bluuebunny/crossref_metadata_2025 huggingface dataset:
Geriatric drug trials on solid tumor are scarce worldwide
Authors: Huang Huiyao , Cui Dandan , Leng Ye , Zhang Kaiting , Yu Anqi , Wang Yanting , Wu Hanli , Tang Yu , Yu Feng , Li Ning
Published: February 2023

Background

Conducting geriatric trials is the most feasible way to address the vast underrepresentation of older adults in clinical trials of cancer therapies. This study is a globally comprehensive examination of geriatric trials for solid tumor worldwide over the last decade.

Methods

Up-to-date information on cancer drug trials in older adults aged over 59 years from the beginning of 2012 to the end of 2021 was collected from Trialtrove and Pharmaprojects. The number of identified trials was the dependent variable and corresponding analysis was conducted from the perspective of time trend, status quo and comparisons by region and country, sponsor type and cancer type, study status and phase.

Results

A total of 292 geriatric cancer drug trials were identified, of which 287 were single-region studies, 219 were initiated by academic groups, and 55 (18.8%) were terminated. Decreasing trends in the annual number of all trials (−9.2% per year) and the annual number of trials by academic groups (−9.4%) were observed over time. Of the geriatric trials, 183 were conducted in Asia; this number was significantly higher than that in Europe (74), North America (37), Oceania (4), and South America (1). Similar difference was found in participation rate in trials by academic groups ranging from 71.7% in Asia to 0.5% in South America. Of the trials, 19 and 97 were initiated before drug and indication approval, respectively, and the remaining 176 were initiated after indication approval. Phase II trials accounted for the highest proportion of trials (213, 72.9%), while phase I trials accounted for the lowest proportion (14, 4.8%). Trials by academic groups had a higher termination rate (21.5% vs. 11.0%) and fewer were phase IV trials (8.2% vs. 21.9%). Treatment was explored for 16 different cancers, with lung, colorectal and breast cancers being the most common.

Conclusion

Geriatric trials of solid tumor drugs are scarce and partially prematurely terminated. Moreover, the number of geriatric trials has decreased and differs according to region. Global guidance and regulatory supervision are needed to facilitate the acquisition of adequate evidence on drug risk-benefit profiles in older adults, and thus to achieve high-quality care and safe medication.
The cytokine milieu of bullous pemphigoid: Current and novel therapeutic targets
Authors: Maglie Roberto , Solimani Farzan , Didona Dario , Pipitò Carlo , Antiga Emiliano , Di Zenzo Giovanni
Published: February 2023

Bullous pemphigoid (BP) is the most common autoimmune bullous disease, characterized by severe pruritus and skin blistering. The loss of tolerance against Collagen XVII, also referred to as BP180, is the main pathogenic event of BP, leading to production of IgG autoantibodies which mainly target the juxtamembranous extracellular non-collagenous 16th A (NC16A) domain of BP180. A complex inflammatory network is activated upon autoantibody binding to the basement membrane zone; this inflammatory loop involves the complement cascade and the release of several inflammatory cytokines, chemokines and proteases from keratinocytes, lymphocytes, mast cells and granulocytes. Collectively, these events disrupt the integrity of the dermal-epidermal junction, leading to subepidermal blistering. Recent advances have led to identify novel therapeutic targets for BP, whose management is mainly based on the long-term use of topical and systemic corticosteroids. As an example, targeting type-2 T-helper cell-associated cytokines, such as Interleukin-4 and interleukin-13 has shown meaningful clinical efficacy in case series and studies; targeting IL-17 and IL-23 has also been tried, owing to an important role of these cytokines in the chronic maintenance phase of BP. In this review article, we discuss the complex cytokine milieu that characterized BP inflammation, highlighting molecules, which are currently investigated as present and future therapeutic targets for this life-threatening disease.
Global distribution, traditional and modern detection, diagnostic, and management approaches of Rhizoctonia solani associated with legume crops
Authors: Akber Muhammad Abdullah , Mubeen Mustansar , Sohail Muhammad Aamir , Khan Sher Wali , Solanki Manoj Kumar , Khalid Rida , Abbas Aqleem , Divvela Praveen Kumar , Zhou Lei
Published: February 2023

Sustainable development relies heavily on a food system that is both safe and secure. Several approaches may lead to sustainability and food safety. An increase in the cultivation of legume crops is one of the approaches for enhancing agricultural viability and ensuring adequate food supply. Legumes may increase daily intake of fiber, folate, and protein as substitutes for meat and dairy. They are also crucial in various intercropping systems worldwide. However, legume production has been hampered by Rhizoctonia solani due to its destructive lifestyle. R. solani causes blights, damping off, and rotting diseases in legume crops. Our knowledge of the global distribution of R. solani associated with legume crops (alfalfa, soybean, chickpea, pea, lentil, common bean, and peanut), detection, diagnosis, and management of legume crops diseases caused by R. solani is limited. Traditional approaches rely on the incubation of R. solani, visual examination of symptoms on host legume crops, and microscopy identification. However, these approaches are time-consuming, require technical expertise, fail to detect a minimal amount of inoculum, and are unreliable. Biochemical and molecular-based approaches have been used with great success recently because of their excellent sensitivity and specificity. Along with conventional PCR, nested PCR, multiplex PCR, real-time PCR, magnetic-capture hybridization PCR, and loop-mediated isothermal amplification have been widely used to detect and diagnose R. solani. In the future, Next-generation sequencing will likely be used to a greater extent to detect R. solani. This review outlines global distribution, survival, infection and disease cycle, traditional, biochemical, molecular, and next-generation sequencing detection and diagnostic approaches, and an overview of the resistant resources and other management strategies to cope with R. solani.
Phenotypic and genetic alterations of Burkholderia pseudomallei in patients during relapse and persistent infections
Authors: Seng Rathanin , Phunpang Rungnapa , Saiprom Natnaree , Dulsuk Adul , Chewapreecha Claire , Thaipadungpanit Janjira , Batty Elizabeth M. , Chantratita Wasun , West T. Eoin , Chantratita Narisara
Published: February 2023

The bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a severe tropical disease associated with high mortality and relapse and persistent infections. Treatment of melioidosis requires prolonged antibiotic therapy; however, little is known about relapse and persistent infections, particularly the phenotypic and genetic alterations of B. pseudomallei in patients. In this study, we performed pulsed-field gel electrophoresis (PFGE) to compare the bacterial genotype between the initial isolate and the subsequent isolate from each of 23 suspected recurrent and persistent melioidosis patients in Northeast Thailand. We used whole-genome sequencing (WGS) to investigate multilocus sequence types and genetic alterations of within-host strain pairs. We also investigated the bacterial phenotypes associated with relapse and persistent infections, including multinucleated giant cell (MNGC) formation efficiency and intracellular multiplication. We first identified 13 (1.2%) relapse, 7 (0.7%) persistent, and 3 (0.3%) reinfection patients from 1,046 survivors. Each of the 20 within-host strain pairs from patients with relapse and persistent infections shared the same genotype, suggesting that the subsequent isolates arise from the infecting isolate. Logistic regression analysis of clinical data revealed regimen and duration of oral antibiotic therapies as risk factors associated with relapse and persistent infections. WGS analysis demonstrated 17 within-host genetic alteration events in 6 of 20 paired isolates, including a relatively large deletion and 16 single-nucleotide polymorphism (stocktickerSNP) mutations distributed across 12 genes. In 1 of 20 paired isolates, we observed significantly increased cell-to-cell fusion and intracellular replication in the second isolate compared with the initial isolate from a patient with persistent infection. WGS analysis suggested that a non-synonymous mutation in the tssB-5 gene, which encoded an essential component of the type VI secretion system, may be associated with the increased intracellular replication and MNGC formation efficiency of the second isolate of the patient. This information provides insights into genetic and phenotypic alterations in B. pseudomallei in human melioidosis, which may represent a bacterial strategy for persistent and relapse infections.
Efficacy of IAPP suppression in mouse and human islets by GLP-1 analogue conjugated antisense oligonucleotide
Authors: Gurlo Tatyana , Prakash Thazha P. , Wang Zhongying , Archang Maani , Pei Lina , Rosenberger Madeline , Pirie Elaine , Lee Richard G. , Butler Peter C.
Published: February 2023

Insulin resistance is the major risk factor for Type 2 diabetes (T2D). In vulnerable individuals, insulin resistance induces a progressive loss of insulin secretion with islet pathology revealing a partial deficit of beta cells and islet amyloid derived from islet amyloid polypeptide (IAPP). IAPP is co-expressed and secreted with insulin by beta cells, expression of both proteins being upregulated in response to insulin resistance. If IAPP expression exceeds the threshold for clearance of misfolded proteins, beta cell failure occurs exacerbated by the action of IAPP toxicity to compromise the autophagy lysosomal pathway. We postulated that suppression of IAPP expression by an IAPP antisense oligonucleotide delivered to beta cells by the GLP-1 agonist exenatide (eGLP1-IAPP-ASO) is a potential disease modifying therapy for T2D. While eGLP1-IAPP-ASO suppressed mouse IAPP and transgenic human IAPP expression in mouse islets, it had no discernable effects on IAPP expression in human islets under the conditions studied. Suppression of transgenic human IAPP expression in mouse islets attenuated disruption of the autophagy lysosomal pathway in beta cells, supporting the potential of this strategy.
Association of inflammation and cognition in the elderly: A systematic review and meta-analysis
Authors: Leonardo Sofia , Fregni Felipe
Published: February 2023

Background

The development of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) may be associated with an inflammatory process. Inflammatory cytokines may be a surrogate for systemic inflammation leading to worsening neurological function. We aim to investigate the association between cognitive impairment and inflammation by pooling and analyzing the data from previously published studies.

Methods

We performed a systematic literature search on MEDLINE, PubMed, Embase, Web of Science, and Scopus for prospective longitudinal and cross-sectional studies evaluating the relationship between inflammation and cognitive functions.

Results

A total of 79 articles were included in our systematic review and meta-analysis. Pooled estimates from cross-sectional studies have demonstrated an increased level of C-reactive protein (CRP) [Hedges’s g 0.35, 95% CI (0.16, 0.55), p < 0.05], IL-1β [0.94, 95% CI (−0.04, 1.92), p < 0.05], interleukin-6 (IL-6) [0.46, 95% CI (0.05, 0.88), p < 0.005], TNF alpha [0.22, 95% CI (−0.24, 0.68), p < 0.05], sTNFR-1 [0.74, 95% CI (0.46, 1.02), p < 0.05] in AD compared to controls. Similarly, higher levels of IL-1β [0.17, 95% CI (0.05, 0.28), p < 0.05], IL-6 [0.13, 95% CI (0.08, 0.18), p < 0.005], TNF alpha [0.28, 95% CI (0.07, 0.49), p < 0.05], sTNFR-1 [0.21, 95% CI (0.05, 0.48), p < 0.05] was also observed in MCI vs. control samples. The data from longitudinal studies suggested that levels of IL-6 significantly increased the risk of cognitive decline [OR = 1.34, 95% CI (1.13, 1.56)]. However, intermediate levels of IL-6 had no significant effect on the final clinical endpoint [OR = 1.06, 95% CI (0.8, 1.32)].

Conclusion

The data from cross-sectional studies suggest a higher level of inflammatory cytokines in AD and MCI as compared to controls. Moreover, data from longitudinal studies suggest that the risk of cognitive deterioration may increase by high IL-6 levels. According to our analysis, CRP, antichymotrypsin (ACT), Albumin, and tumor necrosis factor (TNF) alpha may not be good surrogates for neurological degeneration over time.
Rats chirp with their mouth full: During an experimental meal, adult male Wistar rats emitted flat ultrasonic vocalisations upon feeding
Authors: Champeil-Potokar Gaelle , Kreichati Léa , Rampin Olivier , Denis Isabelle , Darcel Nicolas , Bombail Vincent
Published: February 2023

Rats produce ultrasonic vocalisation (USVs) that are classified into different types, based on their average frequency. In pups 40 kHz USVs are produced upon social isolation, and in adults USVs can be associated with affective states and specific behavioural patterns (i.e., appetitive 50 kHz vocalisations of frequency range 30−100 kHz, or aversive 20 kHz vocalisations of frequency range 18−30 kHz). Generally, USVs of frequency around 50 kHz are linked to activation of brain reward pathways, during anticipation or experience of rewarding stimuli. Previous studies have described several subtypes of 50 kHz USVs, according to their acoustic properties. We asked whether USV production might be relevant to feeding behaviour. We recorded USVs from 14-week old adult rats during the satisfaction of a physiological need: refeeding following mild food deprivation (17 h overnight fast). We analysed a 10 min consummatory phase, preceded by a 10 min anticipatory phase, as a control for the experimental meal. Following identification of USV subtypes, we applied frequentist and Bayesian (Monte Carlo shuffling) statistical analyses to investigate the relationship between USV emission and rat behaviour. We found that it was not total USV quantity that varied in response to food consumption, but the subtype of USV produced. Most importantly we found that rats who feed tend to produce flat USVs of a frequency around 40 kHz. Beyond the previous reports of circumstantial association feeding-flat USVs, our observation directly correlate vocalisation and ingestive behaviour. Our study highlights that, in addition to quantification of the production rate, study of USV subtypes might inform us further on rat consummatory behaviour. Since this vocalisation behaviour can have a communicative purpose, those findings also illustrate nutrition studies might benefit from considering the possible social dimension of feeding behaviour.
Conventional machine learning and deep learning in Alzheimer's disease diagnosis using neuroimaging: A review
Authors: Zhao Zhen , Chuah Joon Huang , Lai Khin Wee , Chow Chee-Onn , Gochoo Munkhjargal , Dhanalakshmi Samiappan , Wang Na , Bao Wei , Wu Xiang
Published: February 2023

Alzheimer's disease (AD) is a neurodegenerative disorder that causes memory degradation and cognitive function impairment in elderly people. The irreversible and devastating cognitive decline brings large burdens on patients and society. So far, there is no effective treatment that can cure AD, but the process of early-stage AD can slow down. Early and accurate detection is critical for treatment. In recent years, deep-learning-based approaches have achieved great success in Alzheimer's disease diagnosis. The main objective of this paper is to review some popular conventional machine learning methods used for the classification and prediction of AD using Magnetic Resonance Imaging (MRI). The methods reviewed in this paper include support vector machine (SVM), random forest (RF), convolutional neural network (CNN), autoencoder, deep learning, and transformer. This paper also reviews pervasively used feature extractors and different types of input forms of convolutional neural network. At last, this review discusses challenges such as class imbalance and data leakage. It also discusses the trade-offs and suggestions about pre-processing techniques, deep learning, conventional machine learning methods, new techniques, and input type selection.
Prader–Willi syndrome: Symptoms and topiramate response in light of genetics
Authors: Louveau Cécile , Turtulici Mimi-Caterina , Consoli Angèle , Poitou Christine , Coupaye Muriel , Krebs Marie-Odile , Chaumette Boris , Iftimovici Anton
Published: February 2023

Introduction

Prader–Willi Syndrome (PWS) is a rare genetic condition, which affects one in 25,000 births and results in various phenotypes. It leads to a wide range of metabolic and endocrine disorders including growth delay, hypogonadism, narcolepsy, lack of satiety and compulsive eating, associated with mild to moderate cognitive impairment. Prognosis is especially determined by the complications of obesity (diabetes, cardiorespiratory diseases) and by severe behavioral disorders marked by impulsivity and compulsion. This heterogeneous clinical picture may lead to mis- or delayed diagnosis of comorbidities. Moreover, when diagnosis is made, treatment remains limited, with high interindividual differences in drug response. This may be due to the underlying genetic variability of the syndrome, which can involve several different genetic mutations, notably deletion or uniparental disomy (UPD) in a region of chromosome 15. Here, we propose to determine whether subjects with PWS differ for clinical phenotype and treatment response depending on the underlying genetic anomaly.

Methods

We retrospectively included all 24 PWS patients who were referred to the Reference Center for Rare Psychiatric Disorders (GHU Paris Psychiatrie and Neurosciences) between November 2018 and July 2022, with either deletion (N = 8) or disomy (N = 16). The following socio-demographic and clinical characteristics were recorded: age, sex, psychiatric and non-psychiatric symptoms, the type of genetic defect, medication and treatment response to topiramate, which was evaluated in terms of eating compulsions and impulsive behaviors. We compared topiramate treatment doses and responses between PWS with deletion and those with disomy. Non-parametric tests were used with random permutations for p-value and bootstrap 95% confidence interval computations.

Results

First, we found that disomy was associated with a more severe clinical phenotype than deletion. Second, we observed that topiramate was less effective and less tolerated in disomy, compared to deletion.

Discussion

These results suggest that a pharmacogenomic-based approach may be relevant for the treatment of compulsions in PWS, thus highlighting the importance of personalized medicine for such complex heterogeneous disorders.
Development of a quantitative measurement on visual clutter in see through display
Authors: Liu Qingfeng , Wang Yanyan , Bai Yu , Yu Mengsun , Cao Zhengtao , Yu Xinli , Ding Li
Published: February 2023

Objective

With the wide use of transmission displays to improve operation performance, the display information highlights clutter because of the contradiction between the massive amount of information and limited display area. Our study aimed to develop a quantitative measurement for declutter design and appraisal.

Methods

Using the ergonomics research system of characters and symbols in a see-through cockpit display, we set the simulated flight task interface at four pixel scale levels by enlarging all the display elements in a certain ratio. Flight task videos of 12 clutter degrees were recorded using each flight interface matched with three flight scene complexity levels. A total of 60 pilots completed the visual search tasks in the flight task video while the eye tracker was used to record the view path in real time. Visual search performance was analyzed to study the effect of various clutter factors and levels on pilots’ performance in visual search tasks, and acquire quantitative clutter measure parameters.

Results

GLM univariate test revealed that there were significant differences among the fixation time in areas of interest (AOI), total Fixation point number, total fixation time at four pixel scale levels, and three flight scene complexity levels (P < 0.05). Visual search performance declined after the cutoff point, while the clutter degree increased. According to the visual search performance data, the recommend feature congestion upper pixel number limit in a 600*800 display was 18,576, and the pixel ratio was 3.87%.

Conclusion

A quantitative measurement for declutter design and appraisal of cockpit displays was developed, which can be used to support see-through display design.
A multi-object deep neural network architecture to detect prostate anatomy in T2-weighted MRI: Performance evaluation
Authors: Baldeon-Calisto Maria , Wei Zhouping , Abudalou Shatha , Yilmaz Yasin , Gage Kenneth , Pow-Sang Julio , Balagurunathan Yoganand
Published: February 2023

Prostate gland segmentation is the primary step to estimate gland volume, which aids in the prostate disease management. In this study, we present a 2D-3D convolutional neural network (CNN) ensemble that automatically segments the whole prostate gland along with the peripheral zone (PZ) (PPZ-SegNet) using a T2-weighted sequence (T2W) of Magnetic Resonance Imaging (MRI). The study used 4 different public data sets organized as Train #1 and Test #1 (independently derived from the same cohort), Test #2, Test #3 and Test #4. The prostate gland and the peripheral zone (PZ) anatomy were manually delineated with consensus read by a radiologist, except for Test #4 cohorts that had pre-marked glandular anatomy. A Bayesian hyperparameter optimization method was applied to construct the network model (PPZ-SegNet) with a training cohort (Train #1, n = 150) using a five-fold cross validation. The model evaluation was performed on an independent cohort of 283 T2W MRI prostate cases (Test #1 to #4) without any additional tuning. The data cohorts were derived from The Cancer Imaging Archives (TCIA): PROSTATEx Challenge, Prostatectomy, Repeatability studies and PROMISE12-Challenge. The segmentation performance was evaluated by computing the Dice similarity coefficient and Hausdorff distance between the estimated-deep-network identified regions and the radiologist-drawn annotations. The deep network architecture was able to segment the prostate gland anatomy with an average Dice score of 0.86 in Test #1 (n = 192), 0.79 in Test #2 (n = 26), 0.81 in Test #3 (n = 15), and 0.62 in Test #4 (n = 50). We also found the Dice coefficient improved with larger prostate volumes in 3 of the 4 test cohorts. The variation of the Dice scores from different cohorts of test images suggests the necessity of more diverse models that are inclusive of dependencies such as the gland sizes and others, which will enable us to develop a universal network for prostate and PZ segmentation. Our training and evaluation code can be accessed through the link: https://github.com/mariabaldeon/PPZ-SegNet.git.
Selenium-enriched plant foods: Selenium accumulation, speciation, and health functionality
Authors: Tangjaidee Pipat , Swedlund Peter , Xiang Jiqian , Yin Hongqing , Quek Siew Young
Published: February 2023

Selenium (Se) is an essential element for maintaining human health. The biological effects and toxicity of Se compounds in humans are related to their chemical forms and consumption doses. In general, organic Se species, including selenoamino acids such as selenomethionine (SeMet), selenocystine (SeCys2), and Se-methylselenocysteine (MSC), could provide greater bioactivities with less toxicity compared to those inorganics including selenite (Se IV) and selenate (Se VI). Plants are vital sources of organic Se because they can accumulate inorganic Se or metabolites and store them as organic Se forms. Therefore, Se-enriched plants could be applied as human food to reduce deficiency problems and deliver health benefits. This review describes the recent studies on the enrichment of Se-containing plants in particular Se accumulation and speciation, their functional properties related to human health, and future perspectives for developing Se-enriched foods. Generally, Se’s concentration and chemical forms in plants are determined by the accumulation ability of plant species. Brassica family and cereal grains have excessive accumulation capacity and store major organic Se compounds in their cells compared to other plants. The biological properties of Se-enriched plants, including antioxidant, anti-diabetes, and anticancer activities, have significantly presented in both in vitro cell culture models and in vivo animal assays. Comparatively, fewer human clinical trials are available. Scientific investigations on the functional health properties of Se-enriched edible plants in humans are essential to achieve in-depth information supporting the value of Se-enriched food to humans.
Effects of kiwi fruit (Actinidia chinensis) polysaccharides on metabolites and gut microbiota of acrylamide-induced mice
Authors: Chen Mengyin , Chen Xuefeng , Wang Ketang , Cai Luyang , Liu Nannan , Zhou Duan , Jia Wei , Gong Pin , Liu Ning , Sun Yujiao
Published: February 2023

Introduction

Kiwifruit (Actinidia chinensis) has rich nutritious and medicinal properties. It is widely consumed worldwide for the intervention of metabolism disorders, however, the underlying mechanism remains unclear. Acrylamide, a well-known toxic ingredient, mainly forms in high-temperature processed carbohydrate-rich food and causes disorders of gut microbiota and systemic metabolism.

Methods

This study explored the protective effects and underlying mechanisms of kiwifruit polysaccharides against acrylamide-induced disorders of gut microbiota and systemic metabolism by measuring the changes of gut microbiota and serum metabolites in mice.

Results

The results showed that kiwifruit polysaccharides remarkably alleviated acrylamide-induced toxicity in mice by improving their body features, histopathologic morphology of the liver, and decreased activities of liver function enzymes. Furthermore, the treatment restored the healthy gut microbiota of mice by improving the microbial diversity and abundance of beneficial bacteria such as Lactobacillus. Metabolomics analysis revealed the positive effects of kiwifruit polysaccharides mainly occurred through amino and bile acid-related metabolism pathways including nicotinate and nicotinamide metabolism, primary bile acid biosynthesis, and alanine, aspartate and glutamate metabolism. Additionally, correlation analysis indicated that Lactobacillus exhibited a highly significant correlation with critical metabolites of bile acid metabolism.

Discussion

Concisely, kiwifruit polysaccharides may protect against acrylamide-induced toxicity by regulating gut microbiota and metabolism.
Transcription factor E2F8 is a therapeutic target in the basal-like subtype of breast cancer
Authors: Zheng Jing , Huang Jingyi , Xia Jinquan , Zhou Wenbin , Dai Lingyun , Lin Sihang , Gao Lin , Zou Chang
Published: February 2023

Introduction

Tumorigenesis in breast cancers usually accompanied by the dysregulation of transcription factors (TFs). Abnormal amplification of TFs leads aberrant expression of its downstream target genes. However, breast cancers are heterogeneous disease with different subtypes that have distinguished clinical behaviours, and the identification of prognostic TFs may enable to provide diagnosis and treatment of breast cancer based on subtypes, especially in Basal-like breast cancer.

Methods

The RNA-sequencing was performed to screen differential TFs in breast cancer subtypes. The GEPIA dataset analysis was used to analyze the genes expression in invasive breast carcinoma. The expression of MYBL2, HOXC13, and E2F8 was verified by qRT-PCR assay in breast cancers. The depiction analysis of co-expressed proteins was revealed using the STRING datasets. The cellular infiltration level analysis by the TISIDB and TIMER databases. The transwell assay was performed to analyze cellular migration and invasion. CCK-8 assay was used to evaluate cellular drug susceptibility for docetaxel treatment. Predicted targeted drugs in breast cancers by GSCA Lite database online.

Results

Kaplan-Meier plotter suggested that high expression of both E2F8 and MYBL2 in Basal-like subtype had a poor relapse-free survival. Functional enrichment results identified that apoptosis, cell cycle, and hormone ER pathway were represented the crucial regulation pathways by both E2F8 and MYBL2. In the meantime, database analysis indicated that high expression of E2F8 responded to chemotherapy, while those patients of high expression of MYBL2 responded to endocrinotherapy, and a positive correlation between the expression of E2F8 and PD-L1/CTLA4. Our cell line experiments confirmed the importance of E2F8 and MYBL2 in proliferation and chemotherapy sensitivity, possibly, the relationship with PD-L1. Additionally, we also observed that the up-regulation of E2F8 was accompanied with higher enrichments of CD4+ T cells and CD8+ T cells in breast cancers.

Conclusion

Taken together, our findings elucidated a prospective target in Basal-like breast cancer, providing underlying molecular biomarkers for the development of breast cancer treatment.
Network pharmacology, molecular docking, and experimental verification reveal the mechanism of San-Huang decoction in treating acute kidney injury
Authors: Liu Jiahui , Li Zhongtang , Lao Yunlan , Jin Xiaoming , Wang Yuzhi , Jiang Beibei , He Riming , Yang Shudong
Published: February 2023

Background: Cisplatin is an effective anti-tumor drug. However, its usage is constrained by side effects such as nephron toxicity. Cisplatin-induced acute kidney injury (AKI) appears in approximately 20%–30% of cases. Hence, finding an effective protective strategy is necessary. San-Huang decoction (SHD) is a Chinese herbal decoction with good efficacy in treating chronic kidney disease (CKD). Nevertheless, the mechanism of SHD on AKI remains unclear. Consequently, we proposed to explore the potential mechanism of SHD against cisplatin-induced AKI.

Methods: Active compounds, core target proteins, and associated signaling pathways of SHD were predicted through network pharmacology. Then confirmed by molecular docking. In vivo experiment, Cisplatin + SHD group was treated with SHD (6.5 g/kg/day) for 6 days before building the model. An AKI model was established with a single intraperitoneal injection of cisplatin at 20 mg/kg. After 72 h of cisplatin injection, all mice were sacrificed to collect blood and kidney tissues for verification of network pharmacology analysis.

Results: We found that calycosin, rhein, and ginsenoside Rh2 may be SHD’s primary active compounds in treating cisplatin-induced AKI, and AKT, TNF-α, IL-6, IL-1β, caspase-3, and MMP9 are the core target proteins. The relationship between the compound and target protein was further confirmed by molecular docking. The Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses predicted that SHD has an anti-inflammatory role through the TNF and IL-17 signaling pathway. Moreover, Western blot and immunohistochemistry validated the potential molecular mechanisms of SHD, predicted from network pharmacology analysis. The mechanism of cisplatin-induced AKI involves apoptosis and inflammation. In apoptosis, Caspase-3, caspase-8, caspase-9, and Bax proteins were down-regulated, while Bcl-2 was up-regulated by SHD. The differential expression of MMP protein is involved in the pathological process of AKI. MMP9 protects from glomerular tubule damage. MMP9 and PI3K/AKT anti-apoptosis pathway were up-regulated by SHD. In addition, we discovered that SHD alleviated AKI by inhibiting the NF-κB signaling pathway.

Conclusion: SHD plays a critical role in anti-inflammation and anti-apoptosis via inhibiting the NF-κB signaling pathway and activating PI3K/AKT anti-apoptosis pathway, indicating that SHD is a candidate herbal drug for further investigation in treating cisplatin-induced AKI.
Identification of the molecular characteristics associated with microsatellite status of colorectal cancer patients for the clinical application of immunotherapy
Authors: Fu Jie , Jin Xiaoxin , Chen Weidong , Chen Zongyao , Wu Peidong , Xiao Wang , Liu Yuhang , Deng Shuangya
Published: February 2023

Background: Mismatch repair-proficient (pMMR) microsatellite stability (MSS) in colorectal cancer (CRC) indicates an unfavorable therapeutic response to immunotherapy with immune checkpoint inhibitors (ICIs). However, the molecular characteristics of CRC patients with pMMR MSS remain largely unknown.

Methods: Heterogeneities between mismatch repair-deficient (dMMR) microsatellite instability (MSI) and pMMR MSS CRC patients were investigated at the single-cell level. Next, an MSS-related risk score was constructed by single-sample gene set enrichment analysis (ssGSEA). The differences in immune and functional characteristics between the high- and low-score groups were systematically analyzed.

Results: Based on the single-cell RNA (scRNA) atlas, an MSS-specific cancer cell subpopulation was identified. By taking the intersection of the significant differentially expressed genes (DEGs) between different cancer cell subtypes of the single-cell training and validation cohorts, 29 MSS-specific cancer cell marker genes were screened out for the construction of the MSS-related risk score. This risk score signature could efficiently separate pMMR MSS CRC patients into two subtypes with significantly different immune characteristics. The interactions among the different cell types were stronger in the MSS group than in the MSI group, especially for the outgoing signals of the cancer cells. In addition, functional differences between the high- and low-score groups were preliminarily investigated.

Conclusion: In this study, we constructed an effective risk model to classify pMMR MSS CRC patients into two completely different groups based on the specific genes identified by single-cell analysis to identify potential CRC patients sensitive to immunotherapy and screen effective synergistic targets.
Advances of berberine against metabolic syndrome-associated kidney disease: Regarding effect and mechanism
Authors: Liu Ya-Fei , Wang Huan-Huan , Geng Yin-Hong , Han Liang , Tu Sheng-Hao , Wang Hui
Published: February 2023

The prevalence of metabolic syndrome (MetS) is drastically growing worldwide, resulting in MetS-associated kidney disease. According to traditional theories, preventing blood pressure, lipid, glycose, and obesity and improving insulin resistance (IR), a couple of medications are required for MetS. It not only lowers patients’ compliance but also elevates adverse reactions. Accordingly, we attempted to seek answers from complementary and alternative medicine. Ultimately, berberine (BBR) was chosen due to its efficacy and safety on MetS through multi-pathways and multi-targets. The effects and mechanisms of BBR on obesity, IR, diabetic nephropathy, hypertension, hyperlipidemia, and hyperuricemia were elaborated. In addition, the overall properties of BBR and interventions for various kidney diseases were also collected. However, more clinical trials are expected to further identify the beneficial effects of BBR.
Evaluating the status of theories of emotion in political science and psychology
Authors: Marcus George E.
Published: February 2023

Emotion is an increasingly influential area of research in psychology, political psychology, political science, and other social sciences. Research is best when driven by theory because the absence of theory generates research that can lack coherence and precision of language and meaning from one study to another, from one program of research to another. In brief, a theory provides essential binding foundations that enable scientific explanations to be rigorously tested. Furthermore, reliance on incomplete or unsound theories tends to generate flawed results. I evaluate four current emotion research programs to assess whether each constitutes a comprehensive theory of emotion. The programs under consideration, in alphabetical order, are appraisal theories in psychology and in political science, emotion regulation, and valence-based accounts. A review of the elements that constitute a theory of emotion of each of these programs persuades me that each has weaknesses that should be addressed. In sum, I find that the ambition to have a comprehensive theory of emotion awaits fulfillment.
The effect of knowledge transfer theory on the selection of crossover winter sports athletes: A systematic literature review
Authors: Gao Yongqi , Soh Kim Geok , Zakaria Noor Syamilah , Mohd Rasdi Roziah , Guo Wei , Soh Kim Lam
Published: February 2023

This article reviews studies on the knowledge transfer theory (KTT) in sport psychology using the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) method to identify any existing research gaps. This review utilizes a systematic process that involves searching for studies aimed at clarifying the relationship between KTT and crossover selection, promoting crossover development of winter sports, and cultivating outstanding athletes across six different databases. This work provides the foundation for future research on KTT in the field of selection of athletes for professional sports and those intending to showcase KTT’s success in the selection of winter sports athletes. This review found that crossover selection of qualified athletes helps solve the issue of the shortage of professional athletes in specific sports.
Theoretical basis and occurrence of internet fraud victimisation: Based on two systems in decision-making and reasoning
Authors: Shang Yuxi , Wang Kaijie , Tian Yuye , Zhou Yingyu , Ma Beibei , Liu Sanyang
Published: February 2023

The influencing factors of internet fraud, including demographics, psychology, experience and knowledge of susceptibility, have been widely studied. Research on the psychological mechanism of the victimisation process of internet fraud is relatively scarce but suggests a new research perspective. To summarise and unify the research in this field, this study systematically searched and analysed articles on the psychological decision-making mechanism of online fraud victims. We found that (a) previous researchers consistently believed that the heuristic processing mode was correlated with susceptibility to online fraud and that the systematic processing mode was helpful to detect and identify fraud. From the overall review results, we do not reject this conclusion, but the verification and intrinsic explanation of this relationship need to be further strengthened. (b) Under the heuristic-systematic model (HSM), with the exception of the trait of suspicion, there is no consensus on whether psychological factors (e.g., personality) influence the likelihood of online fraud through the mediating effect of the selection of the two systems. Objective knowledge and experience in specific fields have been found to be able to achieve this path. Information on the influential variables of equipment and habits is emerging, but how they affect network victimisation through the heuristic processing system needs to be further clarified. (c) The measurement of variables is conducted through simulation experiments. There may be a gap between the likelihood of internet fraud victimisation in the simulation experiment and in the real world. (d) The defence strategies under the HSM are intentional explorations, such as content-based cue recognition technology and simulated scene training.
Does parental phubbing aggravates adolescent sleep quality problems?
Authors: Ding Qian , Dong Siwei , Zhang Yongxin
Published: February 2023

Objective

Based on the theoretical model for the “stress–sleep” relationship, this study investigated the impact of parental phubbing on adolescent sleep quality problems and a moderated mediation mechanism.

Methods

A total of 781 adolescents was surveyed using the Chinese version of Parental Phubbing Scale, the Ultra-brief Screening Scale for Depression and Anxiety Scale, the Self-Control Questionnaire for Chinese children, and the Chinese version of Pittsburgh Sleep Quality Index Scale.

Results

Parental phubbing and negative emotions were significantly and positively correlated to sleep quality problems, but self-control was not correlated to sleep quality problems. Parental phubbing directly influenced sleep quality problems and also indirectly influenced sleep quality problems through the mediating effect of negative emotions. Moreover, self-control played a moderating role in the path of parental phubbing affecting negative emotions. That is, the effect was more significant for adolescents low in self-control relative to those high in self-control.

Conclusion

Parental phubbing is a risk factor for adolescent sleep quality problems. This study is the first to demonstrate empirical evidence for the relationship between parental phubbing and sleep quality problems.
Exercise health belief model mediates the relationship between physical activity and peer support among Chinese college students: A cross-sectional survey
Authors: Sheng Jiazhi , Gong Lamei , Zhou Jian
Published: February 2023

This study explored the influence of the exercise health belief model and peer support on university students’ physical activity PA and clarified the related mechanism. Three hundred and thirty-six healthy university students (aged 19.4 ± 1.3 years, 166 male and 170 female) from Sichuan University of Arts and Science in China were evaluated by the peer support scale, the health belief model scale for exercise, and the physical activity scale (short volume). The results showed that the male students’ exercise self-efficacy and PA were markedly higher than female university students. Peer support was positively correlated with perceived benefits, exercise self-efficacy, perceived severity, and cues to action, and was adversely associated with perceived objective and subjective barriers. PA was positively correlated with perceived benefits and exercise self-efficacy, and negatively correlated with perceived objective and subjective barriers. Among the components of the exercise health belief model, only exercise self-efficacy was suitable for constructing a structural equation model (SEM) with peer support and PA. The analysis showed that the predictive effect of exercise self-efficacy on PA was more significant than peer support, and exercise self-efficacy played a critical intermediary role. It is worth noting that, in the grouping model, the effect of male college students’ exercise self-efficacy on PA was greater than that of female students, and the model fit of male peer support was better than that of female students. Although the impact of peer support on PA was less than that of exercise self-efficacy and the direct effect of peer support was less than the indirect effect, the impact of peer support on the PA of female university students was higher than that of male university students. This study revealed the impact of exercise self-efficacy and peer support on university students’ PA and suggested that exercise self-efficacy is the main path to promoting university students’ PA, followed by peer support. Peer support could affect university students’ PA not only through direct effects but also through indirect effects. This study also suggested that female university students’ peer support has a higher impact on PA than male students. Therefore, when formulating physical exercise courses in the future, it is necessary to give more peer support to female university students to compensate for their low exercise self-efficacy.
Rethinking the risk for depression using the RDoC: A psychophysiological perspective
Authors: Dell’Acqua Carola , Palomba Daniela , Patron Elisabetta , Messerotti Benvenuti Simone
Published: February 2023

Considering that the classical categorical approach to mental disorders does not allow a clear identification of at-risk conditions, the dimensional approach provided by the Research Domain Criteria (RDoC) is useful in the exploration of vulnerability to psychopathology. In the RDoC era, psychophysiological models have an important role in the reconceptualization of mental disorders. Indeed, progress in the study of depression vulnerability has increasingly been informed by psychophysiological models. By adopting an RDoC lens, this narrative review focuses on how psychophysiological models can be used to advance our knowledge of the pathophysiological mechanisms underlying depression vulnerability. Findings from psychophysiological research that explored multiple RDoC domains in populations at-risk for depression are reviewed and discussed. Future directions for the application of psychophysiological research in reaching a more complete understanding of depression vulnerability and, ultimately, improving clinical utility, are presented.
Relationships between parental responsive feeding and infant appetitive traits: The moderating role of infant temperament
Authors: Liu Yan , Kong Yan , Li Zhihui , Zhang Guanghua , Wang Lin , Yu Guiling
Published: February 2023

Introduction

Between the ages of 6 and 12 months is a crucial stage for children to develop appetitive self-regulation. Evidence suggests that a combination of parental responsive feeding and infant temperament (surgency, effortful control, negative affect) shapes infant appetitive traits (food approach, food avoidance). There is a need for research to explore these relationships, in order to provide guidance for the design of an effective intervention to improve appetitive traits. The objective of the current study was to explore the moderating role of infant temperament in the relationship between parental responsive feeding and infant appetitive traits.

Methods

A total of 616 questionnaires, measuring parental responsive feeding, infant appetitive traits, and infant temperament, were collected from parents with infants aged 6–12 months.

Results

Results revealed that responsive feeding was associated with both food approach and food avoidance. Furthermore, only lower levels of surgency significantly moderated the relationship between responsive feeding and food approach, while responsive feeding was associated with food avoidance irrespective of infant temperament.

Discussion

These findings suggest that a strategy embedding responsive feeding interventions should be adopted to reduce infant food avoidance and low-surgent infant food approach, and interventions that are tailored toward food approach for infants with effortful control, negative affect, or higher levels of surgency should be further sought.