bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations between cerebral blood flow and progression of white matter hyperintensities
Authors: Thammasart Siriluk , Harvey Danielle J. , Maillard Pauline , DeCarli Charles , Donnay Corinne A. , Wheeler Gregory J. , Fan Audrey P. 
Published: January 2025

IntroductionIn an aging population, white matter hyperintensities (WMHs), observed on FLAIR MRI sequences, are indicators of cognitive decline, motor impairment, and increased vascular risk. However, the pathophysiological mechanisms underlying WMHs, including dynamic changes in cerebral blood flow (CBF) within and adjacent to lesions, remain poorly understood.MethodsOur study examined a diverse cohort of 300 elderly participants through arterial spin labeling (ASL) on 3 Tesla MRI, analyzing both cross-sectional and longitudinal data. We characterized the relationship between CBF and WMH development in different lesion locations (based on distance from ventricles) and brain tissue types (WMH lesion, penumbra, and normal white matter).ResultsOur findings reveal that WMHs exhibit significantly lower relative CBF (rCBF) compared to penumbra, normal-appearing white matter, and gray matter, with juxtaventricular WMHs (JVWMH) displaying the most substantial reductions. Longitudinally, WMHs that increased in size over a two-year period had lower baseline rCBF than those that remained stagnant, particularly in juxtaventricular and periventricular regions.DiscussionThis study not only highlights the predictive value of rCBF in WMH progression but also provides location-specific hemodynamic information about WMHs that can guide clinical management of WMH-related brain changes and their clinical manifestations.
Lateralized differences in power spectra across different frequency bands during NREM sleep in patients with primary insomnia
Authors: Huang Jiao , Ye Jing , Gao Mingjie , Gao Wentao , Chen Weijia , Zhu Yifeng , Wang Yongbo , Huang Daijin , Lv Yunhui , Shi Hong 
Published: January 2025

ObjectiveTo compare the electroencephalogram power spectrum of patients with primary insomnia and good sleep controls in multiple brain areas and different frequency bands during non-rapid eye movement sleep.Methods48 primary insomnias and 30 age-and gender-matched good sleep controls were recorded overnight with polysomnography. Power spectral analysis was performed in six brain areas (F3, F4, C3, C4, O1 and O2) and across seven frequency bands (delta, sigma, alpha, theta, beta1, beta2, and gamma) during non-rapid eye movement sleep between primary insomnias and good sleep controls.ResultsIn primary insomnias, there were significant differences in frequency bands and areas. Compared to good sleep controls, delta power was lower in primary insomnias, while beta1, beta2, and gamma were higher. Beta2 power was substantially higher in all areas, sigma power was significantly higher on the right side, and gamma power was considerably higher on the left side in primary insomnias. The Beta1 power was positively correlated the number of awakenings (r = 0.3291, p = 0.02) in primary insomnias on the right side.ConclusionThis study marked the first specialized comparison of power spectral analysis during non-rapid eye movement sleep in different areas and across different frequency bands. The result suggested that primary insomnias had reduced deep sleep (lower delta power) and hyperarousal state (higher beta 2 power). Primary insomnia was associated with significant fragmented sleep, and an increase in beta1 power was related to the number of awakenings.SignificanceThese findings revealed the hemispheric lateralization characteristics of power spectral disturbances during non-rapid eye movement sleep in primary insomnias and provided valuable insights for selecting electrode placements in future power spectral analyses of primary insomnias.
Associations of dietary inflammation index and composite dietary antioxidant index with all-cause mortality in COPD patients
Authors: Zhao Sue , Su Yingjie , Yang Hongzhong 
Published: January 2025

BackgroundFew studies have investigated the effects of both dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI) on mortality in patients with Chronic Obstructive Pulmonary Disease (COPD). Our research aimed to explore the associations between the two indicators with all-cause mortality in COPD patients.MethodsWe conducted a prospective cohort analysis based on data from the six cycles of the National Health and Nutrition Examination Survey (NHANES) dataset from 2007 to 2018. Multivariate Cox proportional hazard models were used to analyze the effects of DII and CDAI on all-cause mortality in COPD. We employed restricted cubic spline (RCS) analysis to examine the dose–response relationship between two indicators and all-cause mortality, used threshold effect analysis to determine the inflection point, and conducted subgroup analysis and interaction tests to verify the stability of the results.ResultsA total of 1,457 COPD patients aged over 40 were enrolled in the study. The median follow-up time was 76.8 months. The multivariate Cox proportional hazards model showed that increased DII was associated with an increase in all-cause mortality (HR (95% CI): 1.11(1.04, 1.18), p = 0.002). In contrast, CDAI was negatively correlated with all-cause mortality (HR (95% CI): 0.95(0.91, 0.99), p = 0.01). The RCS analysis showed a nonlinear correlation between DII or CDAI and all-cause mortality. The maximum pro-inflammatory inflection point of DII was 2.32, while the antioxidant threshold of CDAI is −0.12. Subgroup analyses indicated that the relationship between exposure variables and all-cause mortality was stable in most populations.ConclusionReducing the pro-inflammatory diet or increasing the antioxidant diet can reduce all-cause mortality in COPD patients.
MiR-216a-3p inhibits the cytotoxicity of primary natural killer cells
Authors: Abdelbary Rowan , Ragheb Manon , El Sobky Shereen A. , El-Badri Nagwa , Aboud Nourhan , Tawheed Ahmed , Gomaa Asmaa , Zidan Mona , Aziz Ramy K. , Abouzid Abd Elrahman , Salah Radwa Ayman , El-Kassas Mohamed , Waked Imam , Moustafa Ahmed , Fawzy Injie Omar , El-Ekiaby Nada , Abdelaziz Ahmed Ihab 
Published: January 2025

IntroductionThe role of miRNAs in regulating variable molecular functions has been sought by scientists for its promising utility in regulating the immune response and, hence, in treating various diseases. In hepatocellular carcinoma (HCC) specifically, a reduction in the number and efficiency of circulating and intrahepatic natural killer (NK) cells has been reported. Our project aims to investigate the role of miR-216a-3p in the regulation of NK cell cytotoxicity, especially since it plays a tumor suppressor role in the context of HCC.MethodsTo achieve our aim, we isolated NK cells from the whole blood of 86 patients with HCC and 23 healthy controls. We assessed the expression profile of miR-216a-3p in NK cells of patients and controls. Furthermore, we induced the expression of miR-216a-3p in NK cells isolated from healthy controls, followed by measuring the release of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), perforins (PRF) and granzyme B (GrB) using ELISA as well as NK cells cytolytic activity against Huh7 cells using lactate dehydrogenase (LDH) cytotoxicity assay. After that, we performed an in silico analysis to understand the mechanistic regulation imposed by miR-216a-3p on NK cells to study its impact on one of its potential downstream targets.ResultsOur results have indicated that miR-216a-3p has higher expression in NK cells of patients with HCC, and simulating this elevated expression pattern via forcing miR-216a-3p expression in normal NK cells has negatively impacted the release of TNF- α, IFN- γ, GrB, and PRF. Consequently, a decrease in cell cytolysis was observed. Our in silico analysis revealed that the predicted downstream targets of miR-216a-3p are enriched in the FOXO-signaling pathway. Among those targets is FOXO-1, which has been reported to play a role in NK cell maturation. Thus, we evaluated FOXO-1 expression upon mimicking miR-216a-3p in control NK cells that showed significant downregulation of FOXO-1 on both RNA and protein levels.ConclusionIn conclusion, we report miR-216-3p as a negative regulator of NK cell cytotoxicity.
Management of CAR-T cell therapy in patients with multiple myeloma: a systematic review and expert consensus in Australia
Authors: Ho P. Joy , Quach Hang , Sidiqi M. Hasib , Lee Cindy H. , Butler Jason , Spencer Andrew , Micklethwaite Kenneth , Li Jingya , Cusson Elissa , Bagnall Robert , Harrison Simon J. 
Published: January 2025

BackgroundRegulatory bodies have recently approved chimeric antigen receptor (CAR)-T cell therapies for patients with multiple myeloma (MM), but the treatment process involves complex decision making. To support the introduction of these therapies, we aimed to establish consensus expert opinion on best practices of all aspects of the management of patients with MM undergoing CAR-T cell therapy in Australia.MethodsWe conducted a modified RAND/UCLA two-round Delphi panel informed by a systematic literature review (SLR). The SLR included evidence from clinical practice guidelines, interventional trials, and observational studies for CAR-T cell therapy for patients with MM, to synthesize methodological aspects of CAR-T cell therapy related to patient management. The Delphi panel comprised eight hematologists from across Australia, each with significant experience directly treating patients using CAR-T therapy or referring patients for CAR-T cell therapy. Panelists completed the surveys electronically, and attended a virtual meeting held before the second-round questionnaire to discuss the first-round questionnaire responses. Consensus was defined a priori as at least 70% agreement on survey questions.ResultsThe SLR identified 22 interventional or observational studies and 5 clinical practice guidelines reporting on selection and management of patients with MM treated with CAR-T cell therapy from various global regions. The Delphi panel reached consensus on practices related to patient referral, screening, selection, prioritization, treatments requiring wash-out, bridging therapy, lymphodepletion, infusion, and post-infusion monitoring and management. Most consensus results aligned with consistently recommended practices within guidelines included in the SLR. Consensus was not reached for statements related to specific screening practices and post-treatment monitoring, suggesting differing opinions on the specific best practices to implement.ConclusionOur Delphi panel established expert consensus on key considerations for patient selection, administrative processes, and aftercare for patients with MM in Australia undergoing CAR-T therapy. This will guide the development of clinical practice guidelines which are relevant and feasible to Australian health systems.
Case Report: Major right-sided hepatectomies in infants in Uzbekistan: a case series
Authors: Semash K. , Dzhanbekov T. , Islomov S. 
Published: January 2025

IntroductionLiver resection is a critical surgical option for managing benign and malignant tumors, including rare and complex cases in pediatric patients. While such procedures are well-documented in adults, the surgical management of large liver neoplasms in infants poses unique challenges due to anatomical and physiological considerations, as well as the limited number of cases reported globally.AimThis study aimed to describe the initial experiences with major hepatectomies in infants with large liver neoplasms at our center.Materials and methodsFrom December 2023 to May 2024, four major hepatectomies were performed in pediatric patients aged 5 to 11 months. Indications, perioperative data, and surgical outcomes were retrospectively analyzed.ResultsThe outcomes of the four patients in this case series demonstrate the feasibility and safety of major hepatectomies in infants with large liver neoplasms. Among the cases, three involved hepatoblastoma (PRETEXT stages 2–4), and one was an anastomosing hemangioma. Radical resection (R0) was achieved in all cases, with average intraoperative blood loss 120 ml, and only one patient requiring a blood transfusion. Postoperative complications were minimal, with two cases of mild to moderate post-hepatectomy liver insufficiency (Clavien-Dindo grades 1–2) and one bile leak (Clavien-Dindo grade 2) that resolved spontaneously. No perioperative mortality or tumor recurrence was observed during a six-month follow-up.ConclusionThese results highlight the success of careful surgical planning, advanced techniques, and comprehensive perioperative management in achieving favorable outcomes for this high-risk patient population.
Anti-HSV-1 agents: an update
Authors: Lv Wenwen , Zhou Lei , Wu Jia , Cheng Jishuai , Duan Yongzhong , Qian Wen 
Published: January 2025

Herpes simplex virus type I (HSV-1) is a member of the α-herpesvirus subfamily and is capable of causing herpes simplex keratitis, herpes labialis, and herpes simplex encephalitis. HSV-1 is well known for its lytic infections at the primary sites and for establishing latency in the sensory neuronal ganglia, with occasional recurrent infections. To date, there are no approved commercially available vaccines, and anti-HSV-1 drugs such as specific or non-specific nucleotide (nucleoside) analogs and helicase-primase inhibitors have become the main clinical agents for the treatment of HSV-1 infections despite challenges from resistance. Therefore, development of new anti-HSV-1 compounds or therapies is key to addressing the issue of resistance. The present review provides an update on the progress made over approximately 60 years regarding anti-HSV-1 agents while also highlighting future perspectives for controlling HSV-1 infections.
On being and having: a qualitative study of self-perceptions in bipolar disorder
Authors: Ponticiello Matthew N. , Chang Alexis L. , Chang Rebecca J. , Mirza Salahudeen , Martin Andrés 
Published: January 2025

BackgroundBipolar disorder (BD) is a chronic and often severe mental illness. Yet despite the well-documented complexities in its diagnosis and treatment, little research has been dedicated to understanding the complex inner landscape experienced by those living with BD. Even as qualitative research has explored the lived experience of BD across a variety of perspectives, i.e., what BD looks like, there is a lack of research exploring what BD means to those living with the condition. We conducted individual, semi-structured interviews with 20 adults with clinically stable BD to explore their perceptions of the condition, their construction of meaning of their illness, and their view of BD in relation to their sense of self. We coded the transcripts according to the principles of thematic analysis and analyzed the data using an interpretative phenomenological analysis approach.ResultsWe identified three overarching domains: (1) Benefit or burden: a dialectic through which participants weighed the valence of their illness over time; (2) Self or other: the internal or external locus through which they experienced BD; and (3) From ineffability to meaning making: the process of naming, understanding, and incorporating BD into their life’s whole. Within each domain, themes and subthemes outline nuanced and often conflicting perspectives of participants’ illness experiences.ConclusionsAcross the varied and nuanced perspectives uncovered, our work provides a framework of three domains central to the inner reality of lived bipolar experience. Thoughtful understanding of patients’ experiences, perspectives, and desires within these three domains may aid clinicians and loved ones alike in more sensitively and effectively addressing the unique individual needs of those living with BD. It may also be informative for individuals living with BD themselves. By exploring patients’ perspectives in each of the three domains we identified, those with or at risk for BD as well as those caring for people with BD may be better positioned to help identify the inner work and practical interventions (such as finding bipolar community, or pathways to occupational thriving) needed to achieve a rich, meaningful life with BD.
The youth mental health crisis: analysis and solutions
Authors: McGorry Patrick , Gunasiri Hasini , Mei Cristina , Rice Simon , Gao Caroline X. 
Published: January 2025

BackgroundSince the mid-20th century, mental illness has become a leading cause of health burden, particularly among adolescents and emerging adults, with most disorders emerging before the age of 25. Over the past two decades, mental ill health has surged to alarming levels, with evidence confirming that the increase is not just due to better awareness or diagnosis but reflects a genuine public health crisis.Study design/methodWe explore the evolving landscape of youth mental health and its contributing factors, including family dynamics, educational pressures, climate change, social media, and socio-economic challenges, potentially linked to neoliberal policies. A narrative review methodology was employed to analyze these factors and their role in the trends of mental ill-health among young people.Study resultsWe document mental health trends since the mid-1990s, focusing on mental and substance use disorders among young people and their current needs. Potential new explanatory factors and megatrends, potentially flowing from a paradigm shift in the global political economy which has largely passed under the radar, yet which has produced fragmentation and inequality, are identified, with the COVID-19 pandemic further intensifying these trends. We discuss methodologies to estimate the contribution of these megatrends and outline potential barriers to implementation, along with strategies to overcome them.ConclusionThis review calls for a comprehensive global action plan, emphasizing prevention, early intervention, and improved treatment strategies. In addition to strengthening prevention, which may take time and be elusive, immediate action is needed to innovate and expand services, which are currently under-resourced and overwhelmed.
Work-related burnout and its associated factors among kindergarten teachers: a multi-center cross-sectional study in Ethiopia
Authors: Bezie Anmut Endalkachew , Zewude Girum Tareke , Tesfaye Amensisa Hailu , Yirdaw Asmare Asrat , Abie Alebachew Bitew , Abere Giziew 
Published: January 2025

IntroductionWork-related burnout is a state of severe physical and mental fatigue and exhaustion resulting from unmanaged prolonged work stress. Kindergarten teachers are at higher risk of work-related burnout compared to other teaching professionals, due to their dual roles as both caregivers and educators for young children. The demands and stresses of these combined responsibilities, coupled with factors such as low salaries, contribute to an increased risk of burnout in this population. Therefore, this study aimed to investigate work-related burnout prevalence and associated factors among kindergarten teachers in Dessie City, Northeast Ethiopia.MethodsAn institution-based, cross-sectional study was conducted in March and April of 2024. A sample of 422 kindergarten teachers was recruited using simple random sampling techniques. A standardized, self-administered Copenhagen Burnout Inventory was utilized to measure work-related burnout. We used EpiData V4.6 and SPSS V26 for data entry and analysis, respectively. A bivariable logistic regression analysis (p-value &lt; 0.2) was performed to find factors associated with work-related burnout. Variables found significant in the bivariable analysis were then exported into a multivariable logistic regression model to identify statistically significant variables at a p value &lt; 0.05 and a 95% confidence interval.ResultsThe response rate was 95% (401/422). 97.5% of the participants were female, and the participants’ mean (standard deviation) age was 28.5 years (SD ± 5.8). In the past 6 months, the total prevalence of WRB was 39.7% [95% CI (34.8, 44.6)]. Work–family conflicts [AOR: 2.81; 95% CI (1.77, 4.45)], working conditions [AOR: 1.63; 95% CI (1.03, 2.56)], perceived stress [AOR: 1.91; 95% CI (1.21, 3.01)], job dissatisfaction [AOR: 1.75, 95% CI (1.10, 2.79)], and kindergarten type [AOR: 1.66; 95% CI (1.02, 2.68)] were factors significantly associated with WRB.ConclusionAccording to this study, a significant number of kindergarten teachers were affected by burnout due to their working nature. To address this issue, interventions focused at reducing work–family conflicts, increasing job satisfaction, and improving the school environment are necessary to support teachers’ well-being, benefiting both young students and the broader educational landscape.
Aging and urban innovation: a human capital perspective
Authors: Cui Jinghang , Zhou Rong , Crandall K. Jason , Cui Mingxuan , Bai Ruirui , Jia Yi 
Published: January 2025

BackgroundWith population aging, this demographic dividend diminishes, which may have implications for innovation in a region. Understanding the relationship between population aging and innovation is crucial for addressing economic challenges associated with an aging population.MethodsThis study utilized panel data on population aging and innovation from 252 cities between 2005 and 2014. Various estimation methods, including the fixed effects model, the generalized method of moments (GMM), and the mediation model, were used to analyze the data. These methods allowed for a comprehensive examination of the impact of population aging on innovation and the role of human capital in mediating this relationship.ResultsThe findings of the study indicate that both the 60-year-old and 65-year-old population significantly hinder innovation. The GMM suggests that innovation is “path dependent,” meaning that past levels of innovation do not alleviate the negative effects of population aging on future innovation. Additionally, the mediation model analysis demonstrates that human capital plays a crucial role in mediating the relationship between population aging and innovation, highlighting the importance of investing in human capital development.ConclusionThe findings of this research highlight the obstacles that population aging presents to fostering innovation. Overcoming these obstacles necessitates strategic investments in human capital and policies that support innovation. It is imperative for policymakers to implement recommendations that address population aging and encourage innovation in order to navigate the challenges posed by an aging population and promote a vibrant and dynamic economy.