bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional diversity of senescent cells in driving ageing phenotypes and facilitating tissue regeneration
Authors: Nakano Yasuhiro , Johmura Yoshikazu
Published: January 2025

As the global population continues to age, understanding the complex role of cellular senescence and its implications in healthy lifespans has gained increasing prominence. Cellular senescence is defined as the irreversible cessation of cell proliferation, accompanied by the secretion of a range of pro-inflammatory factors, collectively termed the senescence-associated secretory phenotype (SASP), in response to various cellular stresses. While the accumulation of senescent cells has been strongly implicated in the ageing process and the pathogenesis of age-related diseases owing to their pro-inflammatory properties, recent research has also highlighted their essential roles in processes such as tumour suppression, tissue development and repair. This review provides a comprehensive examination of the dual nature of senescent cells, evaluating their deleterious contributions to chronic inflammation, tissue dysfunction and disease, as well as their beneficial roles in maintaining physiological homeostasis. Additionally, we explored the therapeutic potential of senolytic agents designed to selectively eliminate detrimental senescent cells while considering the delicate balance between transient and beneficial senescence and the persistence of pathological senescence. A deeper understanding of these dynamics is critical to develop novel interventions aimed at mitigating age-related dysfunctions and enhancing healthy life expectancies.
Cellular senescence in the cancer microenvironment
Authors: Meguro Satoru , Nakanishi Makoto
Published: January 2025

In this ageing society, the number of patients suffering from age-related diseases, including cancer, is increasing. Cellular senescence is a cell fate that involves permanent cell cycle arrest. Accumulated senescent cells in tissues over time present senescence-associated secretory phenotype (SASP) and make the inflammatory context, disturbing the tumour microenvironment. In particular, the effect of senescent cancer-associated fibroblasts on cancer progression has recently come under the spotlight. Although scientific evidence on the impact of cellular senescence on cancer is emerging, the association between cellular senescence and cancer is heterogeneous and the comprehensive mechanism is still not revealed. Recently, a therapy targeting senescent cells, senotherapeutics, has been reported to be effective against cancer in preclinical research and even clinical trials. With further research, the development of senotherapeutics as a novel cancer therapy is expected.
An unresolving painful condition following a trivial peripheral fracture
Authors: Minisola Salvatore , Colangelo Luciano , Rossi Giuseppe , Gualdi Gianfranco , Pepe Jessica , Cipriani Cristiana
Published: January 2025

Vignette

A 58-yr-old woman presented to our mineral metabolism center, complaining of localized and continuous pain, which worsened with movements, and weakness of the right foot. The patient reported having had a fracture of the fifth metatarsal bone of the right foot about 4 mo ago. She was initially treated with a cast that she did not tolerate and then with an orthopedic brace. After about 1 mo, she noticed swelling of the right foot and started complaining of continuous pain. The physical examination when came to our center seemed partly improved in respect to the initial one referred by the patient even though she still presented with a mild swelling, reddish skin color, and mild sweating on the right foot. Allodynia and hyperalgesia still persisted but at a lower grade. Main biochemical parameters of calcium metabolism were in the normal range. After excluding other clinical conditions, a diagnosis of complex regional pain syndrome type I was made. She was treated with neridronate iv with resolution of symptoms while continuing with physical therapy and pain relievers. Similar milder episodes were reported by the patient in the following months. However, they were immediately resolved by prompt neridronate infusion. No further complaints have been reported during the next 3 yr follow-up.
The real prevalence and clinical courses of non-metastatic castration-resistant prostate cancer: a retrospective single-institutional study
Authors: Takamori Hajime , Goto Takayuki , Kashima Soki , Yoshino Takayuki , Ogata Takashi , Aizawa Rihito , Nakamura Kiyonao , Sano Takeshi , Sawada Atsuro , Akamatsu Shusuke , Yamasaki Toshinari , Inoue Takahiro , Mizowaki Takashi , Ogawa Osamu , Kobayashi Takashi
Published: January 2025

Background

Non-metastatic castration-resistant prostate cancer (PCa) has become clinically important in PCa management, with treatments aiming to delay metastasis. However, limited data exist on its prevalence and patient characteristics in real-world settings.

Methods

We retrospectively investigated the clinical records of 1929 patients who were treated for localized PCa between 2005 and 2018. From this population, we counted patients who progressed to non-metastatic castration-resistant PCa, and summarized the characteristics of the patients.

Results

Among patients who underwent radical prostatectomy (796 patients), radiation therapy (1021 patients), or primary androgen deprivation therapy (ADT) (112 patients), 0.9%, 0.9%, and 5.4%, respectively, were diagnosed with non-metastatic castration-resistant PCa over a median follow-up of 5.5 years. Including referred cases, a total of 45 non-metastatic castration-resistant PCa patients were analyzed. The median age at non-metastatic castration-resistant PCa diagnosis was 76 years, with a median time of 4.8 years from the initiation of ADT to non-metastatic castration-resistant PCa development. From the initial PCa diagnosis, the median time to non-metastatic castration-resistant PCa was 5.9 years. Median metastasis-free survival was 5.2 years, while overall survival was 6.3 years.

Conclusion

This study reports the prevalence of non-metastatic castration-resistant PCa at our institution and provides clinical findings of non-metastatic castration-resistant PCa patients by analyzing consecutive localized PCa cases through comprehensive medical chart reviews for every patient.
Cytokine release syndrome induced by dabrafenib and trametinib therapy in BRAF V600E-mutant non-small cell lung cancer
Authors: Sumi Toshiyuki , Ishigooka Taiki , Matsuura Keigo , Ikeda Takumi , Yamada Yuichi , Chiba Hirofumi
Published: January 2025

Non-small cell lung cancer (NSCLC) with BRAF V600E mutations is responsive to targeted therapies, such as dabrafenib and trametinib. However, these treatments can lead to serious adverse events, including cytokine release syndrome (CRS). Herein, we report the case of a 75-year-old man with stage IVB NSCLC and a BRAF V600E mutation who developed severe CRS, manifesting hepatic and renal dysfunction, following treatment with dabrafenib and trametinib. Despite initial fever management, the patient’s renal function deteriorated rapidly, necessitating hemodialysis. Elevated cytokine levels, including interleukin-6, interferon-γ, and tumor necrosis factor α, were detected. The patient was treated with steroid pulse therapy, which resulted in fever resolution, and his renal function gradually improved. Hemodialysis was discontinued as renal function recovered. This case underscores the importance for early recognition and management of CRS in patients receiving targeted therapies. Prompt intervention with steroids may prevent CRS progression and mitigate associated organ dysfunction. Further investigation is required to clarify the mechanisms of CRS in patients receiving targeted therapy, particularly in the absence of prior immune checkpoint inhibitor use.
Revisiting the individual-level correlates of emigration intentions: Evidence from Central America
Authors: Perelló Lucas
Published: January 2025

Central American countries have grappled with various challenges in recent decades, including economic hardship, insecurity, corruption, and democratic backsliding. In theory, these factors—individually and jointly—contribute to migration. This article builds on a rich body of knowledge and revisits the individual-level correlates of emigration intentions in El Salvador, Guatemala, Honduras, and Nicaragua. I employ a comprehensive dataset spanning over a decade of AmericasBarometer surveys by the Latin American Public Opinion Project from 2006 to 2018–19. The empirical results, which rely on probit maximum likelihood estimators, sketch a statistical outline of the correlates of emigration intentions and reveal to what extent they have changed over time. The statistical analysis confirms that multiple factors correlate to emigration intentions. But a closer look reveals that two variables are more consistent over time and across countries: receiving remittances and crime victimization.
Patterns and Predictors of COVID-19 Vaccine Uptake Among U.S. Active Duty Service Members, 2020-2022: Implications for Future Pandemics
Authors: Sercy Erica , Stewart Laveta , Craig-Kuhn Megan Clare , Stern Caryn , Graham Brock , Michel Amber , Parmelee Edward , Pollett Simon , Burgess Timothy , Tribble David R
Published: January 2025

Introduction

Vaccine mandates have been used to minimize the duty days lost and deaths attributable to infectious disease among active duty Service members (ADSMs). In response to the global COVID-19 pandemic, in August 2021, the U.S. DoD issued a COVID-19 vaccine mandate for all ADSMs. This study aimed to investigate COVID-19 vaccine uptake among the ADSM population, as well as factors associated with timing of COVID-19 vaccine receipt.

Materials and Methods

This study included ADSMs on active duty between January 1, 2020, and June 30, 2022. Univariate analyses investigated associations between demographic factors (age, sex, race, ethnicity, branch of service, rank, and state of residence) and COVID-19 diagnosis with the following outcomes: (1) time to primary series initiation in relation to the DoD vaccine mandate, (2) time between doses of the 2-dose primary series, and (3) time between booster eligibility and receipt. This research received an exempt determination by the USU Human Research Protection Program.

Results

In total, 1,799,466 ADSMs were included, with 90% receiving ≥1 COVID-19 vaccine dose during the study period and 77% initiating the primary series prior to the mandate. Over 80% of ADSMs received a complete primary series, with 96% of those adhering to the recommended regimen. The history of COVID-19 diagnosis was associated with the later receipt of all doses.

Conclusions

COVID-19 vaccine uptake was high among all ADSMs, with the majority initiating the primary series before the mandate. The high vaccine uptake among ADSMs shown here may be used as a guide to both military and civilian pandemic policy and outreach efforts related to enhanced vaccine uptake.
The Hidden Politics of (Public) Music Theory
Authors: Boyd Clifton
Published: January 2025

In this brief essay, I seek to identify and contribute to a growing body of literature that advocates for a healthy suspicion of the political aims of music theory (academic, public, and otherwise), which at times hides its aim to harm and oppress. I describe how (public) music theory can have explicit politics, implicit politics, and, most relevant to this discussion, hidden politics. I conclude by reflecting on how we professional music theorists might continue our work in and on public music theory in ways that align with broader disciplinary goals of dismantling structural inequities.
Flow and intuition: a systems neuroscience comparison
Authors: Kotler Steven , Parvizi-Wayne Darius , Mannino Michael , Friston Karl
Published: January 2025

This paper explores the relationship between intuition and flow from a neurodynamics perspective. Flow and intuition represent two cognitive phenomena rooted in nonconscious information processing; however, there are clear differences in both their phenomenal characteristics and, more broadly, their contribution to action and cognition. We propose, extrapolating from dual processing theory, that intuition serves as a rapid, nonconscious decision-making process, while flow facilitates this process in action, achieving optimal cognitive control and performance without [conscious] deliberation. By exploring these points of convergence between flow and intuition, we also attempt to reconcile the apparent paradox of the presence of enhanced intuition in flow, which is also a state of heightened cognitive control. To do so, we utilize a revised dual-processing framework, which allows us to productively align and differentiate flow and intuition (including intuition in flow). Furthermore, we draw on recent work examining flow from an active inference perspective. Our account not only heightens understanding of human cognition and consciousness, but also raises new questions for future research, aiming to deepen our comprehension of how flow and intuition can be harnessed to elevate human performance and wellbeing.
Petrogenesis and Geochemistry of Upper Paleozoic Komatiites (Mashhad, NE Iran)
Authors: Mobasheri Mohsen , Arndt Nicholas , Cordier Carole , Sobolev Alexander , Ghasemi Habibollah , Marchesi Claudio , Sabzehei Mossaieb , Garrido Carlos J
Published: January 2025

Upper Paleozoic, probably Permian, komatiites have been found in the Paleo-Tethys suture zone in NE Iran. These rocks are divided into three groups: (i) differentiated and undifferentiated komatiite lava flows, (ii) komatiitic basalts, and (iii) ultramafic–mafic pillow lavas. The rocks have a wide range of textures including random olivine spinifex, layered olivine spinifex, random and string-beef pyroxene spinifex, micrographic intergrowths of plagioclase and clinopyroxene, and cumulate textures. MgO contents range from 7.1 wt % in basalts and gabbros in differentiated flows to 38.0 wt % in cumulates, flow margins and samples with olivine spinifex textures. The MgO content of the parental melt is estimated using the Fo content of olivine (89–91) to be between 20 and 25 wt %, and the higher MgO content in spinifex samples (30 to 36 wt %) is attributed to accumulation of olivine. The rocks have low Al2O3/TiO2 and are relatively depleted in heavy rare earth elements. They, therefore, are classified as Al-depleted komatiite, the first report of this magma type in a Phanerozoic locality. These characteristics are attributed to the presence of garnet in the source during mantle melting and melt extraction. The rocks also have relatively low contents of the more incompatible trace elements indicating derivation from a depleted source. Our study indicates that the parental magma formed by 10% to (about) 20% partial melting in a mantle plume at pressures of about 4 to 5 GPa (depths of 120–150 km). Ascent of the plume into the Late Paleozoic subduction zone at the margin of the Paleo-Tethys Ocean is a possible petrogenetic model for the generation of these komatiites.
Take a deep BReath: Manipulating brassinosteroid homeostasis helps cereals adapt to environmental stress
Authors: Zolkiewicz Karolina , Gruszka Damian
Published: January 2025

Global climate change leads to the increased occurrence of environmental stress (including drought and heat stress) during the vegetative and reproductive stages of cereal crop development. Thus, more attention should be given to developing new cereal cultivars with improved tolerance to environmental stress. However, during the development of new stress-tolerant cereal cultivars, the balance between improved stress responses (which occur at the expense of growth) and plant yield needs to be maintained. Thus, the urgent need for developing new cereal germplasm with improved stress tolerance could be fulfilled using semidwarf cereal mutants defective in brassinosteroid (BR) biosynthesis or signaling. BRs are steroid phytohormones that regulate various developmental and physiological processes throughout the plant life cycle. Mutants defective in BR biosynthesis or responses show reduced plant height (dwarfism or semi-dwarfism). Importantly, numerous reports indicate that genetic modification or biotechnological manipulation of BR biosynthesis or signaling genes in cereals such as rice (Oryza sativa), maize (Zea mays), wheat (Triticum aestivum), and barley (Hordeum vulgare), which are of crucial importance for global agriculture, may facilitate the development of cereal germplasm with improved stress tolerance. This review presents a comprehensive overview of the genetic manipulation of BR homeostasis in the above-mentioned cereal crops aimed at improving plant responses to various environmental stresses, such as drought, salinity, oxidative stress, thermal stress, and biotic stresses. We highlight target BR-related genes and the effects of genetic manipulation (gene editing, overexpression, and silencing or microRNA-mediated regulation) on plant adaptability to various stresses and provide future perspectives.
Saddle-Point Approximation to the False-Vacuum Decay at Finite Temperature in 1D Quantum Mechanics
Authors: Harada Koji , Tao Shuichiro , Yin Qiang
Published: January 2025

We calculate the false-vacuum decay rate in 1D quantum mechanics on the basis of the saddle-point approximation in the Euclidean path integral at finite temperature. The saddle points are the finite-T and shifted bounce solutions, which are finite-period analogs of the (zero-temperature) bounce solution, and the shot solutions. We reexamine the zero-temperature result by Callan and Coleman and compare it with the zero-temperature limit of our results. We also perform some numerical calculations to illustrate the temperature dependence of the decay rate and compare it with the result by Affleck.
Euler Systems and Selmer Bounds for GU(2,1)
Authors: Manji Muhammad
Published: January 2025

We investigate properties of the Euler system associated with certain automorphic representations of the unitary similitude group GU(2,1) with respect to an imaginary quadratic field E, constructed by Loeffler–Skinner–Zerbes. By adapting Mazur and Rubin’s Euler system machinery we prove one divisibility of the ‘rank 1’ Iwasawa main conjecture under some mild hypotheses. When p is split in E we also prove a ‘rank 0’ statement of the main conjecture, bounding a particular Selmer group in terms of a p-adic distribution conjecturally interpolating complex L-values. We then prove descended versions of these results, at the integral level, where we bound certain Bloch–Kato Selmer groups. We will also discuss the case where p is inert, which is a work in progress.
Enforcing Chinese charitable trusts
Authors: Zhang Wanyi , Jing Hui
Published: January 2025

This article examines the enforcement mechanisms of Chinese charitable trusts, highlighting the limitations of public law enforcement by civil affairs departments due to resource constraints. Through a comparative analysis of the English particular interest rule, it explores alternative enforcement frameworks, arguing that the beneficiary–recipient debate, while academically insightful, does not address practical enforcement challenges. The study suggests that the public law elements of charitable trusts necessitate a flexible, context-sensitive enforcement approach. For Chinese courts, the focus should be on whether supporting a plaintiff-charitable trust beneficiary’s claim ensures proper management of trust property and preserves the public benefit.
Heat stress matters: insights from United States swine producers
Authors: Johnson Jay S , Stewart Kara R
Published: January 2025

Heat stress (HS) is widely recognized by researchers and veterinarians as a major issue impacting swine health, productivity, and welfare, but there is limited understanding of how HS is perceived and managed at the farm level. Therefore, the study objective was to assess U.S. swine farm managers’ perceptions of HS impacts, thresholds, and management for multiple pig categories including preweaned pigs, nursery pigs, grow-finish pigs, market pigs, nonpregnant and gestating sows, lactating sows, and mature boars. Sixty-two swine farm managers completed an electronic Qualtrics survey, presented in both English and Spanish, which included questions on perceived HS thresholds, ventilation setpoints, mitigation practices, and environmental management support tools. Respondents rated their agreement with HS impacts on productivity, health, and welfare using a Likert scale, and Pearson’s correlations were used to establish relationships between responses. A majority of respondents agreed or strongly agreed that HS negatively affects pig productivity (87.1%), health (83.9%), and welfare (85.5%). However, perceived HS thresholds were variable across pig categories including preweaning pigs (31.22 ± 3.59 °C), nursery pigs (31.46 ± 3.79 °C), grow-finish pigs (28.16 ± 4.27 °C), market pigs (26.22 ± 5.56 °C), nonpregnant sows (27.77 ± 3.81 °C), gestating sows (26.99 ± 3.34 °C), lactating sows (26.71 ± 3.08 °C) and mature boars (26.61 ± 3.99 °C). The standard deviations for reported thresholds ranged from ±3.08 to ±5.56 °C, underscoring the variability in perceptions among respondents. This variability extended to ventilation temperature setpoints with high ventilation temperature setpoints of 24.34 ± 3.75 °C and 25.41 ± 2.80 °C, and low ventilation temperature setpoints of 17.32 ± 3.10 °C and 18.86 ± 2.96 °C for gestation barns and farrowing barns, respectively. Finally, a majority of producers (64.5%) agreed or strongly agreed that a decision support tool for improved HS management would be beneficial to their operation. Producer responses emphasize the need for clearer guidelines and more consistent application of HS management practices to optimize swine health, productivity, and welfare across different production stages.
Drought-responsive transcriptional regulations and expressional marker genes of Japanese cedar, Cryptomeria japonica (L.f.) D. Don
Authors: Nagano Soichiro , Nose Mine , Takashima Yuya , Matsushita Michinari , Hiraoka Yuichiro , Hirao Tomonori
Published: January 2025

The selection of plant genotypes characterized by wellness and stable growth under drought-stress conditions amid ongoing climate change is an important challenge in forest tree breeding. The introduction of molecular markers will enable efficient selection of breeding materials that are resistant to drought stress in forest trees as well as in crop species. Japanese cedar, Cryptomeria japonica (Thunb. ex L.f.) D. Don, the most dominant forest species in Japan, grows well on mesic sites and is characterized by intraspecific variation in its drought-stress response. Here, we analyzed the physiological characteristics and gene expression profiles of multiple C. japonica genotypes under both control and drought-stress conditions to identify drought-responsive genes and develop gene expression markers that could assess the physiological status of cuttings based on their gene expression responses to dehydration. The two representative genes that showed a large expressional change in the later period after water withholding were both homologs of COR47, a gene in the dehydrin protein family, and of ERF016, a member of the dehydration-responsive element-binding transcription factor family in Arabidopsis. We developed both intermediate- and small-scale sets of gene-expression analysis platforms that allowed us to correlate gene expression with the physiological responses of cuttings to drought. The results highlight the potential to assess the environmental adaptability with gene expression analysis in C. japonica.
Proteomics- and metabolomics-based analysis of the regulation of germination in Norway maple and sycamore embryonic axes
Authors: Kalemba Ewa Marzena , Dufour Sara , Gevaert Kris , Impens Francis , Meimoun Patrice
Published: January 2025

Norway maple and sycamore belong to the Acer genus and produce desiccation-tolerant and desiccation-sensitive seeds, respectively. We investigated the seed germination process at the imbibed and germinated stages using metabolomic and proteomic approaches to determine why sycamore seeds germinate earlier and are more successful at establishing seedlings than Norway maple seeds under controlled conditions. Embryonic axes and embryonic axes with protruded radicles were analyzed at the imbibed and germinated stages, respectively. Among the 212 identified metabolites, 44 and 67 differentially abundant metabolites were found at the imbibed and germinated stages, respectively, in both Acer species. Higher levels of amines, growth and defense stimulants, including B vitamins, were found in sycamore. We identified 611 and 447 proteins specific to the imbibed and germinated stages, respectively, in addition to groups of proteins expressed at different levels. Functional analysis of significantly regulated proteins revealed that proteins with catalytic and binding activity were enriched during germination, and proteins possibly implicated in nitrogen metabolism and metabolite interconversion enzymes were the predominant classes. Proteins associated with the control of plant growth regulation and seed defense were observed in both species at both germination stages. Sycamore proteins possibly involved in abscisic acid signal transduction pathway, stress tolerance and alleviation, ion binding and oxygenase activities appeared to accompany germination in sycamore. We identified peptides containing methionine (Met) oxidized to methionine sulfoxide (MetO), and functional analyses of proteins with significantly regulated MetO sites revealed that translation, plant growth and development and metabolism of nitrogen compounds were the main processes under Met/MetO redox control. We propose that higher levels of storage proteins and amines, together with higher levels of B vitamins, supported more efficient nitrogen utilization in sycamore, resulting in faster seedling growth. In conclusion, omic signatures identified in sycamore seem to predispose germinated sycamore seeds to better postgerminative growth.
Thermal Adaptation in Worldwide Collections of a Major Fungal Pathogen
Authors: Minana-Posada Silvia , Lorrain Cécile , McDonald Bruce A. , Feurtey Alice
Published: January 2025

Adaptation to new climates poses a significant challenge for plant pathogens during range expansion, highlighting the importance of understanding their response to climate to accurately forecast future disease outbreaks. The wheat pathogen Zymoseptoria tritici is ubiquitous across most wheat production regions distributed across diverse climate zones. We explored the genetic architecture of thermal adaptation using a global collection of 411 Z. tritici strains that were phenotyped across a wide range of temperatures and then included in a genome-wide association study. Our analyses provided evidence for local thermal adaptation in Z. tritici populations worldwide, with a significant positive correlation between bioclimatic variables and optimal growth temperatures. We also found a high variability in thermal performance among Z. tritici strains coming from the same field populations, reflecting the high evolutionary potential of this pathogen at the field scale. We identified 69 genes putatively involved in thermal adaptation, including one high-confidence candidate potentially involved in cold adaptation. These results highlight the complex polygenic nature of thermal adaptation in Z. tritici and suggest that this pathogen is likely to adapt well when confronted with climate change.
Arginine demethylation of Serine/Arginine‐rich splicing factor 1 enhances miRNA enrichment in small extracellular vesicles derived from pancreatic ductal adenocarcinoma cells
Authors: Bhandari Kritisha , Kong Jeng Shi , Ho Wang‐Ting Tina , Bourne Philip C. , Mooers Blaine H. M. , Ding Wei‐Qun
Published: January 2025

Small extracellular vesicles (sEVs) are enriched in certain miRNAs, impacting the progression of pancreatic ductal adenocarcinoma (PDAC). The mechanisms involved in the selective sEV miRNA enrichment remain to be elucidated. We recently reported that Serine/Arginine‐rich splicing factor 1 (SRSF1) regulates selective sEV miRNA enrichment in PDAC cells. SRSF1 is an onco‐protein that is overexpressed in PDAC, and its function is dictated by posttranslational modifications such as phosphorylation and arginine methylation. The objective of this study was to examine the role of phosphorylation and arginine methylation in SRSF1‐mediated sEV miRNA enrichment in PDAC cells. Treatment of PDAC cells with the protein arginine methyltransferase inhibitors AMI‐5 and EPZ015666, but not with the phosphorylation inhibitor SRPIN340, selectively enhanced the level of sEV miR‐1246, a miRNA known to be highly enriched in PDAC sEVs. Consistently, overexpression of the mutant SRSF1 with the three arginine residues R93, R97, and R109 being replaced with lysinaugmented sEV miR‐1246 levels in both wild‐type and SRSF1‐knockdown PANC‐1 cells. Interestingly, the binding of SRSF1 to miR‐1246 was significantly reduced in PDAC cells overexpressing the mutant SRSF1, which was further confirmed using purified wild‐type and the mutant SRSF1 proteins. We demonstrate that arginine demethylation of SRSF1 reduces SRSF1‐miRNA binding in PDAC cells and enhances selective sEV miRNA enrichment, providing novel insight into SRSF1‐mediated sEV miRNA enrichment in PDAC cells and opening up new avenues of investigation on the biology and function of extracellular vesicles in PDAC.
The crucial role of CEMIP in cancer metastasis: Mechanistic insights and clinical implications
Authors: Ko Yeo Gyeong , Jo Jung Hyun , Song Si Young , Lee Hee Seung
Published: January 2025

Cancer metastasis is the leading cause of cancer‐related deaths, making early detection and the prevention of metastatic progression critical research priorities. Recent studies have expanded our understanding of CEMIP (KIAA1199, HYBID), revealing its involvement in cancer metastasis and its potential role in slowing cancer progression. CEMIP plays critical roles in several stages of cancer metastasis: First, CEMIP promotes cancer cell proliferation to maintain cell heterogeneity before the metastasis process. Second, it facilitates cancer cell detachment by promoting the epithelial‐mesenchymal transition (EMT) through alterations in signaling pathways. Third, CEMIP contributes to cancer cell adherence and attachment by enabling cells to withstand cell death (anoikis and ferroptosis) and hypoxia. Fourth, during the invasion process, CEMIP induces hyaluronan depolymerization and further modulates signaling to promote EMT. Lastly, in the pre‐metastatic niche, CEMIP influences the tumor microenvironment through hypoxia, angiogenesis, signaling pathway changes, and hyaluronan degradation. Recent studies have focused on leveraging CEMIP as a diagnostic tool or a predictor of metastasis and/or targeting CEMIP to overcome cancer resistance and progression. This review aims to explore the role of CEMIP at each stage of cancer metastasis and highlight recent advances in targeting CEMIP to inhibit cancer progression.
Alterations in the inflammatory homeostasis of aging‐related cardiac dysfunction and Alzheimer's diseases
Authors: Huang Shuli , Nunez Jeremiah , Toresco Dai Lan , Wen Changhong , Slotabec Lily , Wang Hao , Zhang Haibei , Rouhi Nadiyeh , Adenawoola Michael I. , Li Ji
Published: January 2025

Alzheimer's disease (AD) is well known among the elderly and has a profound impact on both patients and their families. Increasing research indicates that AD is a systemic disease, with a strong connection to cardiovascular disease. They share common genetic factors, such as mutations in the presenilin (PS1 and PS2) and the apolipoprotein E (APOE) genes. Cardiovascular conditions can lead to reduced cerebral blood flow and increased oxidative stress. These factors contribute to the accumulation of Aβ plaques and the formation of abnormal tau protein tangles, which are both key pathological features of AD. Additionally, Aβ deposits and abnormal protein responses have been observed in cardiomyocytes as well as in peripheral tissues. The toxic Aβ deposition intensifies damage to the microvascular structure associated with blood–brain barrier disruption and the initiation of neuroinflammation, which may accelerate the onset of neurocognitive deficits and cardiovascular dysfunction. Thus, we discuss the main mechanisms linking AD and cardiac dysfunction to enhance our understanding of these conditions. Ultimately, insights into the brain–heart axis may help us develop effective treatment strategies in the future.
Klotho mutation does not accelerate intervertebral disc aging in mice
Authors: Hong Justin , Shah Veeraj , Krishnan Ravi , Gomez‐Stallons M. Victoria , Poudel Sunil , Yutzey Katherine E. , Dahia Chitra L.
Published: January 2025

Aging is a risk factor for several chronic conditions, including intervertebral disc degeneration and associated back pain. Disc pathologies include loss of reticular‐shaped nucleus pulposus cells, disorganization of annulus fibrosus lamellae, reduced disc height, and increased disc bulging. Sonic hedgehog, cytokeratin 19, and extracellular matrix proteins are markers of healthy disc. Preclinical murine models help understand cellular and molecular mechanisms of disc pathologies and the associated neurological symptoms. Klotho (Kl) is a known anti‐aging gene. Kl‐deficient mice (KlKl/KlKl) have a reduced lifespan and display accelerated aging phenotypes in several tissues, including the kidney, pancreas, bone, and brain. To test the suitability of KlKl/KlKl mice for studying accelerated disc pathologies, we characterized the lumbar discs of eight‐week‐old KlKl/KlKl mice compared to wild‐type controls. No structural, morphological, or molecular differences were observed in the discs of KlKl/KlKl mice compared to controls. Next, we tested the hypothesis that KlKl/KlKl mice do not display accelerated disc pathologies due to the absence of Kl expression or response by disc cells. Multiplex qPCR analysis did not detect any Kl isoforms in the disc cells, explaining the absence of disc phenotype in KlKl/KlKl mutants.
A qualitative analysis of PA leaders in Kentucky
Authors: Gadd Noah , Wright Whitney , Dooley Jena , Stumbo Hannah , Marshall Emily , Ewers Will , Valentin Virginia L.
Published: January 2025

Objective:

To describe Kentucky's physician associate/assistant (PA) leadership pathway and provide advice for individual leadership trajectories.

Methods:

A qualitative study using semistructured interviews and inductive coding methodology to identify themes of PA leaders.

Results:

Participants were primarily female (76.2%), ages 35 to 44 years (52.4%), and White (90.5%). They were primarily nonclinical (38.1%), described achieving their current leadership role by pursuing opportunities (42.9%), showed emotional intelligence (61.9%), had grit (61.9%), and did not feel that academic success correlates to leadership (42.9%). Leaders also gave advice consisting of form connections, prioritize personal growth, develop an entrepreneurial mindset, and play to your strengths.

Conclusions:

Leadership is needed in healthcare and PAs are primed to serve in this role. Previous leadership experience is not a requirement, but organization, emotional intelligence, and grit are required. Future PA leaders should follow the playbook laid out by these leaders and begin today with investing in personal leadership development.
Essential Competencies in Nursing Leadership From Asian Leaders’ Perspectives
Authors: Tsai Hsiu-Min , Sakashita Reiko , Wang Hsiu-Hung , Chen Ching-Min , Kim Hae-Won , Oh Eui-Geum , Im Eun-Ok
Published: January 2025

The literature on nursing leadership tends to be mainly based on Western perspectives and models, which could be viewed as an imperialistic and colonialist aspect of nursing knowledge development. Furthermore, leadership competencies and skills could differ across countries due to variations in cultural backgrounds. The purpose of this discussion paper is to identify essential competencies of leaders from Asian nurse leaders’ perspectives and provide suggestions for future nursing leadership. Four themes related to the leadership competencies were identified: “harmony,” “visionary,” “political activism,” and “good character.”
Anterior Cervical Discectomy and Fusion Versus Cervical Corpectomy With Iliac Crest Graft and Fusion in Multilevel Degenerative Myelopathy
Authors: Rivas Palacios Claudio A. , Barbosa Mario M. , Escobar María A. , Garcia-Ballestas Ezequiel , García Camilo , Mattar Salvador M. , Mattar Salvador
Published: January 2025

Study Design:

Cohort retrospective study.

Objective:

We evaluated and compared the outcomes of anterior cervical discectomy with fusion (CDF) and anterior cervical corpectomy with iliac crest graft and fusion (CCF) in patients with ≥3 level degenerative cervical myelopathy (DCM).

Background:

Anterior and posterior approaches are widely employed in DCM when compressive elements predominate in the anterior or posterior spinal cord, respectively. Indications for each approach remain controversial in some contexts.

Methods:

Following the STROBE statement, a retrospective enrollment from records of patients who underwent anterior CDF and/or CCF between June 2015 and June 2022. Linear mixed models were applied to establish the effects of the type of surgery according to the follow-up time (mo).

Results:

In this study, 73 patients met the inclusion criteria, of which 21 (28.8%) were included in the CDF group and 52 (71.2%) in the CCF group. Twenty surgeries were performed at 3 cervical levels and 53 at 4 levels. There was an improvement in the NDI and VAS score, with an Odom mean of 1.63±0.67 at 12 months of follow-up, with no differences between CDF and CCF. In the CDF group, it was reported a greater C2–7 Cobb angle at the third month of follow-up. In the CCF group, the C2–7 Cobb angle had a negative correlation with the NDI and VAS scales, and a positive correlation with the mJOA scale. Intraoperative estimated blood loss (EBL), surgical time, and postoperative hospital stay were shorter in CDF. There were no differences between the 2 groups in medical complications and other radiologic findings.

Conclusion:

Surgery for multilevel DCM using an anterior approach with CDF or CCF showed good clinical outcomes without significant differences between the 2 groups, and equivalent results in medical complications and radiologic parameters. The CDF group had better perioperative results and shorter postoperative hospitalization time.
High CXCL8 expression predicting poor prognosis in triple-negative breast cancer
Authors: Tang Sumin , Zhang Yuqing , Song Liying , Hui Kaiyuan , Jiang Xiaodong
Published: January 2025

Triple-negative breast cancer (TNBC) is highly prone to early relapse and metastasis following standard treatment. CXCL8 is a key factor in tumor invasion and metastasis, but its role in TNBC prognosis and clinicopathological correlations remains poorly understood. This study investigated CXCL8 expression and its clinical significance in TNBC to develop a prognostic nomogram for guiding intensive treatment and follow-up strategies. Public datasets from the gene expression omnibus public datasets platform were analyzed to assess CXCL8 expression. Additionally, paraffin-embedded TNBC specimens collected from our hospital were examined using immunohistochemistry to explore the relationship between CXCL8 expression and clinicopathological features. Survival analysis was performed to evaluate whether CXCL8 serves as an unfavorable prognostic biomarker for TNBC patients. Univariate Cox regression analysis was conducted to identify prognostic factors. Based on these findings, a nomogram was developed to predict TNBC progression risk. CXCL8 expression was significantly higher in TNBC tissues than in adjacent normal tissues (P < 0.05). Among 122 TNBC patients, 46 were CXCL8-positive and 76 were CXCL8-negative. CXCL8 expression was significantly associated with N stage (P < 0.05). Progression-free survival (PFS) was markedly shorter in the CXCL8-positive group compared with the CXCL8-negative group (P < 0.001). Univariate Cox regression identified N1-3, M1, and CXCL8 positivity as significant risk factors for disease progression. A nomogram incorporating these variables (N, M, and CXCL8) was constructed to predict PFS. Time-dependent receiver operating characteristic curve analysis at 12-, 36-, and 48-month demonstrated strong predictive performance, with area under the curve values of 0.857, 0.839, and 0.795, respectively. CXCL8 is highly expressed in TNBC and promotes lymphatic metastasis, serving as an unfavorable prognostic factor. The developed nomogram offers a valuable tool for guiding personalized treatment and follow-up strategies in TNBC patients.
Nurse Experiences in an Electronic Health Record Transition
Authors: Brunner Julian , Amano Alexis , Davila Jessica , Krein Sarah , Sullivan Sheila C. , Church Victoria , Sayre George , Rinne Seppo T.
Published: January 2025

Transitions from one EHR to another can be enormously disruptive to care. Nurses are the largest group of EHR users, but nurse experiences with EHR transitions have not been well documented. We sought to understand nurse experiences with an EHR transition at the US Department of Veterans Affairs. We used a mixed methods design, combining a cumulative 26 longitudinal interviews with 317 survey free-text responses and quantitative measures from a repeated cross-sectional survey, all from nurses at one of the first facilities to transition from the Department of Veterans Affairs' homegrown EHR to a commercial system. We conducted inductive/deductive content analysis of qualitative data and paired qualitative findings with descriptive statistics of survey questions. Analyses yielded insights about three key aspects of the transition: (1) EHR functionality: diverse perceived causes of challenges using the new EHR; (2) transition process: barriers and facilitators of nurses' EHR training and technical support; and (3) outcomes: nurse-perceived impacts on safety, quality, nurse satisfaction, and efficiency. Alongside improvements to EHR functionality, findings underscore the need for organizationally informed training and careful alignment between the new EHR and the organization's nursing practices—all of which have been undertaken by Department of Veterans Affairs nurses informed by this and other studies.
How Do Early Weight Trajectories Explain Social Inequalities in Lung Function in Children With Cystic Fibrosis?: A Longitudinal Interventional Disparity Effects Analysis With Time-varying Mediators and Intermediate Confounders
Authors: Schlüter Daniela K. , Keogh Ruth H. , Daniel Rhian M. , Agbla Schadrac C. , Taylor-Robinson David
Published: January 2025

Background:

Children with cystic fibrosis (CF) from socioeconomically deprived areas have poorer growth, worse lung function, and shorter life expectancy than their less-deprived peers. While early growth is associated with lung function around age 6, it is unclear whether improving early growth in the most deprived children reduces inequalities in lung function.

Methods:

We used data from the UK CF Registry, tracking children born 2000–2010 up to 2016. We extended the interventional disparity effects approach to the setting of a longitudinally measured mediator. Applying this approach, we estimated the association between socioeconomic deprivation (children in the least vs. most deprived population quintile; exposure) and lung function at first measurement (ages 6–8, outcome), and the role of early weight trajectories (ages 0–6) as mediators of this relationship. We adjusted for baseline confounding by sex, birthyear, and genotype and time-varying intermediate confounding by lung infection.

Results:

The study included 853 children, with 165 children from the least and 172 from the most deprived quintiles. The average lung function difference between the least and most deprived quintiles was 4.5% of predicted forced expiratory volume in 1 second (95% confidence interval: 1.1-7.9). If the distribution of early weight trajectories in the most deprived children matched that in the least deprived children, this difference would reduce to 4% (95% confidence interval: 0.57- 7.4).

Conclusion:

Socioeconomic deprivation has a strong negative association with lung function for children with CF. We estimate that improving early weight trajectories in the most deprived children would only marginally reduce these inequalities.
Intraocular Inflammation (IOI) Associated with Faricimab Therapy: One-year Real World Outcomes.
Authors: Montesel Andrea , Sen Sagnik , Preston Ella , Patel Praveen J , Huemer Josef , Hamilton Robin D , Nicholson Luke , Papasavvas Ioannis , Tucker William R , Yeung Ian
Published: January 2025

Purpose.

To report one-year real-world evidence on intraocular inflammation (IOI) adverse events (AEs) in patients undergoing faricimab therapy in a tertiary care hospital.

Methods.

A retrospective review of electronic medical records was conducted for patients receiving faricimab treatment for neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) at Moorfields Eye Hospital between September 1st, 2022, and August 31st, 2023. The primary outcome was the incidence of IOI (excluding endophthalmitis).

Results.

2 318 eyes from 1 860 patients were included and underwent a total of 10 297 injections. A total of 20 eyes (16 patients) had ≥ 1 adverse event of IOI. Estimated incidence of IOI was 0.19% per injection (95%CI 0.12-0.30), 0.86% per eye (95% CI 0.53- 1.33] and 0.86% per patient (95%CI 0.49- 1.39). IOI mostly occurred within the first injections (median 3.5 injections, range 1-10). All cases presented with anterior uveitis and were associated with vitritis in 4 eyes (20%). No cases of posterior uveitis or evidence of retinal vascular occlusion were reported. There was no statistically significant difference between mean visual acuity before and after IOI event (0.40 logMAR and 0.378 logMAR respectively, p = .26).

Conclusion.

In this real-world report, faricimab was well tolerated with an incidence of IOI-related AEs consistent to that observed in registration trials. The AEs were generally mild and had a favourable prognosis.
"Choosing wisely": Intravitreal gas injection as first-line treatment for macular hole-a clinical case perspective.
Authors: González David Pérez , Loewenstein Anat
Published: January 2025

Purpose:

To evaluate the potency and security of Pneumatic Vitreolysis (PVL) as the primary treatment for Full-Thickness Macular Holes (FTMHs) and provide insights into patient selection criteria and procedural outcomes.

Patients and methods:

A retrospective analysis of three clinical cases presenting with FTMHs treated initially with PVL was conducted. Cases were evaluated for anatomical and functional outcomes through comprehensive ophthalmic examination and optical coherence tomography (OCT) imaging. Patient demographics, pre-operative characteristics, procedural details, and post-operative outcomes were documented.

Results:

PVL demonstrated favorable outcomes in two out of three cases, with complete closure of FTMHs and restoration of visual acuity. One case exhibited significant reduction but required subsequent pars plana vitrectomy (PPV) for closure. No intraoperative complications were noted. Factors such as active vitreomacular traction (VMT), head down position and smaller MH sizes appeared to positively correlate with successful closure following PVL. Thorough pre-procedural assessment of retinal periphery and OCT evaluation of MH characteristics aided in patient selection and treatment planning.

Conclusion:

PVL emerges as a promising initial treatment option for select FTMH cases, particularly those with active VMT and smaller MH sizes. Its less invasive nature and favorable outcomes make it a valuable alternative to traditional surgical interventions. Patient selection based on pre-operative characteristics, including VMT status and MH size, is crucial for optimizing treatment success. Further research and long-term studies are warranted to refine patient selection criteria, procedural techniques, and outcomes assessment in PVL for FTMHs.