bluuebunny/crossref_metadata_2025 huggingface dataset:
Wind Stability and Structural Optimization of a Three-Tower Cable-Stayed Suspension Bridge
Authors: Zhang Xinjun , Ni Binbin , Xu Dongjie , Hu Kai
Published: December 2024

By using a computational procedure of three-dimensional aerostatic and aerodynamic stability analysis of long-span bridges, the dynamic characteristics, structural stability including the aerostatic stability and aerodynamic stability are first analyzed for a three-tower cable-stayed suspension bridge with main spans of 1400[Formula: see text]m, then the parametric analysis is conducted, and finally a structural optimization scheme of the example bridge is proposed and confirmed numerically. The results show that the three-tower cable-stayed bridge has significant flexibility with less vertical and especially horizontal stiffness, and is sensitive to the transverse wind action; the three-tower cable-stayed bridge exhibits a coupled aerostatic instability pattern of vertical bending and torsion; the aerodynamic stability is worse than the aerostatic stability, the flutter critical wind speed is significantly reduced due to the static wind action, and thus the aerostatic effect must be involved in the aerodynamic stability analysis; the best wind stability is obtained for the example bridge as 2 auxiliary piers are set in each side span, the cable sag-to-span ratio is 1/6, the suspension-to-span ratio is 0.23, three pairs of cross hangers are set at the transition regions of the cable-stayed and suspension systems, and the girder depth is 4.5[Formula: see text]m.
Bifurcation analysis and network investigation of a Fitzhugh–Nagumo-based neuron model with combined effects of the external current and electrical field
Authors: Jabarouti Hoda , Nazarimehr Fahimeh , Parastesh Fatemeh
Published: December 2024

Analysis of a dynamic system helps scientists understand its properties and utilize it properly in different applications. This study analyzes the effects of various external excitements on a recently proposed mathematical neuron model derived from the original Fitzhugh–Nagumo model. Different bifurcation analyses on this system are conducted to detect chaotic behaviors that are common and of great importance in biological systems, considering the effects of different types of external excitements. Lyapunov exponents (LEs) confirm the existence of chaotic patterns. Furthermore, a bifurcation diagram that looks into the changes in the system dynamics caused by the simultaneous application of the external stimulants is represented. Neurons are bound to play a role in a network in which synchrony is an analytical quality. Therefore, the potential of a network of this model in showing synchronization is examined using the master stability function (MSF) technique. Ultimately, it is concluded that this neural model can produce chaotic behaviors and synchronous networks.
Efficient and Green Large Language Models for Software Engineering: Vision and the Road Ahead
Authors: Shi Jieke , Yang Zhou , Lo David
Published: December 2024

Large Language Models (LLMs) have recently shown remarkable capabilities in various software engineering tasks, spurring the rapid growth of the Large Language Models for Software Engineering (LLM4SE) area. However, limited attention has been paid to developing efficient LLM4SE techniques that demand minimal computational cost, time, and memory resources, as well as green LLM4SE solutions that reduce energy consumption, water usage, and carbon emissions.

This paper aims to redirect the focus of the research community towards the efficiency and greenness of LLM4SE, while also sharing potential research directions to achieve this goal. It commences with a brief overview of the significance of LLM4SE and highlights the need for efficient and green LLM4SE solutions. Subsequently, the paper presents a vision for a future where efficient and green LLM4SE revolutionizes the LLM-based software engineering tool landscape, benefiting various stakeholders, including industry, individual practitioners, and society. The paper then delineates a roadmap for future research, outlining specific research paths and potential solutions for the research community to pursue. While not intended to be a definitive guide, the paper aims to inspire further progress, with the ultimate goal of establishing efficient and green LLM4SE as a central element in the future of software engineering.
Intelligent Learning Management Systems (ILMS): Implications for teaching and learning
Authors: Hill Lilian H. , Conceição Simone C. O.
Published: December 2024

Intelligent learning management systems (ILMS) are transforming education by integrating artificial intelligence (AI) and machine learning. These systems automate administrative tasks, offer personalized learning experiences, and boost student engagement. This article explores the benefits and challenges of ILMS, highlighting how AI can predict learner behavior, customize educational content, and optimize curriculum management. It also delves into the ethical considerations of AI in education, such as data privacy and algorithmic bias. Finally, the article provides insights into the impact of ILMS on teaching and learning and concludes with a discussion of the future of ILMS.
A New Analytical Solution for Single Particle Model Subject to Lithium-Ion Batteries, with Experimental Validation
Authors: Hussain Arif , Li Mei , Ahmad Moin , Khan Arif Ullah , Xu Wenting , Liu Lina , Zhang Jing , Mao Zhiyu , Chen Zhongwei
Published: December 2024

The major aim of this article is to find the analytical solution of the physics-based model for lithium-ion batteries. Because the full-order pseudo two-dimensional model, comprised of a nonlinear algebraic-differential system, has a high computational cost, single particle model (SPM) is considered in this work to lessen the computational burden. First, the governing partial differential equations of the SPM are simplified with the volume average method along with polynomial approximations, and then an exact analytical solution of the simplified differential system is computed with the integrating factor method. The accuracy and reliability of the proposed analytical solution are accessed by comparing discharge curves simulation data with PyBAMM simulations in different operating conditions. It is observed that the error varies between 10 mV–25 mV for low to higher C-rate and the maximum error occurs at the middle and terminal points of the discharge cycling step in most cases. Finally, discharge curves are simulated with the help of the proposed analytical solution for the NMC battery, and then simulation results are compared with the experimental data of the NMC 50 Ah commercial battery. It is observed that the error in simulations is about 1% relative to terminal voltage.
Exploring CTRP6: a biomarker and therapeutic target in metabolic diseases
Authors: Senthil Kumar Jeevotham , Mehboob Muhammad Zubair , Lei Xia
Published: December 2024

The rising prevalence of metabolic diseases is a significant global health concern. Beyond lifestyle management, targeting key molecules involved in metabolic regulation is essential. C1q/TNF-related protein 6 (CTRP6) is notably associated with glucose and lipid metabolism, with numerous studies highlighting its regulatory functions in metabolic diseases. This review summarizes the current knowledge on CTRP6, focusing on its gene expression profiles, protein structure, gene regulation, and role in metabolic diseases. CTRP6 is widely expressed across various tissues and features four distinct domains, with the C1q domain predicted to bind to its receptor. Notably, serum levels of CTRP6 are significantly elevated in patients with obesity and type 2 diabetes. In these conditions, adipose tissue serves as a key source of CTRP6 and its involvement in adipose tissue expansion, inflammation, and nutrient sensing has been observed in several studies. CTRP6 is also implicated in type 1 diabetes, gestational diabetes mellitus, and diabetic complications, particularly diabetic nephropathy. Although some studies have suggested that CTRP6 has protective roles in atherosclerotic cell models, myocardial infarction rat models, and ischemia/reperfusion injury mouse models, methodological issues such as unreliable antibodies and unstrict controls make it difficult to draw accurate conclusions from these studies. Patients with polycystic ovary syndrome (PCOS) exhibit elevated serum levels of CTRP6, although its direct impact on PCOS phenotypes remains unclear. In conclusion, CTRP6 emerges as a promising therapeutic target for metabolic diseases. A deeper understanding of CTRP6 will empower the scientific community to develop effective interventions to address the increasing prevalence of these diseases.
The organum vasculosum of the lamina terminalis contributes to neurohumoral mechanisms of renal vascular hypertension
Authors: Lauar Mariana R. , Pestana-Oliveira Nayara , Collister John P. , Vulchanova Lucy , Evans Louise C. , Osborn John W.
Published: December 2024

Renovascular hypertension (RVHT), accounting for 1%–5% of high blood pressure cases, is the most common secondary hypertension resistant to treatment. In two-kidney one-clip (2K1C) hypertensive rats, renal artery stenosis triggers sympathetic nervous system activation, increased vasopressin, water intake, and inflammation. OVLT lesions prevented these responses, similar to afferent renal denervation. This study suggests that OVLT plays a key role in 2K1C hypertension pathogenesis and interacts with afferent renal nerves. Future studies will explore the underlying mechanisms.
Transcriptomics of SGLT2-positive early proximal tubule segments in mice: response to type 1 diabetes, SGLT1/2 inhibition, or GLP1 receptor agonism
Authors: Kim Young Chul , Das Vivek , Kanoo Sadhana , Yao Huazhen , Stanford Stephanie M. , Bottini Nunzio , Karihaloo Anil , Vallon Volker
Published: December 2024

SGLT2 inhibitors and GLP1 receptor agonists have kidney protective effects. By combining immunostaining-guided laser capture microdissection and RNA sequencing, the study established how the gene expression profile changes in SGLT2-positive proximal tubule cells in response to type 1 Akita diabetes and to pharmacological intervention by SGLT2 inhibition or GLP1R agonism and genetic deletion of SGLT1. The data also indicate genes unresponsive to those treatments that may include new therapeutical candidates.
The Shield of Resilience: Mediating the Effects of Internet Addiction on Adolescent Anger Control
Authors: Bakan Kıraç İnci , Sahmurova Aida , Duradoni Mirko , Guazzini Andrea , Gursesli Mustafa Can
Published: December 2024

Adolescence is a crucial developmental period characterized by physical, emotional, and social changes. This makes adolescents particularly vulnerable to various stressors, including Internet addiction. The increasing prevalence of Internet use has brought new challenges, as excessive and uncontrolled engagement with digital platforms, often referred to as Internet addiction, can disrupt emotional regulation and increase behavioral difficulties. Anger control, an important component of emotional wellbeing at this stage, is particularly affected by Internet addiction and can lead to aggressive tendencies and long‐term emotional problems. This study examines the mediating role of psychological resilience in the relationship between Internet addiction and anger control among adolescents between the ages of 12 and 14. A total of 406 students, selected using convenience sampling, participated in the study. Data were collected from the Internet Addiction Test (IAT), the Trait Anger and Anger Expression (T‐Anger and AngerEX) scale, and the Child and Youth Resilience Measure (CYRM‐12). Statistical analyses, including regression and mediation analyses, were conducted using the PROCESS macro in SPSS with 5000 bootstrap samples. The results show a significant negative relationship between Internet addiction and both psychological resilience and anger control, with Internet addiction explaining 20.2% of the variance in resilience and 11.5% in anger control. In addition, psychological resilience partially mediated the relationship between Internet addiction on anger control, explaining 25.1% of the variance. These findings highlight the importance of enhancing psychological resilience as a protective factor to mitigate the negative impact of Internet addiction on adolescents’ emotional regulation.
Fault Localization in Digital Power Distribution Networks Using a Chaotic Binary Particle Swarm Optimization–Enhanced Matrix Algorithm
Authors: Wan Li , Cheng Wenzhi
Published: December 2024

As digital distribution networks grow in complexity, ensuring efficient fault localization has become critical for reliable power delivery. This paper introduces a novel fault localization method that synergistically combines a matrix algorithm with a chaotic binary particle swarm optimization (CBPSO) algorithm. The matrix algorithm initially identifies faulty network segments and verifies alarm data integrity using a causal correlation matrix. To address instances where alarm data distortion prevents accurate localization, the CBPSO algorithm is employed to refine fault identification, leveraging its chaotic mapping to enhance global search capabilities and prevent premature convergence. Simulation tests conducted on IEEE33 and IEEE123 node systems under various fault scenarios demonstrate the proposed method’s effectiveness. The results highlight a 100% fault localization accuracy, significant dimensionality reduction in the solution space, and faster computation compared to existing methods. This work contributes a robust and efficient solution for fault localization in digital distribution networks, advancing smart grid fault management technologies.
Mental Health Nurses’ Knowledge of Metabolic Syndrome: A Cross‐Sectional Study
Authors: Lien Hsien-Chih , Chiang Kai-Jo , Feng Hsin-Pei , Lin Chia-Huei , Chang Yue-Cune , Tzeng Wen-Chii
Published: December 2024

Background: Adequate knowledge of the metabolic syndrome is essential for mental health nurses as it enhances their ability to recognize and address the physical needs of individuals diagnosed with serious mental illnesses.

Aims: This study investigated the factors influencing the level of metabolic syndrome knowledge among mental health nurses.

Methods: A cross‐sectional study was conducted with 208 mental health nurses recruited from four hospitals in northern Taiwan, including two regional hospitals, one medical center, and one mental health hospital. Nurses’ knowledge was assessed using a validated 20‐item self‐administered questionnaire covering key aspects of metabolic syndrome, including pathophysiology, diagnostic criteria, and management. The questionnaire demonstrated satisfactory reliability (KR‐20 = 0.702) and content validity. Data analysis involved descriptive statistics, independent t‐tests, one‐way analysis of variance, Pearson correlation coefficient, and generalized linear models to identify predictors of knowledge levels.

Results: The overall correct answer rate was 60.1%. Generalized linear modeling demonstrated that nurses’ knowledge was significantly associated with their sources of information (B = 1.371, 95% CI = 0.458–2.285, p = 0.003), the type of hospital they worked in (B = −1.027, 95% CI = −2.015 to −0.039, p = 0.042), and working in a community unit (B = 1.975, 95% CI = 0.067–3.883, p = 0.042).

Conclusions: Our results indicate that mental health nurses possessed a moderate level of knowledge concerning metabolic syndrome in people diagnosed with serious mental illness. Addressing this gap requires targeted education programs that integrate physical health education into psychiatric care and promote the use of diverse, evidence‐based resources tailored to the specific needs of mental health nurses in different settings. Organizational efforts should focus on fostering a supportive culture that enhances access to high‐quality resources, encourages interdisciplinary collaboration, and supports continuous professional development.
Mangiferin and EGCG Compounds Fight Against Hyperlipidemia by Promoting FFA Oxidation via AMPK/PPARα
Authors: Xu Yahui , Zhang Jie , Zhang Ting , Zi Minghui , Zhang Qiao
Published: December 2024

Background: Hyperlipidemia is a critical risk factor for obesity, diabetes, cardiovascular diseases, and other chronic diseases. Our study was to determine the effects and mechanism of mangiferin (MF) and epigallocatechin gallate (EGCG) compounds on improving hyperlipidemia in HepG2 cells.

Methods: HepG2 cells were treated with 0.25 mM palmitic acid (PA) and then incubated with MF (12.5, 25, and 50 μM) or EGCG (25, 50, and 100 μM) or MF:EGCG (0:0, 6.25:12.5, 25:50, and 50:100 μM:μM) for 24 h. The improvement of hyperlipidemia was verified by Oil Red O staining, changes in triglyceride (TG) and free fatty acid (FFA) levels, and the expression of lipid metabolizing proteins in western blotting.

Results: MF (12.5, 25, and 50 μM) or EGCG (25, 50, and 100 μM) markedly lowered lipid accumulations by lipid index levels. Furthermore, we found that the optimum concentration of MF and EGCG compounds was 25:50 (μM:μM), which significantly reduced the FFA level, TG, and total cholesterol (TC) accumulations and increased FFA uptake in HepG2 cells, and the effect was better than that of single phytochemicals. The adenosine 5 ′‐monophosphate (AMP)‐activated protein kinase (AMPK) protein and its downstream proteins sirtuin 1 (SIRT1), peroxisome proliferator‐activated receptor α (PPARα), and those involved in fatty acid translocase (CD36) and carnitine palmitoyltransferase 1 (CPT1) were also markedly increased in HepG2 cells. The upregulation of protein expression was reversed when AMPK‐specific inhibitor Compound C was added.

Conclusions: MF and EGCG (25:50 μM) compounds protect against hyperlipidemia by promoting the FFA oxidation, alleviating TG and TC accumulations via the AMPK/PPARα pathway in PA‐treated HepG2 cells.
Lumbar Facet Joint Radiofrequency Ablation With a 3‐Tined Cannula: A Technical Report and Observational Study
Authors: Künzle Andrea , Kuijk Sander M. J. van , Koetsier Eva
Published: December 2024

Background: Lumbar facet joints are the source of pain in 15%–41% of individuals experiencing low back pain (LBP). Conventional lumbar facet radiofrequency ablation (RFA) has Level II evidence for improving pain and function. The best proven technique, the parallel technique, is technically challenging, time‐consuming, and often uncomfortable for the patient. A novel RFA technique using a 3‐tined cannula offers a potentially less complex and shorter procedure.

Objectives: To describe the novel lumbar facet joint RFA technique with the 3‐tined cannula and to evaluate its efficacy in treating chronic lumbar facet joint pain.

Methods: Eligible adult patients with chronic lumbar facet joint pain, confirmed by positive medial branch blocks (MBBs), refractory to conservative treatment, received the novel RFA treatment with the 3‐tined cannula. The change in pain intensity at 2 months follow‐up compared to baseline, percentage of patients reporting a ≥ 30% and ≥ 50% reduction of pain intensity, patient global impression of change (PGIC), need for pain medication, walking ability, sleep quality, and patient satisfaction were evaluated.

Results: A total of 44 patients were included. Patients experienced a clinically meaningful and significant pain relief at follow‐up and 41% of the patients reported ≥ 50% reduction of pain. Forty‐eight percent experienced at least a score of “much improved” on the PGIC. No severe side effects or complications were observed.

Conclusions: Our observational study suggests that lumbar facet joint RFA using the novel technique achieves significant pain relief. The larger lesions decrease the likelihood of missing the target nerve while obviating the need to conduct numerous lesions. Limiting is the single‐center set‐up with a relatively short‐term follow‐up duration. Randomized controlled clinical trials are warranted to confirm the efficacy of the novel RFA technique to treat lumbar facet joint pain.
Data from Precision Patient Navigation to Improve Rates of Follow-up Colonoscopy, An Individual Randomized Effectiveness Trial
Authors: Coronado Gloria D. , Rawlings Andreea M. , Petrik Amanda F. , Slaughter Matthew , Johnson Eric S. , Hannon Peggy A. , Cole Allison , Vu Thuy , Mummadi Rajasekhara R.
Published: December 2024

AbstractBackground:
Colorectal cancer screening by annual fecal immunochemical test (FIT) with follow-up on abnormal results is a cost-effective strategy to reduce colorectal cancer incidence and mortality. Unfortunately, many patients with abnormal results do not complete a follow-up colonoscopy. We tested whether navigation targeted to patients who are unlikely to complete the procedure may improve adherence and long-term outcomes.
Methods:
Study participants were patients at a large, integrated health system (Kaiser Permanente Northwest) who were ages 50 to 75 and were due for a follow-up colonoscopy after a recent abnormal FIT result. Probability of adherence to follow-up was estimated at baseline using a predictive risk model. Patients whose probability was 70% or lower were randomized to receive patient navigation or usual care, with randomization stratified by probability category (<50%, 50% < 60%, 60% < 65%, 65% d 70%). We compared colonoscopy completion within 6 months between the navigation and usual care groups using Cox proportional hazards regression.
Results:
Participants (n = 415; 200 assigned to patient navigation, 215 to usual care) had a mean age of 62 years, 54% were female, and 87% were non-Hispanic white. By 6 months, 76% of the patient navigation group had completed a colonoscopy, compared with 65% of the usual care group (HR = 1.35; 95% confidence interval, 1.07–1.72; log-rank P value = 0.027).
Conclusions:
In this randomized trial, patient navigation led to improvements in follow-up colonoscopy adherence.
Impact:
More research is needed to assess the value of precision-directed navigation programs.
Plasma n-3 Polyunsaturated Fatty Acid Levels and Colorectal Cancer Risk in the UK Biobank: Evidence of Nonlinearity, as Well as Tumor Site- and Sex-Specificity
Authors: Aldoori Joanna , Zulyniak Michael A. , Toogood Giles J. , Hull Mark A.
Published: December 2024

Background:

The relationship between omega-3 polyunsaturated fatty acid (n-3 PUFA) intake and colorectal cancer risk is unclear. Blood n-3 PUFA concentration is a biomarker of dietary n-3 PUFA intake. We examined the relationship between plasma n-3 PUFA concentrations and colorectal cancer risk in UK Biobank (UKBB) participants.

Methods:

We analyzed the relationship between tertiles (T) of plasma total n-3 PUFAs and n-3 PUFA docosahexaenoic acid (DHA) levels, and overall colorectal cancer (also stratified by tumor location and sex) risk. Cox proportional hazards regression models were adjusted for clinical covariates. Nonlinearity was tested by restricted cubic splines.

Results:

There were 2,602 incident colorectal cancer cases in 234,598 UKBB participants with baseline plasma fatty acid data (mean follow-up 13.4 years). There was an inverse association between the plasma total n-3 PUFA level [T2 HR = 0.88 (95% confidence interval, 0.80–0.97) compared with the T1 reference; T3 = 0.91 (0.83–1.00)], as well as the plasma DHA concentration [T2 = 0.89 (0.80–0.98); T3 = 0.91 (0.82–1.00)], and colorectal cancer risk. The relationship was nonlinear [P for nonlinearity = 0.14 (total n-3 PUFAs) and 0.008 (DHA)], with a plateau effect at the highest n-3 PUFA concentrations. The relationship was more pronounced for proximal colon cancer [T2 = 0.82 (0.69–0.97); T3 = 0.76 (0.64–0.90) for DHA] and was evident for males [T2 = 0.84 (0.74–0.95); T3 = 0.89 (0.78–1.00)], but not for females.

Conclusions:

Higher plasma n-3 PUFAs are associated with reduced colorectal cancer risk in the UKBB.

Impact:

Nonlinearity, as well as tumor site and sex specificities, of the inverse relationship between plasma n-3 PUFA levels and colorectal cancer risk, if confirmed in other diverse populations, has significant implications for nutritional prevention guidelines.
Combination of Bremachlorin PDT and Immune Checkpoint Inhibitor Anti–PD-1 Shows Response in Murine Immunological T-cell–High and T-cell–Low PDAC Models
Authors: McMorrow Roisin , de Bruijn Henriette S. , Farina Stefania , van Ardenne Ruben J.L. , Que Ivo , Mastroberardino Pier G. , Robinson Dominic J. , Mezzanotte Laura , Löwik Clemens W.G.M.
Published: December 2024

Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging types of cancer with little or no response to immune checkpoint inhibitors (ICI). Photodynamic therapy (PDT) has been shown to ablate tumors and induce an immune response. In our study, we investigated the effect of PDT using the photosensitizer Bremachlorin, in its ability to reduce tumor burden and immunologically sensitize T-cell–high and T-cell–low murine PDAC tumors to the ICIs that blocks PD-1 immune checkpoint. In addition, we monitored the effect on survival and investigated if there was a response in PDT-treated and non–PDT-treated distant tumors. Our results showed that Bremachlorin PDT induces direct tumor killing that increased survival in both “hot” T-cell–high and “cold” T-cell–low PDAC tumors and that it can make T-cell–high tumors more sensitive to ICIs blocking PD-1. We found that T-cell–high tumor-bearing mice had an overall greater response to therapy than did T-cell–low tumor-bearing mice. One mouse with T-cell–high tumors exhibited complete tumor regression in both the treated and nontreated distant tumor 90 days after treatment. These results indicate that combining ICIs with Bremachlorin PDT could be a promising therapeutic intervention for enhancing PDAC’s response to therapy.
Figure 7 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma
Authors: Zhang Yichi , Ojalill Marjaana , Boyer Antonia , Chen Xiao Lei , Tahon Elise , Thivolle Lioux Gaëtan , Xia Marvin , Abbas Maryam , Soylu Halime Meryem , Flieder Douglas B. , Connolly Denise C. , Molinolo Alfredo A. , McHale Michael T. , Stupack Dwayne G. , Schlaepfer David D.
Published: December 2024

Nuclear FAK regulation of MKP1 expression is associated with cisplatin resistance. A, KMF FAK-WT and FAK-NLS− cells were treated with increased concentrations of cisplatin (0, 10, or 20 μmol/L) for 12 hours and protein lysates were immunoblotted for GFP-FAK, MKP1, pERK, and total ERK. B, Image quantitation of pERK to total ERK ratio or MKP1 levels (FAK-WT set to 0) from two independent experiments described in A. Values are means ± SD (***, P < 0.001). C, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (24 hours) under control (DMSO) or with MKP1 inhibitor (BCI-215, 1 μmol/L) addition. Protein lysates were immunoblotted for pERK and total ERK. D, Image quantitation of pERK to total ERK ratio from two independent experiments described in C. Values are means ± SD with FAK-WT control set to 1 (*, P < 0.05). E, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (48 hours) as above with MKP1 inhibitor (BCI-215, 1 μmol/L) addition, and cell lysates were immunoblotted for caspase-3 and cleaved caspase-3. F, Determination of IC50 values to cisplatin KMF FAK-WT (green bars) and FAK-NLS− (blue bars) cells in the presence of MKP1 inhibitor (BCI-215, 1 μmol/L) or DMSO control as determined by alamarBlue cell viability assay. Values are means ± SD from three independent experiments (*, P < 0.05; **, P < 0.01; ***, P < 0.001). G, Kaplan–Meier curves from 949 HGSOC patient samples that received adjuvant carbo- or cisplatin-based chemotherapy. Plots show probability of relapse-free survival in months with tumors high (red) or low (black) for MKP1 mRNA (HR = 1.4, P = 0.0024). ns, not significant; WCL, whole-cell protein lysate.
Figure 6 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma
Authors: Zhang Yichi , Ojalill Marjaana , Boyer Antonia , Chen Xiao Lei , Tahon Elise , Thivolle Lioux Gaëtan , Xia Marvin , Abbas Maryam , Soylu Halime Meryem , Flieder Douglas B. , Connolly Denise C. , Molinolo Alfredo A. , McHale Michael T. , Stupack Dwayne G. , Schlaepfer David D.
Published: December 2024

Prevention of FAK expression, activity, or nuclear localization results in elevated cisplatin-stimulated ERK activation. A, KMF FAK-WT and FAK-NLS− cells were treated for 0 or 12 hours with cisplatin (20 μmol/L), and cell lysates were immunoblotted for active ERK (pERK), total ERK, and β-tubulin. B, Image quantitation of pERK to total ERK ratio from two independent experiments from A. Values are means ± SD with control FAK-WT values set to 1 (***, P < 0.001). C, Image quantitation of pERK to total ERK ratio from parental OVCAR3 and FAK-KO AB21 cells treated with cisplatin (1 μmol/L) for 24 hours. Values are means ± SD from two independent experiments with control OVCAR3 values set to 1 (*, P < 0.05). D, Representative pERK, total ERK, and GAPDH loading control immunoblotting of OVCAR3 FAK-WT and FAK-NLS− lysates ± cisplatin (0.5 μmol/L, 12 hours). E, KMF parental cells were preincubated (48 hours) with FAKi (IN10018, 1 μmol/L), FAK-specific PROTAC (FAK PROTAC-1, 1 μmol/L), and FAK-Pyk2 targeting PROTAC (FAK PROTAC FC-11, 1 μmol/L) followed by with cisplatin addition (20 μmol/L, 24 hours), as indicated. Cell lysates were immunoblotted for pY397 FAK, FAK, and Pyk2 and for active (pERK) and total ERK. F, Image quantitation of pERK to total ERK ratio from three independent experiments described in E. Values are means ± SD with control set to 1 (*, P < 0.05; **, P < 0.01; ***, P < 0.001; ****, P < 0.0001). G, Representative immunoblotting of OC49 ovarian PDX cell lysates for pY397 FAK, total FAK, pERK, and total ERK ± cisplatin (3.5 μmol/L, 24 hours). H, Image quantitation of pERK to total ERK ratio from two independent experiments described in G. Values are means ± SD with control set to 1 (*, P < 0.05). I, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (24 hours) with (DMSO) control or MEK1 inhibitor (U0125, 10 μmol/L) addition. Cell lysates were immunoblotted for active and total ERK. J, KMF FAK-WT and FAK-NLS− cells were treated 20 μmol/L cisplatin (48 hours) as above with MEK1 inhibitor and cell lysates blotted for caspase-3, cleaved caspase-3, and β-tubulin. MEKi, MEK inhibitor.
Figure 4 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma
Authors: Zhang Yichi , Ojalill Marjaana , Boyer Antonia , Chen Xiao Lei , Tahon Elise , Thivolle Lioux Gaëtan , Xia Marvin , Abbas Maryam , Soylu Halime Meryem , Flieder Douglas B. , Connolly Denise C. , Molinolo Alfredo A. , McHale Michael T. , Stupack Dwayne G. , Schlaepfer David D.
Published: December 2024

FAK KO and reexpression show that nuclear FAK promotes cisplatin but not paclitaxel resistance in human OVCAR3 cells. A, Immunoblots of cultured FAK KO OVCAR3 (clone AB21) and GFP-FAK-WT or FAK-NLS− reconstituted AB21 cells for HA-tag (at FAK C-terminal), FAK pY397, and β-tubulin as a loading control. B, FAK-WT, and FAK-NLS− OVCAR3 cells were evaluated for cisplatin cytotoxicity after 48 hours in culture. Shown is percent cell viability vs. cisplatin concentration (μmol/L, log10), and points are means of triplicate samples ± SD (n = 3 independent experiments). C, Determination of IC50 values to cisplatin as performed in B (***, P < 0.001). D, FAK-WT and FAK-NLS− OVCAR3 cells were evaluated for paclitaxel cytotoxicity (μmol/L, log10) after 48 hours in culture. E, Analysis of OVCAR3 FAK-WT and FAK-NLS− cells for growth in culture and (F) in the presence of 0.5 μmol/L cisplatin for 72 hours. Values are means ± SD from two independent experiments with triplicate points and FAK-WT values set to 1 (***, P < 0.001; ns not significant). G, Representative images of crystal violet–stained OVCAR3 FAK-WT and FAK-NLS− cell colonies formed in the presence of 0, 0.5, or 1.0 μmol/L cisplatin after 10 days. H, Quantitation of FAK-WT (green bars) and FAK-NLS− (blue bars) colony formation. Values are means ± SD from three independent experiments with triplicate points (*, P < 0.05).
Figure 3 from Nuclear Focal Adhesion Kinase Protects against Cisplatin Stress in Ovarian Carcinoma
Authors: Zhang Yichi , Ojalill Marjaana , Boyer Antonia , Chen Xiao Lei , Tahon Elise , Thivolle Lioux Gaëtan , Xia Marvin , Abbas Maryam , Soylu Halime Meryem , Flieder Douglas B. , Connolly Denise C. , Molinolo Alfredo A. , McHale Michael T. , Stupack Dwayne G. , Schlaepfer David D.
Published: December 2024

FAK nuclear localization enhances murine ovarian tumor cell survival to cisplatin. A, FAK-KO, FAK-WT, and FAK-NLS− KMF cells were evaluated for cisplatin cytotoxicity after 48 hours in culture. Shown is percent cell viability vs. cisplatin concentration (μmol/L, log10), and points are means of triplicate samples ± SD (n = 3 independent experiments). B, Determination of cisplatin IC50 values as performed in A (*, P < 0.05; **, P < 0.01). C, FAK-WT and FAK-NLS− KMF cells were evaluated for paclitaxel cytotoxicity (μmol/L, log10) after 48 hours in culture. D, Analysis of KMF-FAK-WT and KMF-FAK-NLS− cells for growth in culture and (E) in the presence of 20 μmol/L cisplatin for 72 hours. Values are means ± SD from two independent experiments with triplicate points and FAK-WT values set to 1 (**, P < 0.01). F, Representative images of crystal violet–stained KMF FAK-WT and FAK-NLS− cell colonies formed in the presence of 0, 1, or 10 μmol/L cisplatin after 10 days. G, Quantitation of FAK-WT (green bars) and FAK-NLS− (blue bars) colony formation. Values are means ± SD from three independent experiments with triplicate points (***, P < 0.001). H, Representative images of TUNEL staining to detect changes in FAK-WT or FAK-NLS− cell DNA fragmentation after cisplatin (20 μmol/L, 48 hours) addition. TUNEL-positive nuclei (identified by DAPI costain) are marked (white circle) in the merged images. Scale bar, 10 μm. I, Quantification of FAK-WT (green bars) and FAK-NLS− (blue bars) TUNEL staining. Box and whisker plots show the mean ± SD from three independent experiments (****, P < 0.0001). ns, not significant.
Comparison of the efficacy of nal-IRI+5FU/LV and S-1 in patients with advanced pancreatic cancer refractory to gemcitabine and nab-paclitaxel
Authors: Yamaguchi Kazuhisa , Kikuchi Yoshinori , Kimura Yusuke , Iwasaki Susumu , Takuma Kensuke , Okano Naoki , Matsuda Takahisa
Published: December 2024

Introduction: Nanoliposomal irinotecan (nal-IRI) + 5- fluorouracil (FU)/leucovorin (LV) is the new standard second-line therapy for advanced pancreatic cancer (PC). Tegafur, gimeracil, and oteracil potassium (S-1) have been used in advanced PC after gemcitabine (GEM) plus nab-paclitaxel treatment, but the clinical difference between nal-IRI+5-FU/LV and S-1 remains unclear.
Methods: We retrospectively compared the efficacy and safety of nal-IRI+5-FU/LV and S-1 in patients with advanced PC refractory to GEM plus nab-paclitaxel. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety.
Results: We analyzed patients with advanced PC who were refractory to GEM plus nab-paclitaxel from May 2015 to January 2022 at our hospital. Twelve patients treated with nal-IRI+5-FU/LV and 51 patients treated with S-1 were included in this study. Comparing the nal-IRI+5-FU/LV and S-1 groups, the median PFS was 2.95 months vs. 2.10 months (p=0.658), respectively, and the median OS was 8.51 months vs. 5.83 months (p=0.763), respectively. The ORR and DCR were 8.3% and 2.0% (p=0.347) and 58.3% and 49.0% (p=0.750) for the nal-IRI+5-FU/LV and S-1 groups, respectively. There were no significant differences in adverse events between the two groups. In a subgroup analysis, patients under 65 years of age treated with S-1 had a significantly better median OS (HR, 3.46; 95% CI: 1.02-11.71, p=0.046).
Conclusion: Nal-IRI+5-FU/LV and S-1 were equally effective and safe as second-line therapy for PC. However, the results suggest that S1 is an option for younger patients, especially those under 65 years.
Activation of Imprinted Gene
PW1
Promotes Cardiac Fibrosis After Ischemic Injury
Authors: Kou Shan , Lu Zhengkai , Deng Defang , Ye Min , Sui Yu , Qin Lieyang , Feng Teng , Jiang Zhen , Meng Jufeng , Lin Chao-Po , Li Xiajun , Liu Chen , Tang Juan , Zhang Hui
Published: December 2024

BACKGROUND:

Cardiac fibrosis, characterized by excessive extracellular matrix (ECM) deposition in the myocardium, is an important target for heart disease treatments.
Pw1
(paternally expressed gene 3) is an imprinted gene expressed from the paternal allele, and de novo purine biosynthesis (DNPB) is a crucial pathway for nucleotide synthesis. However, the roles of PW1 and DNPB in ECM production by cardiac fibroblasts during myocardial ischemia are not yet understood.

METHODS:

To induce myocardial damage, we performed left anterior descending coronary artery ligation. We generated
Pw1

CreER-2A-eGFP

and
Pw1

2A-CreER

knock-in mouse lines to evaluate the expression of the 2
Pw1
alleles in normal and injured hearts. Bisulfite sequencing was used to analyze the DNA methylation of the
Pw1
imprinting control region. We identified the phosphoribosylformylglycinamidine synthase (
Pfas
) gene, encoding the DNPB enzyme PFAS, as a direct target of PW1 using chromatin immunoprecipitation sequencing and real-time quantitative polymerase chain reaction. The role of DNPB in ECM production and cardiac fibrosis after injury was examined in vitro using cultured cardiac fibroblasts and in vivo with
Pfas
-deficient mice.

RESULTS:

Our study demonstrates that myocardial infarction reduces DNA methylation at the imprinting control region of the maternally imprinted gene
Pw1
, triggering a switch from monoallelic imprinting to biallelic expression of
Pw1
in cardiac fibroblasts. In activated cardiac fibroblasts, increased
Pw1
expression promotes purine biosynthesis and induces ECM production by transcriptionally activating the DNPB factor
Pfas
. We identified that DNPB is essential for ECM production in activated fibroblasts and that loss of
Pfas
in fibroblasts limits cardiac fibrosis and improves heart function after injury.

CONCLUSIONS:

This study demonstrates that
Pw1
imprinting is disrupted after injury and reveals a novel role for the downstream target PFAS in ECM production and cardiac fibrogenesis. Targeting the PW1/PFAS signaling pathway presents a promising therapeutic strategy for improving cardiac repair after injury.
TeleAbsence: A Vision of Past and Afterlife
Telepresence
Authors: Ishii Hiroshi , Pillis Daniel , Pataranutaporn Pat , Xiao Xiao , Noh Hayoun , Li Lucy , Algargoosh Alaa , Labrune Jean-Baptiste
Published: December 2024

This paper presents our vision of TeleAbsence, extending the concept of telepresence to the past and the afterlife to address the vast emotional and temporal distance caused by the memory of loved ones who drifted apart and faded away. Instead of explicit and literal representations of loved ones, TeleAbsence describes poetic encounters with digital and physical traces left by the absence of others. TeleAbsence fosters illusory communications to conjure the feeling of being there with those no longer with us without using synthetic or generative representations and utterances. Our vision is deeply inspired by the Portuguese concept “Saudade”—the “desire for the beloved thing, people, place, and moment, made painful by its absence.” We present our vision through five design principles: presence of absence, illusory communication, the materiality of memory, traces of reflection, and remote time, grounded in historical and cultural contexts. We present exploratory narratives to illustrate these principles and the concept of ambient co-presence using poetry, phone, piano, and pen as mediums. We discuss challenges and opportunities for future work, including representational strategies to depict lost loved ones, ethical issues, and the possible extension of TeleAbsence to historical public figures.
Economy as Religion
Authors: Strijdom Johan
Published: December 2024

Engaging David Chidester’s argument that takes up ideas from Marx and Benjamin, the article argues that the academic study of religion can make a contribution to understand the economy by conceptualising it as functioning like a religion. This is achieved by using theorised concepts of myth (sacred stories), rituals and institutions that serve not only to unite adherents, but also to establish, maintain or challenge power relations. The thesis is tentatively illustrated with reference to the Chinese economy that needs to be compared with other economic systems that function like a religion.
Kabbala Denudata and Christian Knorr von Rosenroth’s Approach to the Zohar
Authors: Rivera Lusdemar Jacquez
Published: December 2024

This paper outlines the role of Kabbala denudata as a work produced conjointly with the 1684 Sulzbach edition of the Zohar and assesses how its compilation contributed to Christian Knorr von Rosenroth’s understanding of the Zohar as a Christological text. In so doing, it presents a history of the work and elaborates on Knorr von Rosenroth’s depiction of the Zohar as a methodological tool.
Newly Poor Women and the Social Safety Net, 1990–2010
Authors: Blank Rebecca M. , Card David , Kuttner Hanns
Published: December 2024

Welfare reforms in the 1990s, particularly the Personal Responsibility and Work Opportunity Reconciliation Act of 1996, were motivated by concerns over the long-term poor. We compare the experiences of newly poor women in 1990–1992, 2001–2003, and 2008–2010 and find that the size and sources of the income shocks generating new spells of poverty remained relatively stable. In dual-head families, the newly poor were most often pushed into poverty by a drop in spousal earnings; in single-mother families, the main cause was a drop in personal earnings. For single mothers in the latter two periods, we find that income from cash transfers after becoming poor was less than in the 1990–1992 benchmark. As these transfers include welfare payments, the timing points to the impacts of the 1996 welfare reforms.
Confronting Poverty: Measuring Its Causes, Costs, and Consequences
Authors: McGranahan Leslie , Schanzenbach Diane W.
Published: December 2024

We introduce this volume, which investigates a range of topics about poverty, including its measurement, policies intended to alleviate it, and the role of the economy in the likelihood of being in poverty. The volume was conceived as a tribute to Rebecca Blank, who was a leader in scholarship and policy translation and served at the highest levels in government and academia. The final section of the volume explores topics of special interest to Blank, including financial aid policy, the evolving roles of women in leadership, the ways in which academics can be more effective in policymaking, and motivations for her work.
Mobility Spaces: Geographical and Professional Distances in Career Mobility
Authors: Liu Sida , Au Anson
Published: December 2024

This article introduces the novel concept of “mobility spaces” to investigate the role of geographical and professional distances in career mobility and how they are influenced by social structural factors. Mobility spaces encompass physical, social, and legal spaces that professionals navigate while shaping their career trajectories over time. The study focuses on the movement of professionals across mobility spaces and examining the constraints and opportunities affecting their career paths. Using empirical data on the mobility of Hong Kong law firm partners from 1994 to 2021, the article demonstrates that social structural factors such as gender, race and ethnicity, firm origins, and firm prestige significantly influence the geographical and professional distances that professionals manage to traverse in their career moves. The mobility spaces theory aims to use space to contextualize the interplay between individual and macrostructural factors in shaping professional career outcomes.
Dynamics of Mucosal Integration of Machined versus Anodized Titanium Implants
Authors: Dworan J. , Aellos F. , Grauer J.A. , Fabbri G. , Harder K.G. , Boccardo S. , Cuevas P.L. , Dawid I. , Vicini M. , Helms J.A.
Published: December 2024

The long-term success of dental implants depends on the ability of soft tissues to form a protective barrier, limiting pathogen infiltration into peri-implant tissues. Here, we investigated the impact of an anodized surface modification on mucosal integration. Scanning electron microscopy and surface chemistry characterization were carried out on miniaturized implants. Following placement in fresh extraction sockets of mice, peri-implant tissues were examined at 4 time points. Histology along with quantitative immunohistochemistry for Keratin14, Vimentin, Laminin5, and CD68 were carried out on postimplant day (PID) 3 to assess early events in soft-tissue repair; on PID7, when peri-implant epithelialization was complete; at PID14, when osseointegration was complete; and at PID28, when soft-tissue maturation was nearing completion. In all cases, an intact junctional epithelium served as a reference. These analyses supported 3 conclusions: first, maturation of the peri-implant epithelium (PIE) is a protracted process, consistent with clinical observations. Second, maturation of the soft tissue–implant interface is slower than maturation of the bone-implant interface. Third, there is a benefit, albeit transient, to soft-tissue maturation around an anodized implant surface. Given its prolonged time course, strategies to improve and/or accelerate PIE maturation are likely to have significant clinical benefit.
Educational Context and Teacher Beliefs Matter: Multimodal Literacy in the Greater Bay Area of China
Authors: Liu Jiajia Eve , Lim Fei Victor
Published: December 2024

Multimodal literacy has been increasingly included as part of the language and literacy curriculum in many education systems across the world. In the Greater Bay Area (GBA) of China (Guangdong, Hong Kong, Macau), multimodal literacy has recently been incorporated into the curriculum guides to varying degrees. Little research has attended to how teachers understand multimodal literacy and how they react to the curriculum initiatives. Through examining the national and regional curriculum documents and conducting individual in-depth interviews with 15 purposively sampled secondary school English language teachers in the GBA, this study explores teachers’ beliefs about teaching multimodal literacy and the factors influencing their beliefs. The findings revealed that while the teachers recognized the importance of multimodal literacy in language education, they expressed mixed understandings of multimodal literacy and articulated diverse perspectives on how to teach it across the three regions. The teachers’ beliefs were found to be mediated by various factors at the macro, meso, and micro levels. The findings provide important implications for curriculum reforms and professional development for multimodal literacy education. This study argues for the importance of clarifying curriculum expectations for multimodal literacy and developing contextually sensitive and responsive approaches to meet teachers’ and students’ needs. It also highlights the cruciality of considering teachers’ beliefs in professional development programmes for multimodal literacy. Focusing on the GBA of China, where regions are just beginning to integrate multimodal literacy into the curriculum, this study builds on earlier research on multimodal literacy in other areas of Asia and discusses its findings in relation to these studies. Collectively, these studies, while situated in Asia, contribute to the ongoing global interest and advancement of multiliteracies education.