Search Results (1,627)

Introduction: Septic-induced cardiomyopathy (SICM) is a life-threatening condition in patients with septic shock. Persistent hypoperfusion despite adequate volume status and vasopressor use is associated with poor outcomes and is currently managed with inotropes. However, the superiority of available inotropic agents remains unclear. This meta-analysis aims to determine which inotropic agent may be more effective in this clinical scenario. Methods: A systematic review and meta-analysis were conducted, including data from randomized clinical trials (RCTs) comparing levosimendan and dobutamine in patients with septic shock and persistent hypoperfusion. Summary effect estimates, including odds ratios (ORs), standardized mean differences (SMDs), and 95% confidence intervals (CIs), were calculated using a random-effects model. Trial sequential analysis (TSA) was also performed. Results: Of 244 studies screened, 11 RCTs were included. Levosimendan was associated with a reduction in in-hospital mortality (OR 0.64; 95% CI: 0.47; 0.88) and ICU length of stay (SMD 5.87; 95% CI: –8.37; 20.11) compared with dobutamine. Treatment with levosimendan also resulted in significant reductions in BNP (SMD –1.87; 95% CI: –2.45; −1.2) and serum lactate levels (SMD –1.63; 95% CI: –3.13; −0.12). However, TSA indicated that the current evidence is insufficient to definitively confirm or exclude effects on in-hospital and 28-day mortality. Conclusions: Levosimendan may improve hemodynamics, tissue perfusion, and biomarkers, and may reduce in-hospital mortality and ICU length of stay in patients with SICM compared with dobutamine. However, TSA highlights the need for further studies to inform clinical practice and optimize inotrope selection. Full article

Background/Objectives: Evidence-based nursing practice (EBNP) is essential in high-acuity settings such as intensive care units (ICUs) and emergency departments (EDs), where nurses are frequently required to make time-critical, high-stakes clinical decisions that directly influence patient safety and outcomes. Despite its recognized importance, the implementation of EBNP remains inconsistent, with frontline nurses often facing barriers to accessing and applying current evidence. Methods: This descriptive, cross-sectional study systematically mapped and prioritized clinical questions generated by ICU and ED nurses at a tertiary hospital in South Korea. Using open-ended questionnaires, 204 clinical questions were collected from 112 nurses. Each question was coded and classified according to the Nursing Interventions Classification (NIC) taxonomy (8th edition) through a structured cross-mapping methodology. Inter-rater reliability was assessed using Cohen’s kappa coefficient. Results: The majority of clinical questions (56.9%) were mapped to the Physiological: Complex domain, with infection control, ventilator management, and tissue perfusion management identified as the most frequent areas of inquiry. Patient safety was the second most common domain (21.6%). Notably, no clinical questions were mapped to the Family or Community domains, highlighting a gap in holistic and transitional care considerations. The mapping process demonstrated high inter-rater reliability (κ = 0.85, 95% CI: 0.80–0.89). Conclusions: Frontline nurses in high-acuity environments predominantly seek evidence related to complex physiological interventions and patient safety, while holistic and community-oriented care remain underrepresented in clinical inquiry. Utilizing the NIC taxonomy for systematic mapping establishes a reliable framework to identify evidence gaps and support targeted interventions in nursing practice. Regular protocol evaluation, alignment of continuing education with empirically identified priorities, and the integration of concise evidence summaries into clinical workflows are recommended to enhance EBNP implementation. Future research should expand to multicenter and interdisciplinary settings, incorporate advanced technologies such as artificial intelligence for automated mapping, and assess the long-term impact of evidence-based interventions on patient outcomes. Full article

Systematic reviews are a cornerstone of evidence-based research, providing comprehensive summaries of existing studies to answer specific research questions. This article offers a detailed guide to conducting high-quality systematic reviews in biology, health and social sciences. It outlines key steps, including developing and registering a protocol, designing comprehensive search strategies, and selecting studies through a screening process. The article emphasizes the importance of accurate data extraction and the use of validated tools to assess the risk of bias across different study designs. Both meta-analysis (quantitative approach) and narrative synthesis (qualitative approach) are discussed in detail. The guide also highlights the use of frameworks, such as GRADE, to assess the certainty of evidence and provides recommendations for clear and transparent reporting in line with the PRISMA 2020 guidelines. This paper aims to adapt and translate evidence-based review principles, commonly applied in clinical research, into the context of biological sciences. By highlighting domain-specific methodologies, challenges, and resources, we provide tailored guidance for researchers in ecology, molecular biology, evolutionary biology, and related fields in order to conduct transparent and reproducible evidence syntheses. Full article

Background/Objectives: The Plague of Justinian marked the beginning of the First Pandemic (541–750 CE), yet no genomic evidence of Yersinia pestis has previously been recovered from the Eastern Mediterranean, where the outbreak was first recorded. This study aimed to determine whether Y. pestis was present in a mid-6th to early 7th century mass grave in Jerash, Jordan, and to characterize its genome within the broader context of First Pandemic strains. Methods: We analyzed samples from multiple individuals recovered from the Jerash mass grave. Initial screening for potential pathogen presence was conducted using proteomics. Select samples were subjected to ancient DNA extraction and whole genome sequencing. Comparative genomic and phylogenetic analyses were conducted to assess strain identity and evolutionary placement. Results: Genomic sequencing recovered Y. pestis DNA from five individuals, revealing highly similar genomes. All strains clustered tightly with other First Pandemic lineages but were notably recovered from a region geographically close to the pandemic’s historical epicenter for the first time. The near-identical genomes across diverse individuals suggest an outbreak of a single circulating lineage at the time of this outbreak. Conclusions: This study provides the first genomic evidence of Y. pestis in the Eastern Mediterranean during the First Pandemic, linking archaeological findings with pathogen genomics near the origin point of the Plague of Justinian. Summary Sentence: Genomic evidence links Y. pestis to the First Pandemic in an ancient city. Full article

A unique line of Holstein cattle has been maintained without selection in Minnesota since 1964. After many generations, unselected cattle produce less milk, but have better reproductive performance and health traits when compared with contemporary cows. Comparisons between this line of unselected Holstein and those under selection provide useful insights that connect selection and complex traits in cattle. Utilizing these unique resources and sequence data, we sought to identify genome changes due to selection. We sequenced 30 unselected and 54 selected Holstein cattle and compared their sequence variants to identify selection signatures. After many years, the two populations showed completely different patterns in their genome-level population structures and linkage disequilibrium. By integrating signals from five different detection methods, we detected consensus selection signatures from at least four methods covering 14,533 SNPs and 155 protein-coding genes. An integrated analysis of selection signatures with gene annotation, pathways, and the cattle QTL database demonstrated that the genomic regions under selection are related to milk productivity, health, and reproductive efficiency. The polygenic nature of these complex traits is evident from hundreds of selection signatures and candidate genes, suggesting that long-term artificial selection has acted on the whole genome rather than a few major genes. In summary, our study identified candidate selection signatures underlying phenotypic differences between unselected and selected Holstein cows and revealed insights into the genetic basis of complex traits in cattle. Full article

Plant pathogenesis-related (PR) proteins are a large and diverse family of proteins with antimicrobial activity, often induced by pathogen attack. Traditionally, PR proteins were thought to mainly participate in plant defense mechanisms against biotic stress. However, in recent years, increasing evidence has shown that these proteins also play important roles in the response to abiotic stress in plants. In the present review, we provide a summary of the latest findings on PR proteins and focus on their response to various abiotic stresses, the mechanism by which PR proteins are activated by external and internal signals, and their biological functions in plant responses to abiotic stresses. In addition, the existing challenges and future applications are also summarized, aiming to provide a reference for further research on PR proteins in the context of plant physiology. Full article

Artificial intelligence (AI) agents are increasingly shaping vital sectors of society, including healthcare, education, supply chains, and finance. As their influence grows, AI alignment research plays a pivotal role in ensuring these systems are trustworthy, transparent, and aligned with human values. Leveraging blockchain technology, proven over the past decade in enabling transparent, tamper-resistant distributed systems, offers significant potential to strengthen AI alignment. However, despite its potential, the current AI alignment literature has yet to systematically explore the effectiveness of blockchain in facilitating secure and ethical behavior in AI agents. While existing systematic literature reviews (SLRs) in AI alignment address various aspects of AI safety and AI alignment, this SLR specifically examines the gap at the intersection of AI alignment, blockchain, and ethics. To address this gap, this SLR explores how blockchain technology can overcome the limitations of existing AI alignment approaches. We searched for studies containing keywords from AI, blockchain, and ethics domains in the Scopus database, identifying 7110 initial records on 28 May 2024. We excluded studies which did not answer our research questions and did not discuss the thematic intersection between AI, blockchain, and ethics to a sufficient extent. The quality of the selected studies was assessed on the basis of their methodology, clarity, completeness, and transparency, resulting in a final number of 46 included studies, the majority of which were journal articles. Results were synthesized through quantitative topic analysis and qualitative analysis to identify key themes and patterns. The contributions of this paper include the following: (i) presentation of the results of an SLR conducted to identify, extract, evaluate, and synthesize studies on the symbiosis of AI alignment, blockchain, and ethics; (ii) summary and categorization of the existing benefits and challenges in incorporating blockchain for AI alignment within the context of ethics; (iii) development of a framework that will facilitate new research activities; and (iv) establishment of the state of evidence with in-depth assessment. The proposed blockchain-based AI alignment framework in this study demonstrates that integrating blockchain with AI alignment can substantially enhance robustness, promote public trust, and facilitate ethical compliance in AI systems. Full article

In response to the global ecological and agricultural challenges posed by coastal saline-alkali areas, this study focuses on Dongying City as a representative region, aiming to develop a high-precision soil salinity prediction mapping method that integrates multi-source remote sensing data with machine learning techniques. Utilizing the SCORPAN model framework, we systematically combined diverse remote sensing datasets and innovatively established nine distinct strategies for soil salinity prediction. We employed four machine learning models—Support Vector Regression (SVR), Random Forest (RF), Extreme Gradient Boosting (XGBoost), and Geographical Gaussian Process Regression (GGPR) for modeling, prediction, and accuracy comparison, with the objective of achieving high-precision salinity mapping under complex vegetation cover conditions. The results reveal that among the models evaluated across the nine strategies, the SVR model demonstrated the highest accuracy, followed by RF. Notably, under Strategy IX, the SVR model achieved the best predictive performance, with a coefficient of determination (R²) of 0.62 and a root mean square error (RMSE) of 0.38 g/kg. Analysis based on SHapley Additive exPlanations (SHAP) values and feature importance indicated that Vegetation Type Factors contributed significantly and consistently to the model’s performance, maintaining higher importance than traditional salinity indices and playing a dominant role. In summary, this research successfully developed a comprehensive, high-resolution soil salinity mapping framework for the Dongying region by integrating multi-source remote sensing data and employing diverse predictive strategies alongside machine learning models. The findings highlight the potential of Vegetation Type Factors to enhance large-scale soil salinity monitoring, providing robust scientific evidence and technical support for sustainable land resource management, agricultural optimization, ecological protection, efficient water resource utilization, and policy formulation. Full article

The fungal kingdom, with an estimated five million species, has undergone extensive diversification over the past billion years and now occupies a wide array of ecological niches from terrestrial to aquatic ecosystems. To thrive in such diverse environments, fungi must exhibit finely tuned physiological and morphological responses orchestrated by conserved molecular pathways. Increasing evidence suggests that aquaporins (AQPs) play a key role in mediating these adaptive responses, particularly under varying abiotic and biotic stress conditions. However, despite notable advances in recent decades, the precise functional roles of AQPs within the fungal kingdom remains largely unresolved in the field of cell biology. AQPs are transmembrane proteins belonging to the major intrinsic proteins (MIPs) superfamily, which is characterized by remarkable sequence and structural diversity. Beyond their established function in facilitating water transport, MIPs mediated the bidirectional diffusion of a range of small inorganic and organic solutes, ions, and gases across cellular membranes. In fungi, MIPs are classified into three main subfamilies: orthodox (i.e., classical) AQPs, aquaglyceroporins (AQGP), and X-intrinsic proteins (XIPs). This review provides a concise summary of the fundamental structural and functional characteristics of fungal aquaporins, including their structure, classification, and known physiological roles. While the majority of the current literature has focused on the aquaporin and aquaglyceroporin subfamilies, this review also aims to offer a comprehensive and original overview of the relatively understudied X-intrinsic protein subfamily, highlighting its potential implication in fungal biology. Full article

Feline infectious peritonitis (FIP) is a severe viral disease with a very high fatality rate. GS-441524 is an adenosine analogue that acts as an antiviral and has shown promise in FIP treatment. However, its commercialization in some regions is not yet authorized. To evaluate the efficacy of GS-441524 based on the published literature, a systematic review was conducted. This systematic review was conducted using PubMed, ScienceDirect, and Google Scholar for studies published from 2018 onwards. Following PRISMA guidelines, 11 studies (totaling 650 FIP cases treated with GS-441524 alone or in combination) were included. Therapeutic efficacy was assessed by FIP form, clinical signs, and dosage. The overall treatment success rate was 84.6%. This rate was higher when GS-441524 was combined with other antivirals and lower in cases of wet FIP or those with neurological complications. Combination therapy with other antivirals may improve outcomes in complicated FIP cases, although further studies are needed. The GS-441524 dosages associated with the best outcomes were 5–10 mg/kg once daily (or equivalent subcutaneous dose), adjusted for FIP type, severity, and presence of neurological/ocular signs. Higher dosages can be used for severe cases or to prevent relapse, but splitting into twice-daily dosing may be necessary to avoid absorption issues. In summary, this synthesis indicates that GS-441524 is a highly promising treatment for FIP, with a high success rate among treated cases. Nevertheless, randomized controlled trials are needed to establish evidence-based therapeutic protocols tailored to different FIP presentations. Full article

Background/Objectives: The gold standard of treatment for both melanoma and non-melanoma skin cancers is wide surgical resection to obtain oncological radicality, which occasionally results in functional or aesthetic impairment, potentially affecting quality of life. Despite the increased complexity of the technique, extended duration of hospitalization, and prolonged surgical operative times, microsurgery can facilitate the reconstruction of locally invasive skin cancers following ablative surgery and may yield superior functional and aesthetic outcomes. Consequently, microsurgical reconstruction is more likely to be necessary if a large skin tumor requires excision. However, the impact of this extensive and complex procedure on patients with skin cancer has not yet been fully elucidated. The objective of this research was to critically analyze the utilization of free flap reconstruction subsequent to skin cancer therapy. Through a comprehensive examination of published data, this study aimed to assess the potential benefits and drawbacks associated with this reconstructive approach. Methods: A systematic review of studies that were published from January 2004 to May 2024 was conducted using the MEDLINE online database search. To present an evidence summary and provide a systematic approach and quality assessment, the GRADE^® rating was applied to the results. Results: This review summarizes the oncological and clinical data, including previous interventions, adjuvant and neoadjuvant therapies, nodal status, distant metastasis, and follow-up time. Surgical outcome parameters such as healing time, flap survival, revision rate success, and minor and major complications were documented. Along with the findings, a quality assessment of the studies was also provided. Conclusions: This systematic review underscores the extensive use and efficacy of microsurgery for reconstruction after skin cancer excision; however, the literature remains limited by inconsistent reporting of oncological outcomes and the lack of a standardized approach to evaluate the impact of free flap reconstruction on both immediate and long-term cancer-specific results. Full article

Background/objectives: In some cases of concomitant use of direct oral anticoagulants (DOAC) and certain anticancer medications, pharmacokinetic interactions are expected; however, clinical data is scarce. This report reviews the recommendations on the use of DOAC concurrently with anticancer drugs according to different clinical decision support systems and sources, with a focus on discrepancies. Methods: We reviewed the recommendations from the American Heart Association (AHA), European Heart Rhythm Association (EHRA), summary of product characteristics (SPC) in FASS (Swedish medicine information portal), the Swedish clinical decision support system Janusmed, and information from the Food and Drug Administration (FDA) on the concomitant use of apixaban, edoxaban, and rivaroxaban (activated factor X (FXa) inhibitors) and 80 anticancer drugs from 11 categories (240 drug pairs). Results: No warnings of expected pharmacokinetic drug interactions between FXa inhibitors and anticancer drugs were found for 155 drug pairs (65%) across all sources. The remaining 35% of drug pairs were flagged as having possible interactions with FXa inhibitors according to at least one source. Discrepancies in the recommendations from the different sources were reported. The reported discrepancies were, for the most part, associated with different assessments of the mechanism and the extent of pharmacokinetic interactions of each anticancer medication. Also, knowledge sources have different approaches to reporting potential interactions, in some cases reporting clinically relevant strictly pharmacokinetic interactions, whereas others include even patient-specific factors. Conclusions: The lack of clinical data and different recommendations can make clinical decisions on the concomitant use of DOAC and anticancer drugs difficult. Our compilation is meant to assist clinicians in making decisions based on the available evidence, even if it is scarce. Full article

Neuro-oncology focuses on the diagnosis and treatment of brain tumors, which, despite their rarity, are associated with high mortality due to their invasiveness and limited treatment options. Emerging evidence suggests that dopamine (DA), a neurotransmitter crucial for cognitive and emotional processes, and its receptors may influence tumor growth and the tumor microenvironment. This study aimed to evaluate the potential anticancer effects of repurposed antipsychotic dopamine-targeting drugs (Clozapine, CLZ; Pimozide, PIM; Olanzapine, OLZ; and Risperidone, RIS) and antiemetic drugs (Domperidone, DOM; Droperidol, DRO) on neuroblastoma (SH-SY5Y) and glioblastoma (A172) cell lines, and to assess whether their efficacy is modulated by oxidative stress and DA synthesis. The drugs were first tested individually, followed by co-treatment with tyrosine (Tyr), a dopamine precursor, and hydrogen peroxide (H₂O₂), an inducer of oxidative stress. Additionally, drug activity was evaluated in the simultaneous presence of H₂O₂ and Tyr. CLZ exhibited the highest cytotoxicity in both cell lines, suggesting strong anticancer potential and also synergism among the different combinations, particularly in SH-SY5Y. Liquid chromatography of the extracellular medium showed greater Tyr consumption in SH-SY5Y compared to A172 cells, indicating a higher dependence on extracellular Tyr to mitigate drug- and/or stress-induced cytotoxicity. In summary, several of the repurposed antipsychotics demonstrated cytotoxic effects on central nervous system tumor cells, with CLZ showing the most promising activity, even under oxidative stress conditions. These findings support further investigation into dopamine-targeting drugs as potential therapeutic agents in neuro-oncology. Full article

Background and Objectives: Lung cancer represents one of the principal causes of cancer-associated mortality worldwide. Despite the numerous novel therapeutic agents, surgical resection remains, in many cases, the mainstay treatment. A growing body of evidence indicates that the anesthetic technique of choice contributes to perioperative immunosuppression, thus having an impact on cancer recurrence and prognosis. The aim of this systematic review is to provide a thorough summary of the current literature regarding the modulation of the immune response induced by the various anesthetic techniques that are used in lung cancer surgery, with a particular emphasis on cellular immunity. Materials and Methods: PubMed, Scopus, and the Cochrane databases were systematically searched from November 2023 up to March 2024 to identify randomized controlled trials (RCTs) that met the eligibility criteria. Results: A total of seven RCTs were included. Four of the RCTs compared the administration of general anesthesia alone versus general anesthesia combined with epidural anesthesia. The subsequent meta-analysis showed that the combination of general and epidural anesthesia exerted a positive impact on the cell counts of the CD3+ cells (SMD −0.42, 95% Cl −0.70 to −0.13 24 h postoperatively and SMD −0.86 95% Cl −1.48 to −0.23 72 h postoperatively), the CD4+ cells (SMD −0.41 95% Cl −0.69 to −0.12 at the end of surgery and SMD −0.56 95% Cl −0.85 to −0.27 72 h later), and the CD4+/CD8+ ratio (SMD −0.31 95% Cl −0.59 to −0.02 immediately after surgery, SMD −0.50 95% Cl −0.86 to −0.14 24 h postoperatively, and SMD −0.60 95% Cl −0.89 to −0.31 72 h later). The pooled results regarding CD8+ and NK cell counts were inconclusive. The remaining three studies compared volatile-based anesthesia with total intravenous anesthesia (TIVA). Due to disparities between these studies, qualitative analysis was inconclusive, whereas quantitative analysis was not feasible. Conclusions: The supplementation of general anesthesia with epidural anesthesia favorably impacts CD3+ and CD4+ cell counts, as well as the CD4+/CD8+ ratio. The present results and the effects of anesthetic technique on other immune cells must be consolidated with further high-quality studies. Full article

Background: Female Sexual Dysfunction (FSD) encompasses a range of conditions that can profoundly impact quality of life and intimate relationships. The primary classifications of FSD include female sexual interest and arousal disorder (FSIAD), genitopelvic pain and penetration disorder (GPPPD), female orgasmic disorder (FOD), and substance or medication-induced sexual dysfunction (SM-ISD). Despite its prevalence, FSD is often underdiagnosed and undertreated. Objectives: This scoping review follows Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to evaluate the existing literature on both U.S. Food and Drug Administration (FDA)-approved and off-label pharmacotherapies for FSD by study type, outcomes, and limitations. Eligibility Criteria: Eligible studies comprised randomized controlled trials (RCTs), systematic reviews, and cohort studies involving adult women (≥18 years) with any subtype of FSD. These studies assessed pharmacologic interventions against a comparator and reported at least one treatment efficacy outcome. Studies outside this scope were excluded. Sources of Evidence: A 25-year literature search was conducted using PubMed/MEDLINE, the Cochrane Library, reference lists of relevant articles, academic handbooks, and targeted journals. Charting Methods: Three independent reviewers screened and extracted data. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Findings were organized into summary tables and categorized by pharmaceutical agent, pertinent study information, outcomes, and limitations. Results: A total of 44 human-based pharmacologic studies met inclusion criteria. FDA-approved agents were the most thoroughly studied pharmacotherapies. Hormonal, topical, and adjunctive agents demonstrated less robust evidence. Heterogeneity in outcome measures and inadequate long-term data were common limitations. Conclusions: Pharmacologic treatment for FSD shows promise but requires further research. Individualized, multifaceted care is essential for optimizing FSD outcomes. Full article