bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Epigenetic in Dental and Oral Regenerative Medicine by Different Types of Dental Stem Cells: A Comprehensive Overview
Authors: Hussain Ahmed , Tebyaniyan Hamid , Khayatan Danial
Published: June 2022

Postnatal teeth, wisdom teeth, and exfoliated deciduous teeth can be harvested for dental stem cell (DSC) researches. These mesenchymal stem cells (MSCs) can differentiate and also consider as promising candidates for dental and oral regeneration. Thus, the development of DSC therapies can be considered a suitable but challenging target for tissue regeneration. Epigenetics describes changes in gene expression rather than changes in DNA and broadly happens in bone homeostasis, embryogenesis, stem cell fate, and disease development. The epigenetic regulation of gene expression and the regulation of cell fate is mainly governed by deoxyribonucleic acid (DNA) methylation, histone modification, and noncoding RNAs (ncRNAs). Tissue engineering utilizes DSCs as a target. Tissue engineering therapies are based on the multipotent regenerative potential of DSCs. It is believed that epigenetic factors are essential for maintaining the multipotency of DSCs. A wide range of host and environmental factors influence stem cell differentiation and differentiation commitment, of which epigenetic regulation is critical. Several lines of evidence have shown that epigenetic modification of DNA and DNA-correlated histones are necessary for determining cells’ phenotypes and regulating stem cells’ pluripotency and renewal capacity. It is increasingly recognized that nuclear enzyme activities, such as histone deacetylases, can be used pharmacologically to induce stem cell differentiation and dedifferentiation. In this review, the role of epigenetic in dental and oral regenerative medicine by different types of dental stem cells is discussed in two new and promising areas of medical and biological researches in recent studies (2010-2022).
Application of Neural Network Algorithm in Medical Artificial Intelligence Product Development
Authors: Xiao Yineng
Published: June 2022

With the continuous deepening of artificial intelligence (AI) in the medical field, the social risks brought by the development and application of medical AI products have become increasingly prominent, bringing hidden worries to the protection of civil rights, social stability, and healthy development. There are many new problems that need to be solved in our country’s existing risk regulation theories when dealing with such risks. By introducing the theory of risk administrative law, it analyzes the social risks of medical AI, organically combines the principle of risk prevention with benefit measurement, and systematically and flexibly reconstructs the theoretical system of medical AI social risk assessment. This paper has completed the following work: (1) reviewed and sorted out the works and papers related to medical AI ethics, medical AI risk, etc., and sorted out the current situation of medical AI social risk regulation at home and abroad to provide help for follow-up research. (2) The related technologies of artificial neural network (ANN) are introduced, and the risk assessment index system of medical AI is constructed. (3) With the self-designed dataset, the trained neural network model is utilized to assess risk. The experimental results reveal that the created BPNN model’s error is relatively tiny, indicating that the algorithm model developed in this research is worth popularizing and applying.
Research on the Style of Art Works based on Deep Learning
Authors: Liu Shulin
Published: June 2022

In view of the unsatisfactory effect and major limitations of the style transfer of art works, this paper takes Chinese ink painting for the research subject. The obvious texture characteristics of Chinese ink painting are selected as the input of the Cycle Generative Adversarial Network (CycleGAN) model builder, and the relativistic evaluator is employed to improve the model loss function and the adversarial loss function. An improved art style transfer method of the CycleGAN model is proposed. The experiment shows that the improved CycleGAN model is efficient and feasible for style transfer. Compared with the traditional CycleGAN model, the proposed model performs better in GAN train and GAN test, with a higher average pass rate, which is an increase of nearly 10%. At the same time, with the increase of the number of iterations, the training time of the improved model is close to that of the original model, but the image of the improved model training is larger, which shows that it has more advantages.
Analysis of Badminton Movement Cognition Algorithm Based on Track Linear Capture
Authors: Wang Zhiwei , Hu Yuxiang
Published: June 2022

At present, more and more sports science and technology are being explored and applied in competitive sports. The birth and popularization of video tracking and capturing technology have provided more fair and just perspectives for many sports events. Track linear capture can replay the player’s behavior in real time, the flight path of the badminton can be analyzed in 3D stereoscopic analysis, and the ball’s motion trajectory can be calculated more accurately. In this paper, an objective trajectory tracking and prediction model is constructed based on the motion cognition algorithm, and the motion characteristics of the objective are extracted from the limited historical trajectory of the objective to achieve more accurate trajectory tracking. Then, the trajectory tracking model is applied to the objective tracking framework to obtain ideal objective tracking results. At the same time, in order to make use of the interaction between scene information and objective, this paper improves the trajectory tracking model. The trajectory prediction model based on neural network is constructed, which learns the pedestrian motion characteristics from the pedestrian trajectory data of the target tracking scene offline and uses its “memory” online to generate the implicit depth motion characteristics of the target according to the limited historical information of the target. It also predicts the most likely location of the future target and calculates the motion similarity between the targets. Finally, a simulation experiment platform is built to prove the effectiveness of the trajectory tracking model and objective tracking algorithm proposed in this paper. Through the research results of this paper, it can play a role in verifying the referee’s judgment on the penalty of some key balls, which is more conducive to maintaining the fairness of the game, and more helpful for athletes to optimize their exercise results according to scientific basis, and has the function of improving their performance.
Exploring Intelligent Teaching for Teachers of Ideology and Politics in the Context of Artificial Intelligence
Authors: Tian Xianghui
Published: June 2022

MooTools (MOOC) is an emerging teaching mode in higher education in recent years, which is rapidly developing and expanding into the traditional teaching field. Based on the characteristics of MOOC platform, this paper explores the intelligent teaching of ideology and politics in the context of artificial intelligence and selects the Internet of Things (IoT) technology course as the research object to combine the MOOC hybrid teaching method with the teaching of IoT technology course. In this paper, a two-level dynamic student model is proposed, which has the following characteristics: (1) comprehensive characteristics of learners are obtained through a combination of tracking and comprehensive evaluation, (2) secondary characteristics of learners are maintained to the instructor in an open and dynamic way, and (3) information of secondary characteristics is organized in the form of running accounts. Based on the two-level dynamic student model, the generalized fuzzy integrated evaluation method is used to evaluate the secondary characteristics of the learners. Through this project, effective improvement of students’ course learning performance and recognition of the course was achieved.
High Performance Computing Simulation of Intelligent Logistics Management Based on Shortest Path Algorithm
Authors: Wei Zongchao
Published: June 2022

At present, e-commerce drives the logistics industry to develop greatly, but at the same time, there is a huge demand in this field, such as lower cost and higher efficiency. Facing the needs of logistics management development, it needs the blessing of intelligent technology, which involves countless fields at present. Intelligent logistics management has become a hot spot at present. What needs to be solved in this respect is how to shorten the transportation distance and save costs. To solve this problem, this paper proposes to introduce the shortest path algorithm. This paper compares the Dijkstra algorithm with the A

∗

algorithm under the background of logistics management and finds that the latter is more suitable for this field with huge amount of information. In order to improve the performance of the A

∗

algorithm, this paper introduces ant colony algorithm, which can better avoid obstacles. Combining these two algorithms, a

∗

-ant colony algorithm is obtained. The algorithm absorbs the advantages of the two algorithms, while maintaining high efficiency and good stability. These characteristics are very satisfying in the field of logistics management. Through the performance test and simulation experiment, it is concluded that the algorithm has excellent optimization ability and can reduce the cost for this field.
Design and Implementation of Software-Defined Data Center (SDDC) for Medical Colleges and Universities
Authors: Lin Wei , Wu YuMing , Jiao Ning
Published: June 2022

The current medical universities culture can reflect their professional nature, showing a strong development trend. The current socialist economy of China is rapidly developing along with cloud computing for data centers. For cultural and educational activities, virtualization and software-defined data center (SDDC) technologies are being used. The most widely used open-source virtualization technologies are SDDC and virtualization. Users may utilize OpenStack to establish private cloud computing environments. The separate control and forwarding architecture of SDDC also make it naturally suitable for the data center’s network environment. Ryu controller has become one of the most widely used SDDC controllers because of its lightweight, high efficiency, and modularity features. Due to the large variety of network operations required by the SDDC, appropriate management and control function modules must be developed on Ryu when it is used as the controller. This study investigates the construction of campus culture at medical colleges and universities using SDDC. Our main objective is to improve the efficiency of data construction in medical colleges and universities and creating a positive cultural environment. On the one hand, the addition of functional modules makes the management of the controller itself easier. Ryu lacks an intuitive interactive platform. Although OpenStack provides an interactive interface, it cannot meet the integration requirements of Ryu. The unified control and school scheduling system have some research and application potential. The experimental results show that our proposed approach of designing an SDDC for medical colleges and universities has a significant impact and has vast potential for future studies.
[Retracted] Developing a Multimodal Model for Detecting Higher‐Grade Prostate Cancer Using Biomarkers and Risk Factors
Authors: Velmurugan Palanivel , Mohanavel Vinayagam , Shrestha Anupama , Sivakumar Subpiramaniyam , Oyouni Atif Abdulwahab A. , Al-Amer Osama M. , Alzahrani Othman R. , Alasseiri Mohammed I. , Hamadi Abdullah , Alalawy Adel Ibrahim
Published: June 2022

A technique to predict crucial clinical prostate cancer (PC) is desperately required to prevent diagnostic errors and overdiagnosis. To create a multimodal model that incorporates long‐established messenger RNA (mRNA) indicators and conventional risk variables for identifying individuals with severe PC on prostatic biopsies. Urinary has gathered for mRNA analysis following a DRE and before a prostatic examination in two prospective multimodal investigations. A first group (n = 489) generated the multimodal risk score, which was then medically verified in a second group (n = 283). The reverse transcription qualitative polymerase chain reaction determined the mRNA phase. Logistic regression was applied to predict risk in patients and incorporate health risks. The area under the curve (AUC) was used to compare models, and clinical efficacy was assessed by using a DCA. The amounts of sixth homeobox clustering and first distal‐less homeobox mRNA have been strongly predictive of high‐grade PC detection. In the control subjects, the multimodal method achieved a total AUC of 0.90, with the most important aspects being the messenger riboneuclic acid features’ PSA densities and previous cancer‐negative tests as a nonsignificant design ability to contribute to PSA, aging, and background. An AUC of 0.86 was observed for one more model that added DRE as an extra risk component. Two methods were satisfactorily verified without any significant changes within the area under the curve in the validation group. DCA showed a massive net advantage and the highest decrease in inappropriate costs.
Lower Blood Lipid Level Is Associated with the Occurrence of Parkinson’s Disease: A Meta-Analysis and Systematic Review
Authors: Hong Xue , Guo Wenting , Li Shanshan
Published: June 2022

Background. The changes of blood lipid levels in patients with Parkinson’s disease (PD) and its clinical relevance remain unclear. We aimed to evaluate the potential association of blood lipid and the occurrence of PD, to provide evidence to the clinical treatment and nursing care of PD. Methods. We searched PubMed, Medline, Web of Science, Cochrane Library, Wanfang Database, Weipu Database, and China National Knowledge Infrastructure for studies related to the blood lipid levels and PD until November 30, 2021. Two researchers independently screened the literature and extricated the data including the levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of included studies. RevMan5.3 and Stata 12.0 software were used for statistical processing and analysis. Results. A total of 15 cohort studies with 9740 participants involving 2032 PD patients and 7708 controls were included. Meta-analysis indicated that TC (SMD = −0.29, 95% CI −0.55∼−0.03,

P
=
0.04

), TG (SMD = −16.83, 95% CI −20.71∼−12.95,

P
<
0.001

), HDL-C (SMD = −0.14, 95% CI −0.26∼−0.02,

P
<
0.001

) and LDL-C (SMD = −0.26, 95% CI −0.50∼−0.01,

P
=
0.04

) level in the PD patients was significantly lower than that of health controls. Sensitivity analysis indicated that the results were stable. No significant publication bias was found between the synthesized outcomes. Conclusions. Lower blood TC, TG, HDL-C, and LDL-C level are associated with the occurrence of PD. Limited by sample size and study population, further high-quality, large-sample clinical trials in different areas are needed to further determine the relationship between blood lipids and PD in the future.
Expression of the FOXP1 Transcription Factor Is Strongly Associated with Inferior Survival in Patients with Diffuse Large B-Cell Lymphoma
Authors: Banham Alison H. , Connors Joseph M. , Brown Philip J. , Cordell Jacqueline L. , Ott German , Sreenivasan Gayatri , Farinha Pedro , Horsman Douglas E. , Gascoyne Randy D.
Published: June 2022

Gene expression profiling studies have reported up-regulated mRNA expression of the FOXP1 forkhead transcription factor in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the prognostic importance of FOXP1 protein expression in an independent series of DLBCL.

First, the specificity of our FOXP1 monoclonal antibody was verified by confirming that it did not recognize the closely related FOXP2, FOXP3, or FOXP4 proteins. FOXP1 protein expression was then analyzed by immunohistochemistry using a DLBCL tissue microarray constructed from 101 previously untreated de novo cases from the British Columbia Cancer Agency. FOXP1 expression was scored as either positive (>30% positive nuclei) or negative (<30% positive nuclei).

The overall survival curves clearly showed that patients grouped as FOXP1-positive (40%) had a significantly decreased overall survival (P = 0.0001). FOXP1-positive patients had a median overall survival of 1.6 years compared with 12.2 years in FOXP1-negative cases. In addition, FOXP1-positive patients showed a clear trend to earlier progression in comparison to the FOXP1-negative patients. The analysis of FOXP1 expression within low, medium, and high International Prognostic Index groupings found that FOXP1-negative patients had better overall survival within each group indicating that FOXP1 expression has predictive value independent of the International Prognostic Index subgrouping, a finding that was confirmed in multivariate analysis. These initial results suggest that FOXP1 expression may be important in DLBCL pathogenesis.
Matrix Metalloproteinase-12 Expression Correlates with Local Recurrence and Metastatic Disease in Non–Small Cell Lung Cancer Patients
Authors: Hofmann Hans-Stefan , Hansen Gesine , Richter Günther , Taege Christiane , Simm Andreas , Silber Rolf-Edgar , Burdach Stefan
Published: June 2022

Purpose: Non–small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix.

Experimental Design: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLC patients. Validation of microarray results was done using reverse transcription-PCR and immunohistology.

Results: MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse–free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells.

Conclusions: MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread of Ovarian Cancer
Authors: Wang Ena , Ngalame Yvonne , Panelli Monica C. , Nguyen-Jackson Hoainam , Deavers Michael , Mueller Peter , Hu Wei , Savary Cherylyn A. , Kobayashi Ryuji , Freedman Ralph S. , Marincola Francesco M.
Published: June 2022

Purpose: Epithelial ovarian cancer (EOC) is characterized by early peritoneal involvement ultimately contributing to morbidity and mortality. To study the role of the peritoneum in fostering tumor invasion, we analyzed differences between the transcriptional repertoires of peritoneal tissue lacking detectable cancer in patients with EOC versus benign gynecologic disease.

Experimental Design: Specimens were collected at laparotomy from patients with benign disease (b) or malignant (m) ovarian pathology and comprised primary ovarian tumors, paired bilateral specimens from adjacent peritoneum and attached stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and peripheral blood mononuclear cells. Specimens were immediately frozen. RNA was amplified by in vitro transcription and cohybridized with reference RNA to a custom-made 17.5k cDNA microarray.

Results: Principal component analysis and unsupervised clustering did not segregate specimens from patients with benign or malignant pathology. Class comparison identified differences between benign and malignant PE and ST specimens deemed significant by permutation test (P = 0.027 and 0.012, respectively). A two-tailed Student's t test identified 402 (bPE versus mPE) and 663 (mST versus bST) genes differentially expressed at a significance level of P2 ≤ 0.005 when all available paired samples from each patient were analyzed. The same comparison using one sample per patient reduced the pool of differentially expressed genes but retained permutation test significance for bST versus mST (P = 0.031) and borderline significance for bPE versus mPE (P = 0.056) differences.

Conclusions: The presence of EOC may foster peritoneal implantation and growth of cancer cells by inducing factors that may represent molecular targets for disease control.
A Predictor Based on the Somatic Genomic Changes of the BRCA1/BRCA2 Breast Cancer Tumors Identifies the Non-BRCA1/BRCA2 Tumors with BRCA1 Promoter Hypermethylation
Authors: Alvarez Sara , Diaz-Uriarte Ramon , Osorio Ana , Barroso Alicia , Melchor Lorenzo , Paz Maria Fe , Honrado Emiliano , Rodríguez Raquel , Urioste Miguel , Valle Laura , Díez Orland , Cigudosa Juan Cruz , Dopazo Joaquin , Esteller Manel , Benitez Javier
Published: June 2022

The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of >50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of >50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability >80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.
Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma
Authors: Yu Ziwei , Weinberger Paul M. , Haffty Bruce G. , Sasaki Clarence , Zerillo Cynthia , Joe John , Kowalski Diane , Dziura James , Camp Robert L. , Rimm David L. , Psyrri Amanda
Published: June 2022

Background: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC).

Experimental Design: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue.

Results: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years.

Conclusions: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.
Impact of Gene Polymorphisms on Clinical Outcome for Stage IV Melanoma Patients Treated with Biochemotherapy: An Exploratory Study
Authors: Liu Dongxin , O'Day Steven J. , Yang Dongyun , Boasberg Peter , Milford Robert , Kristedja Tim , Groshen Susan , Weber Jeffrey
Published: June 2022

Purpose: Biochemotherapy can achieve high response rates in advanced melanoma, but the factors that influence regression and survival remain unknown. The present exploratory study tested the hypothesis that cytokine gene polymorphisms predict clinical outcome in stage IV melanoma patients treated with biochemotherapy.

Experimental Design: Ninety patients with stage IV melanoma were treated with biochemotherapy, including cisplatin, vinblastine, and dacarbazine combined with interleukin (IL)-2 and IFN-α either with or without tamoxifen. Cytokine gene polymorphisms for IFN-γ (+874A→T) and IL-10 (−1082G→A) were assessed. X-ray repair cross-complementing gene 1 (XRCC1; Arg399Gln), xeroderma pigmentosum complementary group D (XPD; Lys751Gln), and excision repair cross-complementing gene 1 (ERCC1; codon 118) DNA repair polymorphisms were also determined.

Results: IFN-γ (+874A→T) gene polymorphism was statistically significantly associated with response (P = 0.001), progression-free survival (P = 0.0012), and overall survival (P < 0.001), whereas the IL-10 polymorphism was marginally associated with response (P = 0.03) and overall survival (P = 0.065). Multivariate analysis revealed that IFN-γ (+874A→T) independently predicted overall survival (P = 0.003). The ERCC1 polymorphism was weakly associated with overall survival (P = 0.045). Combining polymorphisms for IFN-γ, IL-10, and ERCC1 stratified patients into four distinct groups with significantly different clinical outcome (P < 0.001), so that patients with more “favorable” polymorphisms had a better outcome.

Conclusions: Cytokine gene polymorphisms predicted clinical outcome for advanced melanoma patients who received biochemotherapy. The combined effects of multiple genetic polymorphisms may provide more accurate prognostic information. Additional independent studies are needed to confirm these pilot findings.
A Phase I Trial and Pharmacokinetic Study of Tipifarnib, a Farnesyltransferase Inhibitor, and Tamoxifen in Metastatic Breast Cancer
Authors: Lebowitz Peter F. , Eng-Wong Jennifer , Widemann Brigitte C. , Balis Frank M. , Jayaprakash Nalini , Chow Catherine , Clark Geoff , Gantz Susan B. , Venzon David , Zujewski JoAnne
Published: June 2022

Purpose: Farnesyltransferase (FTase) inhibitors, which were designed to inhibit oncogenic Ras, act synergistically with tamoxifen in preclinical breast cancer models. We studied the safety and toxicity of tipifarnib in combination with tamoxifen in metastatic breast cancer. The pharmacokinetics and pharmacodynamics of tipifarnib were also assessed.

Patients and Methods: Patients with metastatic, hormone receptor–positive breast cancer were enrolled. Two cohorts of patients were treated with tipifarnib at either 200 or 300 mg p.o. twice daily for 21 of 28 days. Tamoxifen (20 mg once daily) was started after 1 week of tipifarnib monotherapy to perform pharmacokinetics and FTase inhibition levels in peripheral blood mononuclear cells with tipifarnib alone and with tipifarnib and tamoxifen.

Results: A total of 12 heavily pretreated patients with prior progression on hormonal therapy were enrolled. Minimal toxicity was observed at the 200-mg dose level of tipifarnib. At the 300-mg dose, all six patients required dose reduction of tipifarnib due to toxicities that included grade 2 nausea, rash, and fatigue and grade 3 diarrhea and neutropenia. Tipifarnib pharmacokinetic and pharmacodynamic variables were similar in the presence and absence of tamoxifen. Average FTase inhibition was 42% at 200 mg and 54% at 300 mg in peripheral blood mononuclear cells. Of the 12 patients treated, there were two partial responses and one stable disease for >6 months.

Conclusions: Tipifarnib (200 mg twice daily for 21 of 28 days) and tamoxifen (20 mg once daily) can be given safely with minimal toxicity. Tamoxifen does not have a significant effect on tipifarnib pharmacokinetics.
Accuracy, Feasibility, and Clinical Impact of Prospective Bayesian Pharmacokinetically Guided Dosing of Cyclophosphamide, Thiotepa, and Carboplatin in High-Dose Chemotherapy
Authors: de Jonge Milly E. , Huitema Alwin D.R. , Tukker Annemarie C. , van Dam Selma M. , Rodenhuis Sjoerd , Beijnen Jos H.
Published: June 2022

Purpose: Relationships between toxicity and pharmacokinetics have been shown for cyclophosphamide, thiotepa, and carboplatin (CTC) in high-dose chemotherapy. We prospectively evaluated whether variability in exposure to CTC and their activated metabolites can be decreased with pharmacokinetically guided dose administration and evaluated its clinical effect.

Experimental Design: Patients received multiple 4-day courses of cyclophosphamide (1,000–1,500 mg/m2/d), thiotepa (80–120 mg/m2/d), and carbop latin (area under the plasma concentration-time curve 3.3–5 mg × min/mL/d). Doses were adapted on day 3 based on pharmacokinetic analyses of cyclophosphamide, 4-hydroxycyclophosphamide, thiotepa, tepa, and carboplatin done on day 1 using a Bayesian algorithm. Doses were also adjusted before and during second and third courses. Observed toxicity was compared with that in patients receiving standard dose CTC (n = 43).

Results: A total of 46 patients (108 courses) were included. For cyclophosphamide, thiotepa, and carboplatin, a total of 39, 58, and 65 dose adaptations were done within courses and 17, 40, and 43 before courses. The precision within which the target exposure was reached improved compared with no adaptation, especially after within-course adaptations (precision for cyclophosphamide, thiotepa, and carboplatin is 19%, 16%, and 13%, respectively); >85% led to an exposure within ±25% of the target compared with 60% without dose adjustments. Toxicity was similar to that in a reference population, although the incidence of veno-occlusive disease was reduced.

Conclusions: Bayesian pharmacokinetically guided dosing for CTC was feasible and led to a marked reduction in variability of exposure.
Molecular Mechanisms of Resistance to Therapies Targeting the Epidermal Growth Factor Receptor
Authors: Camp E. Ramsay , Summy Justin , Bauer Todd W. , Liu Wenbiao , Gallick Gary E. , Ellis Lee M.
Published: June 2022

Targeted therapies that inhibit the activity of tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) have shown activity against solid malignancies when used as single agents or in combination with chemotherapy. Although anti-EGFR therapies are active in some patients, eventually disease in nearly all patients will become refractory to therapy. Therefore, a better understanding of the mechanisms of resistance to anti-EGFR therapies is critical to further improve the efficacy of this class of agents. Mechanisms that mediate resistance to anti-EGFR therapies include the presence of redundant tyrosine kinase receptors, increased angiogenesis, and the constitutive activation of downstream mediators. Two recent landmark publications have also shown that specific mutations in the kinase domain of EGFR in some lung carcinomas are associated with markedly improved response rates to an EGFR tyrosine kinase inhibitor. Mutations in the EGFR receptor seem to play a significant role in determining the sensitivity of tumor cells to EGFR inhibitor therapy by altering the conformation and activity of the receptor. As the field of molecular therapeutics continues to evolve, a comprehensive understanding of resistance mechanisms will ultimately lead to refinements in our regimens to provide better care for patients with cancer.
Identification of Gastric Cancer–Related Genes Using a cDNA Microarray Containing Novel Expressed Sequence Tags Expressed in Gastric Cancer Cells
Authors: Kim Jeong-Min , Sohn Ho-Yong , Yoon Sun Young , Oh Jung-Hwa , Yang Jin Ok , Kim Joo Heon , Song Kyu Sang , Rho Seung-Moo , Yoo Hyan Sook , Kim Yong Sung , Kim Jong-Guk , Kim Nam-Soon
Published: June 2022

Purpose: Gastric cancer is one of the most frequently diagnosed malignancies in the world, especially in Korea and Japan. To understand the molecular mechanism associated with gastric carcinogenesis, we attempted to identify novel gastric cancer–related genes using a novel 2K cDNA microarray.

Experimental Design: A 2K cDNA microarray was fabricated from 1,995 novel expressed sequence tags (ESTs) showing no hits or a low homology with ESTs in public databases from our 143,452 ESTs collected from gastric cancer cell lines and tissues. An analysis of the gene expression for human gastric cancer cell lines to a normal cell line was done using this cDNA microarray. Data for the different expressed genes were verified using semiquantitative reverse transcription-PCR, Western blotting, and immunohistochemical staining in the gastric cell lines and tissues.

Results: Forty genes were identified as either up-regulated or down-regulated genes in human gastric cancer cells. Among these, genes such as SKB1, NT5C3, ZNF9, p30, CDC20, and FEN1, were confirmed to be up-regulated genes in nine gastric cell lines and in 25 pairs of tissue samples from patients by semiquantitative reverse transcription-PCR. On the other hand, genes such as MT2A and CXX1 were identified as down-regulated genes. In particular, the SKB1, CDC20, and FEN1 genes were overexpressed in ≥68% of tissues and the MT2A gene was down-expressed in 72% of the tissues. Western blotting and immunohistochemical analyses for CDC20 and SKB1 showed overexpression and localization changes of the corresponding protein in human gastric cancer tissues.

Conclusions: Novel genes that are related to human gastric cancer were identified using cDNA microarray developed in our laboratory. In particular, CDC20 and MT2A represent a potential biomarker of human gastric cancer. These newly identified genes should provide a valuable resource for understanding the molecular mechanism associated with tumorigenesis of gastric carcinogenesis and for the discovery of potential diagnostic markers of gastric cancer.
Breast Differentiation and Its Implication in Cancer Prevention
Authors: Russo Jose , Mailo Daniel , Hu Yun-Fu , Balogh Gabriela , Sheriff Fathima , Russo Irma H.
Published: June 2022

Sporadic breast cancer is a fatal disease most frequently diagnosed in American women from all ethnic groups, suggesting that primary prevention should be the ultimate goal for breast cancer control. We have developed a novel paradigm for breast cancer prevention arising from the well-established knowledge that an early first full-term pregnancy protects the breast against neoplastic transformation, as well as from our studies of the biological principle underlying this protection. We have shown experimentally that the first pregnancy induces the expression of a specific genomic signature in the breast that results from the completion of a cycle in this organ's differentiation driven by the reproductive process. This signature, in turn, is a biomarker associated with a possible overall lifetime decrease in breast cancer risk. We have shown in an experimental model that a short treatment with human chorionic gonadotropin, a placental hormone secreted during pregnancy, induces the same genomic signature that occurs in pregnancy, inhibiting not only the initiation but also the progression of mammary carcinomas, and stopping the development of early lesions such as intraductal proliferations and carcinoma in situ. These observations indicate that human chorionic gonadotropin given for a very short period, only until this genomic signature is acquired, has significant potential as a chemopreventive agent, protecting the normal cell from becoming malignant. This is a novel concept which challenges the current knowledge that a chemopreventive agent needs to be given for a long period of time to suppress a metabolic pathway or abrogate the function of an organ.
Animal Models of Cardiovascular Complications of Pregnancy
Authors: Arany Zolt , Hilfiker-Kleiner Denise , Karumanchi S. Ananth
Published: June 2022

Cardiovascular complications of pregnancy have risen substantially over the past decades, and now account for the majority of pregnancy-induced maternal deaths, as well as having substantial long-term consequences on maternal cardiovascular health. The causes and pathophysiology of these complications remain poorly understood, and therapeutic options are limited. Preclinical models represent a crucial tool for understanding human disease. We review here advances made in preclinical models of cardiovascular complications of pregnancy, including preeclampsia and peripartum cardiomyopathy, with a focus on pathological mechanisms elicited by the models and on relevance to human disease.
Intersexual differences in the exploratory behaviour of blue tits (Cyanistes caeruleus)
Authors: Velasco Adara C. , Ferrer Esperanza S. , Sanz Juan José
Published: June 2022

Breeding performance and survival are mechanisms through which animal personality affects fitness. Exploration behaviour (EB) is an easily obtainable personality trait that correlates to multiple life-history traits, thus it has been widely used in animal personality studies. Through in situ Novel Environment exploration tests, we assessed the exploration behaviour of blue tits (Cyanistes caeruleus) during two breeding seasons. A principal component analysis revealed two behavioural axes regarding the exploration behaviour: slow-fast and timid-daring. We found that male blue tits are significantly slower explorers than female blue tits, suggesting that evolutionary processes act unequally across sexes in our study area. To investigate these processes, we assessed the relationship between exploration behaviour and two fitness aspects: reproduction and survival. Slower-exploring males bred in nests with significantly shorter incubation periods, and timid males had higher local return ratios. Interactions between male and female EB revealed that disassortative pairs were more successful breeders than assortative ones. Further research should explore potential evolutionary implications of intersexual EB differences.
Characterisation of Ditylenchus paraoncogenus n. sp. (Nematoda: Anguinidae), a new stem nematode parasitising tumble thistle
Authors: Hashemi Kobra , Karegar Akbar , Helder Johannes , Holterman Martijn , Mokaram Hesar Abbas
Published: June 2022

During a survey, three populations of a new stem nematode were isolated from galls on the shoots of tumble thistle (Gundelia tournefortii) plants in Fars province, Iran, and identified. Ditylenchus paraoncogenus n. sp. is described based on morphometric and morphological characters. It is characterised by having long-sized females, 1252 (943-1628) μm long, narrow lateral fields with six incisures, rather developed stylet 9.9 (9.0-11.3) μm long with round knobs, usually elongate and offset from intestine basal pharyngeal bulb, oocytes in two rows in distal part of ovary, V = 83.3 (80.3-86.2), post-vulval uterine sac 68.1 (46.9-86.1)% of vulva to anus distance long, bursa covering 63.2 (33.3-74.4)% of tail length, spicules 24.7 (21.0-27.9) μm long with minute processes at the base of its manubrium and anteriorly pointed cuticle parts within the lamina, and thick conical tail, usually with a pointed terminus. In addition, the ITS and 18S rDNA sequences of 17 populations of D. destructor, D. dipsaci, D. medicaginis, D. myceliophagus, D. paraoncogenus n. sp., Ditylenchus sp. and Nothotylenchus geraerti plus one population of Anguinidae sp. were analysed. The results showed a close relationship between D. paraoncogenus n. sp. and the stem nematodes D. oncogenus, D. gigas, D. weischeri and D. dipsaci. Ditylenchus species were divided into two clades, one clade comprising stem nematodes and gall-forming nematodes of the family Anguinidae, and the other clade containing fungivorous species. Observations showed that the second-stage juvenile is the dormant stage of D. paraoncogenus n. sp. and can survive in anhydrobiotic condition for at least 4 years.
The Rock Arts of Metolong: Paintings, Archaeology and Cultural Resource Management in Western Lesotho
Authors: Mallen Lara , Pearce David , Arthur Charles , Mitchell Peter
Published: June 2022

Archaeological mitigation efforts in advance of Lesotho’s Metolong Dam involved comprehensive documentation of rock paintings in the area threatened with inundation, as well as pigment characterisation and direct dating. This paper gives an overview of the rock arts found and their key features. Four traditions are present. Most paintings belong to the fine-line San tradition, but there are also examples of Type 3 images previously only recognised in South Africa’s Eastern Cape Province. Two other traditions are identified as being made by local Basotho communities. Contextual evidence suggests that they relate to male identity and, in the case of ochre smears and handprints, specifically to male initiation rituals. Some of the rock art sites identified are, in fact, used today by male and female initiation schools. The importance of comprehensively documenting rock art in other locations where it is at risk of being lost via development projects is stressed. Metolong sets a standard for rock art recording in cultural resource management work in the wider region.
Laryngopharyngeal Reflux: Effect of Race and Insurance Status on Symptomology
Authors: Varelas Eleni A. , Houser Thomas K. , Husain Inna A.
Published: June 2022

Objectives:

Laryngopharyngeal reflux (LPR) is an extraesophageal variant of gastroesophageal reflux disease associated with intermittent dysphonia, throat-clearing, and chronic cough. This study aims to evaluate the impact of race and insurance status on symptoms often attributable to LPR.

Methods:

Retrospective review of all patients with suspected LPR from 2017 to 2019 was performed at a tertiary care center. The diagnostic criteria comprised evaluation by a fellowship trained laryngologist and Reflux Symptom Index (RSI) scores. Demographics, patient history, and insurance status were recorded. Descriptive statistics were calculated for each parameter using SPSS version 22.

Results:

A total of 170 patients (96 White, 44 Black, 26 Latinx, 4 Asian) were included in this study. About 57.1% had private insurance, 30.6% had Medicare, and 11.8% had Medicaid. Black and Latinx patients demonstrated higher RSI scores (26.67 ± 8.61, P = .017) when compared to their White and Asian counterparts. RSI scores between all 3 insurance types also varied significantly ( P = .035). Medicaid patients reported higher RSI scores (28.65 ± 10.09, P = .028), while private insurance patients reported significantly lower scores (23.75 ± 7.88, P = .03). Controlling for insurance type eliminates the statistically significant association between RSI scores and Black and Latinx patients. Particularly, within the Medicaid group, Black, Latinx, and White patients did not have statistically different RSI scores.

Conclusions:

Black and Latinx patients presented with higher RSI scores than White and Asian patients. Similarly, Medicaid patients reported higher RSI scores than the Non-Medicaid cohort. These findings suggest that access to appropriate healthcare, due to varied insurance coverage and socioeconomic, may potentially influence symptoms attributed to LPR.
Long-Term Observational Study of Chronic Granulomatous Disease About 41 Patients From Tunisia and Comparison to Other Long-Term Follow-Up Studies
Authors: Mellouli Fethi , Ksouri Habib , Lajhouri Maïssa , Ben Khaled Monia , Rekaya Samia , Ben Fraj Elhem , Ouederni Monia , Barbouche Mohamed Ridha , Bejaoui Mohamed
Published: June 2022

Chronic granulomatous disease (CGD) is an inherited autosomal recessive or X-Linked primitive immunodeficiency (PID), due to a defective nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex impairing anti-infectious and anti-inflammatory role of peripheral blood mononuclear cells. It is characterized by severe bacterial and fungal infections and by excessive inflammation leading to granulomatous complications. This work was made over a period of 34 years on 41 Tunisian patients suffering from CGD. Cumulative follow-up of patients was 2768.5 months, median 31 months. Survival was studied by survival curves according to Kaplan-Meier method. Lymphatic nodes, pulmonary and cutaneous infections predominate as revealing manifestations and as infectious events during patients’ monitoring. At study end 12 patients died mainly of invasive pulmonary aspergillosis and septicemia. Median age of death was 30 months. CGD remains compatible with a decent quality of life. Early diagnosis, anti-infectious prophylaxis, and initiation of adequate management, as soon as complication is perceived, promote pretty good evolution.
Boosted viscoelastic and dynamic mechanical behavior of binary nanocarbon based polyurethane hybrid nanocomposite foams
Authors: Navidfar Amir , Bulut Osman , Baytak Tugba , Iskender Hikmet , Trabzon Levent
Published: June 2022

An effective approach for improving dispersion states of multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) was employed via hybrid inclusion of the nanofillers in polyurethane matrix to further enhance viscoelastic properties. Nanocomposites based on MWCNTs, two groups of graphene and hybrid MWCNT/graphene with varied weight fractions and ratios were fabricated via a facile and scalable approach. Dynamic mechanical analysis results indicated an improvement of up to 86% in storage modulus at 25°C for hybrid MWCNT/GNP-S750 at only 0.25 wt% loading, whereas solely MWCNTs and graphene nanocomposites showed 9% and 15% enhancement at the same content, respectively. The glass transition temperature value was enhanced by about 9.5°C with 0.25 wt% inclusion of well-dispersed three-dimensional MWCNT/GNP-S750 structure, which disclosed a noticeable synergistic effect in thermomechanical properties. The reinforcement coefficient, adhesion factor, reinforcement efficiency factor, degree of entanglement and cross-link density of nanocomposites were also examined to evaluate the interaction of single and hybrid carbon nanofillers with PU matrix.