Explicit Role Research Articles

L-Arginine and asymmetric dimethylarginine (ADMA) transport across the mouse blood-brain and blood-CSF barriers: Evidence of saturable transport at both interfaces and CNS to blood efflux

L-Arginine is the physiological substrate for the nitric oxide synthase (NOS) family, which synthesises nitric oxide (NO) in endothelial and neuronal cells. NO synthesis can be inhibited by endogenous asymmetric dimethylarginine (ADMA). NO has explicit roles in cellular signalling and vasodilation. Impaired NO bioavailability represents the central feature of endothelial dysfunction associated with vascular diseases. Interestingly, dietary supplementation with L-arginine has been shown to alleviate endothelial dysfunctions caused by impaired NO synthesis. In this study the transport kinetics of [3H]-arginine and [3H]-ADMA into the central nervous system (CNS) were investigated using physicochemical assessment and the in situ brain/choroid plexus perfusion technique in anesthetized mice. Results indicated that L-arginine and ADMA are tripolar cationic amino acids and have a gross charge at pH 7.4 of 0.981. L-Arginine (0.00149±0.00016) has a lower lipophilicity than ADMA (0.00226±0.00006) as measured using octanol-saline partition coefficients. The in situ perfusion studies revealed that [3H]-arginine and [3H]-ADMA can cross the blood-brain barrier (BBB) and the blood-CSF barrier. [3H]-Arginine (11.6nM) and [3H]-ADMA (62.5nM) having unidirectional transfer constants (Kin) into the frontal cortex of 5.84±0.86 and 2.49±0.35 μl.min-1.g-1, respectively, and into the CSF of 1.08±0.24 and 2.70±0.90 μl.min-1.g-1, respectively. In addition, multiple-time uptake studies revealed the presence of CNS-to-blood efflux of ADMA. Self- and cross-inhibition studies indicated the presence of transporters at the BBB and the blood-CSF barriers for both amino acids, which were shared to some degree. Importantly, these results are the first to demonstrate: (i) saturable transport of [3H]-ADMA at the blood-CSF barrier (choroid plexus) and (ii) a significant CNS to blood efflux of [3H]-ADMA. Our results suggest that the arginine paradox, in other words the clinical observation that NO-deficient patients respond well to oral supplementation with L-arginine even though the plasma concentration is sufficient to saturate endothelial NOS, could be related to altered ADMA transport (efflux).

Circumventing Kinetic Barriers to Metal Hydride Formation with Metal-Ligand Cooperativity.

We report the two-electron, one-proton mechanism of cobalt hydride formation for the conversion of [CoIIICp(PPh2NBn2)(CH3CN)]2+ to [HCoIIICp(PPh2NBn2)]+. This complex catalytically converts CO2 to formate under CO2 reduction conditions, with hydride formation as a key elementary step. Through a combination of electrochemical measurements, digital simulations, theoretical calculations, and additional mechanistic and thermochemical studies, we outline the explicit role of the PPh2NBn2 ligand in the proton-coupled electron transfer (PCET) reactivity that leads to hydride formation. We reveal three unique PCET mechanisms, and we show that the amine on the PPh2NBn2 ligand serves as a kinetically accessible protonation site en route to the thermodynamically favored cobalt hydride. Cyclic voltammograms recorded with proton sources that span a wide range of pKa values show four distinct regimes where the mechanism changes as a function of acid strength, acid concentration, and timescale between electrochemical steps. Peak shift analysis was used to determine proton transfer rate constants where applicable. This work highlights the astute choices that must be made when designing catalytic systems, including the basicity and kinetic accessibility of protonation sites, acid strength, acid concentration, and timescale between electron transfer steps, to maximize catalyst stability and efficiency.

Explicit role of seamount subduction in upper plate deformation as exemplified in the Ryukyu subduction zone

The Ryukyu subduction zone is typical of the subduction of an oceanic ridge (seamount or plateau) and back-arc rifting. How the upper plate responds to the combined effect of subduction of a bathymetric high and back-arc spreading is not fully understood. We investigate the combined effect by calculating the T-axis from regional focal mechanisms. Three patterns are observed from the outer rise to the back arc, showing a coherent trench-normal T-axis along the strike. They can be readily explained by outer-rise plate bending, forearc upper-plate bending induced by seamount subduction, and back-arc spreading associated with slab rollback. A distinct pattern of trench-parallel T-axes along the strike is also observed in the arc. This can be attributed to the difference in the extension rate between forearc extension and back-arc rifting of the upper plate, where the rate of back-arc extension driven by slab rollback is faster than that of forearc trench-normal extension attributed to seamount subduction. We also examine the T-axis patterns in other systems with seamount subduction, including the southern Manila subduction zone and the southern Central to northern South American subduction zones, displaying similar trench-normal T-axes in the forearc. Therefore, our observations have a broader implication in upper-plate deformation in response to seamount subduction.

Abstract B076: Qualitative insights into building an effective community advisory board for cancer disparities research

Abstract To address cancer disparities in minority and underserved communities, many organizations and research studies use a community advisory board (CAB) to better understand the needs, preferences, and perceptions of communities experiencing health inequities. Researchers have described a range of problems resulting in less than optional engagement of CAB members. Academic members of an NCI-funded cancer partnership interviewed 15 of the 20 members of their CAB to better understand their perceptions of their roles and expectations, as well as barriers and facilitators of engagement. Two trained team members coded the transcripts and conducted qualitative analysis using an iterative inductive/deductive framework. Deductively, we used principles of community-engaged research, and inductively we used coded quotes to identify details in the CAB members’ perspectives. The research team collaborated in organizing major themes into a conceptual framework to describe context, expectations, barriers and facilitators, and recommended strategies for strengthening involvement and benefit of CAB participation for its members. CAB members identified individual factors associated with their involvement including skills (communication, problem solving, interpersonal, leadership, professional, and advocacy), and motivations (community commitment, personal or family experience with cancer). The interviews indicated that there is a gap between CAB members’ perceptions of their roles and what they expect from participation and attendance in CAB meetings, and those of the academic team as conveyed verbally, in the CAB manual, and during onboarding activities. Barriers to enthusiastic engagement include disruptions associated with the COVID experience, members’ competing priorities, and role ambiguity. The CAB members’ resources and connections to the community were identified as facilitators. All these factors influenced the amount and quality of engagement of members with the academic partners and the community at large. Participants suggested many useful adaptations of the CAB-academic partnership, including enhanced training, improved communication, explicit role definitions, clear expectations around engagement with research, and better onboarding for new members. Scientists using a CAB to enhance community engagement should approach building a robust CAB as a deliberate process involving considerable planning, organization, and attention. Projects using a CAB can use the findings from this project to organize a community-academic partnership that will effectively and efficiently contribute to clinical, translational, and community-engaged work addressing cancer health disparities. Citation Format: Leah Alexander, Jennifer Erves, Rebecca Selove, Ila McDermott, J'la Jenkins, Phillip Morris, David Schlundt. Qualitative insights into building an effective community advisory board for cancer disparities research [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B076.

Na Vacancy-Driven Phase Transformation and Fast Ion Conduction in W-Doped Na3SbS4 from Machine Learning Force Fields.

Solid-state sodium batteries require effective electrolytes that conduct at room temperature. The Na3PnCh4 (Pn = P, Sb; Ch = S, Se) family has been studied for their high Na ion conductivity. The population of Na vacancies, which mediate ion diffusion in these materials, can be enhanced through aliovalent doping on the pnictogen site. To probe the microscopic role of extrinsic doping and its impact on diffusion and phase stability, we trained a machine learning force field for Na3-x W x Sb1-x S4 based on an equivariant graph neural network. Analysis of large-scale molecular dynamics trajectories shows that an increased Na vacancy population stabilizes the global cubic phase at lower temperatures with enhanced Na ion diffusion and that the explicit role of the substitutional W dopants is limited. In the global cubic phase, we observe large and long-lived deviations of atoms from the averaged symmetry, echoing recent experimental suggestions. Evidence of correlated Na ion diffusion is also presented that underpins the suggested superionic nature of these materials.

Acute care nurses' decisions to recognise and respond to patient improvement: A qualitative study.

To explore and describe acute care nurses' decisions to recognise and respond to improvement in patients' clinical states as they occurred in the real-world clinical environment. A descriptive study. Nine medical and eleven surgical nurses in a large Australian metropolitan hospital were individually observed during nurse-patient interactions and followed up in interview to describe their reasoning and clinical judgements behind observed decisions. Verbal description of observations and interviews were recorded and transcribed. Reflexive thematic analysis was used to analyse the data. The three themes constructed from the data were as follows: nurses checking in; nurses reaching judgements about improvements; and nurses deciding on the best person to respond. Acute care nurses made targeted assessment decisions based on predicted safety risks related to improvement in clinical states. Subjective and objective cues were used to assess for and make judgements about patient improvement. Acute care nurses' judgment of patient safety and a desire to promote patient centred care guided their decisions to select the appropriate person to manage improvement. The outcomes of this research have demonstrated that the proven safety benefits of acute care nurses' decision making in response to deterioration extend to improvement in patients' clinical states. In response to improvement, acute care nurses' decisions protect patients from harm and promote recovery. Early recognition and response to improvement enable acute care nurses to protect patients from risks of unnecessary treatment and promote recovery. This study makes explicit nurses' essential safety role in recognising and responding to improvement in patients' clinical states. Healthcare policy and education must reflect the equal importance of assessment for and management of deterioration and improvement to ensure patients are protected and provided with safe care.

Primordial non-Gaussianity as a saviour for PBH overproduction in SIGWs generated by pulsar timing arrays for Galileon inflation

We investigate the explicit role of negative local non-Gaussianity, fNL, in suppressing the abundance of primordial black holes (PBHs) in the single-field model of Galileon inflation. PBH formation requires significantly enhancing the scalar power spectrum, which greatly affects their abundance. The associated frequencies in the nHz regime are also sensitive to the generation of scalar-induced gravitational waves (SIGWs) which may explain the current data from the pulsar timing arrays (PTAs). Our analysis using the threshold statistics on the compaction function demonstrates that Galileon theory not only avoids PBH overproduction using the curvature perturbation enhancements that give fNL∼O(−6), but also generates SIGWs that conform well with the PTA data.

Exponential output tracking via a saturated RLC for a class of nonlinear systems under PSD of periodic references

This paper considers the same class of zero-relative-degree nonlinear systems for which a saturated Repetitive Learning Control (RLC) has been recently shown to ensure exponential – and not just asymptotical – convergence to zero of both the output and the input tracking errors in the case of periodic output reference signals with a known single period. The explicit role of the nonlinear unstructured uncertainties is here investigated within the more general scenario in which the output reference signal is multi-periodic. Special emphasis is provided to the generation of the input reference whose effect has to be exponentially nullified by the RLC. In particular, the following question is answered. Restrict the design to the sub-class of periodic output reference signals that admit a Periodic Signal Decomposition (PSD) (namely, the ones that can be written as a finite sum of periodic functions) with pairwise-commensurable periods (so that the knowledge of the multiple periods characterizing the input reference is preserved once the common multiple among the single periods is additionally included). Then, which robustness and convergence properties can be still achieved by the same output-feedback (definitely saturated) RLC, once it is intuitively generalized to transiently include an additional bank of learning estimation schemes corresponding to the single periods? Interestingly, the theoretical tools of this paper can be also used to successfully address identifiability and convergence issues regarding the identification of periodic components of general multi-periodic signals.

Testing a model for classroom observation in higher education

In this article, the ongoing development and implementation of a model for collegial exchange is presented. The aim is to modify an existing model for classroom observation and to test and evaluate the design in a pilot study, in order to encourage university teachers to learn from each other. In addition, the model is intertwined with further developing the role of the newly established network of recognized university teachers at a middle-sized Swedish university. In this model, the recognized university teachers are given explicit roles as facilitators, and it has a flexible design in order to suit as many teachers as possible—both newly educated and experienced. Insights from the teachers who actively participated in the pilot study highlight the positive impact of collegial observations. The participants found these observations to be not only inspiring but also valuable for their professional growth. In addition, they emphasized the significance of supporting a trustful relationship and shared intention with fellow teachers during collegial observation. Another conclusion from the pilot study is that it’s important not to rush when implementing this kind of model for long-lasting collegial exchange, but to let it develop gradually.

Quantification of alloy atomic composition sites in 2D ternary MoS2(1-x)Se2x and their role in persistent photoconductivity, enhanced photoresponse and photo-electrocatalysis

Engineering transition metal dichalcogenides-based semiconducting two-dimensional (2D) layered materials for photo(electro)chemical (PEC) hydrogen evolution reaction (HER) by water splitting is an enduring challenge. Here, alloy-assisted photoconductivity and photoresponse from CVD-grown MoS2(1-x)Se2x (MSSE) 2D ternary atomic layered alloy-based photodetector device is presented for the realization of PEC HER. The explicit role of ‘S–Se’ and ‘Se2’ atomic alloy sites including chalcogen-induced vacancy defects on the photoconductivity/photoresponse and PEC HER performance of MSSE 2D alloy is investigated. Alloy formation, atomic site-by-site ‘Se’ composition and atomic structure are characterized using Raman/Photoluminescence (PL) spectroscopy, high-angle annular dark field (HAADF)- scanning transmission electron microscopy (STEM) extensively and supported with Auger Electron Spectroscopy (AES) mapping. Further, the local density and concentration of S–Se, Se2 atomic sites and defects were quantitatively estimated using HAADF-STEM image analysis in correlation with AES and it is found between the range of ∼15–20 % in MSSE alloy. A 10-fold high photoresponsivity in the case of MSSE concerning as-grown MS having fast photocurrent growth time and the prolonged decay time originates from the ‘Se’ and this alloy assisted states to enhance the PEC performance of MSSE alloy. The enhanced PEC HER activity of MSSE alloy was identified in terms of overpotential and current density. In addition, increased density of states as a function of ‘Se’ alloying, shifts in a p-band centre and lowers ΔGH* according to density functional theory calculations, which makes MSSE alloy an efficient HER activity. Further, the PEC stability and presence of the ‘S–Se’ and ‘Se2’ alloying and their role towards HER have been correlated by the spectral line shape analysis of PL and Raman spectra from post-PEC HER catalysts. These experimental and theoretical findings establish the role of chalcogen, and transition metal-based 2D alloy, leading to the design of new PECs of engineered 2D atomic layer interfaces.

Effect of solvent depletion on electrokinetic energy conversion in viscoelastic fluids

We analyze the electrokinetic energy conversion from the pressure-driven flow of viscoelastic fluids akin to dilute polymer solutions. In contrast to the previously reported results, we account for the reduced differential capacitance over the interfacial layer and the solvent-mediated non-electrostatic interactions, cumulatively represented in an extended continuum framework. We attribute a physical basis of our consideration from the perspective of the formation of a polymer-depleted layer at the channel interface, where the explicit role of the solvent appears to dictate the electromechanics–hydrodynamics coupling over the interfacial scales. By adapting a “box-model” depicting the alterations in the solvent permittivity across the interfacial layer and accommodating a non-electrostatic interaction coefficient concomitantly, the interfacial electrokinetics are coupled with the bulk flow of the polymer-rich medium using the simplified Phan-Thien–Tanner (sPTT) constitutive model. A closed-form theory is obtained that includes only two fitting parameters, namely, the span of the interfacial layer and the strength of the non-electrostatic interactions. These parameters are estimated from comprehensive molecular simulation data. The results of the investigation are analytically tractable and enable rationalizing the “electrokinetic” implications of the polymer-depleted interfacial layer and the possibility that the electrokinetic parameters can be extracted from measurements obtained from experiments. This paves the way toward optimizing the induced streaming potential for the conversion of hydraulic energy to electrical power in polymeric solutions.

Emotional labour while working with families: Potential affordances for supporting early childhood educators’ wellbeing

Partnering with families is an explicit regulatory and role requirement for early childhood educators, yet the emotional labour involved is implicit and relatively unacknowledged. While research has found that complex work demands jeopardise educator wellbeing – resulting in unprecedented turnover and attrition in Australia and internationally – little research has investigated emotional labour and associated educator wellbeing in relation to partnering with families. This article argues that the limited research on educators’ emotional labour with families and its ensuing invisibility may pertain to both its positioning within social constructivist and interpretivist paradigms that render such work as naturally inherent and to conceptualisations of emotional labour theory that entrench this work in maternalistic discourses. The article positions emotional labour theory within a critical feminist lens and as a worthwhile line of inquiry to extend this body of research and disrupt maternalistic discourses that diminish educators’ skilful labour. The potential affordances pertaining to the illumination of this work as skilful for early childhood workforce policy are considered.

CONFINTEA VII and the Call to Climate Action: Clarifying Roles for Adult Learning and Education

Climate change and climate education concern more than climate and the environment, as our social and economic systems both rely upon and are impacted by climate and environment. We cannot address the human impact on our global climate and local environments without several nations reconstructing their social and economic systems to be equitable and inclusive. According to several key global guidance documents related to adult learning and education (ALE) and climate education, adult educators have significant roles in developing learners capable of engaging in climate and environmental action. However, defining climate education and roles for adult educators is not well-defined or explicit. To gain clarity in how ALE providers can facilitate learners’ understanding of how social/political, economic, and natural systems intersect to create and perpetuate the oppression, marginalization, and destruction of humans and the world upon which we depend, a close review of global guidance documents is warranted. This article analyzes key documents, such as the Marrakech Framework for Action (MFA), Education for Sustainable Development: A roadmap (ESD for 2030), and the International Council for Adult Education Spotlight Report for CONFINTEA VII. This process resulted in clarification of the definition of climate education from an ALE perspective and suggestions of explicit roles for ALE providers in the realm of climate education.

Instructional Leadership and School Effectiveness: A Correlational Study at Secondary Level Institutions in the Context of District Bannu

This study examines the correlation between instructional leadership and school effectiveness at secondary-level institutions in the context of district Bannu, Khyber Pakhtunkhwa, Pakistan. This study aimed to find out this relationship through a correlational research design. All 1511 teachers from 100 public sector secondary level schools constituted the population of this study. A close-ended 7-point Likert scale questionnaire comprising of 45 items was utilized by the researcher to obtain data from 306 teachers of 80 secondary-level institutions through a stratified random technique. The data that was obtained was analyzed through SPSS using Pearson’s R statistics. The findings reveal a strong, significant correlation between instructional leadership and school effectiveness. The study clearly confirmed that the explicit role of an instructional leader leads to successful school effectiveness.

Institutional view of corporate social responsibility in the Iranian context

PurposeThe purpose of this study is to examine how formal and informal institutions play a role in the Iranian context in shaping corporate social responsibility (CSR) policies and practices.Design/methodology/approachUsing a multiple case-study approach combining comparative and cross-sectional methods with semi-structured interviews, primary data was collected from eight corporations that actively participated in CSR activities in Iran. A microanalysis approach was used to examine the meanings and dynamics in the data. Through thematic analysis and pattern-matching techniques, the authors separately examined the roles of formal and informal institutions. Cross-case analysis was used to highlight the cases’ similarities and differences.FindingsThis study demonstrates that both formal and informal institutional structures exist in Iran and that both types influence CSR. This study also shows that informal institutions (such as personal values, culture, religion, traditions, charity and philanthropy) play a more explicit role than formal institutions (such as legal regulations and laws) in shaping CSR adoption policies and practices. The results indicate that, among institutions linked to CSR, formal and informal institutions are complementary and potentiate each other in Iran. Nevertheless, compared to formal ones, informal institutions play a more prominent role in shaping CSR policies and practices.Research limitations/implicationsThe authors recognize that, although the eight corporations are large, and although they interviewed their key personnel, they do not claim that these findings are generalizable, owing to the qualitative nature of the study and the small number of selected corporations.Originality/valueThis study makes relevant theoretical and empirical contributions. First, it contributes to the growing body of CSR literature that highlights the necessity of linking informal and formal institutions. Although the CSR literature lacks research on informal institutions in developing economies, researchers have yet to push forward and explore how the CSR adoption process works in developing economies that have influential informal institutions.

Transcriptome profiling of MYB-overexpressed transgenic lines provides crucial molecular insights into anthocyanin and remodel the biosynthesis regulatory network in Nicotiana tabacum

Anthocyanin is an important pigment in plants and one of the most powerful antioxidants for the food industry. In plants, anthocyanin biosynthesis is controlled by several structural genes and regulated by MYB transcription factors. However, the molecular mechanism and regulation of anthocyanin biosynthesis and the explicit role of MYB in pigmentation and stress responses have not been elucidated yet. In this study, we conducted transcriptomic profiling of MYB overexpressed transgenic lines, unveiling differentially expressed genes (DEGs) likely involved in anthocyanin biosynthesis and abiotic stress responses. Over-expression of two peanut MYB genes, Arahy.J3K16K (JK) and Arahy.CD1PG8 (C8), individually, as well as their co-expression (CJ), led to alterations in anthocyanin content in tobacco. Notably, JK over-expression line exhibited superior maintenance of growth indices, chlorophyll pigments, and anthocyanin content. Transcriptome profiling identified thousands of DEGs across JK, C8 and CJ transgenic plants. Functional annotation analysis revealed enrichment in metabolic pathways such as flavonoid biosynthesis, MAPK signaling, and hormone signaling transduction among these DEGs. Specifically, the expression of DEGs involved in the anthocyanin pathway, such as PAL, CHS, CHI, F3H, DFR, and ANR, was upregulated in JK lines, suggesting their regulatory role in pigmentation. Additionally, DEGs related to MAPK cascade, ethylene, auxin, and abscisic acid were preferentially expressed in JK lines, indicating their potential involvement in abiotic stress responses. The co-expression complex of MYB, bHLH, and WD40 also revealed the transcriptional activation model of anthocyanin biosynthesis in JK lines. In conclusion, these findings provide crucial molecular insights into MYB-induced regulation of anthocyanin biosynthesis and abiotic stress tolerance in tobacco, offering potential strategies for enhancing anthocyanin content and improving resistance.

Insights from a community of practice: Integrating human rights in fisheries improvement

A recent article authored by Williams and Sparks suggests that fishery improvement projects (FIPs) “as currently constituted and reported, will not be an effective part of the fight against labour exploitation and abuses in global industrial fisheries.” We wish to reinforce their argument that driving social responsibility improvements in global fisheries requires a systemic approach combining genuine worker representation, mandatory human rights due diligence, enforceable and legally binding agreements, changes to purchasing practices, and the ratification and implementation of international labor and human rights conventions, and we acknowledge that the FIP model alone will fall short of this. Based on our collective experience working towards social improvements in fisheries, we wish to bring a slightly more nuanced perspective to bear to demonstrate the critical importance of using a human rights-based approach in fisheries’ sustainability efforts across industrial and artisanal contexts. We structure this response by revisiting each of the main points Williams and Sparks raise, bringing in our own experiences and additional evidence to build upon their original remarks, suggesting: there is a need for continuous monitoring and improvements in dynamic risk environments; voluntary measures can lead to and buttress mandatory and legally binding measures; diverse fisheries require diverse approaches; and humans are inextricably linked to fisheries, thus effective and enduring solutions must consider human wellbeing and environmental sustainability in tandem. We end with a call to action with explicit roles and responsibilities for different actors inside and outside of the Fishery Improvement Project context to support binding and enforceable agreements between buyers and fishworker representative organizations, advancing human and labor rights protections in seafood supply chains.

Unlocking potential biomarkers bridging coronary atherosclerosis and pyrimidine metabolism-associated genes through an integrated bioinformatics and machine learning approach

BackgroundThis study delves into the intricate landscape of atherosclerosis (AS), a chronic inflammatory disorder with significant implications for cardiovascular health. AS poses a considerable burden on global healthcare systems, elevating both mortality and morbidity rates. The pathological underpinnings of AS involve a marked metabolic disequilibrium, particularly within pyrimidine metabolism (PyM), a crucial enzymatic network central to nucleotide synthesis and degradation. While the therapeutic relevance of pyrimidine metabolism in diverse diseases is acknowledged, the explicit role of pyrimidine metabolism genes (PyMGs) in the context of AS remains elusive. Utilizing bioinformatics methodologies, this investigation aims to reveal and substantiate PyMGs intricately linked with AS.MethodsA set of 41 candidate PyMGs was scrutinized through differential expression analysis. GSEA and GSVA were employed to illuminate potential biological pathways and functions associated with the identified PyMGs. Simultaneously, Lasso regression and SVM-RFE were utilized to distill core genes and assess the diagnostic potential of four quintessential PyMGs (CMPK1, CMPK2, NT5C2, RRM1) in discriminating AS. The relationship between key PyMGs and clinical presentations was also explored. Validation of the expression levels of the four PyMGs was performed using the GSE43292 and GSE9820 datasets.ResultsThis investigation identified four PyMGs, with NT5C2 and RRM1 emerging as key players, intricately linked to AS pathogenesis. Functional analysis underscored their critical involvement in metabolic processes, including pyrimidine-containing compound metabolism and nucleotide biosynthesis. Diagnostic evaluation of these PyMGs in distinguishing AS showcased promising results.ConclusionIn conclusion, this exploration has illuminated a constellation of four PyMGs with a potential nexus to AS pathogenesis. These findings unveil emerging biomarkers, paving the way for novel approaches to disease monitoring and progression, and providing new avenues for therapeutic intervention in the realm of atherosclerosis.

Examining the role of firearm involvement in repeat intimate partner violence assaults

BackgroundIntimate partner violence (IPV) remains a pervasive and complex issue with significant social and public health implications. The nexus of firearms and intimate partner violence (IPV) is an especially dangerous one. However, little is known about how firearm involvement can influence the risk of repeat IPV assaults.MethodsWe use data from 346 male perpetrated IPV incidents reported to the Detroit Police Department between December 2016 and April 2017 to examine the role of firearm involvement in IPV recidivism during a 5 and half year follow up period. Employing a conditional gap-time frailty model that accommodates heterogeneity among individuals through a frailty term, we analyze time to multiple IPV assaults that occur over the follow up period. We identify various pathways through which firearms impact the likelihood of subsequent IPV incidents, including intimidation, threats, and use of firearms, while controlling for observable perpetrator characteristics to understand the explicit roles of firearms.ResultsFirearm involvement at the index assault was not associated with IPV recidivism. However, involvement of firearms in past IPV assaults significantly increased the risk of subsequent physical IPV. The discrepancy is likely arising from a high degree of censoring among individuals who were armed with a firearm during the index assault.ConclusionOur research reveals a nuanced relationship between firearm involvement and IPV recidivism, shedding light on the multifaceted dynamics at play. By elucidating the intricate dynamics at the intersection of firearms and intimate partner violence, our study underscores the need for targeted policy interventions and preventative measures aimed at reducing IPV recidivism.

SPINK5 inhibits esophageal squamous cell carcinoma metastasis via immune activity.

Esophageal squamous cell carcinoma (ESCC) is a predominant subtype of esophageal cancer with relatively high mortality worldwide. Serine peptidase inhibitor Kazal-type 5 (SPINK5) is reported to be downregulated in ESCC. However, its explicit role in ESCC remains further investigation. The tumor tissues and adjacent non-cancerous tissues were obtained from 196 patients with ESCC for the determination of SPINK5 mRNA levels. Additionally, the relationship between SPINK5 mRNA levels and clinicopathological features of ESCC patients was explored. The effects of SPINK5 on the invasion and migration of ESCC cells were assessed using Transwell assays. Furthermore, SPINK5 mRNA and LEKTI protein were measured in ESCC cell lines after treatment with poly (I:C), lipopolysaccharide (LPS) or unmethylated CpG DNA. Moreover, the correlation between expression of SPINK5 and nuclear factor-kappa B (NF-κB) signaling pathway-related genes was analyzed in the TCGA-ESCC cohort, and the effects of SPINK5 on NF-κB transcription was analyzed using a luciferase reporter gene assay. Finally, the correlations between SPINK5 and infiltration of immune cells, immune scores, stromal scores and ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) scores were explored. SPINK5 mRNA levels were downregulated in tumor tissues, which was significantly correlated with higher lymph node metastases. Overexpressed SPINK5 inhibited cell invasion and migration in ESCC cell lines. Mechanistically, LPS-induced activation of Toll-like receptor 4 (TLR4) decreased SPINK5 mRNA and LEKTI in KYSE150 and KYSE70 cells. Spearman correlation analysis revealed that SPINK5 mRNA was significantly negatively correlated with a total of seven NF-κB signaling pathway-related genes in TCGA-ESCC patients. Moreover, downregulation of SPINK5 increased and upregulation of SPINK5 decreased the activity of the NF-κB promoter in HEK293T cells. Finally, immune cells infiltration analysis revealed that SPINK5 was significantly correlated with the infiltration of various immune cells, stromal scores, immune scores and ESTIMATE scores. SPINK5 plays critical roles in the TLR4/NF-κB pathway and immune cells infiltration, which might contribute to the ESCC metastasis. The findings of the present study may provide a promising biomarker for the diagnosis and treatment of esophageal squamous cell carcinoma.