bluuebunny/crossref_metadata_2025_split huggingface dataset:
Covariates in population pharmacokinetic studies of critically ill adults receiving β-lactam antimicrobials: a systematic review and narrative synthesis
Authors: Hansel Jan , Mannan Fahmida , Robey Rebecca , Kumarendran Mary , Bladon Siân , Mathioudakis Alexander G , Ogungbenro Kayode , Dark Paul , Felton Timothy W 
Published: February 2024

AbstractIntroductionPopulation pharmacokinetic studies of β-lactam antimicrobials in critically ill patients derive models that inform their dosing. In non-linear mixed-effects modelling, covariates are often used to improve model fit and explain variability. We aimed to investigate which covariates are most commonly assessed and which are found to be significant, along with global patterns of publication.MethodsWe conducted a systematic review, searching MEDLINE, Embase, CENTRAL and Web of Science on 01 March 2023, including studies of critically ill adults receiving β-lactam antimicrobials who underwent blood sampling for population pharmacokinetic studies. We extracted and categorized all reported covariates and assessed reporting quality using the ClinPK checklist.ResultsOur search identified 151 studies with 6018 participants. Most studies reported observational cohorts (120 studies, 80%), with the majority conducted in high-income settings (136 studies, 90%). Of the 1083 identified covariate instances, 237 were unique; the most common categories were patient characteristics (n = 404), biomarkers (n = 206) and physiological parameters (n = 163). Only seven distinct commonly reported covariates (CLCR, weight, glomerular filtration rate, diuresis, need for renal replacement, serum albumin and C-reactive protein) were significant more than 20% of the time.ConclusionsCovariates are most commonly chosen based on biological plausibility, with patient characteristics and biomarkers the most frequently investigated. We developed an openly accessible database of reported covariates to aid investigators with covariate selection when designing population pharmacokinetic studies. Novel covariates, such as sepsis subphenotypes, have not been explored yet, leaving a research gap for future work.
A Robust HPLC Approach for Quantitation of Camptothecin in Mesoporous Silica Nanoparticles Matrix and in the Presence of Its Degradation Products
Authors: Dave Richa , Savaliya Neel , Dobariya Ashish , Patel Rashmin , Patel Mrunali 
Published: February 2024

Abstract

Background
Camptothecin is a potent anticancer drug used for the treatment of various cancers.

Objective
The goal of this research investigation was to develop and validate a new stability-indicating HPLC technique for the quantitative assessment of camptothecin in in-house developed mesoporous silica nanoparticles, a novel nanoformulation matrix for the treatment of cancer.

Method
The Waters Inertsil® HPLC column (C18) was used for the chromatographic separation, with a flow rate of 1 mL/min, a column oven temperature of 40°C, an injection volume of 10 µL, a detection wavelength of 216 nm, and a 10 min runtime overall. An isocratic blend of phosphate buffer (10 mM, pH7.0) and acetonitrile (60:40, v/v) served as the mobile phase. Various stress conditions including acid, alkali, oxidative, photolytic, thermal, and humidity environments were tested for the quantitative estimation of the camptothecin through the proposed method.

Results
The results demonstrated that the proposed method is specific (peak purity ≥0.999), accurate (99.69–100.64% w/w), precise (RSD, % &lt;2.0), and sensitive (LOD—0.17 µg and LOQ—0.56 µg) in accordance with ICH guideline Q2 (R1). Any unidentified degradation products did not interfere with the drug’s estimation. Furthermore, the current method of analysis has eliminated any excipient interference from the matrix effect caused by the numerous excipients of the formulation matrix.

Conclusions
To quantify camptothecin for routine assay purposes, this research work offers a novel and straightforward HPLC methodology with optimized chromatographic parameters, contributing to the research and development community while ensuring an appropriate and efficient use of the drug through a variety of nanoformulation for cancer treatment.

Highlights
The stability-indicating HPLC method was found to be specific and suitable for routine analysis of camptothecin. The absence of any interference from excipients was confirmed by forced degradation studies.
Ecology and management of the crapemyrtle aphid (Hemiptera: Aphididae) on crapemyrtle (Myrtales: Lythraceae) in the southern United States
Authors: Wilson Caleb J , Bertone Matthew A 
Published: February 2024

AbstractCrapemyrtle aphid [Sarucallis kahawaluokalani (Kirkaldy 1907)] (CMA) is an introduced pest of crapemyrtle (Lagerstroemia spp. L.), which is among the most common ornamental tree genera in the southern United States. Native to Southeast Asia, CMA has become established on 5 other continents. CMAs produce honeydew as they feed which supports sooty mold growth and can result in leaf defoliation on infested trees. CMAs tend to be most abundant in crapemyrtles planted in locations with extensive surrounding impervious surface cover. A large community of generalist natural enemies are found in close association with CMA, which suggests that CMAs may help conserve natural enemy communities in urban areas. Due to the long-lasting blooms produced by crapemyrtle, and the attractiveness of these blooms to pollinators, insecticides should be used as a last resort to manage CMA infestations. While CMA is considered a specialist pest of crapemyrtle, it has been recorded on 3 species outside of the genus Lagerstroemia. The wide distribution of CMA, closely overlapping that of crapemyrtle, suggests that CMA can likely be found wherever crapemyrtles are commonly planted.
METTL3 confers protection against mitochondrial dysfunction and cognitive impairment in an Alzheimer disease mouse model by upregulating Mfn2 via N6-methyladenosine modification
Authors: Chen Hao , Xing Huaijie , Zhong Changhui , Lin Xuejuan , Chen Ruipeng , Luo Ning , Chen Lijun , Huang Yusheng 
Published: February 2024

Abstract
Mitofusin 2 (MFN2) has been found to be downregulated in patients with Alzheimer disease (AD) but little is known about its roles in the pathogenesis of AD. We explored the mechanism of N6-methyladenosine (m6A) methylation of Mfn2 in hippocampal mitochondrial dysfunction in an AD mouse model. APP/PS1 transgenic mice underwent stereotaxic injection of adeno-associated viruses and their behaviors were assessed. METTL3 and MFN2 expressions were measured by qRT-PCR and Western blot, accompanied by assessment of mitochondrial morphology, ATP, mitochondrial membrane potential, and amyloid-β content. Binding between METTL3 and MFN2, the total amount of m6A, and the m6A modification of Mfn2 were also determined. METTL3 and MFN2 were downregulated in hippocampal tissues of the AD model mice; METTL3 enhanced MFN2 expression via m6A modification. Overexpression of METTL3 or MFN2 ameliorated mitochondrial dysfunction indicated by fewer damaged mitochondria, increased ATP and JC-1 levels, and reduced Aβ content; improved cognitive impairment in the mice was indicated by the novel object discrimination index and Morris water maze tests. Effects of METTL3 overexpression were abrogated by further knockdown of MFN2. Thus, METTL3 ameliorated mitochondrial dysfunction and cognitive impairment in the AD model mice by increasing MFN2 expression via m6A modification.
Congruence filter pairs, equational filter pairs and adjoints
Authors: Arndt Peter , Luiz Mariano Hugo , Pinto Darllan Conceição 
Published: February 2024

Abstract
Filter pairs are a tool for creating and analyzing logics. A filter pair can be seen as a presentation of a logic, given by presenting its lattice of theories as the image of a lattice homomorphism, with certain properties ensuring that the resulting logic is substitution invariant. Every substitution invariant logic arises from a filter pair. Particular classes of logics can be characterized as arising from special classes of filter pairs. We consider so-called congruence filter pairs, i.e. filter pairs for which the domain of the lattice homomorphism is a lattice of congruences for some quasivariety. We show that the class of logics admitting a presentation by such a filter pair is exactly the class of logics having an algebraic semantics. We study the properties of a certain Galois connection coming with such filter pairs. We give criteria for a congruence filter pair to present a logic in some classes of the Leibniz hierarchy by means of this Galois connection, and its interplay with the Leibniz operator.
A Functional Restoration Program for Active Duty Service Members With Chronic Pain: Examining the Impact of Co-occurring PTSD on Treatment Response
Authors: Espejo Emmanuel P , Sheridan Tara M , Pino Carlos A , Phillips Christopher R , Hanling Steven 
Published: February 2024

ABSTRACT

Introduction
Standard medical intervention for chronic pain may be less effective in the presence of co-occurring PTSD. Functional restoration programs (FRPs), which combine psychological interventions and progressive exercise rehabilitation, represent an alternative to standard medical intervention for chronic pain. The objective of the current study is to evaluate a FRP serving Active Duty Service Members with chronic pain and to examine whether co-occurring PTSD symptoms are associated with differential treatment response.

Methods
This is a retrospective observational study of data previously collected at Naval Medical Center San Diego approved by the Naval Medical Center San Diego Institutional Review Board. The study included 81 Active Duty Service Members, primarily Sailors and Marines, who completed a FRP, and examined pre- to post-treatment changes in Pain Impact Score—a composite measure of pain intensity, pain interference, and physical functioning—as well as measures of mental health and pain cognitions. Co-occurring PTSD symptoms were examined as a potential moderator of treatment response.

Results
Twenty-three patients (28.4%) screened positive for PTSD during baseline assessments. Repeated measures analysis of variance showed statistically significant improvement in Pain Impact Score for the full sample (P &lt;.001). Although no significant interactions with probable PTSD were demonstrated for measures of pain intensity and physical functioning (both Ps &gt;.05), patients screening positive for PTSD demonstrated a lesser decrease in pain interference compared to patients screening negative for PTSD (P &lt;.01). Improvements in measures of mental health and pain cognitions were also statistically significant for the full sample (all P values &lt;.05) and did not differ as a function of PTSD symptoms (all P values &gt;.05).

Conclusion
This FRP primarily serving Sailors and Marines contributed to broad overall improvements in the domains of pain and functioning as well as mental health and pain cognitions. Co-occurring PTSD symptoms were not associated with poorer treatment response on most measured outcomes.
Fecal Carriage of Colibactin-Encoding Escherichia coli Associated With Colorectal Cancer Among a Student Populace
Authors: Akinduti Paul A , Izevbigie Ovbiosa O , Akinduti Omobolanle A , Enwose Ezekiel O , Amoo Emmanuel O 
Published: February 2024

Abstract
Fecal carriage of the colibactin (clb) gene in Escherichia coli is described as a source that could promote carcinogenesis, progressing to colorectal cancer. The present study investigated the demographic, dietary, and antibiotic consumption variables as correlates for fecal carriage of clb+/E coli among the student populace. In a randomized cross-sectional survey, E coli (N = 136) from the fecal samples of eligible students were characterized and evaluated for antibiotic resistance, β-lactamase (blm), biofilm, virulence factor production, and strain tryptophan reverse mutagenic activity. The encoded clb+/E coli were analyzed for correlates with principal component analysis. Of all the E coli strains, a low rate of 2 clb+/E coli (1.5%) and higher rates of biofilm (13.2%) and blm producers (11.8%) were recorded among the mutant strains as compared with the nonmutant types. All the clb+/E coli showed complete resistance to amoxicillin, Augmentin (amoxicillin and clavulanate), gentamicin, and trimethoprim/sulfamethoxazole. The fecal clb-encoded E coli (1.5%) were not associated with demographic status, fiber-based food (odds ratio [OR], 1.03; 95% CI, 56.74–138.7; P = .213), alcohol (OR, 1.27; 95% CI, 61.74–147.1; P = .221), antibiotic consumptions (OR, 1.11; 95% CI, 61.29–145.3; P = .222), and handwashing (OR, 1.17; 95% CI, 60.19–145.5; P = .216). The hierarchical cluster of blm+/E coli revealed high-level resistance with a multiantibiotic resistance index ≥0.2 (P &lt; .05). Only 12% of all strains were tryptophan mutant/blm+, and 1.5% of clb+/ECblm+ were observed in fecal samples with a 452–base pair size. Trimethoprim/sulfamethoxazole and biofilm production positively regressed with clb expression (P &gt; .05). Principal component analysis score plot indicated an association of clb+/ECblm+ with dietary pattern, alcohol, blm, and hemolysin production. The combined activity of blm and biofilm production in the gut microbiota could promote clb+/E coli colonization, facilitating genotoxin production and possible colorectal cancer induction.
Existential Graphs
Authors: Bellucci Francesco , Pietarinen Ahti-Veikko 
Published: February 2024

Abstract
Existential graphs are a notation for first-order logic (alpha and beta departments) and higher-order logics (gamma department) that Charles S. Peirce created in 1896. This chapter surveys the evolution of Peirce’s notational experiments with graphical notations, from his work of the early 1880s up to the discovery of existential graphs in 1896 and beyond. The chapter explains the main notational differences between Peirce’s logical graphs, early and late, including his algebraical systems, by means of two pairs of notational parameters, “linearity/non-linearity” and “type- / occurrence-referentiality,” and shows how Peirce was able to maintain the expressivity of his algebraical systems while abandoning linearity and type-referentiality in the logical graphs.
Theory, Practice, and Deliberation
Authors: Colapietro Vincent 
Published: February 2024

Abstract
There are important texts in which Peirce draws an extremely sharp distinction between theory and practice, none more significant or seemingly extreme as his condemnation of “the Hellenic tendency to mingle Philosophy [theory par excellence] with Practice.” There are, however, passages in which he, at least, implies that theory is itself an instance of practice, a shared form of deliberate conduct. The aim of this chapter is partly to disambiguate theory in Peirce’s writings, highlighting two different but compatible senses. A larger part of its purpose is to show how human rationality is at bottom a deliberative capacity. While the form of deliberation in an urgently practical context is dramatically different from that in a strictly theoretical context, both practical agents and theoretical inquirers are engaged in deliberative practices. Accordingly, deliberation allows us to see both the unity and the differences between practical and theoretical reason.
Peirce and Religion
Authors: Slater Gary 
Published: February 2024

Abstract
This chapter examines the content, subsequent reception, and contemporary applications of Peirce’s writings on religion. The chapter comprises three sections. Section 1 surveys the most important primary texts on religion from within Peirce’s corpus: Peirce’s first Monist series (1891–1893), his Cambridge Lectures (1898), and his “Neglected Argument for the Reality of God” (1908). Section 2 charts a genealogy of the reception of Peirce’s writings within theology and religious studies; this genealogy extends from Josiah Royce through John E. Smith and into the respective projects of such figures as Robert C. Neville, Peter Ochs, Robert S. Corrington, and Michael Raposa. Section 3 traverses the current landscape of scholarship on Peirce and religion and speculates on potential developments within the discourse.
Why Philosophers Must Be Pragmatists
Authors: de Waal Cornelis 
Published: February 2024

Abstract
Having defined philosophy as the discipline that “contents itself with a more attentive scrutiny and comparison of the facts of everyday life,” Peirce observes that when we engage in it, we should not do so aimlessly, but we should do it deliberately. This means that we need to have some idea of what the outcome is likely to be. Philosophy is a deliberate, purpose-directed activity. And that, Peirce argues, naturally leads to pragmatism. In brief, for Peirce, pragmatism is what philosophy should be.
Peirce’s Views on Education and Learning
Authors: Midtgarden Torjus 
Published: February 2024

Abstract
This chapter considers how Peirce’s semiotic work suggests perspectives on learning and education. It focuses mostly on Peirce’s outlines of a speculative grammar from the mid-1890s, but it also considers earlier and later phases of his philosophical development. In the mid-1890s Peirce analyzed signs used in assertions and how the uses of these signs serve as conditions for learning from experience. Peirce qualifies these signs in terms of his symbol/index/icon typology and analyzes how they enable learning in everyday life and further prepare the learner for scientific education and specialization. The chapter shows how Peirce’s analysis may shed further light on learning processes through a comparison with Habermas’s theory of communicative action. Finally, the chapter considers how Peirce’s semiotic analysis can be complemented by perspectives on learning and education that philosophers of education have recently developed from his post-1900 semiotic work.
Morality and Ethics in the Work of Charles Peirce
Authors: Liszka James Jakόb 
Published: February 2024

Abstract
Peirce began the study of ethics once he realized that logic was a normative science and needed the guidance of ethics for a comprehensive account of reasoning. Given the state of ethics, Peirce sided with the eighteenth-century moral sentimentalists that moral sentiments and instincts were a more reliable guide to practical life. Nonetheless, Peirce pursued a science of ethics with the hope that its proper study would prove useful to logic and the conduct of life. Although Peirce never completed a systematic account of ethics, the argument here is that a good picture of his thought emerges from his writings. Based on the divisions of his logic or semiotic, the outlines of an ethics grammar, critic, and rhetoric can be formulated, one that provides interesting insights about morality, relevant to current debates in metaethics.
Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat
Authors: Ahmad Mubashir , Haffner‐Luntzer Melanie , Schoppa Astrid , Najafova Zeynab , Lukic Teodora , Yorgan Timur Alexander , Amling Michael , Schinke Thorsten , Ignatius Anita 
Published: February 2024

AbstractPhysical activity‐induced mechanical stimuli play a crucial role in preserving bone mass and structure by promoting bone formation. While the Wnt pathway is pivotal for mediating the osteoblast response to loading, the exact mechanisms are not fully understood. Here, we found that mechanical stimulation induces osteoblastic Wnt1 expression, resulting in an upregulation of key osteogenic marker genes, including Runx2 and Sp7, while Wnt1 knockdown using siRNA prevented these effects. RNAseq analysis identified Plat as a major target through which Wnt1 exerts its osteogenic influence. This was corroborated by Plat depletion using siRNA, confirming its positive role in osteogenic differentiation. Moreover, we demonstrated that mechanical stimulation enhances Plat expression, which, in turn leads to increased expression of osteogenic markers like Runx2 and Sp7. Notably, Plat depletion by siRNA prevented this effect. We have established that Wnt1 regulates Plat expression by activating β‐Catenin. Silencing Wnt1 impairs mechanically induced β‐Catenin activation, subsequently reducing Plat expression. Furthermore, our findings showed that Wnt1 is essential for osteoblasts to respond to mechanical stimulation and induce Runx2 and Sp7 expression, in part through the Wnt1/β‐Catenin/Plat signaling pathway. Additionally, we observed significantly reduced Wnt1 and Plat expression in bones from ovariectomy (OVX)‐induced and age‐related osteoporotic mouse models compared with non‐OVX and young mice, respectively. Overall, our data suggested that Wnt1 and Plat play significant roles in mechanically induced osteogenesis. Their decreased expression in bones from OVX and aged mice highlights their potential involvement in post‐menopausal and age‐related osteoporosis, respectively.
Analysis of genetic variant associated with heart failure mortality implicates thymic stromal lymphopoietin as mediator of strain‐induced myocardial fibroblast‐mast cell crosstalk and fibrosis
Authors: Pimpalwar Neha , Celik Selvi , Karbalaei Sadegh Mardjaneh , Czuba Tomasz , Gidlöf Olof , Smith J. Gustav 
Published: February 2024

AbstractHeart failure (HF) is a leading cause of death and disability globally. Heritable factors and the extent and pattern of myocardial fibrosis are important determinants of outcomes in patients with HF. In a genome‐wide association study of mortality in HF, we recently identified a genetic polymorphism on chromosome 5q22 associated with HF mortality. Here, we sought to study the mechanisms by which this variant may influence myocardial disease processes. We find that the risk allele is located in an enhancer motif upstream of the TSLP gene (encoding thymic stromal lymphopoietin), conferring increased binding of the transcription factor nescient helix–loop helix 1 (NHLH1) and increased TSLP expression in human heart. Further, we find that increased strain of primary human myocardial fibroblasts results in increased TSLP expression and that the TSLP receptor is expressed in myocardial mast cells in human single nuclei RNA sequence data. Finally, we show that TSLP overexpression induces increased transforming growth factor β expression in myocardial mast cells and tissue fibrosis. Collectively, our findings based on follow‐up of a human genetic finding implicate a novel pathway in myocardial tissue homeostasis and remodeling.
Migrant-Native Disparities in Obstetric Neuraxial Analgesia Use: The Role of Host-Country Language Proficiency
Authors: Hamwi S. , Barros H. , Lorthe E. 
Published: February 2024

(Anesth Analg. 2023;137(4):870–881)
Neuraxial analgesia (NA) is highly effective for labor pain relief, but its use varies among countries and is influenced by factors like ethnicity and region of origin. This study investigated how language proficiency affected NA utilization and satisfaction with labor pain management in migrant women compared to native women. Data came from the baMBINO study in Portuguese public hospitals, including migrant and native women. The study involved interviews conducted in various languages and excluded certain cases, resulting in a sample of 3697 women with singleton vaginal deliveries. This research aimed to explore the impact of language barriers on disparities in labor pain management.