bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in the Epilimnion Ciliate Assemblage Reflect the Reduction of the Nutrient Load of the Reservoir for Two Decades
Authors: Macek Miroslav , Vrba Jaroslav , Hejzlar Josef , Řeháková Klára , Jarošík Jiří , Šorf Michal
Published: May 2024

The awareness of ciliate importance in freshwater has changed dramatically in the last decades, reflecting methodological attempts. We analysed two decades (1994-2018) of data on the surface (0-3 m) ciliate assemblage in the Slapy reservoir (Vltava River, Czech Republic) during two different nutrient-load defined periods. We identified, quantified, and evaluated the biomass of ciliates in the quantitative protargol-stained preparations. We used water age, nutrients, bacteria, heterotrophic nanoflagellates and rhodomonads as the main explanatory background variables. The sampling median and interquartile range data analysis and a non-metric multidimensional scaling were applied. Ciliates were grouped according to their feeding behaviour. The picoplankton filtering species dominated the assemblages in an annual mean (halteriids and minute strobilidiids followed by peritrichs). Algae hunters Balanion planctonicum, urotrichs and nanoplankton filtering tintinnids were important before the spring phytoplankton peak when a maximum of ciliate biomass reflected mixotrophic nanoplankton filtering pelagostrombidiids. Only there, ciliate biomass tightly followed their quantified prey. Heterotrophic and mixotrophic Askenasia and Lagynophrya were typical raptorial/flagellate hunters; only Mesodinium spp. peaked during autumn. The oligotrophication increased the ciliate assemblage biomass in the surface layer during the stratification in concordance with the PEG model.
Humanization of pan-HLA-DR mAb 44H10 Hinges on Critical Residues in the Antibody Framework
Authors: Kassardjian Audrey , Ivanochko Danton , Barber Brian , Jetha Arif , Julien Jean-Philippe
Published: May 2024

Reducing the immunogenicity of animal-derived monoclonal antibodies (mAbs) for use in humans is critical to maximize therapeutic effectiveness and preclude potential adverse events. While traditional humanization methods have primarily focused on grafting antibody Complementarity-Determining Regions (CDRs) on homologous human antibody scaffolds, framework regions can also play essential roles in antigen binding. Here, we describe the humanization of the pan-HLA-DR mAb 44H10, a murine antibody displaying significant involvement of the framework region in antigen binding. Using a structure-guided approach, we identify and restore framework residues that directly interact with the antigen or indirectly modulate antigen binding by shaping the antibody paratope and engineer a humanized antibody with affinity, biophysical profile, and molecular binding basis comparable to that of the parental 44H10 mAb. As a humanized molecule, this antibody holds promise as a scaffold for the development of MHC class II-targeting therapeutics and vaccines.
The Role Of Oxidative Stress As A Mechanism In The Pathogenesis Of Heart Failure In Acute Kidney Injury
Authors: Tasic Danijela
Published: May 2024

Despite a large amount of research on synchronous and mutually induced kidney and heart damage, the basis of the disease is still not fully clarified. Healthy mitochondria are essential for normal kidney and heart function. Mitochondrial dysfunction occurs when the clearance or process of generation and fragmentation of mitochondria is disturbed. The kidney is the second organ after the heart in the number of mitochondria. Kidney tubules are rich in mitochondria due to the high energy requirements for absorption processes of large amounts of ultrafiltrate and dissolved substances.
The place of action of oxidative stress is the influence on the balance in the production and breakdown of mitochondrial reactive oxygen species .
A more precise determination of the place and role of key factors that play a role in the onset of the disease is necessary for understanding the nature of the onset of the disease and the creation of therapy in the future.
The narrative review integrates results found in previously performed studies which have evaluated oxidative stress participation in renocardial syndrome type 3.
Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice
Authors: Simão Jussara de Jesus , Bispo Andressa França de Sousa , Plata Victor Tadeu Gonçalves , Armelin-Correa Lucia Maria , Cardoso Alonso Vale Maria Isabel
Published: May 2024

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.
Looking beyond Traditional Drivers: Climate Effects on Eurozone Sovereign Yields
Authors: Palaios Panagiotis , Leventis Flora
Published: May 2024

In the present study we examine the relationship among sovereign yields, temperature and precipitation using a large monthly panel data set which consists of 20 eurozone members, over the period 1980M1 – 2023M4. To account for possible asymmetries along the distribution of the climate variables we assume a quadratic modelling specification and apply various mean panel estimation techniques of heterogeneous coefficients. At a next step, to consider possible nonlinearities in the distribution of the dependent variable (sovereign yields), we apply the quantile via moments methodology of Machado and Santos Silva (2019), which accounts for possible cross-sectional dependence and slope heterogeneity. We contribute to the existing literature in two main ways. First, by applying a quantile methodology that provides a more in-depth analysis of the climate effects along the distribution of the sovereign yields, especially in the presence of non-normally distributed data. Second, we find that climate change, as proxied by higher temperatures or lower precipitation (drought), will increase the sovereign risk of all countries, but the magnitude of the impact will be higher for countries that are already characterized by higher sovereign risk levels and/or face extreme weather conditions (hotter countries and/or countries with low levels of precipitation).
In Silico Electrophysiological Investigation of Transient Receptor Potential Melastatin-4 Ion Channel Biophysics to Study Detrusor Overactivity
Authors: Mahapatra Chitaranjan , Thakkar Ravindra
Published: May 2024

Enhanced electrical activity in detrusor smooth muscle (DSM) cells is a key factor in detrusor overactivity which causes overactive bladder pathological disorders. Transient receptor potential melastatin-4 (TRPM4) channels, calcium-activated cation channels, play a role in regulating DSM electrical activities. These channels likely contribute to depolarizing the DSM cell membrane, leading to bladder overactivity. Our research focuses on understanding TRPM4 channel function in mouse DSM cells using computational modeling. We aimed to create a detailed computational model of the TRPM4 channel based on existing electrophysiological data. We employed a modified Hodgkin-Huxley model with an incorporated TRP-like current to simulate action potential firing in response to current and synaptic stimulus inputs. Validation against experimental data showed close agreement with our simulations. Our model is the first to analyze the TRPM4 channel's role in DSM electrical activity, potentially revealing insights into bladder overactivity. In conclusion, TRPM4 channels are pivotal in regulating human DSM function and TRPM4 channel inhibitors could be promising targets for treating overactive bladder.
Function of the NAC1 Gene from Fraxinus mandshurica in Cold Resistance and Growth Promotion in Tobacco
Authors: Cao Yang , He Liming , Peng Guangzhou , Li Boyao , Wang Yuling , Zhang Chenxi , Zhang Ye , Zhan Yaguang
Published: May 2024

To elucidate the function of the cold resistance regulatory gene FmNAC1 from Fraxinus mandshurica, this study identified the role that the overexpression of the FmNAC1 gene plays in tobacco growth and cold stress regulation. The cloned FmNAC1 gene from F. mandshurica is 891 bp in length and encodes 296 amino acids. Our subcellular localization analysis confirmed that FmNAC1 is primarily located in the nucleus and functions as a transcription factor. FmNAC1 is responsive to cold and NaCl stress, as well as to the induction of IAA, GA, and ABA hormone signals. To further elucidate its function in cold resistance, four transgenic tobacco lines of FmNAC1 overexpression（FmNAC1-OE）were generated through tissue culture after the agrobacterium-mediated transformation of wild-type (WT) tobacco. These FmNAC1-OE plants exhibited accelerated growth after transplantation. When exposed to low-temperature conditions at -5°C for 24 hours, the rates of wilting and yellowing of the FmNAC1-OE plants were significantly lower than those of the WT tobacco plants. Additionally, the membrane integrity, osmotic regulation, and reactive oxygen species (ROS)-scavenging abilities of the FmNAC1-OE tobacco lines were better than those of the WT plants, indicating the potential of the FmNAC1 gene to improve plant cold resistance. The gene expression results further revealed that the FmNAC1 transcription factor exhibits regulatory interactions with growth-related genes such as IAA and AUX1; cold resistance-related genes such as ICE, DREB, and CBF1; and genes involved in the clearance of reactive oxygen species (ROS), such as CAT and SOD. All of this evidence shows that the FmNAC1 transcription factor from F. mandshurica plays a key role in contributing to the enhancement of growth, cold resistance, and ROS clearance in transgenic tobacco plants.
Iteratively Refined Multi-Channel Speech Separation
Authors: Zhang Xu , Bao Changchun , Yang Xue , Zhou Jing
Published: May 2024

The combination of neural network and beamforming has been proved to be very effective in multi-channel speech separation. But its performance faces a challenge in complex environment. In this paper, an iteratively refined multi-channel speech separation method is proposed for the challenge, where the proposed is composed of initial separation and iterative separation. In initial separation, the time-frequency domain dual-path recurrent neural network neural network (TFDPRNN), minimum variance distortionless response (MVDR) beamformer and post-separation (also TFDPRNN) are cascaded for obtaining the first additional input in iterative separation. In iterative separation, the MVDR beamformer and post-separation are iteratively used, where the output of the MVDR beamformer is used as an additional input of the post-separation network and the final output comes from post-separation module. This iteration of the beamformer and post-separation is fully employed for promoting their individual optimization, which ultimately improves the overall performance of speech separation in multi-speaker scenarios. Experiments on the spatialized version of the WSJ0-2mix corpus show that our proposed method is significantly better than the current popular methods. In addition, the method also has a good effect on the dereverberation task.
A New Approach for Understanding International Hospital Bed Numbers and Application to Local Area Bed Demand and Capacity Planning
Authors: Jones Rodney P
Published: May 2024

A new model for international bed numbers is applied to local area populations for English Clinical Commissioning Groups (CCGs) where the Age Standardized Mortality Rate (ASMR) is used as a measure of population health and hence for total occupied hospital bed demand (elective plus emergency admission types, including acute, rehabilitation, mental health, and maternity), rather than simple bed availability. A 100-unit increase in ASMR (European Standard population) leads to a 15.3 – 30.7 (feasible range) unit increase in occupied beds per 1,000 deaths. ASMR shows why the Australian states of the Northern Territory and Tasmania have an intrinsic higher bed demand than the other states – although in both cases the bed planning methodologies failed to indicate this need and both states show a large bed deficit. Due to the high volatility in bed demand the average bed demand for 2019 was determined by a linear trend using data for 2014/15 to 2019/20 — as the pre-COVID-19 baseline. The slope of the relationship between occupied beds per 1,000 deaths and deaths per 1,000 population shows a power law function. As is to be expected there is scatter around the trend line which will partly arise from uncertainty in the expected occupied beds in 2019, fluctuations in both ASMR and deaths per 1,000 population from one year to another, changes in the number of persons on the elective, outpatient and diagnostic waiting lists, and local area variation in births and consequently upon maternity, neonatal and pediatric bed demand. Additional variation in bed demand will arise from differences in the level of funding for social care, especially elderly care, and to a lesser extent upon patients using private health care, and charitable hospices for palliative care. However, after including the change in bed demand arising from ASMR the model is sufficiently accurate to identify gross differences in bed demand as a prelude to further investigation. The model requires further extension to cover specialty-level demand, and perhaps segregation between elective and emergency types of inpatient demand. A method for benchmarking the whole hospital’s average bed occupancy is given which enables them to run at optimum efficiency and safety. Using this method English hospitals can be shown to operate at highly disruptive and unsafe levels of bed occupancy leading to deleterious ‘turn-away’. Turn-away implies bed unavailability for the next arriving patient. The problems associated with crafting effective bed planning are illustrated using the English NHS as an example.
Multisensory Eating Experiences in Northern Norway: An Exploratory Study
Authors: Tran Huy , Veflen Nina , Jørgensen Eva , Velasco Carlos
Published: May 2024

Intrinsic and extrinsic sensory elements influence our food experiences. However, most research in extrinsic multisensory aspects of food has centered on WEIRD (White, Educated, Industrialized, Rich, and Democratic) urban participants. This study breaks from this by investigating multisensory eating experiences in the context of Northern Norway, a region characterized by distinct seasonal shifts, harsh arctic weather, unique atmospheric phenomena (e.g., the midnight sun and northern lights), limited food growth opportunities, and a rich Sámi cultural heritage. Our exploratory research used participant observation and interviews, involving four researchers from diverse backgrounds who closely examined multisensory food experiences within four Northern Norwegian food-related tourism businesses, all infused with Sámi cultural elements. Four themes emerged: 1) Experience elements, involving elements associated with plants, animals, and non-animate objects. 2) Bipolar concepts, which refer to contradicting dimensions where experience elements varied, notably in the interplay between Sámi and Norwegian traditions. 3) Sensory stories, which highlight the narratives, enriching the eating experience with context, such as tales of dining under the captivating northern lights. 4) Values which indicate guiding principles shaping these experiences on a broader scale, emphasizing support for local traditions and culture. Our main contribution is the presentation of a new contextual framework of multisensory eating experiences which can be applicable to studying eating experiences in other contexts.
Patient Privacy Protection Maturity Evaluation Framework
Authors: GÜRSEL Güney , BAYER Nükhet , TURUNÇ Ömer , ÇALIŞKAN Abdullah , AKKOÇ İrfan , DEMİRCİ Ayhan , ÇETİN Melike , KÖROĞLU Özlem
Published: May 2024

Background: With the rapid improvement of the healthcare technologies, security and privacy of the most sensitive data, health data is at risk. Protecting patient privacy has many components, even though the data are in electronic format. Although patient privacy is thoroughly discussed in the literature, there is no study presenting all components of patient privacy protection. Methods: In this study, a complete evaluation framework is presented, as an evaluation tool, an inventory is developed, reliability and validity of the inventory is examined. Study is conducted in three phases: Conceptual framework development, inventory development and an evaluation case study. In the evaluation, fuzzy conjoint analysis is employed to handle the subjectivity and am-biguity. As the result of the evaluation, the institution is given a patient privacy protection ma-turity grade, between 1 and 5, where 1 is the worst and 5 is the best grade. Results: In the case study, XXX’s biggest hospital, employing 800 nurses, is evaluated. Half of the nurses, 400, have partici-pated in the study. Literature tells healthcare institutions do not invest enough to protect patient privacy, and the study results support this finding. Institution’s maturity grade resulted as level 2, which is bad. Conclusion: The study measures he privacy maturity with many evaluation com-ponents. Result of the evaluation explains to the patients and the public if their data is safe or not. With this maturity grade, patients have an idea about which institution to choose, public can conclude the institutions’ reliability in terms of patient privacy.
Revalidation of DNA Fragmentation Analyses for Human Sperm—Measurement Principles, Comparative Standards, Calibration Curve, Required Sensitivity, and Eligibility Criteria for Test Sperm—A Step-by-Step Approach to Cohort Studies with Multivariable Analyses
Authors: Kaneko Satoru , Okada Yuki
Published: May 2024

(1) Background: Double-strand breaks (DSBs) in a single nucleus are usually measured using the sperm chromatin structure assay (SCSA), sperm chromatin dispersion (SCD) test, and comet assay (CA). We developed mono-dimensional single-cell pulsed-field gel electrophoresis (1D-SCPFGE) and angle-modulated two-dimensional single-cell pulsed-field gel electrophoresis (2D-SCPFGE) to observe DNA fragmentation in separated motile sperm. (2) Methods: We set up comparative standards, calibration curves, the required sensitivity, and eligibility criteria for test sperm to validate their measurement principles. (3) Results: We revealed that the conventional methods overlooked the interference of nucleoproteins in their measurements. In-gel proteolysis improves the measurement accuracies of 1D- and 2D-SCPFGE. We recommend using naked DNA for comparative standards and test specimens. Moreover, we have observed several dysfunctions that may induce DNA damage in the separated motile sperm. Overall, our discussion highlights the need to revisit the conventional univariable analyses based on the SCSA, SCD test, and CA.
(4) Conclusions: Human infertility is a complex syndrome, and the aim of quality control in intracytoplasmic sperm injection is to identify the underlying dysfunctions remaining in the separated motile sperm that render them ineligible for injection. Well-designed, multivariable analyses with special consideration to confounding factors are necessary in future cohort studies.
Does Climate Change and Energy Consumption Affect the Food Security of European Union Countries? Empirical Evidence from a Panel Study
Authors: Łącka Irena , Suproń Błażej , Szczepaniak Iwona
Published: May 2024

This study aims to provide empirical evidence on whether using renewable and non-renewable energy, CO₂ emissions and the resulting changes in temperature and precipitation can alter cereal yields in European Union countries. To this end, a panel data set covering 1992-2021 has been used to analyse the impact of climate change and economic factors on cereal production in European Union countries. The study employed various analytical techniques to understand better the relationship between climate change, energy consumption, and economic growth. These included using annual average temperature and rainfall to measure climate change and energy consumption and economic growth to analyse the economic aspects. To achieve the objective, feasible generalised least squares (FGLS) models with robust standard errors and bootstrap and a quantile regression (QR) model with marginal analysis were employed. The Westerlund cointegration test confirmed the presence of cointegration between cereal production and climate variables, economic growth, and energy consumption. The results indicate that increases in temperature and precipitation may contribute to increased cereal production in European Union countries. In contrast, energy consumption, including renewable energy and CO₂ emissions, may have a nonlinear effect on cereal production. Quantile regression analysis suggests climate change may impact crop yields most in countries with low and moderate cereal production per hectare. Increased CO₂ emissions may increase yields in the initial period, but excessive CO₂ may negatively impact cereal production in the long term. It would be advisable for countries with low and moderate crop productivity to consider implementing technological advances and combating global warming by modernising cultivation methods and making greater use of renewable energy sources.
Molecular Characterization and Risk Factors Associated with Rotavirus among Children with diarrhoea.
Authors: Demekong Gilbert Konlak , Onu Euslar Nnenna , Okorie Nnaemeka , Ituma Azi Cornelius , Udoh Ubong Aniefiok , Uchechukwu Okparaoka Samuel , Ochang Ernest Afu , Okparaoka Chisom Vivian , Akpa Chinedu Obasi , Agada Samuel Oleojo , Okechukwu Ogbonna Emmanuel , Ogbu Ogbonnaya
Published: May 2024

Introduction:
Rotavirus-induced acute diarrhoea continues to pose a significant health threat to children under 5 years old worldwide, despite the availability of effective vaccines. This study aimed to assess the prevalence, associated risk factors, and circulating genotypes of rotavirus among children under 5 admitted to Ikom Medical Centre due to diarrhea. Methodology: Stool samples were collected from 294 children under 5 with diarrhoea at Ikom Medical Centre. Rotavirus antigen detection was performed using rapid chromatographic immunoassay. Molecular techniques such as polyacrylamide gel electrophoresis (PAGE), RT-PCR, and semi-nested multiplex RT-PCR were used to analyze rotavirus strains. Data were obtained through questionnaires, and statistical significance was assessed using the chi-square test (P < 0.05). Results: Among the 294 samples, 20.4% (60/294) tested positive for rotavirus. Significant risk factors influencing rotavirus prevalence included feeding status, toilet system, and duration of diarrhoea. The most prevalent genotype for VP7 was G4 (26.7%), and for VP4, it was genotype P[4] (23.3%). Predominant genotype combinations were G4P [4] (11.6%) and G12P[4] (6.7%), while non-typeable P[NT] was observed in 41.7% of cases. Conclusion: This study highlights the circulation of rotavirus in Ikom, Cross River State, emphasizing its neglected status despite its significant global impact on child mortality. Urgent attention is needed to address rotavirus as a serious public health concern, particularly in low-resource settings.
Immunohistochemical Analysis of Dentigerous Cysts & Odontogenic Keratocysts Associated with Impacted Third Molars: A Systematic Review
Authors: Almeida Luis Eduardo , Loyd David , Boettcher Daniel , Kraft Olivia , Zammuto Samuel
Published: May 2024

Objective: This systematic review investigates the diagnostic, prognostic, and therapeutic implications of immunohistochemical markers in dentigerous cysts (DC) and odontogenic keratocysts (OKC) associated with impacted third molars. Materials and Methods: A comprehensive search strategy was employed across major databases including MEDLINE/PubMed, EMBASE, and Web of Science, from the inception of the databases to March 2024. Keywords and Medical Subject Heading (MeSH) terms such as "dentigerous cysts," "odontogenic kerato-cysts," "immunohistochemistry," "Ki-67," and "p53" were used. The PRISMA 2020 guidelines were followed to ensure methodological rigor. Inclusion criteria encompassed studies on humans and animals providing de-finitive diagnoses or specific signs and symptoms related to DC and OKC, with results on protein expression derived from immunohistochemistry, immune antibody, proteomics, or protein expression methods. Results: Of the 159 studies initially identified, 138 met the inclusion criteria. Our analysis highlighted sig-nificantly higher expressions of Ki-67 (22.1% ± 4.7 vs. 10.5% ± 3.2, p < 0.001), p53 (15.3% ± 3.6 vs. 5.2% ± 1.9, p < 0.001), and Bcl-2 (18.4% ± 3.2 vs. 8.7% ± 2.4, p < 0.001) in OKCs compared to DCs, indicating a higher proliferative index, increased cellular stress, and enhanced anti-apoptotic mechanisms in OKCs. Ad-ditionally, PCNA levels were higher in OKCs (25.6% ± 4.5 vs. 12.3% ± 3.1, p < 0.001). Genetic mutations, particularly in the PTCH1 gene, were frequently observed in OKCs, underscoring their aggressive behavior and potential malignancy. Conclusion: The findings emphasize the significant role of immunohistochemical markers in distinguishing between DCs and OKCs, with elevated levels of Ki-67, p53, Bcl-2, and PCNA in OKCs suggesting a higher potential for growth and recurrence. Genetic insights, including PTCH1 mutations, further support the need for personalized treatment approaches. These markers enhance diagnostic accuracy and inform targeted thera-peutic strategies, potentially transforming patient management in oral and maxillofacial surgery.
Can the Necrophagous Blow Fly Calliphora vicina (Diptera: Calliphoridae) Be Reared on Plant-Based Meal?
Authors: Cook David F. , Tufail Muhammad Shoaib , Voss Sasha C.
Published: May 2024

The oviparous blow fly Calliphora vicina has shown potential as a managed pollination species to support honeybee (Apis mellifera) usage in Australian horticulture. This blow fly species lays eggs onto carrion soon after death and the resultant larvae that hatch are necrophagous and feed on the decomposing tissues of the dead animal. Newly hatched larvae of this fly were provided with plant-based meals (soya bean and canola) and compared with animal-derived meatmeal to determine if plant-based meal could be used to mass rear this blow fly species. Both soyabean and canola meal media did not support the survival of any larvae through to adult eclosion. The addition of only 10% whole egg powder to the plant-based meals enabled survival to eclosion of 39% and 13% on soyabean and canola based medias respectively compared with 76% on animal-based meatmeal with 10% whole egg powder. Larvae fed livestock meatmeal with 10% whole dried egg powder had the fastest development to the pupal stage, the highest pupation rate, the heaviest pupae and the highest subsequent adult eclosion. This study concluded that the use of plant-based meals in the mass rearing of the blow fly C. vicina was neither viable, nor economically viable.
X-ray Single-Crystal Analysis, Pharmaco-Toxicological Profile and Enoyl-ACP Reductase Inhibiting Activity of Leading Sulfonyl Hydrazone Derivatives with Potent Antimycobacterial Activity
Authors: Teneva Yoanna , Simeonova Rumyana , Besarboliev Orlin , Sbirkova-Dimitrova Hristina , Angelova Violina T.
Published: May 2024

Taking into consideration the arising resistance towards the currently available antimycobacterial, there is still an unmet need for the development of new chemotherapeutic agents to combat the infectious agent. This study presents the X-ray single-crystal analysis to verify the structure of leading sulfonyl hydrazone 3b, which have proven their potent antimycobacterial activity against Mycobacterium tuberculosis H37Rv with MIC value of 0.0716 μM, respectively, low cytotoxicity and very high selectivity indexes (SI=2216) and fully characterized by NMR and HRMS methods. Furthermore, this study assessed the ex vivo antioxidant activity, acute and subacute toxicity, and in vitro inhibition capacity against enoyl-ACP reductase of hydrazones 3a and 3b, as 3a was identified as the second leading compound in our previous research. Compared to isoniazid, compounds 3a and 3b demonstrated lower acute toxicity for intraperitoneal administration, with LD50 values of 866 and 1224.7 mg/kg, respectively. Subacute toxicity tests, involving the repeated administration of a single dose of the test samples per day, revealed no significant deviations in hematological and biochemical parameters or pathomorphological tissues. The compounds exhibited potent antioxidant capabilities, reducing malondialdehyde (MDA) levels and increasing reduced glutathione (GSH). Enzyme inhibition assays of the sulfonyl hydrazones 3a and 3b with IC50 values of 18.2 µM and 10.7 µM, respectively and molecular docking studies revealed enoyl acyl carrier protein reductase (InhA) as the possible target enzyme of the compounds to show their antitubercular activities. In conclusion, the investigated sulfonyl hydrazones display promising antitubercular drug-like properties and warrant further investigation.
Facile Access to Solifenacin Impurity K: One-Step Synthesis and an HPLC-MS Method for Its Determination
Authors: Xifra Raúl , Turcu Andreea L.
Published: May 2024

Solifenacin (SFC) is a potent muscarinic antagonist that effectively reduces bladder muscle contraction, thereby alleviating symptoms such as frequency of micturition and urgency. Oxidation of SFC leads to the formation of impurities like Impurity K. Effective analysis and control of this impurity is crucial for ensuring compliance with regulatory standards and safeguarding patient health. To address these challenges, we propose a novel one-step synthesis of Impurity K from SFC. Impurity K was synthesized using cerium ammonium (IV) nitrate (CAN) in water/acetonitrile as the solvent. Additionally, we describe a new HPLC-MS method for the detection of Impurity K in solifenacin succinate tablets.
Exploring the Stress and Resilience Levels of Dental and Nursing Students in Response to Academic Responsibilities
Authors: Mangoulia Polyxeni , Kanellopoulou Antonia , Manta Georgia , Chrysochoou Georgios , Dimitriou Evangelos , Kalogerakou Theodora , Antoniadou Μaria
Published: May 2024

Students studying dentistry and nursing experience anxiety daily, which affects both their general well-being and academic achievement. Anxiety is exacerbated by several circumstances, such as stressors in one's personal life, clinical environment exposure, and academic expectations. To effectively regulate anxiety and support students' achievement, treatments that take these elements into account must be designed. In this study, 271 students from the National and Kapodistrian University of Athens, Greece's departments of dentistry and nursing were polled. Being the following resources, participants filled out an electronic questionnaire that was uploaded to Google Forms and assessed their levels of stress, anxiety, depression, resilience, hope, and spiritual well-being: a) the Depression, Anxiety, Stress Scale (DASS-21), b) the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-12), c) the Adult Hope Scale (AHS), d) the Resilience Assessment Questionnaire (RAQ8), and e) the Brief Resilience Scale (BRS). Additionally, demographic data was gathered, such as gender, educational attainment, family income, and country of origin. Statistical analyses were performed to investigate the relationships between the variables, including hierarchical multiple linear regression and t-tests. The sample consisted of 271 students from the Department of Nursing (n=126, 46.5%) and Dentistry (n=145, 53.5%), with 68.60% of them being female, 80.10% being undergraduate students, and 48.30% being from Athens, the country's capital. Comparatively speaking, 74.50 percent of nursing students were female, while 62.80% of dental students were. Compared to dental students (2.10%), nurses (40.50%) participated in postgraduate studies at a higher rate. Compared to dental students (44.80%), nursing students reported a household income of just 13.90%, which is much less than €35,000. Anxiety was reported by 51.30% of participants overall, with dental students reporting higher anxiety than nursing students. Higher family wealth was associated with reduced stress levels, while female undergraduate students reported higher levels of anxiety than their male counterparts. Hope was a strong predictor of resilience, but stress and worry had a negative correlation. Promoting students' well-being and academic success requires effective stress-reduction and resilience-building techniques aimed to not only improve student performance but also support future healthcare professionals' personal sustainability and holistic growth.
Plasma-Sprayed Osseoconductive Hydroxylapatite Coatings for Endoprosthetic Hip Implants: Phase Composition, Microstructure, Properties, and Biomedical Functions
Authors: Heimann Robert Bertram
Published: May 2024

This contribution attempts to provide a state-of-the-art account on the physicochemical and biomedical properties of plasma-sprayed hydroxylapatite (HAp) coatings that are routinely applied to the surfaces of metallic endoprosthetic and dental root implants, designed to replace or restore lost functions of diseased or damaged tissues of the human body. Even though the residence time of powder particles of HAp in the plasma jet is extremely short, the high temperature applied introduces compositional and structural changes of the precursor hydroxylapatite that severely affect its chemical and physical properties and in turn, its biomedical performance. These changes are based on the incongruent melting behaviour of HAp and can be traced, among many other analytical techniques, by high-resolution synchrotron X-ray diffraction, vibrational (Raman), and nuclear magnetic resonance (NMR) spectroscopies. In vivo reactions of the plasma-sprayed coatings with extracellular fluid (ECF) can be assessed and predicted by in vitro testing using simulated body fluids as proxy agents. Ways are being discussed to safeguard appropriate biological performance of hydroxylapatite coatings in long-term service by controlling their phase content, porosity, surface roughness, residual stress distribution, and adhesion to the implant surface.
Three-Dimensional Exploding Light Wave Packets
Authors: Barriopedro Marcos G. , Porras Miguel A. , Holguín Manuel , Lara-Montoya Pablo de , Mata-Cervera Nilo
Published: May 2024

We describe a family of paraxial and quasi-monochromatic optical wave packets with finite energy and smoothly shaped amplitude in space and time that develops a singularity in the intensity when spatiotemporally focused by imparting a converging spherical wave front and a negative temporal chirp. This singular behavior upon ideal focusing is manifested in actual focusing with finite apertures and in media with high-order dispersion in an "exploding" behavior featuring indefinitely increasing concentration of the energy when opening the aperture radius, thus exercising a continuous control on the focal intensity and spatial and temporal resolution. These wave packets offer a new way of focusing that outperforms what can be achieved with standard Gaussian wave packets in terms of focal intensity and resolution, and new possibilities in applications where energy concentration and its control are crucial.
Influence of Vermicompost on the Concentration of Exogenous Indole-3-Acetic Acid and Its Effect on the Development of Tomato Plants (Lycopersicum esculentum L.)
Authors: Segura-Castruita Miguel Ángel , Valdivia-Dávila Mariano Ángel , Yescas-Coronado Pedro , Gómez-Leyva Juan Florencio , Cueto-Medina Saraí
Published: May 2024

Exogenous auxins such as indole-3-acetic acid (IAA) can modulate the effect of a plant's endogenous auxins. The objectives of this work were to quantify the concentration of IAA in sand-based substrates with vermicompost (S-VC), to establish the relationship between the concentration of exogenous IAA and the amount of vermicompost (VC), as well as determine its influence on the development of tomato plants. S-VC substrates with different percentages based on volume (0, 20, 40 and 50% VC) placed in pots, with five replicates and randomly distributed, were used to transplant tomato seedlings. In each substrate, the concentration of IAA was determined at the beginning and at the end of a culture cycle, as well as the microbial load; In addition, some performance components were measured in the plants. The results showed that gram-positive bacteria were found in the substrates with VC, whose colony-forming units were related to the concentration of IAA and the amount of VC in the substrates. Therefore, the IAA concentration presented a linear and positive relationship with the amount of VC in the substrates (R2 = 0.9171, at the beginning and R2 = 0.9712, at the end of the experiment).
Alternative DNA Markers to Detect Guam-Specific CRB-G (Clade I) Oryctes rhinoceros (Coleoptera: Scarabaeidae) Indicate That the Beetle Did Not Disperse from Guam to the Solomon Islands or Palau.
Authors: Tay Wee Tek , Marshall Sean D.G. , Popa-Baez Angel David , Dulla Glenn F.J. , Blas Andrea L , Sambiran Juniaty W , Hosang Meldy , Millado Justine Bennette H. , Melzer Michael , Rane Rahul V , Hogarty Tim , Cho Demi Yi-Chun , Alouw Jelfina C , Faheem Muhammad , Hoffmann Ben
Published: May 2024

A partial mitochondrial DNA Cytochrome Oxidase subunit I (mtCOI) gene haplotype variant of the coconut rhinoceros beetle (CRB) Oryctes rhinoceros classed as ‘CRB-G (clade I)’ has been the focus of much research since 2007 with reports of invasions into new Pacific Island locations (e.g., Guam, Hawaii, Solomons Islands). For numerous invasive species, inference of invasion biology via whole genome is superior to assessments via the partial mtCOI gene. Here, we explore CRB draft mitochondrial genomes (mitogenomes) from historical and recent collections, with assessment focused on individuals associated within the CRB-G (clade I) classification. We found that all Guam CRB individuals possessed the same mitogenome across all 13 protein coding genes and differed from individuals collected elsewhere, including ‘non-Guam’ individuals designated as CRB-G (clade I) by partial mtCOI assessment. Two alternative ATP6 and COIII partial gene primer sets were developed to enable distinction between CRB (clade I) that invaded Guam and CRB-G (Clade I) individuals collected elsewhere. Phylogenetic analyses based on concatenated ATP6-COIII genes showed that only Guam CRB-G (clade I) individuals clustered together, and therefore Guam was not the source of the CRB that invaded the other locations in the Pacific assessed in this study. The use of the mtCOI and/or mtCOIII genes for initial molecular diagnosis of CRB remained crucial, and assessment of more native CRB populations will further advance our ability to identify the provenance of CRB invasions being reported within the Pacific and elsewhere
Ceftazidime-Avibactam Use in a Cohort of Children with Complex Chronic Conditions: Effectiveness and Absence of Resistance Development Following Difficult-to-Treat or Recurrent Infections
Authors: García-Boyano Miguel , Alós Díez María , Fernández Tomé Lorena , Escosa-García Luis , Moreno Ramos Francisco , Schuffelmann-Gutiérrez Cristina , Cendejas Bueno Emilio , Calvo Cristina , Baquero-Artigao Fernando , Frauca Remacha Esteban
Published: May 2024

The prevalence of multidrug-resistant Gram-negative infections, particularly carbapenem-resistant strains, has become a significant global health concern. Ceftazidime-avibactam (CZA) has emerged as a promising treatment option. However, data on its efficacy and safety in children are scarce, necessitating further investigation. We conducted a retrospective study at a tertiary hospital in Spain from February 2019 to January 2022. Pediatric patients (<16 years) treated with CZA for confirmed or suspected multidrug-resistant Gram-negative infections were included. Clinical and microbiological characteristics, treatment approaches, and outcomes were examined. Eighteen children received CZA treatment. All had complex chronic conditions, with the most frequent underlying main diseases being liver transplantation (n=8) and biliary atresia (n=4). The predominant type of infection for which they received CZA was intra-abdominal infections caused or suspected to be caused by OXA-48-producing Klebsiella pneumoniae. CZA was generally well tolerated. Within the first month of starting CZA therapy, 2 patients died, with one case directly linked to the infection’s fatal outcome. Some patients needed repeated courses of therapy due to recurrent infections, yet no resistance development was noted. In summary, the use of CZA showed effectiveness and safety, while the lack of resistance development highlights CZA’s potential as a primary treatment option against OXA-48-producing infections.
177Lu Anti-angiogenic Radioimmunotherapy Targeting ATP synthase in Gastric Cancer Model
Authors: Park Bok-Nam , An Young-Sil , Kim Su-Min , Lee Su-Jin , Park Yong-Jin , Yoon Joon-Kee
Published: May 2024

This study investigated a novel radioimmunotherapy strategy for targeting tumor angiogenesis. We developed a radiopharmaceutical complex by labeling an anti-adenosine triphosphate syn-thase (ATPS) monoclonal antibody (mAb) with the radioisotope 177Lu using DOTA as a chelating agent. 177Lu-DOTA-ATPS mAb demonstrated high labeling efficiency (99.0%) and stability in se-rum. MKN-45 cancer cells exhibited the highest cellular uptake, which could be specifically blocked by unlabeled ATPS mAb. In mice, 177Lu-DOTA-ATPS mAb accumulated significantly in tumors, with a tumor uptake of 16.0 ± 1.5%ID/g on day 7. 177Lu-DOTA-ATPS mAb treatment sig-nificantly reduced the viability of MKN-45 cells in a dose-dependent manner. In a xenograft tumor model, this radioimmunotherapy strategy led to substantial tumor growth inhibition (82.8%). Furthermore, combining 177Lu-DOTA-ATPS mAb with sunitinib, an anti-angiogenic drug, en-hanced the therapeutic efficacy of sunitinib in the mouse model. Our study successfully developed 177Lu-DOTA-ATPS mAb, a radioimmunotherapy agent targeting tumor blood vessels. This ap-proach demonstrates significant promise for inhibiting tumor growth, both as a single therapy and in combination with other anti-cancer drugs.
Enhancing Corporate Security: A Microservices Approach to Monitoring with Spyware Techniques and Prediction Models
Authors: Rossetto Anubis Graciela de Moraes , Noetzold Darlan , Silva Luis Augusto , Leithardt Valderi Reis Quietinho
Published: May 2024

Due to the increasing use of computer equipment, institutions and companies face challenges, such as sensitive data leaks and the spread of hate speech, which have severe consequences for organizations and their employees. Addressing these challenges is essential to avoid financial losses, reputational damage, and impacts on the psychological health of those involved. This paper presents a solution based on microservices for monitoring computers used by employees in organizations, including capturing information from the equipment using spyware techniques and a web application for managing alerts. The solution seeks to detect data leaks, suspicious behaviour, and hate speech. The results of the evaluation indicate that the proposed solution has an efficient data capture time and can identify unwanted behaviour in a short period. The solution also includes applying prediction models to detect hate speech, achieving an average accuracy of approximately 87%. The performance, scalability, and security evaluation demonstrate that the solution is suitable for dealing with data leakage and hate speech challenges in the corporate environment.
Integrating Network Pharmacology and Experimental Evaluation of Ocimum tenuiflorum (Tulsi) compounds targeting Breast Cancer Markers
Authors: MAHAJAN AMRITA , Badhe Dr. Pravin , Mali Prashant
Published: May 2024

One of the most prevalent and deadly types of cancer is breast cancer. The value and effectiveness of the current pharmacological therapy are, however, constrained. Using computational methods and publicly available data, the current study set out to identify the genes and molecular pathways linked to breast cancer. It also looked into potential treatments for the disease that would target these molecular processes. In this study, we mined genes that were strongly associated with breast cancer using text mining and GeneCodis. Using STRING and Cytoscape, protein-protein interaction (PPI) study was carried out. Candidate medications were then derived based on the drug-gene interaction study of the final genes. 2,658 genes linked to breast cancer were found by our investigation using text mining searches. Out of which 166 genes have been taken which are relevant to breast cancer. Ten genes representing ten pathways—which a total of ten proteins could target—were found by gene enrichment analysis. We have taken Holy Basil as our lead as it contains various bioactive compounds such as flavonoids, terpenoids, and phenolics, which have shown antioxidant, anti-inflammatory, and anticancer properties. For this analysis we choose the molecular docking technique to check the effects of different chemical constituents of Holy Tulsi on breast cancer targeted protein and compare their results. We’ve performed the molecular docking in between chemical constituents of Holy Basil and the targeted proteins and determined the binding affinity with the help of PyRx and BIOVIA Discovery studio software. Anti-mitotic activity of Pisum sativum using tulsi extract to check the cytotoxicity effect was done. To determine the toxicity level of the extract on rat liver was performed in the end. In conclusion, investigating candidate medications that target the genes/pathways relevant to breast cancer in order to uncover possible treatments may be accomplished through drug discovery employing in silico text mining and pathway analysis technologies along with the wet lab experimentation with plants and preclinicals.