bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardio and cerebrovascular diseases risk among Alzheimer's disease patients and racial/ethnic disparities, based on Hawaii Medicare data
Authors: Siriwardhana Chathura , Carrazana Enrique , Liow Kore , Chen John J
Published: November 2024

Background

Alzheimer's disease (AD) and cardiovascular and cerebrovascular diseases (CVD) are significant concerns among the elderly, sharing overlapping risk factors. Hawaii's unique demographic profile, characterized by its strong ethnic diversity, shows marked racial health disparities. For instance, the Native Hawaiian/Pacific Islander (NHPI) population is identified as a high-risk group for multiple health conditions, including CVD.

Objective

This study investigates the impact of AD on the risk of developing CVD, with a focus on racial influences, utilizing Hawaii Medicare data.

Methods

Employing nine years of longitudinal Hawaii Medicare data, this study identified elderly patients diagnosed with AD who subsequently developed heart failure (HF), ischemic heart disease (IHD), atrial fibrillation (AF), acute myocardial infarction (AMI), or stroke. To assess the risk of CVD, we utilized multistate models and employed propensity score-matched controls. Additionally, we evaluated racial and ethnic differences in the risk of these diseases, while accounting for other relevant risk factors.

Results

Our findings revealed an elevated risk of AMI, HF, and IHD among individuals diagnosed with AD. Additionally, socioeconomic status (SE) was identified as a crucial factor in the risk of cardio and cerebrovascular diseases. Within the low SE group, NHPIs exhibited increased risks of HF and IHD compared to their white counterparts. Interestingly, NHPIs demonstrated reduced risks of HF in the higher SE group.

Conclusions

The presence of AD increases the likelihood of developing AMI, HF, and IHD. Moreover, the risk of CVD appears to be influenced by race/ethnicity in Hawaii, as well as socioeconomic status.
Identifying shared diagnostic genes and mechanisms in vascular dementia and Alzheimer's disease via bioinformatics and machine learning
Authors: Zheng Wanning , Lin Dongdong , Shi Shunan , Ren Jiayi , Wu Jiong , Wang Ming , Wan Shu
Published: November 2024

Background

Alzheimer's disease (AD) and vascular dementia (VaD) share overlapping pathophysiological characteristics, yet comparative genetic studies are rare. Understanding these overlaps may aid in identifying common diagnostic markers and therapeutic targets.

Objective

This study identifies shared diagnostic genes and mechanisms linking AD and VaD.

Methods

Datasets GSE5281 and GSE122063 from the GEO database were used to identify differentially expressed genes (DEGs). Intersection DEGs were analyzed using KEGG and GO enrichment to explore signaling pathways. A PPI network was constructed, and LASSO and SVM-RFE were applied to identify core genes. CIBERSORT assessed immune cell composition and their relationship with core genes. Diagnostic efficacy was evaluated using ROC curves, nomogram, and Decision Curve Analysis (DCA). Core genes were used to identify characteristic genes in various brain regions of AD patients.

Results

The analysis identified 9021 DEGs for AD and 373 DEGs for VaD, with 74 co-expressed genes and 8 core genes. ROC curves, nomogram, and DCA indicated high diagnostic accuracy. Core gene analysis revealed differential expression of characteristic genes in various brain regions of AD patients.

Conclusions

This research identified 74 co-expressed genes and 8 pivotal diagnostic genes. These genes likely play roles in signal transduction, neuroinflammation, and autophagy in both AD and VaD. The findings offer potential targets for future research and clinical interventions. Further research should use larger, more diverse datasets and incorporate custom NGS panels to identify novel genetic variants, enhancing precise diagnostic and therapeutic strategies.
Intraocular complement activation is independent of systemic complement activation and is related to macular vascular remodelling in retinal vein occlusion
Authors: Liu Hengwei , Zhou Yufan , Qi Jinyan , Liang Shengnan , Guo Tingting , Chen Juan , Tan Huanhuan , Wang Jie , Xu Heping , Chen Zhongping
Published: November 2024

Background

Retinal vein occlusion (RVO) is a major cause of vision loss. The pathogenesis remains poorly defined although inflammation is known to play a critical role. In this study, we investigated the levels of complement proteins in the aqueous humour and plasma of RVO participants and the relationship between complement levels and retinal pathologies.

Methods

The plasma and aqueous humour were collected from 20 treatment-naive RVO and 20 cataract patients. Retinal lesions were examined by fundus stereoscopy and optical coherence tomography angiography. The levels of C1q, C2, C4, C4b, C3, C3b/iC3b, C5, C5a, CFB, CFD, CFI, CFH, and MBL in the plasma and aqueous humour were measured using the Luminex® x MAP® multiplex assay.

Results

RVO patients had significantly higher levels of C4, C4b, C3b/iC3b, CFB, and CFH in the plasma and aqueous humour compared to controls. The aqueous levels of C1q, C2, C5, C5a, and MBL were also significantly higher in RVO patients than in controls. CRVO patients had higher intraocular levels of C1q, C4, C5, CFI, CFH, and MBL than BRVO patients. C5a was below the detectable limit in the plasma in 18 cataracts and 16 RVO participants. The intraocular levels of C5a positively correlated with C1q, C2, C4, C3, C5, CFB, CFH, and MBL. The intraocular levels of CFD, CFI and MBL positively correlated with CRT, and the levels of C2, C3, C5, CFB, and MBL negatively correlated with the size of the foveal avascular zone. The plasma levels of C4b, C3b/iC3b, and CFD positively correlated with their counterparts in the aqueous humour in cataracts but not in RVO patients. The ratios of aqueous humour/plasma of C1q, C4, C4b, C3b/iC3b, C5, CFB, CFD, CFI, and CFH in the RVO patients were significantly higher than those in the cataract patients.

Discussion and conclusions

The intraocular complement activation in RVO is mediated by the classical and the alternative pathways and is largely independent of systemic complement activation. Intraocular complement activation may be related to retinal oedema and vascular remodeling in RVO patients.
Implementation, barriers, solving strategies and future perspectives of reimbursed community pharmacy services - a nationwide survey for community pharmacies in Germany
Authors: Kroenert Ann-Christin , Bertsche Thilo
Published: November 2024

Background

Since June 2022, the legal framework has been created for German community pharmacies to offer their patients five reimbursed community pharmacy services that go beyond the current operating regulations. However, little is known about barriers that hinder their implementation. We therefore aimed to investigate the implementation of reimbursed community pharmacy services (i), barriers to the implementation (ii), solving strategies to overcome the barriers (iii), and future perspectives (iv). The objective of this study is to find out how the implementation of community pharmacy services can be facilitated for community pharmacies so that more services can be offered.

Methods

In July 2023, we created an online survey and sent it to pharmacists in community pharmacies, including those who offered reimbursed community pharmacy services and those who did not.

Results

Overall, 218 pharmacists from 218 different community pharmacies participated. (i) Of those, 176 (81%) already offered at least one reimbursed community pharmacy service. (ii) For hypertension service, 33% of the offering pharmacists reported barriers in “Communicating with patients,” and 41% reported “Too little patient demand.” For polymedication service, 53% of the offering pharmacists indicated “Barriers in communication with physicians,” and 44% mentioned “Fear of competing with physicians.” (iii) The most frequently reported solving strategies of pharmacists in offering pharmacies were taking advanced training (median of all five services 42%) and developing standardized procedures (median of all five services 34%). In contrast, pharmacists in non-offering pharmacies had not developed any solving strategies (median of all five services 40%). (iv) 64% of the pharmacists in non-offering pharmacies could imagine being able to offer reimbursed community pharmacy services in the future.

Conclusions

Many German pharmacies already offer reimbursed community pharmacy services. However, there are still barriers to widespread implementation. Therefore, customized support regarding the needs of the pharmacies should be provided since most pharmacists who do not yet offer these services today can imagine offering them in the future.
Bayesian tip-dated timeline for diversification and major biogeographic events in Muroidea (Rodentia), the largest mammalian radiation
Authors: López-Antoñanzas Raquel , Simões Tiago R. , Condamine Fabien L. , Dirnberger Moritz , Peláez-Campomanes Pablo
Published: November 2024

Background

Extinct organisms provide vital information about the time of origination and biogeography of extant groups. The development of phylogenetic methods to study evolutionary processes through time has revolutionized the field of evolutionary biology and led to an unprecedented expansion of our knowledge of the tree of life. Recent developments applying Bayesian approaches, using fossil taxa as tips to be included alongside their living relatives, have revitalized the use of morphological data in evolutionary tree inferences. Eumuroida rodents represent the largest group of mammals including more than a quarter of all extant mammals and have a rich fossil record spanning the last ~ 45 million years. Despite this wealth of data, our current understanding of the classification, major biogeographic patterns, and divergence times for this group comes from molecular phylogenies that use fossils only as a source of node calibrations. However, node calibrations impose several constraints on tree topology and must necessarily make a priori assumptions about the placement of fossil taxa without testing their placement in the tree.

Results

We present the first morphological dataset with extensive fossil sampling for Muroidea. By applying Bayesian morphological clocks with tip dating and process-based biogeographic models, we provide a novel hypothesis for muroid relationships and revised divergence times for the clade that incorporates uncertainty in the placement of all fossil species. Even under strong violation of the clock model, we found strong congruence between results for divergence times, providing a robust timeline for muroid diversification. This new timeline was used for biogeographic analyses, which revealed a dynamic scenario mostly explained by dispersal events between and within the Palearctic and North African regions.

Conclusions

Our results provide important insights into the evolution of Muroidea rodents and clarify the evolutionary pathways of their main lineages. We exploited the advantage of tip dating Bayesian approaches in morphology-based datasets and provided a classification of the largest superfamily of mammals resulting from robust phylogenetic inference, inferring the biogeographical history, diversification, and divergence times of its major lineages.
Novel biallelic variants in IREB2 cause an early-onset neurodegenerative disorder in a Chinese pedigree
Authors: Guo Zhenglong , Huo Dawei , Shao Yingying , Yang Wenke , Wang Jinming , Zhang Yuwei , Xiao Hai , Hao Bingtao , Liao Shixiu
Published: November 2024

Background

Cellular iron metabolism is essential for maintaining various biological processes in organisms, and this is influenced by the function of iron-responsive element-binding protein 2 (IRP2), encoded by the IREB2 gene. Since 2019, three cases of a genetic neurodegenerative syndrome resulting from compound heterozygous mutations in IREB2 have been documented, highlighting the crucial role of IRP2 in regulating iron metabolism homeostasis. This study aims to investigate the molecular basis in a single proband born to non-consanguineous healthy parents, presenting with severe psychomotor developmental abnormalities and microcytic anemia.

Methods

Trio-whole exome sequencing (WES) was applied to identify the disease-causing gene in an 8-month-old male patient from China. In silico tools were used to predict the pathogenicity of the identified variants, and in vitro functional studies were performed to evaluate the molecular mechanism.

Results

WES identified novel biallelic variants, c.1111 A > G (P.Ile371Val) and c.2477 A > T (P.Asp826Val), in the IREB2 gene, which encodes the iron metabolism-related protein, IRP2. Functional studies revealed that c.2477 A > T resulted in a significant degradation of IRP2, which led to the misregulation of intracellular ferric iron.

Conclusions

We report the identification of the first functional domain associated with the degradation of IRP2. The biallelic variants that affect protein degradation likely underlie the pathogenesis of the IRP2-related neurodegenerative disorder. Moreover, the use of proteasome inhibitors can potentially restore the expression of IRP2, highlighting a promising therapeutic target for patients with IRP2deficiency.
The Parkinson’s disease risk gene cathepsin B promotes fibrillar alpha-synuclein clearance, lysosomal function and glucocerebrosidase activity in dopaminergic neurons
Authors: Jones-Tabah Jace , He Kathy , Karpilovsky Nathan , Senkevich Konstantin , Deyab Ghislaine , Pietrantonio Isabella , Goiran Thomas , Cousineau Yuting , Nikanorova Daria , Goldsmith Taylor , del Cid Pellitero Esther , Chen Carol X.-Q. , Luo Wen , You Zhipeng , Abdian Narges , Ahmad Jamil , Ruskey Jennifer A. , Asayesh Farnaz , Spiegelman Dan , Fahn Stanley , Waters Cheryl , Monchi Oury , Dauvilliers Yves , Dupré Nicolas , Miliukhina Irina , Timofeeva Alla , Emelyanov Anton , Pchelina Sofya , Greenbaum Lior , Hassin-Baer Sharon , Alcalay Roy N. , Milnerwood Austen , Durcan Thomas M. , Gan-Or Ziv , Fon Edward A.
Published: November 2024

Background

Variants in the CTSB gene encoding the lysosomal hydrolase cathepsin B (catB) are associated with increased risk of Parkinson’s disease (PD). However, neither the specific CTSB variants driving these associations nor the functional pathways that link catB to PD pathogenesis have been characterized. CatB activity contributes to lysosomal protein degradation and regulates signaling processes involved in autophagy and lysosome biogenesis. Previous in vitro studies have found that catB can cleave monomeric and fibrillar alpha-synuclein, a key protein involved in the pathogenesis of PD that accumulates in the brains of PD patients. However, truncated synuclein isoforms generated by catB cleavage have an increased propensity to aggregate. Thus, catB activity could potentially contribute to lysosomal degradation and clearance of pathogenic alpha synuclein from the cell, but also has the potential of enhancing synuclein pathology by generating aggregation-prone truncations. Therefore, the mechanisms linking catB to PD pathophysiology remain to be clarified.

Methods

Here, we conducted genetic analyses of the association between common and rare CTSB variants and risk of PD. We then used genetic and pharmacological approaches to manipulate catB expression and function in cell lines, induced pluripotent stem cell-derived dopaminergic neurons and midbrain organoids and assessed lysosomal activity and the handling of aggregated synuclein fibrils.

Results

We find that catB inhibition impairs autophagy, reduces glucocerebrosidase (encoded by GBA1) activity, and leads to an accumulation of lysosomal content. In cell lines, reduction of CTSB gene expression impairs the degradation of pre-formed alpha-synuclein fibrils, whereas CTSB gene activation enhances fibril clearance. In midbrain organoids and dopaminergic neurons treated with alpha-synuclein fibrils, catB inhibition potentiates the formation of inclusions which stain positively for phosphorylated alpha-synuclein.

Conclusions

These results indicate that the reduction of catB function negatively impacts lysosomal pathways associated with PD pathogenesis, while conversely catB activation could promote the clearance of pathogenic alpha-synuclein.
Network analysis of influential risk factors in adolescent suicide attempters
Authors: Fernandez-Fernandez Jennifer , Jiménez-Treviño Luis , Andreo-Jover Jorge , Ayad-Ahmed Wala , Bascarán Teresa Bobes , Canal-Rivero Manuel , Cebria Annabel , Crespo-Facorro Benedicto , De la Torre-Luque Alejandro , Diaz-Marsa Marina , Gonzalez-Pinto Ana , Gomez Sandra , Grande Iría , Iglesias Noelia , Ortin Francisco , March Katya , Palao Angela , Pérez-Díez Iván , Pérez-Guerra Carla , Ruiz-Veguilla Miguel , Vieta Eduard , Perez-Sola Victor , Saiz Pilar Alejandra
Published: November 2024

Objective

This study aims to investigate the interrelationship of risk factors for suicidal behaviour and their influence on attempt severity in a sample of adolescents who have recently attempted suicide. For it a network analyse was performed.

Method

Data from a sample of adolescents from 12 to 17 years of age with documented suicide attempts were collected and analysed in the context of a larger study conducted in Spain called SURVIVE. Several factors were examined including age, sex, depression, trauma, impulsivity, and substance abuse. Graph analysis was performed to identify relationships and centrality measures among these factors.

Results

A total of 267 participants were enrolled: 233 females and 34 males with a mean age of 15.00 years (SD = 1.52). The results indicate that age and sex do not have a notable relationship with attempt severity in adolescents. Emotional and behavioural difficulties, measured by the Strengths and Difficulties Questionnaire (SDQ), have the greatest influence on other variables. Depression and childhood trauma show varying degrees of association with suicidal behaviour, as does motor impulsivity. Substance use does not appear to be strongly related to suicide attempt severity. The number of suicide attempts is strongly correlated with emotional and behavioural difficulties, depression, and childhood trauma. Lethality of suicide attempts and intensity of suicidal ideation do not show significant associations with the other variables.

Conclusion

This study identifies significant risk factors for adolescent suicide. Emotional and behavioural symptoms, depression, and childhood trauma are strongly linked to suicidal behaviour. However, age, sex, and substance abuse show minimal correlation. Assessing emotional difficulties and depressive symptoms using specific questionnaires could be crucial in evaluating suicidal behaviour in adolescents.
Reducing Exposures to Endocrine Disruptors (REED) study, a personalized at-home intervention program to reduce exposure to endocrine disrupting chemicals among a child-bearing age cohort: study protocol for a randomized controlled trial
Authors: Rochester Johanna R. , Kwiatkowski Carol F. , Lathrop Michael Kupec , Neveux Iva , Daza Eric J. , Grzymski Joseph , Hua Jenna
Published: November 2024

Background

Exposures to endocrine disrupting chemicals (EDCs) have been linked to chronic diseases including breast cancer, metabolic syndrome, diabetes, and infertility. Exposure during pregnancy may have a lifelong impact on the fetus. Services are needed to allow individuals to learn about their personal EDC exposures and how to reduce them. Million Marker (MM) aims to crowdsource and scale the biomonitoring of environmental chemicals and provide actionable results to empower individuals to proactively assess, track, and reduce their EDC exposures. In previous research, we developed and tested the first mobile EDC intervention service (mail-in urine testing and exposure report-back) for its efficacy in increasing EH literacy (EHL), willingness to reduce exposures (i.e., readiness to change, RtC), and system usability. After intervention, we found increased EHL, increased RtC in women (but not men), and decreased EDC exposure. However, some participants did not increase their RtC and had difficulty carrying out the intervention on their own. The reasons for these less optimal results were the difficulty in the EHL subject matter—participants still felt ill-prepared to apply their knowledge to making healthier lifestyle changes. Therefore, in this study, we will address these perceived limitations.

Methods

We will test a self-directed online interactive curriculum with live counseling sessions and individualized support modeled after the highly effective Diabetes Prevention Program (DPP). Recruiting from the Healthy Nevada Project (HNP), one of the largest population health cohorts in the world, we test the effectiveness of our EDC-specific online intervention curriculum via EHL and RtC surveys and determine changes in EDC exposure before and after intervention in a randomized controlled trial. We will also test for common clinical biomarkers via a commercially available at-home test (Siphox). We will recruit and randomize 300 women and 300 men of reproductive age (total n=600) from HNP. Our target population is men and women of reproductive age (18–44 years old).

Discussion

At the conclusion of this project, we will be well-positioned to scale our services to clinics and the general public, with the eventual aims of FDA approval, insurance coverage, and incorporation into routine clinical care.
Assessment of wind energy potential along the Egyptian Mediterranean Coast
Authors: Tonbol Kareem , Elbessa Mohamed , Ibrahim Omneya , El-Geziry Tarek M.
Published: November 2024

Background

Currently, there is no wind park operating along the Egyptian Mediterranean Coast. Therefore, this study aims to find suitable locations for such projects. Wind data from five coastal meteorological stations were used. These are Marsa Matruh (MM), Ras El-Tin (RE), Abu Qir (AQ), Port Said (PS), and Arish (Ar), in that order from west to east. The wind regime dataset, comprising velocity and direction measurements at a 10-m elevation, was collected from January 2007 to December 2022 (16 years), with a complete record of all data points. The Weibull distribution function, along with its different parameters, was used to characterize wind energy along the Egyptian Mediterranean Coast. The coefficient of determination (R2), root mean squared error (RMSE), and relative root mean squared error (RRMSE) for the Weibull parameters, along with the relative percentage errors (RPE) for the wind power density were calculated to assess the concordance between outcomes derived from observed data and those predicted by the Weibull function.

Results

Results revealed that the dominant wind direction along the Egyptian Mediterranean Coast was the NNW to N wind, except at Ar where the dominant wind was S. The wind velocity range of 4–6 m/s dominated RE, AQ, and PS. At MM and Ar, this was reduced to 2–4 m/s. The analysis of wind power density outlined significant insights into the potential for wind energy generation in the region. The overall analysis showed that AQ and PS were potentially the most suitable locations for wind energy projects. However, the high variability at the AQ site required robust system designs to manage the fluctuating wind conditions. PS might be more suitable for projects prioritizing stability and consistency over maximum energy output. Although Arish, characterized by its lower wind power density, may be less conducive for large-scale wind energy projects, it could still be viable for smaller installations or when integrated with other renewable energy sources.

Conclusions

The different statistical indices reflected good model fitting, displaying the reliability of the Weibull distribution as a tool for preliminary wind resource assessment along the Egyptian Mediterranean Coast and facilitating accurate predictions of wind power availability.
A real-time predicting online tool for detection of people’s emotions from Arabic tweets based on big data platforms
Authors: Abdelhady Naglaa , Elsemman Ibrahim E. , Soliman Taysir Hassan A.
Published: November 2024

Emotion prediction is a subset of sentiment analysis that aims to extract emotions from text, speech, or images. The researchers posit that emotions determine human behavior, making the development of a method to recognize emotions automatically crucial for use during global crises, such as the COVID-19 pandemic. In this paper, a real-time system is developed that identifies and predicts emotions conveyed by users in Arabic tweets regarding COVID-19 into standard six emotions based on the big data platform, Apache Spark. The system consists of two main stages: (1) Developing an offline model and (2) Online emotion prediction pipeline. For the first stage, two different approaches: The deep Learning (DL) approach and the Transfer Learning-based (TL) approach to find the optimal classifier for identifying and predicting emotion. For DL, three classifiers are applied: Convolutional Neural Network (CNN), Gated Recurrent Unit (GRU), and Bidirectional GRU (BiGRU). For TL, five models are applied: AraBERT, ArabicBERT, ARBERT, MARBERT, and QARiB. For the second stage, create a Transmission Control Protocol (TCP) socket between Twitter’s API and Spark used to receive streaming tweets and Apache Spark to predict the label of tweets in real-time. The experimental results show that the QARiB model achieved the highest Jaccard accuracy (65.73%), multi-accuracy (78.71%), precision-micro (78.71%), recall-micro (78.71%), f-micro (78.71%), and f-macro (78.55%). The system is available as a web-based application that aims to provide a real-time visualization of people’s emotions during a crisis.
Assessment of mitochondrial function and its prognostic role in sepsis: a literature review
Authors: Nedel Wagner , Strogulski Nathan Ryzewski , Kopczynski Afonso , Portela Luis Valmor
Published: November 2024

Sepsis is characterized by a dysregulated and excessive systemic inflammatory response to infection, associated with vascular and metabolic abnormalities that ultimately lead to organ dysfunction. In immune cells, both non-oxidative and oxidative metabolic rates are closely linked to inflammatory responses. Mitochondria play a central role in supporting these cellular processes by utilizing metabolic substrates and synthesizing ATP through oxygen consumption. To meet fluctuating cellular demands, mitochondria must exhibit adaptive plasticity underlying bioenergetic capacity, biogenesis, fusion, and fission. Given their role as a hub for various cellular functions, mitochondrial alterations induced by sepsis may hold significant pathophysiological implications and impact on clinical outcomes. In patients, mitochondrial DNA concentration, protein expression levels, and bioenergetic profiles can be accessed via tissue biopsies or isolated peripheral blood cells. Clinically, monocytes and lymphocytes serve as promising matrices for evaluating mitochondrial function. These mononuclear cells are highly oxidative, mitochondria-rich, routinely monitored in blood, easy to collect and process, and show a clinical association with immune status. Hence, mitochondrial assessments in immune cells could serve as biomarkers for clinical recovery, immunometabolic status, and responsiveness to oxygen and vasopressor therapies in sepsis. These characteristics underscore mitochondrial parameters in both tissues and immune cells as practical tools for exploring underlying mechanisms and monitoring septic patients in intensive care settings. In this article, we examine pathophysiological aspects, key methods for measuring mitochondrial function, and prominent studies in this field.
CT radiation dose reduction with tin filter for localisation/characterisation level image quality in PET-CT: a phantom study
Authors: Bebbington Natalie Anne , Østergård Lone Lange , Christensen Kenneth Boye , Holdgaard Paw Christian
Published: November 2024

Background

The tin filter has allowed radiation dose reduction in some standalone diagnostic computed tomography (CT) applications. Yet, ‘low-dose’ CT scans are commonly used in positron emission tomography (PET)-CT for lesion localisation/characterisation (L/C), with higher noise tolerated. Thus, dose reductions permissible with the tin filter at this image quality level may differ. The aim was to determine the level of CT dose reduction permitted with the tin filter in PET-CT, for comparable image quality to the clinical reference standard (CRS) L/C CT images acquired with standard filtration.

Materials and methods

A whole-body CT phantom was scanned with standard filtration in CRS protocols, using 120 kV with 20mAs-ref for bone L/C (used in 18F-Sodium Fluoride (NaF) PET-CT) and 40mAs-ref for soft tissue L/C (used in 18F-Fluorodeoxyglucose (FDG) PET-CT), followed by tin filter scans at 100 kV (Sn100kV) and 140 kV (Sn140kV) with a range of mAs settings. For each scan, effective dose (ED) in an equivalent-sized patient was calculated, and image quality determined in 5 different tissues through quantitative (contrast-to-noise ratio) and qualitative (visual) analyses. The relative dose reductions which could be achieved with the tin filter for comparable image quality to CRS images were calculated.

Results

Quantitative analysis demonstrated dose savings of 50–76% in bone, 27–51% in lung and 8–61% in soft tissue with use of the tin filter at Sn100kV. Qualitative analysis demonstrated dose reductions using Sn100kV in general agreement with the dose reductions indicated by quantitative analysis. Overall, CT dose reductions of around 85% were indicated for NaF bone PET-CT, allowing whole-body CT at just 0.2mSv ED, and a 30–40% CT dose reduction for FDG PET-CT using Sn100kV (1.7-2.0mSv), providing comparable image quality to current CRS images with standard filtration. Sn140kV demonstrated limited value in CT dose reduction.

Conclusions

Large CT dose reductions can be made using the tin filter at Sn100kV, when imaging bone, lung and soft tissue at L/C level CT image quality in PET-CT. As well as reducing the risk of inducing a cancer in later life, such dose reductions may also impact PET-CT practice, such as justifying cross-sectional over planar imaging or justifying PET-CT in younger patients.
The risk of upper gastrointestinal bleeding associated with concomitant proton pump inhibitor administration during dual antiplatelet therapy with aspirin and prasugrel: a retrospective single-center study
Authors: Ide Yutaro , Morikawa Go , Yoshida Kyohei , Takano Yuki , Kubota Ken , Okazawa Katsuko , Yasu Takeo
Published: November 2024

Objective

Dual‐antiplatelet therapy (DAPT) and proton pump inhibitor (PPI) are frequently prescribed after percutaneous coronary intervention (PCI) with drug-eluting stents (DES) placement. However, studies that evaluate the optimal PPI when used as primary prevention in patients without a history of peptic ulcer disease or upper gastrointestinal bleeding (UGIB), particularly in the context of DAPT involving prasugrel, are lacking. This study aimed to assess the efficacy and safety of PPI use in preventing UGIB in this patient population.

Methods

This study included patients who underwent PCI with coronary stent placement for acute coronary syndrome or stable angina at our institution from January 2015 to December 2020. Eligible patients started DAPT with aspirin and prasugrel and concomitantly received PPI therapy (lansoprazole or esomeprazole), with a follow-up period of two years. The primary endpoint was UGIB incidence, diagnosed during follow-up, serving as an efficacy measure. Secondary endpoints included the assessment of major bleeding (as defined by the Thrombolysis in Myocardial Infarction major bleeding criteria) and clinically relevant non-major bleeding events. Safety outcomes focused on adverse event incidence attributable to PPI use.

Results

Among the 165 patients analyzed, 109 and 56 were included in the lansoprazole and esomeprazole groups, respectively, with cumulative incidence of UGIB at 96 weeks of 0.9% (1/109) and 3.6% (2/56). No significant differences in terms of major bleeding events or other bleeding outcomes were observed between the two groups. Adverse events related to PPI use were reported as diarrhea/soft stools in 7 (6%) cases and thrombocytopenia in 1 (1%) case in the lansoprazole group, whereas no such events were observed in the esomeprazole group. No clinically significant hematologic or biochemical abnormalities were reported.

Conclusion

This study evaluated the efficacy and safety of PPIs in combination with DAPT, including prasugrel, following PCI, and suggests that lansoprazole and esomeprazole may offer comparable efficacy in preventing UGIB.
Exploring the role of oxidative stress and mitochondrial dysfunction in β-damascone-induced aneuploidy
Authors: Hashizume Tsuneo , Munakata Satoru , Takahashi Tomohiro , Watanabe Taku
Published: November 2024

Background

The rose ketone β-damascone (β-Dam) elicits positive results in the in vitro micronucleus (MN) assay using human lymphocytes, but shows negative outcomes in the Ames test and combined in vivo MN and comet assays. This has led to the interpretation that the in vitro MN result is a misleading positive result. Oxidative stress has been suggested as an indirect mode of action (MoA) for in vitro MN formation, with the α, β-unsaturated carbonyl moiety of the β-Dam chemical structure expected to cause misleading positive results through this MoA. In this study, we investigated the role of oxidative stress in β-Dam-induced in vitro MN formation by co-treatment with the antioxidant N-acetyl-l-cysteine (NAC), thereby highlighting a possible link between mitochondrial dysfunction and aneugenicity.

Results

β-Dam induced MN formation in both CHL/IU and BEAS-2B cells, with the response completely inhibited by co-treatment with NAC. Moreover, β-Dam induced oxidative stress-related reporter activity in the ToxTracker assay and increased reactive oxygen species levels, while decreasing glutathione levels, in BEAS-2B cells in the high-content analysis. All of these effects were suppressed by NAC co-treatment. These findings indicate that β-Dam elicits oxidative stress, which causes DNA damage and ultimately leads to MN induction. However, no significant DNA damage-related reporter activities were observed in the ToxTracker assay, nor was there an increased number of γH2AX foci in the high-content analysis. These data suggest that MN formation is not a DNA-reactive MoA. Considering recent reports of aneuploidy resulting from chromosome segregation defects caused by mitochondrial dysfunction, we investigated if β-Dam could cause such dysfunction. We observed that the mitochondrial membrane potential was dose-dependently impaired in BEAS-2B cells exposed to β-Dam.

Conclusions

These findings suggest that the oxidative stress induced by β-Dam exposure may be explained through an aneugenic MoA via mitochondrial dysfunction, thereby contributing to MN formation in mammalian cells.
Antiosteoporotic activity of lupeol on postmenopausal symptoms through promoting estrogenic activity and bone markers in ovariectomized rats
Authors: Bhalerao Tanmayee , Mandlik Deepa , Rojatkar Supada , Bodhankar Subhash , Sathiyanarayanan Arulmozhi
Published: November 2024

Background

Menopause is caused by age-related follicular degeneration and is marked by menstrual cycle cessation with insufficiency of an ovarian hormone, particularly estrogen. Estrogen insufficiency causes vasomotor and urogenital symptoms, as well as an increased risk of osteoporosis. Lupeol (LP) is a triterpene compound found in aloe leaves, carrot root, mango pulp, melon seeds, cucumber, soybean, and other plants. The present study aims to assess the effect of LP on estrogen insufficiency in ovariectomy-induced postmenopausal osteoporosis in rats. Female rats were ovariectomized bilaterally and placed into five groups (n = 8) as ovariectomy control (OVX), standard (17β-Estradiol 50 µg/kg) group, and LP (25, 50, and 100 mg/kg) groups. Two additional groups Normal Control (NC) and Sham Control (SC) rats went through a sham operation procedure. The rats were given an oral dose for 90 days. The tail skin temperature (TST) was recorded every day, and vaginal cornification was assessed every fourth day. Serum hormones, biochemical parameters, bone physical, radiographic, and histological markers were measured on the 90th day of treatment.

Results

In LP-treated rats, there was a decrease in TST, induction of vaginal cornification, improved serum hormonal and lipid profile, improved bone physical properties, increased bone density, and enhanced cytological and histological alterations.

Conclusions

These findings imply that LP exhibited an antiosteoporotic activity against postmenopausal symptoms in ovariectomized rats, suggesting that it could be used therapeutically to treat menopausal problems.
Seismic poststack impedance inversion using geophysics-informed deep-learning neural network
Authors: Zhang Bo , Pu Yitao , Dai Ruiqi , Cao Danping
Published: November 2024

Traditionally, seismic poststack impedance inversion is implemented using linear optimization algorithms. Recently, deep-learning neural networks have been successfully used to estimate the impedance from seismic data. First, we determine the general workflow of seismic poststack impedance inversion using supervised neural network (SNN). Next, we work to compute seismic impedance using geophysics-informed neural network (GINN). Similar to linear optimization algorithms, the inputs of GINN include real seismograms, a wavelet, and a low-frequency model. The loss function of GINN is designed to minimize the difference between real seismograms and synthetic seismic seismograms that are computed from the estimated impedance and input wavelet. To avoid lateral discontinuity of estimated impedance, the weights of GINN are trained using the seismograms of all seismic traces. We use synthetic and real seismic data to discuss the advantages and limitations of GINN, SNN, and traditional linear optimization algorithms. Not surprisingly, the signal-to-noise ratio (S/N) of seismic data and the phase of seismic wavelet are the most important factors that affect the accuracy of impedance estimated using GINN. The accuracy and resolution of impedance estimated using GINN is higher than linear optimization and SNN if the seismic data have a high S/N. The synthetic examples demonstrate that the accuracy of impedance calculated using SNN increases with the number of available training wells and linear optimization algorithms are more robust to noise than GINN and SNN.
The Early Youth Engagement (EYE-2) intervention in first-episode psychosis services: pragmatic cluster randomised controlled trial and cost-effectiveness evaluation
Authors: Greenwood Kathryn , Jones Christopher , Yaziji Nahel , Healey Andrew , May Carl , Bremner Stephen , Hooper Richard , Rathod Shanaya , Phiri Peter , de Visser Richard , Mackay Tanya , Bartl Gergely , Abramowicz Iga , Gu Jenny , Webb Rebecca , Nandha Sunil , Lennox Belinda , Johns Louise , French Paul , Hodgekins Jo , Law Heather , Plaistow James , Thompson Rose , Fowler David , Garety Philippa , O'Donnell Anastacia , Painter Michelle , Jarvis Rebecca , Clark Stuart , Peters Emmanuelle
Published: November 2024

Background

Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

Aims

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

Method

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Results

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

Conclusions

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.
Note on WAdS3 black holes in extended BHT gravity
Authors: Yekta Davood Mahdavian
Published: November 2024

In this letter, we study a holographic diffeomorphism invariant higher-derivative extension of Bergshoeff-Hohm-Townsend (BHT) cosmological gravity in the context of Wald's formalism. We calculate the entropy, mass and angular momentum of warped anti-de Sitter (WAdS3) black holes in ghost-free BHT massive gravity and its extension using the covariant phase space method. We also compute the central charges of the dual boundary conformal field theories (CFT) from the thermodynamics method.
Optimal Maternal Ventilation During Laparotomy with General Anesthesia in Pregnancy in the Ovine Model
Authors: Bleeser Tom , Joyeux Luc , Vergote Simen , Basurto David , Valenzuela Ignacio , Hubble Talia Rose , Kunpalin Yada , Emam Doaa , Van de Velde Marc , Devroe Sarah , Deprest Jan , Rex Steffen
Published: November 2024

BACKGROUND:

General anesthesia during pregnancy is not uncommon, for example, for trauma surgery, cerclage, or cesarean delivery. Current recommendations are to maintain maternal partial pressure of carbon dioxide in arterial blood (paCO2) at 30 mm Hg, which is based solely on the average maternal paCO2 in awake pregnant women. However, there is no evidence that this target, compared to other targets, would enable optimal conditions for the fetus during general anesthesia. Maternal paCO2 can affect uterine blood flow, affinity of hemoglobin for oxygen, and fetal CO2 elimination. In this study, a range of potential targets of maternal paCO2 was investigated in the ovine model, aiming to determine which target is most conducive to physiological fetal blood gas values during laparotomy with general anesthesia.

METHODS:

Ten time-mated pregnant Swifter ewes with a gestational age of 93 to 104 days were used. During the first phase of the experiment, anesthesia was induced, all ewes were ventilated to target a physiological maternal paCO2 of 30 mm Hg, a maternal laparotomy was performed, and a fetal microcatheter was inserted surgically to enable blood sampling from the fetal aorta. Thereafter, in the second phase of the experiment, the 10 pregnant ewes were randomized to 10 different targets of maternal paCO2 between 27 and 50 mm Hg (1 target for each ewe), and maternal ventilation was adjusted accordingly. Forty-five minutes later, maternal and fetal arterial blood gas samples were analyzed. Linear regression models were used to estimate maternal paCO2 enabling physiologic fetal parameters, including fetal paCO2 (primary outcome).

RESULTS:

A maternal paCO2 of 27.4 mm Hg (95% confidence interval, 23.1–30.3) enabled physiological fetal paCO2. Each increase in maternal paCO2 by 1 mm Hg, on average, increased fetal paCO2 by 0.94 mm Hg (0.69–1.19). This relationship had a strong correlation (r² = 0.906). No fetuses died during the experiment.

CONCLUSIONS:

This study provides experimental support for the clinical recommendation to maintain maternal paCO2 close to the physiologic value of 30 mm Hg during general anesthesia for maternal laparotomy in pregnancy as it is conducive to physiological fetal blood gas values. Given the lower bound of the 95% confidence interval, the possibility that a lower maternal paCO2 would improve fetal gas exchange cannot be excluded.
The Double Disavowals of Theory's “Problem Spaces”: Review of Revolution and Disenchantment
Authors: Bou Ali Nadia
Published: November 2024

The review article provides a critical engagement with Fadi A. Bardawil's Revolution and Disenchantment. Bardawil's historical ethnographic research claims to provide an account of the failures of Marxism in the Levant. The review proposes that Bardawil's theoretical and intellectual commitments may have resulted in projecting failure retroactively on an entire field of theory, Marxism, thereby foreclosing a critical engagement with concepts in relation to praxis.
Stranieri Ovunque—Foreigners Everywhere and the History of Global Modernism
Authors: Powers Holiday
Published: November 2024

Occurring every two years, the Venice Biennale remains a key node for contemporary art. In Venice, in addition to a main exhibition, national pavilions are located primarily between the two main biennale sites, the Giardini and the Arsenale, and collateral events are scattered across the city. Understood as the sum of these many exhibitions, Venice allows visitors and participants to take stock of the current guiding interests and concerns within the art world. The main exhibition of the 60th edition, Stranieri Ovunque—Foreigners Everywhere, is curated by Adriano Pedrosa. The exhibition first and foremost tries to reunite artists who are foreigners, immigrants, or exiles, especially those who have moved between the Global South and the Global North. Pulling from the etymology of romance languages, this concept of the stranger is mobilized to include queer artists, outsider artists, and Indigenous artists. It is further separated into the Nucleo Contemporaneo (Contemporary Nucleus) and a Nucleo Storico (Historic Nucleus) focused on global modernism. Within the main exhibition, the question of how to tell local histories in relation to the globalized contemporary moment emerges through the interplay between the historic and contemporary nuclei, and these rooms emphasize the global entanglements and frictions of modernism. It is significant to organize a biennale that is focused on breaking the Eurocentric barriers of art history. However, this article argues that can only meaningfully be done by expecting the same rigorous approach to global modernism as to the hegemonic Euro-American art histories of modernism.
Sexual Politics: Photobooks by Japanese Women, 1976–79
Authors: Michiko Kasahara , McCormick Kelly Midori
Published: November 2024

In the 1970s, the Japanese photographic world was dominated by men, and Japanese society grappled with changing gender norms. Women photographers raised their cameras in response and challenge to the status quo, carving out a space for new forms of photographic work. This essay examines the works of Ishiuchi Miyako, Matsumoto Michiko, Imai Hisae, and others from the perspective of sexual politics, while at the same time considering the broader historical context of Japan in the 1970s.