Podoplanin (PDPN) is a cell-surface mucin-like glycoprotein that plays a critical role in tumor development and normal development of the lung, kidney, and lymphatic vascular systems. PDPN is overexpressed in several tumors and is involved in their malignancy. PDPN induces platelet aggregation through binding to platelet receptor C-type lectin-like receptor 2. Furthermore, PDPN modulates signal transductions that regulate cell proliferation, differentiation, migration, invasion, epithelial to mesenchymal transition, and stemness, all of which are crucial for the malignant progression of tumor. In the tumor microenvironment (TME), PDPN expression is up-regulated in the tumor stroma, including cancer-associated fibroblasts (CAFs) and immune cells. CAFs play significant roles in the extracellular matrix remodeling and the development of immunosuppressive TME. Additionally, PDPN functions as a co-inhibitory molecule on T cells, indicating the involvement with immune evasion. In this review, we describe the mechanistic basis and diverse roles of PDPN in malignant progression of tumor and discuss the possibility of the clinical application of PDPN-targeted cancer therapy, including cancer-specific monoclonal antibodies, and chimeric antigen receptor T technologies.

Acute ischemic strokes are the third leading cause of death and the leading cause of neurological disability worldwide. The oxygen and glucose deprivation associated with ischemic strokes not only leads to neuronal cell death, but also increases the inflammatory response and decreases functional output of the brain. The only intervention approved by US Federal Drug and Food Administration for treatment of ischemic strokes is tissue plasminogen activator (tPA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its application, and it also might induce detrimental rather than beneficial effects to stroke patients by treatment of the tPA. In order to reduce the infarct volume of an acute ischemic stroke while increasing the time period for treatment, emerging therapies reveal great potential by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors with monoclonal antibody (MAB). With successfully application in the treatment of cancer patient by MAB, in this review, we will focus on recent advances on stroke therapy by using MAB on the treatment of stroke by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors. Therefore, developing specific MAB targeting the signaling pathway of stroke will contribute to stroke therapy.

Neonatal drug information (DI) is essential for safe and effective pharmacotherapy in (pre)term neonates. Such information is usually absent from drug labels, making formularies a crucial part of the neonatal clinician’s toolbox. Several formularies exist worldwide, but they have never been fully mapped nor compared for content, structure and workflow. The objective of this review was to identify neonatal formularies, explore (dis)similarities, and raise awareness of their existence.Neonatal formularies were identified through self-acquaintance, experts and structured search. A questionnaire was sent to all identified formularies to provide details on formulary function. An original extraction tool was employed to collect DI from the formularies on the 10 most commonly used drugs in pre(term) neonates.Eight different neonatal formularies were identified worldwide (Europe, USA, Australia-New Zealand, Middle East). Six responded to the questionnaire and were compared for structure and content. Each formulary has its own workflow, monograph template and style, and update routine. Focus on certain aspects of DI also varies, as well as the type of initiative and funding.Clinicians should be aware of the various formularies available and their differences in characteristics and content to use them properly for the benefit of their patients.

The leading cause of gastroenteritis in children under the age of five is rotavirus infection, accounting for 37% of diarrhoeal deaths in infants and young children globally. Oral rotavirus vaccines have been widely incorporated into national immunisation programs, but whilst these vaccines have excellent efficacy in high-income countries, they protect less than 50% of vaccinated individuals in low- and middle-income countries. In order to facilitate the development of improved vaccine strategies, a greater understanding of the immune response to existing vaccines is urgently needed. However, the use of mouse models to study immune responses to human rotavirus strains is currently limited as rotaviruses are highly species-specific and replication of human rotaviruses is minimal in mice. To enable characterisation of immune responses to human rotavirus in mice, we have generated chimeric viruses that combat the issue of rotavirus host range restriction. Using reverse genetics, the rotavirus outer capsid proteins (VP4 and VP7) from either human or murine rotavirus strains were encoded in a murine rotavirus backbone. Neonatal mice were infected with chimeric viruses and monitored daily for development of diarrhoea. Stool samples were collected to quantify viral shedding, and antibody responses were comprehensively evaluated. We demonstrated that chimeric rotaviruses were able to efficiently replicate in mice. Moreover, the chimeric rotavirus containing human rotavirus outer capsid proteins elicited a robust antibody response to human rotavirus antigens, whilst the control chimeric murine rotavirus did not. This chimeric human rotavirus therefore provides a new strategy for studying human rotavirus-specific immunity, and could be used to investigate factors causing variability in rotavirus vaccine efficacy. This small animal platform therefore has the potential to test the efficacy of new vaccines and antibody-based therapeutics.

CD44 is a cell surface glycoprotein, which is widely expressed on normal and cancer cells. CD44 is involved in cell adhesion, migration, proliferation, survival, stemness, and chemo-resistance. Therefore, CD44 is thought to be a promising target for cancer diagnosis and therapy. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10 ectodomain and screening using enzyme-linked immunosorbent assay. We then characterized them using flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-46; IgG1, kappa) reacted with CD44s-overexpressed Chinese hamster ovary-K1 cells (CHO/CD44s) or esophageal squamous cell carcinoma (ESCC) cell lines (KYSE70 and KYSE770). The KD of C44Mab-46 for CHO/CD44s, KYSE70, and KYSE770 was 1.1×10-8 M, 4.9×10-8 M, and 4.1×10-8 M, respectively. C44Mab-46 detected CD44s of CHO/CD44s and KYSE70, and CD44v of KYSE770 in western blot analysis. Furthermore, C44Mab-46 strongly stained esophageal squamous carcinoma cells in immunohistochemistry using formalin-fixed paraffin-embedded ESCC tissues. Taken together, C44Mab-46 is very useful for detecting CD44 in various applications.

Immunohistochemistry is a widely used technique for research and diagnostic purposes that relies on the recognition by antibodies of antigens expressed in tissues. However, tissue processing and particularly formalin fixation affect the conformation of these antigens through the formation of methylene bridges. Although antigen retrieval techniques can partially restore antigen immunoreactivity, it is difficult to identify antibodies that can recognize their target especially in formalin-fixed paraffin-embedded tissues. Most of the antibodies currently used in immunohistochemistry have been obtained by animal immunization; however, in vitro display techniques represent alternative strategies that have not been fully explored yet. This review provides an overview of phage display-based antibody selections using naïve antibody libraries on various supports (fixed cells, dissociated tissues, tissue fragments, and tissue sections) that have led to the identification of antibodies suitable for immunohistochemistry.

Purpose: This study evaluates the impact of Medicaid expansion under the Affordable Care Act (ACA) on melanoma staging at diagnosis, treatment utilization, and 3-year mortality outcomes. The objective is to determine whether Medicaid expansion led to earlier melanoma diagnosis and improved survival rates among non-elderly adults (ages 40-64) by analyzing data from the National Cancer Database (NCDB). Methods: A total of 12,667 patients, aged 40-64, diagnosed with melanoma from 2010 to 2020 were identified using the NCDB. Difference-in-difference (DID) analysis was performed to analyze tumor staging at presentation between Medicaid expansion states and non-Medicaid expansion states both prior to the expansion and after the expansion. Results: Of the total patients 2,307 were from the pre-expansion time period residing in Medicaid Expansion states (MES) and 1,804 in non-Medicaid expansion states. In the post-expansion time period there were 5,571 residing in the MES and 2,985 in the non-MES. DID analysis revealed a decrease in stage IV melanoma at diagnosis (DID -0.222, p <0.001) between MES and non-MES before and after Medicaid expansion. After expansion, in stage IV, the occurrence of primary surgery was 0.42 in non-MES and 0.44 (difference 0.02), DID analysis was not statistically significant. The use of immunotherapy in MES was significantly higher than non-MES after expansion (p<0.001), although DID analysis did not reveal a statistically significant difference. DID analysis showed a statistically significant decrease in 3-year mortality (DID -0.05, p=0.001) between MES and non-MES before and after Medicaid expansion. Conclusions: This study revealed the positive impact of the ACA’s Medicaid expansion on melanoma stage at presentation showing improved access to healthcare services can facilitate the diagnosis of early-stage melanoma and decrease mortality rate.

Background: An accurate diagnosis of thyroid nodules is crucial for avoiding unnecessary surgical procedures and making timely treatment possible. The objective of the present study was to evaluate the diagnostic accuracy of FNAB (fine-needle aspiration biopsy) using histopathological findings as the reference standards. Patients with the diagnostic categories (DCs) III, IV, V were subjected to a special analysis. In addition, the authors assessed whether other factors, i.e. age, gender, BMI (body mass index), obesity and histopathologically confirmed lymphocytic thyroiditis had an impact on the occurrence of malignant tumors. Methods: A retrospective analysis was conducted on 535 patients who underwent thyroid surgery between October 2022 and September 2023. To assess the FNAB reliability, the result obtained using the Bethesda classification was compared with the histopathological result. Results: The ROM (risk of malignancy) values for DCs I-VI were 38.1%, 15.6%, 29.8%, 18.6%, 91.0%, 93.2%, respectively. DC V (OR 62.34, p< 0.0001) and age≤50 (OR=2.31, p<0.006) had a statistically significant effect on the risk of thyroid cancer. DCs III and IV were not statistically significantly associated with the risk of malignancy (OR=1.68,p=0.16; OR=1.51,p=0.3,respectively). There were no statistically significant differences in sex, BMI and obesity between the patients with benign and malignant lesions. Conclusion: DC V is associated with a high likelihood of malignancy, especially in patients under 50 years of age, and therefore surgery is indicated in this category of subjects. In the DCs III and IV categories, the risk of malignancy is lower and conservative management with active clinical and ultrasound surveillance can be considered. In patients < 50 years of age, with the Bethesda categories III and IV, surgical treatment should be considered.

Rhynchocypris kumgangensis, endemic to Korea, is limited to the upper Hangang River and Gucheondongcheon Stream. As a key and climate-sensitive biological indicator species in Deogyusan National Park, it has a southern range limit in the Gucheondong Valley. Due to climate change, notable shifts in the activity, vertical distribution, and population of R. kumgangensis in the Gucheondongcheon Stream are expected. Owing to the rapidly changing climate, significant changes in the activity, vertical distribution, and population size of R. kumgangensis in the Gucheondongcheon Stream are anticipated, and continuous surveys of the distribution of R. kumgangensis in this river area have been conducted. This study assessed the habitat of R. kumgangensis at 13 sites, including five in the Gucheondongcheon Stream, from July to October 2020 and compared the results with historical data to evaluate the impacts of climate change. At the five Gucheondongcheon Stream sites, 102 individuals were recorded from April to October 2020, and 378 were recorded between June 2018 and July 2019. Additionally, the subdominant species shifted from R. kumgangensis (2014–2018) to Zacco koreanus (2020). In the two southernmost Gucheondongcheon Stream sites, only 18 R. kumgangensis were observed in 2020 compared to 82 in 2019, indicating a significant population decline.

This study presents the experimental and analytical evaluations on an innovative connection class under cyclic loading. The connection was an H- or I-shaped section as a short stub column (SSC) between the end-plate and the column. The stub section was bolted to the column flange on the one side and bolted to the beam along with the welded end-plate on the other side. Stiffeners were installed on the webs and flanges of the beam and stub to ensure the necessary stiffness of the connection. The variables included thickness of stub flange/web and height of stub web. The cyclic loading was applied on a sample of the proposed connection according to AISC ANSI/AISC 341-16 loading protocol. Experimental observations displayed that the proposed connection, one can either employ hot rolling sections or create the connection as a plate girder, in which case the flange thickness and stub web, as well as the distance between two flanges and their height, was obtained according to the demand and performance of the structure. The optimum cross-section of the stub was then obtained. Also, the analytical model was calibrated using the finite element method (FEM), and its performance was confirmed. The effective parameters of the proposed connection were determined by modeling in the FEM software, and the design method was presented.

Objective: In recent years, the field of Essential Thrombocythemia (ET) research has seen a significant accumulation of scientific findings, but comprehensive bibliometric analyses remain lacking. This study aims to fill that gap by performing a thorough bibliometric analysis of ET research, identifying key contributors and collaboration networks, and mapping the development trends to provide insights for future research directions. Methods: A bibliometric analysis of ET-related publications from 2001 to 2024 was conducted using CiteSpace, VOSviewer, and R packages. Data were retrieved from the Web of Science Core Collection, with a focus on publication volume, citation analysis, co-authorship networks, co-citation relationships, and citation bursts. Results: A total of 4,297 studies published in 778 journals were included in the analysis. ET research has seen rapid growth, with researcher clusters in the United States and Europe driving progress through extensive regional and international collaborations. Leading researchers, such as Ayalew Tefferi from the Mayo Clinic and Alessandro M. Vannucchi from the University of Florence, have made significant advances in ET classification, molecular mechanisms, targeted therapies, and disease management. The discovery of driver mutations, such as JAK2, has revolutionized the diagnostic and therapeutic approaches to ET. Research focus has shifted from clinical morphological diagnosis to molecular diagnostics, with the field now entering the era of targeted therapies. However, the inherent heterogeneity of ET continues to present challenges for the widespread implementation of personalized precision treatment. Conclusion: Bibliometric analysis demonstrates significant advances in ET research, particularly in molecular pathology and targeted therapies. However, the heterogeneity of ET remains a major obstacle to personalized treatment. Future research should focus on further elucidating the pathogenesis of ET and improving stratified management approaches to achieve individualized precision therapy.

Phosphorus (P) is an essential element in food production, but it is often largely unavailable for plants as it persists in soils in immobilized forms. Farmers have been using P fertilizers extensively to overcome this unavailability, leading to the exhaustion of non-renewable deposits of phosphorite, rising fertilizers prices and causing several environmental impacts such as eutrophication. Its large-scale utilization is also inefficient since most of the added P becomes quickly unavailable for the plants. Therefore, farming solutions that improve P uptake, P use efficiency of plants and P mobilization in soils are highly important. In this narrative review, we summarized and explored the link between the Silicon (Si) and P cycles in soils. Silicon is quasi-essential for plants, and it has been established that its presence in soil and uptake by plants has several benefits, especially in toxic and nutrient-deficient conditions. Here, we established that Si in soils can affect crop production in P-deficient conditions through: 1) the pH effect – Si improves organic matter decomposition and decreases Al3+ availability; the Si uptake effect – the deposited Si in the plant improves its photosynthetic performance, improves the root ability to uptake P, improves organic matter decomposition and increases P/Mn ration in plant, improving P use; and 3) the Si soil effect – Si stimulates phosphorite rocks weathering and competes with P for the binding places at the surface of Ak and Fe hydroxides, releasing P into soil solution. This positive effect of Si on P mobilization in soils and consequent use by crops should be further disseminated to farmers and other relevant stakeholders.

Cystic fibrosis (CF) diagnosis can be a challenge due to the large spectrum of pathogenic variants in the CFTR gene and the effects of complex alleles. Next-generation sequencing has improved our understanding of the contribution of these complex alleles to the wide spectrum of CF clinical symptoms and to the response to medications. Herein, we studied nine CF patients from six unrelated families carrying the complex allele p.[Ile148Thr;Ile1023_Val1024del] with a frequency of 0.18%. All the patients were from Central Mexico. This complex allele was found in trans with Class I and II pathogenic variants (PVs) such as [c.1521_1523del, p.(Phe508del), and c.3231_3232del, p.(Phe1078Profs*77)]. A targeted search of a dataset of 2,217 exomes from healthy individuals revealed that eight individuals (0.18%) carried the p.(Ile148Thr) variant, but only one (0.022%), who was also born in Central Mexico, was a carrier of the complex allele. These findings led us to hypothesize a founder effect for the p.[Ile148Thr;Ile1023_Val1024del] complex allele in Mexican patients with CF, probably through migration from the French-Canadian population in Mexico. Finally, protein modeling revealed that this complex allele disrupts the secondary structure of the CFTR protein and might alter the ion flow.

The HER2-targeted antibody-drug conjugates (ADCs) trastuzumab emtansine (T-DM1) and Trastuzumab deruxtecan (T-DXd) improved outcomes in breast cancer. Novel combinations and sequential approaches are under investigation to overcome resistance to T-DM1 and T-DXd. Furthermore, the landscape of HER2-targeted therapy is rapidly advancing with the development of ADCs designed to attack cancer cells with greater precision and reduced toxicity. Disitamab Vedotin (RC48) incorporates a HER2 antibody with unique binding epitope and a potent microtubule inhibitor as its cytotoxic moiety. ARX-788 comprises a non-cleavable linker and a novel maytansinoid derivative as the cytotoxic drug, engineered for increased stability and a higher drug-to-antibody ratio. SYD985, a duocarmycin-based ADC, is designed to be activated only in the acidic environment of the tumor, thus reducing off-target effects. BL-M0701 targets a different epitope on the HER2 protein, which might be beneficial in circumventing resistance that affects the binding of other ADCs and incorporate a camptothecin derivative as its payload. Zanidatamab zovodotin (ZW25) is an ADC that binds to two different HER2 epitopes simultaneously, enhancing the internalization and delivery of its cytotoxic payload. These and other ADCs in phase I trials hold the potential to improve outcomes for HER2-positive and HER2-Low breast cancer and possibly other solid tumors.

(1) Background: Hepatitis C virus (HCV) screening mostly uses a one-assay anti-HCV testing approach, which has a higher probability of false-positive results in populations with low HCV prevalence. (2) Methods: In this investigation, 17,926 participants, were screened for HCV, and the reactives were tested using a two-assay anti-HCV approach: Elecsys ElectroChemiLuminescence (ECL) and a ChemiLuminescence ImmunoAssay (CLIA), respectively. A recombinant immunoblot assay (RIBA) was performed to confirm anti-HCV positivity. Statistical analysis was performed. (3) Results: A total of 350 specimens resulted reactive in the ECL screening, of which CLIA retesting showed that 292 (83.4%) were anti-HCV reactive (283 positive, 9 indeterminate, none negative by RIBA), but 58 (16.6%) were not anti-HCV reactive (15 positive, 12 indeterminate, 31 negative by RIBA). The two-assay strategy significantly improved the positive predictive value (PPV: 95.00%) with χ2: 7.59(p&lt;0.01) then the PPV assessed by one assay (PPV: 90.6%) with χ2: 34.51 (p&lt; 0.001). The ROC curve defined a sensibility and specificity for the dual approach of: 99.66% and 100.00%. (4) Conclusions: Compared with a one-assay testing strategy, the two-assay testing strategy may significantly reduce false positives in anti-HCV testing and identify inactive HCV infection in low seroprevalence populations.

Two monoclonal antibodies (mAbs) against human epidermal growth factor receptor 2 (HER2), trastuzumab and pertuzumab, were clinically approved. We previously developed a highly sensitive and specific anti-HER2 mAb, H2Mab-139 (mouse IgG1, kappa). In this study, we produced a defucosylated IgG2a version of anti‑HER2 mAb (H2Mab-139-mG2a-f) to enhance ADCC-mediated antitumor activity. H2Mab-139-mG2a-f exhibits a high binding affinity in flow cytometry with the dissociation constant (KD) determined to be 3.9 × 10‑9 M and 7.7 × 10‑9 M against HER2‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/HER2) and HER2-positive BT-474 cells, respectively. Moreover, we showed that H2Mab-139-mG2a-f exerted ADCC and complement-dependent cytotoxicity against CHO/HER2 and BT-474 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that H2Mab-139-mG2a-f exerts antitumor effects against HER2-positive human breast cancers and could be useful for an antibody treatment regimen for HER2-positive human cancers.

In this paper, various Ni-P composite coatings containing toner, MoS2, and nano-SiO2 particles were deposited on steel substrates by the electroless method. Then, the electrochemical properties of these coatings after a heat treatment process were compared. The microstructural evaluations were also done by using the optical and electron microscopy methods. Both Tafel polarization and electrochemical impedance spectroscopy techniques were utilized to survey the electrochemical behavior of such coatings. The surface morphology of all coatings contained cauliflower-like nodules. The X-ray diffraction patterns showed the crystalline phases of Ni and Ni3P for all coatings after the heat-treatment step. Obtained results showed that all composite coatings exhibited lower corrosion rates with respect to Ni-P coatings. Such a reduction was about 21.6-92.2%. This behavior was attributed to the presence of reinforcement as barriers for corrosive ion diffusion through the coating plus the changes in detected phases and thickness. Electrochemical impedance spectroscopy test results also demonstrated that the increase in the polarization resistance for composites coatings was about 18.4-85.3% after 1 h immersion in a 0.6M NaCl solution; however, when the immersion time increased to 24 h, such increased resistance changed to 18.1 to 73.1%. Totally, despite the lower deposition rate, the presence of MoS2 and nano-SiO2 particles were more effective than toner particles to raise the corrosion rate of the Ni-P coating.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on Z_p of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

It is known that the class of p-normed spaces (0 < p ≤ 1) is an important generalization of usual normed spaces with rich topological and geometrical structure, but the most of tools and general principles in nature with nonlinearity have not been developed yet, thus the main goal of this paper is to develop tools for nonlinear analysis under the framework of p-vector spaces. In particular, we first develop the general fixed point theorems which provide solutions to answer Schauder conjecture since 1930’s in the affirmative for p-vector spaces when p = 1 (which is just general topological vector spaces); then the one best approximation result for upper semi-continuous mappings is given, which is used as a powerful tool to establish fixed points for non-self set-valued mappings with either inward or outward set conditions; and finally we establish comprehensive existence results of solutions for Birkhoff-Kellogg Problems, and the general principle of nonlinear alternative by including Leray-Schauder alternative and related results. The results given in this paper not only include the corresponding results in the existing literature as special cases, but also expected to be useful tools for the study of nonlinear problems arising from theory to practice.

The main aim of this paper is to set some correlations between Boole polynomials and p-adic gamma function in conjunction with p-adic Euler contant. We develop diverse formulas for p-adic gamma function by means of their Mahler expansion and fermionic p-adic integral on ℤ_{p}. Also, we acquire two fermionic p-adic integrals of p-adic gamma function in terms of Boole numbers and polynomials. We then provide fermionic p-adic integral of the derivative of p-adic gamma function and a representation for the p-adic Euler constant by means of the Boole polynomials. Furthermore, we investigate an explicit representation for the aforesaid constant covering Stirling numbers of the first kind.

Hard yellow maize is a crucial crop in Peruvian agriculture, playing a significant role in food security and livestock production. However, intensive fertilization practices in agronomic management have negatively impacted soil health. To explore more sustainable agricultural technologies, researchers have investigated using microorganisms to enhance plant growth. This study assessed the synergistic effects of microbial inoculants and mineral fertilization on INIA 619 and Dekal B-7088 maize varieties' yield and nutritional quality. A split-plot design was employed, incorporating four inoculation treatments—no inoculant, Bacillus subtilis, Trichoderma viride, and Pseudomonas putida—combined with fertilization levels of 0%, 50%, 75%, and 100%. The findings revealed that Bacillus subtilis boosted yields by 13.1% in INIA 619 and 55.5% in Dekal B-7088. Additionally, combined with 100% fertilization, microbial inoculation increased protein content by 47% and carbohydrates by 6% in INIA 619, while maintaining nutritional quality with 75% fertilization. Similarly, in Dekal B-7088, inoculation with total fertilization enhanced protein content by 54% and fiber by 27%. These results demonstrate that microbial inoculation can reduce mineral fertilization by up to 25% while sustaining high yields and improving the nutritional quality of maize.

Background: Total gastrectomy with D2 lymph node dissection is standard for resectable esophagogastric junctional and gastric cancer, but high morbidity challenges perioperative care. ERAS guidelines advise against routine drains, yet conflicting evidence leads to inconsistent practice. Methods: The DRAG (DRains After Gastrectomy) Trial is a prospective, non-randomized study conducted from February 2020 to March 2023 at the 1st Propaedeutic Surgery Department, Hippocration General Hospital, Athens. Patients undergoing open D2 total gastrectomy had perianastomotic drains placed based on newly established criteria, offering a more tailored approach. Immediate and short-term postoperative outcomes, including recovery milestones and complications, were assessed. Results: Sixty patients were included, with 40 receiving a drain. The non-drain group had significantly lower pain scores, earlier mobilization, less postoperative nausea and vomiting, and a shorter hospital stay. Among those with complications, significant differences in surgical site infections, delayed mobilization, extra-abdominal issues, length of stay, readmissions, and reoperations suggest that drain use may increase complications and hinder recovery. Conclusion: Our study suggests that routine prophylactic drain use can be avoided in gastrectomy for esophagogastric junctional and gastric cancer when experienced surgeons in high-volume centers follow clearly defined criteria. Implementing these criteria may improve patient outcomes and reduce complications.

Research background: The globalization processes are not only of an economic and cultural nature but also unify trends in the organization and management of administration, including at the local level. The idea of economizing administration was promoted within the broad stream of reforms described as New Public Management (NPM). This idea was often expressed as a postulate for the territorial reorganization of local governments. These reforms, motivated by the economies of scale, aimed to eliminate the allegedly overly fragmented nature of local government structures. Critics of these reforms advocate for glocalization, which takes local institutional conditions into account. They argue that the NPM concept should emphasize a long-term balance between economics, environment, and society, which are the paradigms of sustainable development (SD). According to them, this approach provides a more holistic and effective method for public management.

A new 2 parameter unit Weibull distribution is defined on the unit interval (0,1). The methodology of deducing its PDF, some of its properties and related functions are discussed. The paper is supplied by many figures illustrating the new distribution and how this can make it illegible to fit a wide range of skewed data. The new distribution holds a name (Attia) as a nickname.

The concept of Palliative Care (PC) is more and more known in medicine and the need for this type of approach is growing in a world with great longevity and exponentially increasing chronic diseases. More and more cases from internal medicine, gastroenterology or cardiology wards could benefit from a better care if their medical team would align with the PC concept and principles. In this sense we try to present the specifical needs for Romanian patients in accordance with the current standards of care and how they must be adapted to the reality of the medical system in which they are cared for. We consider also that for medical staff from chronic disease wards it may be necessary to recapitulate the most important principles that govern medical practice of palliation, emphasizing some important aspects of applicability in daily clinical activity.

This study examines the significant impact of Houthi insurgent activities on maritime traffic within the strategic Red Sea and Suez Canal routes, essential conduits for global trade. It explores the correlation between regional instability, exemplified by Houthi actions from November 19, 2023, to February 5, 2024, and changes in maritime traffic patterns and operational efficiency. This study seeks to answer a critical question in transport geography: How does regional instability, exemplified by Houthi insurgent activities, affect maritime traffic patterns and the operational efficiency of the Red Sea and Suez Canal? Using descriptive statistics, qualitative analysis, and geospatial methods, the research highlights recent trends in maritime traffic and incidents, revealing spatial and geopolitical challenges in this crucial trade route.Findings indicate a notable decline in maritime activity in the Gulf of Aden and Suez Canal due to security concerns from Houthi attacks, prompting a significant shift to alternative routes, particularly around the Cape of Good Hope. This shift underscores the broader implications of regional instability on global trade and the importance of maintaining uninterrupted maritime flow. The study also emphasizes the economic ramifications, such as increased operational costs and freight rates due to longer transit times and enhanced security measures.The research concludes with a call for improved maritime security protocols and international cooperation to protect these strategic maritime pathways. It contributes to the discourse on transport geography by quantifying the direct impacts of regional conflicts on maritime logistics and proposing strategies for future resilience, highlighting the interconnected nature of global trade and security and the need for collective action against evolving geopolitical challenges.

The fall armyworm (FAW), Spodoptera frugiperda, a major pest in maize production, was assessed for its temporal and spatial distribution in maize fields during both the off and rainy seasons of 2021 and 2022. In this study, 30 and 50 maize plants were randomly sampled using a "W" pattern during the dry and rainy seasons, respectively. Larval density, infestation rates, and damage severity were monitored over time. Taylor's power law and the mean crowding aggregation index were applied to evaluate the dispersion patterns of the larvae. The results indicate a higher infestation rate and larval density in agroecological zone AZE 8 (fisheries zone of South Benin) compared to AZE 6 (ferralitic soils zone) during the off-season. In the rainy season, while the percentage of damaged plants was higher in AZE 8, no significant differences in larval density between the two zones were observed. The dispersion analysis revealed moderate aggregation (aggregation index = 1.25) with a basic colony of 2.08 larvae, reflecting the aggregation oviposition behavior of FAW. This study provides valuable monitoring data on the FAW's distribution, offering insights for further research on population dynamics and developing predictive models for integrated pest management strategies.

Objective: To explore the acceptability and feasibility of conducting comprehensive, community-based, hy-brid (in-person and virtual) mental health screening and feedback with diverse youth in the community. Methods: The Screening and Support for Youth intervention provides comprehensive assessment and thera-peutic feedback in community settings including symptoms, diagnoses, functional impairment, suicide, and clinical risk. Symptom severity, seven diagnoses and suicidality were assessed with the Kiddie Computer-ized Adaptive Test. Functional impairment was evaluated by youth self-report on the Weiss Functional Im-pairment Rating Scale. Measures were scored according to nationally developed norms and an algorithm was developed to aggregate symptoms and functioning to determine clinical risk. The results were discussed with participants in a motivational interview to promote insight and engagement in an online intervention. Results: Methodological innovations included using a QR code for recruitment, integrated in-person and virtual participation, and expansion from in-person recruitment within the schools to virtual engagement with youth throughout the community. The final sample included disproportionately more Black or African American and Hispanic youth as compared to school and community statistics, suggesting that hybrid re-search may facilitate recruitment of diverse populations. Qualitative interviews indicated that the screening and feedback raised youth awareness of their wellbeing and/or distress, its impact on their functioning, and engagement with options for improving wellbeing. Conclusion: Hybrid research, developed as a necessity during the pandemic, proved advantageous to the feasibility and acceptability of community-based recruit-ment of at risk, minoritized youth.

In order to deal with imprecision, ambiguity, and uncertainty in data analysis, Pawlak introduced rough set theory in 1982. This paper aims to expand the scope of basic set theory developed by presenting the notions of δP-upper and δP-lower approximations, that are based on the notion of δP-open sets, we additionally examine a few of their fundamental characteristics.

This work reports the role of structure and composition on the determination of the performances of p-type SnOx TFTs deposited by rf magnetron sputtering at room temperature, followed by a post-annealed step up to 200 °C at different oxygen partial pressures (Opp), between 0% and 20%, but where the p-type conduction was only observed between 2.8–3.8%. The role of structure and composition were evaluated by XRD and Mössbauer spectroscopic studies. The study allows to identify the best phases/compositions and thicknesses (around 12 nm) to be used that lead to the production of TFTs with a bottom gate configuration, on glasses coated with conductive Indium Tin Oxide, followed by Aluminium Titanium Oxide dielectric layer with saturation mobility of 4.6 cm²V⁻¹s⁻¹ and on-off ratio above 7 × 10⁴, operating at the enhancement mode with a saturation voltage of −10 V.

We previously developed a highly sensitive and specific anti-PDPN mAb, LpMab-23 (mouse IgG1, kappa). In this study, we produced a humanized IgG1 version (humLpMab-23) and its defucosylated form (humLpMab-23-f) of an anti‑PDPN mAb to potentiate the ADCC activity. The humLpMab-23 could recognize PDPN‑overexpressed Chinese hamster ovary (CHO)-K1 (CHO/PDPN) and PDPN-positive PC-10 and LN319 cells by flow cytometry. Furthermore, we found that humLpMab-23-f exerted ADCC and complement-dependent cytotoxicity against CHO/PDPN, PC-10 and LN319 cells in vitro and exhibited potent antitumor activities in the xenograft models. These results indicated that humLpMab-23-f could be useful for an antibody treatment regimen for PDPN-positive human cancers.

FMD is a highly contagious animal disease that occurs in cloven-hoofed animals including pigs. To prevent FMD, vaccines and adjuvants are used to induce an immune response, but it is not sufficient to show the effect of preventing viral infection. In this study, we conducted to evaluate the increasing effect of FMD vaccine SP antibody by administrating Zn-ASP to 100 pigs from three test pig farms with feed. FMD vaccine antibody titer and immunological index were analyzed using an enzyme-linked immunosorbent assay (ELISA) kit, and hematological and blood biochemical parameters were analyzed using an automatic blood analyzer. The titer of FMD vaccine SP antibody in the 0.2% Zn-ASP-administered group significantly increased compared to that in the positive control group only injected with FMD vaccine at 4 weeks after the first vaccination and at 4, 8 and 16 weeks after the second vaccination, respectively (p&lt;0.05). The FMD vaccine SP antibody positive rate was 100% until shipment. IFN-γ and IgA were significantly increased by Zn-ASP administration 4 weeks after the first vaccination and 4 weeks after the second vaccination (p&lt;0.05). On the other hand, serum AST, and CPK (p&lt;0.001) were significantly decreased by Zn-ASP. Our results show that the administration of Zn-ASP is effective in enhancing the antibody titer and immunity of the FMD vaccine by FMD vaccination, and it is thought that it can be used as an oral adjuvant (OrAd) to prevent viral diseases such as FMD.

The importance of antibodies in health care and the biotechnology research and development demands not only knowledge of their experimental structures at high resolution, but also practical implementation of this knowledge for both effective and efficient design and production of antibody for its use in both medical and research applications. While the experimental wet-lab approach is usually costly, laborious and time-consuming, computational (dry-lab) approaches, in spite of their intrinsic limitations in comparison with its experimental (wet-lab) counterpart, provide a cheaper and faster alternative option. For the first time, this article reports a comprehensive set of structural electrostatic features extracted from experimentally determined antigen-antibody-related structures, including especially those structural electrostatic features at the interfaces of all experimentally determined antigen-antibody complex structures as of February 29, 2020, to facilitate effective and efficient machine learning-based computational antibody design using currently available experimental structures inside Protein Data Bank.

Multiple myeloma (MM) is a common type of cancer that unfortunately leads to a significant number of deaths each year. The majority of the reported MM cases are detected in the advanced stages, posing significant challenges for treatment. Additionally, all MM patients eventually develop resistance or experience relapse, therefore advances in treatment are needed. However, developing new anti-cancer drugs, especially for MM, requires significant financial investment and a lengthy development process. The study of drug repurposing involves exploring the potential of existing drugs for new therapeutic uses. This can significantly reduce both time and costs, which is typically a major concern for MM patients. The utilization of pre-existing non-cancer drugs for various myeloma treatments presents a highly efficient and cost-effective strategy, considering their prior preclinical and clinical development. The drugs have shown promising potential in targeting key pathways associated with MM progression and resistance. Thalidomide exemplifies the success that can be achieved through this strategy. This review delves into the current trends, the challenges faced by conventional therapies for MM, and the importance of repurposing drugs for MM. This review highlights a noncomprehensive list of conventional therapies that have potentially significant anti-myeloma properties and anti-neoplastic effects. Additionally, we offer valuable insights into the resources that can help streamline and accelerate drug repurposing efforts in the field of MM.

Viral diseases are one of the leading causes of morbidity and mortality in the world. Virus-specific vaccines and antiviral drugs are the most powerful tools to combat viral diseases. However, broad-spectrum antiviral agents (BSAAs, i.e. compounds targeting viruses belonging to two or more viral families) could provide additional protection of general population from emerging and re-emerging viral diseases reinforcing the arsenal of available antiviral options. Here, we reviewed discovery and development of BSAAs and summarized the information on 120 safe-in-man agents in freely accessible database (https://drugvirus.info/). Future and ongoing pre-clinical and clinical studies will increase the number of BSAAs, expand spectrum of their indications, and identify drug combinations for treatment of emerging and re-emerging viral infections as well as co-infections.

In this paper, we investigate several relations for p-adic gamma function by means of their Mahler expansion and fermionic p-adic q-integral on ℤ_{p}. We also derive two fermionic p-adic q-integrals of p-adic gamma function in terms of q-Boole polynomials and numbers. Moreover, we discover fermionic p-adic q-integral of the derivative of p-adic gamma function. We acquire a representation for the p-adic Euler constant by means of the q-Boole polynomials. We finally develop a novel, explicit and interesting representation for the p-adic Euler constant including Stirling numbers of the first kind.

In this paper, we investigate p-adic q-integral (q-Volkenborn integral) on ℤ_{p} of p-adic gamma function via their Mahler expansions. We also derived two q-Volkenborn integrals of p-adic gamma function in terms of q-Daehee polynomials and numbers and q-Daehee polynomials and numbers of the second kind. Moreover, we discover q-Volkenborn integral of the derivative of p-adic gamma function. We acquire the relationship between the p-adic gamma function and Stirling numbers of the first kind. We finally develop a novel and interesting representation for the p-adic Euler constant by means of the q-Daehee polynomials and numbers.

C-X-C motif chemokine receptor 3 (CXCR3, CD183) is a G-protein-coupled receptor for CXCL9, CXCL10, and CXCL11. CXCR3 signaling induces chemotaxis of immune cells to inflammation sites and promotes inflammation in inflammatory diseases. Various mouse models to mimic the pathogenesis of each disease have been developed to understand mechanisms and evaluate therapeutics for these diseases. Although CXCR3 is an attractive target to suppress inflammation, anti-CXCR3 therapeutic agents have not been approved. In this study, we established a novel anti-mouse CXCR3 (mCXCR3) monoclonal antibody, Cx₃Mab-4 (rat IgG₁, kappa), using the Cell-Based Immunization and Screening method. Flow cytometric analysis demonstrated that Cx₃Mab-4 bound to mCXCR3-overexpressed Chinese hamster ovary-K1 (CHO/mCXCR3) cells, but did not react to parental CHO-K1 cells. The dissociation constant of Cx₃Mab-4 was determined as 1.3 × 10^-9 M, indicating that Cx₃Mab-4 possesses a high affinity to mCXCR3-expressing cells. Cx₃Mab-4 could be useful for targeting CXCR3-expressing cells in preclinical mouse models.

The C-X-C motif chemokine receptor-1 (CXCR1) is a rhodopsin-like G-protein-coupled receptor, expressed on the cell surface of immune cells and tumors. CXCR1 interacts with some C-X-C chemokines, such as CXCL6, CXCL7, and CXCL8/interleukin-8, which are produced by various cells. Since CXCR1 is involved in several diseases including tumors and diabetes mellitus, drugs targeting CXCR1 has been developed. Therefore, the development of sensitive monoclonal antibodies (mAbs) for CXCR1 has been desired for the diagnosis and treatment. This study established a novel anti-mouse CXCR1 (mCXCR1) mAb; Cx₁Mab-1 (rat IgG₁, kappa), using the Cell-Based Immunization and Screening (CBIS) method. Cx₁Mab-1 reacted with mCXCR1-overexpressed Chinese hamster ovary-K1 (CHO/mCXCR1) and mCXCR1-overexpressed LN229 glioblastoma (LN229/mCXCR1) in flow cytometry. Cx₁Mab-1 demonstrated a high binding affinity for CHO/mCXCR1 and LN229/mCXCR1 with a dissociation constant of 2.6×10^-9 M and 2.1×10^-8 M, respectively. Furthermore, Cx₁Mab-1 could detect mCXCR1 by western blot analysis. These results indicated that Cx₁Mab-1 is useful for detecting mCXCR1, and provides a possibility for targeting mCXCR1-expressing cells in vivo experiments.

The performance of the nanoribbon biosensor upon the use of two different types of molecular probes — the antibodies and the aptamers against HCVcoreAg — has been tested. The sensor chips employed are based on “silicon-on-insulator structures”. Two different HCVcoreAg preparations have been tested: recombinant b-galactosidase-conjugated HCVcoreAg (“Virogen”, USA) and recombinant HCVcoreAg (“Vector-Best”, Russia). Upon the detection of either type of the antigen preparation, the lowest concentration of the antigen detectable in buffer with pH 5.1 has been found to be approximately equal, amounting to ~10^–14 M. This value has been found to be similar upon the use of either type of molecular probes.

Cluster of differentiation 44 (CD44) is a type I transmembrane glycoprotein, and has been shown as a cell surface marker of cancer stem-like cells in various cancers. Especially, the splicing variants of CD44 (CD44v) are overexpressed in cancers, and play critical roles in cancer stemness, invasiveness, and resistance to chemotherapy and radiotherapy. Therefore, the understanding of the function of each CD44v is indispensable for the CD44-targeting therapy. CD44v9 contains the variant 9-encoded region, and its expression predicts poor prognosis in patients with various cancers. CD44v9 plays critical roles in the malignant progression of tumors. Therefore, CD44v9 is a promising target for cancer diagnosis and therapy. Here, we developed sensitive and specific monoclonal antibodies (mAbs) against CD44 by immunizing mice with CD44v3–10-overexpressed Chinese hamster ovary CHO-K1 (CHO/CD44v3–10) cells. We first determined their critical epitopes using enzyme-linked immunosorbent assay, and characterize their applications to flow cytometry, western blotting, and immunohistochemistry. One of the established clones, C₄₄Mab-1 (IgG₁, kappa) reacted with a peptide of the variant 9-encoded region, indicating that C₄₄Mab-1 recognizes CD44v9. C₄₄Mab-1 reacted with CHO/CD44v3–10 cells or colorectal cancer cell lines (COLO201 and COLO205) by flow cytometry. The apparent dissociation constant (K_D) of C₄₄Mab-1 for CHO/CD44v3–10, COLO201, and COLO205 was 2.5 × 10⁻⁸ M, 3.3 × 10⁻⁸ M, and 6.5 × 10⁻⁸ M, respectively. Furthermore, C₄₄Mab-1 was able to detect the CD44v3–10 in western blotting, and endogenous CD44v9 in immunohistochemistry using colorectal cancer tissues. These results indicated that C₄₄Mab-1 is useful for detecting CD44v9 not only in flow cytometry or western blotting but also in immunohistochemistry against colorectal cancers.

CD44 is a cell surface glycoprotein, and its isoforms are produced by the alternative splicing with the standard and variant exons. The CD44 variant exon containing isoforms (CD44v) are overexpressed in carcinomas. CD44v6 is one of the CD44v, and its overexpression predicts poor prognosis in colorectal cancer (CRC) patients. CD44v6 plays critical roles in CRC adhesion, proliferation, stemness, invasiveness, and chemoresistance. Therefore, CD44v6 is a promising target for cancer diagnosis and therapy for CRC. In this study, we established anti-CD44 monoclonal antibodies (mAbs) by immunizing mice with CD44v3-10-overexpressed Chinese hamster ovary-K1 (CHO) cells. We then characterized them using enzyme-linked immunosorbent assay, flow cytometry, western blotting, and immunohistochemistry. One of the established clones (C44Mab-9; IgG1, kappa) reacted with a peptide of variant 6-encoded region, indicating that C44Mab-9 recognizes CD44v6. Furthermore, C44Mab-9 reacted with CHO/CD44v3-10 cells or CRC cell lines (COLO201 and COLO205) by flow cytometry. The apparent KD of C44Mab-9 for CHO/CD44v3-10, COLO201, and COLO205 was 8.1 × 10−9 M, 1.7 × 10−8 M, and 2.3 × 10−8 M, respectively. C44Mab-9 detected the CD44v3-10 in western blotting, and partially stained the formalin-fixed paraffin-embedded CRC tissues in immunohistochemistry. Collectively, C44Mab-9 is useful for detecting CD44v6 in various applications.

Objective: This study aimed to evaluate the antibody responses in two adult age groups after diphtheria vaccination. Study Design: An observational analytic study was carried out to determine the difference in serum titer of anti-diphtheria antibody. Methods: Serum antibody titers were measured just before and 3 months after injection of Diphtheria toxoid vaccine. Vaccine was given to two adult age groups of health care personnel in hospital: the young (< 40 years) and the middle-aged (≥ 40 years). Data were analyzed using the Mann-Whitney test (p < 0.05). Results: Significant increase in serum anti-diphtheria antibody titers were recorded after vaccination in both age group (p < 0.001 in young adult and p = 0.001 in middle-aged adult, respectively). There were no substantial differences between the two groups in terms of antibody titer before vaccination (p = 0.741), 3 months after vaccination (p = 0.317) and in the increase of antibody titer (p = 0.479). Conclusions: This study showed that there was no significant difference in the increase of anti-diphtheria antibody titers between the two age groups, proving that both young and middle-aged adults had an equal immune response to a given diphtheria vaccine.

Chikungunya virus (CHIKV) is an alphavirus that causes febrile illness punctuated by severe polyarthralgia. After the emergence of CHIKV in the Western Hemisphere, multiple reports of congenital infections were published that documented neurological complications, cardiac defects, respiratory distress, and miscarriage. The Western Hemisphere is endemic to several alphaviruses and whether antigenic cross-reactivity can impact the course of infection has not been explored. Recent advances in biomedical engineering have produced cell co-culture models that replicate the cellular interface at the maternal fetal axis. We employed a trans-well assay to determine if cross-reactive antibodies affected the movement and replication of CHIKV across placental cells and into an embryoid body. The data show that antibodies to Venezuelan equine encephalitis virus (VEEV) significantly reduced CHIKV viral load in embryoid bodies. The data highlight that viral pathogenesis can be cell-specific and that exploiting antigenic cross-reactivity could be an avenue for reducing the impact of congenital CHIKV infections.

It is increasingly common for experiments in biology and medicine to involve large numbers of hypothesis tests. A natural graphical method for visualizing these tests is to construct a histogram from the p-values of these tests. In this article, we examine the shapes, both normal and abnormal, that these histograms can take on, as well as present simple inferential procedures that help to interpret the shapes in terms of diagnosing potential problems with the experiment. We examine potential causes of these problems in detail, and discuss potential remedies. Throughout, examples of abnormal-looking p-value histograms are provided and based on case studies involving real biological experiments.

Overactive bladder (OAB) is characterized by urinary urgency and increased urinary frequency, and can impact quality of life significantly. Tamsulosin and mirabegron combination therapy has been studied as a safe and effective treatment option for patients with OAB. This study evaluated the effects of combining these two drugs on their pharmacokinetics and safety profiles in healthy Korean males. In this open-label, fixed-sequence, 3-period, drug-drug interaction phase 1 study, a total of 36 male participants were administered multiple doses of tamsulosin alone (0.2 mg once daily), mirabegron alone (50 mg once daily), and a combination of both drugs. The results showed that the combination of tamsulosin and mirabegron increased tamsulosin exposure in the plasma by approximately 40%. In contrast, the maximum plasma concentration of mirabegron reduced by approximately 17%, when administered along with tamsulosin. No clinically significant changes in safety profiles, vital signs, or clinical laboratory test results were observed in this study. In conclusion, there were no clinically relevant drug-drug interactions between tamsulosin and mirabegron in terms of pharmacokinetics, safety, and tolerability, suggesting that their combination therapy could be a promising treatment option for patients with OAB.

The drug discovery process is a rigorous and time-consuming endeavor, typically requiring several years of extensive research and development. Although classical machine learning (ML) has proven successful in this field, its computational demands in terms of speed and resources are significant. In recent years, researchers have sought to explore the potential benefits of quantum computing (QC) in the context of ML, leading to the emergence of Quantum Machine Learning (QML) as a distinct research field. The objective of the current study is twofold: first, to present a review of the proposed QML algorithms for application in the drug discovery pipeline, and second, to compare QML algorithms with their classical and hybrid counterparts in terms of their efficiency. A query-based search of various databases took place, and five different categories of algorithms were identified in which QML was implemented. The majority of QML applications in drug discovery are primarily focused on the initial stages of the drug discovery pipeline, particularly with regard to the identification of novel drug-like molecules. Comparison results revealed that QML algorithms are strong rivals against the classical ones and a hybrid solution is the recommended approach at present.

Maximizing the indications potential and revenue from drugs that are already marketed offers a new take on the famous mantra of the Nobel Prize-winning pharmacologist, Sir James Black, “The most fruitful basis for the discovery of a new drug is to start with an old drug”. However, rational design of drug mixtures poses formidable challenges because of the lack of or limited information about in vivo cell regulation, mechanisms of genetic pathway activation, and in vivo pathway interactions. Most of the repositioned drugs therefore are the result of “serendipity” - based on late phase clinical studies of unexpected findings. One of the reasons that the connection between drug candidates and their potential adverse drug reactions or new applications could not be identified earlier is that the underlying mechanism associating them is either very intricate and unknown or dispersed and buried in a sea of information. Discovery of such multi-domain pharmacomodules - pharmacologically relevant sub-networks of biomolecules and/or pathways - from collection of databases by independent/simultaneous mining of multiple datasets is an active area of research. Here, while presenting some of the promising bioinformatics approaches and pipelines, we summarize and discuss the current and evolving landscape of computational drug repositioning.

This study investigates the impact of water stress on grapevines, specifically examining the role of rootstocks and aquaporins. Two experiments on potted plants were conducted in central Chile during the summer, under conditions of high water demand, involving various rootstock genotypes and combinations of Cabernet Sauvignon (CS) grafted onto rootstocks. Significant differences were observed among plants in terms of stem water potential, stomatal conductance, and growth rate. Notably, the CS/CS combination consistently displayed the slowest growth rate, regardless of the irrigation treatment. The study also analyzed the expression levels of plasma membrane intrinsic proteins (PIPs) and tonoplast intrinsic proteins (TIPs) aquaporins in the leaves of grafted plants. Specifically, VvPIP2;2 aquaporins showed reduced expression after 14 days without irrigation, whereas VvTIP1;1 and VvTIP2;1 expression levels correlated positively with gs responses in grafted plants, suggesting their role in modulating water content in leaves under water stress. TIP aquaporins likely play a significant role in the differential responses of CS plants towards nearly isohydric or anisohydric behaviour. The CS/CS combination exhibited near isohydric behavior, correlating with lower TIP aquaporin expression, while the combination of CS onto 1103P and 101-14 showed higher expression, indicating anisohydric behavior. The findings suggest that grafted plants are more resilient to water stress, supporting the idea that rootstocks can mitigate the effects of water stress on the scion.

Breast cancer is currently the second leading cause of death worldwide, accounting for 15% of all deaths (8.2 million deaths). Approximately 20% of breast cancer diagnoses are triple-negative breast cancer (TNBC), a type of cancer that lacks receptors for estrogen (ER negative), progesterone (PR negative), and human epidermal growth factor receptor 2 (HER2/neu negative). Consequently, TNBC doesn’t respond to hormonal or targeted therapies, making it challenging to treat due to its rapid growth, metastasis, and high recurrence rate within the first three years of therapy. Alternative chemotherapies are needed to address this problem. Pharmacological dose of vitamin C (high-dose VC) has been identified as a potential treatment for some cancer cells. The present study aimed to evaluate whether VC has a therapeutic effect on TNBC using MDA-MB-231 cells as the model. MTT assay, Hoechst 33342 staining, Nuclear ID Red/Green staining, Rhodamine 123 staining, and Western blot analysis were employed to test the hypothesis that pharmacological dose of VC can kill TNBC cells. Upregulation of Apaf-1, caspases -3, -6, -7, -8, and -9, inhibition of matrix metalloproteinases (MMP-2 and MMP-9), reduction in cell cycle protein expression, and enhancement of tumor suppressor proteins such as p53 and p21 indicated that pharmacological dose of VC has promising anti-cancer properties in the treatment of TNBC.

The rapid pace of urbanization, coupled with the growing need for environmental sustainability and technological innovation, has brought smart city initiatives to the forefront of global urban development. This paper provides a comparative analysis of smart city policies from leading cities such as Oslo, Zurich, and Canberra, and derives strategic insights for Qatar. By examining the strategies, priorities, outcomes, and challenges associated with implementing smart city initiatives in these cities, the study identifies areas of alignment and divergence with Qatar's own smart city policy framework. The research highlights potential opportunities for cross-learning and suggests how Qatar can leverage lessons from international best practices to enhance its smart city initiatives. Key areas of focus include fostering strategic partnerships, promoting innovation, and ensuring effective governance and data management systems. The findings provide actionable insights to improve the effectiveness of Qatar's smart city projects, aligning them with the Qatar National Vision 2030.

Recent studies with ApoE knockout (ApoE-/-) mice deficient for PACAP (pituitary adenylate cyclase-activating polypeptide) or its receptor PAC1 provide evidence for a possible involve-ment of immune- and vasoregulatoy PACAP signaling at the PAC1 receptor in atherogenesis and plaque associated vascular inflammation. Therefore, we tested the PAC1 receptor agonist Maxadilan and the PAC1 selective antagonist M65 on plaque development and lumen stenosis in the ApoE-/- atherosclerosis model for possible anti-atherogenic effects. Adult male ApoE-/- mice were fed a cholesterol-enriched diet (CED) or standard chow (SC) treat-ed with Maxadilan, M65 or Sham. Effects of treatment on atherosclerotic plaques, lumen stenosis, apoptosis and pro-inflammatory signatures were analyzed in the brachiocephalic trunk (BT). The percentage of Maxadilan treated mice exhibiting plaques under SC and CED was lower than that of Sham or M65 treatment indicating opposite effects of Maxadilan and M65. Maxadilan ap-plication inhibited lumen stenosis under SC and CED compared to Sham. In spite of significantly increased cholesterol levels, lumen stenosis of Maxadilan-treated mice was similar under CED and SC. In contrast, M65 under SC or CED did not reveal a significant influence on lumen steno-sis. Maxadilan significantly reduced the TNF-α+ area in the plaques under CED, but not under SC. In contrast, the IL-1β+ area was reduced after Maxadilan treatment under SC, but remained unchanged under CED compared to Sham. Maxadilan reduced the caspase-3+ area in the media under both SC and CED without affecting lipid content in plaques. Despite persisting hypercholesterolemia, Maxadilan reduces lumen stenosis, apoptosis and TNF-α driven inflammation. Our data suggest that Maxadilan provides atheroprotection by act-ing downstream of cholesterol-induced vascular inflammation. This implicates the potential of PAC1-specific agonist drugs against atherosclerosis even beyond statins and PCSK-9.

Background: Urinary tract infections (UTI) are a significant health concern, particularly in women, with almost half of them experiencing at least one UTI in their lifetime. This problem is further compounded by the high recurrence rate within 6-12 months. Postmenopausal women are especially vulnerable to recurrent UTI due to the natural decline in estrogen levels, which alters the urogenital epithelium and subsequently affects the urogenital microbiome. Methods: This study included 674 female patients that were admited at "Dr. Carol Davila" Central Military Emergency University Hospital in Bucharest over a period of 3 years. Results: Of the 674 women with urinary tract infection, 435 (79.3%) had more than one positive culture, and 239 (35.4%) experienced at least one recurrent urinary tract infection 6-12 months after the initial diagnosis. The mean age of women with urinary tract infection was 63 (± 15.61 years). Recurrent urinary tract infections were most prevalent in those aged 65-80 years (52%). Escherichia coli was detected in 71% of the positive cultures. Conclusions: The management of recurrent urinary tract infections in women presents a complex challenge that necessitates a multifaceted approach. The emerging understanding of the urobiome and its role in bladder health offers promising avenues for developing targeted interventions. As research in this field advances, it is imperative to integrate these new insights into clinical practice to balance traditional antibiotic treatments with novel strategies that consider the intricate microbial ecosystem of the urinary tract.

Disruptions in power quality have a negative impact on many energy consumers. These include lighting, where interference manifests itself, among others, in the form of light flickering. The article presents phenomena accompanying the operation of modern light sources against the background of exemplary results of studies on the flicker of conventional light sources, such as incandescent or fluorescent lamps. To assess the effects of these phenomena, it is necessary to use measures other than those traditionally used. The results of measurements carried out in accordance with different recommendations take into account both power supply disturbances and the properties of modern light sources.

Coronavirus disease (COVID-19) is the current global public health threat with no specific, effective, and approved treatment available till date. The outbreak of COVID-19 has led the world into an unimagined and uncertain situation by disrupting the economies, claiming human lives, and leaving many into secondary mental health problems. As per the latest WHO report, approximately 8.2 million people are infected, and nearly 0.44 million lives are lost to COVID. The infection has spread to over 200 countries and territories around the world. The world is in search of efficient diagnostics and therapeutics, including vaccines, biologics and drugs. With the rapid increase in rates of infection and time constraints, drug repurposing seems to be a potential and viable option to find the promising anti-COVID therapeutics. In the wake of a rapid increase in the number of clinical trials involving drugs for repurposing, we aim to provide information on the safety concerns related to the drugs currently investigated in trials. This review also highlights the possible mechanisms of actions, adverse drug reactions, and contraindications of the drugs under repurposing evaluation.

Psoriasis is a chronic, immune-mediated skin disease significantly impacting women, with disease severity often modulated by hormonal fluctuations. This review examines the influence of hormonal changes on the course of psoriasis in women, focusing on key life stages—including the menstrual cycle, pregnancy, postpartum, and menopause—and their impact on disease progression and symptomatology. Estrogen, the principal female sex hormone, plays a critical role in immune modulation. Variations in estrogen levels, which occur naturally throughout a woman's life, are associated with fluctuations in psoriasis severity. Low estrogen levels, as seen during menstruation or menopause, are linked to symptom exacerbation, while elevated levels during pregnancy may reduce symptoms in some women. However, responses are variable, with others experiencing no change or worsening during pregnancy. Postpartum, the rapid decline in estrogen often triggers severe flare-ups, while menopause, marked by a sustained estrogen reduction, frequently correlates with increased disease severity and flare frequency. The review also addresses the profound impact of psoriasis on women’s quality of life, including physical discomfort, psychological distress, and social stigma. Additionally, fertility concerns are discussed, as severe psoriasis and associated treatments may increase the risk of adverse pregnancy outcomes. Consideration is given to hormonal therapies, lifestyle modifications, and their effects on psoriasis, underscoring the need for personalized treatment approaches that account for hormonal influences. Understanding these hormonal dynamics is essential for developing targeted, effective management strategies that enhance quality of life for women affected by psoriasis.

introduction In the professional practice of nursing, differences have been described between the habitus shared in the academic training process and the professional practice developed in the field of health systems; in this scenario, nurses tend to be affected by how their professional habitus has been established, which, in some way, alters the cultural capital established in their academic training process. The research objective was to identify aspects that facilitate and limit the development of the theoretical component in nursing practice.Method: The research was based on a qualitative hermeneutic study addressed from a critical approach that linked Bourdieu's field theory. The study included 17 students, 11 nurses active in health services, and six university professors. Data were collected from a sociodemographic questionnaire, episodic interviews, and focus groups. The information collected was analyzed using the hermeneutic understanding process from the grounded theory.Results: The research revealed a central thematic core called clarification of the role of the nurse (professional habitus) and three secondary thematic cores related to the need to strengthen the nursing essence (identity habitus), the adjustment of training processes (optimization habitus) and, finally, the strengthening of the nurse's credibility (validation habitus).Conclusion: The professional habitus of nursing professionals is shaped by different elements of the social field of the health system. This field is repressed by hierarchical structures that succeed in disconnecting theory from praxis. Aspects such as subordination to the hegemonic biological discourse and the medical profession, the limited appreciation of humanized care, restrictions on the recognition of the nursing process by health institutions, and limited solidarity and leadership end up conditioning the accumulation of symbolic capital and social capital of nursing, which leads to the loss of autonomy and the advancement of professional development.

The present paper tackles the important issue of tensile ultimate strength of ceramic matrix composites, using a multiscale approach. The ultimate strength is investigated at the successive increasing length scales inherent to 2D woven SiC/SiC composites, i.e. single filaments, fiber tow, minicomposites reinforced with a single tow, and 2D woven composite. First experimental results on tensile behavior under strain-controlled conditions are summarized for tows, minicomposites and composites. Then, models of tow ultimate failure under controlled force and strain are presented. A criterion of tow failure is developed for filament fracture initiation and then propagation based on applied stress and on filament strength gradient. The model of ultimate failure of minicomposite under strain-controlled condition is based on the strength of filaments in the presence of matrix cracks and the overstress induced by interactions of broken filaments and the matrix. The variability of ultimate strengths of filaments, minicomposites and composites at various gauge lengths is described by linear p-quantile diagrams which indicates that the data follow normal distribution function. The contribution of structural effects to variability of composite and minicomposite strength under strain-controlled loading is analyzed. Their dependence on specimen size is related to reproducibility of critical flaw population and structural effects.

Helium is a strategic rare gas resource related to national security and the development of high-tech industries, the high-quality development of helium industry chains has a great significance to improve the security of helium resource. This paper through literature and market research, summarizes the progress of helium resource endowmen, exploration and development, supply and demand pattern, trade market and industrial technology, equipment through literature and market research in the world, analyses the development situation of global helium resources industry chains. This study proposes the development status and challenges of China's helium industry and the corresponding development path of helium industry based on the upstream, midstream, downstream and downstream indicators. Most of the countries in the world have not started helium exploration or remain in low exploration level, but the exploration practice shows that global helium resource potential is considerable; helium exploration and development subjects become diversified in recent years, which may change the global helium supply and demand pattern; The helium reservoir forming theory and exploration and development technology are underdeveloped, and the helium extraction equipment is continuously improved; The global helium production capacity, supply and demand，trade pattern market would be profoundly changing. For a long time, the United States has had an absolute say in the global helium trade system, the contradiction between supply and demand would persist for a long time and significant price fluctuations. China's helium development challenges and opportunities coexist considering the global helium industry chain existing pattern and the new trend of development. There is an urgent need to build an independent and controllable , stable and resilient helium industrial chain, and provide helium resources guarantee for the development of high-tech industries.

The proliferation of cloud computing has given rise to challenges in security that established perimeter-based models cannot easily adapt to. The new buzzword Zero Trust, which is based on the principle of "never trust, always verify," has been looked up as one of the promising solutions. Is Zero Trust a certainty or pie in the sky for security in the cloud? This is discussed further in this paper. This philosophical approach leads us through the earlier work and scientific literature available on the subject, presenting Zero Trust's capabilities, advantages when introduced into cloud security architecture, and obstacles about its incorporation. The study finds that Zero Trust holds the potential to enhance cloud security significantly, but it is no silver bullet and demands careful implementation and further studies to understand its intricacies as well as pitfalls.

Insurance companies need to calculate solvency capital requirements in order to ensure that they can meet their future obligations to policyholders and beneficiaries. The solvency capital requirement is a risk management tool essential for, when extreme catastrophic events occur, resulting in a high number of possibly interdependent claims. This paper studies the problem of aggregating the risks coming from several insurance business lines and analyses the effect of reinsurance in the level of risk. Our starting point is to use a Hierarchical Risk Aggregation method, which was initially based on 2-dimensional elliptical copulas. We then propose the use of copulas from the Archimedean family and a mixture of different copulas. Our results show that a mixture of copulas can provide a better fit to the data than an individual copula and consequently avoid over or underestimating of the capital requirement of an insurance company. We also investigate the significance of reinsurance in reducing the insurance company’s business risk and its effect on diversification. The results show that reinsurance does not always reduce the level of risk, but can also reduce the effect of diversification for insurance companies with multiple business lines.

The primary goal of Theory of Everything (ToE) is to unify General Relativity and Quantum Mechanics, establishing a theoretical framework that explains all natural phenomena and fundamental laws of the universe. The rapid development of artificial intelligence in the 21st century presents new opportunities for the establishment of TOE. Research has revealed that the observer and the agent, as key concepts in physics and intelligence science respectively, share intrinsic consistency. Using this as a breakthrough point, we first proposed Standard Agent Model, which, from the perspective of information processing, establishes a unified structure for agents. This model posits that any agent possesses five essential capabilities: input, output, storage, creation, and control of these four capabilities.By setting the values of these five essential capabilities in Standard Agent Model to either zero or infinity, we identify two extreme states of agents: Absolute Zero Agent (α Point) and Omniscient and Omnipotent Agent (Ω Point). Based on the evolution of agents towards these two extreme states, we derive two driving forces for agent evolution: α Gravity and Ω Gravity. These elements collectively form General Model of Agent Evolution.Building on the first two models, we further derive Intelligent Universe Evolution Model, proposing that Universe, as an agent, evolves dynamically between α Point and Ω Point under the influence of α Field and Ω Field. These three models together constitute "Theory of Universal Intelligent Evolution," abbreviated as Ω Theory. According to Ω Theory, we demonstrate that the observer in physics and a wide range of research objects can be unified within the framework of Standard Agent Model. Additionally, we argue that the four fundamental forces have the potential to be unified into α Gravity and Ω Gravity.Within the framework of Ω Theory, through theoretical analysis and experimental validation, it has been demonstrated that the differences between classical mechanics, relativity, and quantum mechanics stem from the varying intelligence levels assigned to observers. Furthermore, it has been discovered that the differences in intelligent characteristics between the theoretical Universe proposed by these three major physical theories and Universe in which humanity currently resides are the root cause of the varying precision and limitations of these theories.

As the global economy pays increasing attention to sustainable development and environmental protection, the role of green finance in promoting regional technological innovation is becoming more and more prominent. This study aims to analyse the impact of green finance on regional technological innovation and its mechanism of action, with special attention to the mediating effect of R&D inputs and the moderating role of regional characteristics. By analysing the panel data of 30 provinces in China from 2008 to 2021 with fixed and mediated effect models, the results show that green finance significantly promotes regional technological innovation. R&D investment intensity partially mediates this effect, while regional innovation and entrepreneurship capacity plays a significant moderating role in this relationship. Specifically, regional innovation and entrepreneurship capacity reinforces the positive impact of green finance on R&D investment, but the marginal effect of R&D investment is reduced in regions with stronger innovation and entrepreneurship capacity. The findings provide a theoretical basis for formulating relevant policies to promote green finance development and sustainable innovation in regional economies.

Here, we describe the bicomplex (p,q)- Fibonacci numbers and the bicomplex (p,q)- Fibonacci quaternions that are based on these numbers and give some of their equations, including the Binet formula, generating function, Catalan, Cassini, d’Ocagne’s identities, and some summation formulas for both of them. Finally, we create a matrix for bicomplex (p,q)- Fibonacci quaternions, and we obtain a determinant of a special matrix that gives the terms of that quaternion.

In this paper, some convexity properties and some inequalities for the (p,k)-analogue of the Gamma function, Г_p,k(x) are given. In particular, a (p,k)-analogue of the celebrated Bohr-Mollerup theorem is given. Furthermore, a (p,k)-analogue of the Riemann zeta function, ζ_p,k(x) is introduced and some associated inequalities are derived. The established results provide the (p,k)-generalizations of some known results concerning the classical Gamma function.

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

Inhibitors of the factor FXI represent a new class of anticoagulant agents that are facing the clinical approval for the treatment of acute coronary syndrome (ACS), venous thromboembolism (VTE), and stroke prevention of atrial fibrillation (AF). These new inhibitors include chemical small molecules (asundexian and milvexian), monoclonal antibodies (abelacimab, osocimab, and xisomab), and antisense oligonucleotides (IONIS-FXIRX and fesomersen), and thus with very peculiar and different pharmacokinetic and pharmacodynamic properties. Besides their clinical efficacy and safety, based on their pharmacological heterogeneity, the use of these drugs in patients with comorbidities may undergo to drug-drug interactions (DDI) with other concomitant therapies. Although only few clinical evidence are available, it is possible to predict clinical relevant DDI by taking into consideration their pharmacokinetic properties, such as the CYP450-dependent metabolism, the interaction with drug transporters and/or the route of elimination. These characteristics may be useful to differentiate their use with the direct oral anticoagulant (DOAC) anti -FXa (rivaroxaban, apixaban, edoxaban) and thrombin (dabigatran), whose pharmacokinetics are strongly dependent from P-gp inhibitors/inducers. In the present review, we summarize the current clinical evidence on DDI of new anti FXI with CYP450/P-gp inhibitors and inducers and indicate potential differences with DOAC anti FXa.

Of the manifold concepts in drug discovery and design, covalent drugs have re-emerged as one of the most promising over the past 20-or so years. All such drugs harness the ability of a covalent bond to drive an interaction between a target biomolecule, typically a protein, and a small molecule. Formation of a covalent bond necessarily prolongs target engagement, opening avenues to targeting shallower binding sites, protein complexes, and other difficult to drug manifolds, amongst other virtues. This opinion piece discusses frameworks around which to develop covalent drugs. Our argument, based on results from our research program on natural electrophile signaling, is that targeting specific residues innately involved in native signaling programs are ideally poised to be targeted by covalent drugs. We outline ways to identify electrophile-sensing residues, and discuss how studying ramifications of innate signaling by endogenous molecules can provide a means to predict drug mechanism and function and assess on- versus off-target behaviors.

C-C motif chemokine receptor-8 (CCR8) belongs to class A of G protein-coupled receptors (GPCRs). CCR8 interacts with the specific chemokine ligand CCL1/I-309 in humans, which is produced by various cells, including tumor-associated macrophages and regulatory T cells (Treg). CCR8 is highly expressed on Treg and T-helper 2 (T_H2) cells recruited to the inflammation site and is implicated in allergy, asthma, and cancer progression. The CCR8⁺Treg has been suggested to be an important regulator in the immunosuppressive tumor microenvironment (TME); therefore, it has been desired to develop sensitive monoclonal antibodies (mAbs) for CCR8. This study developed a specific mAb for human CCR8 (hCCR8), which is useful for flow cytometry by employing the Cell-Based Immunization and Screening (CBIS) method. The established anti-hCCR8 mAb, C₈Mab-21, (mouse IgM, kappa) reacted with hCCR8-overexpressed Chinese hamster ovary-K1 (CHO/hCCR8) cells, TALL-1 (acute T lymphoblastic leukemia), CCRF-HSB2 (human T-lymphoblastic leukemia), and natural killer cells, which express endogenous hCCR8 by flow cytometry. Furthermore, C₈Mab-21 demonstrated a moderate binding affinity for CHO/hCCR8 and TALL-1 with a dissociation constant of 6.5×10^-8 M and 2.0×10^-8 M, respectively. C₈Mab-21, which was established by the CBIS method, could be a useful tool for analyzing the hCCR8-related biological response using flow cytometry.

Background: Understanding factors associated with protective immunity against emerging viral infections is crucial for global health. Pakistan reported its first COVID-19 case on February 26, 2020, but compared to other countries, it experienced relatively low COVID-19-related morbidity and mortality between 2020 and 2022. The underlying reasons remain unclear. Our research aims to shed light on this crucial issue. Methods: We conducted serial household surveys over 16 months (Rounds 1-4, July 2020 - November 2021) in urban (Karachi) and rural (Matiari) Sindh, sampling 1100 households and 3900 individuals. Our comprehensive approach included measuring antibodies in sera, testing a subset of respiratory samples for COVID-19 using RT-PCR and antigen tests, and measuring Hemoglobin, CRP, Vitamin D, and zinc in Round 1. Results Participants showed 23% (95% CI 21.9-24.5) antibody seroprevalence in round 1, increasing across rounds to 29% (95% CI 27.4-30.6), 49% (95% CI 47.2-50.9) and 79% (95% CI 77.4-80.8). Urban residents had 2.6 times (95% CI 1.9-3.6) higher odds of seropositivity than rural residents. Seropositivity did not differ between genders. Individuals aged 20-49 had 7.5 (95% CI 4.6-12.4) times higher odds of seropositivity compared to children aged 0-4. Most participants were asymptomatic, with no reported mortality. Vitamin D deficiency was linked to seroprevalence. COVID-19 was confirmed in 1.8% of individuals via RT-PCR and antigen tests. Conclusions: The data suggests a steady increase in humoral immunity in Pakistan, likely due to increased transmission and potential cross-protective immunity, which may be associated with asymptomatic disease, leading to the reduction of morbidity and mortality observed.

Inhalation allergies caused by cats and dogs can lead to a range of discomforting symptoms, such as rhinitis and asthma, in humans. Given the increasing popularity and care provided to these companion animals, the allergens they produce pose a growing threat to the health of susceptible patients. Allergens from cats and dogs have emerged as significant risk factors for triggering asthma and allergic rhinitis worldwide; however, there remains a lack of systematic measures aimed at assisting individuals in recognizing and preventing allergies caused by these animals. This review provides comprhensive insights into the classification of cat and dog allerges, alongwith their pathogenic mechanisms. The study also discusses implementation strategies for prevention and control measures, including physical methods, gene editing technology, immunological approaches, as well as potential strategies for enhancing allergen immunotherapy combined with immunoinformatics. Finally, it presents future prospects for the prevention and treatment of human allergies caused by cats and dogs. This review will improve knowledge regarding allergies to cats and dogs, while identifying potential targets for the development of next-generation treatments.

Pretilachlor is a chloroacetamide herbicide, mainly used for the control of weeds and broadleaf weeds in rice, and widely used in China. For the detection of residues of pretilachlor in the en-vironment and food, a highly sensitive and specific monoclonal antibody against pretilachlor was prepared, and the half maximum inhibitory concentration (IC50) of the monoclonal antibody was validated to be 31.47±2.35 μg/L. An indirect competitive ELISA (ic-ELISA) based on the antibody with a linear range of 6.25~100 μg/L was developed for the detection of pretilachlor residues in the environment and food crops. The specificity of the antibody was explained by computer simula-tions and experimental validation. No cross-reactivity of this monoclonal antibody to alachlor, acetochlor and metalaxyl, and it cross-reacted less than 3.0% to both butachlor and propisochlor. The limits of detection (LOD) for pretilachlor in lake, rice, and soil samples were 4.83~5.23 μg/L. The recoveries of all samples were 78.3%~91.3%. The ic-ELISA method was validated by high-performance liquid chromatography, thus, it can be used for residue detection of pretilachlor in the environment and grains.

Immune checkpoint blockade therapy has shown successful clinical outcomes in multiple human cancers. In dogs, several types of tumors resemble human tumors in many respects. Therefore, several groups have developed the anti-dog programmed cell death ligand 1 (dPD-L1) monoclonal antibodies (mAbs) and showed efficacy in several canine tumors. To examine the abundance of dPD-L1 in canine tumors, anti-dPD-L1 diagnostic mAbs for immunohistochemistry are required. In this study, we immunized the peptide in the dPD-L1 intracellular domain, and established anti-dPD-L1 mAbs, L1Mab-352 (mouse IgG1, kappa) and L1Mab-354 (mouse IgG1, kappa). In enzyme-linked immunosorbent assay, L1Mab-352 and L1Mab-354 showed high binding affinity to the dPD-L1 peptide, and the dissociation constants (KD) were determined as 6.9 ×10-10 M and 7.2 ×10-10 M, respectively. Furthermore, L1Mab-352 and L1Mab-354 were applicable for the detection of dPD-L1 in immunohistochemical analysis in paraffin-embedded dPD-L1-expressed cells. These results indicated that L1Mab-352 and L1Mab-354 are useful for detecting dPD-L1 in immunohistochemical analysis.

Breast cancer patients with high levels of HER2 (human epidermal growth factor receptor 2) expression had worse clinical outcomes. Anti-HER2 monoclonal antibody (mAb) is the most important therapeutic modality for HER2-positive breast cancer. We previously immunized mice with the ectodomain of HER2 to create the anti-HER2 mAb, H2Mab-77 (mouse IgG1, kappa). This was then altered to produce H2Mab-77-mG2a-f, an afucosylated mouse IgG2a. In the present work, we examined the reactivity of H2Mab-77-mG2a-f and antitumor effects against breast cancers in vitro and in vivo. BT-474, an endogenously HER2-expressed breast cancer cell line, was identified by H2Mab-77-mG2a-f with a strong binding affinity [a dissociation constant (KD): 5.0 × 10-9 M]. H2Mab-77-mG2a-f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in western blot analysis. Furthermore, H2Mab-77-mG2a-f demonstrated strong antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) for BT-474 cells. MDA-MB-468, a HER2-negative breast cancer cell line, was unaffected by H2Mab-77-mG2a-f. Additionally, in the BT-474-bearing tumor xenograft model, H2Mab-77-mG2a-f substantially suppressed tumor development when compared to the control mouse IgG2a mAb. In contrast, the HER2-negative MDA-MB-468-bearing tumor xenograft model showed no response to H2Mab-77-mG2a-f. These findings point to the possibility of H2Mab-77-mG2a-f as a treatment regimen by showing that it has antitumor effects on HER2-positive breast tumors.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate and compare three different boosters in individuals who received two doses of the BBIBP-CorV vaccine including underlying diseases and healthy cases as control. One hundred forty subjects including 63 ones with at least one of three underlying diseases (UD) (including obesity, hypertension, and diabetes mellitus) and 77 healthy ones (HC) who had received a booster dose (either PastoCovac Plus or PastoCovac or BBIBP-CorV) were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 post-booster shot for evaluating safety outcomes. Significantly increased titers of anti-spike, anti-RBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose, although the titer rise of anti-spike IgG and anti-RBD IgG was insignificantly inferior in the UD group compared to the HC group. All antibodies’ titers declined, with no significant differences between the two groups over time. Notably, all specific antibodies persisted up to 180 days; particularly the neutralizing antibody in both groups. Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension sub-group. PastoCovac Plus and PastoCovac boosters induced higher antibodies’ fold rise in UD individuals than BBIBP-CorV booster recipients. Safety outcomes did not show any serious AEs after the booster injection. The overall incidence of AEs post the booster injection was higher in the UD group than the HC group. Furthermore, the highest systemic AEs rate was reported in the UD group receiving the BBIBP-CorV booster. In conclusion, administration of COVID-19 boosters can equally induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with 2-doses of the BBIBP-CorV. Protein-based boosters with higher antibodies' fold rise and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

CC chemokine receptor 6 (CCR6) is one of the members of G protein-coupled receptor (GPCR) family that is upregulated in many immune-related cells, including B lymphocytes, effector and memory T cells, regulatory T cells, and immature dendritic cells. Coordination between CCR6 and its ligand CC motif chemokine ligand 20 (CCL20) is deeply involved in the pathogenesis of various diseases, such as cancer, autoimmune diseases, and psoriasis. Therefore, CCR6 is an attractive target for therapy and is being investigated as a diagnostic marker for patients. In a previous study, we developed an anti-mouse CCR6 (mCCR6) monoclonal antibody (mAb), C6Mab-13 (rat IgG1, kappa), applicable for flow cytometry by immunizing a rat with N-terminal peptide of mCCR6. This study investigated the binding epitope of C6Mab-13 using enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) methods with the synthesized point mutated-peptides within 1-20 amino acids region of mCCR6. In ELISA, C6Mab-13 lost the reaction to the alanine-substituted peptide of D11A. The epitope of C6Mab-13 was identified to be Asp11 in ELISA. Furthermore, in SPR analysis, the dissociation constants (KD) could not be calculated for G9A and D11A mutants due to lack of binding. The SPR analysis demonstrated that the C6Mab-13 epitope comprises Gly9 and Asp11. Taken together, the key binding epitope of C6Mab-13 was determined to be around Asp11 on mCCR6. Based on the epitope information, C6Mab-13 could be useful for further functional analysis of mCCR6 in future studies.

Zika virus (ZIKV) outbreaks in Central and South America caused severe public health problems in 2015 and 2016. These outbreaks were finally contained through several methods, including mosquito control using insecticides and repellents. Additionally, the development of herd immunity in these countries might have contributed to containing the epidemic. While ZIKV is mainly transmitted by mosquito bites, mucosal transmission via bodily fluids, including the semen of infected individuals, has also been reported. We evaluated the effect of mucosal ZIKV infection on continuous subcutaneous challenges in a cynomolgus monkey model. Repeated intravaginal inoculations of ZIKV did not induce detectable viremia or clinical symptoms, and all animals developed a potent neutralizing antibody, protecting animals from the subsequent subcutaneous superchallenge. These results suggest that viral replication at mucosal sites can induce protective immunity without causing systemic viremia or symptoms.

Regulatory T cells (Tregs) are major drivers behind immunosuppressive mechanisms and present a major hurdle for cancer therapy. Tregs are characterized by high expression of CD25, which is a potentially valuable target for Treg depletion to alleviate immune suppression. The preclinical anti-CD25 (αCD25) antibody, clone PC-61, has met with modest anti-tumor activity, due to its capacity to clear Tregs from circulation and lymph nodes but not those that reside in the tumor. Optimization of the Fc domain of this antibody clone has been shown to enhance intratumoral Treg depletion capacity. Here, we generated a stable cell line that produces optimized recombinant Treg depleting antibodies. A genome engineering strategy in which CRISPR-Cas9 was combined with homology directed repair (CRISPR-HDR) was utilized to optimize the Fc domain of the hybridoma PC-61 for effector functions by switching it from the original rat IgG1 to a mouse IgG2a isotype. In a syngeneic tumor mouse model the resulting αCD25-m2a antibody mediated effective depletion of tumor resident Tregs leading to a high effector T cell (Teff) to Treg ratio. Moreover, combination of the αCD25-m2a with αPD-L1 treatment augmented tumor eradication in mice, demonstrating the potential for αCD25 as a cancer immunotherapy.

Since the outbreak of SARS CoV-2 infection (Covid-19), healthcare professionals worldwide have been trying to find disease management and control alternatives to encourage immunotherapies. Immunotherapy is an efficient therapeutic option used against comparable viral contaminations such as MERS-CoV and SARS-CoV. The aim of the current study is to assess the existing knowledge associated with SARS-CoV-2 immunotherapy. Information available in published articles and their quality highlights the importance of following strict scientific rules for clinical outcomes. Thus, these studies have shown enough data to confirm that immunomodulation is the main topic investigated in research about Covid-19 therapy. Therefore, it is possible saying that immunotherapy is certainly the appropriate option against this virus.

To date, viral RNA detection is almost the only way to confirm SARS-CoV-2infectionin practice.However, variousreasons can cause low sensitivity for RNA detection, and thisposes aserious challenge to disease control. We tested the performance of detecting total antibody(Ab) and IgM levels in serum by the methods of chemiluminescence, enzyme-linked immunosorbent assay (ELISA), and colloidal golddetection. The datashowed that the sensitivity and specificity for detecting total Ab and IgM levels were high by all three methods, and the sensitivity was higher for detecting total Ab than for detecting IgM. Evidence from studieshas shown thatviral RNA testingcombinedwith serological testing could increase the diagnostic sensitivity while maintaining a high specificity. Specific serology testsfor SARS-CoV-2 havegreat value for clinical practice and public health.

We introduce the notion of p-adic equiangular lines and derive the first fundamental relation between common angle, dimension of the space and the number of lines. More precisely, we show that if {τj} n j=1 is p-adic γ-equiangular lines in Qd p , then (1) |n| 2 ≤ |d| max{|n|, γ2 }. We call Inequality (1) as the p-adic van Lint-Seidel relative bound. We believe that this complements fundamental van Lint-Seidel [Indag. Math., 1966] relative bound for equiangular lines in the p-adic case. Keywords: Equiangular lines, p-adic Hilbert space.

This article presents a proposed system that enables energy transfer from the dc grid to a single-phase onboard grid, operating at an hi frequency. In addition to the energy transfer function, it additionally enables compensation of reactive power in the ac grid when the converter operates at less than rated power. To operate in compensator mode, it is necessary to decouple the current from the grid into active and reactive components and control them independently. To achieve good dynamics, synchronizers that operate in the dq system are used. In the case of a single-phase grid, it requires such a synchronizer to generate virtual quadrature signals. The used systems based on second-order generalized integrator are good, but to improve dynamics in the work a quadrature generator based on trigonometric calculations was proposed. The developed system was implemented in a proportional resonant current control system. Tests performed in steady state and in dynamic states related to typical grid disturbances showed better dynamic properties than the standard integrator-based system.Keywords: power transfer; compensator; P+R controller

Arc sensors have been used in seam tracking and widely studied since the 80s; commercial arc sensing products for T and V shaped grooves have been developed. However, it is difficult to use these arc sensors in narrow gap welding because arc stability and sensing accuracy are not satisfactory. Pulse gas melting arc welding (P-GMAW) has been successfully applied in narrow gap welding and all position welding processes, so it is worthwhile to research P-GMAW arc sensing technology. In this paper, we derived a linear mathematical P-GMAW model for arc sensing, and the assumptions for the model are verified through experiments and finite element methods. Finally, the linear characteristics of the mathematical model were investigated. In torch height changing experiments, uphill experiments, and groove angle changing experiments the P-GMAW arc signals all satisfied the linear rules. In addition, the faster the welding speed, the higher the arc signal sensitivities; the smaller the groove angle, the greater the arc sensitivities. The arc signal variation rate needs to be modified according to the welding power, groove angles, and swing or rotate speed.

Pardosa pseudoannulata is one of the most common wandering spiders in agricultural fields and a potentially good bioindicator for heavy metal contamination. However, little is known about the mechanism by which spiders respond to heavy metals at the molecular level. In this study, high-throughput transcriptome sequencing was employed to characterize the de novo transcriptome of the spiders and to identify differentially expressed genes (DEGs) after cadmium exposure. We obtained 60,489 assembled unigenes, 18,773 of which were annotated in the public databases. Ultimately, 3450 cDNA simple sequence repeats were identified and validated as potential molecular markers in the unigenes. A total of 2939, 2491 and 3759 DEGs were detected among the three libraries of two Cd-treated groups and the control. Functional enrichment analysis revealed that metabolism processes and digestive system function were predominately enriched in response to Cd stress. At the cellular and molecular levels, significantly enriched pathways in lysosomes and phagosomes as well as replication, recombination and repair demonstrated that oxidative damage resulted from Cd exposure. Based on the selected DEGs, certain critical genes involved in defence and detoxification were analysed. These results may elucidate the molecular mechanism underlying spiders' responses to heavy metal stress.

The emergence of mRNA vaccines represents a significant advancement in public health by conferring protection against a variety of infectious diseases. However, concerns regarding the potential risk of inducing or exacerbating autoimmune disorders, particularly connective tissue diseases (CTDs), have arisen. This paper explores the mechanisms by which mRNA vaccines may lead to the onset or worsening of CTDs, focusing on the immune responses induced by Pathogen-Associated Molecular Patterns (PAMPs), the interactions between Toll-like receptors 7/8 and 9 (TLR7/8 and TLR9), and the activation of self-reactive B cells. Furthermore, guidelines are suggested for administering vaccines to individuals at elevated risk, such as those with a positive antinuclear antibody (ANA) test or specific rheumatic disease genes. Our findings underscore the necessity for targeted vaccination strategies that mitigate risks while maintaining public health efficacy.

Tick-borne encephalitis (TBE) is the most significant arboviral infection in Croatia. The aim of the study was to analyse and correlate 17-year TBE seroprevalence data with winter temperature, precipitation and wildlife abundance to identify possible patterns that can be predictive of TBE incidence. TBE diagnosis was based on IgM/IgG anti-TBE antibodies and individual clinical interpretation of the results. Of the 19,094 analysed patients, 4.2% had acute TBE, significantly more often in older age (p<0.001) and in men (p<0.001). Overall seroprevalence of TBE among the tested population was 5.8%, and varied annually from 2.8% to 10.7%. The mean acute TBE incidence rate was 1.1 per 100.000 population with significant regional differences: 1.7 in the continental vs. 0.2 and 0.5 in the Mediterranean and Alpine regions, respectively. Particularly high incidence of 3.1 was recorded in northern Croatia. TBE displayed a seasonal pattern, peaking in June and July. Moderate negative correlations were observed between TBE acute cases and winter temperatures from December to February (r=-0.461; p=0.062), relative rodent abundance (r=-0.414; p=0.098) and yearly precipitation from one year before (r=-0.401; p=0.123). Considerable efforts are needed to understand the impact on TBE incidence to improve disease prevention.

Understanding the factors that contribute to slope failures, such as soil saturation, is essential for mitigating rainfall-induced landslides. Cost-effective capacitive soil moisture sensors have the po-tential to be widely implemented across multiple sites for landslide early warning systems. How-ever, these sensors need to be calibrated for specific applications to ensure high accuracy in readings. In this study, a soil-specific calibration was performed in a laboratory setting to integrate the soil moisture sensor with an automatic monitoring system using the Internet of Things (IoT). This re-search aims to evaluate a low-cost soil moisture sensor (SKU:SEN0193) and develop calibration equations for the purpose of slope model experiment under artificial rainfall condition using silica sand. The results indicate that a polynomial function is the best fit, with a coefficient of determi-nation (R²) ranging from 0.92 to 0.98 and a root mean square error (RMSE) ranging from 1.17 to 2.67. The calibration equation was validated through slope model experiments, with soil samples taken from the model after the experiment finished. Overall, the moisture content readings from the sensors showed approximately a 10% deviation from the actual moisture content. The findings suggest that the cost-effective capacitive soil moisture sensors has the potential to be used for the development of landslide early warning system.

In the present study, we introduce the two dimensional Chlodovsky type Bernstein operators based on (p,q)−integer. We examine approximation properties of our new operator by the help of Korovkin-type theorem. Further, we present the local approximation properties and establish the rates of convergence by means of the modulus of continuity and the Lipschitz type maximal function. Also, we give a Voronovskaja type theorem for this operators. And, we investigate weighted approximation properties of these operators and estimate rate of convergence in the same space. Finally, with the help of Maple, illustrative graphics show the rate of convergence of these operators to certain functions . The optimization of approximation speeds by operators during system control provides significant improvements in stability and performance. As a result, the control and modeling of dynamic systems become more efficient and effective through innovative methods. These advancements in the fields of modeling fractional differential equations and control theory offer substantial benefits to both modeling and optimization processes, expanding the range of applications in these areas.

This article advances the discourse on sustainable and energy-efficient software by examining the performance and energy efficiency of intelligent algorithms within the framework of green and sustainable computing. Building on previous research, it explores the theoretical implications of Bremermann's Limit on efforts to enhance computer performance through more extensive methods. The study presents an empirical investigation into heuristic methods for search and optimisation, demonstrating the energy efficiency of various algorithms in both simple and complex tasks. It also identifies key factors influencing the energy consumption of algorithms and their potential impact on computational processes. Furthermore, the article discusses cognitive concepts and their interplay with computational intelligence, highlighting the role of cognition in the evolution of intelligent algorithms. The conclusion offers insights into the future directions of research in this area, emphasising the need for continued exploration of energy-efficient computing methodologies.

The last 20 years have seen significant advancements in polymeric drug delivery methods. A formulation or a system that makes it possible for a medicinal ingredient to be injected into the body is known as polymeric drug delivery1. The key choice for many novel medication delivery methods is made achievable by biodegradable and bio-reducible polymers. The research's prospects for practical applications have necessitated the field's development—the choice for a lot of new drug delivery systems. The prospects of the research for practical applications are required for the development in the field. Polymeric drug delivery methods have been developed from natural polymers like arginine, chitosan2, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid. Regarding polymeric drug delivery1, synthetic polymers such as poly(2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide), poly(ethylenimine), dendritic polymers, biodegradable, and bioabsorbable polymers have all been considered. Polymeric drug delivery has also been addressed by focusing on drug-free macromolecular therapies, biomimetic and bio-related polymeric systems, and targeting polymeric drug delivery. Pharmaceutical fields are seeing a tremendous rise in the development of polymeric drug delivery methods based on natural and manmade polymers. The successful advancements in the utilization of biocompatible and bio-related copolymers and dendrimers in cancer treatment, including their application as vehicle systems for highly effective anticancer medications3. A new paradigm for the development of polymeric drug and gene delivery systems will be possible through the fusion of viewpoints from the synthetic and biological domains.

The practical application of a pH-responsive Nanoparticle Drug Delivery System (NDDS) in cancer treatment is often hampered by several issues such as the protection of therapeutic molecules from external stresses, inefficient targeted delivery, sustained drug release, and poor efficacy. This study presents an effective design strategy for the synthesis of a pH-sensitive controlled hydrophobic drug delivery method based on the formulation of chitosan (CS)-coated mesoporous silica nanoparticles (MSNs) through the sol-gel method, where hydrolysis takes place in the acidic medium followed by polycondensation of the hydrolyzed products. For this purpose, NH2 modified-MSNs were prepared by using tetraethyl orthosilicate (TEOS) as precursor and cetyltrimethylammonium bromide (CTAB) as a template, and 3-aminopropyltriethoxysilane (APTES) for amine modification, followed by hydrophobic drug loading and CS coating of various concentrations. Camptothecin (CPT) was used as a model drug. Fabricated monodispersed functionalized nanoparticles had sizes ranging from 200nm to 245nm with an encapsulation efficiency as high as 90%. The highest encapsulation efficiency was found for 1% CS coating, which released 50% drug in 120h at pH 6.4 and 20% at pH 7.4 respectively. These nanoformulations exhibited pH-responsive release patterns of CPT under two different pH values (pH=7.4 and pH=6.4). These results contribute to the optimization of NDDS, with potential implications for nanoformulations designed for controlled and sustained drug release particularly to tumors without affecting healthy cells owing to differences in the pH of the tumor microenvironment and the normal physiological environment of cells.

We discuss further details on the concepts of “drug-likeness”, “lead-likeness”, and “natural product-likeness”. The discussion will first focus on natural products as drugs, then a discussion of previous studies in which the complexities of the scaffolds and chemical space of naturally occurring compounds have been compared with synthetic, semi-synthetic compounds and FDA-approved drugs. This is followed by guiding principles for designing “drug-like” natural product libraries for lead compound discovery purposes. We end up by presenting a tool for measuring “natural product-likeness” of compounds and a brief presentation of machine learning approaches and a binary quantitative structure-activity relationship (QSAR) for classifying drugs from non-drugs and natural compounds from non-natural ones, respectively.

Background: no reports have examined the profile of drug-induced dysphagia in detail. The goal of this study was to investigate if there are any differences in the profiles of drug-induced dysphagia. Methods: This study used the Japanese Adverse Drug Event Report (JADER) database. Further, reported odds ratios (RORs) were used to analyze data on adverse drug events from 2004 to 2021. The top ten drugs with the most drug-induced dysphagia occurrences were used as target drugs. The association between RORs and drug-induced dysphagia caused by the target drugs was evaluated, and the age distribution and time of onset of drug-induced dysphagia for each drug were compared. RORs were the primary endpoint. Moreover, age and time of onset of drug-induced dysphagia were secondary outcomes. Results: In total, 756,965 reports were analyzed. All the target drugs were associated with drug-induced dysphagia. Among them, cevimeline was a novel finding, as no dysphagia was observed during the clinical trial. For most drugs, the onset of drug-induced dysphagia was occurring within approximately 25 days of administration. However, even after long-term use, paroxetine and milnacipran were associated with drug-induced dysphagia. Conclusion: The onset profile of drug-induced dysphagia may differ from one drug to the next.

Drug repurposing is a valuable tool for combating the slowing rates of novel therapeutic discovery. The Computational Analysis of Novel Drug Opportunities (CANDO) platform performs shotgun repurposing of 2030 indications/diseases using 3733 drugs/compounds to predict interactions with 46,784 proteins and relating them via proteomic interaction signatures. An accuracy is calculated by comparing interaction similarities of drugs approved for the same indications. We performed a unique subset analysis by breaking down the full protein library into smaller subsets and then recombining the best performing subsets into larger supersets. Up to 14% improvement in accuracy is seen upon benchmarking the supersets, representing a 100–1000 fold reduction in the number of proteins considered relative to the full library. Further analysis revealed that libraries comprised of proteins with more equitably diverse ligand interactions are important for describing compound behavior. Using one of these libraries to generate putative drug candidates against malaria results in more drugs that could be validated in the biomedical literature than the list suggested by the full protein library. Our work elucidates the role of particular protein subsets and corresponding ligand interactions that play a role in drug repurposing, with implications for drug design and machine learning approaches to improve the CANDO platform.

This article explores how Artificial Intelligence (AI) is drastically changing the logistics industry by transforming operations and significantly improving customer satisfaction. Through meticulous analysis of real-life cases and extensive examination of numerical data, this comprehensive research thoroughly investigates the profound impact of AI on supply chain management. The findings clearly reveal the multifaceted role of AI in significantly reducing costs, greatly improving delivery accuracy, and significantly enhancing inventory control. AI is not just an incremental advancement, but rather a revolutionary leap forward for the future logistics industry, firmly paving the way for unparalleled automation, digital transformation, and operational effectiveness.

Pancreatic cancer, one of the deadliest cancers worldwide, necessitates improved therapeutics due to its low survival rate (12% in 5 years) and typically late-stage diagnosis [1]. This malignancy tends to present asymptomatically until advanced stages, leading to high rates of metastasis and limiting surgical options [2]. Genetic mutations in key genes like KRAS, CDKN2A, TP53, and SMAD4 are central to pancreatic cancer pathogenesis, driving uncontrolled cell proliferation and making treatment difficult [3]. Current treatment modalities include surgery, chemotherapy, radiation, and emerging immunotherapies. Surgery, particularly the Whipple procedure, offers the only potential cure but is applicable in just 15-20% of cases due to the late diagnosis [4]. Chemotherapy, though commonly used, offers limited long-term survival benefits [5]. Radiation therapy has seen advancements with techniques like stereotactic body radiation therapy (SBRT), which shows promise in reducing toxicity and improving outcomes [6] . Immunotherapy, particularly mRNA vaccines, has demonstrated potential in prolonging recurrence-free survival (>18 months), especially when combined with traditional therapies (13.4 months with surgical resection alone) [7] . Combinations of different treatments have been found to be effective. The challenge of early pancreatic cancer diagnosis mirrors the difficulty of disease management. Prophylactic immunotherapies, like vaccines, could offer a crucial breakthrough for prevention and recurrence reduction. As pancreatic cancer remains difficult to treat effectively, continued research and development in preventative and therapeutic strategies are essential to improving outcomes.

In an outstanding article published in 2008, Suzuki obtained a nice generalization of the Banach contraction principle from which derived a characterization of metric completeness. Although Suzuki’s theorem has been successfully generalized and extended in several directions and contexts, we here show by means of a simple example that the problem of achieving, in an obvious way, its full extension to the framework of w-distances does not have an emphatic response. Motivated by this fact we introduce the concept of presymmetric w-distance on metric spaces, we give some properties and examples of this new structure and show that it provides a reasonable setting to obtain a real and hardly forced w-distance generalization of Suzuki’s theorem. This is realized in our main result, which is a fixed point theorem that involves presymmetric w-distances and certain contractions of Suzuki-type. We also discuss the relationship between our main result and the well-known w-distance full generalization of the Banach contraction principle, due to Suzuki and Takahashi. Connected to this approach we prove another fixed point result that compare with our main result through some examples. Finally, we state a characterization of metric completeness by using our fixed point results.

Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) are environmental pollutants with a great persistence, capacity of bioaccumulation, and well known important toxic effects in humans and animals. Incinerators of hazardous, municipal and medical waste, chlorine bleaching of paper pulp, cement plants, and the traffic of motor vehicles are the most frequent emission sources of these compounds. The diet, followed at a great distance by inhalation, is generally the main way of human exposure to PCDD/Fs. Human biomonitoring is of a great importance to prevent potential adverse effects derived from exposure to chemicals such as PCDD/Fs. In relation to this, blood is among the most used biological monitors. In the current review, we have summarized the recent information (2000-2009) published in the scientific literature (databases: Scopus and PubMed) on the concentrations of PCDD/Fs in blood samples of non-occupationally exposed populations, as well as in some groups of occupationally exposed individuals. We have revised a number of studies conducted in various African American, Asian and European countries, and Australia. Unfortunately, the information is quite limited. No data are available for most countries over the world. Based on the results here reviewed –where available- the current health risks for the general populations do not seem to be of concern. Moreover, taking into account the important reductions observed in the levels of PCDD/Fs in foodstuffs, new decreases in the concentrations of PCDD/Fs in blood -and other biological tissues- are very probable in the immediate years.

Understanding the interaction between pharmaceuticals and serum proteins is crucial for optimizing therapeutic strategies, especially in patients with coexisting chronic diseases. The primary goal of this study was to assess the potential changes in binding affinity and competition between glipizide (GLP, a second-generation sulfonylurea hypoglycemic drug) and losartan (LOS, a medication commonly prescribed for hypertension, particularly for patients with concurrent diabetes) with non-glycated (HSA) and glycated (gHSAGLC, gHSAFRC) human serum albumin using multiple spectroscopic techniques (fluorescence, UV-visible absorption, and circular dichroism spectroscopy). The results indicate that FRC is a more effective glycation agent for HSA than GLC, significantly altering the albumin structure and affecting the microenvironment around critical amino acid residues, Trp-214 and Tyr. These modifications reduce the binding affinity of LOS and GLP to gHSAGLC and gHSAFRC, compared to HSA, resulting in less stable drug-protein complexes. The study reveals that LOS and GLP interact nonspecifically with the hydrophobic regions of the albumin surface in both binary (ligand-albumin) and ternary systems (ligand-albumin-ligandconst) and specifically saturate the binding sites within the protein molecule. Furthermore, the presence of an additional drug (GLP in the LOS-albumin complex or LOS in the GLP-albumin complex) complicates the interactions, likely leading to competitive binding or displacement of the initially bound drug in both non-glycated and glycated albumins. Analysis of the CD spectra suggests mutual interactions between GLP and LOS, underscoring the importance of closely monitoring patients co-administered these drugs to ensure optimal therapeutic efficacy and safety. Początek formularzaDół formularza

Objective: The main purpose of this meta-analysis was to assess the efficacy and safety of Oncolytic Viruses (OVs) in glioma therapy. Methods: We searched the literature in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcomes assessed were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs). The risk of bias was evaluated by sensitivity analysis and publication bias. Results: We identified 21 studies with 440 patients in this meta-analysis. In the single-arm analysis, the results showed that the 1-year OS rate was 47% (95% CI: 34%-61%, I2 = 75%) and the 2-year OS rate was 14% (95% CI: 10%-20%, I2 = 0%). The median OS was 12.48 months (95% CI: 10.71-14.25, I2 = 96%). The 1-year PFS rate was 13% (95% CI: 5%-24%, I2 = 0%), with the median PFS being 4.01 months (95% CI: 2.99-45.03, I2 = 96%). The pooled estimate of ORR was 7% (95% CI: 3%-12%, I2 = 23%). Funnel plots for median PFS were asymmetric with Egger’s test P < 0.01 indicating publication exists. The incidence of OVs-related AEs was 49% (95% CI: 20%-79%, I2 = 95%), and AEs > grade 3 was 8% (95% CI: 3%-16%, I2 = 62%). Conclusion: This meta-analysis indicated that OVs therapy was relatively safe but did not significantly extend survival in patients with gliomas.