bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal Age and Behavior during Pregnancy Affect the 2D:4D Digit Ratio in Polish Children Aged 6–13 Years
Authors: Sitek Aneta , Rosset Iwona , Kobus Magdalena , Pruszkowska-Przybylska Paulina , Żądzińska Elżbieta
Published: August 2022

Background: The length of the second and fourth finger calculated as a ratio (2D:4D) is a marker of prenatal exposure to sex hormones. Higher exposure to testosterone is related to a lower 2D:4D digit ratio, and inversely, higher exposure to estrogen is related to a higher 2D:4D. The digit ratio in humans (prenatally determined by sex hormone levels and androgen receptor activity) is associated with multiple biological, cognitive, and behavioral traits, as well as health in later life. The aim of this study was to verify if maternal traits during pregnancy are associated with 2D:4D among their children. Methods: We investigated 537 boys, 646 girls, and their mothers. The investigation consisted of a questionnaire and a measurement part. In the questionnaire, we included questions about maternal traits during pregnancy such as: illnesses, active and passive smoking, work activity, psychological trauma (death or serious illness of a loved one, divorce, job loss), and age. We performed length measurements of the second and fourth fingers on both hands for both study groups. Results: The GLM analysis showed that children of smoking mothers were characterized by a higher 2D:4D R as compared to their peers whose mothers did not smoke (β = 0.10, p = 0.0008). In turn, the offspring of women who worked during pregnancy exhibited lower 2D:4D R values than the children of women who did not work (β = −0.07, p = 0.0233). It should be noted, however, that the effects of those maternal factors were small, as each of them explained less than 1% of 2D:4D R in the population, adjusted for child age and sex. Pearson’s linear correlation revealed that maternal age was negatively correlated with 2D:4D R in daughters (r = −0.11, p = 0.0137), but not in sons (r = 0.02, p = 0.6908). The negative correlation of 2D:4D R with maternal age indicates that the daughters of older mothers exhibited lower values of that ratio relative to the same-age daughters of younger mothers. Conclusions: For both study groups, the right-hand digit ratio was positively correlated with maternal smoking and negatively with maternal work during pregnancy. Maternal age during pregnancy was negatively related to right hand 2D:4D only among girls.
Role of Gut Microbiota through Gut–Brain Axis in Epileptogenesis: A Systematic Review of Human and Veterinary Medicine
Authors: Gernone Floriana , Uva Annamaria , Silvestrino Marco , Cavalera Maria Alfonsa , Zatelli Andrea
Published: August 2022

Canine idiopathic epilepsy is a common neurological disease characterized by the enduring predisposition of the cerebral cortex to generate seizures. An etiological explanation has not been fully identified in humans and dogs, and, among the presumed causes, several studies support the possible involvement of gut microbiota. In this review, the authors summarize the evidence of the reasonable role of gut microbiota in epilepsy through the so-called gut–brain axis. The authors provide an overview of recent clinical and preclinical studies in humans and dogs in which the modulation of intestinal permeability, the alteration of local immune response, and the alteration in production of essential metabolites and neurotransmitters associated with dysbiosis could be responsible for the pathogenesis of canine epilepsy. A systematic review of the literature, following the PRISMA guidelines, was performed in two databases (PubMed and Web of Science). Eleven studies were included and reviewed supporting the connection between gut microbiota and epilepsy via the gut–brain axis.
Progress and Impact of Latin American Natural Product Databases
Authors: Gómez-García Alejandro , Medina-Franco José L.
Published: August 2022

Natural products (NPs) are a rich source of structurally novel molecules, and the chemical space they encompass is far from being fully explored. Over history, NPs have represented a significant source of bioactive molecules and have served as a source of inspiration for developing many drugs on the market. On the other hand, computer-aided drug design (CADD) has contributed to drug discovery research, mitigating costs and time. In this sense, compound databases represent a fundamental element of CADD. This work reviews the progress toward developing compound databases of natural origin, and it surveys computational methods, emphasizing chemoinformatic approaches to profile natural product databases. Furthermore, it reviews the present state of the art in developing Latin American NP databases and their practical applications to the drug discovery area.
The Next Frontier in Health Disparities—A Closer Look at Exploring Sex Differences in Glioma Data and Omics Analysis, from Bench to Bedside and Back
Authors: Diaz Rosario Maria , Kaur Harpreet , Tasci Erdal , Shankavaram Uma , Sproull Mary , Zhuge Ying , Camphausen Kevin , Krauze Andra
Published: August 2022

Sex differences are increasingly being explored and reported in oncology, and glioma is no exception. As potentially meaningful sex differences are uncovered, existing gender-derived disparities mirror data generated in retrospective and prospective trials, real-world large-scale data sets, and bench work involving animals and cell lines. The resulting disparities at the data level are wide-ranging, potentially resulting in both adverse outcomes and failure to identify and exploit therapeutic benefits. We set out to analyze the literature on women’s data disparities in glioma by exploring the origins of data in this area to understand the representation of women in study samples and omics analyses. Given the current emphasis on inclusive study design and research, we wanted to explore if sex bias continues to exist in present-day data sets and how sex differences in data may impact conclusions derived from large-scale data sets, omics, biospecimen analysis, novel interventions, and standard of care management.
Identification of Adipocytokine Pathway-Related Genes in Epilepsy and Its Effect on the Peripheral Immune Landscape
Authors: Chen Jinkun , Sun Ruohan , Jin Di , Yang Quan , Yang He , Long Yu , Li Lixian
Published: August 2022

Epilepsy is a multifactorial neurological disorder with recurrent epileptic seizures. Current research stresses both inflammatory and autoimmune conditions as enablers in the pathophysiological process of epilepsy. In view of the growing concern about the role of adipocytokines in antiepileptic and modulating immune responses, we aimed to investigate the relevance of the adipocytokine signaling pathway in the pathological process of epilepsy and its impacts on peripheral immune characteristics. In this study, expression profiles of 142 peripheral blood samples were downloaded from the Gene Expression Omnibus (GEO) database. Adipocytokine pathway-related genes were screened out by feature selection using machine-learning algorithms. A nomogram was then constructed and estimated for the efficacy of diagnosis. Cluster analysis was employed for the recognization of two distinct epilepsy subtypes, followed by an estimation of the immune cell infiltration levels using single-sample gene-set enrichment analysis (ssGSEA). The biological characteristics were analyzed by functional enrichment analysis. The aberrant regulation of adipocytokine signaling pathway was found in the peripheral blood of patients with epilepsy. Twenty-one differently expressed adipocytokine pathway-related genes were identified and five (RELA, PRKAB1, TNFRSF1A, CAMKK2, and CPT1B) were selected to construct a nomogram. Subsequent validations of its forecasting ability revealed that this model has satisfactory predictive value. The immune cell infiltration degrees, such as those of innate immune cells and lymphocytes, were found to significantly correlate to the levels of adipocytokine pathway-related genes. Additionally, 239 differentially expressed genes (DEGs) were identified and their biological functions were mainly enriched in the regulation of the immune response. In conclusion, our results confirmed the predictive value of adipocytokine pathway-related genes for epilepsy and explored their effects on immune infiltration, thereby improving our understanding of the pathogenesis of epilepsy and providing assistance in the diagnosis and treatment of epilepsy.
MicroRNA-223 Attenuates Stretch-Injury-Induced Apoptosis in Brain Microvascular Endothelial Cells by Regulating RhoB Expression
Authors: Liu Yingliang , Li Wenjing , Liu Yingxiu , Jiang Yang , Wang Yida , Xu Zhiming , Cui Daming , Gao Liang
Published: August 2022

MiR-223 is a miRNA with important functions in apoptosis, carcinogenesis, and inflammation, and it was demonstrated to be over-expressed in brain tissue after traumatic brain injury (TBI). However, few studies have focused on its role in protecting brain microvascular endothelial cells (BMECs). This study evaluated the protective effect of miR-223 on BMECs after stretch injury (SI). bEnd.3 cells (BMECs of mouse) were transfected with overexpressing and blocking lentivirus of miR-223, then were subjected to SI. After immunofluorescence assay, it was demonstrated that miR-223 overexpression significantly rescued the SI-induced loss of ZO-1 (Zonula Occludens 1, tight junction protein) (p < 0.01), while miR-223 blocking exacerbated the loss of ZO-1 (p < 0.05). Flow cytometry confirmed a significant increase in the proportion of apoptotic bEnd.3 cells after SI, and miR-223 overexpression reduced this proportion (p < 0.001). The result of Western blot revealed that miR-223 overexpression significantly reduced the expression of cleaved caspase-3 (cl-caspase 3) (p < 0.05) and RhoB (p < 0.01), while miR-223 blocking increased the expression of these proteins (p < 0.05, p < 0.001). Additionally, knockdown of RhoB significantly reduced the expression of cl-caspase 3 (p < 0.001). These findings suggested that miR-223 can alleviate SI-induced apoptosis of BMECs, and this anti-apoptotic effect is at least partially achieved by inhibiting the expression of RhoB. Moreover, miR-223 may play a role in maintaining the integrity of BBB during TBI.
The Use of Mechanical Ventilation Support at the End of Life in Motor Neurone Disease/Amyotrophic Lateral Sclerosis: A Scoping Review
Authors: Wilson Eleanor , Lee Jeong-Su , Wenzel David , Faull Christina
Published: August 2022

There has been an increase in the use of mechanical ventilation (MV) in motor neurone disease (MND) to alleviate symptoms related to hypoventilation. Little is known about its use at the end of life, and the withdrawal of MV is a challenging topic. A scoping review was conducted to map the existing evidence of ventilation use at the end of life in MND. The Joanna Briggs Institute methodological framework was used, and a total of 31 documents were included in the data extraction. Boarder themes around place, planning, cause and comments on death were identified. Our findings show that the focus of the literature has been on the process of the withdrawal of ventilation, creating the subthemes of timing and reason for withdrawal, along with ethical, emotional, and practical issues, medications used and the time until death. There is a foundation of evidence to guide the process and discuss the ethical and emotional issues of withdrawing ventilation. However, there remains limited evidence from patient and family member perspectives. Importantly, there is almost no evidence exploring dying with ventilation in place, the active or passive decisions around this process, how the interface might impact the dying process, or what families think about this.
Exploring the Key Indicators of Social Impact Assessment for Sponge City PPPs: A Sustainable Development Perspective
Authors: Li Wei , Guo Jiyue , Yuan Jingfeng , Liu Henry J. , Edwards David J.
Published: August 2022

Sponge city (SPC) is currently being promoted as an initiative under the principle of sustainable development to solve the urban water crisis across China. Moreover, with the introduction of the public-private partnerships (PPPs) in SPC development, the public’s concern regarding SPC PPPs has increased in terms of their more sophisticated outcomes and greater social impacts than general urban development. Thus, to develop an effective set of SIA key indicators for SPC PPPs, this study uses social impact theory (SIT) to explore in greater detail the influencing mechanism for the social impact assessment (SIA) conceptual model proposed in the authors’ previous studies. Confirmatory factor analysis (CFA) was applied to examine whether the hypothesized relationships in the influencing mechanism fit the empirical data and to further consolidate the SIA key indicators. Based on a survey questionnaire and CFA results, a verified and refined SIA framework using 23 key indicators and five corresponding dimensions was proposed, particularly within the context of SPC PPPs. Implications generated from the CFA were discussed to improve the comprehensive performance of sponge city PPPs. These 23 key indicators and the clarification of their relationships to the respective SIA dimensions and to the overall SIA results can be a useful tool for enhancing the social benefits of SPC PPPs. Moreover, this study also provides governments with insights into enabling the low-impact and sustainable development of infrastructure within urban areas.
Fuzzy Comprehensive Evaluation of APTS Dispatcher Working Level Based on Cloud Model
Authors: Guan Deyong , Xu Yue , Xue Yuxuan , Meng Kun
Published: August 2022

Many cities in China have built an advanced public transportation system (APTS) in recent years. These systems cannot carry out automated dispatches but rely on the dispatcher to ensure normal operations. Based on the theory of fuzzy comprehensive evaluation, this study created a hierarchical evaluation model to evaluate the work level of the dispatcher. Firstly, a hierarchical evaluation system was established based on the data of line complexity and dispatch workload provided by the APTS. Secondly, we assigned the weight of the evaluating indicator by combing an expert scoring method and the entropy weight method. We then transformed the quantitative data into qualitative evaluation data with a cloud model. Through a comparison with the standard cloud, the work level of an APTS dispatcher can be defined. The evaluation results for 12 cities in China showed that there was no obvious connection between the working level and bus company size, but the work level was always higher in large cities. We finally obtained the standard range of the evaluation indicator through cluster analysis. This method can be used as a reference to evaluate the work level of dispatchers in other cities, and can reflect the correlation between the work level and dispatching system construction, population and city size.
Comparison of Summer Outdoor Thermal Environment Optimization Strategies in Different Residential Districts in Xi’an, China
Authors: Zhang Xuefeng , Wang Yupeng , Zhou Dian , Yang Chao , An Huibin , Teng Teng
Published: August 2022

Residential districts account for the most common type of urban land coverage. Massive developments with high density have a huge impact on the urban climate. In this study, we explored the thermal environment optimization strategies of residential districts with different development intensities (plot ratios) from the perspective of urban renewal and residential district design in Xi’an, China. We selected residential districts with low, medium, and high plot ratios in Xi’an City for field measurements and environmental simulation according to five proposed optimization strategies. By comparing the air temperature, mean radiant temperature, and physiological equivalent temperature at the pedestrian height, 1.5 m from the ground, we explored the thermal environment optimization texture of each strategy. The results showed that the same strategy introduced different effects in different residential districts. Increasing the road reflectivity had the best effect on residential districts that had a low plot ratio, whereas planting trees was the best effect in districts with medium and high plot ratios. Planting lawns had a better effect in districts with high plot ratios. The findings of this study provide suggestions for the optimization and reconstruction of residential districts and contribute to future residential district development and design.
Targeting the Unwindosome by Mebendazole Is a Vulnerability of Chemoresistant Hepatoblastoma
Authors: Li Qian , Demir Salih , Del Río-Álvarez Álvaro , Maxwell Rebecca , Wagner Alexandra , Carrillo-Reixach Juan , Armengol Carolina , Vokuhl Christian , Häberle Beate , von Schweinitz Dietrich , Schmid Irene , Cairo Stefano , Kappler Roland
Published: August 2022

Resistance to conventional chemotherapy remains a huge challenge in the clinical management of hepatoblastoma, the most common liver tumor in childhood. By integrating the gene expression data of hepatoblastoma patients into the perturbation prediction tool Connectivity Map, we identified the clinical widely used anthelmintic mebendazole as a drug to circumvent chemoresistance in permanent and patient-derived xenograft cell lines that are resistant to cisplatin, the therapeutic backbone of hepatoblastoma treatment. Viability assays clearly indicated a potent reduction of tumor cell growth upon mebendazole treatment in a dose-dependent manner. The combination of mebendazole and cisplatin revealed a strong synergistic effect, which was comparable to the one seen with cisplatin and doxorubicin, the current treatment for high-risk hepatoblastoma patients. Moreover, mebendazole treatment resulted in reduced colony and tumor spheroid formation capabilities, cell cycle arrest, and induction of apoptosis of hepatoblastoma cells. Mechanistically, mebendazole causes blockage of microtubule formation and transcriptional downregulation of genes encoding the unwindosome, which are highly expressed in chemoresistant tumors. Most importantly, mebendazole significantly reduced tumor growth in a subcutaneous xenograft transplantation mouse model without side effects. In conclusion, our results strongly support the clinical use of mebendazole in the treatment of chemoresistant hepatoblastoma and highlight the potential theranostic value of unwindosome-associated genes.
A Pan-Cancer Assessment of RB1/TP53 Co-Mutations
Authors: Cai Ling , DeBerardinis Ralph J. , Xiao Guanghua , Minna John D. , Xie Yang
Published: August 2022

Nearly all tumors have multiple mutations in cancer-causing genes. Which of these mutations act in tandem with other mutations to drive malignancy and also provide therapeutic vulnerability? To address this fundamental question, we conducted a pan-cancer screen of co-mutation enrichment (looking for two genes mutated together in the same tumor at a statistically significant rate) using the AACR-GENIE 11.0 data (AACR, Philadelphia, PA, USA). We developed a web tool for users to review results and perform ad hoc analyses. From our screen, we identified a number of such co-mutations and their associated lineages. Here, we focus on the RB1/TP53 co-mutation, which we discovered was the most frequently observed co-mutation across diverse cancer types, with particular enrichment in small cell carcinomas, neuroendocrine carcinomas, and sarcomas. Furthermore, in many cancers with a substantial fraction of co-mutant tumors, the presence of concurrent RB1/TP53 mutations is associated with poor clinical outcomes. From pan-cancer cell line multi-omics and functional screening datasets, we identified many targetable co-mutant-specific molecular alterations. Overall, our analyses revealed the prevalence, cancer type-specificity, clinical significance, and therapeutic vulnerabilities of the RB1/TP53 co-mutation in the pan-cancer landscape and provide a roadmap forward for future clinical translational research.
Association of rs9679162 Genetic Polymorphism and Aberrant Expression of Polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) in Head and Neck Cancer
Authors: Lin Nan-Chin , Shih Yin-Hwa , Chiu Kuo-Chou , Li Po-Jung , Yang Hui-Wu , Lan Wan-Chen , Hsia Shih-Min , Wang Tong-Hong , Shieh Tzong-Ming
Published: August 2022

The polypeptide N-Acetylgalactosaminyltransferase 14 (GALNT14) rs9679162 and mRNA expression were associated with treatment outcome in various cancers. However, the relation of GALNT14 and head and neck cancer were nuclear. A total of 199 patients with head and neck squamous cell carcinoma (HNSCC) were collected in this study, including oral SCC (OSCC), oropharyngeal SCC (OPSCC), laryngeal SCC (LSCC), and others. The DNA and RNA of cancer tissues were extracted using the TRI Reagent method. The rs9679162 was analyzed using polymerase chain reaction (PCR) and sequencing methods in 199 DNA specimens, and the mRNA expression was analyzed using quantitative reverse transcription PCR (RT-qPCR) methods in 68 paired RNA specimens of non-cancerous matched tissues (NCMT) and tumor tissues. The results showed that the genotype of TT, TG, and GG appeared at 30%, 44%, and 26%, respectively. Non-TT genotype or G alleotype were associated with alcohol, betel nut, and cigarette using among patients with OSCC, and it also affected the treatment and survival of patients with OSCC and LSCC. High GALNT14 mRNA expression levels increased lymphatic metastasis of patients with HNSCC, and treatment and survival in patients with OPSCC. Overall, the GALNT14-rs9679162 genotype and mRNA expression level can be used as indicators of HNSCC treatment prognosis.
Identification of Src Family Kinases as Potential Therapeutic Targets for Chemotherapy-Resistant Triple Negative Breast Cancer
Authors: Kohale Ishwar N. , Yu Jia , Zhuang Yongxian , Fan Xiaoyang , Reddy Raven J. , Sinnwell Jason , Kalari Krishna R. , Boughey Judy C. , Carter Jodi M. , Goetz Matthew P. , Wang Liewei , White Forest M.
Published: August 2022

Neoadjuvant chemotherapy (NAC) remains the cornerstone of the treatment for triple negative breast cancer (TNBC), with the goal of complete eradication of disease. However, for patients with residual disease after NAC, recurrence and mortality rates are high and the identification of novel therapeutic targets is urgently needed. We quantified tyrosine phosphorylation (pTyr)-mediated signaling networks in chemotherapy sensitive (CS) and resistant (CR) TNBC patient-derived xenografts (PDX), to gain novel therapeutic insights. The antitumor activity of SFK inhibition was examined in vivo. Treated tumors were further subjected to phosphoproteomic and RNAseq analysis, to identify the mechanism of actions of the drug. We identified Src Family Kinases (SFKs) as potential therapeutic targets in CR TNBC PDXs. Treatment with dasatinib, an FDA approved SFK inhibitor, led to inhibition of tumor growth in vivo. Further analysis of post-treatment PDXs revealed multiple mechanisms of actions of the drug, confirming the multi-target inhibition of dasatinib. Analysis of pTyr in tumor specimens suggested a low prevalence of SFK-driven tumors, which may provide insight into prior clinical trial results demonstrating a lack of dasatinib antitumor activity in unselected breast cancer patients. Taken together, these results underscore the importance of pTyr characterization of tumors, in identifying new targets, as well as stratifying patients based on their activated signaling networks for therapeutic options. Our data provide a strong rationale for studying SFK inhibitors in biomarker-selected SFK-driven TNBC.
Contributions of Circulating microRNAs for Early Detection of Lung Cancer
Authors: Vykoukal Jody , Fahrmann Johannes F. , Patel Nikul , Shimizu Masayoshi , Ostrin Edwin J. , Dennison Jennifer B. , Ivan Cristina , Goodman Gary E. , Thornquist Mark D. , Barnett Matt J. , Feng Ziding , Calin George A. , Hanash Samir M.
Published: August 2022

There is unmet need to develop circulating biomarkers that would enable earlier interception of lung cancer when more effective treatment options are available. Here, a set of 30 miRNAs, selected from a review of the published literature were assessed for their predictive performance in identifying lung cancer cases in the pre-diagnostic setting. The 30 miRNAs were assayed using sera collected from 102 individuals diagnosed with lung cancer within one year following blood draw and 212 controls matched for age, sex, and smoking status. The additive performance of top-performing miRNA candidates in combination with a previously validated four-protein marker panel (4MP) consisting of the precursor form of surfactant protein B (Pro-SFTPB), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and cytokeratin-19 fragment (CYFRA21-1) was additionally assessed. Of the 30 miRNAs evaluated, five (miR-320a-3p, miR-210-3p, miR-92a-3p, miR-21-5p, and miR-140-3p) were statistically significantly (Wilcoxon rank sum test p < 0.05) elevated in case sera compared to controls, with individual AUCs ranging from 0.57–0.62. Compared to the 4MP alone, the combination of 3-miRNAs + 4MP improved sensitivity at 95% specificity by 19.1% ((95% CI of difference 0.0–28.6); two-sided p: 0.006). Our findings demonstrate utility for miRNAs for early detection of lung cancer in combination with a four-protein marker panel.
Oncogenic EFNA4 Amplification Promotes Lung Adenocarcinoma Lymph Node Metastasis
Authors: Zhao Xiangyu , Chen Yuxing , Sun Xiaoqin , He Zaoke , Wu Tao , Wu Chenxu , Chen Jing , Wang Jinyu , Diao Kaixuan , Liu Xue-Song
Published: August 2022

Lymph nodes metastases are common in patients with lung cancer. Additionally, those patients are often at a higher risk for death from lung tumor than those with tumor-free lymph nodes. Somatic DNA alterations are key drivers of cancer, and copy number alterations (CNAs) are major types of DNA alteration that promote lung cancer progression. Here, we performed genome-wide DNA copy number analysis, and identified a novel lung-cancer-metastasis-related gene, EFNA4. The EFNA4 genome locus was significantly amplified, and EFNA4 mRNA expression was significantly up-regulated in lung cancer compared with normal lung tissue, and also in lung cancer with lymph node metastases compared with lung cancer without metastasis. EFNA4 encodes Ephrin A4, which is the ligand for Eph receptors. The function of EFNA4 in human lung cancer remains largely unknown. Through cell line experiments we showed that EFNA4 overexpression contributes to lung tumor cells growth, migration and adhesion. Conversely, EFNA4 knockdown or knockout led to the growth suppression of cells and tumor xenografts in mice. Lung cancer patients with EFNA4 overexpression have poor prognosis. Together, by elucidating a new layer of the role of EFNA4 in tumor proliferation and migration, our study demonstrates a better understanding of the function of the significantly amplified and overexpressed gene EFNA4 in lung tumor metastasis, and suggests EFNA4 as a potential target in metastatic lung cancer therapy.
Critical Investigation of the Usability of Hepatoma Cell Lines HepG2 and Huh7 as Models for the Metabolic Representation of Resectable Hepatocellular Carcinoma
Authors: Schicht Gerda , Seidemann Lena , Haensel Rene , Seehofer Daniel , Damm Georg
Published: August 2022

Metabolic alterations in hepatocellular carcinoma (HCC) are fundamental for the development of diagnostic screening and therapeutic intervention since energy metabolism plays a central role in differentiated hepatocytes. In HCC research, hepatoma cell lines (HCLs) like HepG2 and Huh7 cells are still the gold standard. In this study, we characterized the metabolic profiles of primary human hepatoma cells (PHCs), HCLs and primary human hepatocytes (PHHs) to determine their differentiation states. PHCs and PHHs (HCC-PHHs) were isolated from surgical specimens of HCC patients and their energy metabolism was compared to PHHs from non-HCC patients and the HepG2 and Huh7 cells at different levels (transcript, protein, function). Our analyses showed successful isolation of PHCs with a purity of 50–73% (CK18+). The transcript data revealed that changes in mRNA expression levels had already occurred in HCC-PHHs. While many genes were overexpressed in PHCs and HCC-PHHs, the changes were mostly not translated to the protein level. Downregulated metabolic key players of PHCs revealed a correlation with malign transformation and were predominantly pronounced in multilocular HCC. Therefore, HCLs failed to reflect these expression patterns of PHCs at the transcript and protein levels. The metabolic characteristics of PHCs are closer to those of HCC-PHHs than to HCLs. This should be taken into account for future optimized tumor metabolism research.
Auramine O UV Photocatalytic Degradation on TiO2 Nanoparticles in a Heterogeneous Aqueous Solution
Authors: Kong Cristina Pei Ying , Suhaimi Nurul Amanina A. , Shahri Nurulizzatul Ningsheh M. , Lim Jun-Wei , Nur Muhammad , Hobley Jonathan , Usman Anwar
Published: August 2022

Amongst the environmental issues throughout the world, organic synthetic dyes continue to be one of the most important subjects in wastewater remediation. In this paper, the photocatalytic degradation of the dimethylmethane fluorescent dye, Auramine O (AO), was investigated in a heterogeneous aqueous solution with 100 nm anatase TiO2 nanoparticles (NPs) under 365 nm light irradiation. The effect of irradiation time was systematically studied, and photolysis and adsorption of AO on TiO2 NPs were also evaluated using the same experimental conditions. The kinetics of AO photocatalytic degradation were pseudo-first order, according to the Langmuir–Hinshelwood model, with a rate constant of 0.048 ± 0.002 min−1. A maximum photocatalytic efficiency, as high as 96.2 ± 0.9%, was achieved from a colloidal mixture of 20 mL (17.78 μmol L−3) AO solution in the presence of 5 mg of TiO2 NPs. The efficiency of AO photocatalysis decreased nonlinearly with the initial concentration and catalyst dosage. Based on the effect of temperature, the activation energy of AO photocatalytic degradation was estimated to be 4.63 kJ mol−1. The effect of pH, additional scavengers, and H2O2 on the photocatalytic degradation of AO was assessed. No photocatalytic degradation products of AO were observed using UV–visible and Fourier transform infrared spectroscopy, confirming that the final products are volatile small molecules.
Sex-Dependent Role of Adipose Tissue HDAC9 in Diet-Induced Obesity and Metabolic Dysfunction
Authors: Goo Brandee , Ahmadieh Samah , Zarzour Abdalrahman , Yiew Nicole K. H. , Kim David , Shi Hong , Greenway Jacob , Cave Stephen , Nguyen Jenny , Aribindi Swetha , Wendolowski Mark , Veerapaneni Praneet , Ogbi Mourad , Chen Weiqin , Lei Yun , Lu Xin-Yun , Kim Ha Won , Weintraub Neal L.
Published: August 2022

Obesity is a major risk factor for both metabolic and cardiovascular disease. We reported that, in obese male mice, histone deacetylase 9 (HDAC9) is upregulated in adipose tissues, and global deletion of HDAC9 protected against high fat diet (HFD)-induced obesity and metabolic disease. Here, we investigated the impact of adipocyte-specific HDAC9 gene deletion on diet-induced obesity in male and female mice. The HDAC9 gene expression was increased in adipose tissues of obese male and female mice and HDAC9 expression correlated positively with body mass index in humans. Interestingly, female, but not male, adipocyte-specific HDAC9 KO mice on HFD exhibited reduced body weight and visceral adipose tissue mass, adipocyte hypertrophy, and improved insulin sensitivity, glucose tolerance and adipogenic differentiation gene expression. Furthermore, adipocyte-specific HDAC9 gene deletion in female mice improved metabolic health as assessed by whole body energy expenditure, oxygen consumption, and adaptive thermogenesis. Mechanistically, compared to female mice, HFD-fed male mice exhibited preferential HDAC9 expression in the stromovascular fraction, which may have offset the impact of adipocyte-specific HDAC9 gene deletion in male mice. These results suggest that HDAC9 expressed in adipocytes is detrimental to obesity in female mice and provides novel evidence of sex-related differences in HDAC9 cellular expression and contribution to obesity-related metabolic disease.
Increased Levels of Phosphorylated ERK Induce CTGF Expression in Autophagy-Deficient Mouse Hepatocytes
Authors: Seo Hye-Young , Lee So-Hee , Han Eugene , Hwang Jae Seok , Kim Mi Kyung , Jang Byoung Kuk
Published: August 2022

Autophagy performs essential cell functions in the liver through an intracellular lysosomal degradation process. Several studies have reported that autophagy deficiency can lead to liver injury, including hepatic fibrosis; however, the mechanisms underlying the relationship between autophagy deficiency and liver pathology are unclear. In this study, we examined the expression levels of fibrosis-associated genes in hepatocyte-specific ATG7-deficient mice. The expression levels of the connective tissue growth factor (CTGF) and phosphorylated ERK (phospho-ERK) proteins were increased significantly in primary hepatocytes isolated from hepatocyte-specific ATG7-deficient mice compared to those isolated from control mice. In addition, the inhibition of autophagy in cultured mammalian hepatic AML12 and LX2 cells increased CTGF and phospho-ERK protein levels without altering CTGF mRNA expression. In addition, the autophagy deficiency-mediated enhancement of CTGF expression was attenuated when ERK was inhibited. Overall, these results suggest that the inhibition of autophagy in hepatocytes increases phospho-ERK expression, which in turn increases the expression of CTGF, a biomarker of fibrosis.
Aldosterone Increases Vascular Permeability in Rat Skin
Authors: Aleksiejczuk Michal , Gromotowicz-Poplawska Anna , Marcinczyk Natalia , Stelmaszewska Joanna , Dzieciol Janusz , Chabielska Ewa
Published: August 2022

The aim of this study was to evaluate the effect of acute aldosterone (ALDO) administration on the vascular permeability of skin. ALDO was injected intradermally into rats, and vascular permeability was measured. Eplerenone (EPL), a selective mineralocorticoid receptor (MR) antagonist, was used. Skin biopsies were carried out for immunohistochemical (IHC) staining, and polymerase chain reactions were performed to analyze the expression of MR, 11β-hydroxysteroid dehydrogenase type 2, von Willebrand factor (vWF), vascular endothelial growth factor (VEGF), and zonula occludens 1. Our study showed the presence of MR in the rat skin vasculature for the first time. It was found that ALDO injection resulted in a more than 30% increase in vascular permeability and enhanced the endothelial exocytosis of vWF. The effect of ALDO diminished after EPL administration. An accumulation of vWF and a reduction in VEGF IHC staining were observed following chronic EPL administration. No effect of ALDO or EPL on the mRNA expression of the studied genes or skin structure was observed. The results suggest that ALDO increases vascular permeability in the skin via an MR-dependent mechanism. This effect of ALDO on skin microcirculation may have important therapeutic implications for diseases characterized by increased levels of ALDO and coexisting skin microangiopathy.
School-Based Exercise Programs for Promoting Cardiorespiratory Fitness in Overweight and Obese Children Aged 6 to 10
Authors: Mijalković Stefan , Stanković Dušan , Tomljanović Mario , Batez Maja , Grle Maki , Grle Ivana , Brkljačić Ivan , Jularić Josip , Sporiš Goran , Fišer Suzana Žilič
Published: August 2022

The aim of this study was to conduct a systematic review of the school-based exercise programs for promoting cardiorespiratory fitness in overweight and obese children aged 6 to 10. Electronic databases (Web of Science and PubMed) were used as searching tools for collecting adequate studies published in the past 20 years. A total of 13 studies met the criteria for inclusion in this review, with a total of 2810 participants, both male and female. According to the results of this systematic review, overweight and obese children aged 6 to 10 who underwent certain interventions had their CRF improved. Furthermore, evidence suggested that interventions carried out during a longer period of time suggested led to greater improvement of cardiorespiratory fitness than a shorter one, but the level of cardiorespiratory fitness gradually decreases after the intervention.
Time Course of Motor Activity Wake Inertia Dissipation According to Age
Authors: Tonetti Lorenzo , Occhionero Miranda , Fabbri Marco , Giovagnoli Sara , Grimaldi Martina , Martoni Monica , Natale Vincenzo
Published: August 2022

The time course of motor activity sleep inertia (maSI) dissipation was recently investigated through actigraphy in an everyday life condition from middle childhood to late adulthood. Motor activity sleep inertia was dissipated in 70 min, and the sleep inertia phenomenon was more evident in younger participants than in older participants. The aim of the current secondary analysis of previously published data was to examine, within the same sample, the time course of motor activity wake inertia (maWI) dissipation, i.e., the motor pattern in the transition phase from wakefulness to sleep, according to age. To this end, an overall sample of 374 participants (215 females), ranging in age between 9 and 70 years old, was examined. Each participant was asked to wear an actigraph around their non-dominant wrist for one week. The variation in the motor activity pattern of the wake–sleep transition according to age was examined through functional linear modeling (FLM). FLM showed that motor activity wake inertia dissipated around 20 min after bedtime. Moreover, a lower age was significantly associated with greater motor activity within the last two hours of wakefulness and the first twenty minutes after bedtime. Overall, this pattern of results seems to suggest that maWI dissipation is comparable to that of maSI.
Near-Infrared-Activated MoS2(S)–Ag3PO4 Coating for Rapid Bacteria-Killing
Authors: Xia Honggang , Wang Dongbin , Tian Aixian , Xu Yingde , Gong Hao , Li Zhaoyang , Miao Jun
Published: August 2022

Medical tools and implants used in clinics can be contaminated with bacteria even with disinfection treatment. To avert this situation, titanium (Ti) plates modified with a MoS2(S)–Ag3PO4 coating were designed to kill Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) effectively under near-infrared (NIR) light irradiation. The introduction of Ag3PO4 nanoparticles (NPs) reduced the bandgap of MoS2 and suppressed the recombination of the photogenerated electron–hole pairs. Therefore, Ti–MoS2(S)–Ag3PO4 exhibited a higher photocatalytic performance, leading to the generation of more radical oxygen species (ROS). Furthermore, cooperating with the good photothermal performance of MoS2, the MoS2(S)–Ag3PO4 coating exhibited a high antibacterial efficacy of 99.76 ± 0.15% and 99.85 ± 0.09% against S. aureus and E. coli, respectively, for 15 min in vitro. Moreover, the MoS2(S)–Ag3PO4 coating had no apparent toxicity to cells. The proposed strategy may provide new insights for rapidly eradicating bacteria on medical tools and superficial implants.
Advances in Contextual Action Recognition: Automatic Cheating Detection Using Machine Learning Techniques
Authors: Hussein Fairouz , Al-Ahmad Ayat , El-Salhi Subhieh , Alshdaifat Esra’a , Al-Hami Mo’taz
Published: August 2022

Teaching and exam proctoring represent key pillars of the education system. Human proctoring, which involves visually monitoring examinees throughout exams, is an important part of assessing the academic process. The capacity to proctor examinations is a critical component of educational scalability. However, such approaches are time-consuming and expensive. In this paper, we present a new framework for the learning and classification of cheating video sequences. This kind of study aids in the early detection of students’ cheating. Furthermore, we introduce a new dataset, “actions of student cheating in paper-based exams”. The dataset consists of suspicious actions in an exam environment. Five classes of cheating were performed by eight different actors. Each pair of subjects conducted five distinct cheating activities. To evaluate the performance of the proposed framework, we conducted experiments on action recognition tasks at the frame level using five types of well-known features. The findings from the experiments on the framework were impressive and substantial.
Three-Dimensional Heads-Up vs. Standard Operating Microscope for Cataract Surgery: A Systematic Review and Meta-Analysis
Authors: Ripa Matteo , Kopsacheilis Nikolaos , Kanellopoulou Kanellina , Nomikarios Mikes , Motta Lorenzo
Published: August 2022

Background: The surgical time duration, the postoperative best-corrected visual acuity (BCVA), and the incidence rate of intraoperative complications, alongside the vision and posturing parameters, were estimated by systematic review and meta-analysis to compare the three-dimensional (3D) heads-up visualization system (HUVS) and standard operating microscope (SOM) in cataract surgery. Methods: A literature search was conducted using PubMed, Embase, and Scopus on 26 June 2022. The weighted mean difference (WMD) was used to present postoperative BCVA and the mean surgical time duration, whereas the risk ratio (RR) was used to present the incidence rate of intraoperative complications. Publication bias was evaluated with Egger’s test. The Cochrane Collaboration’s Tool for randomized clinical trials, the methodological index for non-randomized, and the Newcastle-Ottawa Scale were used to assess the risk of bias. The research has been registered with the PROSPERO database (identifier, CRD42022339186). Results: In the meta-analysis of five studies with 1021 participants, the pooled weighted mean difference (WMD) of the postoperative BCVA showed no significant difference between patients who underwent HUVS versus SOM cataract surgery (WMD = −0.01, 95% confidence interval (CI): −0.01 −0.02). In the meta-analysis of nine studies with 5505 participants, the pooled WMD of mean surgical time duration revealed no significant difference between patients who underwent HUVS versus SOM cataract surgery (WMD = 0.17, 95% CI: −0.43–0.76). In the meta-analysis of nine studies with 8609 participants, the pooled risk RR associated with intraoperative complications was 1.00 (95% CI, 1.00–1.01). Conclusions: 3D HUVS and SOM provide comparable surgical time duration, postoperative BCVA, and incidence rate of intraoperative complications.
Development of a Hybrid-Imaging-Based Prognostic Index for Metastasized-Melanoma Patients in Whole-Body 18F-FDG PET/CT and PET/MRI Data
Authors: Küstner Thomas , Vogel Jonas , Hepp Tobias , Forschner Andrea , Pfannenberg Christina , Schmidt Holger , Schwenzer Nina F. , Nikolaou Konstantin , la Fougère Christian , Seith Ferdinand
Published: August 2022

Besides tremendous treatment success in advanced melanoma patients, the rapid development of oncologic treatment options comes with increasingly high costs and can cause severe life-threatening side effects. For this purpose, predictive baseline biomarkers are becoming increasingly important for risk stratification and personalized treatment planning. Thus, the aim of this pilot study was the development of a prognostic tool for the risk stratification of the treatment response and mortality based on PET/MRI and PET/CT, including a convolutional neural network (CNN) for metastasized-melanoma patients before systemic-treatment initiation. The evaluation was based on 37 patients (19 f, 62 ± 13 y/o) with unresectable metastasized melanomas who underwent whole-body 18F-FDG PET/MRI and PET/CT scans on the same day before the initiation of therapy with checkpoint inhibitors and/or BRAF/MEK inhibitors. The overall survival (OS), therapy response, metastatically involved organs, number of lesions, total lesion glycolysis, total metabolic tumor volume (TMTV), peak standardized uptake value (SULpeak), diameter (Dmlesion) and mean apparent diffusion coefficient (ADCmean) were assessed. For each marker, a Kaplan–Meier analysis and the statistical significance (Wilcoxon test, paired t-test and Bonferroni correction) were assessed. Patients were divided into high- and low-risk groups depending on the OS and treatment response. The CNN segmentation and prediction utilized multimodality imaging data for a complementary in-depth risk analysis per patient. The following parameters correlated with longer OS: a TMTV < 50 mL; no metastases in the brain, bone, liver, spleen or pleura; ≤4 affected organ regions; no metastases; a Dmlesion > 37 mm or SULpeak < 1.3; a range of the ADCmean < 600 mm2/s. However, none of the parameters correlated significantly with the stratification of the patients into the high- or low-risk groups. For the CNN, the sensitivity, specificity, PPV and accuracy were 92%, 96%, 92% and 95%, respectively. Imaging biomarkers such as the metastatic involvement of specific organs, a high tumor burden, the presence of at least one large lesion or a high range of intermetastatic diffusivity were negative predictors for the OS, but the identification of high-risk patients was not feasible with the handcrafted parameters. In contrast, the proposed CNN supplied risk stratification with high specificity and sensitivity.
Role of Endomyocardial Biopsy in Diagnostics of Myocarditis
Authors: Vidusa Liga , Kalejs Oskars , Maca-Kaleja Aija , Strumfa Ilze
Published: August 2022

Endomyocardial biopsy as the cornerstone of diagnostics has been re-evaluated throughout the years, leaving unanswered questions on the precedence of it. The reported incidence of myocarditis has increased during the pandemic of coronavirus disease 2019 (COVID-19), reinforcing discussions on appropriate diagnostics of myocarditis. By analysis of evidence-based literature published within the last demi-decade, we aimed to summarize the most recent information in order to evaluate the current role of endomyocardial biopsy in diagnostics and management of myocarditis. For the most part, research published over the last five years showed ongoing uncertainty regarding the use, informativeness, safety and necessity of performing a biopsy. Special circumstances, such as fulminant clinical course or failure to respond to empirical treatment, were reconfirmed as justified indications, with a growing applicability of non-invasive diagnostic approaches for most other cases. We concluded that endomyocardial biopsy, if performed properly and with adjunct diagnostic methods, holds a critical role for treatment correction in specific histological subtypes of myocarditis and for differential diagnosis between immune-mediated myocarditis and secondary infections due to immunosuppressive treatment. A high level of possible misdiagnosing was detected, indicating the need to review terminology used to describe findings of myocardial inflammation that did not meet Dallas criteria.