bluuebunny/crossref_metadata_2025 huggingface dataset:
Cerebral Circulation Time Is a Potential Predictor of Disabling Ischemic Cerebrovascular Events in Patients With Non-disabling Middle Cerebral Artery Stenosis
Authors: Chen Zhenze , Li Mingchun , Wu Zhihuan , Zhang Min , Weng Guomei , Li Minzi , Liao Rongxin , Zhao Peng , Wu Jianming , Zhu Shuzhen , Wang Qing , Li Chunguang , Wei Xiaobo
Published: May 2021

Patients with non-disabling middle cerebral artery (MCA) stenosis (ND-MCAS) are at risk for disabling ischemic cerebrovascular events (DICE) despite aggressive medical therapy. In this study, we aimed to verify whether cerebral circulation time (CCT) was a potential predictor of DICE in patients with ND-MCAS. From January 2015 to January 2020, 46 patients with ND-MCAS treated with aggressive medical therapy were enrolled for digital subtraction angiography (DSA) in this convenience sampling study. They were divided into the DICE (–) and DICE (+) groups based on the occurrence of DICE within 3 months after DSA. The CCT was defined as the time from the appearance of the MCA to the peak intensity of the Trolard vein during DSA. The rCCT (relative CCT) was defined as the ratio of the CCT of the stenotic side (sCCT) to the CCT of the healthy side (hCCT). The differences in sCCT, hCCT, and rCCT between the two groups were analyzed with Mann-Whitney U tests. Logistic regression analysis was performed to evaluate the association between the risk factors and DICE. Receiver operating characteristic (ROC) curves were constructed to assess the predictive value of rCCT in identifying DICE in ND-MCAS patients. The results showed that DICE appeared in 5 of the 46 patients within 3 months. rCCT were significantly increased in the DICE (+) group compared with the DICE (–) group [1.08 (1.05, 1.14) vs. 1.30 (1.22, 1.54), p < 0.001]. Logistic regression analysis found that prolonged rCCT was an independent positive prognostic factor for DICE (odds ratio = 1.273, p = 0.019) after adjustment for potential confounders (age, diabetes, antithrombotic use, and stenosis degree). ROC analysis showed that rCCT provided satisfactory accuracy in distinguishing the DICE (+) group from the DICE (–) group among ND-MCAS patients (area under the curve = 0.985, p < 0.001), with an optimal cutoff point of 1.20 (100% sensitivity, 97.6% specificity). In conclusion, prolonged rCCT is independently associated with the occurrence of DICE in ND-MCAS patients and may be used to identify individuals at risk of DICE.
Framework for the Classification of Emotions in People With Visual Disabilities Through Brain Signals
Authors: López-Hernández Jesús Leonardo , González-Carrasco Israel , López-Cuadrado José Luis , Ruiz-Mezcua Belén
Published: May 2021

Nowadays, the recognition of emotions in people with sensory disabilities still represents a challenge due to the difficulty of generalizing and modeling the set of brain signals. In recent years, the technology that has been used to study a person’s behavior and emotions based on brain signals is the brain–computer interface (BCI). Although previous works have already proposed the classification of emotions in people with sensory disabilities using machine learning techniques, a model of recognition of emotions in people with visual disabilities has not yet been evaluated. Consequently, in this work, the authors present a twofold framework focused on people with visual disabilities. Firstly, auditory stimuli have been used, and a component of acquisition and extraction of brain signals has been defined. Secondly, analysis techniques for the modeling of emotions have been developed, and machine learning models for the classification of emotions have been defined. Based on the results, the algorithm with the best performance in the validation is random forest (RF), with an accuracy of 85 and 88% in the classification for negative and positive emotions, respectively. According to the results, the framework is able to classify positive and negative emotions, but the experimentation performed also shows that the framework performance depends on the number of features in the dataset and the quality of the Electroencephalogram (EEG) signals is a determining factor.
Electroacupuncture Attenuates Neuropathic Pain and Comorbid Negative Behavior: The Involvement of the Dopamine System in the Amygdala
Authors: Zhang Xue-Hui , Feng Chen-Chen , Pei Li-Jian , Zhang Ya-Nan , Chen Liu , Wei Xu-Qiang , Zhou Jia , Yong Yue , Wang Ke
Published: May 2021

Neuropathic pain (NeuP) is an important clinical problem accompanying negative mood symptoms. Neuroinflammation in the amygdala is critically involved in NeuP, and the dopamine (DA) system acts as an important endogenous anti-inflammatory pathway. Electroacupuncture (EA) can improve the clinical outcomes in NeuP, but the underlying mechanisms have not been fully elucidated. This study was designed to assess the effectiveness of EA on pain and pain-related depressive-like and anxiety-like behaviors and explore the role of the DA system in the effects of EA. Male Sprague-Dawley rats were subjected to the chronic constrictive injury (CCI) model to induce NeuP. EA treatment was carried out for 30 min once every other day for 3 weeks. The results showed that CCI caused mechanical hyperalgesia and depressive and anxiety-like behaviors in rats and neuroinflammation in the amygdala, such as an increased protein level of TNFα and IL-1β and activation of astrocytes. EA treatment significantly improved mechanical allodynia and the emotional dysfunction induced by CCI. The effects of EA were accompanied by markedly decreased expression of TNFα, IL-1β, and glial fibrillary acid protein (GFAP) in the amygdala. Moreover, EA treatment reversed CCI-induced down-regulation of DA concentration, tyrosine hydroxylase (TH) expression, and DRD1 and DRD2 receptors. These results suggest that EA-ameliorated NeuP may possibly be associated with the DA system to inhibit the neuroinflammation in the amygdala.
Distinct Genomic Landscape of Colorectal Mucinous Carcinoma Determined via Comprehensive Genomic Profiling: Steps to a New Treatment Strategy
Authors: Huang Liang , Luo Shuanglin , Zhang Xingwei , Cai Yonghua , Xue Fangqin , Hu Huanxin , Zeng Ziwei , Lin Tengjiao , Wang Fei , Wang Weifeng , Zhang Sen , Kang Liang
Published: May 2021

Colorectal mucinous carcinoma (MC) is associated with inferior prognosis and response to treatment compared to adenocarcinoma (AC). The molecular landscapes of MC and adenocarcinoma with mucous composition (AMC) are not well-defined. We aimed to describe the genomic landscape of MC and AMC in a large colorectal cancer cohort. Tumor samples from patients with MC, AMC, or AC were analyzed using next-generation sequencing. MC had a molecular signature distinct from that of AC; genomic features were similar between AMC and MC but not between AMC and AC. HER2 amplification and TP53 and APC mutation rates were lower, whereas SMAD4, PIK3CA, ACVR2A, KMT2D, LRP1, TGFBR2, GRIN2A, BRAF V600E, PTEN, and BRCA2 mutation rates were higher in MC than in AC. The mutation frequencies in MAPK, PI3K, and TGF-β pathways were higher, whereas those of cell cycle proteins and Wnt were lower in MC and AMC than in AC. The proportion of hypermutated tumors was significantly higher in MC and AMC than in AC. As MC has a distinct molecular signature from AC, immunotherapy can be potentially applied in treating MC. Similar molecular profiles of AMC and MC suggest that treatment strategies for MC, but not AC, can be used for AMC treatment.
MRI Radiomics Signature as a Potential Biomarker for Predicting KRAS Status in Locally Advanced Rectal Cancer Patients
Authors: Zhang ZhiYuan , Shen LiJun , Wang Yan , Wang Jiazhou , Zhang Hui , Xia Fan , Wan JueFeng , Zhang Zhen
Published: May 2021

Background and Purpose

Locally advanced rectal cancer (LARC) is a heterogeneous disease with little information about KRAS status and image features. The purpose of this study was to analyze the association between T2 magnetic resonance imaging (MRI) radiomics features and KRAS status in LARC patients.

Material and Methods

Eighty-three patients with KRAS status information and T2 MRI images between 2012.05 and 2019.09 were included. Least absolute shrinkage and selection operator (LASSO) regression was performed to assess the associations between features and gene status. The patients were divided 7:3 into training and validation sets. The C-index and the average area under the receiver operator characteristic curve (AUC) were used for performance evaluation.

Results

The clinical characteristics of 83 patients in the KRAS mutant and wild-type cohorts were balanced. Forty-two (50.6%) patients had KRAS mutations, and 41 (49.4%) patients had wild-type KRAS. A total of 253 radiomics features were extracted from the T2-MRI images of LARC patients. One radiomic feature named X.LL_scaled_std, a standard deviation value of scaled wavelet-transformed low-pass channel filter, was selected from 253 features (P=0.019). The radiomics-based C-index values were 0.801 (95% CI: 0.772-0.830) and 0.703 (95% CI: 0.620-0.786) in the training and validation sets, respectively.

Conclusion

Radiomics features could differentiate KRAS status in LARC patients based on T2-MRI images. Further validation in a larger dataset is necessary in the future.
Tristetraprolin, a Potential Safeguard Against Carcinoma: Role in the Tumor Microenvironment
Authors: Zhang Diwen , Zhou Zhigang , Yang Ruixia , Zhang Sujun , Zhang Bin , Tan Yanxuan , Chen Lingyao , Li Tao , Tu Jian
Published: May 2021

Tristetraprolin (TTP), a well-known RNA-binding protein, primarily affects the expression of inflammation-related proteins by binding to the targeted AU-rich element in the 3’ untranslated region after transcription and subsequently mediates messenger RNA decay. Recent studies have focused on the role of TTP in tumors and their related microenvironments, most of which have referred to TTP as a potential tumor suppressor involved in regulating cell proliferation, apoptosis, and metastasis of various cancers, as well as tumor immunity, inflammation, and metabolism of the microenvironment. Elevated TTP expression levels could aid the diagnosis and treatment of different cancers, improving the prognosis of patients. The aim of this review is to describe the role of TTP as a potential safeguard against carcinoma.
The MicroRNA Landscape of MYCN-Amplified Neuroblastoma
Authors: Misiak Danny , Hagemann Sven , Bell Jessica L. , Busch Bianca , Lederer Marcell , Bley Nadine , Schulte Johannes H. , Hüttelmaier Stefan
Published: May 2021

MYCN gene amplification and upregulated expression are major hallmarks in the progression of high-risk neuroblastoma. MYCN expression and function in modulating gene synthesis in neuroblastoma is controlled at virtually every level, including poorly understood regulation at the post-transcriptional level. MYCN modulates the expression of various microRNAs including the miR-17-92 cluster. MYCN mRNA expression itself is subjected to the control by miRNAs, most prominently the miR-17-92 cluster that balances MYCN expression by feed-back regulation. This homeostasis seems disturbed in neuroblastoma where MYCN upregulation coincides with severely increased expression of the miR-17-92 cluster. In the presented study, we applied high-throughput next generation sequencing to unravel the miRNome in a cohort of 97 neuroblastomas, representing all clinical stages. Aiming to reveal the MYCN-dependent miRNome, we evaluate miRNA expression in MYCN-amplified as well as none amplified tumor samples. In correlation with survival data analysis of differentially expressed miRNAs, we present various putative oncogenic as well as tumor suppressive miRNAs in neuroblastoma. Using microRNA trapping by RNA affinity purification, we provide a comprehensive view of MYCN-regulatory miRNAs in neuroblastoma-derived cells, confirming a pivotal role of the miR-17-92 cluster and moderate association by the let-7 miRNA family. Attempting to decipher how MYCN expression escapes elevated expression of inhibitory miRNAs, we present evidence that RNA-binding proteins like the IGF2 mRNA binding protein 1 reduce miRNA-directed downregulation of MYCN in neuroblastoma. Our findings emphasize the potency of post-transcriptional regulation of MYCN in neuroblastoma and unravel new avenues to pursue inhibition of this potent oncogene.
Cost-Effectiveness of Adding Ribociclib to Endocrine Therapy for Patients With HR-Positive, HER2-Negative Advanced Breast Cancer Among Premenopausal or Perimenopausal Women
Authors: Jeong Eunae , Wang Changjun , Wilson Leslie , Zhong Lixian
Published: May 2021

Purpose

To evaluate the cost-effectiveness of adding ribociclib to endocrine therapy for pre/perimenopausal women with hormone receptor-positive (HR+), human epidermal receptor 2-negative (HER2-) advanced breast cancer from the US payer perspective.

Methods

A partitioned survival analysis model with three health states (progression-free, progressed disease, and death) was developed to compare the cost and effectiveness of ribociclib in combination with endocrine therapy versus endocrine therapy alone based on clinical data from the MONALEESA-7 phase 3 randomized clinical trials. Life years (LYs), quality-adjusted life-years (QALYs), and total costs were estimated and used to calculate incremental cost-effectiveness ratio (ICER) over a lifetime. Deterministic and probabilistic sensitivity analyses were conducted to test the uncertainties of model inputs. Additional scenario analyses were performed.

Results

In the base-case, ribociclib plus endocrine therapy was more effective than endocrine therapy with an additional 1.39 QALYs but also more costly with an ICER of $282,996/QALY. One-way deterministic sensitivity analysis showed that overall survival associated with the treatments and the cost of ribociclib had the greatest impact on the ICER. The probabilistic sensitivity analysis showed that only beyond a willingness-to-pay (WTP) threshold of $272,867, ribociclib plus endocrine therapy would surpass endocrine therapy alone as a cost-effective option.

Conclusions

From the US payer perspective, ribociclib plus endocrine therapy for pre/perimenopausal patients with HR+/HER2- advanced breast cancer is not cost-effective at a WTP threshold of $100,000 or $150,000 per QALY in comparison of endocrine therapy alone.
Population-Based Study of Docetaxel or Abiraterone Effectiveness and Predictive Markers of Progression Free Survival in Metastatic Castration-Sensitive Prostate Cancer
Authors: Briones Juan , Khan Maira , Sidhu Amanjot K. , Zhang Liying , Smoragiewicz Martin , Emmenegger Urban
Published: May 2021

Background

Both Docetaxel (DOC) and Abiraterone (ABI) improve the survival of men with metastatic, castration sensitive prostate cancer (mCSPC). However, the outcome among mCSPC patients is highly variable, while there is a lack of predictive markers of therapeutic benefit. Furthermore, there is limited data on the comparative real-world effectiveness of adding DOC or ABI to androgen deprivation therapy (ADT).

Methods

We conducted a retrospective analysis of 121 mCSPC patients treated at Odette Cancer Centre (Toronto, ON, Canada) between Dec 2014 and Mar 2021 (DOC n = 79, ABI n = 42). The primary endpoint studied was progression free survival (PFS), defined as the interval from start of ADT to either (i) biochemical, radiological, or symptomatic progression, (ii) start of first-line systemic therapy for castration-resistant prostate cancer (CRPC), or (iii) death, whichever occurred first. To identify independent predictive factors for PFS in the entire cohort, a Cox proportional hazard model (stepwise selection) was applied. Overall survival (OS) was among secondary endpoints.

Results

After a median follow-up of 39.6 and 25.1 months in the DOC and ABI cohorts, respectively, 79.7% of men in the DOC and 40.5% in the ABI group experienced a progression event. PFS favored the ABI cohort (p = 0.0038, log-rank test), with 78.0% (95%CI 66.4–91.8%) of ABI versus 67.1% (57.5–78.3%) of DOC patients being free of progression at 12 months. In univariate analysis superior PFS was significantly related to older age at diagnosis of mCSPC, metachronous metastatic presentation, low-volume (CHAARTED), and low-risk (LATITUDE) disease, ≥90% PSA decrease at 3 months (PSA90), and PSA nadir ≤0.2 at 6 months. Age (HR = 0.955), PSA90 (HR = 0.462), and LATITUDE risk stratification (HR = 1.965) remained significantly associated with PFS in multivariable analysis. OS at 12 months was 98.7% (96.3–100%) and 92.7% (85.0–100%) in the DOC and ABI groups (p = 0.97), respectively.

Conclusions

In this real-world group of men undergoing treatment intensification with DOC or ABI for mCSPC, we did not find a significant difference in OS, but PFS was favoring ABI. Age at diagnosis of mCSPC, PSA90 at 3 months and LATITUDE risk classification are predictive factors of PFS in men with mCSPC.
Cellular and Molecular Mechanisms of Pristimerin in Cancer Therapy: Recent Advances
Authors: Chen Run-Ze , Yang Fei , Zhang Min , Sun Zhi-Gang , Zhang Nan
Published: May 2021

Seeking an efficient and safe approach to eliminate tumors is a common goal of medical fields. Over these years, traditional Chinese medicine has attracted growing attention in cancer treatment due to its long history. Pristimerin is a naturally occurring quinone methide triterpenoid used in traditional Chinese medicine to treat various cancers. Recent studies have identified alterations in cellular events and molecular signaling targets of cancer cells under pristimerin treatment. Pristimerin induces cell cycle arrest, apoptosis, and autophagy to exhibit anti-proliferation effects against tumors. Pristimerin also inhibits the invasion, migration, and metastasis of tumor cells via affecting cell adhesion, cytoskeleton, epithelial-mesenchymal transition, cancer stem cells, and angiogenesis. Molecular factors and pathways are associated with the anti-cancer activities of pristimerin. Furthermore, pristimerin reverses multidrug resistance of cancer cells and exerts synergizing effects with other chemotherapeutic drugs. This review aims to discuss the anti-cancer potentials of pristimerin, emphasizing multi-targeted biological and molecular regulations in cancers. Further investigations and clinical trials are warranted to understand the advantages and disadvantages of pristimerin treatment much better.
Current State of Personalized Genitourinary Cancer Radiotherapy in the Era of Precision Medicine
Authors: Kamran Sophia C. , Efstathiou Jason A.
Published: May 2021

Radiation therapy plays a crucial role for the management of genitourinary malignancies, with technological advancements that have led to improvements in outcomes and decrease in treatment toxicities. However, better risk-stratification and identification of patients for appropriate treatments is necessary. Recent advancements in imaging and novel genomic techniques can provide additional individualized tumor and patient information to further inform and guide treatment decisions for genitourinary cancer patients. In addition, the development and use of targeted molecular therapies based on tumor biology can result in individualized treatment recommendations. In this review, we discuss the advances in precision oncology techniques along with current applications for personalized genitourinary cancer management. We also highlight the opportunities and challenges when applying precision medicine principles to the field of radiation oncology. The identification, development and validation of biomarkers has the potential to personalize radiation therapy for genitourinary malignancies so that we may improve treatment outcomes, decrease radiation-specific toxicities, and lead to better long-term quality of life for GU cancer survivors.
LncRNA SNHG6/miR-125b-5p/BMPR1B Axis: A New Therapeutic Target for Triple-Negative Breast Cancer
Authors: Lv Yufei , Lv Xiaohong , Yang Huike , Qi Xiuying , Wang Xiangchen , Li Chao , Shang Xiaochen , Guo Hongmin , Zhang Jianguo , Zhang Yafang
Published: May 2021

Background

Triple-negative breast cancer (TNBC) is a significant cause of patient morbidity. The exactly pathobiological features of this condition has yet to be completely elucidated.

Methods

Breast cancer data obtained from The Cancer Genome Atlas (TCGA) database were evaluated for lncRNA SNHG6 expression. Normal human breast epithelial cell line (MCF-10A) and other breast cancer cell lines (BT-549, MDA-MB-231, Hs 578t, ZR-75-30, SK-BR-3, MCF-7) were also assessed for lncRNA SNHG6 expressions. Cellular proliferative ability was evaluated with colony formation and CCK-8 assays. The ability of cells to migrate was scrutinized with the wound healing and Boyden chamber cell migration assays. qRT-PCR enabled for detection of lncRNA SNHG6, miR-125b-5p and BMPR1B mRNA expressions. Protein BMPR1B expressions were further assessed using Western Blotting. Direct binding sites between transcripts were determined using dual-luciferase reporter assays. We also constructed a xenograft mouse model to further dissect the vivo implications of lncRNA SNHG6. Ki-67 and c-Caspase-3 expressions were detected using immunohistochemistry staining.

Results

Breast cancer cell lines demonstrated higher lncRNA SNHG6 expressions, particularly TNBC cell lines, in contrast to normal breast epithelial cell lines. This finding coincided with those noted on analysis of TCGA breast cancer data. lncRNA SNHG6 knockdown inhibited TNBC cell proliferation, migration, while promoted cell apoptosis. Furthermore, suppressed lncRNA SNHG6 expressions resulted in lower tumor weights and volumes in a xenograft mouse model, as evidenced by Ki-67 and c-Caspase-3 expression profiles in tumor tissues. miR-125b-5p and lncRNA SNHG6/BMPR1B both possessed direct binding sites for each other which was validated utilizing a dual-luciferase reporter assay. Decreasing lncRNA SNHG6 expression in TNBC cells upregulated miR-125b-5p expression. Another side, inhibiting miR-125b-5p upregulated BMPR1B expression in these cells. Moreover, knocking down lncRNA SNHG6 downregulated BMPR1B expression in TNBC cells, and the finding was rescued in cells which were exposed to miR-125b-5p inhibitor. Downregulating miR-125b-5p mitigated the effect of suppressing lncRNA SNHG6 on TNBC cell proliferation, migration, and apoptosis.

Conclusion

Downregulation of lncRNA SNHG6 could inhibit TNBC cell proliferative, migratory capabilities and promote apoptosis capability, likely through modulation of the miR-125b-5p/BMPR1B axis. This axis may be targeted in formulating new therapies for TNBC.
Changes in Urologic Operative Practice at the Beginning of the COVID-19 Pandemic in a Large, National Cohort
Authors: Lewicki Patrick , Arenas-Gallo Camilo , Basourakos Spyridon P. , Punjani Nahid , Venkat Siv , Scherr Douglas S. , Hu Jim C. , Shoag Jonathan E.
Published: May 2021

Objective

To analyze population-level changes in operative practice since the onset of the COVID-19 pandemic to contextualize observations made by individual practices and optimize future responses.

Materials and Methods

This US retrospective analysis used the Premier Perspectives Database. We investigated changes in operative volume through March 2020. Baseline operative volume for urologic surgery was calculated using data from the preceding 12 months and compared on a total and by procedure basis. Multivariable linear regression was used to identify hospital-level predictors of change in response to the pandemic.

Results

At baseline, we captured 23,788 urologic procedural encounters per month as compared with 19,071 during March 2020– a 19.9% decrease. Urologic oncology-related cases were relatively preserved as compared to others (average change in March 2020: +1.1% versus -32.2%). Northeastern (β = -5.66, 95% confidence interval [CI]: -10.2 to -1.18, p = 0.013) and Midwestern hospitals (β = -4.17, 95% CI: -7.89 to -0.45, p = 0.027; both with South as reference region), and those with an increasing percentage of patients insured by Medicaid (β= -0.17 per percentage point, 95% CI: -0.33 to -0.01, p = 0.04) experienced a significantly larger decrease in volume.

Conclusions

There was a 20% decline in urologic operative volume in March 2020, compared with baseline, that preferentially affected hospitals serving Medicaid patients, and those in Northeast and Midwest. In the face of varying mandates on elective surgery, widespread declines in operative volume may also represent hesitancy on behalf of patients to interface with healthcare during the pandemic.
The Anti-Viral and Anti-Inflammatory Properties of Edible Bird’s Nest in Influenza and Coronavirus Infections: From Pre-Clinical to Potential Clinical Application
Authors: Chua Kien Hui , Mohamed Isa Naina , Mohd Yunus Mohd Heikal , Shafinaz Md Nor Norefrina , Kamil Khidhir , Ugusman Azizah , Kumar Jaya
Published: May 2021

Edible bird’s nest (BN) is a Chinese traditional medicine with innumerable health benefits, including anti-viral, anti-inflammatory, neuroprotective, and immunomodulatory effects. A small number of studies have reported the anti-viral effects of EBN against influenza infections using in vitro and in vivo models, highlighting the importance of sialic acid and thymol derivatives in their therapeutic effects. At present, studies have reported that EBN suppresses the replicated virus from exiting the host cells, reduces the viral replication, endosomal trafficking of the virus, intracellular viral autophagy process, secretion of pro-inflammatory cytokines, reorient the actin cytoskeleton of the infected cells, and increase the lysosomal degradation of viral materials. In other models of disease, EBN attenuates oxidative stress-induced cellular apoptosis, enhances proliferation and activation of B-cells and their antibody secretion. Given the sum of its therapeutic actions, EBN appears to be a candidate that is worth further exploring for its protective effects against diseases transmitted through air droplets. At present, anti-viral drugs are employed as the first-line defense against respiratory viral infections, unless vaccines are available for the specific pathogens. In patients with severe symptoms due to exacerbated cytokine secretion, anti-inflammatory agents are applied. Treatment efficacy varies across the patients, and in times of a pandemic like COVID-19, many of the drugs are still at the experimental stage. In this review, we present a comprehensive overview of anti-viral and anti-inflammatory effects of EBN, chemical constituents from various EBN preparation techniques, and drugs currently used to treat influenza and novel coronavirus infections. We also aim to review the pathogenesis of influenza A and coronavirus, and the potential of EBN in their clinical application. We also describe the current literature in human consumption of EBN, known allergenic or contaminant presence, and the focus of future direction on how these can be addressed to further improve EBN for potential clinical application.
Aldehyde Dehydrogenase 2 Protects Against Lipopolysaccharide-Induced Myocardial Injury by Suppressing Mitophagy
Authors: Ji Wenqing , Wan Tiantian , Zhang Fang , Zhu Xiaomei , Guo Shubin , Mei Xue
Published: May 2021

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Sepsis-induced circulatory and cardiac dysfunction is associated with high mortality rates. Mitophagy, a specific form of autophagy, is excessively activated in lipopolysaccharide-induced myocardial injury. The present study investigated whether aldehyde dehydrogenase 2 (ALDH2) regulates mitophagy in sepsis-induced myocardial dysfunction. After lipopolysaccharide administration, cardiac dysfunction, inflammatory cell infiltration, biochemical indicators of myocardial cell injury, and cardiomyocyte apoptosis were ameliorated in mice by ALDH2 activation or overexpression. In contrast, cardiac dysfunction and cardiomyocyte apoptosis were exacerbated in mice followed ALDH2 inhibition. Moreover, ALDH2 activation or overexpression regulated mitophagy by suppressing the expression of phosphatase and tensin homolog-induced putative kinase 1 (PINK1)/Parkin, by preventing the accumulation of 4-hydroxy-trans-nonenal. Conversely, ALDH2 inhibition promoted the expression of LC3B by increasing 4-hydroxy-trans-2-nonenal accumulation. Consequently, ALDH2 may protect the heart from lipopolysaccharide-induced injury by suppressing PINK1/Parkin-dependent mitophagy.
Intracerebroventricularly Injected Streptozotocin Exerts Subtle Effects on the Cognitive Performance of Long-Evans Rats
Authors: Gáspár Attila , Hutka Barbara , Ernyey Aliz Judit , Tajti Brigitta Tekla , Varga Bence Tamás , Zádori Zoltán Sándor , Gyertyán István
Published: May 2021

Intracerebroventricularly injected streptozotocin (STZ)-induced learning impairment has been an increasingly used rat model of Alzheimer disease. The evoked pathological changes involve many symptoms of the human disease (cognitive decline, increase in β-amyloid and phospho-tau level, amyloid plaque-like deposits). However, the model has predominantly been used with Wistar rats in the literature. The objective of the current study was to transfer it to Long-Evans rats with the ulterior aim to integrate it in a complex cognitive test battery where we use this strain because of its superior cognitive capabilities. We performed two experiments (EXP1, EXP2) with three months old male animals. At EXP1, rats were treated with 2 × 1.5 mg/kg STZ (based on the literature) or citrate buffer vehicle injected bilaterally into the lateral ventricles on days 1 and 3. At EXP2 animals were treated with 3 × 1.5 mg/kg STZ or citrate buffer vehicle injected in the same way as in EXP1 at days 1, 3, and 5. Learning and memory capabilities of the rats were then tested in the following paradigms: five choice serial reaction time test (daily training, started from week 2 or 8 post surgery in Exp1 or Exp2, respectively, and lasting until the end of the experiment); novel object recognition (NOR) test (at week 8 or 14), passive avoidance (at week 11 or 6) and Morris water-maze (at week 14 or 6). 15 or 14 weeks after the STZ treatment animals were sacrificed and brain phospho-tau/tau protein ratio and β -amyloid level were determined by western blot technique. In EXP1 we could not find any significant difference between the treated and the control groups in any of the assays. In EXP2 we found significant impairment in the NOR test and elevated β-amyloid level in the STZ treated group in addition to slower learning of the five-choice paradigm and a trend for increased phospho-tau/tau ratio. Altogether our findings suggest that the Long-Evans strain may be less sensitive to the STZ treatment than the Wistar rats and higher doses may be needed to trigger pathological changes in these animals. The results also highlight the importance of strain diversity in modelling human diseases.
Purinergic P2 Receptors: Novel Mediators of Mechanotransduction
Authors: Kong Qihang , Quan Yue , Tian Geer , Zhou Junteng , Liu Xiaojing
Published: May 2021

Mechanosensing and mechanotransduction are vital processes in mechanobiology and play critical roles in regulating cellular behavior and fate. There is increasing evidence that purinergic P2 receptors, members of the purinergic family, play a crucial role in cellular mechanotransduction. Thus, information on the specific mechanism of P2 receptor-mediated mechanotransduction would be valuable. In this review, we focus on purinergic P2 receptor signaling pathways and describe in detail the interaction of P2 receptors with other mechanosensitive molecules, including transient receptor potential channels, integrins, caveolae-associated proteins and hemichannels. In addition, we review the activation of purinergic P2 receptors and the role of various P2 receptors in the regulation of various pathophysiological processes induced by mechanical stimuli.
NmFGF1-Regulated Glucolipid Metabolism and Angiogenesis Improves Functional Recovery in a Mouse Model of Diabetic Stroke and Acts via the AMPK Signaling Pathway
Authors: Zhao Yeli , Ye Shasha , Lin Jingjing , Liang Fei , Chen Jun , Hu Jian , Chen Kun , Fang Yani , Chen Xiongjian , Xiong Ye , Lin Li , Tan Xianxi
Published: May 2021

Diabetes increases the risk of stroke, exacerbates neurological deficits, and increases mortality. Non-mitogenic fibroblast growth factor 1 (nmFGF1) is a powerful neuroprotective factor that is also regarded as a metabolic regulator. The present study aimed to investigate the effect of nmFGF1 on the improvement of functional recovery in a mouse model of type 2 diabetic (T2D) stroke. We established a mouse model of T2D stroke by photothrombosis in mice that were fed a high-fat diet and injected with streptozotocin (STZ). We found that nmFGF1 reduced the size of the infarct and attenuated neurobehavioral deficits in our mouse model of T2D stroke. Angiogenesis plays an important role in neuronal survival and functional recovery post-stroke. NmFGF1 promoted angiogenesis in the mouse model of T2D stroke. Furthermore, nmFGF1 reversed the reduction of tube formation and migration in human brain microvascular endothelial cells (HBMECs) cultured in high glucose conditions and treated with oxygen glucose deprivation/re-oxygenation (OGD). Amp-activated protein kinase (AMPK) plays a critical role in the regulation of angiogenesis. Interestingly, we found that nmFGF1 increased the protein expression of phosphorylated AMPK (p-AMPK) both in vivo and in vitro. We found that nmFGF1 promoted tube formation and migration and that this effect was further enhanced by an AMPK agonist (A-769662). In contrast, these processes were inhibited by the application of an AMPK inhibitor (compound C) or siRNA targeting AMPK. Furthermore, nmFGF1 ameliorated neuronal loss in diabetic stroke mice via AMPK-mediated angiogenesis. In addition, nmFGF1 ameliorated glucose and lipid metabolic disorders in our mouse model of T2D stroke without causing significant changes in body weight. These results revealed that nmFGF1-regulated glucolipid metabolism and angiogenesis play a key role in the improvement of functional recovery in a mouse model of T2D stroke and that these effects are mediated by the AMPK signaling pathway.
Ultrasound-Guided Hydrodilatation With Triamcinolone Acetonide for Adhesive Capsulitis: A Randomized Controlled Trial Comparing the Posterior Glenohumeral Recess and the Rotator Cuff Interval Approaches
Authors: Wang Jia-Chi , Tsai Po-Yi , Hsu Po-Cheng , Huang Jian-Ru , Wang Kevin A. , Chou Chen-Liang , Chang Ke-Vin
Published: May 2021

For patients with adhesive capsulitis, hydrodilatation is typically performed using corticosteroids with ultrasound guidance via the posterior glenohumeral recess. Recently, a new intervention technique via the rotator cuff interval has been described. This study aimed to compare the efficacy of hydrodilatation with triamcinolone acetonide via the posterior glenohumeral recess and the rotator cuff interval in patients with adhesive capsulitis. This prospective randomized controlled trial was conducted in a tertiary care center with a follow-up period of 12 weeks. We enrolled 64 patients diagnosed with shoulder adhesive capsulitis. The subjects were randomly assigned to two groups that received hydrodilatation with corticosteroids either through the posterior glenohumeral recess or though the rotator cuff interval. The injection contained 4 ml of triamcinolone acetonide (40 mg) mixed with 4 ml of 2% lidocaine hydrochloride and 12 ml of normal saline. The shoulder pain and disability index, visual analog scale for pain, and range of motion were analyzed before and at 6 and 12 weeks after the treatment. Both groups experienced improvements in the visual analog scale scores, shoulder pain and disability index scores, and range of motion throughout the study period. A significant group-time interaction was observed in terms of the visual analog scale for pain during motion (p = 0.019), favoring hydrodilatation through the rotator cuff interval. Thus, hydrodilatation through the rotator cuff interval might be a better treatment option than that through the posterior glenohumeral recess for patients with adhesive capsulitis, considering its superior effect in alleviating pain during shoulder movement.
Metabolism and Regulatory Functions of O-Acetylserine, S-Adenosylmethionine, Homocysteine, and Serine in Plant Development and Environmental Responses
Authors: Watanabe Mutsumi , Chiba Yukako , Hirai Masami Yokota
Published: May 2021

The metabolism of an organism is closely related to both its internal and external environments. Metabolites can act as signal molecules that regulate the functions of genes and proteins, reflecting the status of these environments. This review discusses the metabolism and regulatory functions of O-acetylserine (OAS), S-adenosylmethionine (AdoMet), homocysteine (Hcy), and serine (Ser), which are key metabolites related to sulfur (S)-containing amino acids in plant metabolic networks, in comparison to microbial and animal metabolism. Plants are photosynthetic auxotrophs that have evolved a specific metabolic network different from those in other living organisms. Although amino acids are the building blocks of proteins and common metabolites in all living organisms, their metabolism and regulation in plants have specific features that differ from those in animals and bacteria. In plants, cysteine (Cys), an S-containing amino acid, is synthesized from sulfide and OAS derived from Ser. Methionine (Met), another S-containing amino acid, is also closely related to Ser metabolism because of its thiomethyl moiety. Its S atom is derived from Cys and its methyl group from folates, which are involved in one-carbon metabolism with Ser. One-carbon metabolism is also involved in the biosynthesis of AdoMet, which serves as a methyl donor in the methylation reactions of various biomolecules. Ser is synthesized in three pathways: the phosphorylated pathway found in all organisms and the glycolate and the glycerate pathways, which are specific to plants. Ser metabolism is not only important in Ser supply but also involved in many other functions. Among the metabolites in this network, OAS is known to function as a signal molecule to regulate the expression of OAS gene clusters in response to environmental factors. AdoMet regulates amino acid metabolism at enzymatic and translational levels and regulates gene expression as methyl donor in the DNA and histone methylation or after conversion into bioactive molecules such as polyamine and ethylene. Hcy is involved in Met–AdoMet metabolism and can regulate Ser biosynthesis at an enzymatic level. Ser metabolism is involved in development and stress responses. This review aims to summarize the metabolism and regulatory functions of OAS, AdoMet, Hcy, and Ser and compare the available knowledge for plants with that for animals and bacteria and propose a future perspective on plant research.
K-Domain Technology: Constitutive Expression of a Blueberry Keratin-Like Domain Mimics Expression of Multiple MADS-Box Genes in Enhancing Maize Grain Yield
Authors: Song Guo-qing , Han Xue
Published: May 2021

MADS-box genes are considered as the foundation of all agronomic traits because they play essential roles in almost every aspect of plant reproductive development. Keratin-like (K) domain is a conserved protein domain of tens of MIKC-type MADS-box genes in plants. K-domain technology constitutively expresses a K-domain to mimic expression of the K-domains of other MADS-box genes simultaneously and thus to generate new opportunities for yield enhancement, because the increased K-domains can likely prevent MADS-domain proteins from binding to target DNA. In this study, we evaluated utilizing the K-domain technology to increase maize yield. The K-domain of a blueberry’s SUPPRESSOR of CONSTITUTIVE EXPRESSION OF CONSTANS 1 (VcSOC1K) has similarities to five MADS-box genes in maize. Transgenic maize plants expressing the VcSOC1K showed 13–100% of more grain per plant than the nontransgenic plants in all five experiments conducted under different experimental conditions. Transcriptome comparisons revealed 982 differentially expressed genes (DEGs) in the leaves from 83-day old plants, supporting that the K-domain technology were powerful and multiple functional. The results demonstrated that constitutive expression of the VcSOC1K was very effective to enhance maize grain production. With the potential of mimicking the K-domains of multiple MADS-box genes, the K-domain technology opens a new approach to increase crop yield.
An Exploratory Meta-Analytic Review on the Empirical Evidence of Differential Learning as an Enhanced Motor Learning Method
Authors: Tassignon Bruno , Verschueren Jo , Baeyens Jean-Pierre , Benjaminse Anne , Gokeler Alli , Serrien Ben , Clijsen Ron
Published: May 2021

Background: Differential learning (DL) is a motor learning method characterized by high amounts of variability during practice and is claimed to provide the learner with a higher learning rate than other methods. However, some controversy surrounds DL theory, and to date, no overview exists that compares the effects of DL to other motor learning methods.

Objective: To evaluate the effectiveness of DL in comparison to other motor learning methods in the acquisition and retention phase.

Design: Systematic review and exploratory meta-analysis.

Methods: PubMed (MEDLINE), Web of Science, and Google Scholar were searched until February 3, 2020. To be included, (1) studies had to be experiments where the DL group was compared to a control group engaged in a different motor learning method (lack of practice was not eligible), (2) studies had to describe the effects on one or more measures of performance in a skill or movement task, and (3) the study report had to be published as a full paper in a journal or as a book chapter.

Results: Twenty-seven studies encompassing 31 experiments were included. Overall heterogeneity for the acquisition phase (post-pre; I2 = 77%) as well as for the retention phase (retention-pre; I2 = 79%) was large, and risk of bias was high. The meta-analysis showed an overall small effect size of 0.26 [0.10, 0.42] in the acquisition phase for participants in the DL group compared to other motor learning methods. In the retention phase, an overall medium effect size of 0.61 [0.30, 0.91] was observed for participants in the DL group compared to other motor learning methods.

Discussion/Conclusion: Given the large amount of heterogeneity, limited number of studies, low sample sizes, low statistical power, possible publication bias, and high risk of bias in general, inferences about the effectiveness of DL would be premature. Even though DL shows potential to result in greater average improvements between pre- and post/retention test compared to non-variability-based motor learning methods, more high-quality research is needed before issuing such a statement. For robust comparisons on the relative effectiveness of DL to different variability-based motor learning methods, scarce and inconclusive evidence was found.
Proactive Control Mediates the Relationship Between Working Memory and Math Ability in Early Childhood
Authors: Wang Chunjie , Li Baoming , Yao Yuan
Published: May 2021

Based on the dual mechanisms of control (DMC) theory, there are two distinct mechanisms of cognitive control, proactive and reactive control. Importantly, accumulating evidence indicates that there is a developmental shift from predominantly using reactive control to proactive control during childhood, and the engagement of proactive control emerges as early as 5–7 years old. However, less is known about whether and how proactive control at this early age stage is associated with children’s other cognitive abilities such as working memory and math ability. To address this issue, the current study recruited 98 Chinese children under 5–7 years old. Among them, a total of 81 children (mean age = 6.29 years) contributed useable data for the assessments of cognitive control, working memory, and math ability. The results revealed that children at this age period predominantly employed a pattern of proactive control during an AX-Continuous Performance Task (AX-CPT). Moreover, the proactive control index estimated by this task was positively associated with both working memory and math performance. Further regression analysis showed that proactive control accounted for significant additional variance in predicting math performance after controlling for working memory. Most interestingly, mediation analysis showed that proactive control significantly mediated the association between working memory and math performance. This suggests that as working memory increases so does proactive control, which may in turn improve math ability in early childhood. Our findings may have important implications for educational practice.
Self-Efficacy in Habit Building: How General and Habit-Specific Self-Efficacy Influence Behavioral Automatization and Motivational Interference
Authors: Stojanovic Marco , Fries Stefan , Grund Axel
Published: May 2021

In this article, we investigate the role of self-efficacy (SE) in intentional habit building. We analyzed event sampling data from a habit building app we created that helps define and track habit data. We used hierarchical growth curve modeling and multilevel mediation to test our hypotheses. In a first study, N = 91 university students built new study habits over a period of 6 weeks in a controlled study. We found that the trait-like (Level 2) general self-efficacy predicted automaticity (i.e., habit strength) but not the experience of motivational interference (MI). In a second study with real user data, N = 265 idiographic habits have been analyzed. The specific SE associated with these habits – habit-specific self-efficacy (Level 1, HSE) – was measured during habit formation. We found that lagged HSE predicted automaticity and that lagged automaticity predicted HSE, indicating a positive feedback mechanism in habit building. Furthermore, we found that lagged HSE predicted less MI during habit performance. A multilevel mediation analysis showed significant effects of lagged HSE (Level 1) and aggregated HSE (Level 2) on MI, which were both partially mediated by automaticity. These results show the importance of defining the specificity of SE beliefs and how they interact with automaticity in the habit building process.
Antecedents and Moderation Effects of Maladaptive Coping Behaviors Among German University Students
Authors: Mülder Lina Marie , Deci Nicole , Werner Antonia Maria , Reichel Jennifer L. , Tibubos Ana Nanette , Heller Sebastian , Schäfer Markus , Pfirrmann Daniel , Edelmann Dennis , Dietz Pavel , Beutel Manfred E. , Letzel Stephan , Rigotti Thomas
Published: May 2021

Prolonging working hours and presenteeism have been conceptualized as self-endangering coping behaviors in employees, which are related to health impairment. Drawing upon the self-regulation of behavior model, the goal achievement process, and Warr's vitamin model, we examined the antecedents and moderation effects regarding quantitative demands, autonomy, emotion regulation, and self-motivation competence of university students' self-endangering coping behaviors (showing prolonging working hours and presenteeism). Results from a cross-sectional survey of 3,546 German university students indicate that quantitative demands are positively related and autonomy has a u-shape connection with self-endangering coping. Emotion regulation was shown to be a protective factor for prolonging working hours. Moreover, self-motivation moderated the relationship between quantitative demands and prolonging of working hours, but not in the assumed direction. Self-motivation showed a systematic positive relationship with prolonging of working hours, but no relationship with presenteeism. Autonomy moderated the relationship of quantitative demands with both self-endangering behaviors. We found no moderating effects for emotion regulation of quantitative demands or autonomy and self-endangering behaviors. Besides further practical implications, the results suggest that lecturers should design their courses accordingly with less time pressure and university students should be trained in the use of autonomy.