bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of 9 Cases of Takotsubo Syndrome and an Analysis of the Clinical Characteristics of Takotsubo Syndrome From a Chinese Population
Authors: Yan Ju , Madina Mahesutihan , Deng Changjiang , Yuan Qianru , Cao Shixiong , Xie Xiang , Ma Yitong
Published: October 2021

Objective: To summarize the clinical features, hematology and imaging features of Takotsubo syndrome.

Methods: The hospitalization data of Takotsubo syndrome patients in the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2020 were collected, and their clinical characteristics were summarized. Patient outcomes were clarified through follow-up visits, and relevant objective indicators were statistically analyzed before and after admission. The characteristics of TTS incidence in Chinese population were summarized by searching three (Wanfang, CNKI, China's VIP database) major databases in China (PRISMA).

Results: A total of 9 patients were enrolled, including 6 females (66.7%). The mean age of onset was 46.4 years old, the median time from onset to treatment was 1 day. The main symptom of 8 cases (88.9%) was chest pain, 1 case had a main symptom of syncope, and 7 cases (77.8%) had mood fluctuations or mental stimulation as the main symptom of the disease. Paired T-tests were conducted on routine blood, biochemical, coagulation, myocardial markers, inflammatory indicators and objective indicators of ECG before and after admission. The study found that the counts of white blood cells and neutrophils were statistically significant (P < 0.05). Prolongation of the QT interval was observed in all 9 patients. After a mean follow-up of 24 ± 28 months, no adverse cardiovascular events or recurrence occurred.

Conclusion: Takotsubo syndrome is a group of clinical syndromes with emotional or somatic stimulation and chest pain as the main symptoms, partly accompanied by an increase in white blood cells, neutrophilic granulocyte count, creatine kinase, and troponin and is characterized by a prolonged QT interval and no obvious coronary stenosis. The prognosis is generally good, with few serious complications.
Mid-term Patency of the Great Saphenous Bypass to Aorta vs. Non-aortic Arteries in Stanford Type A Aortic Dissection Surgery With Concomitant CABG
Authors: Wang Maozhou , Jia Songhao , Pu Xin , Sun Lizhong , Gong Ming , Zhang Hongjia
Published: October 2021

Background: Stanford type A aortic dissection (STAAD) is often associated with coronary artery problems requiring coronary artery bypass grafting (CABG). However, the prognosis of different proximal graft locations remains unclear.

Methods: From May 2015 to April 2020, 62 patients with acute STAAD who underwent aortic surgery concomitant with CABG were enrolled in our study. Aortic bypass was defined as connecting the proximal end of the vein bridge to the artificial aorta (SVG-AO); non-aortic bypass was defined as connecting the proximal end of the vein bridge to a non-aorta vessel, including left subclavian artery, left common carotid artery, and right brachiocephalic artery (non-SVG-AO). We compared early- and mid-term results between patients in the above two groups. Early results included death and bleeding, and mid-term results graft patency, aortic-related events, and bleeding. Grafts were evaluated by post-operative coronary computed tomography angiography. According to the Fitzgibbon classification, grade A (graft stenosis <50%) is considered a patent graft. Univariate and multivariate analyses were performed to assess differences between aortic and non-aortic bypass in STAAD.

Results: SVG-AO and non-SVG-AO were performed in 15 and 47 patients, respectively. There was no significant difference in death (log-rank test, p = 0.426) or bleeding (p = 0.766) between the two groups in the short term. One year of follow-up was completed in 37 patients (eight in the SVG-AO group and 29 in the non-SVG-AO group), among which 14/15 (93.3%) grafts were patent in the SVG-AO group and 32/33 (97.0%) grafts in the non-SVG-AO at 1 week, without a significant difference (p = 0.532). At 3 months, 12/13 (92.3%) grafts were patent in the SVG-AO group and 16/32 (50.0%) grafts in the non-SVG-AO, with a significant difference (p = 0.015), and 12/13 (92.3%) grafts in the SVG-AO group and 15/32 (46.9%) grafts in the non-SVG-AO group were patents, with a significant difference. Multivariate analysis showed proximal aortic bypass and dual anticoagulation to be protective factors for the 1-year patency of grafts.

Conclusion: In patients requiring aortic dissection surgery with concomitant CABG, no differencess' between SVG-AO and SVG-non-AO in early outcomes were detected, but SVG-AO may have higher mid-term patency.
A Novel Quality-Control Procedure to Improve the Accuracy of Rare Variant Calling in SNP Arrays
Authors: Sun Ting-Hsuan , Shao Yu-Hsuan Joni , Mao Chien-Lin , Hung Miao-Neng , Lo Yi-Yun , Ko Tai-Ming , Hsiao Tzu-Hung
Published: October 2021

Background: Single-nucleotide polymorphism (SNP) arrays are an ideal technology for genotyping genetic variants in mass screening. However, using SNP arrays to detect rare variants [with a minor allele frequency (MAF) of <1%] is still a challenge because of noise signals and batch effects. An approach that improves the genotyping quality is needed for clinical applications.

Methods: We developed a quality-control procedure for rare variants which integrates different algorithms, filters, and experiments to increase the accuracy of variant calling. Using data from the TWB 2.0 custom Axiom array, we adopted an advanced normalization adjustment to prevent false calls caused by splitting the cluster and a rare het adjustment which decreases false calls in rare variants. The concordance of allelic frequencies from array data was compared to those from sequencing datasets of Taiwanese. Finally, genotyping results were used to detect familial hypercholesterolemia (FH), thrombophilia (TH), and maturity-onset diabetes of the young (MODY) to assess the performance in disease screening. All heterozygous calls were verified by Sanger sequencing or qPCR. The positive predictive value (PPV) of each step was estimated to evaluate the performance of our procedure.

Results: We analyzed SNP array data from 43,433 individuals, which interrogated 267,247 rare variants. The advanced normalization and rare het adjustment methods adjusted genotyping calling of 168,134 variants (96.49%). We further removed 3916 probesets which were discordant in MAFs between the SNP array and sequencing data. The PPV for detecting pathogenic variants with 0.01%<MAF≤1% exceeded 99.37%. PPVs for those with an MAF of ≤0.01% improved from 95% to 100% for FH, 42.11% to 85.19% for TH, and 18.24% to 72.22% for MODY after adopting our rare variant quality-control procedure and experimental verification.

Conclusion: Adopting our quality-control procedure, SNP arrays can adequately detect variants with MAF values ranging 0.01%∼0.1%. For variants with MAF values of ≤0.01%, experimental validation is needed unless sequencing data from a homogeneous population of >10,000 are available. The results demonstrated our procedure could perform correct genotype calling of rare variants. It provides a solution of pathogenic variant detection through SNP array. The approach brings tremendous promise for implementing precision medicine in medical practice.
Novel Allele Detection Tool Benchmark and Application With Antibody Repertoire Sequencing Dataset
Authors: Yang Xiujia , Zhu Yan , Chen Sen , Zeng Huikun , Guan Junjie , Wang Qilong , Lan Chunhong , Sun Deqiang , Yu Xueqing , Zhang Zhenhai
Published: October 2021

Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an antibody repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel allele candidates (NACs) using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the NACs detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.
Isolation and Characterization of Mouse Monoclonal Antibodies That Neutralize SARS-CoV-2 and Its Variants of Concern Alpha, Beta, Gamma and Delta by Binding Conformational Epitopes of Glycosylated RBD With High Potency
Authors: Mariotti Sabrina , Capocefalo Antonio , Chiantore Maria Vincenza , Iacobino Angelo , Teloni Raffaela , De Angelis Maria Laura , Gallinaro Alessandra , Pirillo Maria Franca , Borghi Martina , Canitano Andrea , Michelini Zuleika , Baggieri Melissa , Marchi Antonella , Bucci Paola , McKay Paul F. , Acchioni Chiara , Sandini Silvia , Sgarbanti Marco , Tosini Fabio , Di Virgilio Antonio , Venturi Giulietta , Marino Francesco , Esposito Valeria , Di Bonito Paola , Magurano Fabio , Cara Andrea , Negri Donatella , Nisini Roberto
Published: October 2021

Antibodies targeting Receptor Binding Domain (RBD) of SARS-CoV-2 have been suggested to account for the majority of neutralizing activity in COVID-19 convalescent sera and several neutralizing antibodies (nAbs) have been isolated, characterized and proposed as emergency therapeutics in the form of monoclonal antibodies (mAbs). However, SARS-CoV-2 variants are rapidly spreading worldwide from the sites of initial identification. The variants of concern (VOC) B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma) and B.1.167.2 (Delta) showed mutations in the SARS-CoV-2 spike protein potentially able to cause escape from nAb responses with a consequent reduction of efficacy of vaccines and mAbs-based therapy. We produced the recombinant RBD (rRBD) of SARS-CoV-2 spike glycoprotein from the Wuhan-Hu 1 reference sequence in a mammalian system, for mice immunization to isolate new mAbs with neutralizing activity. Here we describe four mAbs that were able to bind the rRBD in Enzyme-Linked Immunosorbent Assay and the transmembrane full-length spike protein expressed in HEK293T cells by flow cytometry assay. Moreover, the mAbs recognized the RBD in supernatants of SARS-CoV-2 infected VERO E6 cells by Western Blot under non-reducing condition or in supernatants of cells infected with lentivirus pseudotyped for spike protein, by immunoprecipitation assay. Three out of four mAbs lost their binding efficiency to completely N-deglycosylated rRBD and none was able to bind the same recombinant protein expressed in Escherichia coli, suggesting that the epitopes recognized by three mAbs are generated by the conformational structure of the glycosylated native protein. Of particular relevance, three mAbs were able to inhibit Wuhan SARS-CoV-2 infection of VERO E6 cells in a plaque-reduction neutralization test and the Wuhan SARS-CoV-2 as well as the Alpha, Beta, Gamma and Delta VOC in a pseudoviruses-based neutralization test. These mAbs represent important additional tools for diagnosis and therapy of COVID-19 and may contribute to the understanding of the functional structure of SARS-CoV-2 RBD.
Trends and Frontiers of Research on Cancer Gene Therapy From 2016 to 2020: A Bibliometric Analysis
Authors: Hu Shoushan , Alimire Alifu , Lai Yancheng , Hu Haonan , Chen Zhuo , Li Yi
Published: October 2021

Background: With rapid development in molecular biology techniques and a greater understanding of cancer pathogenesis, the growing attention has been concentrated on cancer gene therapy, with numerous articles on this topic published in recent 5 years. However, there is lacking a bibliometric analysis of research on cancer gene therapy. Therefore, the aim of the present study was to conduct a bibliometric analysis to provide the trends and frontiers of research on cancer gene therapy during 2016–2020.

Methods: We utilized CiteSpace 5.7.R5 software to conduct a bibliometric analysis of publications on cancer gene therapy published during 2016–2020. The bibliometric records were obtained from the Web of Science Core Collection.

Results: A total of 4,392 papers were included in the bibliometric analysis. Materials Science and Nanoscience and Nanotechnology took an increasing part in the field of cancer gene therapy. Additionally, WANG W was the most productive author, while ZHANG Y ranked top in terms of citations. Harvard Medical School and Sichuan University ranked top in the active institutions. P NATL ACAD SCI USA was identified as the core journal in the field of cancer gene therapy. “Ovarian cancer” was found to be the latest keyword with the strongest burst. The keyword analysis suggested that the top three latest clusters were labeled “gene delivery,” “drug delivery,” and “gene therapy.” In the reference analysis, cluster#2 labeled “gene delivery” held a dominant place considering both the node volume and mean year.

Conclusion: The academic attention on cancer gene therapy was growing at a dramatically high speed. Materials Science and Nanoscience and Nanotechnology might become promising impetus for the development of this field. “Gene delivery” was thought to best reflect the research frontier on cancer gene therapy. The top-cited articles on gene delivery were focused on several novel non-viral vectors due to their specialty compared with viral vectors. “Ovarian cancer” was likely to be the potential research direction. These findings would help medical workers conduct further investigations on cancer gene therapy.
Serum Human Epididymis Protein 4 as a Novel Biomarker in Identifying Patients With Interstitial Lung Disease in Rheumatoid Arthritis
Authors: Liang Liu , Chen Jiali , Di Chun , Zhan Minghua , Bao Huizhang , Xia Changsheng , Fan Chunhong , Liu Yudong
Published: October 2021

Objective: Human epididymis protein 4 (HE4) have been implicated in the pulmonary involvements. We aimed to investigate the clinical utility of HE4 in clinical stratification in patients with rheumatoid arthritis (RA).

Methods: This study included a discovery cohort comprising 70 RA patients and 64 healthy controls (HCs), and a validation cohort comprising 98 RA patients and 75 HCs. Human epididymis protein 4 were determined by electrochemical luminescence analyzer.

Results: The levels of HE4 were significantly elevated in patients with RA compared to HCs. The positive rates of HE4 in patients with RA and HCs were 50.0% and 0, respectively, in the discovery cohort and 53.1 and 1.3%, respectively, in the validation cohort. When RA patients were subgrouped according to HE4 status, HE4-positive group displayed higher prevalence of interstitial lung disease (ILD) compared to HE4-negative group (28.6 vs. 11.4% in discovery cohort and 57.7 vs. 8.7% in the validation cohort). A positive correlation between the levels of HE4 with the degree of lung impairment was identified. Receiver operating curve (ROC) analysis revealed an optimal cut-off value of 104.3 pmol/L in HE4 for distinguishing RA-ILD from RA-non ILD with the areas under the curve (AUC) of 0.790. Multivariate logistic regression analysis illustrated that high levels of HE4 independently identified patients with RA-ILD (OR, 9.080, p < 0.001).

Conclusion: Our findings showed a novel role of HE4 in RA risk stratification, suggest that introducing HE4 to the current RA test panel may serve as an indicator in identifying RA patients for further RA-ILD workups, such as high-resolution computed tomography (HRCT).
R&D Costs of New Medicines: A Landscape Analysis
Authors: Simoens Steven , Huys Isabelle
Published: October 2021

Over the years, questions have been raised over R&D costs of new medicines. The aim of this study is to conduct a landscape review of the (drivers of) R&D costs of a new medicine derived from the peer-reviewed and grey literature. Included studies have drawn data either from confidential company surveys or from publicly available company financial statements, in addition to accessing the literature and medicine information databases. Although there were differences in methodology, parameter values, samples and time periods between studies, estimates of R&D costs per new medicine (accounting for the cost of failures) ranged from US$944m to US$2,826m (adjusted to 2019 prices). The evidence also suggested that R&D costs per new medicine have increased over time. A few studies have broken down total costs and showed that clinical development accounts for 50-58% of R&D costs per new medicine. R&D costs were influenced by costs of discovery and pre-clinical development, costs of clinical development, cost of capital, company and product profile. Finally, cost estimates are likely to be dynamic as the biopharmaceutical industry and the broader environment continue to evolve.
Elucidation of the Translation Initiation Factor Interaction Network of Haloferax volcanii Reveals Coupling of Transcription and Translation in Haloarchaea
Authors: Schramm Franziska , Borst Andreas , Linne Uwe , Soppa Jörg
Published: October 2021

Translation is an important step in gene expression. Initiation of translation is rate-limiting, and it is phylogenetically more diverse than elongation or termination. Bacteria contain only three initiation factors. In stark contrast, eukaryotes contain more than 10 (subunits of) initiation factors (eIFs). The genomes of archaea contain many genes that are annotated to encode archaeal homologs of eukaryotic initiation factors (aIFs). However, experimental characterization of aIFs is scarce and mostly restricted to very few species. To broaden the view, the protein–protein interaction network of aIFs in the halophilic archaeonHaloferax volcaniihas been characterized. To this end, tagged versions of 14 aIFs were overproduced, affinity isolated, and the co-isolated binding partners were identified by peptide mass fingerprinting and MS/MS analyses. The aIF–aIF interaction network was resolved, and it was found to contain two interaction hubs, (1) the universally conserved factor aIF5B, and (2) a protein that has been annotated as the enzyme ribose-1,5-bisphosphate isomerase, which we propose to rename to aIF2Bα. Affinity isolation of aIFs also led to the co-isolation of many ribosomal proteins, but also transcription factors and subunits of the RNA polymerase (Rpo). To analyze a possible coupling of transcription and translation, seven tagged Rpo subunits were overproduced, affinity isolated, and co-isolated proteins were identified. The Rpo interaction network contained many transcription factors, but also many ribosomal proteins as well as the initiation factors aIF5B and aIF2Bα. These results showed that transcription and translation are coupled in haloarchaea, like inEscherichia coli. It seems that aIF5B and aIF2Bα are not only interaction hubs in the translation initiation network, but also key players in the transcription-translation coupling.
The Occurrence of Klebsiella pneumoniae in Drainage Fluid After Pancreaticoduodenectomy: Risk Factors and Clinical Impacts
Authors: Yang Yifei , Fu Xu , Cai Zhenghua , Qiu Yudong , Mao Liang
Published: October 2021

To investigate the risk factors and clinical impacts of the occurrence of Klebsiella pneumoniae isolated from drainage fluid in patients undergoing pancreaticoduodenectomy (PD). Clinicopathological data of all patients who underwent PD from January 2018 to March 2021 were analyzed retrospectively. The univariate and multivariate analyses were performed to identify independent risk factors for the occurrence of K. pneumoniae in drainage fluid and its clinical impacts on postoperative complications. Of the included 284 patients, 49 (17.2%) patients isolated K. pneumoniae in drain samples after PD. Preoperative biliary drainage (OR = 1.962, p = 0.037) independently predicted the contamination of K. pneumoniae in drain samples after PD. The rate of clinically relevant postoperative pancreatic fistula (CR-POPF), major complications (Clavien–Dindo Grade ≥ III), post-pancreatectomy hemorrhage (PPH), organ/space surgical site infection (SSI), and biliary leakage (BL) were significantly higher in K. pneumoniae positive group both in the univariate and multivariate analyses. Preventive measures and treatments for combating K. pneumoniae contamination may be beneficial to the perioperative outcomes of patients after PD.
Systematic Analysis of the Clinical Significance of Hyaluronan-Mediated Motility Receptor in Colorectal Cancer
Authors: Tang Yan-ping , Yin Yi-xin , Xie Ming-zhi , Liang Xin-qiang , Li Ji-lin , Li Ke-zhi , Hu Bang-li
Published: October 2021

Background: The role of hyaluronan-mediated motility receptor (HMMR) in colorectal cancer (CRC) remains unclear. The present study aimed to explore the association of HMMR with the development and prognosis of CRC using sequence datasets, clinical tissues, blood samples, and cell lines.

Methods: CRC datasets were downloaded from TCGA and GEO databases. Forty CRC tissue samples, 120 CRC blood samples, and 100 healthy controls were collected. Four CRC cell lines (HCT116, HT-29, LoVo, and SW480) and one normal human colon mucosal epithelial cell line (NCM460) were cultured. RT-qPCR was used to determine the expression of HMMR in the tissues and cell lines. ELISA was used to measure HMMR levels in the blood samples.

Results: The expression of HMMR was significantly increased in CRC tissues than in corresponding adjacent tissues based on TCGA and GEO datasets, and clinical CRC tissues. No associations were found between the expression of HMMR and the TNM stage or other clinical parameters. The expression of HMMR varied in different CRC cell lines. The blood levels of HMMR tended to be higher in patients with CRC than in healthy controls. TCGA and GEO datasets showed inconsistent results regarding the association of HMMR expression with the survival of patients with CRC.

Conclusion: The expression of HMMR is increased in CRC tissues but not in the blood. The expression of HMMR is independent of CRC development and has no prognostic significance in patients with CRC.
MicroRNAs: Important Players in Breast Cancer Angiogenesis and Therapeutic Targets
Authors: Hussen Bashdar Mahmud , Abdullah Sara Tharwat , Rasul Mohammed Fatih , Salihi Abbas , Ghafouri-Fard Soudeh , Hidayat Hazha Jamal , Taheri Mohammad
Published: October 2021

The high incidence of breast cancer (BC) is linked to metastasis, facilitated by tumor angiogenesis. MicroRNAs (miRNAs or miRs) are small non-coding RNA molecules that have an essential role in gene expression and are significantly linked to the tumor development and angiogenesis process in different types of cancer, including BC. There’s increasing evidence showed that various miRNAs play a significant role in disease processes; specifically, they are observed and over-expressed in a wide range of diseases linked to the angiogenesis process. However, more studies are required to reach the best findings and identify the link among miRNA expression, angiogenic pathways, and immune response-related genes to find new therapeutic targets. Here, we summarized the recent updates on miRNA signatures and their cellular targets in the development of breast tumor angiogenetic and discussed the strategies associated with miRNA-based therapeutic targets as anti-angiogenic response.
The Challenges and Effects of Ascorbic Acid Treatment of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Preclinical and Clinical Studies
Authors: Gao Lin , Chong Eric , Pendharkar Sayali , Phillips Anthony , Ke Lu , Li Weiqin , Windsor John Albert
Published: October 2021

Background: Oxidative stress has been implicated in the pathogenesis of acute pancreatitis (AP), and ascorbic acid (AA), as an important endogenous antioxidant substance, has been shown to reduce AP severity in preclinical studies. However, the effects of AA supplementation in clinical settings remain controversial.

Methods: PubMed, EMBASE, MEDLINE, and SCOPUS databases were searched, and both preclinical and clinical studies were included. For clinical trials, the primary outcome was incidence of organ failure, and for preclinical studies, the primary outcome was histopathological scores of pancreatic injuries.

Results: Meta-analysis of clinical trials showed that compared with controls, AA administration did not reduce the incidence of organ failure or mortality during hospitalization but was associated with significantly reduced length of hospital stay. Meta-analysis of preclinical studies showed that AA supplementation reduced pancreatic injury, demonstrated as decreased histological scores and serum amylase, lipase levels.

Conclusion: AA administration has no effect on survival or organ failure in patients with AP but may reduce the length of hospital stay. However, the evidence to date remains sparse, scattered, and of suboptimal quality, making it difficult to draw any firm conclusion on the clinical benefits of AA in AP.
The Potential Effects of Dielectric Barrier Discharge Plasma on the Extraction Efficiency of Bioactive Compounds in Radix Paeoniae Alba
Authors: Jin Tao , Zhou Zhenghua , Zhou Jian , Ouyang Wenchong , Wu Zhengwei
Published: October 2021

Radix paeoniae alba (RPA) is a kind of herbal medicine of traditional Chinese medicine (TCM) that is widely used for the treatment of liver diseases and rheumatoid arthritis in clinical practice. As a result of the low extraction efficiency of RPA by the conventional method, many patients are given high dosages. In this study, four exposure doses of dielectric barrier discharge (DBD) plasma (0, 60, 120, and 180 s) were applied to modify the extraction efficiency of paeoniflorin, benzoylpaeoniflorin, tannic acid, gallic acid, 2′-hydroxy-4′-methoxyacetophenone, and polysaccharide in RPA. Finally, the application of plasma for 180 s exhibited a 24.6% and 12.0% (p < 0.001) increase of tannic acid and polysaccharide contents, however, a 2.1% (p < 0.05) and 5.4% (p < 0.001) reduction of paeoniflorin and gallic acid composition, respectively, and no significant difference (p > 0.05) in results obtained from benzoylpaeoniflorin and 2′-hydroxy-4′-methoxyacetophenone contents. Our results of scanning electron microscopy (SEM), automatic specific surface area and pore analyzer, Fourier transform infrared spectroscopy (FTIR), X-ray photoelectron spectroscopy (XPS), and thermal gravimetric analysis (TGA) indicated that DBD plasma can etch the surface and undergo graft polymerization by reactive species thereby changing the water/oil holding capacity and eventually changing the extraction efficiency of bioactive compounds in RPA. Overall, our observations provide a scientific foundation for modifying the extraction efficiency of bioactive ingredients related to the pharmacological activities of RPA.
An Interactive Review on the Role of Tocotrienols in the Neurodegenerative Disorders
Authors: Naomi Ruth , Shafie Nurul Husna , Kaniappan Priyatharisni , Bahari Hasnah
Published: October 2021

Neurodegenerative disorders, such as Parkinson's and Alzheimer's disease, are claimed to be of major concern causing a significant disease burden worldwide. Oxidative stress, mitochondrial dysfunction and nerve damage are the main reasons for the emergence of these diseases. The formation of reactive oxygen species (ROS) is the common chemical molecule that is formed from all these three interdependent mechanisms which is highly reactive toward the neuronal cells. For these reasons, the administration of tocotrienols (T3s), which is a potent antioxidant, is proven to cater to this problem, throughin vitroandin vivoinvestigations. Interestingly, their therapeutic potentials are not only limited to antioxidant property but also to being able to reverse the neuronal damage and act as a shield for mitochondria dysfunction. Thereby, T3s prevents the damage to the neurons. In regards to this statement, in this review, we focused on summarizing and discussing the potential therapeutic role of T3s on Alzheimer's and Parkinson's diseases, and their protective mechanisms based on evidence from thein vitroandin vivostudies. However, there is no clinical trial conducted to prove the efficacy of T3s for Alzheimer's and Parkinson's subjects. As such, the therapeutic role of T3s for these neurodegenerative disorders is still under debate.
The Anti-Colon Cancer Effects of Essential Oil of Curcuma phaeocaulis Through Tumour Vessel Normalisation
Authors: Feng Yewen , Deng Lu , Guo Hengrui , Zhao Yumin , Peng Fu , Wang Gang , Yu Chenghao
Published: October 2021

Background

Normalising tumour vessels had become a significant research focus in tumour treatment research in recent years. Curcumae rhizoma (CR) is an essential plant in traditional Chinese medicine as it promotes blood circulation and removes blood stasis. Similarly, CR improves local blood circulation.

Purpose

We explored the anti-colon cancer effects of essential oil from CR (OCR) by investigating its role in normalising tumour vessels. We also provided a basis for research and development into new anti-cancer drugs.

Methods

We used colon cancer as a research focus to investigate OCR. We established an in vitro co-culture model of colon cancer cells and human umbilical vein endothelial cells (HUVEC). We also established an in vivo subcutaneous implant colon cancer model in nude mice. These studies allowed us to evaluate the comprehensive effects of OCR in in vivo and in vitro colon cancer and its role in normalising tumour blood vessels.

Results

In vitro, we found that OCR inhibited Human colon cancer cells (HCT116) and HUVEC cell proliferation and inhibited vascular endothelial growth factor-a (VEGFa) mRNA and protein expression in HUVECs in a co-culture system. Our in vivo studies showed that OCR inhibited colon cancer tumour growth, reduced angiogenesis in tumours and increased vascular endothelial (VE)-cadherin and pericyte coverage in tumour vessels.

Conclusions

OCR inhibited colon cancer growth both in in vivo and in vitro models, reduced angiogenesis in tumours, improved tumour vessel structures and normalised tumour vessels.
Association of Systemic Inflammation and Malnutrition With Survival in Nasopharyngeal Carcinoma Undergoing Chemoradiotherapy: Results From a Multicenter Cohort Study
Authors: Wang Xin , Yang Ming , Ge Yizhong , Tang Meng , Rao Benqiang , Chen Yongbing , Xu Hongxia , Cong Minghua , Guo Zengqing , Shi Hanping
Published: October 2021

Background

Malnutrition and systemic inflammation are common in patients with nasopharyngeal carcinoma (NPC). The Patient-Generated Subjective Global Assessment (PG-SGA) score and neutrophil-to-lymphocyte ratio (NLR) reflect the integrated nutritional status and inflammatory level of patients with NPC, respectively. We performed this study to identify whether NLR and PG-SGA score are associated with outcome and survival time for patients with NPC undergoing chemoradiotherapy.

Methods

The multicenter cohort study included 1,102 patients with NPC between June 2012 and December 2019. The associations of all-cause mortality with NLR and PG-SGA score were calculated using the Kaplan–Meier method and the log-rank test. We also did a multivariate-adjusted Cox regression analysis to identify the independent significance of different parameters. Restricted cubic spline regression was carried out to evaluate the association between NLR and overall survival (OS). A nomogram was established using the independent prognostic variables. Interaction terms were used to investigate whether there was an interactive association between NLR and PG-SGA.

Results

A total of 923 patients with NPC undergoing chemoradiotherapy were included in this study: 672 (72.8%) were males and 251 (27.2%) were females, with a mean age of 49.3 ± 11.5 years. The Kaplan–Meier curves revealed that patients with malnutrition (PG-SGA score >3) had worse survival than patients who were in the well-nourished group (PG-SGA score ≤3) (p < 0.0001). In addition, patients in the high NLR group (NLR ≥ 3) had worse survival than those in the low NLR group (NLR < 3) (p < 0.0001). Patients with high PG-SGA and high NLR had the worst survival (p < 0.0001). An increase in NLR had an inverted L-shaped dose–response association with all-cause mortality. A nomogram was developed by incorporating domains of NLR and PG-SGA score to accurately predict OS 12–60 months for patients [the C-index for OS prediction of nomogram was 0.75 (95% CI, 0.70–0.80)]. The interaction of PG-SGA with NLR was significant (p = 0.009). Patients with high PG-SGA and high NLR had a nearly 4.5-fold increased risk of death (HR = 4.43, 95% CI = 2.60–7.56) as compared with patients with low PG-SGA and low NLR.

Conclusions

Our study provided clear evidence that high PG-SGA score and high NLR adversely and interactively affects the OS of patients with NPC undergoing chemoradiotherapy.
Case Report: Transoral Endoscopic Thyroidectomy via Vestibular Approach in Pediatric Thyroid Cancer
Authors: Ngo Duy Q. , Le Duong T. , Hoang Giap N. , Ngo Quy X. , Le Quang V.
Published: October 2021

Background: Transoral endoscopic thyroidectomy via vestibular approach (TOETVA) is a new technique that has become more popular worldwide because of its many advantages. However, this novel approach for thyroid cancer treatment in children is highly challenging, even for high-volume surgeons. In our study, we report our experiences with TOETVA for pediatric patients with thyroid cancer.

Patients and Methods: This study included four pediatric patients who underwent TOETVA performed by a single surgeon between June and December 2020. Patient demographics and surgical outcomes including operative time, incidence of complications, and length of hospital stay were evaluated.

Results: Four patients successfully underwent TOETVA with no complications. All patients were girls, aged from 13 to 18. Three patients underwent lobectomy and isthmusectomy, plus prophylactic unilateral central neck dissection. One patient had a total thyroidectomy, plus prophylactic bilateral central neck dissection. The mean operative time was 85 min for the lobectomy and 120 min for total thyroidectomy plus central neck dissection. The median hospital stay was 4.1 days. No drains were used. The histological examination showed four cases of malignant disease (papillary thyroid carcinoma). The mean number of harvested lymph nodes was 4.2 (ranged 3 to 8).

Conclusion: In the hands of a high-volume surgeon, TOETVA is a novel, feasible, and safe approach for treating selected pediatric patients with thyroid cancer.
Measurement of Corner-Mode Coupling in Acoustic Higher-Order Topological Insulators
Authors: Li Xiao , Wu Shiqiao , Zhang Guanqing , Cai Wanzhu , Ng Jack , Ma Guancong
Published: October 2021

Recent developments of band topology have revealed a variety of higher-order topological insulators (HOTIs). These HOTIs are characterized by a variety of different topological invariants, making them different at a fundamental level. However, despite such differences, the fact that they all sustain higher-order topological boundary modes poses a challenge to phenomenologically tell them apart. This work presents experimental measurements of the coupling effects of topological corner modes (TCMs) existing in two different types of two-dimensional acoustic HOTIs. Although both HOTIs have a similar four-site square lattice, the difference in magnetic flux per unit cell dictates that they belong to different types of topologically nontrivial phases—one lattice possesses quantized dipole moments, but the other is characterized by quantized quadrupole moment. A link between the topological invariants and the response line shape of the coupled TCMs is theoretically established and experimentally confirmed. Our results offer a pathway to distinguish HOTIs experimentally.
BK in Double-Membrane Organelles: A Biophysical, Pharmacological, and Functional Survey
Authors: González-Sanabria Naileth , Echeverría Felipe , Segura Ignacio , Alvarado-Sánchez Rosangelina , Latorre Ramon
Published: October 2021

In the 1970s, calcium-activated potassium currents were recorded for the first time. In 10years, this Ca2+-activated potassium channel was identified in rat skeletal muscle, chromaffin cells and characterized in skeletal muscle membranes reconstituted in lipid bilayers. This calcium- and voltage-activated potassium channel, dubbed BK for “Big K” due to its large ionic conductance between 130 and 300 pS in symmetric K+. The BK channel is a tetramer where the pore-forming α subunit contains seven transmembrane segments. It has a modular architecture containing a pore domain with a highly potassium-selective filter, a voltage-sensor domain and two intracellular Ca2+ binding sites in the C-terminus. BK is found in the plasma membrane of different cell types, the inner mitochondrial membrane (mitoBK) and the nuclear envelope’s outer membrane (nBK). Like BK channels in the plasma membrane (pmBK), the open probability of mitoBK and nBK channels are regulated by Ca2+ and voltage and modulated by auxiliary subunits. BK channels share common pharmacology to toxins such as iberiotoxin, charybdotoxin, paxilline, and agonists of the benzimidazole family. However, the precise role of mitoBK and nBK remains largely unknown. To date, mitoBK has been reported to play a role in protecting the heart from ischemic injury. At the same time, pharmacology suggests that nBK has a role in regulating nuclear Ca2+, membrane potential and expression of eNOS. Here, we will discuss at the biophysical level the properties and differences of mitoBK and nBK compared to those of pmBK and their pharmacology and function.
Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia
Authors: Prokopidis Konstantinos , Chambers Edward , Ni Lochlainn Mary , Witard Oliver C.
Published: October 2021

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover,in vivoandin vitrostudies demonstrate the action of specific gut bacteria (LactobacillusandBifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut microbiota phenotypes on amino acid utilization and the postprandial stimulation of muscle protein synthesis in older adults.
Genome-Wide Identification and Analysis of Small Nucleolar RNAs and Their Roles in Regulating Latex Regeneration in the Rubber Tree (Hevea brasiliensis)
Authors: Chen Xiang , Deng Zhi , Yu Dingwei , Zhang Xiaofei , An Zewei , Wu Wenguan , Liang Qun , Huang Xiao , Huang Huasun , Cheng Han
Published: October 2021

Small nucleolar RNAs (snoRNAs) are a class of conserved nuclear RNAs that play important roles in the modification of ribosomal RNAs (rRNAs) in plants. In rubber trees, rRNAs are run off with latex flow during tapping and need to be regenerated for maintaining the functions of the laticifer cells. SnoRNAs are expected to play essential roles in the regeneration of rRNAs. However, snoRNAs in the rubber tree have not been sufficiently characterized thus far. In this study, we performed nuclear RNA sequencing (RNA-seq) to identify snoRNAs globally and investigate their roles in latex regeneration. We identified a total of 3,626 snoRNAs by computational prediction with nuclear RNA-seq data. Among these snoRNAs, 50 were highly expressed in latex; furthermore, the results of reverse transcription polymerase chain reaction (RT-PCR) showed the abundant expression of 31 of these snoRNAs in latex. The correlation between snoRNA expression and adjusted total solid content (TSC/C) identified 13 positively yield-correlated snoRNAs. To improve the understanding of latex regeneration in rubber trees, we developed a novel insulated tapping system (ITS), which only measures the latex regenerated in specific laticifers. Using this system, a laticifer-abundant snoRNA, HbsnoR28, was found to be highly correlated with latex regeneration. To the best of our knowledge, this is the first report to globally identify snoRNAs that might be involved in latex regeneration regulation and provide new clues for unraveling the mechanisms underlying the regulation of latex regeneration.
Molecular Phylogeny and Taxonomy of the Genus Spumella (Chrysophyceae) Based on Morphological and Molecular Evidence
Authors: Jeong Minseok , Kim Jong Im , Nam Seung Won , Shin Woongghi
Published: October 2021

The genusSpumella, established by Cienkowsky in 1870, is characterized by omnivory, two (rarely three) flagella, a short stick-like structure beneath the flagella, a threadlike stalk, cell division via constriction and cyst formation. Since the first phylogenetic study ofSpumella-like flagellates, their paraphyly has consistently been shown, with separation into several genera. More recently,Spumellawas carefully investigated using molecular and morphological data to propose seven new species. Classification of this genus and knowledge of its species diversity remain limited becauseSpumella-like flagellates are extremely difficult to identify based on limited morphological characters. To understand the phylogeny and taxonomy ofSpumella, we analyzed molecular and morphological data from 47 strains, including 18 strains isolated from Korean ponds or swamps. Nuclear SSU, ITS and LSU rDNA data were used for maximum likelihood and Bayesian analyses. The molecular data divided the strains into 15 clades, including seven new lineages, each with unique molecular signatures for nuclear SSU rRNA from the E23-2 to E23-5 domains, the spacer between the E23-8 and E23-9 domains of the V4 region and domain 29 of the V5 region. Our results revealed increased species diversity inSpumella. In contrast to the molecular phylogeny results, the taxa showed very similar cell morphologies, suggesting morphological convergence into simple nanoflagellates to enable heterotrophy. Three new species produced stomatocysts in culture. Aspects of stomatocyst morphology, including collar structure, surface ornamentation, and cyst shape, were very useful in differentiating the three species. The general ultrastructure ofSpumella bureschiistrain Baekdongje012018B8 andS. benthicastrain Hwarim032418A5 showed the typical chrysophyte form for the leucoplast, a vestigial chloroplast surrounded by four envelope membranes, supporting the hypothesis thatSpumellaevolved from a phototroph to a heterotroph via the loss of its photosynthetic ability. Seven new species are proposed:S. benthica,S. communis,S. longicolla,S. oblata,S. rotundata,S. similis, andS. sinechrysos.
Development of a Panel of Genotyping-in-Thousands by Sequencing in Capsicum
Authors: Jo Jinkwan , Kim Youngin , Kim Geon Woo , Kwon Jin-Kyung , Kang Byoung-Cheorl
Published: October 2021

Genotyping by sequencing (GBS) enables genotyping of multiple loci at low cost. However, the single nucleotide polymorphisms (SNPs) revealed by GBS tend to be randomly distributed between individuals, limiting their direct comparisons without applying the various filter options to obtain a comparable dataset of SNPs. Here, we developed a panel of a multiplex targeted sequencing method, genotyping-in-thousands by sequencing (GT-seq), to genotype SNPs in Capsicum spp. Previously developed Fluidigm® SNP markers were converted to GT-seq markers and combined with new GT-seq markers developed using SNP information obtained through GBS. We then optimized multiplex PCR conditions: we obtained the highest genotyping rate when the first PCR consisted of 25 cycles. In addition, we determined that 101 primer pairs performed best when amplifying target sequences of 79 bp. We minimized interference of multiplex PCR by primer dimer formation using the PrimerPooler program. Using our GT-seq pipeline on Illumina Miseq and Nextseq platforms, we genotyped up to 1,500 (Miseq) and 1,300 (Nextseq) samples for the optimum panel size of 100 loci. To allow the genotyping of Capsicum species, we designed 332 informative GT-seq markers from Fluidigm SNP markers and GBS-derived SNPs. This study illustrates the first application of GT-seq in crop plants. The GT-seq marker set developed here will be a useful tool for molecular breeding of peppers in the future.
The Construction of Positive Social Psychology During the COVID-19 Pandemic: Exploring the Relationship Between Social Support and Peace of Mind Through a Three-Wave Longitudinal Cross-Lag Study
Authors: Xi Yiheng , Zhou Li , Wang Ying
Published: October 2021

The ongoing COVID-19 pandemic has sparked a major global crisis that has infected public social mentality. Drawing on the concept of peace of mind (PoM), a culture-specific positive emotion construct developed in the Chinese cultural context, this study explored the ways to build a positive public social mentality in the time of the pandemic. PoM is indicative of a calm and stable emotional state marked by self-control and spiritual cultivation and is believed to align with the perceptions of subjective well-being in Chinese or eastern cultures. A three-wave cross-lag study using an online questionnaire survey was conducted on 107 employees in Chinese enterprises during the pandemic. The research findings suggest that social support had a significant positive time-cross effect on later PoM, i.e., social support-T1 had a significant predictive effect on PoM-T2 (β = 0.16, SE = 0.09, p < 0.05) and social support-T2 had a significant predictive effect on PoM-T3 (β = 0.38, SE = 0.19, p < 0.05), whereas PoM failed to show a positive time-cross effect on later social support, i.e., the predictive effects of PoM-T1 on social support-T2 (β = 0.04, SE = 0.07, p > 0.05) and of PoM-T2 on social support-T3 (β = 0.13, SE = 0.09, p > 0.05) were not significant. This study provided a dynamic picture of the construction of public social mentality in the time of public health emergencies and also contributed to the research on PoM antecedents.