bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated Homocysteine Levels Predict Hospital-Acquired Pneumonia and Poor Functional Outcomes in Primary Intracerebral Hemorrhage
Authors: Peng Jun , Zhu Guanghua , Xiao Sheng , Liu Shucheng
Published: June 2022

Background

Homocysteine (Hcy) has been extensively acknowledged to be correlated with inflammation. In this study, the relationship between Hcy and hospital-acquired pneumonia (HAP) in primary intracerebral hemorrhage (pICH) was explored.

Methods

We conducted a hospital-based study on screened eligible patients with primary intracerebral hemorrhage admitted within 24 h after symptom onset from January 2019 to June 2021. The associations between Hcy and HAP and poor outcomes in pICH were investigated using univariate and multivariate logistic regression analyses. The predictive accuracy of Hcy was assessed by the receiver operating characteristic curve and the optimal cutoff value of Hcy was determined by Youden Index. The patterns and magnitudes of associations between Hcy and HAP and poor outcomes were evaluated using a restricted cubic spline (RCS).

Results

A total of 579 patients with pICH were included in the study. Hcy level was significantly higher in patients with HAP and poor outcomes (p < 0.001). The univariate and multivariate logistic regression analyses demonstrated that elevated Hcy was independently associated with both HAP and poor outcomes (p < 0.001). Furthermore, receiver operating characteristic analysis indicated that Hcy exhibited a moderate predictive accuracy for both HAP and poor outcomes after pICH. The RCS model showed that there were linear relationships between Hcy and HAP and poor outcomes.

Conclusions

Higher Hcy level was independently associated with HAP and poor outcomes in patients with pICH.
Differential Attention Functioning in Pediatric Chronic Kidney Disease
Authors: Duquette Peter J. , Gipson Debbie S. , Hooper Stephen R.
Published: June 2022

Objective

To compare specific attention functions for school-age children with chronic kidney disease (CKD) to those of a typically developing control group.

Methods

A cross-sectional study examined attention dimensions for children and adolescents with CKD (n = 30) in comparison to a typically developing control group (n = 41). The CKD group consisted of those receiving maintenance dialysis (n = 15) and those with mild/moderate CKD treated conservatively (n = 15). Measures aligning with Mirsky’s conceptual multidimensional model of attention were selected to compare groups across five dimensions of attention: Focus/Execute, Sustain, Stability, Shift, and Encode.

Results

Significant group differences were revealed, with the CKD group performing worse than controls on the Focus/Execute, Sustain, and Encode dimensions. The CKD group also had a larger proportion of children with scores one standard deviation or more below the mean on the Shift and Encode domains, suggesting an at-risk level of functioning in these dimensions. Secondary analyses showed disease severity to be correlated with worse attention functions for children with CKD.

Conclusion

Children with CKD may be vulnerable to subtle, specific deficits in numerous attention dimensions relative to their typically developing peers, particularly for those with more severe disease.
Astrocytes in Neurodegeneration: Inspiration From Genetics
Authors: Huang Jingxuan , Li Chunyu , Shang Huifang
Published: June 2022

Despite the discovery of numerous molecules and pathologies, the pathophysiology of various neurodegenerative diseases remains unknown. Genetics participates in the pathogenesis of neurodegeneration. Neural dysfunction, which is thought to be a cell-autonomous mechanism, is insufficient to explain the development of neurodegenerative disease, implying that other cells surrounding or related to neurons, such as glial cells, are involved in the pathogenesis. As the primary component of glial cells, astrocytes play a variety of roles in the maintenance of physiological functions in neurons and other glial cells. The pathophysiology of neurodegeneration is also influenced by reactive astrogliosis in response to central nervous system (CNS) injuries. Furthermore, those risk-gene variants identified in neurodegenerations are involved in astrocyte activation and senescence. In this review, we summarized the relationships between gene variants and astrocytes in four neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson’s disease (PD), and provided insights into the implications of astrocytes in the neurodegenerations.
Conditional Deletion of EphA4 on Cx3cr1-Expressing Microglia Fails to Influence Histopathological Outcome and Blood Brain Barrier Disruption Following Brain Injury
Authors: Soliman Eman , Mills Jatia , Ju Jing , Kaloss Alexandra M. , Basso Erwin Kristobal Gudenschwager , Groot Nathalie , Kelly Colin , Kowalski Elizabeth A. , Elhassanny Mohamed , Chen Michael , Wang Xia , Theus Michelle H.
Published: June 2022

Erythropoietin-producing human hepatocellular receptors play a major role in central nervous system injury. Preclinical and clinical studies revealed the upregulation of erythropoietin-producing human hepatocellular A4 (EphA4) receptors in the brain after acute traumatic brain injury. We have previously reported that Cx3cr1-expressing cells in the peri-lesion show high levels of EphA4 after the induction of controlled cortical impact (CCI) injury in mice. Cx3cr1 is a fractalkine receptor expressed on both resident microglia and peripheral-derived macrophages. The current study aimed to determine the role of microglial-specific EphA4 in CCI-induced damage. We used Cx3cr1CreER/+ knock-in/knock-out mice, which express EYFP in Cx3cr1-positive cells to establish microglia, EphA4-deficient mice following 1-month tamoxifen injection. Consistent with our previous findings, induction of CCI in wild-type (WT) Cx3cr1CreER/+EphA4+/+ mice increased EphA4 expression on EYFP-positive cells in the peri-lesion. To distinguish between peripheral-derived macrophages and resident microglia, we exploited GFP bone marrow-chimeric mice and found that CCI injury increased EphA4 expression in microglia (TMEM119+GFP–) using immunohistochemistry. Using Cx3cr1CreER/+EphA4f/f (KO) mice, we observed that the EphA4 mRNA transcript was undetected in microglia but remained present in whole blood when compared to WT. Finally, we found no difference in lesion volume or blood-brain barrier (BBB) disruption between WT and KO mice at 3 dpi. Our data demonstrate a nonessential role of microglial EphA4 in the acute histopathological outcome in response to CCI.
Dose-Response and Substitution Analyzes of Sweet Beverage Consumption and Body Weight in Dutch Adults: The Lifelines Cohort Study
Authors: Buso Marion E. C. , Brouwer-Brolsma Elske M. , Naomi Novita D. , Harrold Joanne A. , Halford Jason C. G. , Raben Anne , Feskens Edith J. M.
Published: June 2022

Background/Methods

Prospective studies investigating sweet beverages and body weight associations show inconsistent results. Within the SWEET project, we examined prospective dose-response associations of sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice with body weight-related outcomes among 78,286 Dutch adults followed for ~4 years. Baseline intakes were assessed using a validated food-frequency questionnaire (FFQ) with 150 ml representing a standard serving. Outcome variables were body weight change, waist circumference change, overweight/obesity, and abdominal obesity. Associations were investigated by using linear and non-linear dose-response analysis, as well as substitution models while adjusting for multiple socio-demographic, lifestyle, health, and dietary variables.

Results

Participants were 46 ± 13 (mean ± SD) years old and 60% were women. Adjusted dose-response analyzes indicated an association between SSB and LNCB, and both body weight (+0.02 kg/year; SE 0.01 and +0.06 kg/year; SE 0.01) and waist circumference changes (+0.04 cm/year; SE: 0.01 and +0.11 cm/year; SE: 0.01). Associations for overweight/obesity and abdominal obesity incidence were +3% (95%CI: 1.00–1.06) and +2% (95%CI: 0.99–1.06) for SSB and +8% (95%CI: 1.06–1.11) and +5% (95%CI: 1.03–1.07) for LNCB, respectively. Substitution of SSB with LNCB was associated with higher weight change (+0.04 kg/year), waist circumference change (+0.09 cm/year), overweight/obesity incidence (+6%), but not abdominal obesity incidence. For fruit juice, we observed beneficial associations for intake levels below ~1 serving/day with weight, waist circumference change, and overweight/obesity incidence, and no association with abdominal obesity. Subsequent substitution analyzes indicated a small beneficial association for the replacement of SSB with fruit juice on weight (−0.04 kg/year) and waist circumference (−0.04 cm/year), but not with other outcomes.

Conclusions

Overall, our results suggest that habitual consumption of both SSB and LNCB may adversely affect weight-related outcomes. In contrast, fruit juice consumption <150 ml may be beneficial with respect to weight and waist circumference.
In vitro Digestion Characteristics of Hydrolyzed Infant Formula and Its Effects on the Growth and Development in Mice
Authors: Feng Lifang , Ye Wei , Zhang Kuo , Qu Daofeng , Liu Weilin , Wu Min , Han Jianzhong
Published: June 2022

Infant formula, an important food for babies, is convenient and nutritious, and hydrolyzed formulas have attracted much attention due to their non-allergicity. However, it is uncertain whether hydrolyzed formulars cause obesity and other side effects in infants. Herein, three infant formulas, standard (sIF), partially hydrolyzed (pHIF), and extensively hydrolyzed (eHIF), were analyzed in an in vitro gastrointestinal digestion model. With increasing degree of hydrolysis, the protein moleculars, and allergenicity of the proteins decreased and the long-chain polyunsaturated fatty acid content increased. Moreover, the digestion model solutions quickly digested the small fat globules and proteins in the hydrolyzed formula, allowing it to become electrostatically stable sooner. The eHIF-fed mice presented larger body sizes, and exhibited excellent exploratory and spatial memory abilities in the maze test. Based on villus height and crypt depth histological characterizations and amplicon sequencing, eHIF promoted mouse small intestine development and changed the gut microbiota composition, eventually favoring weight gain. The mouse spleen index showed that long-term infant formula consumption might be detrimental to immune system development, and the weight-bearing swimming test showed that eHIF could cause severe physical strength decline. Therefore, long-term consumption of infant formula, especially eHIF, may have both positive and negative effects on mouse growth and development, and our results might shed light on feeding formula to infants.
Metabolic Disruption by Naturally Occurring Mycotoxins in Circulation: A Focus on Vascular and Bone Homeostasis Dysfunction
Authors: Malvandi Amir Mohammad , Shahba Sara , Mehrzad Jalil , Lombardi Giovanni
Published: June 2022

Naturally occurring food/feed contaminants have become a significant global issue due to animal and human health implications. Despite risk assessments and legislation setpoints on the mycotoxins' levels, exposure to lower amounts occurs, and it might affect cell homeostasis. However, the inflammatory consequences of this possible everyday exposure to toxins on the vascular microenvironment and arterial dysfunction are unexplored in detail. Circulation is the most accessible path for food-borne toxins, and the consequent metabolic and immune shifts affect systemic health, both on vascular apparatus and bone homeostasis. Their oxidative nature makes mycotoxins a plausible underlying source of low-level toxicity in the bone marrow microenvironment and arterial dysfunction. Mycotoxins could also influence the function of cardiomyocytes with possible injury to the heart. Co-occurrence of mycotoxins can modulate the metabolic pathways favoring osteoblast dysfunction and bone health losses. This review provides a novel insight into understanding the complex events of coexposure to mixed (low levels) mycotoxicosis and subsequent metabolic/immune disruptions contributing to chronic alterations in circulation.
MiR-378a-3p Acts as a Tumor Suppressor in Colorectal Cancer Stem-Like Cells and Affects the Expression of MALAT1 and NEAT1 lncRNAs
Authors: Castellani Giorgia , Buccarelli Mariachiara , Lulli Valentina , Ilari Ramona , De Luca Gabriele , Pedini Francesca , Boe Alessandra , Felli Nadia , Biffoni Mauro , Pilozzi Emanuela , Marziali Giovanna , Ricci-Vitiani Lucia
Published: June 2022

MiR-378a-3p plays a critical role in carcinogenesis acting as a tumor suppressor, promoting apoptosis and cell cycle arrest and reducing invasion and drug resistance in several human cancers, including colorectal cancer (CRC), where its expression is significantly associated with histological classification and prognosis. In this study, we investigated the biological and cellular processes affected by miR-378a-3p in the context of CRC carcinogenesis. In agreement with the literature, miR-378a-3p is downregulated in our cohort of CRC patients as well as, in 15 patient-derived colorectal cancer stem-like cell (CRC-SC) lines and 8 CRC cell lines, compared to normal mucosae. Restoration of miR-378a-3p restrains tumorigenic properties of CRC and CRC-SC lines, as well as, significantly reduces tumor growth in two CRC-SC xenograft mouse models. We reported that miR-378a-3p modulates the expression of the lncRNAs MALAT1 and NEAT1. Their expression is inversely correlated with that of miR-378a-3p in patient-derived CRC-SC lines. Silencing of miR-378a-3p targets, MALAT1 and NEAT1, significantly impairs tumorigenic properties of CRC-SCs, supporting the critical role of miR-378a-3p in CRC carcinogenesis as a tumor-suppressor factor by establishing a finely tuned crosstalk with lncRNAs MALAT1 and NEAT1.
Thymomas With Intravascular and Intracardiac Growth
Authors: Arrossi Andrea Valeria , Dermawan Josephine K. , Bolen Michael , Raymond Daniel
Published: June 2022

Thymomas are derived from the epithelial component of the thymus and constitute the most common tumor of the anterior mediastinum. These neoplasms are considered malignant for their potential for invasion and metastases. Several histopathologic subclassification schemes have been proposed over the years, however, correlation of histotypes with prognosis remains controversial. In contrast, studies invariably have shown that staging and resection status correlate with oncologic behavior and disease outcomes. In this regard, several staging systems have been presented, though transcapsular invasion and degree of involvement of adjacent anatomic structures are common denominators of all schemes. Involvement of the great vessels and heart most commonly results from direct invasion, which may lead to unusual clinical presentations such as superior vena cava syndrome. Moreover, intravascular and intracardiac growth with or without direct mural invasion rarely occurs. We provide an overview of thymomas with intravascular and intracardiac involvement.
Deep Learning Radiomics Nomogram to Predict Lung Metastasis in Soft-Tissue Sarcoma: A Multi-Center Study
Authors: Liang Hao-yu , Yang Shi-feng , Zou Hong-mei , Hou Feng , Duan Li-sha , Huang Chen-cui , Xu Jing-xu , Liu Shun-li , Hao Da-peng , Wang He-xiang
Published: June 2022

Objectives

To build and evaluate a deep learning radiomics nomogram (DLRN) for preoperative prediction of lung metastasis (LM) status in patients with soft tissue sarcoma (STS).

Methods

In total, 242 patients with STS (training set, n=116; external validation set, n=126) who underwent magnetic resonance imaging were retrospectively enrolled in this study. We identified independent predictors for LM-status and evaluated their performance. The minimum redundancy maximum relevance (mRMR) method and least absolute shrinkage and selection operator (LASSO) algorithm were adopted to screen radiomics features. Logistic regression, decision tree, random forest, support vector machine (SVM), and adaptive boosting classifiers were compared for their ability to predict LM. To overcome the imbalanced distribution of the LM data, we retrained each machine-learning classifier using the synthetic minority over-sampling technique (SMOTE). A DLRN combining the independent clinical predictors with the best performing radiomics prediction signature (mRMR+LASSO+SVM+SMOTE) was established. Area under the receiver operating characteristics curve (AUC), calibration curves, and decision curve analysis (DCA) were used to assess the performance and clinical applicability of the models.

Result

Comparisons of the AUC values applied to the external validation set revealed that the DLRN model (AUC=0.833) showed better prediction performance than the clinical model (AUC=0.664) and radiomics model (AUC=0.799). The calibration curves indicated good calibration efficiency and the DCA showed the DLRN model to have greater clinical applicability than the other two models.

Conclusion

The DLRN was shown to be an accurate and efficient tool for LM-status prediction in STS.
Systemic Immun e–Inflammation Index as a Predictor for Head and Neck Cancer Prognosis: A Meta-Analysis
Authors: Wang Yun-Ting , Kuo Liang-Tseng , Weng Hsu-Huei , Hsu Cheng-Ming , Tsai Ming-Shao , Chang Geng-He , Lee Yi-Chan , Huang Ethan I. , Tsai Yao-Te
Published: June 2022

Background

Studies have reported inconsistent results regarding the prognostic value of the systemic immune–inflammation index (SII) in head and neck cancer (HNC). Thus, the present meta-analysis assessed the literature on the prognostic value of SII in those with HNC.

Methods

The Cochrane Library, EMBASE, and PubMed databases were searched, and study methodological quality was assessed using the Newcastle–Ottawa quality assessment scale. To determine the association of the SII with survival outcomes, pooled hazard ratios (HRs) as well as the associated 95% confidence intervals (CIs) were used. To assess the associations of the SII with clinicopathological features, the odds ratios (ORs) and corresponding 95% CIs were considered. Begg’s funnel plot and Egger’s linear regression test were used to assess publication bias.

Results

A total of 12 studies that together enrolled 4369 patients with HNC were analyzed. In the pooled results, a high pretreatment SII was correlated with poorer overall survival (HR = 2.09, 95% CI = 1.62–2.70,p< 0.001), disease-free survival (HR = 2.79, 95% CI = 1.99−3.89,p< 0.001), and progression-free survival (HR = 1.80, 95% CI = 1.30−2.48,p< 0.001). A stratified analysis indicated that SII for overall survival was applicable regardless of tumor site, treatment modality, overall stage, sample size, SII cutoff, and method for determining the SII cutoff. Furthermore, a high SII was correlated with a more advanced T classification (OR = 1.14, 95% CI = 1.09–1.18,p< 0.001) and nodal metastasis (OR = 1.55, 95% CI = 1.18–2.05,p= 0.002) in patients with HNC.

Conclusions

An elevated pretreatment SII predicts more advanced tumor and nodal status and poorer survival outcomes in cases of HNC. Because the measurement of SII is convenient and its use is cost-effective, we suggest that it can be applied by clinicians in the management of HNC.
Intra- and Peritumoral Radiomics Model Based on Early DCE-MRI for Preoperative Prediction of Molecular Subtypes in Invasive Ductal Breast Carcinoma: A Multitask Machine Learning Study
Authors: Zhang Shuhai , Wang Xiaolei , Yang Zhao , Zhu Yun , Zhao Nannan , Li Yang , He Jie , Sun Haitao , Xie Zongyu
Published: June 2022

Purpose

The aim of this study is to investigate radiomics features extracted from the optimal peritumoral region and the intratumoral area on the early phase of dynamic contrast-enhanced MRI (DCE-MRI) for predicting molecular subtypes of invasive ductal breast carcinoma (IDBC).

Methods

A total of 422 IDBC patients with immunohistochemical and fluorescence in situ hybridization results from two hospitals (Center 1: 327 cases, Center 2: 95 cases) who underwent preoperative DCE-MRI were retrospectively enrolled. After image preprocessing, radiomic features were extracted from the intratumoral area and four peritumoral regions on DCE-MRI from two centers, and selected the optimal peritumoral region. Based on the intratumoral, peritumoral radiomics features, and clinical–radiological characteristics, five radiomics models were constructed through support vector machine (SVM) in multiple classification tasks related to molecular subtypes and visualized by nomogram. The performance of radiomics models was evaluated by receiver operating characteristic curves, confusion matrix, calibration curves, and decision curve analysis.

Results

A 6-mm peritumoral size was defined the optimal peritumoral region in classification tasks of hormone receptor (HR)-positive vs others, triple-negative breast cancer (TNBC) vs others, and HR-positive vs human epidermal growth factor receptor 2 (HER2)-enriched vs TNBC, and 8 mm was applied in HER2-enriched vs others. The combined clinical–radiological and radiomics models in three binary classification tasks (HR-positive vs others, HER2-enriched vs others, TNBC vs others) obtained optimal performance with AUCs of 0.838, 0.848, and 0.930 in the training cohort, respectively; 0.827, 0.813, and 0.879 in the internal test cohort, respectively; and 0.791, 0.707, and 0.852 in the external test cohort, respectively.

Conclusion

Radiomics features in the intratumoral and peritumoral regions of IDBC on DCE-MRI had a potential to predict the HR-positive, HER2-enriched, and TNBC molecular subtypes preoperatively.
The Isoforms of Estrogen Receptor Alpha and Beta in Thyroid Cancer
Authors: Gong Zhongqin , Yang Shucai , Wei Minghui , Vlantis Alexander C. , Chan Jason Y. K. , van Hasselt C. Andrew , Li Dongcai , Zeng Xianhai , Xue Lingbin , Tong Michael C. F. , Chen George G.
Published: June 2022

The incidence of thyroid cancer was predominant in women, indicating that the sex hormone may have a role in thyroid cancer development. Generally, the sex hormone exerts its function by binding to the correspondent nuclear receptors. Therefore, aberrant of these receptors may be involved in the development of thyroid cancer. Estrogen receptor alpha (ERα) and beta (ERβ), two main estrogen receptors, have been reported to have an important role in the pathogenesis of thyroid cancer. When the ERα and ERβ genes undergo the alternative RNA splicing, some ERα and ERβ isoforms with incomplete functional domains may be formed. To date, several isoforms of ERα and ERβ have been identified. However, their expression and roles in thyroid cancer are far from clear. In this review, we summarized the expressions and roles of ERα and ERβ isoforms in thyroid cancer, aiming to provide the perspective of modulating the alternative RNA splicing of ERα and ERβ against thyroid cancer.
Plac1 Remodels the Tumor Immune Evasion Microenvironment and Predicts Therapeutic Response in Head and Neck Squamous Cell Carcinoma
Authors: Meng Xiaoyan , Liu Zhonglong , Zhang Lingfang , He Yue
Published: June 2022

Head and neck squamous cell carcinoma (HNSCC or HNSC) is the sixth most common cancer worldwide. Placenta-specific 1 (Plac1) belongs to the cancer testis antigen family and is highly expressed in malignant cells in HNSC. However, the biological function and prognostic value of plac1 in HNSC are still unclear. In the current research, we performed a comprehensive analysis of plac1 using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) bulk RNA sequencing databases as well as a single-cell sequencing dataset. We constructed a 15-gene prognostic signature through screening plac1-related immunomodulators and validated its efficiency and accuracy in immunotherapy cohorts and a pancancer database. We found that plac1 expression level is a prognostic predictor of poor overall survival in patients with HNSC. Plac1 is associated with epithelial–mesenchymal transition and tumor invasion. Plac1 has a “dual immunosuppressive function” on tumor microenvironment. On one hand, plac1-positive cells promote extracellular matrix formation and suppress immune cell infiltration. On the other hand, plac1-positive cells enhance the interaction between dendritic cells and macrophages, which further suppresses antitumor immunity. Finally, we constructed a 15-gene prognostic signature, the efficiency and accuracy of which were validated in immunotherapy cohorts and a pancancer database. In conclusion, plac1 is a promising candidate biomarker for prognosis, a potential target for immunotherapy, and a novel point for studying the immunosuppressive mechanisms of the tumor microenvironment in HNSC.
Relevance of Fc Gamma Receptor Polymorphisms in Cancer Therapy With Monoclonal Antibodies
Authors: Mata-Molanes Juan J. , Rebollo-Liceaga Joseba , Martínez-Navarro Elena Mª , Manzano Ramón González , Brugarolas Antonio , Juan Manel , Sureda Manuel
Published: June 2022

Therapeutic monoclonal antibodies (mAbs), including immune checkpoint inhibitors (ICIs), are an important breakthrough for the treatment of cancer and have dramatically changed clinical outcomes in a wide variety of tumours. However, clinical response varies among patients receiving mAb-based treatment, so it is necessary to search for predictive biomarkers of response to identify the patients who will derive the greatest therapeutic benefit. The interaction of mAbs with Fc gamma receptors (FcγR) expressed by innate immune cells is essential for antibody-dependent cellular cytotoxicity (ADCC) and this binding is often critical for theirin vivoefficacy. FcγRIIa (H131R) and FcγRIIIa (V158F) polymorphisms have been reported to correlate with response to therapeutic mAbs. These polymorphisms play a major role in the affinity of mAb receptors and, therefore, can exert a profound impact on antitumor response in these therapies. Furthermore, recent reports have revealed potential mechanisms of ICIs to modulate myeloid subset composition within the tumour microenvironment through FcγR-binding, optimizing their anti-tumour activity. The purpose of this review is to highlight the clinical contribution of FcγR polymorphisms to predict response to mAbs in cancer patients.
A Novel Matrisomal-Related LncRNA Signature Associated With Survival Outcome and Immune Evasion in Patients With Gastric Cancer
Authors: Yang Yuan , Shi Li , Zhang Jun , Zheng Ya , Wu Guozhi , Sun Jie , Liu Min , Chen Zhaofeng , Wang Yuping , Ji Rui , Guo Qinghong , Zhou Yongning
Published: June 2022

Background

Different matrisomal patterns are shared across carcinomas. However, little is known about whether there exists a unique tumor matrisome that modulates GC progression and immune regulation.

Methods

We conducted a genome-wide analysis based on matrisomal-related lncRNAs (MRLs) in 375 patients with GC from the Cancer Genome Atlas (TCGA) database. Patients were split into the training set and validation set at a ratio of 1:1 using the R package cart. Pearson correlation analysis (PCA) was performed to identify lncRNAs that correlated with matrisome based on differential expression genes. Subsequently, we performed univariate Cox regression analyses and lasso Cox analysis on these lncRNAs to construct a risk model. Considering the primary effect of GRASLND on the GC prognosis, we chose it for further validation in an experimental setting.

Results

We identified a 15-MRL signature to predict overall survival and immune cell infiltration of patients with GC. The AUC values to predict 5-year outcome in three sets were 0.89, 0.65, and 0.78, respectively. Further analyses suggested that the high-risk group showed more obvious immune cell infiltration, and demonstrated an immunologically “cold” profile. In vitro, knockdown of GRASLND could inhibit the invasion capability of GC cells, and downregulate the protein expression of crucial matrisomal-related gene MMP9.

Conclusions

The 15-MRL gene signature might serve as a relatively good predictive tool to manage patients with GC.
Red Light Phototherapy Using Light-Emitting Diodes Inhibits Melanoma Proliferation and Alters Tumor Microenvironments
Authors: Austin Evan , Huang Alisen , Wang Jennifer Y. , Cohen Marc , Heilman Edward , Maverakis Emanual , Michl Josef , Jagdeo Jared
Published: June 2022

Background

Total annual cancer rates have decreased due to improved treatment and prevention. However, the incidence of melanoma is rising, and not all patients respond to immune and targeted approaches. Therefore, we sought to determine the efficacy of red light (RL) phototherapy in preclinical models of melanoma.

Methods

Melanoma cells (A375, B16F10, MNT-1) were irradiated with RL. Melanoma proliferation, apoptosis, oxidative stress, and p53 phosphorylation were measured in vitro. In C57BL/6 mice, phototherapy safety, B16F10 tumor growth, and immunocyte infiltration were assessed following RL.

Results

In vitro, 640 J/cm2 RL decreased cellular proliferation without increasing apoptosis, while 1280 J/cm2 increased apoptosis. RL increased intracellular reactive oxygen species generation and p53 phosphorylation. In animal models, 2560 J/cm2 RL significantly prevented melanoma growth and increased the expression of CD103+ dendritic cells. 1280 and 1920 J/cm2 RL decreased tumor volume, but not significantly. RL did not cause skin inflammation or erythema in normal skin.

Conclusion

RL represents a potentially safe and effective melanoma therapeutic. RL prevented tumor growth and increased the expression of immune markers, such as CD103, that are associated with favorable melanoma outcomes. Further research is needed to determine the optimal clinical treatment regimen for melanoma using RL.
Esophageal Dysphagia in Children: State of the Art and Proposal for a Symptom-Based Diagnostic Approach
Authors: Lanzoni Gloria , Sembenini Camilla , Gastaldo Stefano , Leonardi Letizia , Bentivoglio Vincenzo Pio , Faggian Giovanna , Bosa Luca , Gaio Paola , Cananzi Mara
Published: June 2022

Pediatric esophageal dysphagia (PED) is an infrequent condition that can be determined by a large number of disorders. The etiologic diagnosis is challenging due to overlapping clinical phenotypes and to the absence of pediatric diagnostic guidelines. This review aims to summarize the most relevant causes of ED during childhood, highlight the clinical scenarios of PED presentation and discuss the indications of available diagnostic tools. Available information supports that PED should always be investigated as it can underlie life-threatening conditions (e.g., foreign body ingestion, mediastinal tumors), represent the complication of benign disorders (e.g., peptic stenosis) or constitute the manifestation of organic diseases (e.g., eosinophilic esophagitis, achalasia). Therefore, the diagnosis of functional PED should be made only after excluding mucosal, structural, or motility esophageal abnormalities. Several clinical features may contribute to the diagnosis of PED. Among the latter, we identified several clinical key elements, relevant complementary-symptoms and predisposing factors, and organized them in a multi-level, hierarchical, circle diagram able to guide the clinician through the diagnostic work-up of PED. The most appropriate investigational method(s) should be chosen based on the diagnostic hypothesis: esophagogastroduodenoscopy has highest diagnostic yield for mucosal disorders, barium swallow has greater sensitivity in detecting achalasia and structural abnormalities, chest CT/MR inform on the mediastinum, manometry is most sensitive in detecting motility disorders, while pH-MII measures gastroesophageal reflux. Further studies are needed to define the epidemiology of PED, determine the prevalence of individual underlying etiologies, and assess the diagnostic value of investigational methods as to develop a reliable diagnostic algorithm.
Higher Body Fat in Children and Adolescents With Type 1 Diabetes–A Systematic Review and Meta-Analysis
Authors: Zheng Yuwen , Rostami Haji Abadi Mahdi , Gough Jonathan , Johnston James J. D. , Nour Munier , Kontulainen Saija
Published: June 2022

Aims

Higher prevalence of overweight and obesity in children and adolescents with type 1 diabetes (T1D) suggests alterations are required in body composition. However, differences in body composition between children with T1D and typically developing children (TDC) have not been synthesized using meta-analysis. Therefore, we conducted a systematic review and meta-analysis to compare body composition between children with T1D and TDC, and to explore the role of disease and non-disease related factors in potential body composition differences.

Methods

Studies were performed comparing dual-energy x-ray absorptiometry-acquired total body fat and lean mass, absolute (kg) and relative (%) values, between children with T1D and TDC. We reported mean differences with 95% confidence intervals (CI) from meta-analysis and relative between-group %-differences. We used meta-regression to explore the role of sex, age, height, body mass, body mass index, Hemoglobin A1c, age of onset, disease duration, and insulin dosage in the potential body composition differences between children with T1D and TDC, and subgroup analysis to explore the role of geographic regions (p < 0.05).

Results

We included 24 studies (1,017 children with T1D, 1,045 TDC) in the meta-analysis. Children with T1D had 1.2 kg more fat mass (kg) (95%CI 0.3 to 2.1; %-difference = 9.3%), 2.3% higher body fat % (0.3–4.4; 9.0%), but not in lean mass outcomes. Age of onset (β = −2.3, −3.5 to −1.0) and insulin dosage (18.0, 3.5–32.6) were negatively and positively associated with body fat % mean difference, respectively. Subgroup analysis suggested differences among geographic regions in body fat % (p < 0.05), with greater differences in body fat % from Europe and the Middle East.

Conclusion

This meta-analysis indicated 9% higher body fat in children with T1D. Earlier diabetes onset and higher daily insulin dosage were associated with body fat % difference between children with T1D and TDC. Children with T1D from Europe and the Middle East may be more likely to have higher body fat %. More attention in diabetes research and care toward body composition in children with T1D is needed to prevent the early development of higher body fat, and to minimize the cardiovascular disease risk and skeletal deficits associated with higher body fat.
Beneficial Effects of Gracillin From Rhizoma Paridis Against Gastric Carcinoma via the Potential TIPE2-Mediated Induction of Endogenous Apoptosis and Inhibition of Migration in BGC823 Cells
Authors: Liu Wenming , Wang Yanting , Chen Junjie , Lin Zhenhe , Lin Mengjie , Lin Xiantong , Fan Yanyun
Published: June 2022

Tumor necrosis factor-α inducible protein-8 (TIPE2), initially recognized as a negative immune regulator, exerts an important role in suppressing the progression of numerous cancers. In our previous investigation, we found that TIPE2 expression displayed a decrease or absence in gastric tumor tissue, and the overexpression of TIPE2 suppressed the growth of gastric cancer tumors and cells, demonstrating that TIPE2 could be a potential medicinal target for gastric cancer treatment. However, it’s seldomly reported that several medicinal agents or candidates targeted TIPE2 for treating diseases, including gastric cancer. To identify the candidate targeting TIPE2 to fight against gastric cancer, several extractions from traditional natural medicinal plants with anti-tumor functions were employed to screen the active compounds according to bioassay-guided isolation. Interestingly, gracillin, a component from the ethyl acetate extraction of Rhizoma Paridis, was identified to induce the expression of TIPE2 and inhibit the cell proliferation in gastric cancer BGC-823 cells. Furthermore, the underlying mechanisms that restrain gastric cancer were evaluated by clone formation, EdU staining, flow cytometry, and other assays. Meanwhile, the role of TIPE2 in the anti-tumor effect of gracillin was elucidated via the use of siTIPE2 RNA. It was determined that gracillin could fight against gastric cancer cells by inhibiting the cell proliferation participated by the PI3K/AKT pathway and cell cycle arrest, suppressing the EMT pathway-regulating cell migration, and inducing bcl2-associated mitochondrial apoptosis. Additionally, TIPE2 maybe contribute to the benefits of gracillin. These results of the present study are an important step toward the medicinal development of gracillin, and are also of use in understanding the effect of TIPE2 as a potential tumor target.
A New Strategy to Investigate the Efficacy Markers Underlying the Medicinal Potentials of Orthosiphon stamineus Benth.
Authors: Li Zheng , Qu Biao , Zhou Lei , Chen Hongwei , Wang Jue , Zhang Wei , Chen Caifa
Published: June 2022

Orthosiphon stamineus Benth. (OSB) is a well-known herbal medicine exerting various pharmacological effects and medicinal potentials. Owing to its complex of phytochemical constituents, as well as the ambiguous relationship between phytochemical constituents and varied bioactivities, it is a great challenge to explore which constituents make a core contribution to the efficacy of OSB, making it difficult to determine the efficacy makers underlying the varied efficacies of OSB. In our work, a new strategy was exploited and applied for investigating efficacy markers of OSB consisting of phytochemical analysis, in vivo absorption analysis, bioactive compound screening, and bioactive compound quantification. Using liquid chromatography coupled with mass spectrometry, a total of 34 phytochemical components were detected in the OSB extract. Subsequently, based on in vivo absorption analysis, 14 phytochemical constituents in the form of prototypes were retained as potential bioactive compounds. Ten diseases were selected as the potential indications of OSB based on previous reports, and then the overall interaction between compounds, action targets, action pathways, and diseases was revealed based on bioinformatic analysis. After refining key pathways and targets, the interaction reversing from pathways, targets to constituents was deduced, and the core constituents, including tanshinone IIA, sinensetin, salvianolic acid B, rosmarinic acid, and salvigenin, were screened out as the efficacy markers of OSB. Finally, the contents of these five constituents were quantified in three different batches of OSB extracts. Among them, the content of salvianolic acid B was the highest while the content of tanshinone IIA was the lowest. Our work could provide a promising direction for future research on the quality control and pharmacological mechanism of OSB.
Trilobatin, a Naturally Occurring Food Additive, Ameliorates Exhaustive Exercise-Induced Fatigue in Mice: Involvement of Nrf2/ARE/Ferroptosis Signaling Pathway
Authors: Xiao Ran , Wei Yu , Zhang Yueping , Xu Fan , Ma Congjian , Gong Qihai , Gao Jianmei , Xu Yingshu
Published: June 2022

Nrf2-mediated oxidative stress is a promising target of exhaustive exercise-induced fatigue (EEIF). Trilobatin (TLB) is a naturally occurring food additive with antioxidant effect and Nrf2 activation potency. The present study aimed to investigate the effect of TLB on EEIF and elucidate its underlying mechanism. Our results showed that TLB exerted potent anti-EEIF effect, as reflected by the rope climbing test and exhaustive swimming test. Moreover, TLB also effectively reduced the levels of lactate, creatine kinase, and blood urea nitrogen, and increased liver glycogen and skeletal muscle glycogen in mice after EEIF insult. Additionally, TLB also balanced the redox status as evidenced by decreasing the generation of reactive oxygen species and improving the antioxidant enzyme activities including superoxide dismutase, catalase, and glutathione peroxidase, as well as the level of glutathione both in the tissue of muscle and myocardium. Furthermore, TLB promoted nuclear factor erythroid 2-related factor 2 (Nrf2) from the cytoplasm to the nucleus, and upregulated its downstream antioxidant response element (ARE) including quinone oxidoreductase-1 and heme oxygenase-1. Intriguingly, TLB also upregulated the GPx4 protein expression and reduced iron overload in mice after EEIF insult. Encouragingly, the beneficial effect of TLB on EEIF-induced oxidative stress and ferroptosis were substantially abolished in Nrf2-deficient mice. In conclusion, our findings demonstrate, for the first time, that TLB alleviates EEIF-induced oxidative stress through mediating Nrf2/ARE/ferroptosis axis.
The Putative Role of Astaxanthin in Neuroinflammation Modulation: Mechanisms and Therapeutic Potential
Authors: Wang Shuai , Qi Xin
Published: June 2022

Neuroinflammation is a protective mechanism against insults from exogenous pathogens and endogenous cellular debris and is essential for reestablishing homeostasis in the brain. However, excessive prolonged neuroinflammation inevitably leads to lesions and disease. The use of natural compounds targeting pathways involved in neuroinflammation remains a promising strategy for treating different neurological and neurodegenerative diseases. Astaxanthin, a natural xanthophyll carotenoid, is a well known antioxidant. Mounting evidence has revealed that astaxanthin is neuroprotective and has therapeutic potential by inhibiting neuroinflammation, however, its functional roles and underlying mechanisms in modulating neuroinflammation have not been systematically summarized. Hence, this review summarizes recent progress in this field and provides an update on the medical value of astaxanthin. Astaxanthin modulates neuroinflammation by alleviating oxidative stress, reducing the production of neuroinflammatory factors, inhibiting peripheral inflammation and maintaining the integrity of the blood-brain barrier. Mechanistically, astaxanthin scavenges radicals, triggers the Nrf2-induced activation of the antioxidant system, and suppresses the activation of the NF-κB and mitogen-activated protein kinase pathways. With its good biosafety and high bioavailability, astaxanthin has strong potential for modulating neuroinflammation, although some outstanding issues still require further investigation.
The Inflammatory Factor SNP May Serve as a Promising Biomarker for Acitretin to Alleviate Secondary Failure of Response to TNF-a Monoclonal Antibodies in Psoriasis
Authors: Lin Lanmei , Wang Yilun , Lu Xiaonian , Wang Tianxiao , Li Qunyi , Wang Runnan , Wu Jinfeng , Xu Jinhua , Du Juan
Published: June 2022

Psoriasis is a common immune-mediated inflammatory skin disease. Although biological agents have achieved good clinical efficacy in the treatment of moderate-to-severe psoriasis, the phenomenon of secondary non-response (SNR) has been gradually recognized. SNR refers to the gradual decline of efficacy after the patient achieves clinical remission with biological agents such as TNF-α biologics. Acitretin, as an immunomodulatory systemic drug for psoriasis, can improve the SNR to biological agents with good tolerance, but there are still individual differences in efficacy. Single-nucleotide polymorphisms (SNPs) of many related inflammatory cytokines have been shown to be important factors of individual differences in drug response in psoriasis, but there have been few reports on the use of pharmacogenomics to alleviate the SNR to biological agents. This study recruited 43 patients with psoriasis and 24 normal controls to investigate whether SNPs of inflammatory cytokines could be used as biomarkers for acitretin to alleviate SNR to TNF-α biologics in psoriasis, including rs1800795 (IL-6), rs6887695 (IL-12b), rs3212227 (IL-12b), rs10484879 (IL-17a), rs4819554 (IL-17ra), rs763780 (IL-17F), rs11209032 (IL23R), rs11209026 (IL23R), and rs2201841 (IL23R). The study also analyzed the correlation between the abovementioned SNPs and the efficacy of acitretin-only patients so as to understand whether the improvement is attributable to the intervention of acitretin on SNR or a simple response of acitretin. We found that in patients with homozygous AA (χ2 = 6.577, p = 0.02) at the SNP rs112009032 (IL-23R), acitretin could improve the SNR to TNFα monoclonal antibody. Patients with the genotype of TG (χ2 = 6.124, p = 0.035) at rs3212227 (IL-12B) were more sensitive to using acitretin in the treatment of psoriasis. Rs3212227 (χ2 = 7.664, p = 0.022) was also associated with the susceptibility to psoriasis. The study might provide a clinical decision reference for personalized treatment of secondary loss of response to psoriasis biologics.
Reconstruction of Unfolding Sub-Events From Social Media Posts
Authors: Li Ren-De , Guo Qiang , Zhang Xue-Kui , Liu Jian-Guo
Published: June 2022

Event detection plays a crucial role in social media analysis, which usually concludes sub-event detection and correlation. In this article, we present a method for reconstructing the unfolding sub-event relations in terms of external expert knowledge. First, a Single Pass Clustering method is utilized to summarize massive social media posts. Second, a Label Propagation Algorithm is introduced to detect the sub-event according to the expert labeling. Third, a Word Mover’s Distance method is used to measure the correlation between the relevant sub-events. Finally, the Markov Chain Monte Carlo simulation method is presented to regenerate the popularity of social media posts. The experimental results show that the popularity dynamic of the empirical social media sub-events is consistent with the data generated by the proposed method. The evaluation of the unfolding model is 50.52% ∼ 88% higher than that of the random null model in the case of “Shanghai Tesla self-ignition incident.” This work is helpful for understanding the popularity mechanism of the unfolding events for online social media.
Laser-Induced Forward Transfer of Silver Nanoparticles for a Black Metal Absorber
Authors: Li Ruo-Zhou , Guo Lvjiu , Liu Leilei , Yang Mingqing , Fang Yuming , Yu Ying , Yan Jing
Published: June 2022

Plasmonic nanostructures emerged as an appealing approach for black metal absorbers (BMAs) to provide significant light absorption. We present the simple and rapid fabrication of BMAs using laser-induced forward transfer of silver nanoparticles (AgNPs). Randomly distributed plasmon silver nanostructures at a multiscale were produced simultaneously during laser transfer, providing significant light absorption and antireflection features. The laser-transferred BMAs exhibit excellent absorption capacity of a value over 96% and a minimum reflection of 0.38%. A high scanning speed of 10 m/s was used that can complete the laser-induced forward transfer (LIFT) process within 2 s for a 1 cm2 area. The nearfield light confinement is discussed in terms of the morphology of the obtained nanostructures. Photothermal conversion with macroscale temperature rising was demonstrated for the LIFT process is an effective method for the industrial production of BMAs with excellent absorption capacity.