bluuebunny/crossref_metadata_2025 huggingface dataset:
Unconscious classification of quantitative electroencephalogram features from propofol versus propofol combined with etomidate anesthesia using one-dimensional convolutional neural network
Authors: Zhou Pan , Deng Haixia , Zeng Jie , Ran Haosong , Yu Cong
Published: September 2024

Objective

Establishing a convolutional neural network model for the recognition of characteristic raw electroencephalogram (EEG) signals is crucial for monitoring consciousness levels and guiding anesthetic drug administration.

Methods

This trial was conducted from December 2023 to March 2024. A total of 40 surgery patients were randomly divided into either a propofol group (1% propofol injection, 10 mL: 100 mg) (P group) or a propofol-etomidate combination group (1% propofol injection, 10 mL: 100 mg, and 0.2% etomidate injection, 10 mL: 20 mg, mixed at a 2:1 volume ratio) (EP group). In the P group, target-controlled infusion (TCI) was employed for sedation induction, with an initial effect site concentration set at 5–6 μg/mL. The EP group received an intravenous push with a dosage of 0.2 mL/kg. Six consciousness-related EEG features were extracted from both groups and analyzed using four prediction models: support vector machine (SVM), Gaussian Naive Bayes (GNB), artificial neural network (ANN), and one-dimensional convolutional neural network (1D CNN). The performance of the models was evaluated based on accuracy, precision, recall, and F1-score.

Results

The power spectral density (94%) and alpha/beta ratio (72%) demonstrated higher accuracy as indicators for assessing consciousness. The classification accuracy of the 1D CNN model for anesthesia-induced unconsciousness (97%) surpassed that of the SVM (83%), GNB (81%), and ANN (83%) models, with a significance level of p < 0.05. Furthermore, the mean and mean difference ± standard error of the primary power values for the EP and P groups during the induced period were as follows: delta (23.85 and 16.79, 7.055 ± 0.817, p < 0.001), theta (10.74 and 8.743, 1.995 ± 0.7045, p < 0.02), and total power (24.31 and 19.72, 4.588 ± 0.7107, p < 0.001).

Conclusion

Large slow-wave oscillations, power spectral density, and the alpha/beta ratio are effective indicators of changes in consciousness during intravenous anesthesia with a propofol-etomidate combination. These indicators can aid anesthesiologists in evaluating the depth of anesthesia and adjusting dosages accordingly. The 1D CNN model, which incorporates consciousness-related EEG features, represents a promising tool for assessing the depth of anesthesia.

Clinical Trial Registration

https://www.chictr.org.cn/index.html.
Focus on the role of calcium signaling in ferroptosis: a potential therapeutic strategy for sepsis-induced acute lung injury
Authors: Xu Yifei , Qu Xintian , Liang Minghao , Huang Di , Jin Minyan , Sun Lili , Chen Xianhai , Liu Fen , Qiu Zhanjun
Published: September 2024

By engaging in redox processes, ferroptosis plays a crucial role in sepsis-induced acute lung injury (ALI). Although iron stimulates calcium signaling through the stimulation of redox-sensitive calcium pathways, the function of calcium signals in the physiological process of ferroptosis in septic ALI remains unidentified. Iron homeostasis disequilibrium in ferroptosis is frequently accompanied by aberrant calcium signaling. Intracellular calcium overflow can be a symptom of dysregulation of the cellular redox state, which is characterized by iron overload during the early phase of ferroptosis. This can lead to disruptions in calcium homeostasis and calcium signaling. The mechanisms controlling iron homeostasis and ferroptosis are reviewed here, along with their significance in sepsis-induced acute lung injury, and the potential role of calcium signaling in these processes is clarified. We propose that the development of septic acute lung injury is a combined process involving the bidirectional interaction between iron homeostasis and calcium signaling. Our goal is to raise awareness about the pathophysiology of sepsis-induced acute lung injury and investigate the relationship between these mechanisms and ferroptosis. We also aimed to develop calcium-antagonistic therapies that target ferroptosis in septic ALI and improve the quality of survival for patients suffering from acute lung injury.
Rosa roxburghii fermented juice mitigates LPS-induced acute lung injury by modulation of intestinal flora and metabolites
Authors: Chen Zhiyu , Zhang Shuo , Sun Xiaodong , Meng Duo , Lai Chencen , Zhang Min , Wang Pengjiao , Huang Xuncai , Gao Xiuli
Published: September 2024

Acute lung injury (ALI) is a severe pulmonary condition with high mortality and morbidity, lacking effective pharmacotherapeutic options. Rosa roxburghii Tratt, a unique fruit from southwestern China, is valued for its rich nutritional content and functional properties. Fermentation is known to enhance the nutritional value, flavor, and shelf life of foods. In this study, we investigated the effects of fermented Rosa roxburghii juice (RRFJ) on gut microbiota, metabolites, and the levels of short-chain fatty acids in the intestines, as well as its impact on lung tissue and intestine tissue injury, inflammation, and oxidative stress in murine models. The results showed that RRFJ modulated gut microbiota and metabolites, increased short-chain fatty acid levels, and consequently reduced lung tissue injury, inflammation, and oxidative stress in mice with ALI. These findings suggest that RRFJ has the potential to serve as a functional dietary adjunct in the management of acute lung injury, providing a scientific basis for its therapeutic role.
Genome-wide survey of the bipartite structure and pathogenesis-related genes of Neostagonosporella sichuanensis, a causal agent of Fishscale bamboo rhombic-spot disease
Authors: Liu Lijuan , Yang Chunlin , Liang Fang , Li Chengsong , Zeng Qian , Han Shan , Li Shujiang , Liu Yinggao
Published: September 2024

Bamboo resources have garnered significant global attention due to their excellent capacity for regeneration and high yield. Rhombic-spot disease, a substantial threat to fishscale bamboo (Phyllostachys heteroclada), is primarily caused by Neostagonosporella sichuanensis. This study first reported the genome assemblies and characteristics of two N. sichuanensis isolates using PacBio and Illumina sequencing platforms. The genomes of N. sichuanensis strain SICAUCC 16–0001 and strain SICAUCC 23–0140, with sizes of 48.0 Mb and 48.4 Mb, respectively, revealed 10,289 and 10,313 protein-coding genes. Additionally, they contained 34.99 and 34.46% repetitive sequences within AT-rich regions, with notable repeat-induced point mutation activity. Comparative genome analysis identified 1,049 contracted and 45 expanded gene families in the genome of N. sichuanensis, including several related to pathogenicity. Several gene families involved in mycotoxin metabolism, secondary metabolism, sterol biosynthesis and transport, and cell wall degradation were contracted. Compared to most analyzed necrotrophic, hemibiotrophic, and phaeosphaeriacous pathogens, the genomes of two N. sichuanensis isolates exhibited fewer secondary metabolite enzymes, carbohydrate-active enzymes, plant cell wall degrading enzymes, secreted proteins, and effectors. Comparative genomics analysis suggested that N. sichuanensis shares more similar characteristics with hemibiotrophic pathogens. Based on single carbon source tests, N. sichuanensis strains demonstrated a higher potential for xylan decomposition than pectin and cellulose. The proportion of cell wall-degrading enzyme effectors occupied a high proportion of the total effectors of the N. sichuanensis genomes. These findings provide valuable insights into uncovering the pathogenesis of N. sichuanensis toward the efficient management of rhombic-spot disease of fishscale bamboo.
Multifaceted neuroprotective approach of Trolox in Alzheimer's disease mouse model: targeting Aβ pathology, neuroinflammation, oxidative stress, and synaptic dysfunction
Authors: Tahir Muhammad , Kang Min Hwa , Park Tae Ju , Ali Jawad , Choe Kyonghwan , Park Jun Sung , Kim Myeong Ok
Published: September 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aβ1 − 42-induced AD mouse model. Aβ1 − 42 5μL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and β-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1β (IL-1β), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases.
The intricate interplay between microglia and adult neurogenesis in Alzheimer’s disease
Authors: Früholz Iris , Meyer-Luehmann Melanie
Published: September 2024

Microglia, the resident immune cells of the central nervous system, play a crucial role in regulating adult neurogenesis and contribute significantly to the pathogenesis of Alzheimer’s disease (AD). Under physiological conditions, microglia support and modulate neurogenesis through the secretion of neurotrophic factors, phagocytosis of apoptotic cells, and synaptic pruning, thereby promoting the proliferation, differentiation, and survival of neural progenitor cells (NPCs). However, in AD, microglial function becomes dysregulated, leading to chronic neuroinflammation and impaired neurogenesis. This review explores the intricate interplay between microglia and adult neurogenesis in health and AD, synthesizing recent findings to provide a comprehensive overview of the current understanding of microglia-mediated regulation of adult neurogenesis. Furthermore, it highlights the potential of microglia-targeted therapies to modulate neurogenesis and offers insights into potential avenues for developing novel therapeutic interventions.
Elevated neopterin and decreased IL-4, BDNF levels and depression in lymphoma patients receiving R-CHOP chemotherapy
Authors: Mishra Pinki , Bhurani Dinesh , Nidhi
Published: September 2024

Objective

Depression is the most commonly observed psychological manifestation experienced by individuals diagnosed with cancer. The purpose of the study was to investigate the association between levels of IL-4, BDNF, neopterin, and depressive symptoms in lymphoma patients receiving consecutive cycles of chemotherapy.

Methods

Newly diagnosed lymphoma patients scheduled to receive R-CHOP chemotherapy were enrolled. Effects of R-CHOP on circulatory biomarkers and depressive symptoms were assessed at three-time points [baseline assessment 7 days before the first dose of chemotherapy (TP1), interim assessment after the third cycle of chemotherapy (TP2), and follow-up assessment after the 6th cycle of chemotherapy (TP3)].

Results

Seventy lymphoma patients, with a mean age of 44.17 ± 13.67 years, were enrolled. Patients receiving R-CHOP were found significantly increased neopterin levels between given time points TP1 vs. TP2, TP1 vs. TP3, and TP2 vs. TP3 (p < 0.001). However, IL-4 and BDNF levels significantly decreased with consecutive cycles of chemotherapy (p < 0.001). On Patient Health Questionnaire assessment (PHQ-9), scores of items like loss of interest, feeling depressed, sleep problems, loss of energy, and appetite problems were found significantly affected with consecutive cycles of chemotherapy (p < 0.001). The study found weak negative correlations between IL-4, BDNF, and neopterin levels and changes in PHQ-9 scores at both TP2 and TP3, suggesting a potential inverse relationship between these markers and depression symptoms.

Conclusion

In conclusion, the present study suggests a potential link between elevated neopterin levels, decreased IL-4, and BDNF levels, and the presence of depression in lymphoma patients receiving R-CHOP chemotherapy. This study provides valuable insights into understanding the emotional challenges faced by cancer patients, offering information for more personalized interventions and comprehensive support approaches within the oncology setting.
A tree-based approach to identify indispensable foods in minimum-cost food baskets
Authors: Koenen Melissa F. , Geelen Romée , Balvert Marleen , Fleuren Hein
Published: September 2024

Introduction

Optimization techniques, such as linear programming, can be used to estimate the minimum cost of a nutrient-adequate food basket, to determine if individuals or households can afford nutritious diets. These cost estimates typically account for seasonal fluctuations but often overlook significant disruptions in the availability of affordable nutritious food that can severely impact food and nutrition security.

Methods

This paper proposes a tree-based method, the binary search tree, to assess the resilience of the cost estimate of the minimum-cost food basket. In particular, this method aims to identify indispensable foods in these baskets — those whose unavailability would lead to a substantial cost increase. The binary search tree operates by iteratively excluding essential food items while ensuring the construction of minimum-cost nutritious baskets. It considers all relevant combinations of foods up to a specified size and avoids unnecessary optimizations, thereby saving computation time. We describe how the resulting tree can be evaluated and condensed to capture only the necessary information for decision makers. The construction and evaluation of the binary search tree are independent of the (dietary) restrictions or type of optimization model (i.e., linear, non-linear or integer) included.

Results

In general, the binary search tree can identify all (combinations of) foods whose exclusion leads to a significant cost increase of a nutritious food basket. Furthermore, it can detect possible substitute effects between foods and identify key limiting nutrients. A case study is presented in which the binary search tree is applied to data from Ebonyi, Nigeria, modeled using linear programming. We report all combinations of up to five foods that, when unavailable, can impact food and nutrition security in Ebonyi.

Conclusion

The BST can provide insights into local food and nutrition security when facing drastic disruptions in access to nutritious foods by identifying indispensable foods. Its results can be used to inform and design interventions in the context of humanitarian operations.
Effects of exercise with or without β-hydroxy-β-methylbutyrate supplementation on muscle mass, muscle strength, and physical performance in patients with sarcopenia: a systematic review and meta-analysis
Authors: Feng Yiwei , Chen Peng , Li Tao , Wan Ping , Shi Rengfei
Published: September 2024

Objectives

This systematic review and meta-analysis aimed to assess the effects of exercise with/without β-hydroxy-β-methylbutyrate (HMB) supplementation on muscle mass, muscle strength, physical performance, and body composition in patients with sarcopenia.

Methods

A literature search for randomized controlled trials (RCTs) on the effects of exercise with or without HMB supplementation on muscle mass, muscle strength, physical performance, and body composition in patients with sarcopenia was conducted using PubMed, Web of Science, EBSCO, The Cochrane Library, EMBASE, Scopus, Science Direct, China Knowledge Resource Integrated Database (CNKI), and Wan Fang database. The search was limited to studies published up to April 2024 for each database. The outcome measures included muscle mass, muscle strength, physical performance, and body composition. The Cochrane Risk of Bias Assessment Tool was used to evaluate the quality of the included literature, and RevMan 5.4 software was employed to perform a meta-analysis of the outcome indicators.

Results

Five RCTs involving 257 elderly patients with sarcopenia were included in this study. Meta-analysis showed that in terms of physical performance, exercise with HMB supplementation significantly increased gait speed in sarcopenic patients compared to the exercise combined with the placebo group (SMD = 0.48, 95% CI: 0.15 to 0.82, p = 0.005), but exercise combined with HMB supplementation did not have significant effects on SMI (SMD = 0.06, 95% CI: −0.20 to 0.32, p = 0.66), grip strength (SMD = 0.23, 95% CI: −0.05 to 0.52, p = 0.11), five-time chair stand test (SMD = –0.83, 95% CI: −1.88 to 0.21, p = 0.12), fat-free mass (SMD = 0.04, 95% CI: –0.26 to 0.35, p = 0.78), BMI (SMD = –0.09, 95% CI: –0.43 to 0.25, p = 0.60), and fat mass (SMD = 0.01, 95% CI: –0.25 to 0.27, p = 0.94).

Conclusion

The current evidence indicates that exercise with HMB supplementation may enhance physical performance in patients with sarcopenia compared to exercise with the placebo group. However, the effects on muscle mass, muscle strength, and body composition are likely minimal. The above findings are limited by the number of included studies and require further validation through high-quality studies.

Systematic Review Registration

Prospero (CRD42024500135).
Health benefits of fermented olives, olive pomace and their polyphenols: a focus on the role of lactic acid bacteria
Authors: Montagano Federica , Dell’Orco Francesca , Prete Roberta , Corsetti Aldo
Published: September 2024

Fermented foods have regained popularity in Western diets for their health-promoting potential, mainly related to the role of lactic acid bacteria (LAB) during the fermentation process. Nowadays, there is an increasing demand for vegetable-based fermented foods, representing an environmentally sustainable options to overcome the limitations of lactose intolerance, vegetarian, or cholesterol-restricted diets. Among them, table olives and their co-products (i.e., olive pomace) represent important plant-origin matrices, whose exploitation is still limited. Olives are an important source of fiber and bioactive molecules such as phenolic compounds with recognized health-promoting effects. Based on that, this minireview offer a brief overview about the potential beneficial role of fermented table olives/olive pomace, with a particular focus on the role of LAB to obtain healthy and/or probiotic-enriched fermented foods.
Radiomics-based machine learning models for differentiating pathological subtypes in cervical cancer: a multicenter study
Authors: Liu Huiling , Lao Mi , Zhang Yalin , Chang Cheng , Yin Yong , Wang Ruozheng
Published: September 2024

Purpose

This study was designed to determine the diagnostic performance of fluorine-18-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics-based machine learning (ML) in the classification of cervical adenocarcinoma (AC) and squamous cell carcinoma (SCC).

Methods

Pretreatment 18F-FDG PET/CT data were retrospectively collected from patients who were diagnosed with locally advanced cervical cancer at two centers. Radiomics features were extracted and selected by the Pearson correlation coefficient and least absolute shrinkage and selection operator regression analysis. Six ML algorithms were then applied to establish models, and the best-performing classifier was selected based on accuracy, sensitivity, specificity, and area under the curve (AUC). The performance of different model was assessed and compared using the DeLong test.

Results

A total of 227 patients with locally advanced cervical cancer were enrolled in this study (N=136 for the training cohort, N=59 for the internal validation cohort, and N=32 for the external validation cohort). The PET radiomics model constructed based on the lightGBM algorithm had an accuracy of 0.915 and an AUC of 0.851 (95% confidence interval [CI], 0.715-0.986) in the internal validation cohort, which were higher than those of the CT radiomics model (accuracy: 0.661; AUC: 0.513 [95% CI, 0.339-0.688]). The DeLong test revealed no significant difference in AUC between the combined radiomics model and the PET radiomics model in either the training cohort (z=0.940, P=0.347) or the internal validation cohort (z=0.285, P=0.776). In the external validation cohort, the lightGBM-based PET radiomics model achieved good discrimination between SCC and AC (AUC = 0.730).

Conclusions

The lightGBM-based PET radiomics model had great potential to predict the fine histological subtypes of locally advanced cervical cancer and might serve as a promising noninvasive approach for the diagnosis and management of locally advanced cervical cancer.
Elucidating the molecular markers and biological pathways associated with extrahepatic cholangiocarcinoma: a transcriptome sequencing study
Authors: Zhao Bin , Gu Yanmei , Shi Daixiu , Chen Xiaokang , Li Yumin
Published: September 2024

Background

Cholangiocarcinoma is a malignancy with high aggressiveness, and extrahepatic cholangiocarcinoma (ECCA) represents the predominant subtype. However, the molecular architecture and underlying pathogenic mechanisms of ECCA remain poorly understood. The objective of this study is to elucidate the molecular markers and biological pathways associated with ECCA.

Methods

In order to identify the factors influencing ECCA, we conducted transcriptome sequencing on a cohort of 8 surgically resected ECCA specimens. To validate our findings, we integrated data from The Cancer Genome Atlas and Gene Expression Omnibus (GEO) databases using batch integration analysis. Finally, we confirmed our results using clinical samples.

Results

The findings of this study reveal that through the analysis of sequencing data, we have successfully identified the genes that are differentially expressed and have a significant role in the development of ECCA. Utilizing the Weighted Gene Co-expression Network Analysis approach, we have integrated these identified gene modules with the GEO dataset, leading to the identification of four key genes (PTGDS, ITIH2, LSAMP, HBB) that are strongly associated with the progression-free survival of ECCA. We screened a key gene LSAMP from four genes using immunohistochemistry. The gene primarily participate in crucial biological processes such as the ECCA cell cycle and DNA replication. The qRT-PCR reaction and Western Blot conducted on the tissues provided confirmation of the expression levels of the gene, which exhibited consistency with the outcomes of our analysis.

Conclusions

Our study has successfully identified potential biomarkers LSAMP for ECCA, which can serve as valuable tools for early detection and targeted therapeutic interventions in clinical settings.
The current state of inflammation-related research in prostate cancer: a bibliometric analysis and systematic review
Authors: Li Weida , Wang Jian
Published: September 2024

Background

Prostate cancer (PCa) is the second most prevalent malignancy among men globally. The diagnosis, treatment, and prognosis of prostate cancer frequently fall short of expectations. In recent years, the connection between inflammation and prostate cancer has attracted considerable attention. However, there is a lack of bibliometric studies analyzing the research on inflammation within the domain of prostate cancer.

Research methods

We utilized the Web of Science Core Collection (WOSCC) as our data source to extract articles and reviews related to inflammation in prostate cancer, published up until April 12, 2024. The collected data underwent meticulous manual screening, followed by bibliometric analysis and visualization using the Biblioshiny package in R.

Results

This study encompasses an analysis of 2,786 papers focusing on inflammation-related research within the realm of prostate cancer. Recent years have seen a significant proliferation of publications in this area, with the United States and China being the foremost contributors. The most prolific author in this domain is Demarzoam, with Johns Hopkins University standing out as the most influential institution. The leading journal in disseminating these studies is PROSTATE. Keyword co-occurrence analysis reveals that ‘inflammation-related biomarkers’, ‘inflammation index’, and ‘tumor immune microenvironment’ represent the current research hotspots and frontiers.

Conclusion

The findings of this bibliometric study serve to illuminate the current landscape of inflammation-related research in the field of prostate cancer, while further augmenting the discourse on inflammation-mediated cancer therapeutics. Of particular note is the potential of these discoveries to facilitate a more nuanced understanding among researchers regarding the interplay between inflammation and prostate cancer.
Physical space of thirty pediatric intensive care units in the United States of America: a national survey
Authors: Karam Oliver , Ahmed Aziez , Bizzarro Matthew , Bogue Clifford , Giuliano John S. ,   PICU Space Collaborative
Published: September 2024

Introduction

The design of Pediatric Intensive Care Unit (PICU) rooms significantly impacts patient care and satisfaction. The aims were first, to describe the current physical space across PICUs in the USA, and second, to identify what proportion of PICUs are compliant with current guidelines.

Methods

A descriptive cross-sectional survey was conducted, targeting division chiefs and medical directors of PICUs nationwide. The survey collected data on unit type, construction and renovation dates, room sizes, and available amenities. According to the Guidelines for Design and Construction of Hospitals, PICU rooms are recommended to be single rooms, at least 200 sq ft, have a window and a private bathroom. Data were anonymized and reported as median and interquartile ranges or frequencies and percentages.

Results

Thirty units responded. Among the respondents, 26 had general PICUs, 9 had cardiac ICUs, and 3 had intermediate care units, with some units containing multiple types of ICUs. The median annual admissions were 1,125, with a median occupancy rate of 78%. Twenty-three percent of units had at least one double room, and 3% had triple or quadruple rooms. The median room size was 265 sq ft (IQR 230; 304), the smallest room size was 220 sq ft (IQR 179; 275), and the largest single room size was 312 sq ft (IQR 273; 330). Thirty-seven percent of units had bathrooms in every room, while 80% had windows in every room. Additionally, 46% of units had dialysis capabilities in every room, and 7% had negative pressure capabilities in every room. The median building year was 2008 (IQR 2001;2014), with 36% of units having undergone at least one renovation. Larger rooms were associated with more recent build dates (p = 0.01). Only 30% of the PICUs met the guidelines for physical space. These compliant units were built at a median of 4 years ago (IQR 1; 8).

Conclusion

This study highlights the variability in PICU room design and amenities across healthcare facilities. Many units still fall short of meeting the guidelines for room size, windows, and private bathrooms. Future research should investigate the relationship between room characteristics and patient outcomes to inform better design practices, with a goal of improving patient experiences and clinical outcomes.
Activation of AMPK/SIRT1/FOXO3a signaling by BMS-477118 (saxagliptin) mitigates chronic colitis in rats: uncovering new anti-inflammatory and antifibrotic roles
Authors: Elmorsy Elsayed A. , Youssef Mahmoud E. , Abdel-Hamed Mohamed R. , Amer Maha M. , Elghandour Sahar R. , Alkhamiss Abdullah S. , Mohamed Nahla B. , Khodeir Mostafa M. , Elsisi Hossam A. , Alsaeed Thamir Saad , Kamal Manal M. , Ellethy Abousree T. , Elesawy Basem H. , Saber Sameh
Published: September 2024

Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK/SIRT1/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK/SIRT1/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients.
Extrachromosomal circular DNAs in prostate adenocarcinoma: global characterizations and a novel prediction model
Authors: He Qingliu , Su Qingfu , Wei Chengcheng , Zhang Pu , Liu Weihui , Chen Junyi , Su Xiaoping , Zhuang Wei
Published: September 2024

Background

The role of focal amplifications and extrachromosomal circular DNA (eccDNA) is still uncertain in prostate adenocarcinoma (PRAD). Here, we first mapped the global characterizations of eccDNA and then investigate the characterization of eccDNA-amplified key differentially expressed encoded genes (eKDEGs) in the progression, immune response and immunotherapy of PRAD.

Methods

Circular_seq was used in conjunction with the TCGA-PRAD transcriptome dataset to sequence, annotate, and filter for eccDNA-amplified differentially expressed coding genes (eDEGs) in PRAD and para-cancerous normal prostate tissues. Afterwards, risk models were created and eKDEGs linked to the PRAD prognosis were identified using Cox and Lasso regression analysis. The immune microenvironment of the risk model was quantified using a variety of immunological algorithms, which also identified its characteristics with regard to immunotherapy, immune response, and immune infiltration.

Results

In this research, there was no significant difference in the size, type, and chromosomal distribution of eccDNA in PRAD and para-cancerous normal prostate tissues. However, 4,290 differentially expressed eccDNAs were identified and 1,981 coding genes were amplified. Following that, 499 eDEGs were tested in conjunction with the transcriptome dataset from TCGA-PRAD. By using Cox and Lasso regression techniques, ZNF330 and PITPNM3 were identified as eKDEGs of PRAD, and a new PRAD risk model was conducted based on this. Survival analysis showed that the high-risk group of this model was associated with poor prognosis and validated in external data. Immune infiltration analysis showed that the model risks affected immune cell infiltration in PRAD, not only mediating changes in immune cell function, but also correlating with immunophenotyping. Furthermore, the high-risk group was negatively associated with anti-CTLA-4/anti-PD-1 response and mutational burden. In addition, Tumor Immune Dysfunction and Exclusion analyses showed that high-risk group was more prone to immune escape. Drug sensitivity analyses identified 10 drugs, which were instructive for PRAD treatment.

Conclusion

ZNF330 and PITPNM are the eKDEGs for PRAD, which can be used as potential new prognostic markers. The two-factor combined risk model can effectively assess the survival and prognosis of PRAD patients, but also can predict the different responses of immunotherapy to PRAD patients, which may provide new ideas for PRAD immunotherapy.
Augmenting surveys with social media discourse on the workings of democracy from a cross-national perspective
Authors: Reveilhac Maud , Morselli Davide
Published: September 2024

This paper introduces an unsupervised framework that illustrates how insights gathered from opinion surveys regarding the functionality of democracy can be connected to social media messages of politicians on an international scale. By concentrating on the influence of social media messages from elected officials, the study adopts a “top-down” theoretical approach that links citizens’ attitudes towards democracy with the viewpoints about democracy expressed by politicians within social media discourses. Using a word embedding classification strategy, democracy-related themes are extracted from politicians’ messages. The research is conducted across 11 European countries, namely, Austria, Finland, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, and the United Kingdom. Switzerland is also included in the study because of its direct democracy system. The 10th round of the European Social Survey serves as the basis for assessing citizens’ democratic attitudes. The study encompasses two main analytical segments. First, aggregated analyses conducted at the country level reveal the degree of alignment between prominent democracy-related themes present in politicians’ discourse and citizens’ perceived significance of these same themes. Second, individual-level connections between social media data and survey respondents are established through their preferred political party (or orientation). Variable importance analysis is subsequently applied to explore which democracy-related themes conveyed by politicians hold significance in predicting public contentment with democracy.
Nothing personal, it’s the organization! Links between organizational culture, workplace bullying, and affective commitment
Authors: Galanaki Eleanna , Papalexandris Nancy , Zografou Irene , Pahos Nikolaos
Published: September 2024

Extensive attention in organizational research has been dedicated to workplace bullying, primarily focusing on its frequency and impact on both the victim and the bully, emphasizing interpersonal dynamics. This study extends current research by shifting the focus to the organizational level, examining the relationship between organizational culture and affective commitment, mediated by workplace bullying. Utilizing data from two surveys (N = 650 in 2012 and N = 553 in 2017), the study reveals that dimensions of organizational culture, such as assertiveness, performance orientation, and ingroup collectivism significantly influence work-related workplace bullying. Performance orientation and assertiveness are positively associated with increased bullying, whereas ingroup collectivism serves as a deterrent. In turn, work-related bullying negatively impacts affective commitment, while a culture characterized by high ingroup collectivism not only links negatively with bullying but also links positively with affective commitment. This work is one of the first studies to investigate the interplay among several dimensions of organizational culture, workplace bullying, and affective commitment, underscoring the importance of supportive organizational cultures in fostering healthy work environments.
Health literacy in adolescents and young adults in Benin: French translation and validation of the health literacy measure for adolescents (HELMA)
Authors: Ikediashi Bonaventure G. , Ehrmann Cristina , Michel Gisela
Published: September 2024

Background

The Health Literacy Measure for Adolescents (HELMA) is a self-assessment validated tool used to measure health literacy in adolescents. This study aims to evaluate the psychometric properties of the French translation of the Health Literacy Measure for Adolescents (F-HELMA).

Methods

The HELMA questionnaire was translated according to the World Health Organization's (WHO) recommendation for translation and adaptation of instruments. It was pre-tested with 30 students. Subsequently, 495 adolescents and young adults from five senior secondary high schools in Benin completed the questionnaire. A sample of 44 participants completed the questionnaire twice over a 2-week period to determine the test-retest reliability. Construct validity was evaluated using confirmatory factor analysis (CFA) and convergent validity was analyzed the Health Literacy Assessment Tool.

Results and discussion

The F-HELMA—French translation of the Health Literacy Measure for Adolescents, showed moderate to good psychometric properties. CFA showed good fit indices for a seven-factor model. Reliability figures fell within an acceptable range; Cronbach's alpha ranged from 0.64 (moderate) to 0.89 (good) across the different subscales, and the intraclass coefficient (ICC) ranged from 0.82 to 0.96, indicating good test-retest reliability. Pearson correlation with HLAT-8 showed good convergent validity (r = 0.54, p < 0.001). This study provides support for the use of the F-HELMA, as a valid and reliable instrument to measure health literacy in adolescents and young adults in West African French speaking countries.
Methodological aspects of the highly adaptive testing design for PISA
Authors: Fink Aron , König Christoph , Frey Andreas
Published: September 2024

This methods paper describes the methodological and statistical underpinnings of the highly adaptive testing design (HAT), which was developed for the Programme for International Student Assessment (PISA). The aim of HAT is to allow for a maximum of adaptivity in selecting items while taking the constraints of PISA into account with appropriate computer algorithms. HAT combines established methods from the area of computerized adaptive testing (a) to improve item selection when items are nested in units, (b) to make use of the correlation between the dimensions measured, (c) to efficiently accomplish constraint management, (d) to control for item position effects, and (e) to foster students’ test-taking experience. The algorithm is implemented using the programming language R and readers are provided with the necessary code. This should facilitate future implementations of the HAT design and inspire other adaptive testing designs that aim to maximize adaptivity while meeting constraints.
Dynamics of following and leading: association of movement synchrony and depression severity
Authors: Jennissen Simone , Sandmeir Anna , Schoenherr Desiree , Altmann Uwe , Nikendei Christoph , Schauenburg Henning , Friederich Hans-Christoph , Dinger Ulrike
Published: September 2024

Objective

Depression negatively affects interpersonal functioning and influences nonverbal behavior. Interpersonal theories of depression suggest that depressed individuals engage in behaviors that initially provoke others’ support and reassurance, but eventually lead to rejection that may also be expressed nonverbally.

Methods

This study investigated movement synchrony as a nonverbal indicator of support and rejection and its association with depression severity in a sample of depressed and healthy individuals. Semi-standardized diagnostic interview segments with N = 114 dyads were video recorded. Body movement was analyzed using Motion Energy Analysis, synchrony intervals were identified by computing windowed cross-lagged correlation and a peak-picking-algorithm. Depression severity was assessed via both self-rating (BDI-II) and clinician rating (HAMD).

Results

Both self-rated and clinician-rated depression severity were negatively correlated with patient-led, but not clinician-led movement synchrony measures. The more depressed patients were, the less they initiated movement synchrony with their clinicians. These correlations remained significant after controlling for gender, age, gross body movement, and psychopharmacological medication.

Conclusion

Findings suggest that depression may negatively affect patients’ active initiative in interaction situations. Automatized methods as used in this study can add valuable information in the diagnosis of depression and the assessment of associated social impairments.
Accelerating rare disease detection: an experience of multidisciplinary team model in undiagnosed diseases program in a children’s hospital
Authors: Shi Yu , Miao Shijian , Yuan Yuan , Fu Yang , Sun Chengjun , Wang Hongsheng , Ge MengMeng , Li Dongyun , Shen Guomei , Gao Xuan , Zhai Xiaowen
Published: September 2024

Background

A definite diagnosis goes undiscovered for a percentage of children with undiagnosed disorders, with significant medical, psychological, and social effects. Other than specialized clinical centers, exceptional molecular studies, common procedures, and devoted activities at the national and international levels, children with complex undiagnosed disorders require innovative approaches.

Methods

In March 2016, Children’s hospital of Fudan university represented the Children’s Undiagnosed Diseases Program (UDP). The purpose of this study is to describe the project findings and underline the critical significance of multidisciplinary teamwork in China’s undiagnosed rare illnesses program. We investigated the 758 cases in our UDP system retrospectively. Demographic information, laboratory test results, and genetic information were gathered.

Results

Between January 2017 and December 2021, 758 cases were examined. Males made up 436 (57.5%) of the total. Over half of the patients were children under the age of five. The average patient course time preceding admission to UDP was 6.0 months (95% CI 10.512.6). These patients visited an average of 1.8 clinics during their diagnostic journey. Except for 69 individuals (90.9%), all had more than one presenting symptom in various organs: 460 (60.7%) had neurology difficulties, 151 (19.9%) had endocrine problems, and 141 (18.6%) had immunology problems. UDP has a diagnosis rate of 61.3%. Genetic testing was performed on 469 of the 758 patients, for a genetic diagnosis rate of 15.8%. The UDP method has a sensitivity of 94.5%, a specificity of 86.4%, a positive predictive value of 92.8%, and an negative predictive value of 89.5%.

Conclusion

Our UDP targets an unmet need, namely the diagnosis of patients with complicated, multisystem illnesses. Using a multidisciplinary team model approach, this UDP pilot study achieved a reasonable diagnosis success rate, increasing the possibility of more diagnoses and new scientific discoveries of difficult and rare diseases.
Loneliness and pain among community-dwelling middle-aged and older Black, Latino, and White adults in the United States
Authors: Camacho David , Burnette Denise , Aranda Maria P. , Moxley Jerad H. , Lukens Ellen P. , Reid M. Carrington , Wethington Elaine
Published: September 2024

Background

Prior research has demonstrated a strong and independent association between loneliness and pain, but few studies to date have explored this relationship in racially and ethnically diverse groups of midlife and older adults. We drew on the diathesis stress model of chronic pain and cumulative inequality theory to examine the relationship of loneliness and the presence and intensity of pain in a nationally representative sample of Black, Latino, and White adults aged 50 or older in the United States.

Methods

Data were from Wave 3 of the National Social Life, Health, and Aging Project (n = 2,706). We used weighted logistic and ordinary least squares regression analyses to explore main and interactive effects of loneliness and race and ethnicity while adjusting for well-documented risk and protective factors (e.g., educational attainment, perceived relative income, inadequate health insurance, perceived discrimination) and salient social and health factors.

Results

Almost half (46%) of the participants reported feeling lonely and 70% reported the presence of pain. Among those who reported pain (n = 1,910), the mean intensity score was 2.89 (range = 1–6) and 22% reported severe or stronger pain. Greater loneliness was associated with increased odds of pain presence (AOR = 1.154, 95% CI [1.072, 1.242]) and higher pain intensity (β = 0.039, p < 0.01). We found no significant interaction effects involving Black participants. However, Latino participants who reported greater loneliness had significantly higher levels of pain (β = 0.187, p < 0.001) than their White counterparts with similar levels of loneliness.

Discussion

Loneliness is an important correlate of pain presence and intensity and may have a stronger effect on pain intensity among Latino adults aged 50 or older. We discuss clinical and research implications of these findings, including the need for more fine-grained analyses of different types of loneliness (e.g., social, emotional, existential) and their impact on these and other pain-related outcomes (e.g., interference). Our findings suggest a need for interventions to prevent and manage pain by targeting loneliness among middle-aged and older adults, particularly Latino persons.
Uncertainty quantification in multi-class image classification using chest X-ray images of COVID-19 and pneumonia
Authors: Whata Albert , Dibeco Katlego , Madzima Kudakwashe , Obagbuwa Ibidun
Published: September 2024

This paper investigates uncertainty quantification (UQ) techniques in multi-class classification of chest X-ray images (COVID-19, Pneumonia, and Normal). We evaluate Bayesian Neural Networks (BNN) and the Deep Neural Network with UQ (DNN with UQ) techniques, including Monte Carlo dropout, Ensemble Bayesian Neural Network (EBNN), Ensemble Monte Carlo (EMC) dropout, across different evaluation metrics. Our analysis reveals that DNN with UQ, especially EBNN and EMC dropout, consistently outperform BNNs. For example, in Class 0 vs. All, EBNN achieved a UAcc of 92.6%, UAUC-ROC of 95.0%, and a Brier Score of 0.157, significantly surpassing BNN's performance. Similarly, EMC Dropout excelled in Class 1 vs. All with a UAcc of 83.5%, UAUC-ROC of 95.8%, and a Brier Score of 0.165. These advanced models demonstrated higher accuracy, better discriaminative capability, and more accurate probabilistic predictions. Our findings highlight the efficacy of DNN with UQ in enhancing model reliability and interpretability, making them highly suitable for critical healthcare applications like chest X-ray imageQ6 classification.