bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of subtypes of hepatocellular carcinoma and screening of prognostic molecular diagnostic markers based on cell adhesion molecule related genes
Authors: Sun Ruge , Gao Yanchao , Shen Fengjun
Published: November 2022

Cell adhesion molecules can predict liver hepatocellular carcinoma (LIHC) metastasis and determine prognosis, while the mechanism of the role of cell adhesion molecules in LIHC needs to be further explored. LIHC-related expression data were sourced from The Cancer Genome Atlas (TCGA) and the gene expression omnibus (GEO) databases, and genes related to cell adhesion were sourced from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. First, the TCGA-LIHC dataset was clustered by the nonnegative matrix factorization (NMF) algorithm to find different subtypes of LIHC. Then the difference of prognosis and immune microenvironment between patients of different subtypes was evaluated. In addition, a prognostic risk model was obtained by least shrinkage and selection operator (LASSO) and Cox analysis, while a nomogram was drawn. Furthermore, functional enrichment analysis between high and low risk groups was conducted. Finally, the expressions of model genes were explored by quantitative real-time polymerase chain reaction (qRT-PCR). The 371 LIHC patients were classified into four subtypes by NMF clustering, and survival analysis revealed that disease-free survival (DFS) of these four subtypes were clearly different. Cancer-related pathways and immune microenvironment among these four subtypes were dysregulated. Moreover, 58 common differentially expressed genes (DEGs) between four subtypes were identified and were mainly associated with PPAR signaling pathway and amino acid metabolism. Furthermore, a prognostic model consisting of IGSF11, CD8A, ALCAM, CLDN6, JAM2, ITGB7, SDC3, CNTNAP1, and MPZ was built. A nomogram consisting of pathologic T and riskScore was built, and the calibration curve illustrated that the nomogram could better forecast LIHC prognosis. Gene Set Enrichment Analysis (GSEA) demonstrated that DEGs between high and low risk groups were mainly involved in cell cycle. Finally, the qRT-PCR illustrated the expressions of nine model genes between normal and LIHC tissue. A prognostic model consisting of IGSF11, CD8A, ALCAM, CLDN6, JAM2, ITGB7, SDC3, CNTNAP1, and MPZ was obtained, which provides an important reference for the molecular diagnosis of patient prognosis.
Identifying key m6A-methylated lncRNAs and genes associated with neural tube defects via integrative MeRIP and RNA sequencing analyses
Authors: Yang Jing , Xu Jing , Zhang Luting , Li Yingting , Chen Min
Published: November 2022

Objective: N6-methyladenosine (m6A) is a common post-transcriptional modification of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs). However, m6A-modified lncRNAs are still largely unexplored. This study aimed to investigate differentially m6A-modified lncRNAs and genes involved in neural tube defect (NTD) development.

Methods: Pregnant Kunming mice (9–10 weeks of age) were treated with retinoic acid to construct NTD models. m6A levels and methyltransferase-like 3 (METTL3) expression were evaluated in brain tissues of the NTD models. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were performed on the NovaSeq platform and Illumina HiSeq 2,500 platform, respectively. Differentially m6A-methylated differentially expressed lncRNAs (DElncRNAs) and differentially expressed genes (DEGs) were identified, followed by GO biological process and KEGG pathway functional enrichment analyses. Expression levels of several DElncRNAs and DEGs were evaluated by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for validation.

Results: m6A levels and METTL3 expression levels were significantly lower in the brain tissues of the NTD mouse model than in controls. By integrating MeRIP-seq and RNA-seq data, 13 differentially m6A-methylated DElncRNAs and 170 differentially m6A-methylated DEGs were identified. They were significantly enriched in the Hippo signaling pathway and mannose-type O-glycan biosynthesis. The qRT-PCR results confirmed the decreased expression levels of lncRNAs, such as Mir100hg, Gm19265, Gm10544, and Malat1, and genes, such as Zfp236, Erc2, and Hmg20a, in the NTD group.

Conclusion:METTL3-mediated m6A modifications may be involved in NTD development. In particular, decreased expression levels of Mir100hg, Gm19265, Gm10544, Malat1, Zfp236, Erc2, and Hmg20a may contribute to the development of NTD.
Proteomic characteristics of saliva in patients with different subgroups of IgG4-RD
Authors: Lin Sheng-Yan , Zhou Tianshu , Cai Shaozhe , Hu Zi-Wei , Zhong Jixin , Dong Lingli
Published: November 2022

Background

Immunoglobulin G4-related disease (IgG4-RD) is a newly defined disease entity, with great heterogeneity among IgG4-RD subgroups with different organ involvement patterns. Identification of the proteomic characteristics of IgG4-RD subgroups will be critical for the understanding of the pathogenic mechanisms of IgG4-RD.

Method

In this study, we performed proteomic analysis using Tandem Mass Tags (TMT) technology with “high field” mass analyzer with improved resolution and sequencing speed to investigate the proteomic profile of saliva and plasma samples from ten untreated IgG4-RD patients and five healthy controls (HCs). Differentially expressed proteins (DEPs) were identified by “t test” function in R package. Functional enrichment analysis was used to investigate pathways enriched in IgG4-RD samples.

Results

Most salivary DEPs identified in IgG4-RD patients compared with HCs were mainly enriched in neutrophil mediated GO bioprocess. Within the comparisons between four IgG4-RD subgroups, more DEPs were identified in the comparison of Mikulicz group and Head and neck group. Among four subgroups of IgG4-RD, Head and neck group showed the most distinctive proteomic expression pattern when compared with HCs. Moreover, “Neutrophil mediated process” related GO bioprocess was commonly identified between comparisons of Mikulicz group and Head and neck group, Head and neck group and Retroperitoneal aorta group, Head and neck group and HCs, IgG4-RD patients with saliva gland involvement and those without saliva gland involvement. Key DEPs that involved in this GO bioprocess were identified. Besides, we performed proteomic analysis for plasma samples between ten IgG4-RD and five HCs and there were several DEPs identified overlapped in saliva and plasma.

Conclusion

We identified multiple processes/factors and several signaling pathways in saliva that may be involved in the IgG4-RD pathogenesis.
Predictive biomarkers of colon cancer immunotherapy: Present and future
Authors: Hou Wanting , Yi Cheng , Zhu Hong
Published: November 2022

Immunotherapy has revolutionized colon cancer treatment. Immune checkpoint inhibitors (ICIs) have shown clinical benefits for colon cancer patients, especially those with high microsatellite instability (MSI-H). In 2020, the US Food and Drug Administration (FDA)-approved ICI pembrolizumab as the first-line treatment for metastatic MSI-H colon cancer patients. Additionally, neoadjuvant immunotherapy has presented efficacy in treating early-stage colon cancer patients. Although MSI has been thought of as an effective predictive biomarker for colon cancer immunotherapy, only a small proportion of colon cancer patients were MSI-H, and certain colon cancer patients with MSI-H presented intrinsic or acquired resistance to immunotherapy. Thus, further search for predictive biomarkers to stratify patients is meaningful in colon cancer immunotherapy. Except for MSI, other biomarkers, such as PD-L1 expression level, tumor mutation burden (TMB), tumor-infiltrating lymphocytes (TILs), certain gut microbiota, ctDNA, and circulating immune cells were also proposed to be correlated with patient survival and ICI efficacy in some colon cancer clinical studies. Moreover, developing new diagnostic techniques helps identify accurate predictive biomarkers for colon cancer immunotherapy. In this review, we outline the reported predictive biomarkers in colon cancer immunotherapy and further discuss the prospects of technological changes for biomarker development in colon cancer immunotherapy.
Study on liver histopathology of chronic HBV infected patients with different normal ALT values
Authors: Zeng Zhan , Hao Hongxiao , Bi Xiaoyue , Lin Yanjie , Yang Liu , Wang Shiyu , Shen Ge , Chang Min , Jiang Tingting , Deng Wen , Lu Huihui , Sun Fangfang , Lu Yao , Gao Yuanjiao , Liu Ruyu , Xu Mengjiao , Chen Xiaoxue , Hu Leiping , Zhang Lu , Li Minghui , Xie Yao
Published: November 2022

Aims

Comparison of liver histopathological findings to explore the occurrence of liver inflammation in patients with chronic hepatitis B (CHB) under different alanine aminotransferase (ALT) normal values.

Methods

The patients who were diagnosed as chronic hepatitis B virus (HBV) infection by liver histopathology at the Department of Pathology, Beijing Ditan Hospital due to clinical difficulty in defining the degree of liver inflammation or fibrosis were retrospectively enrolled from May 2008 to November 2020. Study of the incidence of significant hepatic histopathology in enrolled patients according to different ALT normal values. Using logistic regression to investigate the relevant factors of significant hepatic histopathology.

Results

A total of 1474 patients were enrolled, 56.20% of the patients were male, and the overall patients’ age was 36.80 ± 10.60 years. 39.00% of patients had liver inflammation grade G > 1, 34.70% liver fibrosis stage S > 1, and 48.17% patients had significant hepatic histopathology (G > 1 and/or S > 1). Among patients with normal ALT values, 36.40% and 40.40% had significant hepatic histopathology by American Association for the Study of Liver Diseases (AASLD) criteria and Chinese guideline criteria, respectively, but the difference was not statistically significant (χ2 =3.38, P =0.066). In contrast, among patients with abnormal ALT values, 58.90% and 62.20% of patients had significant hepatic histopathology by AASLD criteria and Chinese guideline criteria, respectively, with no significant difference (χ2 =2.28, P =0.131). ALT (P <0.001, OR=1.019), hepatitis B surface antigen (HBsAg) (P <0.001, OR=0.665) and hepatitis B e antigen (HBeAg) status (P <0.001, OR=2.238) were relevant factors in the occurrence of significant hepatic histopathology. ALT was positively corelated with grade of inflammation G (r =0.194, P <0.001) and negatively correlated with liver fibrosis stage S (r =-0.066, P =0.021).

Conclusions

Our study found no statistically significant differences in the presence of significant hepatic histopathology under the two ALT criteria. ALT, HBsAg and HBeAg status were related to the occurrence of significant hepatic histopathology.
Botanical and microbial insecticides application in aquaponics - is there a risk for biofilter bacteria and fish?
Authors: Rašković Božidar , Gebauer Radek , Folorunso Ewumi Azeez , Božić Gavrilo , Velíšek Josef , Dvořák Petr , Bořík Adam , Grabic Roman , Mráz Jan
Published: November 2022

Aquaponics is a food production system that combines aquaculture with hydroponics. The simultaneous existence of fish, beneficial bacteria and plants in the same water loop predisposes the fish and bacteria to a possible detrimental effect of plant protection products. Additionally, there is an inadequate exploration of scientific studies on the impact of pesticides on fish and bacteria in aquaponics systems. This study investigated the effects of three commercial insecticides based on the following active ingredients: pyrethrum, azadirachtin, and spinosad, on aquaponics systems. Due to ethical concerns in animal testing, applying insecticides directly to aquaponics setup was impossible. Therefore, three separate experiments were conducted: (1) Pesticide runoff rate – in which insecticides were applied to basil (Ocimum basilicum) plants grown in two hydroponic systems: media bed and floating raft. The concentrations of applied insecticides were measured in the water of nutrient solutions of the hydroponics after 1, 3, 6, 12, 24, 36, 48, 72 and 96h to establish a pattern of degradation of insecticides. The result from this experiment showed that pyrethrum and spinosad were detected in unquantifiable concentrations in the nutrient solutions. Hence, further experiments were conducted only with azadirachtin. In a biofilter trial (2) – azadirachtin, at three concentrations (1.5 µg L-1; 7.5 µg L-1; and 15 µg L-1), was added to a running biofilter to investigate the effects on nitrifying bacteria. Mild effects were recorded in the nitrification and bacteria microbiome. In the third trial (3) – Nile tilapia (Oreochromis niloticus) were exposed to similar concentrations of azadirachtin for seven days (and the same period for recovery) to investigate effects on fish hematology, blood biochemistry, antioxidative enzymes in the brain, gills, muscle, liver and intestine and histopathology of gills and liver. Results showed mild effects in hematology and biochemistry profile in fish and higher levels of lipid peroxidation in the liver during the exposure. The results indicate a safe use of pyrethrum and spinosad in aquaponics setup, while azadirachtin has to be used with care, especially in coupled aquaponics systems.
Use of recycled coal bottom ash in reinforced concrete beams as replacement for aggregate
Authors: Karalar Memduh , Bilir Turhan , Çavuşlu Murat , Özkiliç Yasin Onuralp , Sabri Sabri Mohanad Muayad
Published: November 2022

In this research, it is studied the crack and flexural behavior of reinforced concrete beams with various bottom ash ratios (BARs) considered as fine aggregate in an experimental and numerical investigation. For experimental purposes, different concrete series are considered varying aggregate sizes ranging from 0 to 25 mm. To supplement concrete, bottom ash is put to use in conjunction with material from 0–5 mm in size aggregate particles as replacement for fine aggregates with ratios of 25%, 50%, 75%, and 100%. Experiments were done to investigate the behavior of the beams and how flexural and fracture behaviors are represented. 75% BARs gave optimum results in terms of displacement capacity. Increasing BAR to 100% decrease deflection capacity of the beam. Also, ANSYS software is used to build 3D finite element models (FEMs) of beams to compare with experiment data. Experimental and 3D numerical tests show exceptionally tight flexural and fracture behaviors. Following this, a computer-generated structure is made by running SAP 2000, and the strength of the beams is then utilised in an RC structural model. Every stage of the building’s construction is thoroughly assessed utilizing multiple types of seismic testing, employing the SAP2000 program, with the resulting analysis providing significant findings on how the seismic force of 75% BAR affects horizontal displacement of each floor. The results showed that the weight of the structure dramatically decreases as the number of columns and RCBs are raised while also increasing the number of BARs. Moreover, the magnitude of earthquake and BAR have a significant effect on the horizontal displacement behavior of reinforced concrete structures. The strength of the concrete structure varies between close- and far-fault earthquakes, and for close-fault earthquakes, concrete strength is stronger than for far-fault earthquakes. This brings us to the second disadvantage of BAR which is the 75% strain produces a severe displacement of reinforced concrete structures. Besides, it was seen that the simulations and experiments yield tiny cracks with very identical configurations.
Evaluation of the cell-free DNA integrity index as a liquid biopsy marker to differentiate hepatocellular carcinoma from chronic liver disease
Authors: Kumar Sonu , Nadda Neeti , Paul Shashi , Gamanagatti Shivanand , Dash Nihar Ranjan , Vanamail Perumal , Saraya Anoop , Shalimar  , Nayak Baibaswata
Published: November 2022

Background: Hepatocellular carcinoma (HCC) occurs in the majority of patients with underlying chronic liver disease (CLD) of viral and non-viral etiologies, which requires screening for early HCC diagnosis. Liquid biopsy holds great promise now for early detection, prognosis, and assessment of response to cancer therapy. Cell-free DNA (cfDNA) as a liquid biopsy marker can be easily detected by a real-time quantitative PCR (RT-qPCR) assay for a change in its concentration, integrity, and fragmentation in cancer.

Methods: Patients with HCC (n = 100), CLD (n = 100), and healthy (n = 30) controls were included in the study. The cfDNA was isolated from serum and real-time quantitative PCR (RT-qPCR) was carried out using primer pairs for large (>205 bp) and small (110 bp) fragments of repetitive elements (ALU and LINE1) and housekeeping genes (β-Actin and GAPDH). Total cfDNA concentrations and integrity index were determined by the absolute quantitation method (L/S ratio or cfDII-integrity). The cfDII as a measure of fragmentation was determined by comparative Ct (2–ΔΔCt) method of relative quantification (cfDII-fragmentation). Using a receiver operating characteristic (ROC) curve, cfDII-integrity and cfDII-fragmentation were used to differentiate HCC from CLD patients or healthy controls.

Results: The total cfDNA concentrations in the sera of HCC (244 ng/ml) patients were significantly higher than those of CLD (33 ng/ml) patients and healthy (16.88 ng/ml) controls. HCC patients have shown poor DNA integrity or excess cfDNA fragmentation than CLD patients and healthy controls. The cfDII-integrity of GAPDH and ALU fragment significantly differentiate HCC from CLD at AUROC 0.72 and 0.67, respectively. The cfDII-fragmentation following normalization with cfDNA of healthy control has shown significant differential capabilities of HCC from CLD at AUROC 0.67 using GAPDH and 0.68 using the ALU element. The ROC curve of LINE1 and β-actin cfDII was not found significant for any of the above methods. The cfDII-fragmentation trend in HCC patients of different etiologies was similar indicating increased cfDNA fragmentation irrespective of its etiology.

Conclusion: The cfDII measuring both DNA integrity (L/S ratio) and fragmentation of the Alu and GAPDH genes can differentiate HCC from CLD patients and healthy individuals.
Non-genetic adaptive resistance to KRASG12C inhibition: EMT is not the only culprit
Authors: Ning Wenjuan , Marti Thomas M. , Dorn Patrick , Peng Ren-Wang
Published: November 2022

Adaptions to therapeutic pressures exerted on cancer cells enable malignant progression of the tumor, culminating in escape from programmed cell death and development of resistant diseases. A common form of cancer adaptation is non-genetic alterations that exploit mechanisms already present in cancer cells and do not require genetic modifications that can also lead to resistance mechanisms. Epithelial-to-mesenchymal transition (EMT) is one of the most prevalent mechanisms of adaptive drug resistance and resulting cancer treatment failure, driven by epigenetic reprogramming and EMT-specific transcription factors. A recent breakthrough in cancer treatment is the development of KRASG12C inhibitors, which herald a new era of therapy by knocking out a unique substitution of an oncogenic driver. However, these highly selective agents targeting KRASG12C, such as FDA-approved sotorasib (AMG510) and adagrasib (MRTX849), inevitably encounter multiple mechanisms of drug resistance. In addition to EMT, cancer cells can hijack or rewire the sophisticated signaling networks that physiologically control cell proliferation, growth, and differentiation to promote malignant cancer cell phenotypes, suggesting that inhibition of multiple interconnected signaling pathways may be required to block tumor progression on KRASG12C inhibitor therapy. Furthermore, the tumor microenvironment (TME) of cancer cells, such as tumor-infiltrating lymphocytes (TILs), contribute significantly to immune escape and tumor progression, suggesting a therapeutic approach that targets not only cancer cells but also the TME. Deciphering and targeting cancer adaptions promises mechanistic insights into tumor pathobiology and improved clinical management of KRASG12C-mutant cancer. This review presents recent advances in non-genetic adaptations leading to resistance to KRASG12C inhibitors, with a focus on oncogenic pathway rewiring, TME, and EMT.
Diagnosis and management of gastroenteropancreatic neuroendocrine neoplasms by nuclear medicine: Update and future perspective
Authors: Ma Xing , Ding Ying , Li Wenliang , Li Qiang , Yang Hui
Published: November 2022

Gastrointestinal (GI) cancers are the second most common cause of cancer related deaths in the World. Neuroendocrine neoplasms (NENs) is a rare tumor that originated from peptidergic neurons and neuroendocrine cells. NENs occurs in all parts of the body, especially in stomach, intestine, pancreas and lung. These rare tumors are challenging to diagnose at earlier stages because of their wide anatomical distribution and complex clinical features. Traditional imaging methods including magnetic resonance imaging (MRI) and computed tomography (CT) are mostly of useful for detection of larger primary tumors that are 1cm in size. A new medical imaging specialty called nuclear medicine uses radioactive substances for both diagnostic and therapeutic purposes. Nuclear medicine imaging relies on the tissue-specific uptake of radiolabeled tracers. Nuclear medicine techniques can easily identify the NENs tissues for their ability to absorb and concentrate amine, precursors, and peptides, whereas the traditional imaging methods are difficult to perform well. The somatostatin receptor (SSTR) is a targetable receptor frequently expressed in the gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs), and is a promising target for tumor-targeted therapies and radiography. SSTR based somatostatin receptor imaging and peptide receptor radionuclide therapy (PRRT) has emerged as a new hot subject in the diagnosis and treatment of GEP-NENs due to the rapid development of somatostatin analogues (SSAs) and radionuclide. This review aims to provide an overview of the current status of nuclear medicine imaging modalities in the imaging of GEP-NENs, and puts them in perspective of clinical practice.
Paget’s disease of the breast: Our 20 years’ experience
Authors: Scardina Lorenzo , Di Leone Alba , Magno Stefano , Franco Antonio , Biondi Ersilia , Sanchez Alejandro Martin , D’Archi Sabatino , Gentile Damiano , Fabi Alessandra , Masetti Riccardo , Franceschini Gianluca
Published: November 2022

Introduction

Paget’s disease (PD) represents 1%–3% of all breast cancers and mostly occurs in postmenopausal women. Multiple studies have confirmed that breast-conserving surgery (BCS) followed by radiotherapy is a safe option for patients with in situ or invasive PD, ensuring local control and survival rates similar to those achieved with mastectomy.

Materials and methods

We retrospectively analyzed 115 patients affected by PD treated in our institution between January 2000 and May 2021. Median age at diagnosis was 60 years and median follow-up was 82 months; 69 patients were treated with BCS and 46 were treated with modified radical mastectomy or skin-sparing mastectomy.

Results

At histological examination, 59 patients (59/115, 51.0%) had an underlying invasive carcinoma; in 11 patients (11/115, 9.0%), only PD was found. In 45 patients (45/115, 40.0%), only noninvasive cancer was found. Nine patients (9/115, 7.8%) developed a local recurrence, 7 patients (7/115, 6.0%) are alive with distant metastasis, and 10 patients (10/115, 8.6%) died.

Discussion

In our series, no statistically significant differences were shown between PD alone, PD associated with in situ cancer, and PD with invasive cancer, regardless of the surgical procedure. BCS followed by radiotherapy appears to be an effective and safe option for patients with PD.

Conclusion

PD is a rare form of breast cancer and, in half of the cases, is associated with an invasive carcinoma. Separating our sample into three subgroups based on tumor histology, there were no significant differences in terms of LC, DFS, and OS rate in patients treated with different types of surgery. This study presents some limitations due to its retrospective nature and being confined to a single institution.
Gonadal Y-chromosome mosaicism with 45, X Turner syndrome complicated with bilateral HCG-secreting gonadoblastoma
Authors: Zheng Rujiang , Chen Qiuli , Ma Huamei , Liu Juncheng , Chen Huadong , Liang Jianbo , Chen Hongshan , Zhang Jun , Li Yanhong , Guo Song , Wang Bing , Du Minlian
Published: November 2022

We report a rare case of bilateral HCG-secreting gonadoblastomas (Gb) in a 5.25-year-old girl of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism. The clinical data were summarized, and the literatures were reviewed. The patient had enlarged breasts for 2 years and 3 months, with elevated β-HCG of blood found for 8 months. The level of β-HCG of cerebrospinal fluid, cranial MRI, chest and abdominal CT, and pelvic MRI were normal. After surgical gonad exploration, biopsy and excision, gonad venous blood hormone examination and SRY gene detection of gonad tissue, the diagnosis was confirmed as HCG-secreting Gb (bilateral) and TS (45, X) with gonad Y chromosome mosaicism. The patient received 4 courses of chemotherapy, and regular outpatient follow-up. At 9 months after gonadectomy, there was no clinical, laboratory, or radiological evidence of recurrence. We reported a nonclassical case of 45, X Turner syndrome (TS) with gonadal Y chromosome mosaicism, who presented with breast development as the first manifestation and then virilization due to bilateral HCG-secreting gonadoblastomas. Detection of serum β-HCG and AFP is requisite for the diagnosis of precocious puberty, karyotyping is important for virilizing phenotypic female, and virilization in Turner syndrome implies the existence of Y chromosome(substance) (peripheral blood or tissue mosaicism) and the occurrence of gonadal tumors.
Platycodin D induces apoptosis through JNK1/AP-1/PUMA pathway in non-small cell lung cancer cells: A new mechanism for an old compound
Authors: Chen Shuntai , Wang Qing , Ming Sarah , Zheng Honggang , Hua Baojin , Yang Hsin-Sheng
Published: November 2022

Platycodin D, a triterpenoid monomer, has been shown to possess an anti-tumor effect on various types of cancer. Although Platycodin D has been reported to suppress tumorigenesis, the detailed underlying mechanism remains elusive. Platycodin D treatment significantly reduced the cell viability, decreased the number of colonies, impaired the mitochondrial function, and induced apoptosis in non-small cell lung cancer (NSCLC) cells. To understand the mechanism by which platycodin D induces apoptosis, the expression levels of apoptosis-related proteins were examined, and we found that the expression of PUMA (p53 upregulated modulator of apoptosis) was upregulated upon platycodin D treatment. Knockdown of PUMA resulted in attenuation of platycodin D-induced apoptosis, indicating that PUMA up-regulation is essential for platycodin D to induce apoptosis. The induction of PUMA expression by platycodin D treatment was through activation of AP-1 since mutation of AP-1 binding site in the PUMA promoter abolished the PUMA promoter activity. In addition, the chromatin immunoprecipitation further demonstrated that platycodin D promoted AP-1 binding to PUMA promoter. Moreover, knockdown of JNK1, but not JNK2, significantly abolished the phosphorylation of c-Jun at Ser63 (a component of AP-1), decreased the platycodin D-induced expression of PUMA and cleaved caspase 3, indicating that platycodin D inhibits JNK1/AP-1 signaling pathway. Furthermore, immunohistochemical staining studies showed that tumors from the mice treated with platycodin D activated JNK by translocation of JNK into nuclei, increased phosphorylation of JNK and c-Jun at Ser63 in nuclei, and boosted the PUMA expression. Taken together, our in vitro and in vivo data revealed a novel mechanism by which platycodin D up-regulates PUMA to induce apoptosis through JNK1/AP-1 axis in NSCLC.
Registration of photoacoustic tomography vascular images: Comparison and analysis of automatic registration approaches
Authors: Yu Qinran , Liao Yixing , Liu Kecen , He Zhengyan , Zhao Yuan , Li Faqi , Shan Tianqi
Published: November 2022

Image registration is crucial in the clinical application of photoacoustic tomography (PAT) for vascular growth monitoring. Aiming to find an optimized registration scheme for PAT vascular images acquired at different times and with varying imaging conditions, we compared and analyzed different commonly used intensity-based and feature-based automatic registration schemes. To further improve the registration performance, we proposed a new scheme that combines phase correlation with these commonly used intensity-based registration methods and compared their performances. The objective evaluation measures: peak signal-to-noise ratio (PSNR), structural similarity index metric (SSIM), root mean square error (RMSE), and quantitative visual perception (jump percentage P), as well as subjective evaluation using mean opinion score (MOS), were combined to evaluate the registration performance. Results show that the feature-based approaches in this study were not suitable for PAT image registration. And by adding phase correlation as rough registration, the overall registration performance was improved significantly. Among these methods, the proposed scheme of phase correlation combined with mean square error (MSE) similarity measure and regular-step-gradient-descent optimizer provides the best visual effect, accuracy, and efficiency in PAT vascular image registration.
Validation study of the Italian brief version of the multidimensional jealousy scale: Psychometric properties, measurement invariance across gender, and convergent validity
Authors: Diotaiuti Pierluigi , Valente Giuseppe , Mancone Stefania , Girelli Laura , Cavicchiolo Elisa , Chirico Andrea
Published: November 2022

Introduction

The multidimensional jealousy scale (MJS) is among the most internationally used instruments for the assessment of jealousy in its three dimensions: cognitive, emotional, and behavioral. This study aimed to replicate the Italian validation process of the shortened MJS in order to confirm its psychometric properties and measurement invariance across gender.

Materials and methods

Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted in a large sample of adults (n = 2,928). To reliably estimate mean differences across gender, the measurement invariance of the scale was first established by means of CFA. Convergent validity was than tested by administrating the tool to a convenient sample (n = 304).

Results

A 15-item version of the Italian MJS was retained in its three-factor structure. The tool showed good fit with both the CFA (χ2 = 211.827, CFI = 0.969, TLI = 0.959, RMSEA = 0.047, RMSEA 90% CI = 0.039–0.055) and the results confirmed the strong measurement invariance of the MJS across gender. The internal consistency measures were found to be fully satisfactory. Predictive associations with constructs such as avoidance and anxiety referred to attachment in relationships (ECR-R), obsessive jealousy, depressive jealousy, jealousy associated with separation anxiety, paranoid jealousy (QUEGE), and basic self-esteem (BSE) were confirmed.

Discussion

The MJS is particularly apt to collect information quickly and efficiently about jealousy in a current relationship. The multidimensional and brief structure makes it particularly suitable for preliminary screening, couple therapy assessment, and research purposes.
Visual attention span as a predictor of reading fluency and reading comprehension in Arabic
Authors: Awadh Faris H. R. , Zoubrinetzky Rachel , Zaher Ahmed , Valdois Sylviane
Published: November 2022

Introduction

Visual attention span is a measure of multielement parallel processing. Individuals with higher visual attention span are expected to allocate more attention to letters within strings, which boosts letter identification and translates into more efficient reading. Given the high visual complexity of the Arabic writing system, we expected visual attention span to be an important predictor of reading in the Arabic language.

Methods

Native Arabic readers from Grade 4 and Grade 5 were recruited in Iraqi schools. We assessed the contribution of visual attention span to their reading fluency performance in tasks of fully vowelized word and pseudo-word reading, non-vowelized text reading, and written text comprehension. Their phonological awareness, IQ, and single letter processing speed were further evaluated.

Results

Results showed that visual attention span was a significant unique predictor of all the reading measures. Visual attention span and phonological awareness accounted for a similar amount of variance in word and pseudo-word reading fluency. Visual attention span was a far higher predictor than phonological awareness for text reading fluency and the sole predictor of text comprehension.

Discussion

The role of visual attention span to reading is discussed by reference to current word recognition models. Higher involvement of visual attention is expected in vowelized script to compensate for increased crowding in the presence of diacritics. Visual attention would thus contribute to sub-lexical orthographic parsing and favor orthography-to-phonology mapping, in particular for the pseudo-words that do not benefit from efficient lexical feedback. In non-vowelized script, higher visual attention would enhance the accurate and fast identification of root letters within words, thus resulting in faster word recognition.
The influence of cognitive level on the guaranteed behavioral response of landless farmers in the context of rural revitalization–An empirical study based on partial least squares structural equation modeling
Authors: Lu Yangjie , Dong Hao , Wang Huanyuan
Published: November 2022

With the continuous acceleration of urbanization and agricultural modernization in China, the trend of concentration of rural land transfer is irreversible. For landless farmers, the absence of land guaranteed function inevitably gives rise to the substitution effect of other guaranteed methods. And the subjective preferences exhibited by farmers in making guaranteed behavior decisions can be quantitatively described as guaranteed behavioral responses (GBRs). Based on the analytical framework of distributed cognitive theory, this paper adopts the validated factor analysis method of structural equation modeling to quantitatively study the cognitive basis and behavioral responses of landless farmers’ guaranteed behavior by combining the survey data of rural households in typical rural areas of Wuhan urban area. The study shows that the GBRs of landless farmers are significantly influenced by the cognitive level. “Locality power,” “cultural power,” and “personal power” are the main, important, and effective cognitive levels that influence farmers’ GBRs, respectively. Policy-based protection occupies a dominant position in the rural social guaranteed system, savings-based protection still plays an important function in rural areas, and market-based protection has greater development potential.
Measuring engagement among older adults using a multidimensional approach to communication
Authors: Radnan Madeleine Jessica , Li Weicong , Stevens Catherine J. , Hill Clair , Jones Caroline
Published: November 2022

Characterizing older adult engagement is important to determine the effectiveness of interventions. Engagement refers to the occupying of oneself in external stimuli and is observable across multiple dimensions of behavior. Engagement of older adults is commonly investigated using a single behavioral dimension. There is a dearth of analytical methods that can simultaneously quantify both verbal and non-verbal forms of communication as proxies for engagement. In this article, we present a multidimensional technique to measure engagement of older adults using techniques appropriate for people with varying degrees of dementia. The new analytical approach measures facial movement, lexical use, and prosodic patterns of speech as indices of affective and behavioral outcomes of engagement. Contexts for engagement included a dyadic reminiscence therapy interview and a 12-week technology-driven group reminiscence therapy. Illustrative examples of the technique are described by two participants from two different groups in a naturalistic setting. Application of these analytical techniques can enhance measurement precision and further develop the science and evidence base, especially for, but not confined to, non-pharmacological interventions.
Development of a measure quantifying helpful psychotherapy interventions: The Helpful Therapeutic Attitudes and Interventions Scale
Authors: Li Xiaobao , Gu Hong , Zhao Xudong , Chen Fazhan , Liu Liang
Published: November 2022

Background

Despite the number of empirical studies identifying the helpful factors correlated with beneficial psychotherapy outcomes, there is no validated scale that measures helpful therapeutic attitudes and interventions applied by therapists within the actual therapy process in China. In the current study, we developed the Helpful Therapeutic Attitudes and Interventions Scale (HTAIS) as an accessible client-rated instrument to measure useful interventions applied by the therapist during psychotherapy sessions.

Materials and methods

Based on the results of previous literature and our prior psychotherapy process studies, a 40-item measure was initially designed. Two studies with a total of 2,780 Chinese participants who received psychotherapy were carried out to evaluate the structure, reliability, and validity of the developed scale.

Results

Principal component analysis yielded a three-component HTAIS containing 26 items. The scale included dimensions labeled “Empathy, respect and neutrality,” “Using techniques to solve practical issues,” and “In-depth exploration and expansion.” Confirmatory factor analysis showed the construct validity of the derived three components model. And the developed scale had high internal consistency and test-retest reliability. The scale scores of the HTAIS were positively correlated with those of the Working Alliance Scale and Session Rating Scale, as well as clients’ perceived therapy satisfaction, thus supporting its concurrent validity.

Conclusion

The HTAIS allows an immediate examination, as experienced by the client, of the extent to which certain useful therapeutics interventions have been conducted during therapy and could help to improve the clinician’s subsequent therapy strategies. Future research is suggested to further validate the scale, especially to assess its psychometric properties in various populations with different clinical complaints.
Smoking cessation in the elderly as a sign of susceptibility to symptomatic COVID-19 reinfection in the United States
Authors: Ando Wataru , Horii Takeshi , Jimbo Mitsuki , Uematsu Takayuki , Atsuda Koichiro , Hanaki Hideaki , Otori Katsuya
Published: November 2022

Background

We aimed to clarify the relationship between coronavirus disease 2019 (COVID-19) reinfection and basic disease and smoking status.

Methods

The electronic health records of 165,320 patients with COVID-19 from January 1, 2020, to August 27, 2021, were analyzed. Data on age, race, sex, smoking status (never, current, former), and basic disease were analyzed using Cox proportional hazard models.

Results

In total, 6,133 patients (3.7%) were reinfected. The overall reinfection rate for never, current, and former smokers was 4.2, 3.5, and 5.7%, respectively. Although the risk of reinfection was highest among former smokers aged ≥65 years (7.7% [422/5,460]), the reinfection rate among current smokers aged ≥65 years was 6.2% (341/5,543). Among reinfected patients, the number of basic diseases was higher in former smokers (2.41 ± 1.16) than in current (2.28 ± 1.07, P = 0.07) and never smokers (2.07 ± 1.05, P < 0.001). Former smokers who are older may have been exposed to factors that increase their risk of symptomatic COVID-19 reinfection.
A GEE toolkit for water quality monitoring from 2002 to 2022 in support of SDG 14 and coral health in marine protected areas in Belize
Authors: Callejas Ileana A. , Osborn Katie , Lee Christine , Mishra Deepak R. , Auil Gomez Nicole , Carrias Abel , Cherrington Emil A. , Griffin Robert , Rosado Andria , Rosado Samir , Jay Jennifer
Published: November 2022

Coral reefs are highly diverse ecosystems that provide many goods and ecosystem services globally. Coral reef ecosystems are also threatened by environmental stressors from anthropogenic sources and shifting climates. The United Nations Sustainable Development Goal 14 (“Life Below Water”) addresses the need to conserve and sustainably use the ocean, seas, and marine ecosystems, including reef systems. Belize’s coral reef system is the second largest in the world, providing sources of income to Belizeans through tourism and fisheries as well as coastline protection. In order to conserve their marine ecosystems, Belize has a network of Marine Protected Areas (MPAs) throughout their coastal waters. Using Aqua MODIS satellite imagery from 2002 to 2022, Google Earth Engine, and RStudio, we present a workflow to calculate stress days on MPAs and a coral vulnerability index based on sea surface temperature (SST) and Kd (490), a proxy of water clarity. The Corozal Bay, Swallow Caye, Port Honduras, and South Water Caye MPAs had the highest percentages of stress days and coral vulnerability stress index score based on these two parameters among the 24 MPAs analyzed. Additionally, SST in the warmest month of the year in Belize were seen to increase across all MPAs from 2002 to 2022 (p < 0.01). This GEE toolkit provides a straightforward and accessible tool to help governments monitor both water quality and risks to coral reefs in accordance with SDG 14.
Performance analysis of code division multiplexing communication under evaporation duct environment
Authors: Liu Wenjing , Liu Xiqing , Yan Shi , Zhao Linglan , Peng Mugen
Published: November 2022

The evaporation duct is an effective means for realizing non-line-of-sight (NLOS) wireless transmission over the sea. However, the effects of marine weather conditions on electromagnetic propagation have rarely been studied. In this study, the influence of the marine atmospheric environment on electromagnetic propagation was analyzed through numerical simulation. Additionally, the impacts of antenna height, transmission distance, and electromagnetic wave frequency on path loss were studied. Finally, the link capacity of the code division multiplexing (CDM) communication system in the evaporation duct environment was studied via numerical analysis and simulations. Simulation results demonstrated that CDM communication technology can improve the link capacity under an evaporation duct compared with that of the spread-spectrum communication technology.
Cold for gravity, heat for microgravity: A critical analysis of the “Baby Astronaut” concept
Authors: Meigal Alexander , Gerasimova-Meigal Liudmila
Published: November 2022

The existing literature suggests that temperature and gravity may have much in common as regulators of physiological functions. Cold, according to the existing literature, shares with gravity common effects on the neuromuscular system, while heat produces effects similar to those of microgravity. In addition, there are studies evidencing unidirectional modification of the motor system to heat and hypoxia. Such agonistic relationship in a triad of “microgravity, heat, and hypoxia” and in a pair of “cold and gravity” in their effect on the neuromuscular system may have evolutionary origins. To address this problem, ten years ago, we came up with a concept with the working name Baby Astronaut hypothesis, which posed that “Synergetic adaptation of the motor system to different environments comes from their ontogenetic synchronicity.” More specifically, the synchronicity of microgravity (actually, the “wet immersion” model of microgravity), higher temperature, and hypoxia are the characteristics of the intrauterine environment of the fetus. After childbirth, this group of factors is rapidly replaced by the “extrauterine,” routine environment characterized by Earth gravity (1 G), normoxia, and lower ambient temperature. The physiological effect of cold and gravity on the motor system may well be additive (synergistic). We earlier estimated a “gravity-substitution” potential of cold-induced activity and adaptation to cold as 15–20% of G, which needs further validation and correction. In this study, we sought to critically analyze the interaction of temperature and gravity, based on the concept of Baby Astronaut, using data from the new academic literature. We have come to the conclusion that the concept of Baby Astronaut can be regarded as valid only for species such as a rat (immature, altricial species), but not for a human fetus. Several confirmatory experiments were suggested to verify (or falsify) the concept, which would allow us to consider it as empirical. In addition, the interaction of temperature and gravity may be of practical interest in the fields of neurorehabilitation and habilitation in childhood for constructing a physical environment, which would help strengthen or weaken muscle tone in specific muscles.
Can the Foods We Eat Help Treat Alzheimer’s Disease?
Authors: Gualtieri Claudia , Smith Zachary M. , Cruz Abby , Parry Crystal , Vonhoff Fernando J.
Published: November 2022

Can you imagine a world in which doctors prescribe food when we are sick? Traditionally, doctors have prescribed medications to treat sickness. Most of these medications, known as pharmaceuticals, were developed by researchers. Pharmaceuticals are made to interact with molecules associated with specific diseases, to reduce patients’ symptoms. Recent studies have shown that natural compounds found in foods can alleviate illnesses. In contrast to pharmaceuticals, we can take in these compounds, called nutraceuticals, through the foods we eat every day. Nutraceuticals have been studied in various organisms, and their effects on the bacteria that live in the digestive system have also been examined. Studies in fruit flies have shown that nutraceuticals can be beneficial for treating some brain diseases. This article will describe promising nutraceuticals that could be used to treat Alzheimer’s disease, which affects many older people worldwide.
Three-dimensional ready-to-pick reservoir-based preconcentrator with a pillar-structured channel for miRNA applications
Authors: Lee Seungmin , Kim Jinhwan , Lee Na Eun , Kim Kang Hyeon , Park Seong Jun , Park Jeong Soo , Kim Cheonjung , Hong Ji Hye , Yoon Dae Sung , Yoo Yong Kyoung , Lee Jeong Hoon
Published: November 2022

A sample preconcentration technique that exceeds a microfluidic device’s limited processing volume (up to microliters) is critical for real sample pretreatment applications. Here, we have developed a 3D-printed preconcentrator with a pillar structure (3DP2) to enrich the biological samples up to hundreds of microliter scales (700 μL) within 20 min by utilizing ion concentration polarization (ICP). We designed three-dimensional ready-to-pick reservoirs serially connected with a pillar-structured channel to enable large-volume preconcentration by balancing the preconcentrating forces (depletion, electrophoretic, and electroosmotic force) generated by ICP. Using the I-t and I-V curves, we confirmed that ICP performance was enhanced due to a pillar structure’s suppression of the vortex. Finally, we preconcentrated bovine serum albumin (BSA) and micro ribonucleic acid-21 (miRNA-21) two-fold. Moreover, depending on their size and charge, these were concentrated at different locations and could be extracted easily using pipettes. We believe that this study provides a novel strategy for downstream applications.