bluuebunny/crossref_metadata_2025 huggingface dataset:
Dermatological Neoplastic Diseases Complicating Treatment with Monoclonal Antibody for Multiple Sclerosis
Authors: Bile Floriana , Sparaco Maddalena , Ruocco Eleonora , Miele Giuseppina , Maida Elisabetta , Vele Renato , Mele Davide , Bonavita Simona , Lavorgna Luigi
Published: July 2024

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.
A Spatial-Seasonal Study for Dynamics of Pollutant Concentration in Water on the Danube River in the Adjacent Danube Delta Area and the Evaluation of the Attenuation and Transfer Coefficients. Part 1 – Case Study – Monitored Heavy Metals
Authors: Topa Catalina , Murariu Gabriel , Calmuc Valentina-Andreea , Calmuc Madalina , Arseni Maxim , Serban Cecila , Chițescu Carmen Lidia
Published: July 2024

Monitoring and protecting flowing watercourses is a complex and challenging task that requires the collaboration and coordination of various stakeholders such as governments, industries, farmers, consumers and environmental groups. The study of the dynamics of the concentration of polluting factors and especially the concentrations of heavy metals and highlighting a seasonal variation is a necessary element from this point of view. In this article, we present the results of our analyzes carried out in two measurement campaigns executed in 10 monitoring points along the Danube River, between Braila city and Isaccea city in the pre-deltaic area, during the summer season and autumn season 2022. The importance of this area is given by the fact that the Dan-ube Delta is part of the UNESCO heritage and the monitoring of polluting factors is a necessity in the desire to protect this area. The data measured during the July and August 2022 campaign co-vers a wide range of chemical species: Phosphate, CCO, CBO5, NH4+, N-NO2, N-NO3-, N-Total, P-PO4 3-, SO42-, Cl-, phenols, as well as metals with a harmful effect: Aluminum, Arsenic, Cad-mium, Chromium, Iron. The study includes an evaluation based on the statistical approach of the results to highlight the significant correlations and differences identified between the two data sets. Next, to highlight the obtained results, a numerical model was considered using HEC-RAS and ESRI ArcGis applications in a two-dimensional unsteady flow model in order to get the non-homogenous concentrations’distributions in the studied area. These two-dimensional models have been less studied in the specialized literature. In this way, interesting results could be ob-tained and prediction methods regarding the dynamics of metal concentrations could be struc-tured. The data obtained was used for the terrain model from the USGS service and the flows of the Danube and its two tributaries were simulated using the data provided by the national ser-vices. In this work, we present the results obtained for the dynamics of the concentrations of the metals Aluminum, Arsenic, Cadmium, Chromium and Iron and the evaluation of the specific ab-sorption coefficients for the explanation and correlation with the results of the measurements. The study is part of a more complex project in which the spatio-temporal distribution of the polluting factors in the water was evaluated and the habitats in the study area were inventoried - especially those of community interest. the aspects related to the influence of the distribution of polluting factors on the state of health will be the subject of another article.
Early Prediction of Kimchi Cabbage Height using Drone Imagery and Long Short-Term Memory (LSTM) Model
Authors: Go Seung-hwan , Park Jong-hwa
Published: July 2024

This study introduces a novel method for early prediction of Kimchi cabbage (Brassica rapa subsp. pekinensis (Lour.) Hanelt) height, utilizing drone imagery and a long short-term memory (LSTM) model. The research was conducted on a testbed at the National Institute of Agricultural Sciences (NAS) in South Korea, encompassing two distinct soil types (loam and sandy loam) to investigate their impact on growth. High-resolution drone images were captured throughout the growing season to generate a canopy height model (CHM) for estimating plant height at various stages. Missing height data were interpolated using a logistic growth curve, and an LSTM model was trained on this data to predict the final height of Kimchi cabbage at harvest. Three LSTM models were developed using time-series data collected at 29, 36, and 44 days after planting (DAP). The model trained on data from DAP 44 demonstrated the highest accuracy with a coefficient of determination (R²) of 0.83, a mean absolute error (MAE) of 2.48 cm, and a root mean square error (RMSE) of 3.26 cm, outperforming models trained on earlier data. Color-coded maps were generated to visualize the spatial distribution of predicted Kimchi cabbage heights, revealing variations in growth patterns across the testbed and confirming the model's potential for site-specific management. Considering the trade-off between accuracy and prediction timing, the model trained on DAP 36 data (MAE = 2.77 cm) was deemed optimal for informing cultivation management decisions. This research demonstrates the feasibility and effectiveness of integrating drone imagery, logistic growth curves, and LSTM models for early and accurate prediction of Kimchi cabbage height. The proposed technology enables data-driven decision-making for farmers, facilitating timely interventions based on predicted growth patterns. This could lead to improved crop yields, resource optimization, and a more sustainable agricultural future. Future research will focus on refining the model's accuracy and exploring its applicability to other crops, further expanding the potential of precision agriculture technologies.
A First Model Foundation Design of Wood Pillar in Banjarmasin Swampland
Authors: Agusniansyah Nursyarif , Rahman Akbar , Sarbini Gusti Novi , Tharziansyah Muhammad
Published: July 2024

Swampy land in Banjarmasin has special characteristics for building house constructions. The foundation for very low soil bearing capacity requires special treatment as well. Many building collapses are caused by foundation failures due to mismatched building loads and foundation functions, as well as construction material errors. The need for house design follows the development of building functions. Nowadays, a one-story house is no longer sufficient due to limited land. The need to elevate houses to two stories or to develop houses (renovations) often leads to foundation construction errors. The commonly used foundation, wooden pile foundation, has limited load-bearing capacity, necessitating modification steps in the form of foundation reinforcement. Several steps, including material combinations or combinations of various types of foundations, can be implemented. Therefore, a specific model is required to obtain a foundation design that can accommodate construction needs. The aim of the research is to create a foundation design model capable of reinforcing wooden pile foundations for both house construction development and as a reference for building one-story and two-story houses. In this research, field observations will be conducted at various house construction sites in Banjarmasin, both residential and individual objects. Data will be presented descriptively and analyzed to obtain an applicable model as a reference for house construction on swampy land. The model will provide an applicable depiction and will be tested against foundation construction implementation methods.
Economic Reforms and Consumption Trends: A Deep Dive into Saudi Arabia's Economic Evolution
Authors: Mohammed Mwahib
Published: July 2024

This study examines the aggregate consumption function of Saudi Arabia from 2000 to 2022, focusing on identifying key determinants of household consumption and evaluating the impacts of disposable income, household wealth, government expenditure, interest rates, and oil revenues. The research uses advanced econometric methods, including the Autoregressive Distributed Lag (ARDL) model and Johansen cointegration test, to analyze the relationships among these variables. The findings reveal that disposable income, household wealth, and government expenditure significantly and positively influence consumption, whereas interest rates show a negative correlation. Oil revenues also play a critical role, reflecting the country's economic reliance on oil. The study highlights the necessity for economic diversification to reduce the impact of oil price volatility on household income and consumption stability. The results offer crucial insights for policymakers, emphasizing the need for strategies that enhance household income and wealth, maintain robust public sector spending, and effectively manage interest rates. These findings also support the importance of consistent and predictable income sources for sustaining consumption. Additionally, this study suggests directions for future research, including developing sophisticated forecasting models to predict consumption trends and exploring other influencing factors such as demographic shifts and technological progress.
Numerical Simulation of Non-Darcy Flow in Naturally Fractured Tight Gas Reservoirs for Enhanced Gas Recovery
Authors: Debossam João Gabriel Souza , de Freitas Mayksoel Medeiros , de Souza Grazione , Amaral Souto Helio Pedro , Pires Adolfo Puime
Published: July 2024

In this work, we analyzed non-Darcy two-component single-phase isothermal flow in naturally fractured tight gas reservoirs for enhanced gas recovery (EGR) and carbon dioxide storage as a possible application. We used the Peng-Robinson equation of state to evaluate the thermodynamic properties of the components, and we performed the discretization of the governing partial differential equations using the Finite Volume Method. This process leads to two subsystems of algebraic equations, which, after linearization and use of an operator splitting method, are solved by the Conjugate Gradient (CG) and Biconjugate Gradient Stabilized (BiCGSTAB) methods for determining the pressure and fraction molar, respectively. We include inertial effects using the Barree and Conway model, gas slippage via a more recent model than Klinkenberg’s and we use a simplified model for the effects of effective stress. We also utilize a mesh refinement technique to represent the discrete fractures. Finally, we implemented simulations to show the influence of inertial, slippage and stress effects on production in fractured tight gas reservoirs.
Watermelon Plant Silage: A Viable Alternative to Alfalfa Hay for Feeding Murciano-Granadina Goats
Authors: Pardo Zaira , Palma-Hidalgo Juan Manuel , Sánchez-García Alberto Manuel , Martín-García Antonio Ignacio
Published: July 2024

The study aimed to evaluate the nutritional value of watermelon plant silage (WPS) and to assess the effect of replacing alfalfa hay (AH) with WPS in a diet formulated for dairy goats. The study used four goats as donors of rumen microbiota to analyze in vitro fermentation parameters. The chemical composition analysis revealed that WPS and AH had similar protein content (21.1 vs. 18.9 g CP/100 g DM), but WPS had lower contents of organic matter (77.4 vs. 89.6 g/100 g DM), NDF (36.3 vs. 49.4 g/100 g DM), ADF (26.4 vs. 34.6 g/100 g DM), LAD (6.40 vs. 8.01 g/100 g DM), and amino acids (716 vs. 874 g AA/kg N) compared to AH. Conversely, WPS had higher fat content (3.09 vs. 1.29 g CF/100 g DM) and different macro- and micromineral content values than AH. In a first in vitro experiment, WPS and AH were incubated independently to compare their fermentation behaviour, indicating that the metabolizable energy (ME) tended to be higher for WPS compared to the AH diet (6.67 vs. 5.72 MJ/kg DM; p = 0.058). WPS fermentation produced lower concentrations of total VFA than AH (66.6 vs. 115 mM; p = 0.011), lower proportions of propionate and valerate (p ≤ 0.022), and higher proportions of isobutyrate (p = 0.001), without altering gas production (GP) kinetics as degradation rate and its potential release. In a second in vitro trial, a formulated goat diet (consisting of commercial concentrate and AH in a 1:1 ratio) was used as a control to assay the impact of AH replacing by WPS at 25% and 50% respectively. Trends were observed in several parameters, such as a linear increase in GP rate (p = 0.088), organic matter digestibility (p = 0.067), and CH4 concentration in the gas produced (p = 0.094) as AH was replaced by WPS. The study concluded that WPS could serve as a viable fodder to replace AH in conventional dairy goat diets while simultaneously reducing agricultural waste and serving as a regenerative model for implementing the circular economy strategy in the affected sectors.
Multitemporal Analysis of Land Cover Changes in Areas with Contrasted Forest Management and Conservation Policies in Northern Mexico
Authors: Sandoval-García Rufino , Rascón-Solano Joel , Alanís-Rodríguez Eduardo , García-García Samuel , Sigala José A. , Aguirre-Calderón Oscar
Published: July 2024

This study evaluates and contrasts the changes in vegetation cover over three decades in two forest areas in northern Mexico with different management statuses: one with sustainable forest exploitation and the other under protection as a Flora and Fauna Protection Area (FFPA). The hypothesis proposed that both areas would maintain or increase their vegetation cover since 1995. Using QGIS 3.32 “Lima” software and supervised and unsupervised classification methods, satellite images from the periods 1995-2008, 2008-2014, 2014-2021, and 1995-2022 were analyzed. The results showed that the Ejido El Largo y Anexos significantly increased forest areas and reduced grasslands due to sustainable management practices, with notable expansion of pine-oak and pine forests. In contrast, the Tutuaca Flora and Fauna Protection Area (FFPA) showed a notable loss of oak and oak-pine forests, suggesting ineffectiveness in its conservation policies. However, a lesser loss of Douglas fir forest was observed, indicating some effective protection efforts. The comparison reveals opposing dynamics: while Ejido El Largo y Anexos demonstrates success in sustainable management, the Tutuaca FFPA faces conservation challenges. In conclusion, this study highlights the need for active management approaches to maintain ecosystem cover and functionality.
Biomarkers and Rehabilitation for Functional Neurological Disorder
Authors: Mark Victor W
Published: July 2024

Functional neurological disorder, or FND, is widely misunderstood, particularly when considering recent research that suggests that the illness has a biological rather than a psychiatric basis. Nonetheless, the long-held view that FND is a purely psychiatric disorder without biological basis, or even a contrived (malingered) illness, remains pervasive both in modern medical care and general society. This is because FND involves an intermittent course of involuntary disability that rapidly alternates with improved neurological control. This has in turn caused shaming, low self-efficacy, and social isolation of the patients. Little research has examined the numerous biomarkers that are shared between FND and canonical neurological disorders and the encouraging outcomes that can follow conventional neurological rehabilitation, modified for this disorder. This review summarizes current research on FND biomarkers and physical rehabilitation results. General healthcare providers would benefit their care for their patients through their improved understanding the illness and recourses for support and treatment that are provided in this review.
Novel Treatment for Pre-XDR-Tuberculosis Linked with a Lethal Case of Acute Myocarditis
Authors: Kotoulas Serafeim – Chrysovalantis , Poulios Pavlos , Chasapidou Georgia , Angeloudi Elena , Bargiota Triantafyllenia , Stougianni Maria , Manika Katerina , Mouloudi Eleni
Published: July 2024

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.
Biochar and Deactivated Yeast as Seed Coatings for Restoration: Performance on Alternative Substrates
Authors: Cann Jennifer , Tang Esther , Thomas Sean C.
Published: July 2024

Seedling establishment is often a critical bottleneck to revegetation of mine tailings and similar substrates with a low capacity to retain water and plant nutrients. Biochar and deactivated yeast are potential sustainable, low-cost materials with high nutrient- and water-holding capacity that could be used in this context as seed coatings to aid in seedling establishment on challenging sub-strates. We conducted a greenhouse study to assess the effectiveness of biochar and deactivated yeast, applied alone in a factorial combination, as seed coatings, on the germination, establish-ment, and early growth of white clover (Trifolium repens) and purple prairie clover (Dalea pur-purea). Coated seeds were applied to a mine tailing, a coarse granitic sand, and potting soil mix substates; seedling establishment and growth were monitored over 75 days. Results indicate strong interactive effects of seed coatings with species and substrate. Biochar coatings enhanced seedling establishment of Trifolium, with biochar or biochar plus yeast coatings giving the best results. In some cases, these effects persisted throughout the experiment: biochar coatings resulted in a ~5-fold increase in Trifolium biomass at harvest for plants in the potting soil mix but had neutral effects on sand or tailings. Biochar seed coatings also enhanced Dalea germination in some cases, but benefits did not persist. Our results indicate that biochar-based seed coatings can have lasting effects on plant growth well beyond germination, but also emphasize highly spe-cies-specific responses that highlight the need for further study of broader patterns and mecha-nisms.
Oral Administration of Berberine Hydrochloride Based on Chitosan/Carboxymethyl-β-Cyclodextrin Hydrogel
Authors: Clemence Bukatuka Futila , Xiao Lin , Yang Guang
Published: July 2024

In this study, a novel oral formulation of berberine hydrochloride (BBH) hydrogel was successfully synthesized through physical cross-linking using chitosan (CS) and carboxymethyl-β-cyclodextrin (CMCD). The characterization results confirmed the successful synthesis of CS/CMCD hydrogel and the subsequent loading of BBH into this composite (CS/CMCD/BBH) was effectively accomplished. BBH was used as a model drug and the resulting hydrogel demonstrated a sustained drug release profile. In addition to its improved solubility and sustained release characteristics, the hydrogel exhibited excellent antibacterial activity against common pathogens such as Escherichia coli (E. coli), Staphylococcus aureus (S. aureus), and Candida albicans (C. albicans). Additionally, in vitro studies indicated that the hydrogel was not cytotoxic to NIH3T3 and HaCaT cells, suggesting its safety for biomedical applications. This lack of cytotoxic effects, combined with the mechanical strength, solubility improvements, and antibacterial properties of the hydrogel, positions the CS/CMCD/BBH hydrogel as a promising candidate for effective oral delivery of BBH. By addressing the solubility and delivery challenges of BBH, this hydrogel offers a viable solution for the oral administration of berberine hydrochloride, with potential applications in various biomedical fields.
Improved Apriori Method for Safety Signal Detection using Post-Marketing Clinical Data
Authors: Sarkar Reetika , Sun Jianping
Published: July 2024

Safety signal detection, an integral component of Pharmacovigilance (PhV), aims to identify new or known adverse events (AEs) resulting from the use of pharmacotherapeutic products. Post-marketing spontaneous reports from different sources are commonly utilized as a data source for detecting these signals but there are underlying challenges arising from data complexity. This paper investigates the implementation of the Apriori algorithm, a popular method in association rule mining, to identify frequently co-occurring drugs and AEs within safety data. We discuss previous applications of the Apriori algorithm for safety signal detection and conduct a detailed study of an improved method specifically tailored for this purpose. This enhanced approach refines the classical Apriori method to effectively reveal potential associations between drugs/vaccines and AEs from post-marketing safety monitoring datasets, especially when AEs are rare. Detailed comparative simulation studies across varied settings, coupled with the application of the method to vaccine safety data from the Vaccine Adverse Event Reporting System (VAERS), demonstrate the efficacy of the improved approach. In conclusion, the improved Apriori algorithm is shown to be a useful screening tool for detecting rarely occurring potential safety signals from the use of drugs/vaccines using post-marketing safety data.
Novel Insight into the Effect of Balneotherapy on Changes in the Functional State in Patients with Chronic Low Back Pain: Integration of Physical and Mental Healthcare Indicators and Patients’ Health Perception
Authors: Terzic Markovic Dragana , Kocic Sanja , Bradic Jovana , Jurisic Skevin Aleksandra , Jakovljevic Biljana , Majstorovic Biljana , Dimoski Zvonko , Stojanovic Goran , Maksimovic Vesna , Pavlovic Jugovic Katarina , Dabic Marijana , Jezdimirovic Danijela , Zivanovic Sandra
Published: July 2024

Background: Alarming data indicates that low back pain (LBP) affected around 619 million people globally in 2020, that presenting significant health and economic burden. Importantly, the chronic LBP (cLBP) strongly impairs quality of life and leads to disability and premature retirement thus emphasizing the urgent need for providing deeper insight into the factors that affect treatment outcomes and offer thorough guidance for the assessment and management of this disease. Taking into consideration the rising prevalence of cLBP and knowledge gap referring to the overall health benefits of balneotherapy (BT), the aim of this study was to assess the effects of BT on functional status, quality of life and psychological symptoms in patients with cLBP. Methods: A total 210 patients were recruited and divided into two groups: patients receiving conventional pharmacological therapy (CT) and receiving BT. The effectiveness of the treatment was assessed on the basis of Visual Analog Scale for pain intensity, EuroQol (EQ-5D) for the patient’s self-rated health and Work Ability Index Questionnaire to evaluate functional ability. In order to provide deeper insight into the quality of life and also factors associated with the functional status and mental health affected by BT, we also used the Short Form Health Survey Questionnaire and Center of Epidemiologic Studies Depression Scale. Results: Our findings suggest that BT significantly contributed to reduction of pain, better functionality and disability perception status. Conclusions: Understanding the association between individual perceptions of functionality, emotional and social elements provides basis for providing comprehensive guidelines and recommendations for cLBP management.
Aquitard Structure Plays Important Role in Leakage: Evidence from Knn Method
Authors: Du Zhaoguo , Liu Yutao , Dong Yihan , Chen Yaoxuan , Zhai Yuanzheng
Published: July 2024

Leakage is important in groundwater cycle research and water resource management, the key is to construct the spatial distribution of aquitard. Influenced by natural and anthropogenic factors, the density of boreholes restricts the accuracy of aquitard structure. This paper explores the K-Nearest Neighbor (KNN) method to construct multi-layer aquitard structure in the hinterland of Songnen Plain, Northeast China, with limited boreholes, and compare it with Inverse Distance Weight (IDW) and Ordinary Kriging (OK) methods to evaluate the leakage. The KNN needs to first identify the eigenvalue-k of each layer, which is used to enhance the trainset to obtain the testset with a larger amount of sample data enhanced, and to make a prediction to obtain the 3-dimensional structure of aquitard. KNN is more accurate than the IDW and OK. The aquitrad structure obtained by the KNN is different from the IDW and OK, the thickness difference is 3.53%-54.00%, the area difference is 2.28%-23.91%, and the difference in leakage can be up to 24.51%. KNN also has a high degree of identification of aquitard edges, which can help the prevention of groundwater pollution. The results provide guidance for water balance analysis, borehole engineering design, water resources management and exploitation.
Marijuana Use and Associated Risk Behavior Factors among High School Students in Mississippi: Youth Risk Behavior Surveillance System 2021
Authors: Mitra Amal K. , Zhang Zhen , Schroeder Julie A.
Published: July 2024

Marijuana is the most used illicit drug among youths in the United States. The objectives of the study were to identify the association between marijuana use and other risk behaviors including suicidality among high school students. The 2021 Mississippi Youth Risk Behavior Survey data sets were combined for this study. Crude odds ratio (OR) and adjusted odds ratio (AOR) with a 95% confidence interval were generated using the survey packages in R to account for weights and the complex sampling design of YRBS data. Tobacco products and alcohol use were significantly associated with marijuana use. Students who responded “Yes” to questions “currently used an electronic vapor product?”, “currently smoked cigarettes or cigars?” or “currently drank alcohol?” were more likely to use marijuana compared to students who responded “No”, after adjusting for other risk factors. Marijuana use is also significantly associated with students who had sex, compared to those who never had sex. The adjusted odds ratio is nearly doubled in those who had sex with the same sex or both sexes, compared to those who had heterosexual sex only. After adjusting for other health risk factors, the association between current marijuana use and attempted suicide was not statistically significant. The impact of students’ not sleeping in their parent's or guardian's home on current marijuana use was not significant after adjusting for other risk factors. Marijuana use is evenly burdened between males and females and between all race categories among Mississippi high school students. The identified associations seem to indicate that electronic vapor, tobacco products, and alcohol use could be the forerunners for drug use and should be treated accordingly in drug use prevention programs.
A Multi-target Pharmacological Correction of a Lipoyltransferase LIPT1 Gene Mutation in Patient-Derived Cellular Models
Authors: Gómez-Fernández David , Romero-González Ana , Suárez-Rivero Juan M. , Cilleros-Holgado Paula , Álvarez-Córdoba Mónica , Piñero-Pérez Rocío , Romero-Domínguez José Manuel , Reche-López Diana , López-Cabrera Alejandra , Ibañez-Mico Salvador , Castro de Oliveira Marta , Rodríguez-Sacristán Andrés , Gónzalez-Granero Susana , García-Verdugo José Manuel , Sánchez-Alcázar José A
Published: July 2024

Mutations in the lipoyltransferase 1 (LIPT1) gene are rare inborn errors of metabolism leading to a fatal condition characterized by lipoylation defects of the 2-ketoacid dehydrogenase complexes causing early-onset seizures, psychomotor retardation, abnormal muscle tone, severe lactic aci-dosis and increased urine lactate, ketoglutarate, and 2-oxoacids levels. In this article, we characterized the disease pathophysiology using fibroblasts and induced neurons derived from a patient bearing a compound heterozygous mutation in LIPT1. Western blot analysis revealed reduced expression of LIPT1 and absent expression of lipoylated pyruvate dehydrogenase E2 (PDH E2) and alpha-ketoglutarate dehydrogenase E2 (α-KGDH E2) subunits. Accordingly, activities of PDH and α-KGDH were markedly reduced, associated with cell bioenergetics failure, iron accumulation and lipid peroxidation. In addition, using a pharmacological screening, we identified a cocktail of antioxidants and mitochondrial boosting agents consisting of pantothenate, nicotinamide, vitamin E, thiamine, biotin, and alpha-lipoic acid, which is capable of rescuing LIPT1 patho-physiology, increasing LIPT1 expression and lipoylation of mitochondrial proteins, improving cell bioenergetics, and eliminating iron overload and lipid peroxidation. Furthermore, our data suggest that the beneficial effect of the treatment is mainly mediated by SIRT3 activation. In conclusion, we have identified a promising therapeutic approach for correcting LIPT1 mutations.
BRAC1 & BRCA2 Methylation as a Prognostic and Predictive Biomarker in Cancer: Implementation in Liquid Biopsy in the Era of Precision Medicine
Authors: Panagopoulou Maria , Panou Theodoros , Gkountakos Anastasios , Tarapatzi Gesthimani , Karaglani Makrina , Chatzaki Ekaterini
Published: July 2024

BReast CAncer gene 1 (BRCA1) and BReast CAncer gene 2 (BRCA2) encode for tumor suppressor proteins which are critical regulators of the homologous recombination (HR) pathway, the most precise and important DNA damage response mechanism. Dysfunctional HR proteins cannot repair double-stranded DNA breaks in mammalian cells, a situation called HR deficiency. Since their identification, pathogenic variants and other alterations of BRCA1 and BRCA2 genes have been associated with an increased risk of developing mainly breast and ovarian cancer. Interestingly, HR deficiency is also detected in tumors not carrying BRCA1/2 mutations, a condition termed “BRCAness”. One of the main mechanisms causing the BRCAness phenotype is the methylation of the BRCA1/2 promoters and this epigenetic modification is associated with carcinogenesis and poor prognosis mainly among patients with breast and ovarian cancer. BRCA1 promoter methylation has been suggested as an emerging biomarker of great predictive significance, especially concerning Poly (ADP-ribose) Polymerase inhibitors (PARP inhibitor-PARPi) responsiveness, along with or beyond BRCA1/2 mutations. However, as its clinical exploitation is still insufficient, the impact of BRCA1/2 promoter methylation status needs to be further evaluated. The current review aims to gather the latest findings about the mechanisms that underline BRCA1/2 function as well as the molecular characteristics of tumors associated with BRCA1/2 defects, by focusing on DNA methylation. Furthermore, we critically analyze their translational meaning and the validity of BRCA methylation biomarkers in predicting treatment response and we suggest a diagnostic pipeline that could be implemented in liquid biopsy to aid precision pharmacotherapy in BRCA-associated tumors.
Lassa Fever: Critical Review and Prospects for Control
Authors: Besson Marianne E , Pepin Michel , Metral Pierre-Alexandre
Published: July 2024

Lassa Fever is a deadly viral haemorrhagic disease, causing annually several hundreds of deaths in the Gulf of Guinea. This zoonotic disease is primarily transmitted to humans by rodents of the genus Mastomys, while secondary interhuman transmission accounts for approximately 20% of cases. Although this disease has been endemic in rural zones of the Gulf for hundreds of years, it is also characterised by epidemic outbreaks in the dry season, responsible for heavy death tolls. No licensed vaccine or satisfying treatment is currently available. Disease management is hindered by the incomplete knowledge of the epidemiology and distribution of the disease, resulting from an inadequate health and surveillance system. Additional scientific constraints such as the genetic diversity of the virus and the lack of understanding of the mechanisms of immune protection complexify the development of a vaccine. The intricate socio-economic context in the affected regions, and the lack of monetary incentive for drug development, allow the disease to persist in some of West Africa’s poorest communities. The increase in the number of reported cases and in the fatality rate, the expansion of the endemic area, as well as the threat Lassa Fever represents internationally should urge the global community to work on the disease control and prevention. The disease control requires collaborative research for medical countermeasures and tailored public health policies. Lassa Fever, created by the interconnection between animals, humans, and ecosystems, and embedded in an intricate social context, should be addressed with a ‘One Health’ approach. This article provides an overview of Lassa Fever, focusing on Nigeria, and discusses the perspectives for the control of disease.
Low-Resource Time-to-Digital Converters for Field 4 Programmable Gate Arrays: A Review
Authors: Real Diego , Calvo David
Published: July 2024

A fundamental aspect in the evolution of Time-to-Digital Converters (TDCs) implemented within Field-Programmable Gate Arrays (FPGAs), given the increasing demand for detection channels, is the optimization of resource utilization. This study reviews the principal methodologies employed for implementing low-resource TDCs in FPGAs. It outlines the foundational architectures and interpolation techniques utilized to bolster TDC performances without unduly burdening resource consumption. Low-resource Tapped Delay Line, Vernier Ring Oscillator, and Multi-Phase Shift Counter TDCs, including the use of SerDes, are reviewed. Additionally, novel low-resource architectures are scrutinized, including Counter Gray Oscillator TDCs and interpolation expansions using Voltage-Temperature-Consumption stable IODELAYS. Furthermore, the advantages and limitations of each approach are critically assessed, with particular emphasis on resolution, precision, non-linearities, and, especially, resource utilization. A comprehensive summary table encapsulating existing works on low-resource TDCs is provided, offering a comprehensive overview of the advancements in the field.
Conjunctival Melanoma: A Clinical Review and Update
Authors: Butt Karam , Hussain Rumana , Coupland Sarah Ellen , Krishna Yamini
Published: July 2024

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global inci-dence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked leading to vision loss either from destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised treatment of cutaneous melanoma, which share some similarities to Co-M. A better understanding of Co-M and its precursor lesions is urgently needed to lead the development of novel targeted and immuno-therapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge of Co-M, its epidemiology, pathogenesis, presentation, diagnosis, management, and recent advances in novel biological therapies for personalised treatment of this disease.
Correction of Rectal Prolapse in an Infant through Anterior Ventral Rectopexy Laparoscopic in an Infant: A Case Report
Authors: Thomas-Olivares Pastor , Vergara-Utria Luz Caroly , Pinzón-Redondo Hernando , Fontalvo-Rivera Dilia Mildret
Published: July 2024

Background: Rectal prolapse is usually self-limiting in early childhood. Laparoscopic rectopexy has become a safe and effective method for treating children with rectal prolapse recurrence, especially those older than 4 years of age. We present the clinical case of an infant with recurrent rectal prolapse and secondary complications. The infant required surgical intervention with laparoscopic rectopexy after the failure of conservative management. Case presentation: A 2-year- and 7-month-old infant with a 15-month history of rectal prolapse who did not respond to conservative management developed bloody diarrhea, intestinal infection and electrolyte imbalance. Laparoscopic surgical correction was performed via anterior ventral rectopexy, and the results were satisfactory. Conclusion: Infants with recurrent rectal prolapse and associated complications who do not respond to conservative measures may benefit from laparoscopic rectopexy.
The Interaction Effect of Leverage and Dividend Policy on Firm Value: Empirical Evidence from Nigerian Firms
Authors: Njoku Okechukwu , Lee Younghwan
Published: July 2024

This study investigates the dynamic relationship between leverage and dividend policy in Nigerian manufacturing enterprises. Utilizing panel data from 26 firms between 2016 and 2020, our findings reveal that while dividend payments boost firm value, leverage typically diminishes it. Intriguingly, when leverage interacts with dividend policy, the combined effect on firm value becomes significantly positive. This observation, despite Nigeria's institutional differences from advanced economies, supports modern capital structure theories such as the pecking order and static trade-off theories. Our results suggest that for mature Nigerian companies with limited growth opportunities, high leverage and dividends effectively mitigate the "free cash flow" problem, curbing managerial tendencies to overinvest or underinvest. Thus, leverage and dividends serve as complementary mechanisms for monitoring and controlling managerial discretion. Consequently, firms with high leverage ratios can leverage dividend policies as disciplinary tools, and vice versa. This underscores the necessity for Nigerian manufacturing firms to carefully balance debt and equity to sustain market confidence and investment potential.
Genome-Wide Association Study (GWAS) For Left Displaced Abomasum in Highly Productive Russian Holstein Cattle
Authors: Plemyashov Kirill , Krutikova Anna , Belikova Angelina , Kuznetsova Tatiana , Semenov Boris
Published: July 2024

Left displaced abomasum (LDA) is a multifactorial disease of cattle that occurs mainly during the transition postpartum period and is characterized by a decrease in milk production and an increased risk of culling. Despite the widespread prevalence of this pathology, its etiology remains unclear. It is believed that unbalanced nutrition, disturbances in energy and calcium metabolism in the post-calving period lead to impaired motility of the gastrointestinal tract of cows. However, studies have been conducted confirming the hereditary nature of predisposition to this disease. Currently, the search for genetic determinants reliably associated with predisposition to LDA is actively underway. The aim of our study is to identify genetic associations characterizing the genomic variability of susceptibility to LDA in Holstein cattle in the Leningrad region of the Russian Federation. The object of the study was 360 highly productive dairy cows divided into two groups: with LDA and healthy ones (control). Fourteen candidate SNPs were found to be significantly associated with leftward displacement of the abomasum (P<1e-4). When performing functional annotation of genes containing associated polymorphisms or located close to them, candidate genes presumably associated with the development of LDA were identified: ABCB11, SRP72, RGS18, SOX4, GSG1L, FBXL19, PNPLA4.
Variation of External and Internal Intensities, and Impact of Maturational Age on Soccer Training Tasks
Authors: García-Ceberino Juan M. , Cantonero-Cobos José Manuel , Conde Cristina , Fernández-Ozcorta Eduardo J.
Published: July 2024

During the peak height velocity, it is crucial to adjust training intensity to optimize performance and minimize injury risk. This cross-sectional study compared external and internal intensities according to the type of training task (i.e., analytical tasks, small-sided games, and training matches). Similarly, the effect of these training tasks on the maturation age of young players was analyzed. Fifty-five U-15 and U-16 boys, representatives of two soccer clubs in southwestern Spain, were monitored using inertial measurement units and heart rate monitors. These devices reported data on training intensities. Their anthropometric data were also taken, along with the date of birth and measurement, to estimate the maturation age. To identify specific differences between groups, the nonparametric Friedman test and pairwise comparisons were performed using the Durbin-Conover post-hoc test. In addition, Spearman's rank correlation coefficients were calculated to better understand the impact of the variables. There were significant differences in favor of training matches in distance covered, maximum and average speed, and maximum and average heart rate compared to small-sided games and analytical tasks. In addition, high intensity actions and sprints were significantly higher during training matches compared to analytical tasks, and during small-sided games compared to analytical tasks. Player Load per minute was significantly higher during training matches compared to small-sided games, and during small-sided games compared to analytical tasks. Maximum speed, and maximum and average heart rate were also significantly higher during small-sided games compared to analytical tasks. Positive correlations between maturational age and high-intensity actions, accelerations, and decelerations were found, indicating higher intensity activities in more mature players. A negative correlation between Player Load per minute and maturational age suggests more efficient load management in mature players. No significant differences were found in distance per minute, sprints, speed, and heart rate, implying other factors influence these variables. These findings underscore the importance of considering biological maturation and the variability of training tasks in the planning and evaluation of the development and performance of youth athletes.
Integration of Automatic Test Generators For Maximizing the Code Coverage Level
Authors: Jakovljević Ivan , Radovan Aleksander
Published: July 2024

This paper explores the development of a sophisticated system for automatic test generation tailored specifically for Java web applications utilizing REST interfaces. Writing tests ensures the quality of the software solution event after the introduction of subsequent changes, because automated regression testing can detect potential bugs in the code event before the application is resealed into production. By utilizing and comparing various automatic test generators, the system described provides users with a visual representation of code structure and coverage, enhancing insights through call graph visualization. The paper describes the concepts of theoretical automatic test generators, gives an overview of generators, and details the design and implementation of the implemented solution, which integrates the system test generator and the unit test generator based on open source to achieve the maximum code coverage level.
Controlling the Shape of a Double DNA-like Helix as an Element of Metamaterials
Authors: Semchenko Igor V , Mikhalka Ivan S , Samofalov Andrey L , Khakhomov Sergei A
Published: July 2024

A simulation is performed to analyze the forces that arise in a conducting DNA-like double helix in the field of a microwave electromagnetic wave under half-wave resonance conditions. The helix is comprised of twenty-and-a-half turns and has geometric parameters proportional to the size of an actual DNA molecule. The forces acting on the strands of a double helix, both in the central region and at the edges of the helix, are investigated. It has been demonstrated that the afore-mentioned forces induce a change in the shape of the helix, specifically mutual repulsion of the strands, as well as their stretching and twisting in the field of electromagnetic waves. As opposed to a pair of parallel straight conductors, there is a radial repulsion of strands in all regions of a double DNA-like helix, including the center and the edges. This unique interaction of currents in a double DNA-like helix can be attributed to its pitch angle, a characteristic that has been estab-lished through empirical evidence. Consequently, exposure to an electromagnetic wave under half-wave resonance can damage the double helix. Conversely, the impact of electromagnetic waves has the potential to introduce novel avenues for controlling the shape of the double helix. These nonlinear effects must be considered for both actual DNA molecules and double DNA-like helices that serve as components of metamaterials and metasurfaces.