bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal cognitive and behavioral interventions for patients with MCI: a systematic review and meta-analysis on cognition and mood
Authors: Ying Gelan , Perez-Lao Ambar , Marsiske Michael , Levy Shellie-Anne , Smith Glenn E. 
Published: April 2024

BackgroundResearch has increasingly suggested a benefit to combining multiple cognitive or behavioral strategies in a single treatment program for cognitively impaired older adults. Therefore, this systematic review and meta-analysis aimed to summarize results on the effects of multimodal cognitive and behavioral interventions versus control conditions on changes in cognition and mood in patients with mild cognitive impairment (pwMCI).MethodsThe review followed a general PRISMA guideline for systematic literature review with a format consisting of participants, interventions, comparators, and outcomes (PICO). Multilevel meta-analyses of aggregated efficacy were performed to assess the pooled effect sizes for cognitive and mood outcomes. Risk-of-bias, heterogeneity across studies, and publication bias were assessed for each outcome.ResultsAfter primary and reference searches, 18 studies with low or some concerns of risk of bias were included. Low heterogeneity was found for mood and cognition. Funnel plots did not indicate publication bias. All the studies assessed changes in cognition (n = 1,555) while seven studies with mood outcomes (n = 343) were included. Multilevel meta-analyses demonstrated moderate effect (Hedge’s g = 0.44, 95% CI = [0.21–0.67]) in cognitive outcomes and large effect in mood (g = 0.65, 95% CI = [0.37–0.93]). Subdomain analyses found low-moderate effects in global cognition, verbal and non-verbal memory, executive function, visuospatial abilities, and semantic fluency (0.20 &lt; g &lt; 0.50).ConclusionThese findings showed comparable to larger effects of multimodal cognitive and behavioral interventions on cognition than pharmacological treatment. Future studies should focus on the longitudinal effects of multimodal interventions in delaying dementia.Systematic review registration: PROSEPRO, CRD42022349297.
Research status and global trends of late-life depression from 2004 to 2023: bibliometric analysis
Authors: Du Ruonan , Yang Kebing , Li Wei , Wang Zhiren , Cai Haipeng 
Published: April 2024

BackgroundGlobal research hotspots and future research trends in the neurobiological mechanisms of late-life depression (LLD) as well as its diagnosis and treatment are not yet clear.ObjectivesThis study profiled the current state of global research on LLD and predicted future research trends in the field.MethodsLiterature with the subject term LLD was retrieved from the Web of Science Core Collection, and CiteSpace software was used to perform econometric and co-occurrence analyses. The results were visualized using CiteSpace, VOSviewer, and other software packages.ResultsIn total, 10,570 publications were included in the analysis. Publications on LLD have shown an increasing trend since 2004. The United States and the University of California had the highest number of publications, followed consecutively by China and England, making these countries and institutions the most influential in the field. Reynolds, Charles F. was the author with the most publications. The International Journal of Geriatric Psychiatry was the journal with the most articles and citations. According to the co-occurrence analysis and keyword/citation burst analysis, cognitive impairment, brain network dysfunction, vascular disease, and treatment of LLD were research hotspots.ConclusionLate-life depression has attracted increasing attention from researchers, with the number of publications increasing annually. However, many questions remain unaddressed in this field, such as the relationship between LLD and cognitive impairment and dementia, or the impact of vascular factors and brain network dysfunction on LLD. Additionally, the treatment of patients with LLD is currently a clinical challenge. The results of this study will help researchers find suitable research partners and journals, as well as predict future hotspots.
Carbenoxolone mitigates extensive fibrosis formation in PLP-induced EAE model and multiple sclerosis serum-exposed pericyte culture
Authors: Ucar Ege Anil , Ozkan Esra , Shomalizadeh Narges , Sekerdağ-Kilic Emine , Akpunar Fatmanur , Sapanci Selin , Kesibi Judy , Ozler Ceyda , Bilgez Alara Su , Gursoy-Ozdemir Yasemin 
Published: April 2024

IntroductionMultiple sclerosis (MS) is one of the most common causes of disability in young adults. Nearly, 85% of MS cases start with attacks and remissions, classified as relapsing-remitting multiple sclerosis (RRMS). With repeating attacks, MS causes brain-spinal cord atrophy and enhanced disability as disease progresses. PLP-induced EAE is one of the most established models for pathophysiology and treatment of RRMS. Recent studies demonstrated the possible role of pericytes in perivascular and intra-lesional fibrosis in PLP-induced EAE, whose importance remains elusive. Hence, we have investigated the possible role of pericytes in fibrosis formation and amelioration with a hemichannel blocker, Carbenoxolone (CBX).MethodsPLP-induced experimental autoimmune encephalitis (EAE) model is used and the effect of CBX is investigated. Clinical scores were recorded and followed. Perivascular Collagen 1 and 3 accumulations were demonstrated as markers of fibrosis in the spinal cord. To delineate the role of pericytes, human brain vascular pericytes (HBVP) were incubated with the sera of MS patients to induce in-vitro MS model and the fibrosis formation was investigated.ResultsIn the PLP induced in-vivo model, both intracerebroventricular and intraperitoneal CBX have significantly mitigated the disease progression followed by clinical scores, demyelination, and fibrosis. Moreover, CBX significantly mitigated MS-serum-induced fibrosis in the HBVP cell culture.DiscussionThe study demonstrated two important findings. First, CBX decreases fibrosis formation in both in-vivo and in-vitro MS models. Secondly, it improves neurological scores and decreases demyelination in the EAE model. Therefore, CBX can be potential novel therapeutic option in treating Multiple Sclerosis.
Return to work after aneurysmal subarachnoid hemorrhage
Authors: Sorteberg Angelika , Lashkarivand Aslan , Western Elin 
Published: April 2024

IntroductionSurvivors of aneurysmal subarachnoid hemorrhage (aSAH) often recover without severe physical or cognitive deficits. However, strikingly low levels of engagement in productive employment have also been reported in aSAH patients with good or excellent outcomes. Knowledge about return to work (RTW) after aSAH and predictors of no RTW remain limited and controversial. The study aimed to delineate the return to maximum work capacity up to 5 years after the ictus in a larger number of consecutive aSAH patients from the entire aSAH severity spectrum and to identify demographic and medical predictors of no RTW.MethodsData were acquired from a prospective institutional database. We included all 500 aSAH survivors aged &gt; 18 years who were treated between January 2012 and March 2018. In addition to gathering data on work status and the type of work at ictus, we retrieved demographical data and assessed aSAH severity based on the quantification of subarachnoid, intraventricular, and intraparenchymal blood (ICH), as well as the World Federation of Neurological Societies (WFNS) grade. We registered the mode of aneurysm repair (endovascular or surgical) and recorded complications such as vasospasm, newly acquired cerebral infarctions, and chronic hydrocephalus.ResultsFurthermore, work status and the grade of fatigue at follow-up were registered. RTW was assessed among 299 patients who were employed at ictus. Among them, 63.2% were women, and their age was 51.3 ± 9.4 (20–71) years. Return to gainful employment was 51.2%, with complete RTW accounting for 32.4%. The independent predictors of no RTW at ictus were age, the WFNS grade 3, and active smoking. The strongest independent predictor was the presence of clinically significant fatigue, which increased the risk of not returning to work by 5-fold. The chance to return to gainful employment significantly increased with the individual's years of education prior to their hemorrhage. The mode of aneurysm repair was not relevant with regard to RTW. Patients in the WFNS grades 1–2 more often returned to work than those in the WFNS grades 3–5, but our results indicate that neurological motor deficits are linked closer to no RTW than aSAH severity per se.ConclusionFatigue needs to be addressed as an important element on the path to return to work integration.
Assessment of nutritional status and health behaviors in yoga-trained women versus exercisers
Authors: Gogojewicz Anna , Pilaczyńska-Szcześniak Łucja , Popierz-Rydlewska Natalia , León-Guereño Patxi , Malchrowicz-Mośko Ewa 
Published: April 2024

IntroductionRecreational physical activity is becoming more popular due to the increased public awareness about the beneficial effects on health status and quality of life. The aim of the study was to assess the nutritional status and health behaviors of women who regularly practice yoga as a form of physical recreation and to compare them with those who had not practiced before and had just signed up for yoga classes. A total of 143 women took part in this study.MethodsThe nutritional status was assessed based on the obtained anthropometric measurements. The following indicators were calculated: Body Mass Index (BMI) and waist-to-hip ratio (WHR), determining the visceral accumulation of fat tissue. Health behaviors were assessed using a standardized five-point scale Health Behavior Inventory (HBI).ResultsThere were significant differences in the value of the general health behavior index, the sten scale, and the subscale regarding proper eating habits in the study groups compared to women who had not practiced yoga before (control group). Health behaviors indicators, particularly proper eating habits, are significantly higher in women participating regularly in yoga exercises, indicating a higher awareness among yoga practitioners.ConclusionIt can be suggested that yoga participation as a recreational physical activity can be an appropriate option for pursuing healthy habits.
Sociodemographic characteristics help predict Canadian urbanites’ acceptability of restaurant food environment policies
Authors: Lambert-De Francesch Jessica , Saint-Onge Kadia , Muhajarine Nazeem , Gauvin Lise 
Published: April 2024

IntroductionPublic acceptability of policies aiming to improve the healthfulness of the restaurant food environment is key to their successful implementation. Yet, the acceptability of these policies remains ambiguous, especially across diverse population groups. This study aims to examine associations between sociodemographic characteristics and acceptability levels of three restaurant food environment policies of varying degrees of intrusiveness across 17 urban Canadian jurisdictions.MethodsData was extracted from the THEPA survey, one of the largest and most jurisdictionally comprehensive surveys on intervention acceptability (N = 27,162). To account for potential jurisdictional differences in acceptability, for each policy, multilevel logistic regression models were developed.ResultsResults indicated that, on average, those in complete agreement with the implementation of the targeted policies represented 20.3%–26.9% of participants, depending on the policy. Acceptability varied according to policy intrusiveness, jurisdiction, and participants’ sociodemographic characteristics. Women, individuals with household incomes of &lt;$40,000/year, immigrants from a high-income country other than Canada, and Indigenous peoples were more likely to express complete agreement with all policies, versus men, participants with household incomes of $40,000–$79,999/year, Canadian-born individuals, and non-Indigenous individuals. A lower likelihood of expressing complete agreement with all policies was observed for those with a $80,000–$119,999/year household income, versus those with a $40,000–$79,999/year household income. For selected policies and models, other sociodemographic characteristics (i.e., age, education, and being born in a low-or middle-income country) predicted acceptability. The examined sociodemographic characteristics did not explain jurisdictional differences in acceptability.DiscussionUnderstanding jurisdictional differences in acceptability merits further research. Policy implications involve engaging diverse sociodemographic groups in conversations about acceptable ways in which their restaurant food environment could be rendered more healthful.
A Mendelian randomization study to examine the causal associations of circulating micronutrient levels with frailty risk
Authors: Kuribanjiang Kaidiriyan , Min Yiping , Yan Shikang , Chen Simin , Aiheti Nuerbiyamu , Wupuer Abudunaibi , Wang Jie , Peng Xing , Li Yihan , Li Huilong , Dong Yiran , Fan Yuanlin , Yang Lei , Zhao Jianping 
Published: April 2024

BackgroundObservational studies have shown that micronutrients can affect the occurrence of frailty. However, it is not clear whether there is a causal relationship between the two. This study aimed to explore the causal relationship between circulating micronutrient levels and frailty risk using a two-sample Mendelian randomization (TSMR) approach.MethodsWe gathered and screened instrumental variables (IVs) for six circulating micronutrients, including vitamin B12, vitamin B6, folate, vitamin C, vitamin D, and vitamin E, from published genome-wide association studies (GWAS) and the IEU OpenGWAS open database. Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We performed two independent TSMR analyses and a meta-analysis based on the two independent MR estimates to assess the causal relationship between circulating micronutrientn and frailty.ResultsOur study found, no causal relationship between genetically predicted vitamin D (β = −0.059, p = 0.35), vitamin B6 (β = 0.006, p = 0.80), vitamin E (β = −0.011, p = 0.79), vitamin C (β = −0.044, p = 0.06), vitamin B12 (β = −0.027, p = 0.37), and folate (β = 0.029, p = 0.17), with frailty.ConclusionThis study showed that these six micronutrients did not reduce the risk of developing frailty. However, we think it is necessary further to investigate the relationship and mechanisms between micronutrients and frailty using methods such as randomized controlled trials.
MAMILNet: advancing precision oncology with multi-scale attentional multi-instance learning for whole slide image analysis
Authors: Wang Qinqing , Bi Qiu , Qu Linhao , Deng Yuchen , Wang Xianhong , Zheng Yijun , Li Chenrong , Meng Qingyin , Miao Kun 
Published: April 2024

BackgroundWhole Slide Image (WSI) analysis, driven by deep learning algorithms, has the potential to revolutionize tumor detection, classification, and treatment response prediction. However, challenges persist, such as limited model generalizability across various cancer types, the labor-intensive nature of patch-level annotation, and the necessity of integrating multi-magnification information to attain a comprehensive understanding of pathological patterns.MethodsIn response to these challenges, we introduce MAMILNet, an innovative multi-scale attentional multi-instance learning framework for WSI analysis. The incorporation of attention mechanisms into MAMILNet contributes to its exceptional generalizability across diverse cancer types and prediction tasks. This model considers whole slides as “bags” and individual patches as “instances.” By adopting this approach, MAMILNet effectively eliminates the requirement for intricate patch-level labeling, significantly reducing the manual workload for pathologists. To enhance prediction accuracy, the model employs a multi-scale “consultation” strategy, facilitating the aggregation of test outcomes from various magnifications.ResultsOur assessment of MAMILNet encompasses 1171 cases encompassing a wide range of cancer types, showcasing its effectiveness in predicting complex tasks. Remarkably, MAMILNet achieved impressive results in distinct domains: for breast cancer tumor detection, the Area Under the Curve (AUC) was 0.8872, with an Accuracy of 0.8760. In the realm of lung cancer typing diagnosis, it achieved an AUC of 0.9551 and an Accuracy of 0.9095. Furthermore, in predicting drug therapy responses for ovarian cancer, MAMILNet achieved an AUC of 0.7358 and an Accuracy of 0.7341.ConclusionThe outcomes of this study underscore the potential of MAMILNet in driving the advancement of precision medicine and individualized treatment planning within the field of oncology. By effectively addressing challenges related to model generalization, annotation workload, and multi-magnification integration, MAMILNet shows promise in enhancing healthcare outcomes for cancer patients. The framework’s success in accurately detecting breast tumors, diagnosing lung cancer types, and predicting ovarian cancer therapy responses highlights its significant contribution to the field and paves the way for improved patient care.
A hybrid deep learning scheme for MRI-based preliminary multiclassification diagnosis of primary brain tumors
Authors: Wang Zhichao , He Chuchu , Hu Yan , Luo Haifeng , Li Chao , Wu Xiandong , Zhang Yang , Li Jingjing , Cai Jun 
Published: April 2024

ObjectivesThe diagnosis and treatment of brain tumors have greatly benefited from extensive research in traditional radiomics, leading to improved efficiency for clinicians. With the rapid development of cutting-edge technologies, especially deep learning, further improvements in accuracy and automation are expected. In this study, we explored a hybrid deep learning scheme that integrates several advanced techniques to achieve reliable diagnosis of primary brain tumors with enhanced classification performance and interpretability.MethodsThis study retrospectively included 230 patients with primary brain tumors, including 97 meningiomas, 66 gliomas and 67 pituitary tumors, from the First Affiliated Hospital of Yangtze University. The effectiveness of the proposed scheme was validated by the included data and a commonly used data. Based on super-resolution reconstruction and dynamic learning rate annealing strategies, we compared the classification results of several deep learning models. The multi-classification performance was further improved by combining feature transfer and machine learning. Classification performance metrics included accuracy (ACC), area under the curve (AUC), sensitivity (SEN), and specificity (SPE).ResultsIn the deep learning tests conducted on two datasets, the DenseNet121 model achieved the highest classification performance, with five-test accuracies of 0.989 ± 0.006 and 0.967 ± 0.013, and AUCs of 0.999 ± 0.001 and 0.994 ± 0.005, respectively. In the hybrid deep learning tests, LightGBM, a promising classifier, achieved accuracies of 0.989 and 0.984, which were improved from the original deep learning scheme of 0.987 and 0.965. Sensitivities for both datasets were 0.985, specificities were 0.988 and 0.984, respectively, and relatively desirable receiver operating characteristic (ROC) curves were obtained. In addition, model visualization studies further verified the reliability and interpretability of the results.ConclusionsThese results illustrated that deep learning models combining several advanced technologies can reliably improve the performance, automation, and interpretability of primary brain tumor diagnosis, which is crucial for further brain tumor diagnostic research and individualized treatment.
MK591 (Quiflapon), a 5-lipoxygenase inhibitor, kills pancreatic cancer cells via downregulation of protein kinase C-epsilon
Authors: Monga Jitender , Ghosh Ritisha , Guddeti Rohith , Chitale Dhananjay , Khan Gazala , Ghosh Jagadananda 
Published: April 2024

IntroductionPancreatic tumors and cell lines derived from them exhibit elevated expression of 5-lipoxygenase (5-Lox), whereas non-tumor glands or normal cells do not exhibit this overexpression. Arachidonic acid stimulates pancreatic cancer cell growth via metabolic conversion through the 5-Lox pathway, and inhibition of 5-Lox activity decreases the viability of pancreatic cancer cells. However, the downstream signaling mechanisms through which 5-Lox exerts its effects on the survival of pancreatic cancer cells remain to be elucidated.MethodsThe effects of 5-Lox inhibition on cell proliferation, apoptosis, and invasive potential were investigated in pancreatic cancer cells. The protein expression was analyzed by Western blot. Apoptosis was analyzed by Annexin-V binding assay and by detecting the degradation of chromatin-DNA to nucleosomal fragments. The protein kinase C-epsilon (PKCε) activity was measured by an immunoprecipitation-kinase assay. The in vivo effects of MK591 were evaluated in pancreatic tumor xenograft model.ResultsMK591, a specific inhibitor of 5-Lox activity, killed pancreatic cancer cells via induction of apoptosis, involving externalization of phosphatidylserine, cleavage of PARP (poly-ADP ribose polymerase) and degradation of chromatin DNA to nucleosomes. MK591 effectively blocked in vitro invasion and soft-agar colony formation by pancreatic cancer cells and decreased pancreatic tumor growth in nude mice xenografts. Furthermore, inhibition of 5-Lox downregulated K-Ras and inhibited phosphorylation of c-Raf and ERKs. Interestingly, 5-Lox inhibition induced apoptosis in pancreatic cancer cells without the inhibition of Akt but the protein level of PKCε was dramatically downregulated. Furthermore, inhibition of 5-Lox decreased the phosphorylation of Stat3 at Serine-727. Pre-treatment of pancreatic cancer cells with peptide activators of PKCε prevented apoptosis induced by 5-Lox inhibition, suggesting that the mechanism by which 5-Lox inhibition causes cell death in pancreatic cancer involves downregulation of PKCε. The combination of low doses of MK591 and gemcitabine synergistically reduced the oncogenic phenotype and killed pancreatic cancer cells by inducing apoptosis.DiscussionThese findings indicate that inhibition of 5-Lox interrupts an Akt-independent, PKCε-dependent survival mechanism in pancreatic cancer cells and suggest that metabolism of arachidonic acid through the 5-Lox pathway plays an integral part in the survival of pancreatic cancer cells via signaling through PKCε, an oncogenic, pro-survival serine/threonine kinase.