Search Results (2,457)

Surgical site infections (SSIs) remain a significant complication in spine surgery, especially in instrumented procedures with long operative times. Although guidelines recommend cefazolin as the first-line agent due to its efficacy against Staphylococcus aureus, predictable pharmacokinetics, and safety, its real-world practice is highly variable, with inappropriate and prolonged regimens reported across Europe. Vancomycin is often used as the first choice of therapy empirically and without screening, exposing patients to risks such as delayed infusion, nephrotoxicity, and the emergence of vancomycin-resistant enterococci (VRE).This review assesses the present function of vancomycin in relation to cefazolin for spinal prophylaxis and examines wider trends in the misuse of surgical antibiotic prophylaxis, which were identified through PubMed and Scopus searches. Evidence from randomized and prospective studies consistently supports cefazolin as the preferred prophylactic agent in clean spinal surgery. Observational data suggest that adjunctive or topical vancomycin may reduce infection rates in selected high-risk or revision cases, though the results are inconsistent and frequently limited by retrospective designs and heterogeneous outcome reporting. Importantly, the most rigorous randomized controlled trial found no benefit of intrawound vancomycin over the placebo. A small number of available investigations in vancomycin use with major design limitations have resulted in no significant VRE emergency. Unexpectedly, widespread use of vancomycin was followed by a notable transition toward Gram-negative and opportunistic organisms. In summary, vancomycin may only be considered in patients with documented MRSA colonization, β-lactam allergy, or selected revision procedures, but its widespread empirical use as a first-choice therapy is not supported. Full article

This paper describes two low-cost, modular instruments developed for rapid room-temperature characterization of mainly thermoelectrics. The first instrument measures the Seebeck coefficient across diverse sample geometries and incorporates a four-point probe configuration for simultaneous electrical conductivity measurement, including disk-shaped samples. The second instrument implements the Van der Pauw method, enabling detailed investigation of charge carrier behavior within materials. Both devices prioritize accessibility, constructed primarily from 3D-printed components, basic hardware, and readily available instrumentation, ensuring ease of reproduction and modification. A unique calibration protocol using pure elemental disks and materials with well-established properties was employed for both instruments. Validation against comparable systems confirmed reliable operation. Control and data acquisition software for both devices was developed in-house and is fully documented and does not require an experienced operator. We demonstrate the utility of these instruments by characterizing the electronic properties of polycrystalline SnSe thermoelectric materials doped with Bi, Ag, and In. The results reveal highly complex charge carrier behavior significantly influenced by both dopant type and concentration. Full article

The southeastern Tibet region is characterized by rugged terrain and relative isolation, which has significantly constrained the development of agriculture. However, due to the extremely limited archaeological and historical records available, its important role in the history of agricultural development in Tibet has been overlooked. This study focuses on the Linzhi and Changdu regions of southeastern Tibet, integrating limited archival, historical, and documentary data. By reconstructing historical settlement patterns and population data, this study estimates the arable land area during the Tubo, Yuan, Ming, and Qing dynasties. Using a grid-based model, it reconstructs the distribution patterns of arable land during these periods, aiming to provide a reference for the development of agriculture in Tibet. The research findings indicate the following: (1) During historical periods, settlements in southeastern Tibet were primarily distributed in flat, resource-rich alluvial plains at medium to high altitudes. Settlement types exhibited spatial differentiation: Post stations were primarily situated along major transportation routes that connected river valleys, as well as at high mountain passes. Temples tended to occupy moderately steep slopes, while manors were concentrated in low-lying valleys. (2) During the Tubo, Yuan, Ming, and Qing periods, the total arable land area and cultivation rate in southeastern Tibet were generally low, with total arable land areas of 28,085 hm², 29,449 hm², 25,319 hm², and 24,371 hm², respectively, and cultivation rates of 0.12%, 0.13%, 0.11%, and 0.11%, respectively. (3) Farmland was predominantly distributed along the Yarlung Zangbo, Jinsha, Lancang, and Nu Rivers and their broader tributary valleys. Natural constraints resulted in a highly fragmented farmland distribution. Full article

Reproducibility is a cornerstone of scientific progress, yet in X-ray computed tomography (CT) reconstruction, it remains a critical and unresolved challenge. Current benchmarking practices in CT are hampered by the scarcity of openly available datasets, the incomplete or task-specific nature of existing resources, and the lack of transparent implementations of widely used methods and evaluation metrics. As a result, even the fundamental property of reproducibility is frequently violated, undermining objective comparison and slowing methodological progress. In this work, we analyze the systemic limitations of current CT benchmarking, drawing parallels with broader reproducibility issues across scientific domains. We propose an extended data model and formalized schemes for data preparation and quality assessment, designed to improve reproducibility and broaden the applicability of CT datasets across multiple tasks. Building on these schemes, we introduce checklists for dataset construction and quality assessment, offering a foundation for reliable and reproducible benchmarking pipelines. A key aspect of our recommendations is the integration of virtual CT (vCT), which provides highly realistic data and analytically computable phantoms, yet remains underutilized despite its potential to overcome many current barriers. Our work represents a first step toward a methodological framework for reproducible benchmarking in CT. This framework aims to enable transparent, rigorous, and comparable evaluation of reconstruction methods, ultimately supporting their reliable adoption in clinical and industrial applications. Full article

Biofilm formation is a key factor in microbial survival and persistence, often contributing to reduced antimicrobial susceptibility. This systematic literature review investigates whether increased biofilm formation correlates with decreased antibiotic susceptibility. The literature search was conducted in the Pubmed database and we identified and screened 328 studies, with 35 ultimately meeting the inclusion criteria for detailed analysis. Findings reveal that the relationship between biofilm size and antimicrobial susceptibility is highly variable and influenced by multiple factors, including microbial species, strain-specific traits, antibiotic type, and experimental methodologies. While some studies report a positive correlation between biofilm biomass and reduced susceptibility, others show weak or no such relationships, and statistical support for a correlation is often lacking (also due to small sample sizes). The lack of standardized biofilm quantification methods and susceptibility metrics further complicates cross-study comparisons. These findings underscore the need for standardized protocols and more comprehensive datasets to clarify the complex interplay between biofilm formation and antibiotic susceptibility. Regardless of these difficulties, the available data clearly indicate that ‘bigger’ biofilms are not by definition less susceptible. Future research should prioritize diverse and sufficiently large strain collections and consistent methodologies to better understand and address biofilm-associated antimicrobial tolerance. Full article

Background/Objectives: This study analyzes the epidemiology of invasive pneumococcal disease (IPD) and the dynamics of Streptococcus pneumoniae (SP) serotypes in the Comunidad Valenciana (CV) region, Spain, over a 10-year period (2014–2024), with particular focus on vaccine coverage of PCV13 compared to the newer PCV20 and PCV21 formulations. Methods: A total of 2.014 isolates of SP obtained from sterile fluids were included, with available serotype, demographic data, and vaccination status, which were collected from the Epidemiological Surveillance System (AVE) and the Microbiological Surveillance Network of the CV region (RedMIVA). Results: Overall vaccination coverage was low (22.4%), with the highest rates observed in children under 10 years (78%) compared to only 16% in those aged 10–64 years and 22% in those over 64. Serotype distribution revealed 120 distinct serotypes, with serotype 8 (17.6%) and serotype 3 (14.7%) being the most frequent. Serotype 8 predominated among unvaccinated individuals, while serotype 3 remained highly prevalent despite inclusion in PCV13. Other relevant serotypes included 22F, 9N, 19A, 6C, and 23A. Temporal analysis showed that serotype 3 has continued to increase in recent years, whereas serotype 8 rose during the pandemic period but has remained stable in the most recent interval, while 19A, 15A, and 11A significantly declined. Among serotypes with <2% incidence, some, such as 4, 24F, and 38, showed upward trends. Conclusions: The findings suggest that PCV20 currently provides broad coverage of dominant serotypes, but PCV21 may offer advantages should serotypes like 23A, 9N, or 15A increase further due to serotype replacement. Continuous epidemiological surveillance is essential to guide evidence-based vaccine policy and anticipate future vaccine reformulations. Full article

The emergence of H5N1 highly pathogenic avian influenza virus (HPAIV) clade 2.3.4.4b in dairy cattle across multiple U.S. states in early 2024 marks a major shift in the virus’s host range and epidemiological profile. Traditionally limited to bird species, the ongoing detection of H5N1 in cattle, a mammalian host not previously considered vulnerable, raises urgent animal and human health concerns about zoonoses and mammalian adaptation. We assessed the feasibility of using commercially available pasteurized milk as a sentinel matrix for the molecular detection and genetic characterization of H5N1 HPAIV. Our aim was to determine whether retail milk could serve as a practical tool for virological monitoring and to evaluate the use of full-length genome segment amplification for extracting genomic sequence information from this highly processed matrix. Our results link HPAIV sequences in store-bought milk to the cattle outbreak and highlight both the potential and the limitations of retail milk as a surveillance window. Together, these findings provide evidence that influenza A virus RNA can be repeatedly detected in retail milk in patterns linked to specific supply chains, with genomic data confirming close relationships with the viruses circulating in cattle. Full article

(1) Chronic heart failure (CHF) is a typical component of the polymorbid profile of an elderly patient. The aim of this systematic review was to search for data from pharmacokinetic (PK) studies of any drugs in patients with CHF to systematize information on changes in PK parameters depending on the physicochemical properties (PCPs) of the drug and route of its administration. (2) A systematic review of PK studies in patients with CHF was performed using Elibrary.ru, United States National Library of Medicine (PubMed), China National Knowledge Infrastructure (CNKI), and Directory of Open Access Journals (DOAJ). The final number of included articles was 106. A descriptive and correlation analysis of PK data and PCPs of drugs included in the study was carried out. Inclusion criteria: PK study, available PK parameters, demographic data, and diagnosed CHF. Risk of bias was assessed using ROBINS-I. (3) Evaluation of correlations between PCPs of drugs and their PK revealed a link between (i) plasma protein binding (PPB) and volume of distribution for lipophilic drugs; (ii) PCPs, half-life, and clearance for drugs with high PPB; and (iii) PPB and clearance for hydrophilic and amphiphilic drugs. (4) Hypoalbuminemia associated with CHF may lead to an increased volume of distribution of lipophilic drugs; lipophilic drugs used in CHF patients may be associated with prolongation of the half-life period and reduction in clearance; highly protein-bound drugs may manifest with reduced clearance. PK characteristics identified in this review should guide modifications to dosing regimens in CHF patients receiving medications from different groups. Full article

Environmental degradation and soil desertification are among the most severe environmental issues of recent decades worldwide. Over time, these processes have led to increasingly extreme and highly dynamic climatic conditions. In Brazil, the Northeast Region is characterized by semi-arid and arid areas that exhibit high climatic variability and are extremely vulnerable to environmental changes and pressures from human activities. The application of geotechnologies and geographic information system (GIS) modeling is essential to mitigate the impacts and pressures on the various ecosystems of Northeastern Brazil (NEB), where the Caatinga biome is predominant and critically threatened by these factors. In this context, the objective was to map and assess the spatiotemporal patterns of land use and land cover (LULC), detecting significant trends of loss and gain, based on surface reflectance data and precipitation data over two decades (2000–2019). Remote sensing datasets were utilized, including Landsat satellite data (LULC data), MODIS sensor data (surface reflectance product) and TRMM data (precipitation data). The Google Earth Engine (GEE) software was used to process orbital images and determine surface albedo and acquisition of the LULC dataset. Satellite data were subjected to multivariate analysis, descriptive statistics, dispersion and variability assessments. The results indicated a significant loss trend over the time series (2000–2019) for forest areas (Z_MK = −5.872; Tau = −0.958; p < 0.01) with an annual loss of −3705.853 km² and a total loss of −74,117.06 km². Conversely, farming areas (agriculture and pasture) exhibited a significant gain trend (Z_MK = 5.807; Tau = 0.947; p < 0.01), with an annual gain of +3978.898 km² and a total gain of +79,577.96 km², indicating a substantial expansion of these areas over time. However, it is important to emphasize that deforestation of the region’s native vegetation contributes to reduced water production and availability. The trend analysis identified an increase in environmental degradation due to the rapid expansion of land use. LULC and albedo data confirmed the intensification of deforestation in the Northern, Northwestern, Southern and Southeastern regions of NEB. The Northwestern region was the most directly impacted by this increase due to anthropogenic pressures. Over two decades (2000–2019), forested areas in the NEB lost approximately 80.000 km². Principal component analysis (PCA) identified a significant cumulative variance of 87.15%. It is concluded, then, that the spatiotemporal relationship between biophysical conditions and regional climate helps us to understand and evaluate the impacts and environmental dynamics, especially of the vegetation cover of the NEB. Full article

Cable service providers face significant challenges in managing Hybrid Fiber–Coaxial (HFC) networks due to the growing demand for high-speed services. Ensuring high service availability is critical to preventing customer attrition. This study employs machine learning techniques, specifically Decision Tree and Random Forest models, for proactive fault detection in HFC networks using data from the Simple Network Management Protocol (SNMP). Two operational scenarios were considered: a network-wide model and node-specific models. The dataset for fault detection exhibited a severe class imbalance, with outage events being extremely rare. To address this, the Synthetic Minority Oversampling Technique (SMOTE), which generates synthetic samples of the minority class to balance the dataset, was applied. This significantly improved recall and F1-scores—the harmonic mean of precision and recall—while maintaining high precision. The results demonstrate that these machine learning algorithms achieve up to 98% accuracy, and the SMOTE-enhanced models provide more reliable detection of connectivity faults. This approach is highly effective for cable operators in maintaining quality of service, enabling proactive management of problems and enhancement of network performance. Full article

This review of thiazolidinedione or glitazone, which have a five-membered heterocyclic ring C₃NS, shows their versatile properties in terms of pharmacological actions such as antimicrobial, antifungal, insecticidal, pesticidal, antidiabetic, anti-inflammatory, anti-proliferative, anti-neurotoxicity, anticonvulsant, anti-thyroidal, and anti-tubercular uses. While having a wide range of biological activities, the TZDs mainly act via binding to the peroxisome proliferator-activated receptor (PPAR) members. PPAR-γ are ligand-activated transcription factors, which are members of the nuclear hormone receptors group. Activations of PPAR-γ regulate cell proliferation and differentiation, glucose homeostasis, apoptosis, lipid metabolism, and inflammatory responses. This review explores the synthesis of a thiazolidinedione and its derivatives, focusing on their pharmacological profiles and antidiabetic activity. It highlights the benefits of synthesis, reaction profiles, and catalyst recovery, which may encourage further investigation into these scaffolds by researchers. Based on synthesized derivatives, some glimpses of the structure–activity relationships of some compounds have been compiled. All the synthesized derivatives have been reviewed concerning their standard drugs already available and concluded with the highly or moderately active synthesized derivatives of thiazolidinedione. The data for this review was collected by an extensive review of current scientific literature, including on the synthesis, biological evaluation, SAR, and patents (2015–25). Full article

Chickpea (Cicer arietinum L.) is a key legume crop of global economic and nutritional importance, yet its cultivation in Kazakhstan is constrained by a narrow genetic base and exposure to stress-prone environments. To characterize the diversity available for breeding and conservation, 27 accessions (22 kabuli and 5 desi) were evaluated for phenotypic and molecular diversity to assess its potential for use in breeding programs. Seven agronomic traits were assessed, including plant height, the first pod’s height, the number of main stems per plant, and seed yield components. The collection showed considerable variability across traits, with the plant height ranging from 37 to 75 cm and hundred-seed weight ranging from 21 to 42 g. Strong positive correlations between the number of fertile nodes, number of seeds per plant, and yield per plant (r > 0.83) highlighted their utility as indirect selection criteria. Genotyping with 28 SSR markers revealed 110 alleles (mean 3.9 ± 0.4 per locus) with moderate polymorphism (PIC = 0.493 ± 0.089). Loci CaM00495 and TAI71 were highly informative (PIC > 0.804), while two accessions showed low polymorphism, indicating genetic uniformity. Population structure analysis grouped accessions into four highly admixed clusters. Overall, Kazakh chickpea germplasm exhibits substantial phenotypic and genetic diversity under optimal conditions, providing valuable preliminary data for selecting parental lines for future breeding programs, which should include targeted stress screening to evaluate resilience. Full article

Chimeric Antigen Receptor (CAR)-T cell therapy has transformed the treatment landscape of cancer, yet major challenges remain in enhancing efficacy, reducing adverse effects, and expanding accessibility. Autologous CAR-T cells, derived from individual patients, have achieved remarkable clinical success in hematologic malignancies; however, their highly personalized nature limits scalability, increases costs, and delays timely treatment. Allogeneic CAR-T cells generated from healthy donors provide an “off-the-shelf” alternative but face two critical immune barriers: graft-versus-host disease (GvHD), caused by donor T-cell receptor (TCR) recognition of host tissues, and host-versus-graft rejection, mediated by recipient immune responses against donor HLA molecules. Recent advances in genome engineering, particularly Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9, allow precise modification of donor T cells to overcome these limitations. For example, TRAC gene knockout eliminates TCR expression, preventing GvHD, while disruption of HLA molecules reduces immunogenicity without impairing cytotoxicity. Beyond hematologic cancers, CRISPR-edited allogeneic CAR-T cells targeting the NKG2D receptor have shown promise in preclinical studies and early-phase trials. NKG2D CAR-T cells recognize stress ligands (MICA/B, ULBP1–6) expressed on over 80% of diverse solid tumors, including pancreatic and ovarian cancers, thereby broadening therapeutic applicability. Nevertheless, the genomic editing process carries risks of off-target effects, including potential disruption of tumor suppressor genes and oncogenes, underscoring the need for stringent safety and quality control. This review examines the distinguishing features of allogeneic versus autologous CAR-T therapy, with a particular focus on NKG2D-based allogeneic CAR-T approaches for solid tumors. We summarize current strategies to mitigate immune barriers, discuss practical manufacturing challenges, and analyze available clinical data on NKG2D CAR-T trials. Collectively, these insights underscore both the promise and the hurdles of developing safe, universal, and scalable allogeneic CAR-T therapies for solid malignancies. Full article

Background: Atypical teratoid rhabdoid tumor (ATRT) is a highly aggressive, rare pediatric central nervous system malignancy. Prognostic factors for optimizing risk stratification and management in a large uniformly treated cohort are lacking. Methods: We conducted a single-center retrospective cohort study analyzing clinical and outcome data for 100 newly diagnosed ATRT patients aged <18 years treated at the Children’s Cancer Hospital, Egypt, from 2008 to 2022. They were treated uniformly as per the Dana-Farber Cancer Institute modified IRS-III protocol. Molecular subgroups (MYC, SHH, and TYR) were determined via a DNA methylation array for patients who had sufficient DNA material available for the methylation analysis. Treatment toxicities were graded per the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: The median age at diagnosis was 1.88 years (IQR 0.99, 3.01); 28% were under 1 year of age, 45% were between 1 and 3 years old, and 26% were above 3 years of age. At diagnosis, 39% of patients had metastatic disease. A total of 60% of patients had gross residual disease following surgical excision. In multivariable analysis, age < 1 year and metastatic disease had a significant impact on event-free survival (EFS) (p = 0.047 and p = 0.002, respectively); however, only metastatic disease had a significantly negative effect on overall survival (OS) and cumulative incidence of relapse (CIR) (p = 0.002 for OS and p < 0.001 for CIR). DNA methylation was performed for 69 patients who were classified as having a TYR (n = 13), SHH (n = 34), MYC (n = 17), or non-ATRT diagnosis (n = 5). In the cohort of the 64 patients with ATRT defined by methylation, no significant survival differences were observed. Treatment-related deaths were reported in 28% of our studied group. Gram-negative septicemia was the most common cause of toxic death. The 5-year EFS and OS of the whole cohort were 12% and 13%, respectively. Conclusions: In this cohort, no significant survival differences were observed among the methylation subgroups. The higher treatment-related mortality in our cohort compared to the original protocol’s toxic-related deaths suggested that intensive and lengthy chemotherapy regimens may need modification for our population. The need for a short intensified approach, including a limited induction cycle followed by an intensified high-dose consolidation therapy, may be more appropriate for our patients with low socioeconomic status to avoid a repeated and prolonged course of protracted neutropenia. Full article

Background: Entrusted budgets were introduced as part of the primary healthcare (PHC) system in Poland in July 2022. This initiative aimed to increase the role of PHC and enhance the accessibility of diagnostic services and specialist consultations/advice for patients. Methods: Data from the National Health Fund (NHF) databases regarding contracts between the NHF and healthcare providers in the field of PHC from 2022 to 2025 were analyzed. The share of contracts with entrusted budgets in the total number of PHC physician contracts was estimated in individual voivodships, as well as in counties, using the example of the Małopolskie Voivodship. It was assessed whether there were significant differences between voivodships and counties as well as the pace of implementation of the new solution. Results: Only 43.1% of PHC physicians have signed contracts with the NHF for coordinated care services for 2025, with this percentage varying significantly between voivodships, ranging from 24.8% in Opolskie Voivodship to 66.3% in Lubelskie Voivodship (p < 0.0001). For the vast majority of voivodships, no statistically significant increase in the share of service providers was demonstrated in the period from 2022 to 2025. Access to services between counties is also highly varied (from 10.0% to 76.5%), although the differences were not statistically significant (p = 0.217). Conclusions: The results indicate regional and local inequalities in access to services. It is necessary to implement incentive mechanisms within the contracting of health services between the NHF and providers that will ensure equal access to PHC services within entrusted budgets for all patients. The range of available services should be equal regardless of at which PHC facility a patient is registered. The current regulations concerning entrusted budgets, including the voluntary involvement of service providers, are not sufficient. Full article