimilar compared to Herceptin patients. OS (log-rank test p = 0.98) and risk of mortality (HR: 1.29, 95% CI: 0.72–2.30, p-value = 0.39) did not significantly differ between treatment groups. Conclusions: Biosimilar trastuzumab demonstrated similar safety and effectiveness to Herceptin. The findings can help improve confidence in and use of biosimilars and demonstrate the value of real-world evidence generation for supporting biosimilar implementations and reassessments.
Comparison of Tissue Factors in the Ontogenetic Aspects of Human Cholesteatoma
Authors: Dambergs Kristaps , Sumeraga Gunta , Pilmane Māra
Published: March 2024

Background: An acquired cholesteatoma is a benign but locally aggressive lesion in the middle ear. It is characterized by chronic inflammation and the destruction of surrounding bone. Therefore, the aim of this study was to compare defensins HβD-2 and HβD-4; pro- and anti-inflammatory cytokines IL-1α and IL-10; proliferation marker Ki-67; transcription factor NF-κβ; angiogenetic factor VEGF; Sonic hedgehog gene protein SHH; and remodeling factors MMP-2, MMP-9, TIMP-2, and TIMP-4 in adult and pediatric cholesteatoma tissue, and to compare these groups with control skin tissue. Methods: The study included 25 cholesteatoma tissue material samples from children, 25 from adults, and 7 deep external ear canal skin samples from cadavers. The tissues were stained immunohistochemically and evaluated using semi-quantitative methods. Nonparametric tests, such as the Kruskal–Wallis test and Spearman rank correlation, were used. Results: There were no statistically discernible differences between the adult and children groups when comparing the relative numbers of factor-positive cells. Conclusions: There are no histopathological differences between adult and children cholesteatoma tissues.
Modeling of the Flight Performance of a Plasma-Propelled Drone: Limitations and Prospects
Authors: Grosse Sylvain , Moreau Eric , Binder Nicolas
Published: March 2024

The resurgence in interest in aircraft electro-aerodynamic (EAD) propulsion has been sparked due to recent advancements in EAD thrusters, which generate thrust by employing a plasma generated through electrical discharge. With potentially quieter propulsion that could contribute to the generation of lift or the control of attitude, it is important to determine the feasibility of an EAD-propelled airplane. First, the main propulsive characteristics (thrust generation and power consumption) of EAD thrusters were drawn from the literature and compared with existing technologies. Second, an algorithm was developed to couple standard equations of flight with EAD propulsion performance and treat the first-order interactions. It fairly replicated the performance of the only available autonomous EAD-propelled drone. A test case based on an existing commercial UAV of 10 kg equipped with current-generation EAD thrusters anticipated a flight of less than 10 min, lower than 30 m in height, and below 8 m · s −1 in velocity. Achieving over 2 h of flight at 30 m of height at 10 m · s −1 requires the current EAD thrust to be doubled without altering the power consumption. For the same flight performance as the baseline UAV, the prediction asked for a tenfold increase in the thrust at the same power consumption.
Spirituality, Quality of Life, and Health: A Japanese Cross-Sectional Study
Authors: Yoshizawa Takeshi , Makram Abdelrahman M. , Elsheikh Randa , Nakamura Sadako , Makram Engy Mohamed , Kubota Kazumi , Huy Nguyen Tien , Moji Kazuhiko
Published: March 2024

Background: Current reports suggest a positive association between spirituality and quality of life (QoL) in elders. While most studies are qualitative studies and there has been little validation in quantitative studies using scales to measure spirituality. Hence, we aimed to study the effect of spirituality on mental health and QoL in older people residing in Kumejima Town in Japan. Methods: An interview-based survey was conducted between September 2010 and 2011 on residents of Kumejima Town aged 65 years or older. This survey-based study employed the Spirituality Health Scale for the Elderly (SP Health Scale) alongside assessments of basic attributes (e.g., age, sex); physical, mental, social health, spirituality, and QoL. We conducted a causal structure model to explore causal relationships between these factors. Results: Our study included 338 participants, including 72.5% female with an average age and standard deviation of 77.2 ± 6.4 years. Our analysis revealed a significant association between spiritual health and QoL even after accounting for the impact of physical and mental health, which challenged the conventional belief that QoL inevitably diminishes with age and declining health. These results suggest that enhancing spirituality may offer a means to prevent declines in QoL, fostering a positive outlook on life as individuals age. Conclusion: Our study suggests that improving spiritual health can enhance QoL, even in the presence of health challenges and aging. This novel perspective opens doors to redefining health as a state that coexists with illness, with spirituality serving as an integral component. A shift in our understanding of health that prioritizes spirituality, could benefit people of all ages, offering a more holistic approach to well-being that aligns with new medical technologies and evolving perceptions of health.
A Fully Coupled Gas–Water–Solids Mathematical Model for Vertical Well Drainage of Coalbed Methane
Authors: Wang Chengwang , Zhao Haifeng , Liu Zhan , Wang Tengfei , Chen Gaojie
Published: March 2024

The coupling relationship between the deformation field, the diffusion field, and the seepage field is an important factor in fluid transport mechanisms in the long-term coalbed methane (CBM) exploitation process. A mathematical model of gas–water two-phase fluid–structure coupling in a double-porosity medium in coal reservoirs is established in this paper. Taking Hancheng Block, a typical production block in Qinshui Basin, as the geological background critical desorption pressure, reservoir permeability anisotropy is considered in the model. COMSOL Multiphysics (COMSOL_6.0) was used to create the model. The accuracy and rationality of the model were verified by comparing field production data with the results of the simulation. Using the simulation, the influence law of various reservoir geological characteristics parameters (Langmuir strain constant, ratio of critical desorption pressure to reservoir pressure of coal seam (CDPRP), elastic modulus, initial water saturation, Langmuir pressure, etc.) on CBM productivity, reservoir pressure, and permeability ratio was discussed, and a thorough analysis of the factors affecting productivity was obtained using the orthogonal test method. The findings of this study indicate that the change in permeability is the result of the superposition effect of many factors. Different stages of drainage have different primary regulating factors. Rock skeleton stress has a consequence on coal matrix permeability in the early drainage stage, and coal matrix shrinkage is primarily impacted in the later drainage stage. Besides the initial water saturation, other reservoir geological parameters (e.g., CDPRP, Langmuir volume, Langmuir strain constant, elastic modulus) have a strong relationship with productivity. When the value of coal geological parameters increases, the degree of productivity release is higher (as the initial water saturation increases, the production decreases correspondingly). Different coal and rock parameters have varying levels of impact on the drainage stage of CBM wells. The influences of the CDPRP, Langmuir volume, Langmuir strain constant, and elastic modulus on gas production are mainly concentrated in the initial and intermediate drainage stages and begin to fall off during the last drainage stage. Per the multi-factor analysis, the main coal–rock parameters affecting the productivity release are the Langmuir strain constant, followed by the CDPRP and other parameters. The analysis findings can offer theoretical guidance for CBM well selection and layer selection and enhance the block’s overall CBM development level. The improved productivity prediction model for CBM, which is based on fluid–structure coupling theory, can offer a new technical benchmark for CBM well productivity prediction.
A Retrofit Streetlamp Monitoring Solution Using LoRaWAN Communications
Authors: Schneider Sören , Goetze Marco , Krug Silvia , Hutschenreuther Tino
Published: March 2024

Ubiquitous street lighting is essential for urban areas. While nowadays, LED-based “smart lamps” are commercially available, municipalities can only switch to them in the long run due to financial constraints. Especially, older types of lamps require frequent bulb replacements to maintain the lighting infrastructure’s function. To speed up the detection of defects and enable better planning, a non-invasively retrofittable IoT sensor solution is proposed that monitors lamps for defects via visible light sensors, communicates measurement data wirelessly to a central location via LoRaWAN, and processes and visualizes the resulting information centrally. The sensor nodes are capable of automatically adjusting to shifting day- and nighttimes thanks to a second sensor monitoring ambient light. The work specifically addresses aspects of energy efficiency essential to the battery-powered operation of the sensor nodes. Besides design considerations and implementation details, the paper also summarizes the experimental validation of the system by way of an extensive field trial and expounds upon further experiences from it.
Performance Evaluation of Cable Shaft Fireproof Sealing System in High-Rise Buildings: A Comparative Test Method
Authors: Zhang Bizhen , Shu Shengwen , Zheng Zhicong , Qu Bo , Li Xin , Xiang Xingyao , Xia Shuai
Published: March 2024

The effectiveness of fireproof sealing systems in preventing the spread of fire in high-rise building cable shafts relies on the properties of various sealing materials and the construction process. Therefore, a comprehensive evaluation is necessary. The authors of this paper propose a comparative test method based on an entity test platform for a performance evaluation of cable shaft fireproof sealing systems in high-rise buildings. The test platform measures changes in temperature, humidity, and smoke mass during fire tests to compare the performance of four sets of fireproof sealing systems in terms of thermal insulation, smoke sealing capacity, and overall integrity. In addition, a fire dynamics simulation (FDS) of fireproof sealing systems was carried out on the entity test platform, and the sealing failure process in the case of cracking in the fireproof sealing system was revealed. The simulation results for the temperature trends in the lower space align with the fire test results. Furthermore, as the gap size increases, the diffusion of smoke and flame accelerates. Consequently, the performance of cable shaft fireproof sealing systems depends not only on the sealing material but also on the construction process.
In Vitro Low-Bortezomib Doses Induce Apoptosis and Independently Decrease the Activities of Glutathione S-Transferase and Glutathione Peroxidase in Multiple Myeloma, Taking into Account the GSTT1 and GSTM1 Gene Variants
Authors: Zmorzynski Szymon , Popek-Marciniec Sylwia , Biernacka Beata , Szudy-Szczyrek Aneta , Chocholska Sylwia , Styk Wojciech , Czerwik-Marcinkowska Joanna , Swiderska-Kolacz Grazyna
Published: March 2024

Background: Multiple myeloma (MM) is a malignancy derived from plasma cells. Bortezomib affects the concentration of reduced glutathione (GSH) and the activity of glutathione enzymes. The aim of our study was to analyze deletion (null/present) variants of GSTT1 and GSTM1 genes and their association with the levels of glutathione and its enzymes in bortezomib-treated cell cultures derived from MM patients. Materials and Methods: This study included 180 individuals (80 MM patients and 100 healthy blood donors) who were genotyped via multiplex PCR (for the GSTT1/GSTM1 genes). Under in vitro conditions, MM bone marrow cells were treated with bortezomib (1–4 nM) to determine apoptosis (via fluorescence microscopy), GSH concentration, and activity of glutathione enzymes (via ELISA). Results: Bortezomib increased the number of apoptotic cells and decreased the activity of S-glutathione transferase (GST) and glutathione peroxidase (GPx). We found significant differences in GST activity between 1 nM (GSTT1-null vs. GSTT1-present), 2 nM (GSTT1-null vs. GSTT1-present), and 4 nM (GSTM1-null vs. GSTM1-present) bortezomib: 0.07 vs. 0.12, p = 0.02; 0.06 vs. 0.10, p = 0.02; and 0.03 vs. 0.08, p = 0.01, respectively. Conclusions: Bortezomib affects the activities of GST and GPx. GST activity was associated with GSTT1 and GSTM1 variants but only at some bortezomib doses.
Landslide Risks to Bridges in Valleys in North Carolina
Authors: Lin Sophia , Chen Shen-En , Tang Wenwu , Chavan Vidya , Shanmugam Navanit , Allan Craig , Diemer John
Published: March 2024

This research delves into the intricate dynamics of landslides, emphasizing their consequences on transportation infrastructure, specifically highways and roadway bridges in North Carolina. Based on a prior investigation of bridges in Puerto Rico after Hurricane Maria, we found that bridges above water and situated in valleys can be exposed to both landslide and flooding risks. These bridges faced heightened vulnerability to combined landslides and flooding events due to their low depth on the water surface and the potential for raised flood heights due to upstream landslides. Leveraging a dataset spanning more than a century and inclusive of landslide and bridge information, we employed logistic regression (LR) and random forest (RF) models to predict landslide susceptibility in North Carolina. The study considered conditioning factors such as elevation, aspect, slope, rainfall, distance to faults, and distance to rivers, yielding LR and RF models with accuracy rates of 76.3% and 82.7%, respectively. To establish that a bridge’s location is at the bottom of a valley, data including landform, slope, and elevation difference near the bridge location were combined to delineate a bridge in a valley. The difference between bridge height and the lowest river elevation is established as an assumed flooding potential (AFP), which is then used to quantify the flooding risk. Compared to traditional flood risk values, the AFP, reported in elevation differences, is more straightforward and helps bridge engineers visualize the flood risk to a bridge. Specifically, a bridge (NCDOT ID: 740002) is found susceptible to both landslide (92%) and flooding (AFT of 6.61 m) risks and has been validated by field investigation, which is currently being retrofitted by North Carolina DOT with slope reinforcements (soil nailing and grouting). This paper is the first report evaluating the multi-hazard issue of bridges in valleys. The resulting high-fidelity risk map for North Carolina can help bridge engineers in proactive maintenance planning. Future endeavors will extend the analysis to incorporate actual flooding risk susceptibility analysis, thus enhancing our understanding of multi-hazard impacts and guiding resilient mitigation strategies for transportation infrastructure.
Drug–Drug Interactions of FXI Inhibitors: Clinical Relevance
Authors: Ferri Nicola , Colombo Elisa , Corsini Alberto
Published: March 2024

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus, they have very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo drug–drug interactions (DDIs) with other concomitant therapies. Although only little clinical evidence is available, it is possible to predict clinically relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters, and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDIs of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.
Comparative Analyses of Targeted Myeloid Cancer Next-Generation Sequencing Panel in Fresh Blood, Bone Marrow and FFPE Material
Authors: Hobeck Andrea Daniela , Wendt Sophia , Krohn Saskia , Knuebel Gudrun , Bartels Stephan , Schipper Elisa , Junghanss Christian , Murua Escobar Hugo
Published: March 2024

Next-generation sequencing is a vital tool for personalized diagnostics and therapies in cancer. Despite numerous advantages, the method depends on multiple parameters regarding the sample material, e.g., sample fixation. A panel’s ability to ensure balanced pre-amplification of the regions of interest is challenging, especially in targeted sequencing approaches, but of significant importance to its applicability across hematological malignancies and solid tumors. This study comparatively evaluated the technical performance of the commercially available OncomineTM Myeloid Panel in fresh and Formalin-fixed paraffin-embedded (FFPE) material by using an Ion Torrent™ Personal Genome Machine™ System and Ion GeneStudio S5 System platform. In total, 114 samples were analyzed, including 55 fresh materials and 59 FFPE samples. Samples were sequenced with a minimum of one million reads. Amplicons with coverage below 400 reads were classified as underperforming. In fresh material, 49/526 amplicons were identified as performing insufficiently, corresponding with 18 genes. Using FFPE material, 103/526 amplicons underperformed. Independent of input material, regions in 27 genes, including ASXL1, BCOR and BRAF, did not match quality parameters. Subsequently, exemplary mutations were extracted from the Catalogue of Somatic Mutations in Cancer database. This technical evaluation of the OncomineTM Myeloid Panel identified amplicons that do not achieve adequate coverage levels and which need to be considered when interpreting sequencing.
The RopGEF Gene Family and Their Potential Roles in Responses to Abiotic Stress in Brassica rapa
Authors: Zhang Meiqi , Wu Xiaoyu , Chen Luhan , Yang Lin , Cui Xiaoshuang , Cao Yunyun
Published: March 2024

Guanine nucleotide-exchange factors (GEFs) genes play key roles in plant root and pollen tube growth, phytohormone responses, and abiotic stress responses. RopGEF genes in Brassica rapa have not yet been explored. Here, GEF genes were found to be distributed across eight chromosomes in B. rapa and were classified into three subfamilies. Promoter sequence analysis of BrRopGEFs revealed the presence of cis-elements characteristic of BrRopGEF promoters, and these cis-elements play a role in regulating abiotic stress tolerance and stress-related hormone responses. Organ-specific expression profiling demonstrated that BrRopGEFs were ubiquitously expressed in all organs, especially the roots, suggesting that they play a role in diverse biological processes. Gene expression analysis revealed that the expression of BrRopGEF13 was significantly up-regulated under osmotic stress and salt stress. RT-qPCR analysis revealed that the expression of BrRopGEF13 was significantly down-regulated under various types of abiotic stress. Protein–protein interaction (PPI) network analysis revealed interactions between RopGEF11, the homolog of BrRopGEF9, and the VPS34 protein in Arabidopsis thaliana, as well as interactions between AtRopGEF1, the homolog of BrRopGEF13 in Arabidopsis, and the ABI1, HAB1, PP2CA, and CPK4 proteins. VPS34, ABI1, HAB1, PP2CA, and CPK4 have previously been shown to confer resistance to unfavorable environments. Overall, our findings suggest that BrRopGEF9 and BrRopGEF13 play significant roles in regulating abiotic stress tolerance. These findings will aid future studies aimed at clarifying the functional characteristics of BrRopGEFs.
Plasma miR-203a-3p as a Novel Predictor of Dementia in Patients with Parkinson’s Disease
Authors: Hsu Ya-Fang , Lin Shau-Ping , Chu Yung-Tsai , Tsai Yi-Tzang , Huang Jing-Wen , Phoa Frederick Kin Hing , Wu Ruey-Meei
Published: March 2024

The early detection of cognitive decline in Parkinson’s disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = −0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.
In Vitro Antibacterial Activity of Ozonated Olive Oil against Bacteria of Various Antimicrobial Resistance Profiles Isolated from Wounds of Companion Animals
Authors: Lenart-Boroń Anna , Stankiewicz Klaudia , Bulanda Klaudia , Czernecka Natalia , Heliasz Miłosz , Hunter Walter , Ratajewicz Anna , Khachatryan Karen , Khachatryan Gohar
Published: March 2024

Frequent colonization and bacterial infection of skin wounds in small animals prevent or impair their healing. However, the broadly applied antimicrobial therapy of wounds is not always necessary and promotes the spread of bacterial resistance. Thus, alternatives to antimicrobial therapy, including preventive measures in the form of wound dressings with antibiotic properties, should be searched for. The aim of this study was to develop a new, efficient, cost-effective and non-toxic formulation with antimicrobial properties to serve as an alternative to antibiotic administration in wound-healing stimulation in companion animals. Nano/microencapsulated ozonated olive oil in a hyaluronan matrix was developed, with ozone concentration high enough to prevent bacterial growth. The presence and size of nano- and microcapsules were determined with scanning electron microscopy (SEM). Antibacterial activity of developed formulations was examined in vitro on 101 Gram-positive and Gram-negative bacteria isolated from the wounds of companion animals. The highest ozone concentration in the developed formulations inhibited the growth of 40.59% bacteria. Species and genus-specific differences in reactions were observed. Enterococcus spp. proved the least susceptible while non-pathogenic Gram-positive bacteria were the most susceptible to the examined formulations. Changes in the bacterial morphology and cell structure of Psychrobacter sanguinis suspension mixed with Ca-stabilized formulations with nano/microencapsulated ozonized olive oil were revealed during SEM observations. The combination of compounds that promote wound healing (hyaluronic acid, olive oil, ozone and calcium) with the antibacterial activity of the developed formula makes it a promising bionanocomposite for use as a topical dressing.
Extracellular Vesicle Protein Expression in Doped Bioactive Glasses: Further Insights Applying Anomaly Detection
Authors: Nascimben Mauro , Abreu Hugo , Manfredi Marcello , Cappellano Giuseppe , Chiocchetti Annalisa , Rimondini Lia
Published: March 2024

Proteomic analysis of extracellular vesicles presents several challenges due to the unique nature of these small membrane-bound structures. Alternative analyses could reveal outcomes hidden from standard statistics to explore and develop potential new biological hypotheses that may have been overlooked during the initial evaluation of the data. An analysis sequence focusing on deviating protein expressions from donors’ primary cells was performed, leveraging machine-learning techniques to analyze small datasets, and it has been applied to evaluate extracellular vesicles’ protein content gathered from mesenchymal stem cells cultured on bioactive glass discs doped or not with metal ions. The goal was to provide additional opportunities for detecting details between experimental conditions that are not entirely revealed with classic statistical inference, offering further insights regarding the experimental design and assisting the researchers in interpreting the outcomes. The methodology extracted a set of EV-related proteins whose differences between conditions could be partially explainable with statistics, suggesting the presence of other factors involved in the bioactive glasses’ interactions with tissues. Outlier identification of extracellular vesicles’ protein expression levels related to biomaterial preparation was instrumental in improving the interpretation of the experimental outcomes.
Bone Regeneration and Repair Materials
Authors: Beloti Marcio Mateus , Rosa Adalberto Luiz
Published: March 2024

Bone tissue has a remarkable ability to regenerate following injury and trauma [...]