bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Destructive Multi-Feature Analysis of a Historic Wooden Floor
Authors: Cruz Carlos , Gaju Miquel , Gallego Antolino , Rescalvo Francisco , Suarez Elisabet
Published: December 2022

Wood is very present in the structures of old buildings and real estate with historical value. Yet, as a biodegradable material, it is highly vulnerable to adverse environmental conditions, such as permanent high humidity and attacks by xylophages. Furthermore, being a natural material, wood has great potential for low-carbon building within a circular economy. To preserve historical wooden structures, periodic inspections, preferably non-destructive or minimally invasive, are needed. Inspection may involve visual or resistographic testing techniques. However, both of these methods are time consuming and inaccurate. In this work, the joint use of techniques is proposed, in order to make multi-feature decisions about the repair or replacement of elements. The acoustic emission technique is proposed to determine active xylophages, the elastic wave technique to determine the dynamic elastic modulus and the resistance class, and finite element numerical modelling to determine the state of deformation and structural capacity. An old beam floor from a historic building in the center of Granada, Spain, was used as a practical case. The results demonstrate the effectiveness of a multi-analysis, instead of a single analysis, in arriving at correct decision making.
A Critical Scoping Review of Disability Employment Research in the Construction Industry: Driving Social Innovation through More Inclusive Pathways to Employment Opportunity
Authors: Bailey Susan , Carnemolla Phillippa , Loosemore Martin , Darcy Simon , Sankaran Shankar
Published: December 2022

Innovation research in construction has almost exclusively focused on economic and technological innovation. In contrast, the emerging concept of social innovation has been largely ignored. This is despite the global growth of social procurement policies which incentivize construction firms to innovate in providing employment opportunities for equity-seeking groups. While there is an emerging body of research which is starting to explore innovative employment pathways into construction for certain equity-seeking groups such as women, refugees and Indigenous people, there has been relatively little research into employment pathways for people with a disability. Addressing this gap in research, this paper reports the results of a critical scoping review of Web of Science, Scopus, PubMed and Google Scholar publications on the employment of people with disability in construction. Using the Preferred Reporting Items for Systematic reviews (PRISMA-ScR) approach, extant research was mapped across seven themes of hiring disability practices. Results indicate that research into the employment of people with disability in construction internationally remains nascent with significant knowledge gaps compared to mainstream disability employment research. These key gaps include: barriers to employment based on the lived experiences of people with disability seeking employment in construction; the facilitation of cross-sector relationships with organizations that support people with disability into employment; the reduction of biases, ingrained stigmas and inequalities in recruitment practices for people with disability; and the role of informal norms and practices in undermining formal laws, regulations and policies designed to reduce barriers to employment. The scoping review also identifies a methodological gap in the research reviewed by highlighting the need for more construction research designs to include people with disability as prioritized research participants as well as research investigators and to adopt phenomenological and interpretive approaches which respect the lived experiences of people with a disability seeking work in the construction industry.
Evolution of RAS Mutations in Cell-Free DNA of Patients with Tissue RAS Wild-Type Metastatic Colorectal Cancer Receiving First-Line Treatment: The PERSEIDA Study
Authors: Valladares-Ayerbes Manuel , Garcia-Alfonso Pilar , Muñoz Luengo Jorge , Pimentel Caceres Paola Patricia , Castillo Trujillo Oscar Alfredo , Vidal-Tocino Rosario , Llanos Marta , Llorente Ayala Beatriz , Limon Miron Maria Luisa , Salud Antonieta , Cirera Nogueras Luis , Garcia-Carbonero Rocio , Safont Maria Jose , Falco Ferrer Esther , Aparicio Jorge , Vicente Conesa Maria Angeles , Guillén-Ponce Carmen , Garcia-Teijido Paula , Medina Magan Maria Begoña , Busquier Isabel , Salgado Mercedes , Lloansí Vila Ariadna
Published: December 2022

The serial analysis of cell-free DNA (cfDNA) enables minimally invasive monitoring of tumor evolution, providing continuous genetic information. PERSEIDA was an observational, prospective study assessing the cfDNA RAS (KRAS/NRAS) mutational status evolution in first-line, metastatic CRC, RAS wild-type (according to baseline tumor tissue biopsy) patients. Plasma samples were collected before first-line treatment, after 20 ± 2 weeks, and at disease progression. One hundred and nineteen patients were included (102 received panitumumab and chemotherapy as first-line treatment—panitumumab subpopulation). Fifteen (12.6%) patients presented baseline cfDNA RAS mutations (n = 14 [13.7%], panitumumab subpopulation) (mutant allele fraction ≥0.02 for all results). No patients presented emergent mutations (cfDNA RAS mutations not present at baseline) at 20 weeks. At disease progression, 11 patients (n = 9; panitumumab subpopulation) presented emergent mutations (RAS conversion rate: 19.0% [11/58]; 17.7% [9/51], panitumumab subpopulation). In contrast, three (5.2%) patients presenting baseline cfDNA RAS mutations were RAS wild-type at disease progression. No significant associations were observed between overall response rate or progression-free survival and cfDNA RAS mutational status in the total panitumumab subpopulation. Although, in patients with left-sided tumors, a significantly longer progression-free survival was observed in cfDNA RAS wild-type patients compared to those presenting cfDNA RAS mutations at any time. Continuous evaluation of RAS mutations may provide valuable insights on tumor molecular dynamics that can help clinical practice.
Feasibility of Breast Cancer Metastasis Assessment of Ex Vivo Sentinel Lymph Nodes through a p-H&E Optical Coherence Microscopic Imaging System
Authors: Lin Sey-En , Chang Wei-Wen , Hsiao Ping-Kun , Hsieh Mao-Chih , Chen Wei-Yu , Fang Chia-Lang , Tsai Chien-Chung
Published: December 2022

Frozen-sectioned hematoxylin–eosin (H&E) image evaluation is the current method for intraoperative breast cancer metastasis assessment through ex vivo sentinel lymph nodes (SLNs). After frozen sectioning, the sliced fatty region of the frozen-sectioned specimen is easily dropped because of different freezing points for fatty tissues and other tissues. Optical-sectioned H&E images provide a nondestructive method for obtaining the insight en face image near the attached surface of the dissected specimen, preventing the freezing problem of fatty tissue. Specimens from 29 patients at Wanfang Hospital were collected after excision and were analyzed at the pathology laboratory, and a fluorescence-in-built optical coherence microscopic imaging system (OCMIS) was then used to visualize the pseudo-H&E (p-H&E) images of the SLNs for intraoperative breast cancer metastasis assessment, and the specificity, sensitivity, and accuracy were 100%, 88.9%, and 98.8% (n = 83), respectively. Compared with gold-standard paraffin-sectioned H&E images, the specificity, sensitivity, and accuracy obtained with the frozen-sectioned H&E images (n = 85) of the specimens were the same as those obtained with the p-H&E images (n = 95). Thus, OCMIS is a useful noninvasive image-assisted tool for breast cancer metastasis assessment based on SLN images.
Association between Proton Pump Inhibitor Use and the Risk of Female Cancers: A Nested Case-Control Study of 23 Million Individuals
Authors: Nguyen Nhi Thi Hong , Huang Chih-Wei , Wang Ching-Huan , Lin Ming-Chin , Hsu Jason C. , Hsu Min-Huei , Iqbal Usman , Nguyen Phung-Anh , Yang Hsuan-Chia
Published: December 2022

Background: Firm conclusions about whether long-term proton pump inhibitor (PPI) drug use impacts female cancer risk remain controversial. Objective: We aimed to investigate the associations between PPI use and female cancer risks. Methods: A nationwide population-based, nested case-control study was conducted within Taiwan’s Health and Welfare Data Science Center’s databases (2000–2016) and linked to pathologically confirmed cancer data from the Taiwan Cancer Registry (1979–2016). Individuals without any cancer diagnosis during the 17 years of the study served as controls. Case and control patients were matched 1:4 based on age, gender, and visit date. Conditional logistic regression with 95% confidence intervals (CIs) was applied to investigate the association between PPI exposure and female cancer risks by adjusting for potential confounders such as the Charlson comorbidity index and medication usage (metformin, aspirin, and statins). Results: A total of 233,173 female cancer cases were identified, consisting of 135,437 diagnosed with breast cancer, 64,382 with cervical cancer, 19,580 with endometrial cancer, and 13,774 with ovarian cancer. After matching each case with four controls, we included 932,692 control female patients. The number of controls for patients with breast cancer, cervical cancer, endometrial cancer, and ovarian cancer was 541,748, 257,528, 78,320, and 55,096, respectively. The use of PPIs was significantly associated with reduced risk of breast cancer and ovarian cancer in groups aged 20–39 years (adjusted odds ratio (aOR): 0.69, 95%CI: 0.56–0.84; p < 0.001 and aOR: 0.58, 95%CI: 0.34–0.99; p < 0.05, respectively) and 40–64 years (aOR: 0.89, 95%CI: 0.86–0.94; p < 0.0001 and aOR: 0.87, 95%CI: 0.75–0.99; p < 0.05, respectively). PPI exposure was associated with a significant decrease in cervical and endometrial cancer risks in the group aged 40–64 years (with aOR: 0.79, 95%CI: 0.73–0.86; p < 0.0001 and aOR: 0.72, 95%CI: 0.65–0.81; p < 0.0001, respectively). In contrast, in elderly women, PPI use was found to be insignificantly associated with female cancers among users. Conclusions: Our findings, based on real-world big data, can depict a comprehensive overview of PPI usage and female cancer risk. Further clinical studies are needed to elucidate the effects of PPIs on female cancers.
Activation of OSM-STAT3 Epigenetically Regulates Tumor-Promoting Transcriptional Programs in Cervical Cancer
Authors: Noh Junho , You Chaelin , Kang Keunsoo , Kang Kyuho
Published: December 2022

Despite improvements in preventative strategies, such as regular screenings with Pap tests and human papillomavirus (HPV) tests as well as HPV vaccinations, effective treatment for advanced cervical cancer remains poor. Deregulation of STAT3 is an oncogenic factor that promotes tumorigenesis and epithelial-to-mesenchymal transition (EMT) in various cancers. Oncostatin M (OSM), a pleiotropic cytokine, induces STAT3 activation, exacerbating cervical cancer. However, the mechanism by which the OSM-STAT3 axis epigenetically regulates tumor-progression-related genes in cervical cancer is not well understood. Here, we show that OSM-mediated STAT3 activation promotes pro-tumorigenic gene expression programs, with chromatin remodeling in cervical cancer. Reanalysis of scRNA-seq data performed in cervical cancer uncovered an interaction between the oncostatin M receptor (OSMR) on tumor cells and OSM induced by tumor-associated macrophages (TAMs). Our gene expression profiling (bulk RNA-seq) shows that OSM-induced genes were involved in hypoxia, wound healing, and angiogenesis, which were significantly inhibited by SD-36, a STAT3-selective degrader. Additionally, ATAC-seq experiments revealed that STAT3 binding motifs were preferentially enriched in open chromatin regions of the OSM-STAT3-regulated genes. Among the 50 candidate genes that were regulated epigenetically through the OSM-STAT3 axis, we found that the expression levels of NDRG1, HK2, PLOD2, and NPC1 were significantly correlated with those of OSMR and STAT3 in three independent cervical cancer cohorts. Also, higher expression levels of these genes are significantly associated with poor prognosis in cervical cancer patients. Collectively, our findings demonstrate that the OSM-STAT3 signaling pathway regulates crucial transcriptomic programs through epigenetic changes and that selective inhibition of STAT3 may be a novel therapeutic strategy for patients with advanced cervical cancer.
Interventional Oncolytic Immunotherapy with LTX-315 for Residual Tumor after Incomplete Radiofrequency Ablation of Liver Cancer
Authors: Zhou Guanhui , Kan Xuefeng , Zhang Feng , Ji Hongxiu , Sun Junhui , Yang Xiaoming
Published: December 2022

Objective: To investigate the feasibility of interventional oncolytic immunotherapy with LTX-315 for residual tumors after incomplete radiofrequency ablation (iRFA) of VX2 liver tumors in a rabbit model. Methods: For in vitro experiments, VX2 tumor cells were treated with: (1) phosphate buffered saline, (2) radiofrequency hyperthermia (RFH), (3) LTX-315, and (4) RFH plus LTX-315. The residual tumors after iRFA of VX2 liver tumors were treated with: (1) phosphate buffered saline served as control, (2) 2 mg LTX-315, and (3) 4 mg LTX-315. MTS assay, fluorescence microscopy, and flow cytometry were used to compare cell viabilities and apoptosis among different groups. Ultrasound imaging was used to follow up the tumor growth, which were correlated with the optical imaging and subsequent histology. Results: For in vitro experiments, compared with the other three groups, MTS assay demonstrated the lowest cell viability, fluorescence microscopy showed the least survival cells, and apoptosis analysis revealed the highest percentage of apoptosis cells in the combination treatment groups (p < 0.001). For in vivo experiments, ultrasound imaging showed the smallest tumor volume in the group with 4 mg LTX-315 therapy compared with the other two groups (p < 0.001). The optical imaging and histopathological analysis showed complete necrosis of the tumors in the group with 4 mg LTX-315 therapy. A significant increase of CD8+ T cells and HSP70 and a significant decrease of Tregs were observed in residual tumors in the group with 2 mg LTX-315 therapy compared with the control group (p < 0.001). Conclusion: Interventional oncolytic immunotherapy with LTX-315 for residual tumors after iRFA of liver cancer is feasible, which may open up new avenues to prevent residual tumors after RFA of intermediate-to-large liver cancers.
Endocrine Therapy-Based Strategies for Metastatic Breast Cancer with Different Endocrine Sensitivity Statuses: A Systematic Review and Network Meta-Analysis
Authors: Wang Jiani , Han Yiqun , Wang Jiayu , Li Qing , Xu Binghe
Published: December 2022

Background: Novel endocrine therapies (ETs) and targeted therapeutic regimens have been developed to dramatically improve the outcome of hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (mBC). Methods: We performed a systematic search with a predefined search strategy in PubMed, Embase and Cochrane CENTRAL databases to perform a network meta-analysis and evaluate the relative efficacies of ET-based treatment regimens in HR+/HER2- mBC patients with different endocrine sensitivity statuses. The study was registered in the PROSPERO database (CRD42021235570). Results: A total of 47 trials (20,267 patients) were included. Analysis of progression-free survival (PFS) in endocrine therapy-sensitive (ETS) patients revealed cyclin-dependent kinases 4/6 inhibitors (CDK4/6i) + fulvestrant 500 mg (Ful 500) (random effect (RE): hazard ratio (HR), 0.46; 95% credibility interval (CrI), 0.27–0.78; surface under the cumulative ranking curve (SUCRA), 0.93; fixed effect (FE): HR, 0.48; 95% CrI, 0.40–0.58; SUCRA, 0.99) to be the best therapy followed by CDK4/6i + aromatase inhibitors (AIs) (RE: HR, 0.53; 95% CrI, 0.40–0.72; SUCRA, 0.86; FE: HR, 0.54; 95% CrI, 0.48–0.61; SUCRA, 0.91). Chemotherapy followed by CDK4/6i + Ful 500 appears to be the most effective option for the endocrine therapy-resistant (ETR) group. Analysis of overall survival revealed CDK4/6i + Ful 500 (SUCRA: 0.99) and AKTi + Ful 500 (SUCRA: 0.87) to be the first-rank regimen for the ETS group and ETR groups, respectively. Conclusion: Our comprehensive analysis suggests that CDK4/6i combined with ETs may be the best treatment option in terms of PFS for ETS patients and chemotherapy for ETR patients with HR+/HER2- mBC. Different endocrine sensitivity statuses required various optimal treatment strategies, which may provide guidance for clinical practice.
Undifferentiated Pancreatic Carcinomas, Clinical Features and Therapeutic Options: What We Know
Authors: Mugaanyi Joseph , Lu Changjiang , Huang Jing , Lu Caide
Published: December 2022

Undifferentiated pancreatic carcinomas are rare malignant tumors of the pancreas that are very aggressive and challenging to diagnose. The WHO categorizes them into undifferentiated osteoclast-like giant cell, sarcomatoid, and rhabdoid pancreatic carcinomas. Patients present with nonspecific symptoms such as jaundice, vague abdominal or back pain and itchy skin. Their histological characteristics include positive pan-cytokeratin mononuclear pleomorphic cells, osteoclast-like giant cells and CD68. Patients may have KRAS, TP53 and SMAD4 alterations, homozygous deletions of CDKN2A and CDKN2B, as well as INI1 deficiency. Surgical resection is the only curative treatment. Patients may benefit from postoperative adjuvant therapy. There are no widely accepted guidelines specific to this type of tumor; however, some chemotherapy regimens may be promising. The patient prognosis is mostly poor, especially in patients with unresectable tumors. However, several studies have shown patients achieving long-term survival with adjuvant therapy. In conclusion, although undifferentiated pancreatic carcinoma is rare and very aggressive, there is still potential for improved patient survival with proper diagnosis and treatment.
Systematic Investigation of the Multifaceted Role of SOX11 in Cancer
Authors: Sun Qingqing , Du Jun , Dong Jie , Pan Shuaikang , Jin Hongwei , Han Xinghua , Zhang Jinguo
Published: December 2022

SRY-box transcription factor 11 (SOX11), as a member of the SOX family, is a transcription factor involved in the regulation of specific biological processes and has recently been found to be a prognostic marker for certain cancers. However, the roles of SOX11 in cancer remain controversial. Our study aimed to explore the various aspects of SOX11 in pan-cancer. The expression of SOX11 was investigated by the Genotype Tissue-Expression (GTEX) dataset and the Cancer Genome Atlas (TCGA) database. The protein level of SOX11 in tumor tissues and tumor-adjacent tissues was verified by human pan-cancer tissue microarray. Additionally, we used TCGA pan-cancer data to analyze the correlations among SOX11 expression and survival outcomes, clinical features, stemness, microsatellite instability (MSI), tumor mutation burden (TMB), mismatch repair (MMR) related genes and the tumor immune microenvironment. Furthermore, the cBioPortal database was applied to investigate the gene alterations of SOX11. The main biological processes of SOX11 in cancers were analyzed by Gene Set Enrichment Analysis (GSEA). As a result, aberrant expression of SOX11 has been implicated in 27 kinds of cancer types. Aberrant SOX11 expression was closely associated with survival outcomes, stage, tumor recurrence, MSI, TMB and MMR-related genes. In addition, the most frequent alteration of the SOX11 genome was mutation. Our study also showed the correlations of SOX11 with the level of immune infiltration in various cancers. In summary, our findings underline the multifaceted role and prognostic value of SOX11 in pan-cancer.
Mechanisms of Resistance in Gastroenteropancreatic Neuroendocrine Tumors
Authors: Shi Chanjuan , Morse Michael A.
Published: December 2022

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs), although curable when localized, frequently metastasize and require management with systemic therapies, including somatostatin analogues, peptide receptor radiotherapy, small-molecule targeted therapies, and chemotherapy. Although effective for disease control, these therapies eventually fail as a result of primary or secondary resistance. For small-molecule targeted therapies, the feedback activation of the targeted signaling pathways and activation of alternative pathways are prominent mechanisms, whereas the acquisition of additional genetic alterations only rarely occurs. For somatostatin receptor (SSTR)-targeted therapy, the heterogeneity of tumor SSTR expression and dedifferentiation with a downregulated expression of SSTR likely predominate. Hypoxia in the tumor microenvironment and stromal constituents contribute to resistance to all modalities. Current studies on mechanisms underlying therapeutic resistance and options for management in human GEP-NETs are scant; however, preclinical and early-phase human studies have suggested that combination therapy targeting multiple pathways or novel tyrosine kinase inhibitors with broader kinase inhibition may be promising.
Prediction of Radiotherapy Compliance in Elderly Cancer Patients Using an Internally Validated Decision Tree
Authors: Osong Biche , Bermejo Inigo , Lee Kyu Chan , Lee Seok Ho , Dekker Andre , van Soest Johan
Published: December 2022

This study aims to analyze the relationship between the available variables and treatment compliance in elderly cancer patients treated with radiotherapy and to establish a decision tree model to guide caregivers in their decision-making process. For this purpose, 456 patients over 74 years of age who received radiotherapy between 2005 and 2017 were included in this retrospective analysis. The outcome of interest was radiotherapy compliance, determined by whether patients completed their scheduled radiotherapy treatment (compliance means they completed their treatment and noncompliance means they did not). A bootstrap (B = 400) technique was implemented to select the best tuning parameters to establish the decision tree. The developed decision tree uses patient status, the Charlson comorbidity index, the Eastern Cooperative Oncology Group Performance scale, age, sex, cancer type, health insurance status, radiotherapy aim, and fractionation type (conventional fractionation versus hypofractionation) to distinguish between compliant and noncompliant patients. The decision tree’s mean area under the curve and 95% confidence interval was 0.71 (0.66–0.77). Although external validation is needed to determine the decision tree’s clinical usefulness, its discriminating ability was moderate and it could serve as an aid for caregivers to select the optimal treatment for elderly cancer patients.
Loss of Mature Lamin A/C Triggers a Shift in Intracellular Metabolic Homeostasis via AMPKα Activation
Authors: Zhou Ying , Yang Jia-Jie , Cheng Yuan , Feng Ge-Xuan , Yang Rong-Hui , Yuan Yuan , Wang Li-Yong , Wang Miao , Kong Lu
Published: December 2022

The roles of lamin A/C in adipocyte differentiation and skeletal muscle lipid metabolism are associated with familial partial lipodystrophy of Dunnigan (FPLD). We confirmed that LMNA knockdown (KD) in mouse adipose-derived mesenchymal stem cells (AD-MSCs) prevented adipocyte maturation. Importantly, in in vitro experiments, we discovered a significant increase in phosphorylated lamin A/C levels at serine 22 or 392 sites (pLamin A/C-S22/392) accompanying increased lipid synthesis in a liver cell line (7701 cells) and two hepatocellular carcinoma (HCC) cell lines (HepG2 and MHCC97-H cells). Moreover, HCC cells did not survive after LMNA knockout (KO) or even KD. Evidently, the functions of lamin A/C differ between the liver and adipose tissue. To date, the mechanism of hepatocyte lipid metabolism mediated by nuclear lamin A/C remains unclear. Our in-depth study aimed to identify the molecular connection between lamin A/C and pLamin A/C, hepatic lipid metabolism and liver cancer. Gain- and loss-of-function experiments were performed to investigate functional changes and the related molecular pathways in 7701 cells. Adenosine 5’ monophosphate-activated protein kinase α (AMPKα) was activated when abnormalities in functional lamin A/C were observed following lamin A/C depletion or farnesyltransferase inhibitor (FTI) treatment. Active AMPKα directly phosphorylated acetyl-CoA-carboxylase 1 (ACC1) and subsequently inhibited lipid synthesis but induced glycolysis in both HCC cells and normal cells. According to the mass spectrometry analysis, lamin A/C potentially regulated AMPKα activation through its chaperone proteins, ATPase or ADP/ATP transporter 2. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of the two HCC cell lines more efficiently than lonafarnib alone by inhibiting glycolysis or the maturation of prelamin A.
SCAND1 Reverses Epithelial-to-Mesenchymal Transition (EMT) and Suppresses Prostate Cancer Growth and Migration
Authors: Eguchi Takanori , Csizmadia Eva , Kawai Hotaka , Sheta Mona , Yoshida Kunihiro , Prince Thomas L. , Wegiel Barbara , Calderwood Stuart K.
Published: December 2022

Epithelial–mesenchymal transition (EMT) is a reversible cellular program that transiently places epithelial (E) cells into pseudo-mesenchymal (M) cell states. The malignant progression and resistance of many carcinomas depend on EMT activation, partial EMT, or hybrid E/M status in neoplastic cells. EMT is activated by tumor microenvironmental TGFβ signal and EMT-inducing transcription factors, such as ZEB1/2, in tumor cells. However, reverse EMT factors are less studied. We demonstrate that prostate epithelial transcription factor SCAND1 can reverse the cancer cell mesenchymal and hybrid E/M phenotypes to a more epithelial, less invasive status and inhibit their proliferation and migration in DU-145 prostate cancer cells. SCAND1 is a SCAN domain-containing protein and hetero-oligomerizes with SCAN-zinc finger transcription factors, such as MZF1, for accessing DNA and the transcriptional co-repression of target genes. We found that SCAND1 expression correlated with maintaining epithelial features, whereas the loss of SCAND1 was associated with mesenchymal phenotypes of tumor cells. SCAND1 and MZF1 were mutually inducible and coordinately included in chromatin with hetero-chromatin protein HP1γ. The overexpression of SCAND1 reversed hybrid E/M status into an epithelial phenotype with E-cadherin and β-catenin relocation. Consistently, the co-expression analysis in TCGA PanCancer Atlas revealed that SCAND1 and MZF1 expression was negatively correlated with EMT driver genes, including CTNNB1, ZEB1, ZEB2 and TGFBRs, in prostate adenocarcinoma specimens. In addition, SCAND1 overexpression suppressed tumor cell proliferation by reducing the MAP3K-MEK-ERK signaling pathway. Of note, in a mouse tumor xenograft model, SCAND1 overexpression significantly reduced Ki-67(+) and Vimentin(+) tumor cells and inhibited migration and lymph node metastasis of prostate cancer. Kaplan–Meier analysis showed high expression of SCAND1 and MZF1 to correlate with better prognoses in pancreatic cancer and head and neck cancers, although with poorer prognosis in kidney cancer. Overall, these data suggest that SCAND1 induces expression and coordinated heterochromatin-binding of MZF1 to reverse the hybrid E/M status into an epithelial phenotype and, inhibits tumor cell proliferation, migration, and metastasis, potentially by repressing the gene expression of EMT drivers and the MAP3K-MEK-ERK signaling pathway.
Enhanced Photodynamic Therapy: A Review of Combined Energy Sources
Authors: Rodrigues José A. , Correia José H.
Published: December 2022

Photodynamic therapy (PDT) has been used in recent years as a non-invasive treatment for cancer, due to the side effects of traditional treatments such as surgery, radiotherapy, and chemotherapy. This therapeutic technique requires a photosensitizer, light energy, and oxygen to produce reactive oxygen species (ROS) which mediate cellular toxicity. PDT is a useful non-invasive therapy for cancer treatment, but it has some limitations that need to be overcome, such as low-light-penetration depths, non-targeting photosensitizers, and tumor hypoxia. This review focuses on the latest innovative strategies based on the synergistic use of other energy sources, such as non-visible radiation of the electromagnetic spectrum (microwaves, infrared, and X-rays), ultrasound, and electric/magnetic fields, to overcome PDT limitations and enhance the therapeutic effect of PDT. The main principles, mechanisms, and crucial elements of PDT are also addressed.
Detection of De Novo Dividing Stem Cells In Situ through Double Nucleotide Analogue Labeling
Authors: Itaman Sheed , Enikolopov Grigori , Podgorny Oleg V.
Published: December 2022

Tissue-specific somatic stem cells are characterized by their ability to reside in a state of prolonged reversible cell cycle arrest, referred to as quiescence. Maintenance of a balance between cell quiescence and division is critical for tissue homeostasis at the cellular level and is dynamically regulated by numerous extrinsic and intrinsic factors. Analysis of the activation of quiescent stem cells has been challenging because of a lack of methods for direct detection of de novo dividing cells. Here, we present and experimentally verify a novel method based on double labeling with thymidine analogues to detect de novo dividing stem cells in situ. In a proof of concept for the method, we show that memantine, a drug widely used for Alzheimer’s disease therapy and a known strong inducer of adult hippocampal neurogenesis, increases the recruitment into the division cycle of quiescent radial glia-like stem cells—primary precursors of the adult-born neurons in the hippocampus. Our method could be applied to assess the effects of aging, pathology, or drug treatments on the quiescent stem cells in stem cell compartments in developing and adult tissues.
Exosomes Derived from BMMSCs Mitigate the Hepatic Fibrosis via Anti-Pyroptosis Pathway in a Cirrhosis Model
Authors: Zhang Yichi , Zhangdi Hanjing , Nie Xinsheng , Wang Lijuan , Wan Zhuzhi , Jin Hao , Pu Ronghui , Liang Meihui , Chang Yuan , Gao Yang , Zhang Hailong , Jin Shizhu
Published: December 2022

Researchers increasingly report the therapeutic effect of exosomes derived from rat bone marrow mesenchymal stem cells (Exos-rBMMSC) on liver disease, while the optimal dose of Exos-rBMMSC in liver cirrhotic treatment has not been reported. In this study, we aimed to explore the efficacy and dose of Exos-rBMMSC in a hepatic cirrhosis rat model. The therapeutic effects of a low dose, medium dose and high dose of Exos-rBMMSC were assessed by liver function tests and histopathology. After four-weeks of Exos-rBMMSC therapy, pyroptosis-related expression levels in the medium dose and the high dose Exos-rBMMSC groups were significantly decreased compared to those in the liver cirrhosis group (p < 0.05). The hepatic function assay and histopathology results showed significant improvement in the medium dose and the high dose Exos-rBMMSCs groups. The localization of PKH67-labeled Exos-rBMMSC was verified microscopically, and these particles were coexpressed with the PCNA, NLRP3, GSDMD and Caspase-1. Our results demonstrated that Exos-rBMMSC accelerated hepatocyte proliferation and relieved liver fibrosis by restraining hepatocyte pyroptosis. More importantly, we confirmed that the high dose of Exos-rBMMSC may be the optimal dose for liver cirrhosis, which is conducive to the application of Exos-rBMMSC as a promising cell-free strategy.
Molecular Detection of Lymph Node Metastases in Lung Cancer Patients Using the One-Step Nucleic Acid Amplification Method:Clinical Significance and Prognostic Value
Authors: Hermida-Romero María Teresa , Estévez-Pérez Lara S. , Alen Begoña O. , Picchi Florencia , Fernández-Prado Ricardo , de la Torre-Bravos Mercedes , Concha Ángel
Published: December 2022

The one-step nucleic acid amplification (OSNA) method allows for the quantitative evaluation of the tumor burden in resected lymph nodes (LNs) in patients with lung cancer. This technique enables to detect macro and micrometastases, facilitating the correct classification of patients for appropriate follow-up of the disease after surgery. Of 160 patients with resectable lung cancer whose LNs were examined by OSNA, H&E and CK19 IHC between July 2015 and December 2018, 110 patients with clinical stages from IA1 to IIIB were selected for follow-up. LN staging in lung cancer by pathological study led to understaging in 13.64% of the cases studied. OSNA allowed to quantify the tumor burden and establish a prognostic value. Patients with a total tumor load of ≥1650 cCP/uL were associated with a significantly increased likelihood of recurrence. Moreover, the survival of patients with <4405 cCP/uL was significantly higher than patients with ≥4405 cCP/uL. The OSNA assay is a rapid and accurate technique for quantifying the tumor burden in the LNs of lung cancer patients and OSNA quantitative data could allow to establish prognostic values for recurrence-free survival and overall survival in this type of malignancy.
Tensile Adhesion Strength of Atmospheric Plasma Sprayed MgAl2O4, Al2O3 Coatings
Authors: Zayatzev Andrey , Lukianova Albina , Demoretsky Dmitry , Alexandrova Yulia
Published: December 2022

This study analyses the distribution of stress during the testing of glued cylindrical specimens with thermally sprayed MgAl2O4, Al2O3 oxide coatings in order to evaluate the tensile adhesion strength. The set of studies that make up this work were conducted in order to evaluate the influence of the geometric parameters of cylindrical test specimens, 25 mm in diameter by 16–38.1 mm in height, on the measured tensile adhesion strength of the specimens. The stress and strain states inside the coating and at the coating-substrate interface were determined using the finite element modelling method. The debonding mechanisms, failure mode and influence of the coating microstructure on bond strength are also discussed. The finite element stress analysis shows a significant level of non-uniform stress distribution in the test specimens. The analysis of the results of the modelling stresses and strains using the finite element method for six types of cylindrical specimens, as well as the values obtained for the adhesion testing of MgAl2O4, Al2O3 coatings, show a need to increase the height of the standard cylindrical specimen (according to ASTM C633-13 (2021), GOST 9.304-87). The height should be increased by no less than 1.5–2.0 times to reduce the level of a non-uniform stress distribution in the separation area.
Spark Plasma Sintering of Variable SiC α/β Ratio with Boron and Carbon Additions—Microstructure Transformation
Authors: Kostecki Marek , Petrus Mateusz , Płociński Tomasz , Olszyna Andrzej Roman
Published: December 2022

This study investigated the possibility of obtaining dense silicon carbide sinters with the use of a spark plasma sintering (SPS) process by changing the composition of SiC α/β polymorphs in a starting powder mixture. Amorphous boron was used as the basic additive to activate the sintering processes. Some of the compositions were prepared with additional carbon in two different forms: multilayer graphene flakes and carbon black. The well-described effect of the β–α transition in the form of elongated lamellar grains in the sintered structure was confirmed. The obtained sinters were analyzed qualitatively and quantitatively in terms of the microstructure and density. The hardness and the participation of the polytypes in the sinter structures were examined. During the study, SPS sintering allowed us to obtain a material with a density close to the theoretical (relative density of 99.5% and hardness of 27 MPa) without the addition of carbon. It was found that the role of carbon was not limited to the activation of the sintering process. Additional effects accompanying its presence, depending on the initial α/β composition, included grain size reduction and an influence on the transformation kinetics.
The Influence of Contextual Factors on the Relative Age Effect in Male International Rugby Union: The Impact of Sociocultural Influences and Playing Position
Authors: Brustio Paolo Riccardo , Kelly Adam Leigh , Lupo Corrado , Ungureanu Alexandru Nicolae
Published: December 2022

The purpose of this study is not only to establish whether the relative age effect (RAE) exists in male international rugby union players, but also to investigate the impact of sociocultural influences (i.e., northern and southern hemispheres) and playing position (i.e., backs, forwards, and scrum-halves). The birth date and the playing position of 7144 senior male professional rugby players included in the rosters of the season 2020–2021 were collected from the top 10 nations of the World Rugby rankings (i.e., Argentina, Australia, England, France, Ireland, Japan, New Zealand, Scotland, South Africa, and Wales). Data were analyzed using a chi-square goodness-of-fit test to compare the observed and expected birth quarter (Q) distributions. Results showed that relatively older players were overrepresented in all the sample (p < 0.001; Q1 = 28.8% vs. Q4 = 20.3%). In players competing in both hemispheres, the RAE was weak despite a more pronounced RAE emerging for southern players. In addition, the RAE was present in backs and forwards, but inconsistent for scrum-halves. In general, the data suggest that relatively older players may be more likely to reach expertise at senior levels than their later-born peers, and that the effect was consistent in different sociocultural contexts as well as in backs and forwards.
Lifestyle Risk Factors for Overweight/Obesity in Spanish Children
Authors: Miguel-Berges María L. , De Miguel-Etayo Pilar , Larruy-García Alicia , Jimeno-Martinez Andrea , Pellicer Carmen , Moreno Aznar Luis
Published: December 2022

Childhood obesity is one of the main public health concerns in Europe. The aim was to identify possible risk factors associated with overweight/obesity in Spanish preschool and school-age children. The sample (1075 (50.7% girls) children aged 3 to 12) is part of the project ‘Alimentando el Cambio’ whose objective is to promote healthy lifestyles in schools. Child height and weight were measured, and parents filled out questionnaires related to the children’s lifestyle. There was a positive and significant association between sweetened beverage consumption and body mass index (BMI) z-score in both sexes and age groups. There was a negative and significant association between BMI z-score and dairy products in girls of both age groups. There was also a protective effect of regular nut consumption on overweight/obesity in girls 6–12 y. Night-time sleep during weekdays showed a negative association with BMI z-score for older boys and girls. A positive and significant association was found between total screen time and BMI z-score during weekdays. Regarding emotional well-being and self-esteem, having girls 6–12 y laughing and feeling happy and good about themselves in the last week was a protective factor against overweight/obesity. Childhood obesity prevention efforts may benefit from targeting these key risk factors.
Physical Well-Being of Children and Adolescents during the SARS-CoV-2 Pandemic: Findings from the “Come te la Passi?” Cross Sectional Survey in Bologna, Italy
Authors: Salussolia Aurelia , Lenzi Jacopo , Montalti Marco , Rallo Flavia , Paternò Martina , Agosta Marta , Resi Davide , Stillo Michela , Guaraldi Federica , Gori Davide , Dallolio Laura , Masini Alice
Published: December 2022

Background: The COVID-19 had a strong impact on the physical and general well-being of the youngest. In Italy, citizens were forced to change their habits, especially during the national lockdown, causing increased levels of sedentary and unhealthy behaviors. “Come te la passi?” was a cross-sectional study aimed at investigating changes in the physical activity levels (PA) and well-being of children and adolescents in the City of Bologna. Methods: An anonymous survey was administered to parents/guardians of children and adolescents aged 6–18 years. Results: 1134 questionnaires were collected during June 2021; 457 (40.3%) were females, and the mean age was 13.0 ± 3.4 years. Regarding the general well-being perception, 61.3% of the participants reported concerns about the future, 46.3% reported sleep difficulties, and 72.8% reported experiencing attention difficulty, with higher percentages among adolescents. Considering the PA frequency, an overall reduction was found, with the percentage of those who rarely did PA and those who frequently did PA both increasing. No gender differences were found. Conclusions: Our findings suggest that the current pandemic has strongly impacted the well-being of children and adolescents. It appears to have primarily affected adolescents, with a significant reduction in PA levels, even after the end of the national lockdown.
Microalgal Carotenoids: Therapeutic Application and Latest Approaches to Enhance the Production
Authors: Sirohi Priyanka , Verma Hariom , Singh Sandeep Kumar , Singh Vipin Kumar , Pandey Jyoti , Khusharia Saksham , Kumar Dharmendra , Kaushalendra  , Teotia Pratibha , Kumar Ajay
Published: December 2022

Microalgae are microscopic photosynthetic organisms frequently found in fresh and marine water ecosystems. Various microalgal species have been considered a reservoir of diverse health-value products, including vitamins, proteins, lipids, and polysaccharides, and are broadly utilized as food and for the treatment of human ailments such as cancer, cardiovascular diseases, allergies, and immunodeficiency. Microalgae-derived carotenoids are the type of accessory pigment that possess light-absorbing potential and play a significant role in metabolic functions. To date, nearly a thousand carotenoids have been reported, but a very less number of microalgae have been used for the commercial production of carotenoids. This review article briefly discussed the carotenoids of microalgal origin and their therapeutic application. In addition, we have briefly compiled the optimization of culture parameters used to enhance microalgal carotenoid production. In addition, the latest biotechnological approaches used to improve the yields of carotenoid has also been discussed.
Development of Post-Stroke Cognitive and Depressive Disturbances: Associations with Neurohumoral Indices
Authors: Zhanina Marina Y. , Druzhkova Tatyana A. , Yakovlev Alexander A. , Vladimirova Elena E. , Freiman Sofia V. , Eremina Natalia N. , Guekht Alla B. , Gulyaeva Natalia V.
Published: December 2022

Neuropsychiatric complications, in particular cognitive and depressive disorders, are common consequences of ischemic stroke (IS) and complicate the rehabilitation, quality of life, and social adaptation of patients. The hypothalamic–pituitary–adrenal (HPA) system, sympathoadrenal medullary system (SAMS), and inflammatory processes are believed to be involved in the pathogenesis of these disorders. This study aimed to explore these systems in IS patients, including those with post-stroke cognitive and depressive disorders, within a year after IS. Indices of the HPA axis, inflammatory system, and SAMS were measured in blood serum (cortisol, interleukin-6 (IL-6)), plasma (adrenocorticotropic hormone), and saliva (cortisol, α-amylase). During one year after mild/moderate IS (NIHSS score 5.9 ± 4.3), serum cortisol and salivary α-amylase levels remained elevated in the total cohort. In the group with further cognitive decline, serum and salivary cortisol levels were elevated during the acute period of IS. In the group with poststroke depressive disorder, salivary α-amylase was constantly elevated, while serum IL-6 was minimal during the acute period. The results suggest prolonged hyperactivation of the HPA axis and SAMS after IS. Specifically, post-stroke cognitive impairment was associated with hyperactivation of the HPA axis during the acute IS period, while post-stroke depressive disorder was associated with the chronic inflammatory process and hyperactivation of SAMS during the follow-up period.
Influence of Exposure Conditions and Particulate Deposition on Anodized Aluminum Corrosion
Authors: Fontinha Isabel , Eustáquio Elsa
Published: December 2022

Anodizing is commonly used for corrosion protection of aluminum and its alloys in the construction industry. The anodic aluminum oxide (AAO) coating has a high ability to prevent the development of extensive pitting corrosion in aluminum substrates, particularly in marine sites, as was observed during a 10-year atmospheric corrosion study carried out in several marine and industrial sites. However, this study also evidenced that this coating can be highly affected by the deposition of particulate material in industrial polluted environments, sometimes in unexpected ways. This study presents information on the atmospheric corrosion of anodized aluminum exposed at two different chemical industrial complexes: a fertilizer production plant and a pulp and paper mill. Visual assessment of surface changes, pitting depth and mass variation with exposure were determined to quantify the degradation suffered. Additionally, SEM/EDS analyses were carried out on the exposed surfaces. Based on the results obtained, the role played by the deposition of airborne particles present in the two environments with respect to the type and level of damage observed is discussed. Deposits of roasted pyrite ash and phosphates or of wood chips and lime particles enhanced pitting corrosion or caused dissolution of the AAO coating.
In-Vitro Efficacy Investigation and an Open-Label, Single-Arm Clinical Study of a Gentle Micropeeling Cream for Sensitive and Non-Sensitive Skin
Authors: Namkoong Jin , Goswami Sayantani , Tartar Océane , Diaz Isabel , Wu Joanna
Published: December 2022

Skin exfoliators, specifically alpha and beta hydroxy acids, have been shown to improve overall skin health and the clinical signs of aging. A micropeeling cream was developed with hydroxy acids and a brown algae extract and the efficacy and tolerability were evaluated in two parts. In the first part of the pre-clinical investigation, the micropeeling cream and the placebo control were evaluated by ELISA, immunostaining, qPCR and an activity assay using ex vivo and in vitro models. In the second part of the clinical efficacy study, 36 female subjects were enrolled for bioinstrumental measurements, visual imaging and clinical evaluation for 28 days. Fifty percent of subjects had sensitive skin. The ex-vivo study showed an increase in loricrin, superoxide dismutase 2, and extracellular matrix expression, without stimulating inflammatory biomarkers. The dermatologist observed a significant enhancement in all the parameters evaluated at day 28, and radiance, homogeneity, and roughness were significantly better after the first cream application. The homogeneity, desquamation and pore diameter showed significant improvement at day 7. The cream improved markers associated with skin aging and protection ex vivo. It was well tolerated, even on sensitive skin, and provided a significant improvement of fine lines, skin texture, and overall skin characteristics.