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Population pharmacokinetic analysis of intravenous voriconazole in cancer patients

Purpose The pharmacokinetics of voriconazole have been studied across various populations but data specific to the Pakistani cancer population has not yet been reported. The aim of present study was to explore and identify covariates that affect pharmacokinetics of intravenous voriconazole in Pakistani cancer population. Methods The therapeutic drug monitoring data from January1st, 2023 to December 31st, 2023 of cancer patients receiving intravenous voriconazole for systemic fungal infections were taken from electronic medical record of the hospital. The data were used for the development of population pharmacokinetic model using NONMEM. Impact of various covariates such as age, weight, sex, liver function test, serum creatinine, creatinine clearance, type of cancer (primary diagnosis) and type of fungal infection were assessed through stepwise covariate modeling. Bootstrap analysis and goodness of fit plots were used to evaluate robustness and predictive performance of final model. Results One compartment model best described the included data with first order elimination. The value of voriconazole clearance was 6.17 L/h with interindividual variability of 83.7% while volume of distribution was 55.9 L. The clearance of voriconazole was significantly influenced by renal status of patients. Creatinine clearance and primary diagnosis were significant covariates affecting clearance of voriconazole in covariate analysis. Conclusion The findings suggest that this model can be used for dosage adjustment based on creatinine clearance and primary diagnosis as they impact significantly on voriconazole clearance in cancer patients. This approach is especially valuable in resource-limited settings like Pakistan, where individualized therapy can enhance the safety and efficacy of antifungal treatment, addressing the unique clinical and demographic challenges in vulnerable populations.

Author Correction: ThyroNet-X4 genesis: an advanced deep learning model for auxiliary diagnosis of thyroid nodules’ malignancy

Correction: A novel technique using integral transforms and residual functions for nonlinear partial fractional differential equations involving Caputo derivatives

Expression analysis and possible functional roles of semaphorin/plexin/CRMP families in mouse pancreatic islets

The influence of fitness mobile apps on workout behavior intention among Chinese young adults

Exercise was one of the most widely promoted methods to improve physical health while socially restricted. Despite the extensive notion of the advantages of sports activities, many young adults in China do not get the suggested amount of physical activity. Moreover, little is known about how one’s intentions regarding workout behavior are connected to one’s beliefs about using fitness mobile apps. The present study put into effect an online survey with random respondents of 5686 adults to examine a model combining the theory of planned behavior and the health belief model to predict Chinese adults’ attitudes, subjective norms, and perceived behavioral control when using fitness apps to work out, and to investigate associations between users’ beliefs and workout behavior intentions. The three main independent variables assessed were (1) attitude, (2) subjective norms, and (3) perceived behavioral control. Three components of belief were examined: self-efficiency, perceived barriers, and perceived benefits. The analyses found that attitudes and perceived behavioral control were positive and significant correlates of workout behavior intentions. The analysis also found that subjective norms were insignificantly associated with workout behavior intentions. Finally, the moderation test showed that belief moderated the assignations between the independent factors and workout behavior intentions. The findings suggest that the role of predictors within an integrated model using planned behavior theory and the health beliefs models provides a valid framework in the Chinese context of fitness app users. The research results have implications for the advancement and improvement of mobile phone apps that provide fitness functions, as well as for encouraging Chinese adults to promote the quantity and quality of their sport exercise.

Predicting badminton outcomes through machine learning and technical action frequencies

NIH has cut one mRNA-vaccine grant. Will more follow?

The relationship between preoperative serum indirect bilirubin and postoperative delirium in geriatric patients undergoing joint replacement

Background Postoperative delirium (POD) is one of the most common complications in geriatric patients following surgery. Physiological concentration of bilirubin possesses anti-inflammatory, antioxidant and neuroprotective effects, which are important protective mechanisms against POD. This study aimed to explore the relationship between preoperative serum bilirubin and POD in geriatric patients undergoing joint replacement. Methods Geriatric patients who underwent hip or knee joint replacement surgery under intrathecal anesthesia were included. These patients had American Society of Anesthesiologists (ASA) grades I to III. The patients with a history of psychiatric or neurological disorders, infectious diseases or sepsis, hemolytic anemia, liver diseases, performed general anesthesia or intrathecal anesthesia combined with general anesthesia, or insufficient surgical information were excluded. Patients’ age, gender, weight, height, ASA classification, liver function and bilirubin within one week before surgery, preoperative Mini–Mental State Examination (MMSE) scores, surgical type, dosage of medications, intraoperative bleeding volume, postoperative average numeric rating scale (NRS) pain scores, the occurrence of POD and Delirium Rating Scale–Revised–98 (DRS–R–98) scores for POD were collected. Results A total of 269 patients were eligible for inclusion in the study, with 23.05% (62/207) exhibiting POD. Patients with POD exhibited higher age and ASA classification, and had lower weight, serum total serum bilirubin (TBIL) and indirect bilirubin (IBIL) within one week before surgery, and preoperative MMSE scores (all p < 0.05). Univariate logistic regression analysis showed that the above variables were correlated with the occurrence of POD (all p < 0.05). Multivariate logistic regression analysis revealed that age was a risk factor (p < 0.001, OR = 1.14, 95% CI [1.07–1.21]), while weight (p = 0.041, OR = 0.96, 95% CI [0.92–0.99]), IBIL levels within one week before surgery (p = 0.012, OR = 0.65, 95% CI [0.47–0.91]) and preoperative MMSE scores (p < 0.001, OR = 0.84, 95% CI [0.78–0.91]) served as protective factors against the occurrence of POD. The serum IBIL concentration within one week before surgery was performed receiver operating characteristic (ROC) curve analysis. The estimated cutoff value for predicting the occurrence of POD was 6.65 μmol/L, and area under the curve (AUC) was 0.63. Patients with preoperative serum IBIL concentration below 6.65 μmol/L had a higher incidence of POD. Conclusion Patients with lower preoperative serum IBIL levels exhibited a higher incidence of POD in geriatric patients undergoing joint replacement. Low serum IBIL was a risk factor and a predictor for the occurrence of POD.

Author Correction: The role of genetic polymorphisms in the sulfation of pregnenolone by human cytosolic sulfotransferase SULT2B1a

Supporting healthcare in rural communities in Thailand: An exploratory qualitative study to understand the role and current mental health practices of village health volunteers

Introduction Village health volunteers (VHVs) are the backbone of primary healthcare in many low-and-middle-income countries, including Thailand, where healthcare professionals are scarce. Previous studies looking at their role have been broader and lacked a specific mental health focus. In 2019, Thailand introduced a policy endorsing a recovery orientation in mental health care, however, the potential for VHVs to implement the approach remains underexplored. This study aims to: [1] describe VHVs’ mental health practices, [2] explore stakeholders’ perspectives on these practices, and [3] understand stakeholders’ views on their potential to deliver recovery-oriented community care. Method This exploratory qualitative study involved nineteen semi-structured interviews conducted between August 2023 and March 2024 in a rural subdistrict of Northern Thailand. Participants included ten VHVs, four nurses, four caregivers, and one individual with mental health conditions. Purposeful and snowball sampling techniques were used. Reflexive thematic analysis was used to analyse interview data. Official documents related to VHVs’ job descriptions, training, and recruitment policies were also examined to understand the scope of the role. Results The analysis identified three main themes: [1] Mental health practices and roles perceptions, highlighting variability among VHVs; [2] Organisational constraints on mental health practice in the community, demonstrating limited policy support and training for VHVs; and [3] Factors influencing the implementation of recovery-oriented approaches by VHVs, including barriers such as stigma and workload, and enabling factors such as specialist training and professional support. Conclusions This study reveals that VHVs in Thai rural communities prioritise physical health due to policy adopting a biomedical approach and limited training on providing mental health care. A range of culturally adapted approaches are needed to expand and enhance the contribution that VHVs can make to improving the quality of life of individuals experiencing mental health conditions in rural communities in Thailand.

The curriculum planning and implementation for mindfulness education and diversified humanism based on big data

Analytical solution of MHD bioconvection Williamson nanofluid flow over an exponentially stretching sheet with the impact of viscous dissipation and gyrotactic microorganism

Nanofluids achieve high thermal transport efficiency by uniformly dispersing small particles in base liquids, significantly enhancing the heat transfer coefficients and making them vital in various thermal engineering applications. The research examines non-uniform thermal conductivity and activation energy critical for accurately describing fluid behaviour. The study incorporates bioconvection to prevent nanoparticle settling and ensure fluid stability through motile microorganisms. The governing partial differential equations are converted into ordinary differential equations that are solved using the Homotopy Analysis Method (HAM), to provide a strong mathematical framework for the analysis. This study finds that the velocity of the fluid decreases with magnetic constraint intensification and time retardation. however, heat transfer increases at higher radiation, and heat absorption/emission parameters but decreases with a higher Prandtl number, while an increased Schmidt number leads to decreased concentration profiles. This paper investigates a nano-Williamson fluid (NWF) flow over an exponentially stretched surface in a permeable medium, considering essential variables such as mixed convection, electromagnetic forces, non-linear thermal radiation, heat production, Joule heating and ohmic dissipation that are essential for understanding its complicated behavior.

Transfer of patients’ tibiofemoral kinematics and loads to a six-degree-of-freedom (6-DOF) joint simulator under consideration of virtual ligaments

Abstract Preclinical testing of total knee replacements (TKR) is crucial for evaluating new implant designs. Dynamic experimental testing focus mostly on level walking and squats, failing to represent a full range of daily activities. Moreover, the contribution of the ligament apparatus is often simplified. Therefore, this study transferred five daily activity load cases—level walking, downhill walking, stair descent, squat, and sit-to-stand—onto a six-degree-of-freedom (6-DOF) joint simulator with a cruciate-retaining bicondylar TKR and a virtual ligament apparatus. Forces and kinematics were based on telemetric data from an ultra-congruent TKR. The resulting kinematics, kinetics, and tibiofemoral contact surfaces were evaluated. Additionally, variations of the virtual ligament apparatus on the joint simulator, e.g. resection of the posterior cruciate ligament (PCL), have been used to assess its influence on the resulting joint dynamics. Results showed that tibiofemoral contact area was more influenced by dynamics than kinematics. Virtual PCL resection shifted the tibia posteriorly (up to 3 mm) and increased abduction (up to 0.5°). Different results were seen across all load cases. The exceptions are the squat and sit-to-stand load cases with similar patterns. Thus, cruciate-retaining TKR can be tested using telemetric data from ultra-congruent TKR, aiding in comprehensive evaluations.

Cognitive impairment and dementia—Are they linked to childhood health and socioeconomic status? A systematic review

Background Dementia is a major public health concern, with its incidence rising as the population ages. Recent studies suggest links between childhood health, socioeconomic status, and later-life cognitive impairment and dementia, though findings remain inconclusive. This systematic review evaluates the influence of childhood health and socioeconomic status on cognitive impairment and dementia. Method and findings A systematic search conducted in MEDLINE, CiNAHL, and PsycINFO in December 2024 identified 44 studies matching our inclusion criteria. Findings are presented under five key themes: (1) childhood health, (2) childhood educational attainment, (3) family socioeconomic and educational factors, (4) childhood experiences, and (5) childhood reading habits and social interactions. Conclusion Our results highlight the need for further longitudinal studies to establish causal relationships between early-life risk factors and later cognitive decline. Policymakers should prioritize early childhood development programs that integrate health, nutrition, education, and social support to help mitigate cognitive impairment and dementia in later life.

Pathogen-specific stomatal responses in cacao leaves to Phytophthora megakarya and Rhizoctonia solani

Abstract Cacao is a globally significant crop, but its production is severely threatened by diseases, particularly Black Pod Rot (BPR) caused by Phytophthora spp. Understanding plant-pathogen interactions, especially stomatal responses, is crucial for disease management. Machine learning offers a powerful, yet largely untapped, approach to analyze and interpret complex plant responses in plant biology and pathology, particularly in the context of plant-pathogen interactions. This study explores the use of machine learning to analyze and interpret complex stomatal responses in cacao leaves during pathogen interactions. We investigated the impact of the black pod rot pathogen ( Phytophthora megakarya ) and a non-pathogenic fungus ( Rhizoctonia solani ) on stomatal aperture in two cacao genotypes (SCA6 and Pound7) under varying light conditions. Image analysis revealed diverse stomatal responses, including no change, opening, and closure, that were influenced by the interplay of genotype, pathogen isolate, and light conditions. Notably, SCA6 exhibited stomatal opening in response to P. megakarya specifically under a 12-hour light/dark cycle, suggesting a light-dependent activation of pathogen virulence factors. In contrast, Pound7 displayed stomatal closure in response to both P. megakarya and R. solani , indicating the potential recognition of conserved Pathogen-Associated Molecular Patterns (PAMPs) and a broader defense response. To further analyze these interactions, we employed machine learning techniques to predict stomatal area size. Our analysis identified key morphological features, with size-related traits being the strongest predictors. Shape-related traits also played a significant role when size-related traits were excluded from the prediction. This study demonstrates the power of combining image analysis and machine learning for discerning subtle, multivariate traits in stomatal dynamics during plant-pathogen interactions, paving the way for future applications in high-throughput disease phenotyping and the development of resistant crop varieties.

A novel use of HIV surveillance and court data to understand and improve care among a population of people with HIV experiencing criminal charges in North Carolina 2017–2020

Objectives To enumerate and describe the population of people with HIV (PWH) with criminal charges and to estimate associations between charges and HIV outcomes. We hypothesized that being charged in the court system will be associated with declines in viral suppression. Methods We linked statewide North Carolina (NC) criminal court records to confidential HIV records (both 2017-2020) to identify a population of defendants with diagnosed HIV. We used generalized estimating equations to examine changes in viral suppression (outcome) in the time 12-month periods pre- and post-criminal charges (exposure), adjusting for other demographic and legal system factors. Results 9,534 PWH experienced criminal charges. Compared to others with charges, PWH were more likely to be male and report Black race. The median duration of unresolved charges was longer for PWH. A slightly larger proportion of PWH experienced viral suppression in the 12-month post-charge period compared to the pre-charge period (72% vs 70%, p < 0.05). Similarly, when adjusting for demographic factors, the 12-month period following resolution of charges was modestly associated with an increased likelihood of viral suppression (aRR 1.03, 95% confidence interval [CI] 1.02-1.04) compared to the pre-charge period. Conclusions A significant portion of PWH in NC had criminal charges during a three-year period, and these charges went unresolved for a longer time than those without HIV. There was a modest statewide increase in viral suppression in the 12-month period after resolution of charges. Considering the exploratory nature of study, the modest association between charges and viral suppression should not be interpreted causally. In contrast to our expectation, we did not find any evidence that charges were associated with a decline in viral suppression. We suggest future lines of research to improve upon this exploratory analysis and area of study.

Identification of driving behavior in continuous diverging sections of expressway system interchange based on CNN-BiLSTM

Correction: Combination of computational techniques and RNAi reveal targets in Anopheles gambiae for malaria vector control

Overwinter and prespawning movements by a vulnerable freshwater pelagophilic minnow

Abstract The decline of pelagophil minnows is related to river fragmentation across the southern Great Plains landscape. Because we know little about pelagophil movement patterns and timing, we aimed to quantify the movements of the vulnerable Arkansas River shiner (ARS) during the winter (November–March) and prespawning (April–June) seasons. We tagged 4233 ARS using visible implant elastomer, passive integrated transponder, or p-Chip micro-transponder tags in 2018–2020. We sampled to recapture tagged fish weekly during the winter and biweekly during the spring. Tagged fish exhibited a downstream movement bias and movement was weakly related to increasing temperature, discharge, and photoperiod during winter, however most of the variability was explained by a random individual effect. Larger individuals moved greater distances than smaller fish. Upstream movements by a migratory portion of the population appeared to begin around late February based on the presence of fish at previously unoccupied sites. However, the first long-distance (30-km) upstream movement by a tagged fish was documented in late May. We show evidence that some ARS may be resident fish at sites throughout winter and spring of multiple years. To conserve freshwater pelagophil minnows, our results indicate water management strategies improving river connectivity in late winter through the spawning season may benefit spawning by migratory individuals, whereas lateral connectivity might benefit the resident portion of the population. Research efforts under experimental flows could provide insight to improved recovery options.

A Bayesian game approach for node-based attribution defense against asymmetric information attacks in IoT networks

In the rapidly evolving landscape of the Internet of Things (IoT), traditional defense mechanisms struggle to counter sophisticated attribution attacks, especially under asymmetric information conditions. This paper introduces a novel Bayesian game framework—the Node-Based Attribution Attack-Defense Bayesian Game (NAADBG) Model—to address these challenges in IoT networks. The model incorporates a comprehensive set of attacker and defender profiles, capturing the complexities of real-world security scenarios. We develop a refined method for quantifying the payoffs of node-level attack-defense actions and explore the existence of a Mixed Strategy Bayesian Nash Equilibrium (MSBNE), enabling optimal defense strategy selection. Our simulations demonstrate that the NAADBG model significantly enhances network defense performance by optimizing resource allocation and preempting potential threats. This approach provides critical insights into developing proactive defense strategies against attribution attacks, contributing to more resilient IoT security frameworks. The results show that this method not only improves network defense performance but also presents practical applications in strengthening real-time IoT environments.