bluuebunny/crossref_metadata_2025_split huggingface dataset:
MIF/NR3C2 axis regulates glucose metabolism reprogramming in pancreatic cancer through MAPK–ERK and AP-1 pathways
Authors: Yang Shouhui , Tang Wei , Azizian Azadeh , Gaedcke Jochen , Ohara Yuuki , Cawley Helen , Hanna Nader , Ghadimi Michael , Lal Trisha , Sen Subrata , Creighton Chad J , Gao Jianjun , Putluri Nagireddy , Ambs Stefan , Hussain Perwez 
Published: April 2024

Abstract
Inflammation and aberrant cellular metabolism are widely recognized as hallmarks of cancer. In pancreatic ductal adenocarcinoma (PDAC), inflammatory signaling and metabolic reprogramming are tightly interwoven, playing pivotal roles in the pathogenesis and progression of the disease. However, the regulatory functions of inflammatory mediators in metabolic reprogramming in pancreatic cancer have not been fully explored. Earlier, we demonstrated that pro-inflammatory mediator macrophage migration inhibitory factor (MIF) enhances disease progression by inhibiting its downstream transcriptional factor nuclear receptor subfamily 3 group C member 2 (NR3C2). Here, we provide evidence that MIF and NR3C2 interactively regulate metabolic reprogramming, resulting in MIF-induced cancer growth and progression in PDAC. MIF positively correlates with the HK1 (hexokinase 1), HK2 (hexokinase 2) and LDHA (lactate dehydrogenase) expression and increased pyruvate and lactate production in PDAC patients. Additionally, MIF augments glucose uptake and lactate efflux by upregulating HK1, HK2 and LDHA expression in pancreatic cancer cells in vitro and in mouse models of PDAC. Conversely, a reduction in HK1, HK2 and LDHA expression is observed in tumors with high NR3C2 expression in PDAC patients. NR3C2 suppresses HK1, HK2 and LDHA expression, thereby inhibiting glucose uptake and lactate efflux in pancreatic cancer. Mechanistically, MIF-mediated regulation of glycolytic metabolism involves the activation of the mitogen-activated protein kinase–ERK signaling pathway, whereas NR3C2 interacts with the activator protein 1 to regulate glycolysis. Our findings reveal an interactive role of the MIF/NR3C2 axis in regulating glucose metabolism supporting tumor growth and progression and may be a potential target for designing novel approaches for improving disease outcome.
Synthesis of transparent polymer hybrids consisting of gelatin, as a natural polymer, and zinc oxide
Authors: Iwamura Takeru , Akimoto Yuta , Mizoguchi Yuya , Matsumoto Hana , Hashimoto Yoshikuni , Adachi Kaoru 
Published: April 2024

Abstract
Gelatin and zinc oxide (ZnO) polymer hybrids were prepared via the sol–gel reaction of zinc acetate dihydrate in the presence of gelatin. When the gelatin/ZnO ratio was 9/1, a transparent polymer hybrid was obtained. This hybrid contained no phase separations consisting of organic and inorganic phases. Microscopic or submicroscopic aggregations and separations between gelatin and ZnO were clearly observed in the sample with a high inorganic content. The results of thermal analysis showed that the yield of ceramic decreased as ZnO content increased, and a 10% weight loss temperature increased as gelatin content increased. FT-IR measurements suggested the formation of intermolecular interactions, thought to be hydrogen bonds, between gelatin and ZnO. Furthermore, the results of XRD measurements revealed that the hybrid with a ZnO content of 10% is amorphous.
Reconceptualizing selective moral disengagement mechanisms as continuums of moral influence: a theoretical expansion
Authors: Frazer Rebecca , Grizzard Matthew 
Published: April 2024

Abstract
Mass communication researchers have applied Bandura’s selective moral disengagement (SMD) concept in diverse contexts to explain audiences’ acceptance of moral violations and reduced condemnation. Recent updates to moral psychology—specifically the application of social intuitionist theories—challenge SMD’s underlying assumptions, necessitating a reconceptualization. In this article, we incorporate modern social intuitionist theories of moral judgment into SMD’s underlying assumptions. We further propose a two-stage moral signal detection process consistent with current decision-making theory in order to explain how SMD reflects a modulation of both moral condemnation and moral commendation. Building on these extensions, we reconceptualize SMD’s eight original mechanisms as expanded continuums of moral influence applicable to diverse forms of moral perceptions and moral judgments. This reconceptualization of SMD removes unnecessary boundary conditions, improves the internal consistency of the theory, and can begin to resolve scholarly disagreements. We conclude the article by providing concrete suggestions for future empirical research.
Lipid-lowering approaches to manage statin-intolerant patients
Authors: Ruscica Massimiliano , Bertoletti Alessandra , Gobbi Cecilia , Sirtori Cesare R , Carugo Stefano , Corsini Alberto 
Published: April 2024

Abstract
Statins have improved the potential to prevent cardiovascular disease events and to prolong the lives of patients. Statins, among the most widely used drugs worldwide, reduce the levels of low-density lipoprotein cholesterol (LDL-C) by an average of 30–50%. However, non-adherence to statin therapy, due to statin intolerance, might be as high as 60% after 24 months of treatment and is associated with a 70% increase in the risk of cardiovascular disease events. Statin intolerance can be classified as a complete inability to tolerate any dose of a statin or a partial intolerance with the inability to tolerate the dose necessary to achieve the patient-specific therapeutic objective. Reasons for discontinuation are many, with statin-associated muscle symptoms being cited as the most frequent reason for stopping therapy and the incidence of muscle symptoms increasing with treatment intensity. Considering the causal effect of LDL-C in the atherosclerotic process, clinicians should consider that regardless of the lipid-lowering drugs patients are willing to take, any reduction in LDL-C they achieve will afford them some benefit in reducing cardiovascular risk. Besides statins, the current therapeutic armamentarium offers different strategies to reach LDL-C targets in statin-intolerant patients (i.e. a fixed combination between a lower dose of statin plus ezetimibe, bempedoic acid, or proprotein convertase subtilisin/kexin type 9 inhibition).
Factor XI inhibition in patients with acute coronary syndrome
Authors: Raffo Carmelo , Capodanno Davide 
Published: April 2024

Abstract
A hypercoagulable condition is typical of patients with acute coronary syndrome and is a determining factor in the genesis of recurrent ischaemic events. Modern pharmacological therapies consisting of antiplatelets and anticoagulants derive their rationale for use on the pathophysiological mechanisms most commonly associated with myocardial infarction (MI); they have contributed to reducing the ischaemic risk of these patients, but left ample room for improvement. In particular, trials that have studied the association of an anticoagulant with antiplatelet drugs have provided promising results in terms of efficacy, but highlighted a significant bleeding risk. Evidence derived from experimental animal and epidemiological studies has shown how factor XI (FXI) deficiency is associated with a reduction in thrombotic events but with modest bleeding. These data added to the role that FXI plays in the coagulation cascade constituted an incipit for the pharmacological attempt to decouple thrombosis from haemostasis by means of the inhibition of this factor. The theoretical assumption that FXI inhibitor drugs may be able to reduce the ischaemic risk without significantly increasing the haemorrhagic risk makes these compounds a potential therapeutic aid for patients in secondary prevention after acute MI. To date, on these patients, we only have data from a Phase 2 trial, PACIFIC-AMI (Study to Gather Information About the Proper Dosing and Safety of the Oral FXIa Inhibitor BAY 2 433 334 in Patients Following an Acute Heart Attack). In this study, the primary endpoint—represented by the Bleeding Academic Research Consortium (BARC) composite of Type 2, 3, or 5 bleeding—showed no significant differences between the various doses of asundexian tested (10, 20, and 50 mg quoque die), and between these and placebo (asundexian all doses vs. placebo: hazard ratio, 0.98; 90% confidence interval, 0.71–1.35). The data on efficacy, however, showed neutral results, but it should be noted that the study did not have the adequate statistical power to evaluate this outcome. Valuable information could, therefore, derive in the future from the ongoing Phase 3 trial with milvexian, LIBREXIA-ACS (A Study of Milvexian in Participants After a Recent Acute Coronary Syndrome) and from any future studies that could be started by testing different molecules.
Mortgage Borrowing and Chronic Disease Outcomes in Older Age: Evidence From Biomarker Data in the Health and Retirement Study
Authors: Rhodes Alec , Moulton Stephanie , Loibl Cäzilia , Haurin Donald , Joseph Joshua 
Published: April 2024

Abstract

Objectives
The medical diagnosis of a disease is common in older age and can carry significant financial costs. For many older adults, equity in a home is their primary component of wealth; however, housing wealth is illiquid. We analyze the relationship between the liquidation of housing wealth through mortgage borrowing on older homeowners’ ability to successfully control a disease.

Methods
We use data on homeowners aged 65 and older from the 1998–2016 waves of the Health and Retirement Study (N = 3,457). We use biomarkers and physical health indicators to measure disease control following a medical diagnosis of diabetes, heart condition, high blood pressure, lung disease, or cancer. Random effects linear probability and instrumental variable regressions estimate the associations of housing wealth, new mortgage borrowing, and disease control.

Results
Descriptively, 28% of older homeowners who borrow against home equity are not controlled on their disease, compared to 33% of non-borrowers. Panel data instrumental variable regressions show that each $10,000 borrowed from home equity after diagnosis is associated with a 17-percentage-point reduction in the probability of the disease not being controlled.

Discussion
Many older adults are not able or willing to liquidate housing wealth, and the ability to borrow also depends on changes in home values. Thus, housing wealth is not a uniform social determinant of health but is shaped by older adults’ participation in financial markets.
Adjoint sensitivity kernels for free oscillation spectra
Authors: Adourian S , Dursun M S , Lau H C P , Al-Attar D 
Published: April 2024

SUMMARY
We apply the adjoint method to efficiently calculate sensitivity kernels for long-period seismic spectra with respect to structural and source parameters. Our approach is built around the solution of the frequency-domain equations of motion using the direct solution method (DSM). The DSM is currently applied within large-scale mode coupling calculations and is also likely to be useful within finite-element type methods for modelling seismic spectra that are being actively developed. Using mode coupling theory as a framework for solving both the forward and adjoint equations, we present numerical examples that focus on the spectrum close to four eigenfrequencies (the low-frequency mode, 0S2, and higher frequency modes, namely 2S2, 0S7 and 0S10 for comparison). For each chosen observable, we plot sensitivity kernels with respect to 3-D perturbations in density and seismic wave speeds. We also use the adjoint method to calculate derivatives of observables with respect to the matrices occurring within mode coupling calculations. This latter approach points towards a generalization of the two-stage splitting function method for structural inversions that does not rely on inaccurate self-coupling or group-coupling approximations. Finally, we verify through direct calculation that our sensitivity kernels correctly predict the linear dependence of the chosen observables on model perturbations. In doing this, we highlight the importance of non-linearity within inversions of long-period spectra.
Re-envisioning contributory health schemes to achieve equity in the design of financial protection mechanisms in low- and middle-income countries
Authors: Tegbe Muyiwa , Moon Kyle , Nawaz Saira 
Published: April 2024

Abstract
Universal health coverage has emerged as a global health priority, requiring that financing strategies that ensure low-income and medically and financially at-risk individuals can access health services without the threat of financial catastrophe. Contributory financing schemes and social health insurance (SHI) schemes, in particular, predominate in low- and middle-income countries (LMICs), despite evidence that suggests the most vulnerable remain excluded from such schemes. In this commentary, we discuss the need to re-envision schemes to prioritize equity, offering 3 concrete recommendations: adopt participatory designs for the co-design of schemes with beneficiaries, establish linkages between contributory financial protection schemes with economic empowerment initiatives, and prioritize the needs and preferences of beneficiaries over political expediency. Co-design alone does not necessarily translate into more equitable schemes, underscoring the need for greater monitoring and evaluation of these schemes that consider differential impacts across contexts and subgroups. In doing so, SHI schemes can be both attractive and accessible to populations that have long been excluded from financial protections in LMICs, acting as 1 channel in a broader financing strategy to achieve universal health coverage.
How can solar panels collectors enhance energy efficiency? Utilization of the novel optimization techniques
Authors: Kuterbekov Kairat A , Kabyshev Asset M , Bekmyrza Kenzhebatyr Zh , Kubenova Marzhan M , Ayalew Abebe T 
Published: April 2024

Abstract
Solar energy, which is widely acknowledged for its economic feasibility and sustainable nature, functions as a critical substitute for finite fossil fuels, effectively alleviating ecological consequences. The purpose of this study is to investigate the implementation of solar collectors as a means of harnessing the ample and unaltered solar radiation in Iran, specifically in locations situated within the solar belt. The incorporation of solar energy not only aids in the expansion of energy sources through diversification but also mitigates the rising expenses linked to fossil fuels. The preservation of natural resources, coupled with limited renewable energy options, further accentuates the importance of solar energy. The optimization of solar panel collector angles in photovoltaic systems assumes paramount importance for maximizing energy efficiency. This study, conducted in Yazd, Iran, utilized innovative mathematical and particle swarm optimization (PSO) models to assess ideal inclination angles. Results indicate peak solar energy absorption during June and July, contrasting with minimal absorption in January. The Klein model prescribes inclination angles based on γ values, while the PSO algorithm determines optimal slope and azimuth angles across various periods. Significant enhancements in energy generation, ranging from 23.24 to 25.02% across optimization models, were observed compared to a horizontal surface. These findings underscore the imperative of optimizing solar panel placement in urban settings to augment energy generation. Utilizing the optimal orientation for the photovoltaic power supply system can result in an annual reduction of 1169.6 kg of CO2 emissions in the building, emphasizing the positive environmental impact achievable through strategic solar panel configurations.
Cost-effectiveness of 4CMenB Vaccination Against Gonorrhea: Importance of Dosing Schedule, Vaccine Sentiment, Targeting Strategy, and Duration of Protection
Authors: Nikitin Dariya , Whittles Lilith K , Imai-Eaton Jeffrey W , White Peter J 
Published: April 2024

Abstract

Background
Observational evidence suggests the 4CMenB meningococcal vaccine may partially protect against gonorrhea, with 1 dose being two-thirds as protective as 2 doses. We examined the cost-effectiveness of vaccinating men who have sex with men (MSM) in England, with 1- or 2-dose primary vaccination.

Methods
Integrated transmission-dynamic health-economic modeling explored the effects of targeting strategy, first- and second-dose uptake levels, and duration of vaccine protection, using observational estimates of vaccine protection.

Results
Vaccination with 1 or 2 primary doses is always cost-saving, irrespective of uptake, although vaccine sentiment is an important determinant of impact and cost-effectiveness. The most impactful and cost-effective targeting is offering “vaccination according to risk” (VaR), to all patients with gonorrhea plus those reporting high numbers of sexual partners. If VaR is not feasible to implement then the more restrictive strategy of “vaccination on diagnosis” (VoD) with gonorrhea is cost-effective, but much less impactful. Under conservative assumptions, VaR (2-dose) saves £7.62M (95% credible interval [CrI], 1.15–17.52) and gains 81.41 (95% CrI, 28.67–164.23) quality-adjusted life-years (QALYs) over 10 years; VoD (2-dose) saves £3.40M (95% CrI, .48–7.71) and gains 41.26 (95% CrI, 17.52–78.25) QALYs versus no vaccination. Optimistic versus pessimistic vaccine-sentiment assumptions increase net benefits by approximately 30% (VoD) or approximately 60% (VaR).

Conclusions
At UK costs, targeted 4CMenB vaccination of MSM gains QALYs and is cost-saving at any uptake level. Promoting uptake maximizes benefits and is an important role for behavioral science.
A Phronetic Ethics of Securitization
Authors: Gates Michael P 
Published: April 2024

Abstract
Intervening in recent debates on normativity in securitization theory, I draw on Aristotle’s notion of phronesis and Morgenthau’s formulation of prudence to articulate an ethical theory that takes seriously the idea that securitization is a deeply intersubjective process. First, I critique Rita Floyd's extant “just securitization theory,” which develops universal moral criteria akin to those of just war theory. While insightful, I argue that both her approach to the study of securitization as an empirical phenomenon and to moral theory are flawed. Then, I develop a novel theory by articulating how securitizing actors ought to exercise phronesis as a mode of ethical reasoning rather than a set of rules to follow. Securitizing actors exercise phronesis when they continuously deliberate about the ends of their actions, consider potential long-term consequences, utilize both abstract knowledge and experience, engage in critical self-reflection, and practice restraint. Throughout the paper, I redeploy the “universal” just securitization concepts of just cause and proportionality as rhetorical devices to help stimulate phronetic judgement.
Triazole antifungal drug interactions—practical considerations for excellent prescribing
Authors: Lewis Russell , Niazi-Ali Saarah , McIvor Andrew , Kanj Souha S , Maertens Johan , Bassetti Matteo , Levine Deborah , Groll Andreas H , Denning David W 
Published: April 2024

Abstract
Systemic antifungal therapy is critical for reducing the mortality from many invasive and chronic fungal infections. Triazole antifungals are the most frequently prescribed antifungals but require attention to dosing and drug interactions. Nearly 600 severe drug–drug interactions and over 1100 moderate interactions requiring dose modifications are described or anticipated with systemic antifungal agents (see https://www.aspergillus.org.uk/antifungal-drug-interactions/). In this article, we address the common and less common, but serious, drug interactions observed in clinical practice with triazole antifungals, including a group of drugs that cannot be prescribed with all or most triazole antifungals (ivabradine, ranolazine, eplerenone, fentanyl, apomorphine, quetiapine, bedaquiline, rifampicin, rifabutin, sirolimus, phenytoin and carbamazepine). We highlight interactions with drugs used in children and new agents introduced for the treatment of haematological malignancies or graft versus host disease (midostaurin, ibrutinib, ruxolitinib and venetoclax). We also summarize the multiple interactions between oral and inhaled corticosteroids and triazole antifungals, and the strategies needed to optimize the therapeutic benefits of triazole antifungal therapy while minimizing potential harm to patients.
18 High Mobility Group Box-1 Is Not Correlated with the Persistent Hyperinflammatory Response After Burn Injury
Authors: Pinto Desiree , Le Tuan D , Pusateri Anthony , Matthew Shane , McLawhorn Melissa M , Moffatt Lauren T , Shupp Jeffrey W 
Published: April 2024

Abstract

Introduction
Severe burn injury results in a hyperinflammatory response, that has been linked to mortality. Damage-associated molecular patterns (DAMPS), endogenous molecules released during cell necrosis/apoptosis, are released into circulation immediately after burn injury and contribute to the upregulation of the immune system. The change in DAMP levels and their continued impact on the immune system after burn injury is less known. This study aims to evaluate the evolution of high mobility group box 1 (HMGB1), a specific DAMP, after burn injury and its role in the development of a persistent hyperinflammatory state.

Methods
This was a prospective observational study that included patients admitted to a regional burn center. Blood samples to measure HMGB1 and cytokine protein levels (IL-1, IL-6, IL-10, IL-12, TNF-a) were collected at admission and at set time intervals up to 21 days after admission. The patients were divided into groups based on mortality status. Differences in HMGB1 levels between groups were compared by using a two-sample t-test or Wilcoxon rank-sum test and chi-square or Fisher exact test for data at admission and a mixed-effect model for repeated measures. HMGB1 levels were correlated to cytokine protein levels using Pearson Correlation Coefficient. A p-value of &lt; 0.05 signified statistical significance.

Results
There were 115 patients with both HMGB1 and cytokine protein levels out of the 158 patients enrolled. Overall mortality was 12.9%, median TBSA was 11.8%, and median age was 40. At admission, the HMGB1 level was significantly higher for patients who died than survived (&gt;10ng/mL vs 6.2ng/mL). For all patients the peak level of HMGB1 was at admission and then markedly decreased over the next 48 hours. A significant difference between patients who died and lived persisted for 48 hours (4.4ng/mL vs 2.9ng/mL). At admission, all cytokine protein levels were significantly elevated. Over the next 48-72 hours, the cytokine protein levels continued to increase for IL-1, IL-6, IL-12, and TNF alpha, and decreased for IL-10. At admission, there was a low positive correlation between HMGB1 and IL-6 (0.21), IL-10 (0.25), and TNF-alpha (0.26), and no positive correlation after admission (p &lt; 0.05).

Conclusions
Mortality was associated with significantly higher levels of a HMGB1 at admission and up to 48 hours after injury. While HMGB1 and other DAMPS may trigger the initial hyperinflammatory response, their contribution to the persistent hyperinflammatory response following burn injury is less clear.

Applicability of Research to Practice
HMGB1, a specific DAMP, has some utility in predicting mortality and serving as a biomarker for inflammation at admission. However, HMGB1 may not be the most appropriate biomarker to determine the development of a persistent hyperinflammatory state in the burn population.