bluuebunny/crossref_metadata_2025 huggingface dataset:
Harnessing the AI/ML in Drug and Biological Products Discovery and Development: The Regulatory Perspective
Authors: Mirakhori Fahimeh , Niazi Sarfaraz K.
Published: November 2024

Artificial Intelligence (AI) has the disruptive potential to transform patients’ lives via innovations in pharmaceutical sciences, drug development, clinical trials, and manufacturing. However, it presents significant challenges, ethical concerns, and risks across sectors and societies. AI’s rapid advancement has revealed regulatory gaps as existing public policies struggle to keep pace with the challenges posed by these emerging technologies. The term AI itself has become commonplace to argue that greater “human oversight” for “machine intelligence” is needed to harness the power of this revolutionary technology for both potential and risk management, and hence to call for more practical regulatory guidelines, harmonized frameworks, and effective policies to ensure safety, scalability, data privacy, and governance, transparency, and equitable treatment. In this review paper, we employ a holistic multidisciplinary lens to overview the current regulatory landscape with a synopsis of the FDA workshop perspectives on the use of AI in drug and biological product development. We discuss the promises of responsible data-driven AI, challenges and related practices adopted to overcome limitations, and our practical reflections on regulatory oversight. Finally, the paper outlines a path forward and future opportunities for lawful ethical AI. This review highlights the importance of risk-based regulatory oversight, including diverging views in the field, in reaching a consensus.
VLR Net-An Ensemble Model to Enhance the Accuracy of Classification of Colposcopy Images
Authors: Chatterjee Priyadarshini , Siddiqui Shadab , Abdul Kareem Razia Sulthana
Published: November 2024

Early detection of cervical cancer is the need of the hour to stop the fatality from this disease. There have been various CAD approaches in the past that promise to detect cervical cancer in an early stage, each of them having some constraints.This study proposes a novel ensemble deep learning model, VLR (variable learning rate), aimed at enhancing the accuracy of cervical cancer classification. The model architecture integrates VGG16, Logistic Regression, and ResNet50, combining their strengths in an offbeat ensemble design. VLR learns in two ways: firstly, by dynamic weights from three base models, each of them trained separately; secondly, by attention mechanisms used in the dense layer of the base models. Hyperparameter tuning is applied to further reduce loss, fine tune the model’s performance, and maximize classification accuracy. We performed K-fold cross-validation on VLR to evaluate any improvements in metric values resulting from hyperparameter fine tuning. We have also validated our model on images captured in three different solutions and on a secondary dataset. Our proposed VLR model outperformed existing methods in cervical cancer classification, achieving a remarkable training accuracy of 99.95% and a testing accuracy of 99.89%.
Assessment of Formaldehyde’s Impact on Indoor Environments and Human Health via the Integration of Satellite Tropospheric Total Columns and Outdoor Ground Sensors
Authors: Barrese Elena , Valentini Marco , Scarpelli Marialuisa , Samele Pasquale , Malacaria Luana , D’Amico Francesco , Lo Feudo Teresa
Published: November 2024

Formaldehyde (HCHO) is harmful to human health and an adequate assessment of its concentrations, both in outdoor and indoor environments, is necessary in the effort of risk mitigation. In this research, ground indoor and outdoor HCHO measurements have been integrated with the analysis of tropospheric total columns obtained by satellite surveys to assess the concentrations of HCHO in a number of environments, exploiting the proximity of a World Meteorological Organization – Global Atmosphere Watch (WMO/GAW) observation site in Calabria, Southern Italy to a National Institute for Insurance against Accidents at Work (INAIL) department in the municipality of Lamezia Terme. Meteorological parameters gathered at the WMO station have also been used to provide additional data and test new correlations. Using statistical significance tests, the study demonstrates the presence of a correlation between indoor and outdoor HCHO concentrations, thus showing that an exchange between indoor and outdoor formaldehyde does occur. Rooms located in the building where indoor measurements took place have also demonstrated degrees of susceptibility to HCHO exposure which are correlated with the orientation of prevailing wind corridors in the area. The new findings constitute an unprecedented characterization of HCHO hazards in Calabria and provide regulators with new tools on how to mitigate formaldehyde-related risks.
Hyperelastic and Stacked Ensemble-Driven Predictive Modeling of PEMFC Gaskets Under Thermal and Chemical Aging
Authors: Park Su Yeon , Kareem Akeem Bayo , Mustapha Toyyeebah Ajibola , Joo Woo Jeong , Hur Jang-Wook
Published: November 2024

This study comprehensively investigates the stress distribution and aging effects in Ethylene Propylene Diene Monomer (EPDM) and Liquid Silicone Rubber (LSR) gasket materials through a novel integration of hyperelastic modeling and advanced machine learning techniques. By employing the Mooney-Rivlin, Ogden, and Yeoh hyperelastic models, we evaluate the mechanical behavior of EPDM and LSR under conditions of no aging, heat aging, and combined heat and sulfuric acid exposure. Each model reveals distinct sensitivities to stress distribution and material deformation, providing unique insights into material degradation processes. Additionally, we utilize machine learning for predictive analysis, enhancing our understanding of stress responses and identifying critical aging effects. The findings offer practical implications for selecting suitable gasket materials and developing predictive maintenance strategies in industrial applications, such as fuel cells, where material integrity under stress and aging is paramount. This dual approach highlights the mechanical resilience and vulnerabilities of EPDM and LSR and opens avenues for real-time predictive analytics and material performance optimization.
Coxsackievirus A6 UK Genetic and Clinical Epidemiology Pre- and Post-SARS-CoV-2 Pandemic
Authors: Joyce Alice , Hill Jack D. , Tsoleridis Theocharis , Astbury Stuart , Berry Louise , Howson-Wells Hannah C. , Allen Nancy , Canning Ben , Jones Carl B. , Clark Gemma , Irving William L. , Tarr Alexander W. , McClure C Patrick
Published: November 2024

Coxsackievirus A6 (CVA6) has become increasingly clinically relevant as a cause of Hand, Foot and Mouth Disease (HFMD) globally since 2008. However, most laboratories do not routinely determine the enteroviral type of positive samples. The non-pharmaceutical measures introduced to curb transmission during the SARS-CoV-2 pandemic may also have been perturbed CVA6 epidemiology. We thus aimed to determine the prevalence, clinical presentation and genetic relationship of CVA6 across three complete epidemic seasons: one pre- and two post-SARS-CoV-2-emergence in our regional healthcare setting. Surplus diagnostic nucleic acid from diagnosed enteroviral positives diagnosed between September to December 2018 and May 2021 to April 2023 was subject to VP1 gene sequencing to determine CVA6 cases and interrogate their phylogenetic relationship. Confirmed CVA6 cases were also retrospectively clinically audited. CVA6 infections were identified in 33 and 69 individuals pre- and post-pandemic respectively, with cases peaking in November of 2018 and 2022, but in October of 2021. HFMD was the primary diagnosis in 85.5% of post-pandemic cases, but only 69.7% pre-pandemic, where respiratory and neurological symptoms (45.5% and 12.1% respectively) were significantly elevated. Complete VP1 sequence was retrieved for 94% of CVA6 cases, revealing study infections were genetically diverse and suggestive of multiple local and international transmission chains. CVA6 presented a significant clinical burden in our regional UK hospital setting both pre- and post-pandemic and was subject to dynamic clinical and genetic epidemiology.
Exploring the Impact of Vehicle Lightweighting in Terms of Energy Consumption: Analysis and Simulation on Real Driving Cycle
Authors: Sandrini Giulia , Chindamo Daniel , Gadola Marco , Candela Andrea , Magri Paolo
Published: November 2024

Today, reducing vehicle energy consumption is a crucial topic. For electric vehicles, reducing energy consumption is essential to address some of the most critical issues associated with this type of vehicle, such as the limited range of electric powertrains and the long battery recharging times. To lower the environmental impact during the vehicle’s use phase and reduce energy consumption, vehicle mass reduction (lightweighting) is an effective strategy. The objective of this work is to analyze the vehicle parameters that influence lightweighting outcomes on a real driving cycle, representative of the home-to-work travel in the northern Italy. In particular, a previous work carried out on standard driving cycles is repeated, in order to observe whether it is possible to draw the same conclusions regarding the variability of the lightweighting outcome. This study was conducted using two opposite vehicle models, a compact car and an N1 vehicle, simulated through a well-established vehicle simulation tool for energy consumption estimation. The study reveals that even for the real driving cycle, as for the WLTC and US06 standards, the parameters that most influence the outcome of the lightening are rolling resistance, the characteristics of the battery pack, the aerodynamic coefficients and the efficiency of the transmission. Finally, the standard cycle that best fits with the real one considered in this study is the Artemis Urban Cycle.
A Potential Link Between Outcome of Periodic Fever, Aphthous Stomatitis, Pharyngitis, Cervical Adenitis (PFAPA) Syndrome in Children and Breastfeeding: A Retrospective Single-Center Cohort Snapshot
Authors: Rigante Donato , Candelli Marcello
Published: November 2024

Background/Objectives: Periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis syndrome, often referred to as PFAPA syndrome, may enigmatically recur for an undetermined time in the affected children: a potential reason to explain its recurring pattern for an unpredictable period and its self-limitation is currently unknown. We explored the relationship of PFAPA symptom evolution during a variable follow-up with PFAPA disease pictures and breastfeeding for less than 6 months during infancy. Methods: In the Outpatients Clinic of Pediatric Rheumatology of our Institution we have retrospectively screened 150 Italian children with history of PFAPA syndrome during the period 2014-2024, all without any recognized chronic diseases: 88 males, 62 females, mean age at onset of 2.5±1.7 years, age range of 0.3-9.4 years, and mean age at diagnosis of 4.5±2.0 years. Results and Conclusions: After dividing patients into two groups based on either the disappearance or persistence of PFAPA symptoms during a variable median follow-up we found that positive family history of recurring fevers, cervical lymphadenopathy, arthralgia, myalgia, and breastfeeding for less than 6 months were associated with the persistence of the disease over time. Inherited autoinflammatory disorders were excluded on a genetic basis in 16.3% of the cohort. Performing a multivariate analysis adjusted for sex and age we found that only breastfeeding for more than 6 months and a higher level of education in PFAPA patients’ mothers were independently associated with the resolution of the recurring PFAPA symptoms.
Examining Particle Size Compliance of Total Suspended Solids in Produced Water for Hydraulic Fracturing and Water Injection in the Bakken
Authors: Njie Claudius Epie , Ling Kegang , Jakaria Md
Published: November 2024

The analysis of suspended particle size distribution in produced water for hydraulic fracturing and for water injection operations is vital for the effective development of tight reservoir formations like the Middle Bakken. Several reservoir engineering studies and industry guidelines recommend that particle sizes fall between 1/7th and 1/3rd of the square root of the formation permeability measured in millidarcies, to avoid pore throat clogging and subsequent formation damage. In the tight Bakken formation, with an average permeability of 0.04 millidarcies, the ideal particle size range for total suspended solids should fall within the 0.03 to 0.06 microns range. This study evaluates whether produced water used for hydraulic fracturing and enhanced oil recovery in the Middle Bakken meets this recommendation, as there are no established regulations in North Dakota addressing this issue. Using laser diffraction, particle size distribution was measured in treated and untreated produced water samples. The results show that current treatment methods do not reduce particle sizes to the recommended range. Treated water had particle diameters ranging from 8.5 to 40 μm, while untreated water had diameters ranging from 8.2 to 10 μm. None of the samples met the particle size requirements for safe use in hydraulic fracturing and water injection. This study highlights the inadequacy of current water recycling practices and offers empirical evidence that may guide future regulations on produced water reuse hydraulic fracturing and water injection in the Bakken.
Peripheral Hemodynamics Estimation Using Photoplethysmography Method
Authors: Shimuta Toru , Hanada Kaname , Ryu Kazuteru , Idei Koichi , Kanai Nobuyuki
Published: November 2024

Diseases such as diabetes are known to reduce blood circulation in the capillaries and arterioles; however, there are no devices that can easily measure this on a daily basis. In this study, we developed a tool for measuring finger photoplethysmograms using green-light and near-infrared LEDs. We then conducted photoplethysmography on 25 diabetic inpatients/outpatients as well as 21 adult males and females who had not been diagnosed or treated for diabetes, hypertension, or cardiovascular disease (as a control group). In the diabetic patients, the inverse full width at half maximum velocity plethysmogram (1/FWHMVPG) tended to be smaller compared to the control group, and the delay in the green light a-wave peak relative to the near-infrared light a-wave peak in the acceleration plethysmogram was significantly increased. The results suggest that peripheral hemodynamics could be easily estimated at home using a photoplethysmography device mounted on a ring-wearable device.
Research on the Detection Method of Information Data in Complex Environment Based on UKF-BPNN
Authors: Zhou Chao , Zuo Yanhong , Xia Shilong , Yang Kun
Published: November 2024

In engineering practice, information data in the detection process can not be avoided by the working environment and equipment performance and other factors, resulting in unpredictable measurement errors, greatly affecting the reliability of the manufacturing system and decision-making system decision-making scientific. This paper analyzes the application characteristics of untraceable Kalman filter (UKF) and BP neural network algorithm (BPNN) in information data fusion, and tries to realize the complementary advantages of the two through the combination of UKF and BPNN (UKF+BPNN). The information data fusion algorithm based on UKF-BPNN is established to effectively fuse the information data measurement errors brought by multiple influencing factors in order to improve the detection accuracy of the information data, and the feasibility and validity of the method are verified through the application of the algorithm in the measurement of key information data of rolling bearings.
The Coupling Constant of Dirac Magnetic Monopoles Is Not 34.259 but 308.331
Authors: Kühne Rainer
Published: November 2024

Textbooks tell us that the coupling constant of Dirac magnetic monopoles is 34.259. Here I show by using the quark hypothesis that at zero temperature the coupling constant is as high as 308.331. Moreover I show that it is a running coupling constant and is smaller than 0.5 at the Planck temperature.
A Meta-Indicator for the Assessment of Misleading Sustainability Claims
Authors: Parastatidou Georgia , Chatzis Vassilios
Published: November 2024

In order to address environmental and climate change in a sustainable manner, it is necessary for corporations to make commitments in accordance with sustainable principles, which can be communicated through the use of indicators. In certain cases, indicators are subject to manipulation for the benefit of corporations, a strategy also referred to as "greenwashing". One method of misleading is the transfer of non-sustainable activities of a company to other collaborating companies. This paper proposes and defines the Sustainability meta-Indicator (SmI) which can serve as a tool for the assessment of misleading sustainability claims. Its value depends on the sustainability indicators of the other collaborating companies where the company in question pays money and the corresponding amount of paid money. The results of the use of SmI on synthetic data demonstrate that the proposed meta-indicator facilitates the assessment of misleading sustainability claims. Additionally, it can be used as a communication mechanism to enhance the value of companies and to support new partnerships and business strategies. For policymakers, this meta-indicator serves as a tool to support measures against consumer misinformation and deception.
Cationic Lipid Derived From a Basic Amino Acid: Design and Synthesis
Authors: Bravo Estupiñan Diana Marcela , Montaño-Samaniego Mariela , Mora Rodríguez Rodrigo Antonio , Ibáñez Hernández Miguel Angel
Published: November 2024

One of the major challenges in gene therapy (GT) is the efficient and safe introduction of nucleic acids (NA) into eukaryotic cells. This process requires overcoming various biological barriers and navigating complex pathways to reach target cells and achieve their biological function. To address this obstacle, numerous transfection methods have been developed, including physical techniques and the use of genetic vectors, both viral and non-viral. However, until now, no transfection method is 100% safe and efficient. Within the spectrum of non-viral genetic vectors, cationic liposomes formed by cationic lipids (CL), stand out for their ability to protect and deliver therapeutic NA. These liposomes offer greater biocompatibility and lower immunogenicity compared to viral vectors, although they still do not match the efficiency of viral delivery systems. Consequently, ongoing research focuses on synthesizing a wide variety of cationic lipids in the search for compounds that provide high transfection efficiency with minimal cytotoxicity. This study aimed to design and synthesize a novel CL (CholCadLys) derived from natural cellular molecules for transferring genetic material to eukaryotic cells. The lipid was synthesized using: cholesteryl chloroformate for the hydrophobic region, cadaverine as a linker, and lysine for the polar region, connected by carbamate and amide bonds, respectively. Identification was confirmed through thin-layer chromatography, purification by preparative chromatography, and characterization via infrared spectroscopy and mass spectrometry. The synthesis yielded a 60% success rate, with stable nanoliposomes averaging 76 nm in diameter. Liposomes were formed using this CL and commercial neutral lipids, characterized by transmission electron microscopy and Nanoparticle Tracking Analysis. These liposomes, combined with plasmid DNA, formed lipoplexes used to transfect Hek-293 FT cells, achieving up to 40% transfection efficiency without cytotoxicity in the mixture of CholCadLys and CholCad. This novel CL demonstrates potential as an efficient, safe, and cost-effective gene transfer system, facilitating further development in gene therapy.
Bioaccessibility and Antioxidant Capacity of Alkaloids from Microencapsulated Biomass of Eggplant (Solanum Melongena L.)
Authors: Germán-Soto Brianda Giselle , Heredia José Basilio , Leyva-López Nayely , Gutiérrez-Grijalva Erick Paul , García-Carrasco Melissa , Bastidas-Bastidas Pedro de Jesús , Contreras-Angulo Laura Aracely
Published: November 2024

Eggplant is a vegetable grown worldwide, and due to quality standards, large amounts of biomass are generated after harvest. Biomass is considered a source of bioactive compounds with antioxidant properties. Therefore, this research aimed to evaluate microencapsulated alkaloids' bioaccessibility (BA) and antioxidant capacity from eggplant fruit biomass. Eggplant biomass was collected, and the total alkaloid content, antioxidant capacity, and alkaloid profile were determined before and after the digestion in vitro for encapsulated and non-encapsulated alkaloids. The bioaccessibility of microencapsulated alkaloids (12 % BA) increased three-fold compared to non-encapsulated (4 %BA). The antioxidant capacity of digested microcapsules measured by ORAC and TEAC assays was increased (30 and 8 µmol TE/g powder, respectively), and their bioaccessibility was higher than non-encapsulate alkaloids. Solamargine and solasonine decreased during in vitro digestion by 17 and 15 %BA, respectively. However, microencapsulation showed the protection of these alkaloids during in vitro digestion. This study demonstrates that microencapsulated alkaloids from eggplant biomass manage to protect bioactive compounds from in vitro digestion, having antioxidant potential mainly through hydrogen atom transfer. Therefore, microencapsulation represents an alternative to protect alkaloids and give added value to eggplant plant biomass.
Complexity Measurement and Bifurcation Analysis of a New Lake Model: Coincidence with the Hénon Map
Authors: zeraoulia Rafik
Published: November 2024

This study presents a novel lake ecosystem model that captures the intricate dynamics of nutrient cycling through nonlinear interactions. The model incorporates external phosphorus loading and internal recycling rates to explore a range of ecological outcomes, from stable equilibria to chaotic oscillations. We investigate the bifurcation phenomena within this model, revealing how changes in parameters can lead to significant shifts in ecosystem behavior. Our analysis demonstrates that the model can replicate behaviors similar to the Hénon map under specific parameter settings. Through numerical simulations, we examine the system's sensitivity to variations in nutrient parameters, uncovering the potential for unpredictable dynamics and chaos as the recycling rate increases. The emergence of chaotic behavior is further supported by entropy analysis, highlighting the model's complexity and its implications for real-world ecosystems. Notably, our findings resonate with the work of Tay et al., demonstrating that increased nutrient recycling can lead to bistability and abrupt shifts in ecosystem stability, emphasizing the critical importance of effective nutrient management to avert detrimental ecological consequences. This research contributes valuable insights into the dynamics of freshwater ecosystems, underscoring the intricate interplay between nutrient inflow, recycling, and bifurcation in maintaining ecological balance.
Protective Effects of Quercetin and Sucrose on Cold-Preservation Injury in Porcine Kidneys Donated After Cardiac Death
Authors: Ishii Daisuke , Toriumi Asuka , Obara Hiromichi , Satake Yoshiyasu , Okada Yoko , Dewa Haruka , Imamura Masashi , Nishikawa Yuji , Matsuno Naoto
Published: November 2024

Background/Objectives: The University of Wisconsin (UW) solution is the gold standard for kidney preservation. The addition of quercetin (QE) to the preservation solution reduces damage to renal kidney tubular cells, and the addition of sucrose (Suc) is beneficial for kidney preservation. The aim of this study was to investigate the protective effects of QE and Suc and to evaluate whether their use improves mitigates ischemia-reperfusion (I/R) injury after simple cold storage (CS) in porcine kidneys. Methods: Kidney grafts were procured after 30 min of warm ischemia, followed by preservation under two conditions for 22 h: group 1, preserved with CS/UW solution (n = 4), and group 2, preserved with CS/UW solution containing QE (33.1 μM) and Suc (0.1 M; (n = 6). All grafts were evaluated using an ex- vivo isolated kidney- reperfusion model with oxygenated, diluted, autologous blood at room temperature. Results: At the end of reperfusion, creatinine phosphokinase and lactate dehydrogenase levels were significantly lower in group 2 than those in group 1. Additionally, group 2 had a significantly higher number more of anti-ERG-positive endothelial- cell nuclei than group 1 at the end of reperfusion. Conclusions: Our results suggest that the addition of QE and Suc to the UW solution can improve mitigate I/R injury to the donated kidney after CS.
Astrocyte-Secreted Lcn2 Modulates Dendritic Spine Morphology
Authors: Doliwa Marta , Kuzniewska Bozena , Nader Karolina , Reniewicz Patryk , Kaczmarek Leszek , Michaluk Piotr , Kalita Katarzyna
Published: November 2024

Learning and memory formation rely on synaptic plasticity, the process that changes synaptic strength in response to neuronal activity. In the tripartite synapse concept, molecular signals that affect synapse strength and morphology originate not only from the pre- and post-synaptic neuronal terminals but also from astrocytic processes ensheathing many synapses. Despite sig-nificant progress made in understanding astrocytic contribution to synaptic plasticity, only a few astrocytic plasticity-related proteins have been identified so far. In this study, we present evi-dence indicating the role of astrocyte-secreted Lipocalin-2 (Lcn2) in neuronal plasticity. We show that Lcn2 expression is induced in astrocytes in a kainate-evoked aberrant plasticity model. Next, we demonstrate that chemically induced long-term potentiation (cLTP), similarly increases Lcn2 expression in astrocytes of mix hippocampal cultures and that glutamate causes the immediate release of Lcn2 from these cultures. Additionally, through experiments in primary astrocytic cultures, we reveal that Lcn2 release is triggered by calcium signaling and we demonstrate that brief treatment of hippocampal neurons with Lcn2 alters morphology of dendritic spines. Based on these findings, we propose Lcn2 as an activity-dependent molecule released by astrocytes that influences dendritic spines morphology.
Effect of the COVID-19 Pandemic on Suicide Mortality in Brazil: An Interrupted Time Series Analysis
Authors: Meira Karina Cardoso , Guimarães Raphael Mendonça , Jomar Rafael Tavares , Silva Cosme Marcelo Furtado Passos da , Braiti Fabiana Serpa , Dantas Eder Samuel Oliveira
Published: November 2024

The objective of this study was to analyze the effect of the COVID-19 pandemic on suicide rates among Brazilian residents, stratified by sex. This study evaluated the behavior of monthly suicide rates based on an interrupted time series analysis of the months preceding (from January 2017 to February 2020) and following (from March 2020 to December 2022) the first diagnosed case of Covid-19 in Brazil. We used an interrupted time series model (quasi-Poisson), accounting for the presence of serial autocorrelation in the residuals and seasonality.Among men, we identified an abrupt decrease (RR<1, p<0.05) in monthly suicide rates at the onset of the pandemic, followed by a progressive increase (RR>1, p<0.05). An exception to this trend occurred in the Northeast region and among elderly men, where there was an abrupt increase in suicide rates at the start of the pandemic. For women, a reduction in monthly suicide rates was observed during the early stages of the pandemic only in the Central-West and Northeast regions, as well as in the 20-39 age group.The pandemic's effect was not uniform across Brazilian men and women, according to stratification variables; however, we observed a progressive upward trend over the course of the pandemic.
Successful and Safe Real-Time Tdm-Guided Treatment of Invasive Pulmonary Aspergillosis Using Isavuconazole Administered by Enteral Tube
Authors: Corral-Alaejos Alvaro , Jiménez-Casaus Jose , López-Delgado Angel , Zarzuelo Castañeda Aranzazu
Published: November 2024

Invasive aspergillosis (IA) is an opportunistic infection affecting immunocompromised patients. Current clinical guidelines support the use of voriconazole for the treatment of IA, although this treatment is not free of interactions in this group of patients who are often treated with polytherapy; in these cases, isavuconazole may be a safe alternative with a lower risk of interactions.
The oral route is commonly preferred to the parenteral route, but in patients who do not have access to the enteral route, the use of isavuconazole is limited to the parenteral route only, since the technical information sheet does not recommend the handling of tablets for enteral administration, stating that the capsules should not be chewed, crushed, dissolved or opened.
This paper presents the case of a patient with diffuse large B-cell lymphoma with confirmed AI on treatment with isavuconazole by enteral tube. It is detailed here that isavuconazole concentrations are maintained when administered by enteral tube, as measured by therapeutic pharmacokinetic monitoring of its plasma concentrations.
Administering isavuconazole by enteral tube was found to be a safe practice with monitoring of its plasma concentrations.
The Influence of Matrix Resin Toughening on the Compressive Properties of Carbon Fiber Composites
Authors: OuYang Xinfeng , Wang Xiao , Chen Qiufei , Ge Guojie , Liu Dong , Lin Kang , Liu Yunpeng , Zong Yangyang , Duan Shuo , Niu Kangmin
Published: November 2024

The poor impact resistance of carbon fiber reinforced composites limits their application in broader fields. In this study, a toughened epoxy resin (E2) modified with toughening agents and a micron-sized toughening particle (TP) were developed. Standard epoxy resin (E1), toughened epoxy resin (E2), and TP-toughened E2 resin (E3) were prepared into prepregs with SYT55-12K carbon fiber and ultimately fabricated into carbon fiber reinforced composites. The mechanical properties of the resins and the composites, particularly the compression properties, were characterized. The failure morphology of the composites and the distribution of toughening particles were observed using scanning electron microscopy (SEM), ultrasonic C-scan testing, and metallographic microscopy. It was found that the toughening agents improved the bending strength of the resin by approximately 12%, while the incorporation of TP enhanced the impact performance of the resin by 122%. Further characterization of the mechanical properties of the carbon fiber reinforced composites revealed that, with the addition of toughening agents, the resin increased the 0° bending strength of the composites by 29.9% and the 0° compressive strength by 34.3%. Additionally, significant enhancements were observed in interlaminar shear strength and open-hole compressive strength. After the addition of TP, the compressive strength of EC3 compared to EC2 increased by 74.3% after impact, while the mode I interlaminar fracture toughness increased by 34.8% and the mode II interlaminar fracture toughness improved by 67.9%. C-scan analysis indicated that the damage area of EC3 decreased by 60.7% compared to EC2, demonstrating that the particle toughening significantly enhanced the impact resistance of the composites. The compression failure of the TP-toughened EC3 exhibited typical characteristics of kink band failure, and the micron-sized particles were able to significantly balance and absorb loads. The findings of this study indicate that resin toughening can significantly improve the 0° compressive strength of carbon fiber reinforced composites, and that the use of micron-sized toughening particles can markedly enhance the post-impact compressive strength of the composites through interlaminar toughening. This research provides insights for improving the compressive and impact resistance performance of carbon fiber reinforced composites, with implications for industrial application and guidance for further industrialization trials.
Abdominal Aortic Diameter Appears Unaffected by Systemic Hypertension in Computed Tomography Measurements in Dogs
Authors: Ide Yutaro , Yasunaga Kent , Miura Naoki
Published: November 2024

Dogs with chronically elevated blood pressure require prompt treatment to prevent systemic hypertension-related tissue damage. Non-invasive oscillometry and Doppler sphygmomanom-etry are the conventional techniques to ascertain this indication, but imaging modalities may enable easier blood pressure assessments based on vascular geometry. This area is little studied in canine medicine, with only one report on abdominal ultrasonography, and none on computed tomography (CT). Accordingly, we retrospectively evaluated 32 dogs which underwent CT ex-aminations and blood pressure measurements on the same day, to determine whether CT-derived abdominal aortic diameter ratios (versus the caudal vena cava [Ao/CVC] and the first lumbar vertebra [Ao/L1]) differed between hypertensive and normotensive dogs. Neither Ao/CVC nor Ao/L1 ratio showed any such significant difference (P=0.393 or P=0.229). We concluded that CT-derived abdominal aortic ratios demonstrated no utility for blood pressure assessments in this study population, an inconsistency with previously reported ultrasonographic findings. Our results may reflect the inappropriateness of CT as an imaging modality, or aortic diameter as an index, for assessing hypertension in dogs. Further large-scale studies are needed to address this question.
Numerical Simulation of Earthquake Impacts on Marine Structures: A Comprehensive Review
Authors: Kabi Adel , Leon-Medina Jersson X. , Pozo Francesc
Published: November 2024

Earthquakes present a significant risk to marine and underwater structures such as seawalls, piers, dolphins, breakwaters, buried pipelines, and sheet-piled constructions. These structures are particularly susceptible to the destabilizing effects of seismic events, which can result in severe damage. Furthermore, earthquakes can indirectly threaten these installations by destabilizing the underlying soil. Soil liquefaction, induced by seismic shaking, can undermine the stability and integrity of structures. This review discusses advanced simulation programs that have been systematically developed and validated using comparisons with commercial software and existing research . It extensively examines various factors that influence earthquake-induced dynamics in marine environments, including soil conditions, quality of structural components, tunnel length, mooring intervals, seismic wave propagation, and seaquake impacts . Over the past four decades, significant insights have been gained into the seismic design of marine structures, leading to the development of comprehensive guidelines. Recently, the simulation of marine infrastructure—such as breakwaters, platform jackets, and tunnels—has progressed considerably, driven by rapid economic growth and technological advancements in engineering. This review aims to evaluate and categorize recent studies on the numerical simulation of marine structures under seismic forces, with a focus on mitigating earthquake-related damage.
The Study of the Cytotoxicity and Oxidative Impact of Metal Oxide Nanoparticle on Allium cepa L Root Cell
Authors: Jibunor Victor , Elebo Abuchi
Published: November 2024

Metal oxide nanoparticles (NPs) such as CuO, and ZnO can have significant effects on plant root cells, depending on factors like concentration, size, and surface properties of the nanoparticles. These metal oxide nanoparticles can cause toxic and genotoxic effects on plant root cells, affecting overall plant growth and development. This study evalaute the cytological and oxidative effect of varying concentration (100v/v, 80 v/v, 40 v/v and 20 v/v) of CuO-NPs, ZnO-NPs and CuO/ZnO-NPs on Onion (Allium cepa L) root tip cells. The synthesized CuO-NPs, ZnO-NPs and CuO/ZnO-NPs were of average particle sizes of 12.78nm, 13.76 nm and 13.35 nm respectively as revealed from the XRD study. The SEM analysis showed that CuO-NP and ZnO-NP appeared to have an irregular and granular particle shape, while the CuO/ZnO-NPs appeared to have a flower like structure. The chromosomal aberrations of nanopartcle treated Allium cepa L exhibited anormolies. The study revealed that at higher concentration (100% and 80%) of CuO-NPs, ZnO-NPs and CuO/ZnO-NPs exhibited higher chromosomal damage as evidence from the higher abnormality percentage (72.50 and 56.2%), (69.10% and 61.20%), and (81.10% and 74.25%) respectively. The effect of concentration revealed that the mitotic index was concentration dependent with 20v/v concentration showing reduced mitotic activities across all samples. The study reveals that the uncontrolled application of these nanoparticles may have harmful effect on plants cell growth when exposed in polluted soil.
Increasing SBA-15 Amphoteric Properties by Direct Zr Addition During Synthesis
Authors: Hernández-Morales Romeo , Escobar José , Pacheco-Sosa José Guadalupe , Torres-Torres José Gilberto , García-Zaleta David S. , Guerra-Que Zenaida , Del Angel Vicente Paz , Barrera María C. , de la Cruz-Romero Durvel
Published: November 2024

Strategies followed to improve SBA-15 surface (essentially inert) included modifications by adding acidic or basic (or both) species during or after silica synthesis. Amphoteric properties are especially important as some reactions (alcohols dehydrations, for instance) require of both type of sites to efficiently take place. In this work, single Zr (nominal 3, 5 and 10 wt%, as ZrOCl2•8H2O) direct addition during SBA-15 synthesis was used to impart amphoteric characteristics (as determined by NH3 and CO2 TPD) to mesostructured SiO2 matrices. Additional materials characterization included textural (N2 physisorption) and structural (XRD, FTIR and UV-vis spectroscopies, and HRTEM as well) studies. Actual solids composition was also determined (EDS). Degree of Zr incorporation to mesoporous silica was enhanced with nominal content in binary formulations, although not necessarily integrated in SBA-15 walls forming Zr-O-Si linkages. It seemed that single ZrO2 domains (framework and extra-framework) could provide suitable amphoteric properties by significantly increasing number and strength of both acid and basic sites (especially formulation containing nominal 5 wt% Zr), as to those over mesostructured silica matrices. Also, potentially deleterious strong acid sites were avoided. The binary oxides present great potential to be applied in reactions requiring vicinal acid-basic pairs (alcohols dehydration, for instance).
In the Footsteps of Tradition: Reinventing the Paths of the Santa Faz within the Paradigm of Sustainability and Territorial Development in Alicante
Authors: Rosser Pablo , Soler Seila
Published: November 2024

The Santa Faz Pilgrimage, with over 600 years of history and as Spain’s second most significant pilgrimage, is at a critical point due to urbanization and inadequate planning. This study ex-plores revitalizing and enhancing the historical Santa Faz routes, integrating cultural tourism, environmental sustainability, and socioeconomic benefits. Recognized as Intangible Cultural Heritage, the pilgrimage impacts Alicante’s cultural landscape, yet faces pressure from modern urban development. Using a multidisciplinary approach aligned with the UN’s 2030 Sustainable Development Goals, the study proposes alternative routes, such as a “green route” through ancient paths and water routes, a Villafranqueza route, and one from the former Monastery of Los Ánge-les. These paths would be revived through local reforestation, sustainable tourism infrastructure, and rest areas for pilgrims. The restoration of the Santa Faz paths is seen as vital for cultural her-itage conservation, sustainable tourism, and job creation, with both opportunities and challenges in integrating these routes into the Council of Europe’s Cultural Routes. The study advocates modifying the urban plan and promoting employment in heritage and tourism management, em-phasizing the need for ongoing research and cross-disciplinary collaboration to secure the long-term preservation and development of these culturally significant spaces.
DataLDA: Analyzing Data Quality in Big Data Using Traditional Approaches vs. Latent Dirichlet Allocation - Systematic Review
Authors: Sayeed Sayed Abu , Kshetri Naresh , Rahman Mir Mehedi , Alam Samiul , Rahman Abdur
Published: November 2024

Big data quality is all about ensuring that the huge amounts of data are accurate, reliable, and useful. It is important because decisions made based on this data can affect many things, like business strategies, customer experiences, and even public policies. Many researchers are studying data quality in the context of big data. This study aims to analyze the research trends and patterns within the domain of big data quality. This method reveals hidden themes in large datasets, helping to understand data quality better. The findings show that Latent Dirichlet Allocation (LDA) is effective for topic modeling in big data, highlighting data quality challenges and opportunities. The research identified key trends and effective assessment methods. For researchers, using LDA in a systematic review helps summarize existing studies and find gaps, guiding future research. Practitioners and future researchers get useful direction for managing data quality and improving efficiency and decisions in various industries.
Single Cell Sequencing: Genomic and Transcriptomics Approaches in Cancer Cell Biology
Authors: Ortega-de Martínez Ana , Jaén-Alvarado Yanelys , Moreno-Labrador Dilan , Gómez Natasha , García Gabriela , Guerrero Erika N
Published: November 2024

This article reviews the transformative impact of single-cell whole genome sequencing (scWGS) on cancer biology research. ScWGS has revolutionized our understanding of tumor heterogeneity, clonal evolution, and the tumor microenvironment by enabling high-resolution analysis of individual cells' genomic, transcriptomic, and epigenomic profiles. The technology's unique capabilities, including detection of rare genomic events, simultaneous capture of multiple genomic features, and association with phenotypic data, have opened new avenues for cancer research and precision medicine. Integration of scWGS with other single-cell omics technologies has provided a multidimensional view of cellular states and regulatory mechanisms in cancer. Advanced data analysis tools, including machine learning and AI algorithms, have been crucial in interpreting the vast amounts of data generated, leading to the identification of new biomarkers and development of predictive models for patient stratification. The article also discusses emerging technologies like spatial transcriptomics and in situ sequencing, which promise to further enhance our understanding of tumor spatial organization and cellular interactions. As scWGS and related technologies continue to evolve, they are expected to drive significant advances in personalized cancer diagnostics, prognosis, and therapy, ultimately improving patient outcomes in the era of precision oncology.
Prophylactic Use of Continuous Norepinephrine at a Dose of 0.05 mcg/kg BW/min in Spinal Anaesthesia for Cesarean Section Patients in Ketapang
Authors: Rachman Abdul
Published: November 2024

Background: Norepinephrine infusion decreases hypotension after spinal anesthesia during a cesarean section. There is an increasing attitude toward using norepinephrine to prevent spinal hypotension. There hasn't been much investigation on the use of norepinephrine in spinal anesthesia in Indonesia, particularly for cesarean sections in rural areas.
Methods: In this single-blinded norepinephrine group. Randomized clinical trial: The norepinephrine group was given continuous norepinephrine before spinal anesthesia. Parturients for elective and emergency cesarean section were allocated to receive norepinephrine infusion (0.05 mcg/kg BW/mnt. Our primary outcome was the incidence of hypotension within 36 min of spinal anesthesia administration. Secondary outcomes included side effects such as nausea, vomiting, and chills during surgery.

Result: In total, 92 patients were enrolled. Of these patients included in the ﬁnal analysis. Patients who suffered hypotension showed hypotension at minute zero and minute twelve (14.13 %), minute twenty-four (13.04 %), and minute thirty-six (18.47 % )—the frequency of chills and nausea/vomiting. Three (3.26 %) and eight (8.89 %) participants in the norepinephrine group reported feeling chills and nausea/vomiting.

Conclusion: prophylactic norepinephrine infusion may reduce HR without increasing the risk of post-spinal hypotension following cesarean delivery.
Dexmedetomidine Adjuvant in Awake Intubation as Difficult Airway Management for Submandibular Abscess with Mediastinum Infiltration
Authors: Arianto Ardana Tri , Utama Sigit Prastya , Faras Asaduddien
Published: November 2024

Background: Maintaining a secure airway in difficult airway settings is important due to morbidity and mortality. Conventional intubation relies on benzodiazepines, opioids, and propofol which have a respiratory depression effect. Dexmedetomidine has a minimal to no central respiratory depression effect. A submandibular abscess can result in laryngeal edema which narrows or occludes the airway.
Case Ilustration: A 65-year-old male complained of difficulty breathing and shortness of breath accompanied by neck and right jaw pain that radiated to the right cheek. The patient also complained of a salty taste every time the patient swallows. Obtained blood pressure 112/73 mmHg on norepinephrine support syringe pump 0.1 mcg/kg/minute (5.4 cc/hour), pulse rate 120 bpm, respiratory rate 32 times per minute with the help of respiratory muscles. The patient’s temperature was 36.7oC. The patient’s initial Glasgow Coma Scale was E3V5M6. Difficult airway was observed due to submandibular mass, 1-2 finger mouth opening, trismus, mallampati was difficult to evaluate, limited neck motion due to pain, and missing teeth. Imaging showed a soft tissue mass in the neck region. The patient underwent awake intubation using a video laryngoscope and Nasoendotracheal tube number 6.5 was installed with 70 mcg of dexmedetomidine syringe pump in 10 minutes (with pump rate of 105 ml per hour) and lidocaine mouth rinse. The intubation process went smoothly and the patient was admitted to the Intensive Care Unit for further monitoring.
Conclusion: Management of difficult airway settings is important due to morbidity and mortality. The use of dexmedetomidine is considered safe and effective in securing the airway in patients with difficult airway.