bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of multiple genomic-factors affecting the homologous recombination deficiency (HRD) in Chinese ovarian cancer.
Authors: Wang Min , Nguyen Thi Phuong Anh , Ding ShouTai , Ye Linxiong , Fei Liping , He Hongsheng , Luo Peng
Published: August 2023

88

Background: A large proportion of (but not all) ovarian cancers with high homologous recombination deficiency (HRD) scores are sensitive to Poly (ADP-ribose) polymerase inhibitors (PARPi). This study aimed to identify multiple genomic factors that could increase HRD scores, helped us understand the potential causes for high HRD scores, and thus make therapy decisions. Methods: A total of 370 Chinese ovarian cancer patients were retrospectively obtained from ovarian patients for HRD status and HRR gene alterations from October, 2021 to January, 2023. Patient information including age, gender, pathology type was collected. All specimens were detected by OncoDrug-SeqTM603-gene panel assay through next-generation sequencing (NGS) using Illumina NovaSeq 6000. The interaction between genomic alternation and its overall instability was analyzed to look for multi-factors affecting HRD. Results: Of 370 patients, there were 296 (80.08%) patients with over 50 years, 225(76.01%) with positive HRD, and 48 (16.2%) patients with BRCA1/2 mutations. The top ten commonly mutated genes were TP53 (54.05%), BRCA1 (8.1%), BRCA2 (8.11%), KRAS (8.11%), PDE1C (8.11%), ARID1A (5.41%), BRAF (5.41%), CDK12 (5.41%), CHEK2 (5.41%), and MSH2 (5.41%).Among of them, there were 24.32% of patients with both HRR and TP53 mutations, and 13.51% of patients had both BRCA1/2 and TP53 mutations. Furthermore, in the trio negative of BRCA1/2, TP53, and HRD groups, KRAS mutations were found in 30 (50%)patients. The mutations in TP53, BRAC1/2, and other HRR genes had positive correlations with HRD scores. Importantly, BRCA1/2-negative patients with mutant TP53 other than wild type had a significantly high HRD score (p<0.05). Although it did not hold true for other HRR gene (excluding BRCA) negative patients (p>0.05), an increasing trend in HRD score was still observed. Conclusions: Alterations of multiple genes including TP53, BRAC1/2, and other HRR genes are correlated with higher HRD scores. In this Chinese cohort, a large number of BRCA1/2-negative patients with TP53 mutations tend to have higher HRD scores. Whether this specific subgroup of Chinese ovarian cancers can benefit from PARPi is in question, although they present high HRD scores.
The relationship between telomerase reverse transcriptase promoter rs2853669 allele C accompanied by C228T and the grade of thyroid malignancy.
Authors: Nakazato Yoko , Miya Toshimichi , Hirano Koichi , Kondo Haruhiko
Published: August 2023

91

Background: Two-point mutations (C228T and C250T) in the promoter region of the telomerase reverse transcriptase (TERT) gene are considered molecular indicators of adverse thyroid tumor biology. The regulatory single nucleotide polymorphism rs2853669 (TrSNP) is located near these TERT promoter mutations and its association with the grade of various cancers has been recently reported. To clarify whether the TrSNP can be a clinically useful molecular marker, we analyzed the relationship of the TrSNP with tumor growth and malignant potential in papillary thyroid cancer and follicular tumors. Methods: DNA was extracted from blood and FFPE specimens of 218 patients with thyroid tumors (133 papillary and 85 follicular), and TrSNP, C228T, and C250T were analyzed. BRAFV600E and NRAS Q61R mutations were also analyzed. The association of these genotypes and mutations with clinicopathological parameters were investigated. Results: The C allele of TrSNP from blood and FFPE specimens were validated with 97.3% concordance, so the C allele of TrSNP from blood samples were used in this study. Univariate analysis of 133 papillary carcinomas for clinicopathologic features showed that the C allele of TrSNP significantly correlated with tumor size as did the C228T mutation (p<0.05, p<0.001). Co-expression of the TrSNP and C228T were significantly corelated with tumor size, extrathyroidal invasion and lymph nodal metastasis (p<0.01, p<0.05). Eighty-five follicular tumors (19 follicular carcinomas and 66 follicular adenomas) were examined. Univariate analysis showed no significant association between the C allele of TrSNP, C228T, or C250T and tumor size. Multivariate analysis demonstrated the C allele TrSNP and C228T were significantly frequent in follicular carcinoma (p<0.05, p<0.001) and therefore were considered a risk factor for malignancy. Conclusions: This study demonstrates that the C-allele of the TrSNP is an indicator of tumor growth of papillary carcinoma and co-expression of the TrSNP and C228T relate tumor progression and malignant grade. These genetic features are expected to be a useful molecular marker for differential diagnosis of benign and malignant tumors and for determining treatment strategies.
A novel pathological finding, "BABA", for a prognostic factor in oral tongue carcinoma.
Authors: Baba Daisuke , Sakashita Shingo , Adachi Masahiro , Sakamoto Naoya , Kojima Motohiro , Matsuura Kazuto , Nakatsura Tetsuya , Hayashi Ryuichi , Ishii Genichiro
Published: August 2023

92

Background: Oral tongue carcinoma is one of the cancers with poor prognosis. The UICC staging classification is commonly used to predict outcomes and to select the treatments, although there are cases where cancer relapse early despite being at the same Stages, indicating a need for additional prognostic factors to predict patient outcomes accurately. Recent advances in RNA sequencing of tumor and immune cells, as well as elucidation of the tumor microenvironment, have enabled the identification of many genes associated with recurrence risk and immunosuppressive environment around the tumor, which essential for precision treatment of the patients with high risks of recurrence. However pathological findings remain the first step in selecting samples with a high risk of recurrence for further analysis of RNA sequencing or the tumor microenvironment. In this study, we identified a novel pathological feature named as “BABA” (Broadening Amoeboid Behavior of Advanced tumor cells) that appears around the invasive front of tumors. It describes the way in which cancer cells progress like amoeba between muscle fibers and affect the prognosis of oral tongue carcinoma, making it a potential factor for the future analysis of next-generation sequencing or tumor microenvironment. Methods: Patients with oral tongue squamous cell carcinoma who underwent surgery were recruited, excluding those who had received salvage treatment for recurrence, those with simultaneous occurrence of carcinoma, those who had undergone palliative therapy, postoperative therapy, or those who lacked any pathological findings. Survival analyses for existing pathological findings, such as pT (pathological primary stage), pN (pathological nodal stage), ENE (extra nodal extension) status, lymphatic invasion, venous invasion, perineural extension, margin status, WPOI (worst pattern of invasion) and BABA were conducted. Results: A total number of 211 patients were analyzed in this study. Patients with positive for BABA had a two-year overall survival rate and recurrence-free survival rate of 0.78(p=0.02) and 0.39 (p<0.001), respectively, according to Kaplan-Meier analysis. In the multivariate analysis for overall survival using Cox regression model, venous invasion and pN ≥1 were significant prognostic factors, with HR (95%CI) of 3.0 (1.5-6.3) and 2.4 (1.2-4.5), respectively. In the multivariate analysis for recurrence free survival using Cox regression model, positive for lymphatic invasion, venous invasion, BABA, pN ≥1 were significant factors, with HR (95%CI) of 2.1 (1.2-3.6), 2.0 (1.1-3.4), 2.2 (1.3-3.7) and 2.0 (1.2-3.6), respectively. Conclusions: BABA is the novel risk factor for recurrence in oral tongue carcinoma. Identifying BABA could help clinicians better predict recurrence and develop more personalized treatment strategies.
Clinical implications of drug-metabolizing genes CYP3A4 and GSTP1 single nucleotide polymorphisms in oral cancer patients undergoing induction chemotherapy.
Authors: Sahoo Pranab Kumar , Mistry Tanuma , GHOSH SUSHMITA , Mahata Sutapa , Sarkar Sinjini , Pal Ranita , Choudhury Trisha , Datta Sriparna , Mandal Syamsundar , Bhowmick Anup Kumar , MUKHERJEE KALYAN KUSUM , Nasare Vilas
Published: August 2023

95

Background: Despite well-established induction chemotherapeutics for advanced-stage oral cavity cancer (OCC), there are no reliable markers to detect drug-induced toxicity and clinical efficacy. The presence of genetic polymorphisms can cause certain enzymes to behave differently in various populations, which can lead to varied outcomes. Thus, we analyzed the effect of metabolizing (CYP3A4) and detoxifying (GSTP1) genes involved in taxane/platinum/5-fluorouracil (TPF) or paclitaxel/carboplatin (PC) metabolism and their clinical outcomes in OCC patients. Methods: The current study included 121 OCC patients who received fixed dose of TPF or PC-based chemotherapy. PCR-RFLP was used to assess the polymorphism of the metabolising gene. SNPs were tested for toxicity and progression-free survival. Results: The grade ≥2 patients (47.9%) having higher fever (33.8%) and vomiting (34.7%) as a result of chemotherapy, showed significant association with the gene CYP3A4 (rs2687105) in both the PM and IM genotypes. For PM genotypes, the odd ratio (OR) of CYP3A4 for fever was 2.33E8 (95% CI: 4.702E7-1.154E9, p = 0.000), and for IM genotypes, it was 6.99E8 (95% CI: 1.89E8-2.581E9, p = 0.000). Meanwhile, the patients with grade ≥2 (58.6%) having anaemia (11.5%) and nausea (32.2%) also found to be significantly associated with GSTP1 (rs749174) in PM genotypes; the odds ratio was (OR: 8; 95%CI:1. 1001-63.963; p=0.05) and (OR: 2.667; 95%CI:1.043-6.815; p=0.04). Moreover, patients with these SNPs showing poor survival rate, however there was no significant association observed between the genotypes of each SNPs with progression-free survival (PFS). Conclusions: In conclusion, our data showed that the rs2687105 in CYP3A4 and the rs749174 in GSTP1 were associated with adverse events of TPF or PC chemotherapeutic regimens among the oral cancer patients. Therefore these genes might be used as predictive markers for minimising the adverse effects caused by chemotherapy and for optimization of drug dose in oral cancer patients.
Disparities in African-American patient enrollment in pivotal phase 3 immunotherapy trials that led to FDA drug approval in patients with non-small cell lung cancer.
Authors: Ubbaonu Chimezie , Ou Sai-Hong Ignatius
Published: August 2023

99

Background: Blacks/African American have historically been underrepresented in enrollment into clinical trials. This leads to uncertainty regarding the efficacy and tolerability of treatments in this patient population following drug approval by the FDA. One of the approval criterion for the FDA is the patient population represents the diversity of patient population in the US as argued by the US FDA in the ORIENT-11 trial (NCT03607539). We abstracted the percentage of African-American into clinical enrolled into pivotal randomized phase 3 trials that led to approval of immunotherapy in advanced NSCLC. Methods: We abstracted the racial composition of randomized phase 3 trials that led to immunotherapy approval including neoadjuvant, adjuvant, consolidation/maintenance, first line and second line indication of immunotherapy in the U.S. Results: We identified a total of 20 randomized phase 3 trials that led to immunotherapy indication in NSCLC by the FDA including neoadjuvant (N = 1), adjuvant (N = 2), consolidation/maintenance (N = 1), first-line (N = 12), and second line (N = 4). We excluded 3 trials (ENPOWER-Lung01, -Lung03, and Checkmate-227) that did not report the racial composition of the patient participants. A total of 12490 subjects participated in the 17 trials analyzed. Of these, 66.3% were male and 33.7% were female. Distribution by race revealed 75.7% White (range 55.9% - 94.3%); 1.9% African-American (range 0.03% - 3.6%); 18.6% Asian (range 1.3% - 34.6%); and 3.8% (0.5% - 7.6%) were either mixed race, American Indian, Pacific Islander or unknown. Conclusions: African-Americans comprised an estimated 13.6% of the U.S. population respectively but our survey indicated only 1.9% of the trial population that led to immunotherapy approval in the US were African-Americans. The patient population in the clinical trials leading to immunotherapy regimen approval in the U.S. significantly under-represented African-Americans and here the true efficacy of and potential unknown adverse events of immunotherapy in African-Americans may over- or under-estimated. The U.S. FDA has the power to approve immunotherapy trials that are more representative of the US population.
ERK5 Cooperates With MEF2C to Regulate Nr4a1 Transcription in MA-10 and MLTC-1 Leydig Cells
Authors: de Mattos Karine , Dumas Félix-Olivier , Campolina-Silva Gabriel Henrique , Belleannée Clémence , Viger Robert S , Tremblay Jacques J
Published: August 2023

Leydig cells produce hormones required for the development and maintenance of sex characteristics and fertility in males. MEF2 transcription factors are important regulators of Leydig cell gene expression and steroidogenesis. ERK5 is an atypical member of the MAP kinase family that modulates transcription factor activity, either by direct phosphorylation or by acting as a transcriptional coactivator. While MEF2 and ERK5 are known to cooperate transcriptionally, the presence and role of ERK5 in Leydig cells remained unknown. Our goal was to determine whether ERK5 is present in Leydig cells and whether it cooperates with MEF2 to regulate gene expression. We found that ERK5 is present in Leydig cells in testicular tissue and immortalized cell lines. ERK5 knockdown in human chorionic gonadotrophin–treated MA-10 Leydig cells reduced steroidogenesis and decreased Star and Nr4a1 expression. Luciferase assays using a synthetic reporter plasmid containing 3 MEF2 elements revealed that ERK5 enhances MEF2-dependent promoter activation. Although ERK5 did not cooperate with MEF2 on the Star promoter in Leydig cell lines, we found that ERK5 and MEF2C do cooperate on the Nr4a1 promoter, which contains 2 adjacent MEF2 elements. Mutation of each MEF2 element in a short version of the Nr4a1 promoter significantly decreased the ERK5/MEF2C cooperation, indicating that both MEF2 elements need to be intact. The ERK5/MEF2C cooperation did not require phosphorylation of MEF2C on Ser387. Taken together, our data identify ERK5 as a new regulator of MEF2 activity in Leydig cells and provide potential new insights into mechanisms that regulate Leydig cell gene expression and function.
What Can Historically Black Colleges and Universities Teach about Improving Higher Education Outcomes for Black Students?
Authors: Price Gregory N. , Viceisza Angelino C. G.
Published: August 2023

Historically Black colleges and universities are institutions that were established prior to 1964 with the principal mission of educating Black Americans. In this essay, we focus on two main issues. We start by examining how Black College students perform across HBCUs and non-HBCUs by looking at a relatively broad range of outcomes, including college and graduate school completion, job satisfaction, social mobility, civic engagement, and health. HBCUs punch significantly above their weight, especially considering their significant lack of resources. We then turn to the potential causes of these differences and provide a glimpse into the “secret sauce” of HBCUs. We conclude with potential implications for HBCU and non-HBCU policy.
Μελέτη ανοσολογικών μηχανισμών στην παθογένεια διάμεσων νοσημάτων του πνεύμονα
Authors: Καραμπιτσάκος Θεόδωρος
Published: August 2023

Εισαγωγή: O καρκίνος πνεύμονα φαίνεται να είναι συχνός σε ασθενείς με IPF, ωστόσο επί του παρόντος εκλείπουν από τη βιβλιογραφία μεγάλες βάσεις δεδομένων. Επιπρόσθετα, με βάση την υψηλή επίπτωση του καρκίνου στην IPF αλλά και με βάση το παράδειγμα repositioning του nintedanib, μελέτη ανοσολογικών μηχανισμών σχετικών με τον καρκίνο στην IPF μπορεί να έχει θετικά αποτελέσματα. Σκοπός: Να δημιουργήσουμε μία βάση δεδομένων για ασθενείς με IPF και καρκίνο πνεύμονα. Να μελετήσουμε προ-καρκινικά μονοπάτια στην IPF και συγκεκριμένα, 1) το ρόλο της SHP2 και 2) αν η λεμφαδενοπάθεια μεσοθωρακίου στην IPF αντικατοπτρίζει συγκεκριμένη ανοσολογική απόκριση και ειδικά αν παρατηρείται έκφραση των PD-1/PD-L1. Αποτελέσματα: Ταυτοποιήσαμε 324 ασθενείς με καρκίνο πνεύμονα μεταξύ 3178 ασθενών με IPF (10.2%). Δέκα έτη μετά τη διάγνωση της IPF, το 26.6% των εν ζωή ασθενών είχε καρκίνο πνεύμονα. Οι ασθενείς με IPF και καρκίνο πνεύμονα είχαν αυξημένο κίνδυνο θνητότητας σε σχέση με τους ασθενείς με IPF [HR: 1.51, (95% CI: 1.22 ως 1.86), p<0.0001]. Ασθενείς με IPF και καρκίνο πνεύμονα που έλαβαν αντι-ινωτική αγωγή [HR: 0.61, (95% CI: 0.42 ως 0.87), p=0.006] ή υπεβλήθησαν σε χειρουργική εξαίρεση του όγκου [πολυπαραγοντική ανάλυση-HR: 0.30 (95% CI: 0.11 ως 0.86), p=0.02] είχαν καλύτερη πρόγνωση σε σχέση με όσους δεν υπεβλήθησαν στην αντίστοιχη θεραπευτική αντιμετώπιση.Πνευμονικοί ινοβλάστες ποντικιών που έφεραν την D61G/+, η οποία καθιστά την SHP2 ενεργή, είχαν μειωμένο πολλαπλασιασμό (1.6-fold, p<0.05), μειωμένη μετανάστευση (2-fold, p<0.05) και επαγόμενη από τον TGFB-1 διαφοροποίηση σε μυοϊνοβλάστες σε σχέση με πνευμονικούς ινοβλάστες από wild-type ποντίκια.Αυξημένη % έκφραση του PD-1 παρατηρήθηκε στα λεμφοκύτταρα μεσοθωρακικών λεμφαδένων ασθενών με IPF συγκριτικά με την έκφραση σε ασθενείς με μη μικροκυτταρικό καρκίνο πνεύμονα. Υποτροπιδικοί λεμφαδένες ποντικιών που έλαβαν μπλεομυκίνη, είχαν αυξημένο μέγεθος και αυξημένη έκφραση PD-1 την ημέρα 14 σε σχέση τους λεμφαδένες ποντικιών που έλαβαν ορό. Το pembrolizumab εμφάνισε αντι-ινωτικές ιδιότητες με βάση το Ashcroft score και τη μηχανική της αναπνοής. Συμπέρασμα: Ο καρκίνος πνεύμονα είναι συχνός σε ασθενείς με IPF και έχει αρνητικό αντίκτυπο ως προς τη ζωή τους. Η μελέτη προκαρκινικών μονοπατιών στην IPF μπορεί να οδηγήσει σε σημαντικά ευρήματα. Η SHP2 και η αναστολή του PD-1 είχαν αντι-ινωτικές ιδιότητες και χρήζουν περαιτέρω διερεύνησης.
Culturally Engaged Career Advising: Gordon's Model Expanded
Authors: Streufert Billie , Smith Kimberly , Hebreard Dana
Published: August 2023

Although Virginia Gordon framed an effective model for career advising, student respondents in national surveys continue to report unmet needs. Several national organizations have called for further integration of academic and career advising. Previous scholars, however, have not fully acknowledged environmental constraints or provided a recent comprehensive overview of culturally engaged career advising. After updating Gordon's framework with inclusive and institutional design practices, the authors provide examples of culturally engaged strategies they deployed. Practitioners can use this framework and institutional examples to advance and expand advising on their campuses.
Corporate Fraud: How to Protect Your Business
Authors: Bernstein Adam
Published: August 2023

In this article, Adam Bernstein discusses the types of fraud that can affect care homes and what can be done to avoid being scammed.
Addressing the Challenges of Electrification
Authors: Knight Helen
Published: August 2023

Project to investigate electrified network and integrate vehicle systems
Supercar to be Lightest Ever
Authors: Knight Helen
Published: August 2023

The T.50 will go on sale for more than £2m
Sebaceous Carcinoma of The Nasal Vestibule: A Case Report
Authors: Gavare Vladislava , Nesterenko Renata , Vilks Ingus
Published: August 2023

Sebaceous carcinoma (SC) is a highly malignant tumour derived from the sebaceous glands. SCs have traditionally been divided into two categories, ocular and extraocular. Tumours arising in extraocular sites are rare and less aggressive than SCs of the eyelid. SC of the nasal vestibule is a very rare pathology, and for today there have been only a few reported cases worldwide. Here, we report a case of a 60-year-old man who presented with a 1-month history of a painful, recurrent bleeding tumour in the right nasal vestibule. Based on the histologic findings, a diagnosis of sebaceous carcinoma of the nasal vestibule was established. We discuss incidence as well as clinical, histologic, diagnostic, prognostic, and management issues of this aggressive neoplasm.
Combining the age-male-albumin-bilirubin-platelets score and shear wave elastography stratifies carcinogenic risk in hepatitis C patients after viral clearance
Authors: Masaoka Rion , Gyotoku Yoshinori , Shirahashi Ryosaku , Suda Toshikuni , Tamano Masaya
Published: August 2023

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
Five-year outcomes of immediate implant placement for mandibular molars with and without chronic apical periodontitis: A retrospective study
Authors: Yang Hua , Luo Dan , Yuan Mu-Jie , Yang Jian-Jun , Wang Da-Shan
Published: August 2023

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
Acquired haemophilia as a complicating factor in treatment of non-muscle invasive bladder cancer: A case report
Authors: Ryšánková Kateřina , Gumulec Jaromír , Grepl Michal , Krhut Jan
Published: August 2023

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
Caution in the use of sedation and endomyocardial biopsy for the management of pediatric acute heart failure caused by endocardial fibroelastosis
Authors: Xin Xiao-Xuan , Se Yo-Yeng
Published: August 2023

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.
Astragalus polysaccharide promotes osteogenic differentiation of human bone marrow derived mesenchymal stem cells by facilitating ANKFY1 expression through miR-760 inhibition
Authors: Hu Xianfeng , Yang Liu , Du Yanhua , Meng Xiangping , Shi Yuanyuan , Zeng Juan
Published: August 2023

Aims

Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation.

Methods

Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay.

Results

The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs.

Conclusion

APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression.

Cite this article: Bone Joint Res 2023;12(8):476–485.
Propagation of Love Waves Through an Irregular Surface of a Layered Poroelastic Rock Structure
Authors: Negi Anil , Kapoor Saurabh
Published: August 2023

The present study adduces the dynamic properties of the propagating Love waves passing through the irregular upper surface of transversely isotropic poroelastic structure. The dispersion relation for scattered Love waves in a closed form and induced reflected displacement caused by scattering of waves have been derived. The impact of the porosity of the upper layer and half-space on the phase velocity and also on the reflected displacement have also been studied. The porosity of both upper layer and half-space have significant effect on the phase velocity of Love waves. Moreover, the nature of induced reflected displacement with the change in vertical irregularity parameter is also analyzed. The vertical irregularity parameter (associated with the vertical depth of irregularity) has escalating impact on the induced reflected displacement. The comparative analysis of reflected displacement in three distinct scenarios of vertical irregularity has also been done.
Modelling of Artificial Neural Network to Validate the Experimental Data of a Laboratory Scale ROT
Authors: Biswas Prabir , Chakraborty Kaustav , Raha Pratik Kumar , Mandal Pranibesh
Published: August 2023

Run Out Tables (ROTs) are critical in the metallurgical sector for producing unique steel grade. The cooling rate controls the fine structure of steel, which is influenced by a number of factors such as the convective heat transfer coefficient, mean film temperature and many others. As a result, achieving a new steel grade necessitates the optimum combination of all of these factors. The cooling rate as a function of steel characteristics is obtained employing laboratory data such as convective heat transfer coefficient, mean film temperature, and mass flow rate of coolant at preset upper and lower nozzle distances from the experimental setup. Three Artificial Neural Network programs have been used to validate and check the performance of the experimental setup for optimize the cooling rate.
Zkušenosti s efektivní realizací průzkumů obsazenosti vozidel MHD prostřednictvím automatizovaných systémů
Authors: Turek Richard , Bystrianský Adam , Striegler Radim , Krátký Jan
Published: August 2023

Předmětem článku je představení moderních způsobů, pomocí kterých lze provádět dopravní průzkumy v městské hromadné dopravě a zkušeností s jejich použitím. Jde o příspěvek k metodologii práce znalců oboru doprava, odvětví doprava silniční, specializace posuzování provozu veřejné hromadné dopravy. Ještě nedávno se tyto průzkumy dělaly tzv. „čárkováním“, tedy za pomocí sčítačů a zapisovacích archů. Tento způsob je i dodnes využíván jako rezerva při selhání moderních technologií. V Centru dopravního výzkumu byla vytvořena mobilní aplikace a webové rozhraní pro automatizaci těchto průzkumů, úsporu času a zvýšení efektivity práce v terénu.
Vliv nastavení geometrie přední nápravy nákladního vozidla na opotřebení pneumatik a spotřebu paliva
Authors: Sláma Vladimír
Published: August 2023

Tento příspěvek je zaměřen na vliv nesprávně nastavené geometrie přednínápravy na opotřebení běhounu pneumatiky a spotřebu nákladního vozidla.Příspěvěk se zaměřuje na sbíhavost, jako na klíčový parametr nastavenípřední nápravy. Testování proběhlo na třech totožných tahačích DAF XFsrozdílně nastavenou geometrií. Geometrie jednoho vozidla byla nastavenadle požadavků výrobce a u dalších dvou vozidel byla sbíhavost zvýšena.Předpokladem je zvýšené opotřebení běhounu pneumatik vlivem vyššísbíhavosti a rovněž vyšší spotřeba paliva. Kromě opotřebení pneumatika spotřeby paliva se příspěvěk zaměřuje i na ekonomickou stránku danéproblematiky. Aby byla zajištěna věrohodnost výsledků, testování probíhalodlouhodobě při komerčním provozu na pozemních komunikacích.
Alberto Blest Gana and the Unhappy Endings of Beautiful Men
Authors: Vilches Patricia
Published: August 2023

ABSTRACT: This essay analyzes Alberto Blest Gana’s portrayal of masculine beauty in Rafael San Luis and Abelardo Manríquez through the lens of patriotism and social order. The divine, angelic looks of these two young characters come with a high cost. San Luis, from Martín Rivas (1862), and Manríquez, from El ideal de un calavera (1863), are exceedingly handsome but devoid of means, a fact that makes their circumstances especially harsh. They are also deeply in love with privileged, wealthy Santiago women, which causes the heroes to suffer. They challenge Chile’s capitalist social order, resist their outsider status, and follow the Weltanschauung of a pipiolo (liberal). They confront danger and fight the good fight. Yet these two brave men cannot escape past behaviors and decisions. It is their unhappy fate to lose their beautiful ladies to less attractive men, and ultimately to die in battle (San Luis) and by execution (Manríquez).
Damn the Suit and the Tailor Who Made It: Power Struggle between the Narrator and the Editor in Nuevas coplas y cantares del temible bardo Eudomóndaro Higuera alias el Tuerto
Authors: Carpenter Victoria
Published: August 2023

ABSTRACT: The collection of poems by a supposedly long-dead Sinaloan poet Eudomóndaro Higuera (referred to in the study as “the Narrator”), Nuevas coplas y cantares del temible bardo Eudomóndaro Higuera alias el Tuerto , is an intriguing read. Compiled and annotated by Mario Bojórquez (who will be referred to as “the Editor”), it contains a strange mix of bawdy lyrics, insulting epitaphs, and soul-searching coded poems. The collection presents a challenge to the reader, who is forced to choose between the Narrator’s often simplistic writing and the Editor’s high academic analyses thereof. Using the theory of text ownership, I will analyze this contradictory combination to determine who—if anyone—controls the text of the collection. I will explore the roles of the narrator and the editor, taken up by both the Narrator and the Editor, in order to challenge the apparent parodic nature of the collection.
Defending the Samurai: Alice Mabel Bacon and Meiji Japan at War / 侍を擁護して:アリス・メーベル・ベーコンと戦時下の明治日本
Authors: Henning Joseph M.
Published: August 2023

Abstract: Alice Mabel Bacon (1858–1918), a friend and colleague of Ōyama Sutematsu and Tsuda Ume, authored three books on Japan and edited the English translation of a Japanese soldier’s war memoir. She and her work cross a wide range of terrain in the gender, diplomatic, and military histories of U.S.-Japanese relations in the Meiji period. In her writing, she depicted the samurai as the driving force in Japanese history from feudalism up to the present. Praising them for their role in developing Meiji Japan into a world power, Bacon identified evidence for her claims in the First Sino-Japanese War and the Russo-Japanese War. In the United States, she challenged the construction of war reporting as a male domain when she questioned press accounts of a massacre carried out by Japanese troops, utilizing her expertise on Japan to stand her ground against a male reporter who emphasized her gender in an effort to undermine her argument. During and after the war with Russia, Bacon extolled bushido as the samurai ethos, which she depicted as having evolved into selfless devotion to the emperor. She also challenged the construction of war itself as a male domain by emphasizing the sacrifices of women on the home front. Bacon thus worked to familiarize Americans with three discourses promoted by the Meiji state and its supporters: the “good wife, wise mother” ideology, the “human bullet” myth, and bushido.
Sarah Fielding's Double Stratagem in The Lives of Cleopatra and Octavia
Authors: Wilputte Earla
Published: August 2023

Abstract: The Lives of Cleopatra and Octavia is not simply a fanciful delivering of history but also a clever interrogation of biography and fiction. A narratological analysis of Sarah Fielding's introduction and The Lives reveals how Fielding's adaptation is simultaneously true and untrue, and how she subtly parallels her authorial practice with Cleopatra's contrivances. Fielding's constant elision among author, subject, and genres reveals the unsettling, yet alluring, power of fiction, and of prose narrative generally. Exposing the false dialectic between biography and fiction, Fielding challenges readers to judge the eponymous women, her own artful performances, and the purported dialectic between fiction and history.
Harriet Martineau's Early Tales for the Young
Authors: Lai Shu-Fang
Published: August 2023

ABSTRACT: This study analyzes two of Harriet Martineau's early children's tales: Christmas-Day, or, the Friends (1824) and Mary Campbell, or, the Affectionate Granddaughter (1828). Although Martineau's early tales and tracts have received little critical attention, they are significant in terms of revealing her literary potential and gateway to authorship. These two tales reflect Martineau's own experiences with grief and loss, and provide insights into her advocacy of such moral values as love and friendship, hard work and duty. This early fiction anticipates the educational ideas further developed in Household Education (1849), which addresses the need to guide children through hardship and to cultivate their intellectual and moral character through nurturance rather than "the taking-down system" of child-rearing that was typical of the age.
Communities and Anti-communities: Caroline Helstone's Societies in Charlotte Brontë's Shirley
Authors: Gupta Pallabi
Published: August 2023

ABSTRACT: To address the era's "condition of women" question, Charlotte Brontë's Shirley employs Caroline Helstone's storyline through two frameworks: community and anti-community. Woman's community consists of those who identify and nurture her needs and ambitions as an individual within the broader social network; an anti-community discourages female individualism, instead emphasizing restraint and conformity. This perspective offers a useful framework through which to consider the condition-of-women-question, its relation to the angel in the house, and its depiction in Shirley . In addition, it serves to defend the novel against two prominent critical complaints: that Shirley lacks thematic or structural unity, and that its conformist ending contradicts its feminist premise.
Decolonization of Tribal Schools
Authors: Kivalahula-Uddin Hannah
Published: August 2023

Abstract: This study utilized the culturally responsive qualitative methodology of phenomenology to provide an opportunity for eight Puyallup tribal elders to share their lived stories while providing insights into the impact of intergenerational historical trauma upon their lives. The elders provided suggestions about how to improve student achievement by facilitating a decolonization intervention program for tribal school employees derived from elder Indigenous knowledge. The goals of the program would be to provide information about tribal history, historical trauma, the Twulshootseed (txʷəlšucid) language, and our traditional ways along with professional learning communities, peer mentoring, and follow-up trainings. The study findings suggest a decolonization intervention program is the most important first step for P-12 tribal schools to improve academic achievement.
Reflections on the Applications of Immunohistochemistry to Understanding the Maintenance of Electrochemical Gradients in the Inner Ear
Authors: Schulte Bradley A.
Published: August 2023

The author of the accompanying classic paper from the Journal of Histochemistry and Cytochemistry (Crouch JJ, Sakaguchi N, Lytle C, Schulte BA. Immunohistochemical localization of the Na-K-Cl Co-transporter (NKCC1) in the Gerbil Inner Ear. Journal of Histochemistry & Cytochemistry 1997;45(6):773-778) comments on how the immunohistochemical techniques used in the study provided critical new information that helped define the cellular and molecular mechanisms involved in the generation and maintenance of electrochemical gradients in the ear, particularly the presence of the Na,K,2Cl symporter (NKCC) in the inner ear. (J Histochem Cytochem 71: 509–510, 2023)
Modeling the role of the thalamus in resting-state functional connectivity: Nature or structure
Authors: Cabrera-Álvarez Jesús , Doorn Nina , Maestú Fernando , Susi Gianluca
Published: August 2023

The thalamus is a central brain structure that serves as a relay station for sensory inputs from the periphery to the cortex and regulates cortical arousal. Traditionally, it has been regarded as a passive relay that transmits information between brain regions. However, recent studies have suggested that the thalamus may also play a role in shaping functional connectivity (FC) in a task-based context. Based on this idea, we hypothesized that due to its centrality in the network and its involvement in cortical activation, the thalamus may also contribute to resting-state FC, a key neurological biomarker widely used to characterize brain function in health and disease. To investigate this hypothesis, we constructed ten in-silico brain network models based on neuroimaging data (MEG, MRI, and dwMRI), and simulated them including and excluding the thalamus, and raising the noise into thalamus to represent the afferences related to the reticular activating system (RAS) and the relay of peripheral sensory inputs. We simulated brain activity and compared the resulting FC to their empirical MEG counterparts to evaluate model’s performance. Results showed that a parceled version of the thalamus with higher noise, able to drive damped cortical oscillators, enhanced the match to empirical FC. However, with an already active self-oscillatory cortex, no impact on the dynamics was observed when introducing the thalamus. We also demonstrated that the enhanced performance was not related to the structural connectivity of the thalamus, but to its higher noisy inputs. Additionally, we highlighted the relevance of a balanced signal-to-noise ratio in thalamus to allow it to propagate its own dynamics. In conclusion, our study sheds light on the role of the thalamus in shaping brain dynamics and FC in resting-state and allowed us to discuss the general role of criticality in the brain at the mesoscale level.
Segregational drift hinders the evolution of antibiotic resistance on polyploid replicons
Authors: Garoña Ana , Santer Mario , Hülter Nils F. , Uecker Hildegard , Dagan Tal
Published: August 2023

The emergence of antibiotic resistance under treatment depends on the availability of resistance alleles and their establishment in the population. Novel resistance alleles are encoded either in chromosomal or extrachromosomal genetic elements; both types may be present in multiple copies within the cell. However, the effect of polyploidy on the emergence of antibiotic resistance remains understudied. Here we show that the establishment of resistance alleles in microbial populations depends on the ploidy level. Evolving bacterial populations under selection for antibiotic resistance, we demonstrate that resistance alleles in polyploid elements are lost frequently in comparison to alleles in monoploid elements due to segregational drift. Integrating the experiments with a mathematical model, we find a remarkable agreement between the theoretical and empirical results, confirming our understanding of the allele segregation process. Using the mathematical model, we further show that the effect of polyploidy on the establishment probability of beneficial alleles is strongest for low replicon copy numbers and plateaus for high replicon copy numbers. Our results suggest that the distribution of fitness effects for mutations that are eventually fixed in a population depends on the replicon ploidy level. Our study indicates that the emergence of antibiotic resistance in bacterial pathogens depends on the pathogen ploidy level.
The community acceptance of COVID-19 vaccines in Rakhine State: A cross-sectional study in Myanmar
Authors: Simon Saw , Min Kaung Myat , Latt Tun Zaw , Moe Pa Pa , Tun Kyaw Myo
Published: August 2023

The global pandemic situation of SARS-CoV-2 (COVID-19) has been ongoing for more than 2 years with the emergence of different variants. With the rapid development of vaccines, countries including Myanmar rolled out vaccination programs to reduce the morbidity and mortality due to COVID-19 with the ultimate goal to end the pandemic. This study seeks to explore the acceptance of the general adult population towards the COVID-19 vaccines administered by the Ministry of Health, and barriers to vaccine acceptance. A quantitative cross-sectional study was conducted by adopting valid and reliable questionnaires from similar studies around the world. Simple random sampling was used to select 288 participants from 12 townships of Rakhine State, Myanmar. The interview was performed using standardized paper-based documents. While the data entry and manipulation were performed using Microsoft Excel, the data analysis process was performed using the Statistical Package for Social Science (SPSS) software. As descriptive statistics, the level of vaccine acceptance, and barriers to vaccine acceptance were calculated. Chi-square analysis and bivariate logistics regression was performed to explore the associated socio-demographic characteristics, COVID-19 and vaccine-related experience, and perceptions of participants on the health belief model (HBM) domains related to vaccine acceptance. A total of 276 participants entered the study and revealed an overall vaccine acceptance level of 91.3%. Higher level of education, working in skilled manual and sales services, monthly income of more than 200,000 MMK (111 USD), history of previous vaccination, not experiencing side effects of vaccine after previous immunization, and elements of the health belief model (HBM) were associated with higher vaccine acceptance. The barriers to vaccine acceptance were mistrust of the efficacy of vaccines and potential major adverse events of COVID-19 vaccines. The high level of vaccine acceptance among the general population in Rakhine state provides an opportunity for health authorities to achieve high vaccination coverage within the community. Nevertheless, the vaccine-related education campaigns should be targeted and conveyed frequently to the sub-groups of the population with vaccine hesitancy to obtain the highest achievable level of vaccine coverage within the community for the ultimate goal to end the pandemic.
Nonalcoholic steatohepatitis-associated hepatocarcinogenesis in mice fed a modified choline-deficient, methionine-lowered, L-amino acid-defined diet and the role of signal changes
Authors: Suzuki-Kemuriyama Noriko , Abe Akari , Nakane Sae , Yuki Megumi , Miyajima Katsuhiro , Nakae Dai
Published: August 2023

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and even hepatocellular carcinoma (HCC). The incidence of NASH-associated HCC is increasing, posing a serious public health threat. Unfortunately, the underlying pathological mechanisms, including the possible differences between neoplastic and non-neoplastic lesions, remain largely unknown. Previously, we reported a dietary mouse NASH model with a choline-deficient, methionine-lowered, L-amino-acid-defined, high-fat diet containing shortening without trans fatty acids (CDAA-HF-T[−]), which rapidly induces fibrosis and proliferative lesions in the liver. This study aimed to develop a mouse CDAA-HF-T(−) model capable of assessing NASH-associated hepatocarcinogenesis and identifying key signaling factors involved in its underlying mechanisms. Multiple large masses, histopathologically hepatocellular adenomas and carcinomas, and hemangiosarcomas were detected in the liver samples of mice fed CDAA-HF-T(−) for 52 or 63 weeks, along with highly advanced fibrosis and numerous foamy, phagocytic macrophages in the adjacent nontumoral area. Multiple metastatic nodules were found in the lungs of one of the animals, and lymphoid clusters were found in all CDAA-HF-T(−) group mice. In the Ingenuity Pathways Analysis of RNA expression data, the CDAA-HF-T(−) feeding revealed common signal changes in nontumoral and tumoral liver tissues, including increased IL-8 and RhoGTPases signaling and decreased lipid metabolism. Meanwhile, macrophage inflammatory protein 2 (MIP-2) expression levels were upregulated in nontumoral liver tissue from the end of Week 13 of CDAA-HF-T(−) feeding to the end of Week 63. On the other hand, MIP-2 was expressed on macrophages in non-tumor areas and hepatocytes in tumor areas. Therefore, the CDAA-HF-T(−) mouse model is useful for assessing NASH and NASH-associated hepatocarcinogenesis, and IL-8 signaling plays important roles in NASH-associated carcinogenesis and cirrhosis, but it may also play different roles in nontumoral liver tissue and tumorigenesis.