bluuebunny/crossref_metadata_2025 huggingface dataset:
Rapamycin Improved Retinal Function and Morphology in a Mouse Model of Retinal Degeneration
Authors: Zhao Meng , Lv Houting , Yang Na , Peng Guang-Hua
Published: February 2022

The retina is an important visual organ, which is responsible for receiving light signals and transmitting them to the optic nerve center step by step. The retina contains a variety of cells, among which photoreceptor cells receive light signals and convert them into nerve signals, and are mainly responsible for light and dark vision. Retinal degeneration is mainly the degeneration of photoreceptor cells, and retinitis pigmentosa (RP) is characterized by rod degeneration followed by cone degeneration. So far, there is still a lack of effective drugs to treat RP. Here, we established a stable RP model by tail vein injection of methyl methanesulfonate to study the mechanism of retinal photoreceptor degeneration. Mechanistic target of rapamycin (mTOR) is located in the central pathway of growth and energy metabolism and changes in a variety of diseases in response to pathological changes. We found that the mTOR was activated in this model. Therefore, the inhibitor of mTOR, rapamycin was used to suppress the expression of mTOR and interfere with photoreceptor degeneration. Electroretinogram assay showed that the function of mice retina was improved. Hematoxylin and eosin staining results displayed that retinal photoreceptor thickness and morphology were improved. Also, the autophagy in rapamycin group was activated, which revealed that rapamycin may protect the retinal photoreceptor by inhibiting mTOR and then activating autophagy.
Oligoclonal Bands in Multiple System Atrophy: Case Report and Proposed Mechanisms of Immunogenicity
Authors: Neilson Lee E. , Hollen Christopher , Hiller Amie , Wooliscroft Lindsey
Published: February 2022

Multiple System Atrophy (MSA) is a neurodegenerative disease with heterogeneous manifestations and is therefore difficult to diagnose definitively. Because of this, oftentimes an extensive workup for mimickers is undertaken. We herein report a case where the history and cerebrospinal fluid (CSF) findings of oligoclonal bands suggested an inflammatory disorder. Immunomodulatory therapy failed to ameliorate symptoms or alter the trajectory of continued physical decline, prompting re-visitation of the diagnosis. Oligoclonal bands, while generally viewed as specific to multiple sclerosis or other inflammatory conditions, may be seen in other disease processes. Therefore, this finding should not exclude consideration of neurodegenerative disease.
Polysaccharides as Potential Anti-tumor Biomacromolecules —A Review
Authors: Guo Rui , Chen Min , Ding Yangyang , Yang Pengyao , Wang Mengjiao , Zhang Haihui , He Yuanqing , Ma Haile
Published: February 2022

Cancer, as one of the most life-threatening diseases, has attracted the attention of researchers to develop drugs with minimal side effects. The bioactive macromolecules, such as the polysaccharides, are considered the potential candidates against cancer due to their anti-tumor activities and non-toxic characteristics. The present review provides an overview on polysaccharides' extraction, isolation, purification, mechanisms for their anti-tumor activities, structure-activity relationships, absorption and metabolism of polysaccharides, and the applications of polysaccharides in anti-tumor therapy. Numerous research showed extraction methods of polysaccharides had a significant influence on their activities. Additionally, the anti-tumor activities of the polysaccharides are closely related to their structure, while molecular modification and high bioavailability may enhance the anti-tumor activity. Moreover, most of the polysaccharides exerted an anti-tumor activity mainly through the cell cycle arrest, anti-angiogenesis, apoptosis, and immunomodulation mechanisms. Also, recommendations were made to utilize the polysaccharides against cancer.
The Role of Circular RNAs in the Carcinogenesis of Bladder Cancer
Authors: Ghafouri-Fard Soudeh , Najafi Sajad , Hussen Bashdar Mahmud , Basiri Abbas , Hidayat Hazha Jamal , Taheri Mohammad , Rashnoo Fariborz
Published: February 2022

Circular RNAs (circRNAs) are a group of transcripts with enclosed configurations which can regulate gene expression. These transcripts have important roles in normal development and in the pathogenesis of disorders. Recent evidence has supported involvement of circRNAs in the development of bladder cancer. Several circRNAs such as circ_0058063, hsa-circRNA-403658, circPDSS1, circCASC15, circRNA-MYLK, and circRNA_103809 have been upregulated in bladder cancer samples. On the other hand, hsa_circ_0137606, BCRC-3, circFUT8, hsa_circ_001598, circSLC8A1, hsa_circ_0077837, hsa_circ_0004826, and circACVR2A are among downregulated circRNAs in bladder cancer. Numerous circRNAs have diagnostic or prognostic value in bladder cancer. In this review, we aim to outline the latest findings about the role of circRNAs in bladder cancer and introduce circRNAs for further investigations as therapeutic targets.
Efficacy and Safety of Radiofrequency Ablation vs. Endoscopic Surveillance for Barrett’s Esophagus With Low-Grade Dysplasia: Meta-Analysis of Randomized Controlled Trials
Authors: Wang Yizi , Ma Bin , Yang Shize , Li Wenya , Li Peiwen
Published: February 2022

Background and Aims

Barrett’s esophagus with low-grade dysplasia (BE-LGD) carries a risk of progression to Barrett’s esophagus with high-grade dysplasia (BE-HGD) and esophageal adenocarcinoma (EAC). Radiofrequency ablation (RFA) appears to be a safe and efficacious method to eradicate Barrett’s esophagus. However, a confirmed consensus regarding treatment of BE-LGD with RFA vs. endoscopic surveillance is lacking. Therefore, this study aimed to elucidate the efficacy and safety for RFA vs. endoscopic surveillance in decreasing the risk of BE-LGD progression to BE-HGD or EAC.

Methods

Relevant studies published before May 1, 2021 were identified by searching relevant medical databases. The primary outcome was the rate of progression BE-LGD to HGD and/or EAC after treatment with RFA and endoscopic surveillance. The secondary outcome was the rate of complete eradication of dysplasia (CE-D) and complete eradication of intestinal metaplasia (CE-IM) after treatment with RFA and endoscopic surveillance. Adverse events were also extracted and evaluated.

Results

Three randomized controlled trials were eligible for analysis. The pooled estimate of rate of neoplastic progression of BE-LGD to HGD or EAC was much lower in the RFA group than the endoscopic surveillance group (RR, 0.25; 95% CI, 0.07–0.93; P = 0.04), with moderate heterogeneity (I2 = 55%). Subgroup analysis based on progression grade was performed. The pooled rate of progression of BE-LGD to HGD was much lower in the RFA group than the endoscopic surveillance group (RR, 0.25; 95% CI, 0.07–0.71; P = 0.01), with low heterogeneity (I2 = 15%). Although the pooled risk of progression of BE-LGD to EAC was slightly lower in the RFA group than the endoscopic surveillance group (RR, 0.56; 95% CI, 0.05–6.76), the result was not statistically significant (P = 0.65). RFA also was associated a higher rate of CE-D and CE-IM both at the end of endoscopic treatment and during follow-up. However, the rate of adverse events was slightly higher after RFA treatment.

Conclusion

RFA decreases the risk of BE-LGD progression to BE-HGD. However, given the uncertain course of LGD and the potential for esophageal stricture after RFA, treatment options should be fully considered and weighed.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021266128, identifier PROSPERO (CRD42021266128).
Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study
Authors: Daneels Willem , Rosskamp Michael , Macq Gilles , Saadoon Estabraq Ismael , De Geyndt Anke , Offner Fritz , Poirel Hélène A.
Published: February 2022

We determined first- and second-line regimens, including hematopoietic stem cell transplantations, in all diffuse large B cell lymphoma (DLBCL) patients aged ≥20 yr (n = 1,888), registered at the Belgian Cancer Registry (2013–2015). Treatments were inferred from reimbursed drugs, and procedures registered in national health insurance databases. This real-world population-based study allows to assess patients usually excluded from clinical trials such as those with comorbidities, other malignancies (12%), and advanced age (28% are ≥80 yr old). Our data show that the majority of older patients are still started on first-line regimens with curative intent and a substantial proportion of them benefit from this approach. First-line treatments included full R-CHOP (44%), “incomplete” (R-)CHOP (18%), other anthracycline (14%), non-anthracycline (9%), only radiotherapy (3%), and no chemo-/radiotherapy (13%), with significant variation between age groups. The 5-year overall survival (OS) of all patients was 56% with a clear influence of age (78% [20–59 yr] versus 16% [≥85 yr]) and of the type of first-line treatments: full R-CHOP (72%), other anthracycline (58%), “incomplete” (R-)CHOP (47%), non-anthracycline (30%), only radiotherapy (30%), and no chemo-/radiotherapy (9%). Second-line therapy, presumed for refractory (7%) or relapsed disease (9%), was initiated in 252 patients (16%) and was predominantly (71%) platinum-based. The 5-year OS after second-line treatment without autologous stem cell transplantation (ASCT) was generally poor (11% in ≥70 yr versus 17% in <70 yr). An ASCT was performed in 5% of treated patients (n = 82). The 5-year OS after first- or second-line ASCT was similar (69% versus 66%). After adjustment, multivariable OS analyses indicated a significant hazard ratio (HR) for, among others, age (HR 1.81 to 5.95 for increasing age), performance status (PS) (HR 4.56 for PS >1 within 3 months from incidence), subsequent malignancies (HR 2.50), prior malignancies (HR 1.34), respiratory and diabetic comorbidity (HR 1.41 and 1.24), gender (HR 1.25 for males), and first-line treatment with full R-CHOP (HR 0.41) or other anthracycline-containing regimens (HR 0.72). Despite inherent limitations, patterns of care in DLBCL could be determined using an innovative approach based on Belgian health insurance data.
High Systemic Immune Inflammation Index Is Associated With Low Skeletal Muscle Quantity in Resectable Pancreatic Ductal Adenocarcinoma
Authors: Aziz Mohammad Hosein , van Dongen Jelle C. , Saida Lawlaw , Suker Mustafa , van Vugt Jeroen L. A. , van Putten Yordi , Sideras Kostandinos , Groen Jesse V. , Mieog J. Sven D. , Lucassen Claudia J. , Droop Anneke , Mauff Katya , Shahbazi Feshtali Shirin , Groot Koerkamp Bas , Mustafa Dana A. M. , van Eijck Casper J.
Published: February 2022

Background and Aims

Failing immune surveillance in pancreatic ductal adenocarcinoma (PDAC) is related to poor prognosis. PDAC is also characterized by its substantial alterations to patients’ body composition. Therefore, we investigated associations between the host systemic immune inflammation response and body composition in patients with resected PDAC.

Methods

Patients who underwent a pancreatectomy for PDAC between 2004 and 2016 in two tertiary referral centers were included. Skeletal muscle mass quantity and muscle attenuation, as well as subcutaneous and visceral adipose tissue at the time of diagnosis, were determined by CT imaging measured transversely at the third lumbar vertebra level. Baseline clinicopathological characteristics, laboratory values including the systemic immune inflammation index (SIII), postoperative, and survival outcomes were collected.

Results

A total of 415 patients were included, and low skeletal muscle mass quantity was found in 273 (65.7%) patients. Of the body composition indices, only low skeletal muscle mass quantity was independently associated with a high (≥900) SIII (OR 7.37, 95% CI 2.31-23.5, p=0.001). The SIII was independently associated with disease-free survival (HR 1.86, 95% CI 1.12-3.04), and cancer-specific survival (HR 2.21, 95% CI 1.33-3.67). None of the body composition indices were associated with survival outcomes.

Conclusion

This study showed a strong association between preoperative low skeletal muscle mass quantity and elevated host systemic immune inflammation in patients with resected PDAC. Understanding how systemic inflammation may contribute to changes in body composition or whether reversing these changes may affect the host systemic immune inflammation response could expose new therapeutic possibilities for improving patients’ survival outcomes.
Benefits of Prophylactic Cranial Irradiation in the MRI Era for Patients With Limited Stage Small Cell Lung Cancer
Authors: Qi Chao , Li Wang , Li Hanming , Wen Fengyun , Zhou Lu , Sun Xiaohu , Yu Hong
Published: February 2022

Purpose

Previous studies have shown that prophylactic cranial irradiation (PCI) can improve the survival of patients with limited-stage small cell lung cancer (LS-SCLC). PCI is recommended for patients who respond well to chemoradiotherapy. However, whether PCI could be extrapolated to the LS-SCLC patients in the modern era of MRI is unknown. This study aimed to explore the value of PCI in patients with LS-SCLC in the era of brain MRI.

Methods

This study included 306 patients with LS-SCLC at the Cancer Hospital of China Medical University. All patients received brain MRI at diagnosis and after radiochemotherapy to exclude brain metastases. A propensity score matching was performed to reduce the influence of potential confounders. Overall survival (OS), progression-free survival (PFS), and recurrence failure types were compared between PCI and non-PCI groups.

Results

Among the 306 eligible patients, 81 underwent PCI, and 225 did not. After propensity score matching, there was no statistical difference in baseline data between the two groups, with 75 patients in each group. PCI did not achieve OS (median OS: 35 vs. 28 months, p = 0.128) or PFS (median PFS: 15 vs. 10 months, p = 0.186) benefits. During follow-up, 30 patients (20.0%) developed brain metastases, including 13 patients (17.3%) in the PCI group and 17 patients (22.7%) in the non-PCI group. Regarding death as a competitive risk, patients who received PCI had a lower cumulative incidence of brain metastasis than those who did not (3 years: 14.7% vs. 22.7%; Gray’s test, p = 0.007).

Conclusions

When brain MRI was performed at diagnosis and pre-PCI, PCI could reduce the cumulative rate of brain metastases, but it did not achieve survival benefits for LS-SCLC patients.
Influence of Dexamethasone Premedication on Acute Lung Toxicity in Lung SBRT
Authors: Alite Fiori , Shaikh Parvez M. , Mahadevan Anand
Published: February 2022

Introduction

The cooperative group experience of thoracic sterotactic body radiation therapy (SBRT) in medically inoperable patients with early stage non-small cell lung cancer (NSCLC) historically utilized corticosteroid premedication. Patterns of care have been mixed as to whether premedication adds benefit in terms of improved lung toxicity and treatment tolerance.

Methods

Patients treated for NSCLC from 2014 to 2017 with definitive thoracic SBRT (BED10≥100) at a single institution, in a prospectively collected database were evaluated. Pretreatment clinicopathologic characteristics, including Eastern Cooperative Oncology Group (ECOG) performance status, PFT parameters of FEV1, and diffusing capacity for carbon monoxide (DLCO) were collected. Treatment and dosimetric characteristics were collected, and patients were scored as to whether dexamethasone was prescribed and utilized with each fraction. Toxicity was graded on multiple domains including lung as during and 30 days after completion of treatment using Common Terminology Criteria for Adverse Events Version 4. Univariate analysis was performed with Fisher’s exact test for categorical variables and two-tailed Student’s t-test for continuous variables. Multivariate analysis was performed with Cox proportional hazards model to adjust for age, pretreatment DLCO, ECOG, tumor size, central versus peripheral location, and biological effective dose.

Results

A total of 86 patients treated with thoracic SBRT with 54–60 Gy in 3–8 fractions met inclusion criteria, with the majority (70%) receiving 5 fractions. Of these patients, 45 (52%) received 4 mg dexamethasone premedication prior to each fraction of SBRT and 41 (48%) were treated without dexamethasone premedication. Overall acute lung toxicity was low in both groups. Between the two groups of patients, 5/45 (11%) developed grade 2 or higher lung toxicity including hospital admission in the dexamethasone premedication arm vs. 2/41 (5%) without premedication (p = 0.4370, Fisher’s exact test). Freedom from acute SBRT lung toxicity was no different between dexamethasone premedication arm and no premedication (Log rank, p = 0.45). On multivariate Cox proportional hazard modeling adjusting for age, ECOG, tumor size, central vs. peripheral location, pretreatment DLCO, and BED, there was no difference in freedom from acute lung toxicity without dexamethasone premedication (HR: 0.305; 95% CI: 0.033, 2.792; p = 0.293).

Conclusions

In this retrospective analysis, pretreatment steroid prophylaxis with dexamethasone confers a similar acute toxicity profile and no added clinical benefit to treatment without pretreatment steroid prophylaxis.
Nomograms for Predicting Hepatocellular Carcinoma Recurrence and Overall Postoperative Patient Survival
Authors: Ma Lidi , Deng Kan , Zhang Cheng , Li Haixia , Luo Yingwei , Yang Yingsi , Li Congrui , Li Xinming , Geng Zhijun , Xie Chuanmiao
Published: February 2022

Background

Few studies have focused on the prognosis of patients with hepatocellular carcinoma (HCC) of Barcelona Clinic Liver Cancer (BCLC) stage 0‒C in terms of early recurrence and 5-years overall survival (OS). We sought to develop nomograms for predicting 5-year OS and early recurrence after curative resection of HCC, based on a clinicopathological‒radiological model. We also investigated whether different treatment methods influenced the OS of patients with early recurrence.

Methods

Retrospective data, including clinical pathology, radiology, and follow-up data, were collected for 494 patients with HCC who underwent hepatectomy. Nomograms estimating OS and early recurrence were constructed using multivariate Cox regression analysis, based on the random survival forest (RSF) model. We evaluated the discrimination and calibration abilities of the nomograms using concordance indices (C-index), calibration curves, and Kaplan‒Meier curves. OS curves of different treatments for patients who had recurrence within 2 years after curative surgery were depicted and compared using the Kaplan–Meier method and the log-rank test.

Results

Multivariate Cox regression revealed that BCLC stage, non-smooth margin, maximum tumor diameter, age, aspartate aminotransferase levels, microvascular invasion, and differentiation were prognostic factors for OS and were incorporated into the nomogram with good predictive performance in the training (C-index: 0.787) and testing cohorts (C-index: 0.711). A nomogram for recurrence-free survival was also developed based on four prognostic factors (BCLC stage, non-smooth margin, maximum tumor diameter, and microvascular invasion) with good predictive performance in the training (C-index: 0.717) and testing cohorts (C-index: 0.701). In comparison to the BCLC staging system, the C-index (training cohort: 0.787 vs. 0.678, 0.717 vs. 0.675; external cohort 2: 0.748 vs. 0.624, 0.729 vs. 0.587 respectively, for OS and RFS; external cohort1:0.716 vs. 0.627 for RFS, all p value<0.05), and model calibration curves all showed improved performance. Patients who underwent surgery after tumor recurrence had a higher reOS than those who underwent comprehensive treatments and supportive care.

Conclusions

The nomogram, based on clinical, pathological, and radiological factors, demonstrated good accuracy in estimating OS and recurrence, which can guide follow-up and treatment of individual patients. Reoperation may be the best option for patients with recurrence in good condition.
Case Report: First Case of Non-restrictive Ventricular Septal Defect With Congestive Heart Failure in a Chinese Han Male Infant Carrying a Class II Chromosome 17p13.3 Microduplication
Authors: Yang Yung-Yu , Liu Chun-Ting , Pai Li-Fan , Hu Chih-Fen , Chen Shyi-Jou , Hsu Wan-Fu
Published: February 2022

Chromosome 17p13.3 microduplication syndrome is considered a multisystem disorder that results in a wide variety of clinical manifestations including dysmorphic facial characteristics, brain structural malformations, developmental restriction, growth restriction, and neurocognitive disorders. The two major classes of chromosome 17p13.3 microduplication, which have different clinical presentations, are associated with specific genetic regions. Among the various known phenotypes, scattered cases with congenital heart disease (CHD) have been reported for both classes of chromosome 17p13.3 microduplication syndrome. Unfortunately, there is insufficient understanding of the correlation between chromosome anomaly induced alterations in gene expression and aberrant cardiac development, and thus early diagnosis of CHD among patients with chromosome 17p13.3 microduplication is difficult without routine prenatal cardiac assessment. One such congenital heart anomalies known to affect a substantial number of newborns worldwide is ventricular septal defect (VSD), which has been found in 17p13.3 microduplication carriers, and seems to sometimes undergo spontaneous closure. We report an unprecedented case of moderate sized perimembranous-outlet VSD and congestive heart failure (CHF) in a Chinese Han male infant with a class II chromosome 17p13.3 microduplication. Despite the fact that cytogenic testing and fetal echocardiography confirmed a 249-Kb chromosome duplication within 17p13.3 that encompassed the PAFAH1B1 gene and showed the presence of VSD during prenatal period, this patient still developed a range of symptoms including sustained prolonged feeding, dyspnea, diaphoresis and retarded growth. A physical examination indicated hepatomegaly and a grade III/VI pan-systolic murmur along the left upper sternal border. Laboratory testing showed a high serum pro–B-type natriuretic peptide (pro-BNP). Imaging studies revealed cardiomegaly and a persistent VSD with related pulmonary stenosis. Since the clinical findings were compatible with CHF, we provided mainline treatment with digoxin, captopril, and furosemide, as well as fluid restriction. Despite sustained poor weight gain, the feeding behavior and the respiratory conditions of the patient improved gradually. This case report and literature review suggest that patients carrying chromosome 17p13.3 microduplication who have VSD may have an increased risk of developing CHF as young infants and hence a comprehensive cardiac evaluation is warranted to allow the early diagnosis and management of any severe heart anomalies.
Developing a National Minimum Data Set for Kawasaki Disease Registry in Iran
Authors: Qazizadeh Zainab , Shahbaznejad Leila , Navaeifar Mohammad Reza , Rezai Mohammad Sadegh
Published: February 2022

Background

Kawasaki Disease is an acute and self-limited systemic inflammatory and febrile illness, which is the most common cause of acquired heart disease in children in developed countries. The incidence of KD in Asian countries is high. But, data is not available from the Middle East. So, the aim of this study was to develop an MDS to set up a national registry for KD to estimate the burden of disease in Iran.

Materials and Methods

This cross-sectional and descriptive study was conducted in 2020. Literature review, data collection from patients medical records, and expert panel approach were used to design this MDS. Data elements with a Content Validity Ratio (CVR) of more than 0.56 were selected as the MDS of the registry.

Results

Overall, 99 data elements were recognized. Of which, 51 and 48 data elements were verified and rejected, respectively. Moreover, 17 data elements were added as required by experts. Eventually, 68 data elements were chosen as the MDS of the national KD registry of IRAN; of which, 17 and 51 data elements were classified as administrative and clinical data, respectively.

Conclusions

These precise, integrated, and comprehensive developed data elements and the national KD registry will lead to effective disease management and thus, improve the quality of care and, consequently, improve public health.
Antimicrobial Diterpenes: Recent Development From Natural Sources
Authors: Saha Poushali , Rahman Fahad Imtiaz , Hussain Fahad , Rahman S. M. Abdur , Rahman M. Mukhlesur
Published: February 2022

Antimicrobial resistance has been posing an alarming threat to the treatment of infectious diseases over the years. Ineffectiveness of the currently available synthetic and semisynthetic antibiotics has led the researchers to discover new molecules with potent antimicrobial activities. To overcome the emerging antimicrobial resistance, new antimicrobial compounds from natural sources might be appropriate. Secondary metabolites from natural sources could be prospective candidates in the development of new antimicrobial agents with high efficacy and less side effects. Among the natural secondary metabolites, diterpenoids are of crucial importance because of their broad spectrum of antimicrobial activity, which has put it in the center of research interest in recent years. The present work is aimed at reviewing recent literature regarding different classes of natural diterpenes and diterpenoids with significant antibacterial, antifungal, antiviral, and antiprotozoal activities along with their reported structure–activity relationships. This review has been carried out with a focus on relevant literature published in the last 5 years following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A total of 229 diterpenoids from various sources like plants, marine species, and fungi are summarized in this systematic review, including their chemical structures, classification, and significant antimicrobial activities together with their reported mechanism of action and structure–activity relationships. The outcomes herein would provide researchers with new insights to find new credible leads and to work on their synthetic and semisynthetic derivatives to develop new antimicrobial agents.
The SKA3-DUSP2 Axis Promotes Gastric Cancer Tumorigenesis and Epithelial-Mesenchymal Transition by Activating the MAPK/ERK Pathway
Authors: Zhang Chao , Zhao Shutao , Tan Yuen , Pan Siwei , An Wen , Chen Qingchuan , Wang Xudong , Xu Huimian
Published: February 2022

Background: Spindle and kinetochore-related complex subunit 3 (SKA3), a member of the SKA family of proteins, is associated with the progression of multiple cancers. However, the role of SKA3 in gastric cancer has not been studied.

Methods: The expression levels of SKA3 and dual-specificity phosphatase 2 (DUSP2) proteins were detected by immunohistochemistry. The effects of SKA3 and DUSP2 on the proliferation, migration, invasion, adhesion, and epithelial-mesenchymal transition of gastric cancer were studied in vitro and in vivo.

Results: Immunohistochemical analysis of 164 cases of gastric cancer revealed that high expression of SKA3 was negatively correlated with DUSP2 expression and related to N stage, peritoneal metastasis, and poor prognosis. In vitro studies showed that silencing SKA3 expression inhibited the proliferation, migration, invasion, adhesion and epithelial-mesenchymal transition of gastric cancer. In vivo experiments showed that silencing SKA3 inhibited tumor growth and peritoneal metastasis. Mechanistically, SKA3 negative regulates the tumor suppressor DUSP2 and activates the MAPK/ERK pathway to promote gastric cancer.

Conclusion: Our results indicate that the SKA3-DUSP2-ERK1/2 axis is involved in the regulation of gastric cancer progression, and SKA3 is a potential therapeutic target for gastric cancer.
Roles of MicroRNA-21 in Skin Wound Healing: A Comprehensive Review
Authors: Xie Jie , Wu Weizhou , Zheng Liying , Lin Xuesong , Tai Yuncheng , Wang Yajie , Wang Le
Published: February 2022

MicroRNA-21 (miR-21), one of the early mammalian miRNAs identified, has been detected to be upregulated in multiple biological processes. Increasing evidence has demonstrated the potential values of miR-21 in cutaneous damage and skin wound healing, but lack of a review article to summarize the current evidence on this issue. Based on this review, relevant studies demonstrated that miR-21 played an essential role in wound healing by constituting a complex network with its targeted genes (i.e., PTEN, RECK. SPRY1/2, NF-κB, and TIMP3) and the cascaded signaling pathways (i.e., MAPK/ERK, PI3K/Akt, Wnt/β-catenin/MMP-7, and TGF-β/Smad7-Smad2/3). The treatment effectiveness developed by miR-21 might be associated with the promotion of the fibroblast differentiation, the improvement of angiogenesis, anti-inflammatory, enhancement of the collagen synthesis, and the re-epithelialization of the wound. Currently, miRNA nanocarrier systems have been developed, supporting the feasibility clinical feasibility of such miR-21-based therapy. After further investigations, miR-21 may serve as a potential therapeutic target for wound healing.
The Impact of a Multifaceted Pharmacist-Led Antimicrobial Stewardship Program on Antibiotic Use: Evidence From a Quasi-Experimental Study in the Department of Vascular and Interventional Radiology in a Chinese Tertiary Hospital
Authors: Xu Jinhui , Huang Jian , Yu YanXia , Zhou Dayong , Wang Ying , Xue Sudong , Shang Erning , Sun Jiantong , Ding Xinyuan , Shi Lu , Duan Lufen , Tang Lian , Zhou Qin , Li Xin
Published: February 2022

Objective: The objective of the study was to assess the impact of multifaceted clinical pharmacist-led antimicrobial stewardship (AMS) program on the rational use of antibiotics for patients who receive vascular and interventional radiology therapies.

Methods: A quasi-experimental retrospective intervention design with a comparison group was applied to the practice of antibiotic use in the department of vascular and interventional radiology in a Chinese tertiary hospital. We used difference-in-differences (DID) analysis to compare outcomes before and after the AMS intervention between the intervention group and control group, to determine whether intervention would lead to changes in irrationality of antibiotic prescribing, antibiotic utilization, cost of antibiotics, and length of hospital stay.

Results: The DID results showed that the intervention group was associated with a reduction in the average consumption of antibiotics (p = 0.017) and cost of antibiotics (p = 0.006) and cost per defined daily dose (DDD) (p = 0.000). There were no significant differences in the mean change of total costs and length of stay between the two groups (p > 0.05). The average inappropriate score of perioperative antimicrobial prophylaxis in the intervention group declined by 0.23, while it decreased by 0.02 in the control group [0.21 (95% CI, −0.271 to −0.143); p = 0.000]. The average inappropriate score of non-surgical antimicrobial prophylaxis in the intervention group declined by 0.14, while it increased by 0.02 in the control group [0.16 (95% CI, −0.288 to −0.035); p = 0.010]. The average inappropriate score of the therapeutic use of antibiotics in the intervention group declined by 0.07, while it decreased by 0.01 in the control group [0.06 (95% CI, −0.115 to −0.022); p = 0.003].

Conclusions: This study provides evidence that implementation of AMS interventions was associated with a marked reduction of antibiotic use, cost of antibiotics, and irrationality of antibiotic prescribing in China.
Anti-Invariant Lorentzian Submersions From Lorentzian Concircular Structure Manifolds
Authors: Siddiqi M. Danish , Khan Meraj A. , Ishan Amira A. , Chaubey S. K.
Published: February 2022

This research article attempts to investigate anti-invariant Lorentzian submersions and the Lagrangian Lorentzian submersions (LLS) from the Lorentzian concircular structure [in short (LCS)n] manifolds onto semi-Riemannian manifolds with relevant non-trivial examples. It is shown that the horizontal distributions of such submersions are not integrable and their fibers are not totally geodesic. As a result, they can not be totally geodesic maps. Anti-invariant and Lagrangian submersions are also explored for their harmonicity. We illustrate that if the Reeb vector field is horizontal, the anti-invariant and LLS can not be harmonic.
A High-Efficiency and Reconfigurable Rectenna Array for Dynamic Output DC Power Control
Authors: Wang Yuchao , Song Yangkun , Zhang Bohan , Chen Shaonan , Chen Qiang , Zhang Cheng
Published: February 2022

In this paper, an output power reconfigurable rectenna array is proposed for the first time to harvest RF energy. The proposed rectenna array can be used to capture abundant RF energy with high conversion efficiency in a wide range of input power levels and load impedance at 1.88, 2.35, 3.5, and 4.9 GHz simultaneously. The output DC power of the proposed rectenna array can be changed exponentially by altering the on-off state of the switches located between the antenna and the rectifier. The measured result shows that the output power is linearly related to the number of opened switches. Therefore, the proposed rectenna array can be flexibly applied to battery-free or low-power-requiring devices according to their different power needs.
Polyene Phosphatidylcholine Ameliorates High Fat Diet-Induced Non-alcoholic Fatty Liver Disease via Remodeling Metabolism and Inflammation
Authors: Lu Yang , Feng Tingting , Zhao Jinxiu , Jiang Pengfei , Xu Daxiang , Zhou Menglu , Dai Mengyu , Wu Jiacheng , Sun Fenfen , Yang Xiaoying , Lin Qisi , Pan Wei
Published: February 2022

Recent years have witnessed a rise in the morbidity of non-alcoholic fatty liver disease (NAFLD), in line with the global outbreak of obesity. However, effective intervention strategy against NAFLD is still unavailable. The present study sought to investigate the effect and mechanism of polyene phosphatidylcholine (PPC), a classic hepatoprotective drug, on NAFLD induced by high fat diet (HFD). We found that PPC intervention reduced the mass of liver, subcutaneous, epididymal, and brown fats in HFD mice. Furthermore, PPC supplementation significantly mitigated liver steatosis and improved glucose tolerance and insulin sensitivity in HFD mice, which was accompanied by declined levels of hepatic triglyceride, serum triglyceride, low density lipoprotein, aspartate aminotransferase, and alanine aminotransferase. Using transcriptome analysis, there were 1,789 differentially expressed genes (| fold change | ≥ 2, P < 0.05) including 893 upregulated genes and 896 downregulated genes in the HFD group compared to LC group. A total of 1,114 upregulated genes and 1,337 downregulated genes in HFD + PPC group were identified in comparison to HFD group. With the help of Gene Ontology (GO) analysis, these differentially expressed genes between HFD+PPC and HFD group were discovered related to “lipid metabolic process (GO: 0006629),” “lipid modification (GO: 0030258),” and “lipid homeostasis (GO: 0055088)”. Though Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, we found pathways associated with hepatic homeostasis of metabolism and inflammation. Notably, the pathway “Non-alcoholic fatty liver disease (mmu04932)” (P-value = 0.00698) was authenticated in the study, which may inspire the potential mechanism of PPC to ameliorate NAFLD. The study also found that lipolysis, fatty acid oxidation, and lipid export associated genes were upregulated, while the genes in uptake of lipids and cholesterol synthesis were downregulated in the liver of HFD mice after PPC supplementation. Interestingly, PPC attenuated the metabolic inflammation via inhibiting pro-inflammatory macrophage in the livers of mice fed by HFD. In summary, this study demonstrates that PPC can ameliorate HFD-induced liver steatosis via reprogramming metabolic and inflammatory processes, which inspire clues for further clarifying the intervention mechanism of PPC against NAFLD.
Higher Muscle Damage Triggered by Shorter Inter-Set Rest Periods in Volume-Equated Resistance Exercise
Authors: Senna Gilmar Weber , Dantas Estélio Henrique Martin , Scudese Estevão , Brandão Paula Paraguassú , Lira Vitor A. , Baffi Matheus , Ribeiro Luiz Claudio Pereira , Simão Roberto , Thomas Ewan , Bianco Antonino
Published: February 2022

Objectives

The aim of the manuscript was to analyze the effects of two rest periods between volume-equated resistance exercise (RE) on inflammatory responses (cytokines and leukocyte) and muscle damage.

Methods

Ten trained men (26.40 ± 4.73 years, 80.71 ± 8.95 kg, and 176.03 ± 6.11 cm) voluntarily participated in training sessions consisting of five sets of 10 reps performed at 10-RM on (1) the barbell bench press followed by (2) leg press, with either 1- or 3-min rest between sets and exercises. Circulating concentrations of different biomarkers was measured before (Pre), and after 3 h (excepted for cytokines), 6, 12, and 24 h from exercise. The rate of perceived exertion (RPE) was recorded after each set on both planned visits.

Results

We found greater increases triggered by the 1-min rest period in Creatine Kinase (CK), occurring from 12 to 24 h post-exercise compared to the 3-min rest condition. A significant increase in the 1-min rest condition was also observed in the total number of leukocytes, neutrophils, and monocytes. The 1-min rest period also triggered increases compared to baseline in pro-inflammatory cytokines [Interleukin 1 beta (IL-1β), p = 0.004; tumor necrosis factor α (TNF-α), p = 0.01; and granulocyte-macrophage colony-stimulating factor (GM-CSF), p = 0.01], which were more evident after 6 and 12 h post-exercise. Similarly, increases in anti-inflammatory cytokines [Interleukin 5 (IL-5), p = 0.01; Interleukin 6 (IL-6), p = 0.01; and Interleukin 10 (IL-10), p = 0.01] at all time-points were observed.

Conclusion

Our results indicate that a 1-min rest condition in volume-equated RE promoted greater overall muscle tissue damage with a longer duration of the inflammatory processes compared to a 3-min rest.
Reliability of Symbolic Analysis of Heart Rate Variability and Its Changes During Sympathetic Stimulation in Elite Modern Pentathlon Athletes: A Pilot Study
Authors: Gąsior Jakub S. , Rosoł Maciej , Młyńczak Marcel , Flatt Andrew A. , Hoffmann Bartosz , Baranowski Rafał , Werner Bożena
Published: February 2022

Background and Purpose

Most studies on heart rate variability (HRV) in professional athletes concerned linear, time-, and frequency-domain indices, and there is lack of studies on non-linear parameters in this group. The study aimed to determine the inter-day reliability, and group-related and individual changes of short-term symbolic dynamics (SymDyn) measures during sympathetic nervous system activity (SNSa) stimulation among elite modern pentathletes.

Methods

Short-term electrocardiographic recordings were performed in stable measurement conditions with a 7-day interval between tests. SNSa stimulation via isometric handgrip strength test was conducted on the second day of study. The occurrence rate of patterns without variations (0V), with one variation (1V), two like (2LV), and two unlike variations (2UV) obtained using three approaches (the Max–min, the σ, and the Equal-probability methods) were analyzed. Relative and absolute reliability were evaluated.

Results

All SymDyn indices obtained using the Max–min method, 0V, and 2UV obtained using the σ method, 2UV obtained using the Equal-probability method presented acceptable inter-day reliability (the intraclass correlation coefficient between .91 and .99, Cohen’s d between −.08 and .10, the within-subject coefficient of variation between 4% and 22%). 2LV, 2UV, and 0V obtained using the Max–min and σ methods significantly decreased and increased, respectively, during SNSa stimulation—such changes were noted for all athletes. There was no significant association between differences in SymDyn parameters and respiratory rate in stable conditions and while comparing stable conditions and SNSa stimulation.

Conclusion

SymDyn indices may be used as reliable non-respiratory-associated parameters in laboratory settings to detect autonomic nervous system (ANS) activity modulations in elite endurance athletes. These findings provide a potential solution for addressing the confounding influence of respiration frequency on HRV-derived inferences of cardiac autonomic function. For this reason, SymDyn may prove to be preferable for field-based monitoring where measurements are unsupervised.
Patient-Specific Modeling Could Predict Occurrence of Pediatric Stroke
Authors: Horn John D. , Johnson Michael J. , Starosolski Zbigniew , Meoded Avner , Milewicz Dianna M. , Annapragada Ananth , Hossain Shaolie S.
Published: February 2022

Moyamoya disease (MMD) is a progressive steno-occlusive cerebrovascular disease leading to recurrent stroke. There is a lack of reliable biomarkers to identify unilateral stroke MMD patients who are likely to progress to bilateral disease and experience subsequent contralateral stroke(s). We hypothesized that local hemodynamics are predictive of future stroke and set out to noninvasively assess this stroke risk in pediatric MMD patients. MR and X-ray angiography imaging were utilized to reconstruct patient-specific models of the circle of Willis of six pediatric MMD patients who had previous strokes, along with a control subject. Blood flow simulations were performed by using a Navier–Stokes solver within an isogeometric analysis framework. Vascular regions with a wall shear rate (WSR) above the coagulation limit (>5,000 s−1) were identified to have a higher probability of thrombus formation, potentially leading to ischemic stroke(s). Two metrics, namely, “critical WSR coverage” and “WSR score,” were derived to assess contralateral stroke risk and compared with clinical follow-up data. In two patients that suffered a contralateral stroke within 2 months of the primary stroke, critical WSR coverages exceeding 50% of vessel surface and WSR scores greater than 6× the control were present in multiple contralateral vessels. These metrics were not as clearly indicative of stroke in two additional patients with 3–5 year gaps between primary and contralateral strokes. However, a longitudinal study of one of these two cases, where a subsequent timepoint was analyzed, suggested disease stabilization on the primary stroke side and an elevated contralateral stroke risk, which was confirmed by patient outcome data. This indicates that post-stroke follow-up at regular intervals might be warranted for secondary stroke prevention. The findings of this study suggest that WSR-based metrics could be predictive of future stroke risk after an initial stroke in pediatric MMD patients. In addition, better predictions may be possible by performing patient-specific hemodynamic analysis at multiple timepoints during patient follow-up to monitor changes in the WSR-based metrics.
Validation of Potential Reference Genes for Real-Time qPCR Analysis in Pharaoh Ant, Monomorium pharaonis (Hymenoptera: Formicidae)
Authors: Ding Guo , Gao Qionghua , Chen Jun , Zhao Jie , Zhang Guojie , Liu Weiwei
Published: February 2022

Ants are highly diverse social insects living in colonies consisted of up to millions of individuals with reproductive division of labors. Due to the interests in disclosing the genetic and epigenetic regulation mechanisms underlying the distinct developmental trajectories between castes and division of labor in colonies, many ant species have recently been established as laboratory models for evolutionary development and social behavior studies. These functional studies often request a precise quantification of the relative gene expression level, which relies on a stably expressed reference genes for normalization. A core set of reliable reference genes for this purpose however has not been established yet in ants. In the present study, we tested the expression patterns and amplification efficiencies of 12 abundantly expressed candidate genes in Monomorium pharaonis, one of the few ant species that are suitable for laboratory rearing and experimentation. We quantified the expression levels of these genes by RT-qPCR in seven different conditions: embryo development, sexual development, worker development, adult phenotypes, tissues, and two abiotic manipulative treatments in pharaoh ant. Finally, five genes, elongation factor-1 alpha (EF1A), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), TATA-box-binding protein (TATA), tubulin gamma-2 chain-like (TBLg2), heat shock protein 67B2-like (HSP67) were found to be the most stable reference genes across seven conditions. We also identified the most stable reference genes applicable for each distinct condition and the optimal number of reference genes entailed were evaluated. Our study validates reliable reference genes for RT-qPCR analysis which lays the foundation for future studies in pharaoh ant.
Enhancing Sorghum Yield Through Efficient Use of Nitrogen – Challenges and Opportunities
Authors: Ostmeyer Troy J. , Bahuguna Rajeev Nayan , Kirkham M. B. , Bean Scott , Jagadish S. V. Krishna
Published: February 2022

Sorghum is an important crop, which is widely used as food, forage, fodder and biofuel. Despite its natural adaption to resource-poor and stressful environments, increasing yield potential of sorghum under more favorable conditions holds promise. Nitrogen is the most important nutrient for crops, having a dynamic impact on all growth, yield, and grain-quality-determining processes. Thus, increasing nitrogen use efficiency (NUE) in sorghum would provide opportunities to achieve higher yield and better-quality grain. NUE is a complex trait, which is regulated by several genes. Hence, exploring genetic diversity for NUE can help to develop molecular markers associated with NUE, which can be utilized to develop high NUE sorghum genotypes with greater yield potential. Research on improving NUE in sorghum suggests that, under water-deficit conditions, traits such as stay-green and altered canopy architecture, and under favorable conditions, traits such as an optimized stay-green and senescence ratio and efficient N translocation to grain, are potential breeding targets to develop high NUE sorghum genotypes. Hence, under a wide range of environments, sorghum breeding programs will need to reconsider strategies and develop breeding programs based on environment-specific trait(s) for better adaptation and improvement in productivity and grain quality. Unprecedented progress in sensor-based technology and artificial intelligence in high-throughput phenotyping has provided new horizons to explore complex traits in situ, such as NUE. A better understanding of the genetics and molecular pathways involving NUE, accompanied by targeted high-throughput sensor-based indices, is critical for identifying lines or developing management practices to enhance NUE in sorghum.
COVID and World Stock Markets: A Comprehensive Discussion
Authors: Jabeen Shaista , Farhan Muhammad , Zaka Muhammad Ahmad , Fiaz Muhammad , Farasat Mobina
Published: February 2022

The COVID-19 outbreak has disturbed the victims' economic conditions and posed a significant threat to economies worldwide and their respective financial markets. The majority of the world stock markets have suffered losses in the trillions of dollars, and international financial institutions were forced to reduce their forecasted growth for 2020 and the years to come. The current research deals with the impact of the COVID-19 pandemic on the global stock markets. It has focused on the contingent effects of previous and current pandemics on the financial markets. It has also elaborated on the pandemic impact on diverse pillars of the economy. Irrespective of all these destructive effects of the pandemic, still hopes are there for a sharp rise and speedy improvement in global stock markets' performance.