bluuebunny/crossref_metadata_2025 huggingface dataset:
Blocking Cross-Species Secondary Binding When Performing Double Immunostaining With Mouse and Rat Primary Antibodies
Authors: Mao Shanping , Xiong Guoxiang , Johnson Brian N. , Cohen Noam A. , Cohen Akiva S.
Published: May 2021

Immunostaining is a powerful technique and widely used to identify molecules in tissues and cells, although critical steps are necessary to block cross-reaction. Here we focused on an overlooked cross immunoreactivity issue where a secondary antibody (secondary) cross-reacts with a primary antibody (primary) from a different species. We first confirmed the previously reported cross-species binding of goat anti-mouse secondary to rat primary. This was accomplished by staining with a rat primary against glial fibrillary acidic protein (GFAP) and visualizing with goat (or donkey) anti-mouse secondary. We then further revealed the converse cross-species binding by staining with a mouse primary against neuronal nuclear protein (NeuN) and visualizing with anti-rat secondaries. We speculate that mouse and rat primaries share antigenicity, enabling either secondary to recognize either primary. To block this cross-species binding in double staining experiments, we compared three protocols using mouse anti-NeuN and rat anti-GFAP, two primaries whose antigens have non-overlapping distributions in brain tissues. Simultaneous staining resulted in cross-species astrocytic staining (anti-mouse secondary to rat anti-GFAP primary) but no cross-species neuronal staining (anti-rat secondary to mouse anti-NeuN primary). Cross-species astrocytic staining was missing after sequential same-species staining with mouse anti-NeuN primary, followed by rat anti-GFAP. However, cross-species astrocytic staining could not be diminished after sequential same-species staining with rat anti-GFAP primary, followed by mouse anti-NeuN. We thus hypothesize that a competition exists between anti-mouse and anti-rat secondaries in their binding to both primaries. Single staining for NeuN or GFAP visualized with dual secondaries at different dilution ratio supported this hypothesis.
Kynurenines and Neurofilament Light Chain in Multiple Sclerosis
Authors: Pukoli Dániel , Polyák Helga , Rajda Cecilia , Vécsei László
Published: May 2021

Multiple sclerosis is an autoimmune, demyelinating, and neurodegenerative disease of the central nervous system. In recent years, it has been proven that the kynurenine system plays a significant role in the development of several nervous system disorders, including multiple sclerosis. Kynurenine pathway metabolites have both neurotoxic and neuroprotective effects. Moreover, the enzymes of the kynurenine pathway play an important role in immunomodulation processes, among others, as well as interacting with neuronal energy balance and various redox reactions. Dysregulation of many of the enzymatic steps in kynurenine pathway and upregulated levels of these metabolites locally in the central nervous system, contribute to the progression of multiple sclerosis pathology. This process can initiate a pathogenic cascade, including microglia activation, glutamate excitotoxicity, chronic oxidative stress or accumulated mitochondrial damage in the axons, that finally disrupt the homeostasis of neurons, leads to destabilization of neuronal cell cytoskeleton, contributes to neuro-axonal damage and neurodegeneration. Neurofilaments are good biomarkers of the neuro-axonal damage and their level reliably indicates the severity of multiple sclerosis and the treatment response. There is increasing evidence that connections exist between the molecules generated in the kynurenine metabolic pathway and the change in neurofilament concentrations. Thus the alterations in the kynurenine pathway may be an important biomarker of the course of multiple sclerosis. In our present review, we report the possible relationship and connection between neurofilaments and the kynurenine system in multiple sclerosis based on the available evidences.
Harmonized Segmentation of Neonatal Brain MRI
Authors: Grigorescu Irina , Vanes Lucy , Uus Alena , Batalle Dafnis , Cordero-Grande Lucilio , Nosarti Chiara , Edwards A. David , Hajnal Joseph V. , Modat Marc , Deprez Maria
Published: May 2021

Deep learning based medical image segmentation has shown great potential in becoming a key part of the clinical analysis pipeline. However, many of these models rely on the assumption that the train and test data come from the same distribution. This means that such methods cannot guarantee high quality predictions when the source and target domains are dissimilar due to different acquisition protocols, or biases in patient cohorts. Recently, unsupervised domain adaptation techniques have shown great potential in alleviating this problem by minimizing the shift between the source and target distributions, without requiring the use of labeled data in the target domain. In this work, we aim to predict tissue segmentation maps on T2-weighted magnetic resonance imaging data of an unseen preterm-born neonatal population, which has both different acquisition parameters and population bias when compared to our training data. We achieve this by investigating two unsupervised domain adaptation techniques with the objective of finding the best solution for our problem. We compare the two methods with a baseline fully-supervised segmentation network and report our results in terms of Dice scores obtained on our source test dataset. Moreover, we analyse tissue volumes and cortical thickness measures of the harmonized data on a subset of the population matched for gestational age at birth and postmenstrual age at scan. Finally, we demonstrate the applicability of the harmonized cortical gray matter maps with an analysis comparing term and preterm-born neonates and a proof-of-principle investigation of the association between cortical thickness and a language outcome measure.
Effects of Flavonoid Supplementation on Common Eye Disorders: A Systematic Review and Meta-Analysis of Clinical Trials
Authors: Davinelli Sergio , Ali Sawan , Scapagnini Giovanni , Costagliola Ciro
Published: May 2021

Background: Emerging studies show that certain plant compounds may reduce the severity of most prevalent ocular abnormalities. The aim of this systematic review and meta-analysis was to assess the effect of dietary flavonoids on major eye disorders.

Methods: Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Cochrane Library databases for all articles published up to April 2021. The literature search yielded 1,134 articles, and a total of 16 studies were included in the systematic review. A meta-analysis of 11 intervention trials involving a total of 724 participants was performed.

Results: Using a random-effects model, the pooled results revealed an overall significant effect of flavonoids on common ophthalmic disorders (standard mean difference = −0.39; 95% CI: −0.56, −0.21, p < 0.01). Of the subclasses of flavonoids, flavan-3-ols (standard mean difference = −0.62; 95% CI: −1.03, −0.22, p < 0.01), and anthocyanins (standard mean difference = −0.42; 95% CI: −0.63, −0.21, p < 0.01) were the only effective intervention for improving the outcomes of ocular conditions. For several of the other flavonoid subclasses, evidence on efficacy was insufficient.

Conclusion: Our findings indicate that flavonoids may improve the clinical manifestations associated with ocular disorders. However, further well-constructed clinical trials are required to confirm these results and examine the effect of flavonoids on eye disorders other than those identified in this review.

Systematic Review Registration: PROSPERO, identifier CRD42021247332.
3D Spatial Distribution of Nanoparticles in Mice Brain Metastases by X-ray Phase-Contrast Tomography
Authors: Longo Elena , Sancey Lucie , Cedola Alessia , Barbier Emmanuel L. , Bravin Alberto , Brun Francesco , Bukreeva Inna , Fratini Michela , Massimi Lorenzo , Greving Imke , Le Duc Geraldine , Tillement Olivier , De La Rochefoucauld Ombeline , Zeitoun Philippe
Published: May 2021

Characterizing nanoparticles (NPs) distribution in multiple and complex metastases is of fundamental relevance for the development of radiological protocols based on NPs administration. In the literature, there have been advances in monitoring NPs in tissues. However, the lack of 3D information is still an issue. X-ray phase-contrast tomography (XPCT) is a 3D label-free, non-invasive and multi-scale approach allowing imaging anatomical details with high spatial and contrast resolutions. Here an XPCT qualitative study on NPs distribution in a mouse brain model of melanoma metastases injected with gadolinium-based NPs for theranostics is presented. For the first time, XPCT images show the NPs uptake at micrometer resolution over the full brain. Our results revealed a heterogeneous distribution of the NPs inside the melanoma metastases, bridging the gap in spatial resolution between magnetic resonance imaging and histology. Our findings demonstrated that XPCT is a reliable technique for NPs detection and can be considered as an emerging method for the study of NPs distribution in organs.
Rectosigmoid-Junction Squamous Cell Carcinoma With pMMR/MSS Achieved a Partial Response Following PD-1 Blockade Combined With Chemotherapy: A Case Report
Authors: He Yanxin , Wang Lunqing , Li Xiao , Zhang Tongsong , Song Tingting , Zhang Junling , Yu Yangyang , Chen Shiqing , Song Haiping
Published: May 2021

Colorectal squamous cell carcinoma (SCC) is extremely rare and associated with a poor prognosis. And the pMMR/MSS colorectal cancer is related to a limited response to programmed death ligand-1 (PD-1) blockade monotherapy. However, the clinical activity of PD-1 blockade monotherapy or combination therapy in colorectal SCC is unknown. One patient with rectosigmoid-junction SCC was treated with PD-1 blockade combined with chemotherapy. After 3 months of PD-1 blockade and chemotherapy, the computed tomography imaging showed that this patient achieved a partial response. The next generation sequencing and immunohistochemistry analysis showed that the patient had tumors with proficient mismatch repair (pMMR) and microsatellite stability (MSS), strong PD-L1 expression, and tumor mutational burden-high (TMB-High), respectively. This case suggests that PD-1 blockade combined with chemotherapy might be an effective therapy for colorectal SCC with pMMR/MSS status. Moreover, the PD-L1 expression and TMB might be the potential predictors of PD-1 blockade response for colorectal SCC patients.
The Efficacy and Safety of Carbon Ion Radiotherapy for Meningiomas: A Systematic Review and Meta-Analysis
Authors: Li Jie-yun , Li Jing-wen , Jin Yuan-chang , Li Mei-xuan , Guo Li-ping , Bing Zhi-tong , Zhang Qiu-ning , Bai Fei , Wang Xiao-hu , Li Xiu-xia , Yang Ke-hu
Published: May 2021

Objective

The purpose of this systematic review and meta-analysis is to evaluate the efficacy and safety of carbon ion radiotherapy (CI-RT) in improving meningioma by comparing photon and protons radiotherapy.

Methods

A comprehensive search for relevant studies published until March 17, 2021, was conducted in PubMed, the Cochrane Library, Chinese Biomedical Literature Database and EMBASE. Statistical analyses were performed with R 4.0.3.

Results

We identified 396 studies, of which 18 studies involving 985 participants were included. Except for one low quality study, the quality of the included studies was found to be either moderate or high quality. The analyses conducted according random effects model indicated that the 1-year overall survival rate (OS) of benign and non-benign meningiomas after the CI-RT treatment was 99% (95%CL=.91-1.00, I2 = 0%). The overall average 5-year OS for meningiomas was 72% (95%CL=0.52-0.86, I2 = 35%), not as effective as proton radiotherapy (PR-RT) 85% (95%CL=.72-.93, I2 = 73, Q=4.17, df=2, p=.12). Additionally, 5-year OS of atypical meningiomas (81%) was found to be significantly higher than anaplastic meningiomas (52%). The 10-year OS after CI-RT of patients with mixed grade meningioma was 91% (95%CL=.75-.97, I2 = 73%). The 15-year OS after CI-RT 87% (95%CL=.11-1.00) or PR-RT 87% (95%CL=.23-.99, I2 = 79%) were the same (Q=0, df=1, p=.99). After undergoing CI-RT for 3 and 5 years, the LC for benign meningioma was 100% and 88%, respectively, while the 2-year LC of non-benign meningiomas (atypical/anaplastic) was 33%. Headache, sensory impairment, cognitive impairment, and hearing impairment were found to be the most common adverse reactions, with individual incidences of 19.4%, 23.7%, 9.1%, and 9.1%, respectively.

Conclusion

CI-RT is a rapidly developing technique that has been proven to be an effective treatment against meningioma. The efficacy and safety of CI-RT for meningiomas were similar to those of PR-RT, better than photon radiotherapy (PH-RT). However, there is a need for more prospective trials in the future that can help provide more supportive evidence.
Immunotherapy in Treating EGFR-Mutant Lung Cancer: Current Challenges and New Strategies
Authors: To Kenneth K. W. , Fong Winnie , Cho William C. S.
Published: May 2021

Lung cancer is the leading cause of cancer-related deaths worldwide. Immune checkpoint inhibitors, including monoclonal antibodies against programmed death-1 (PD-1) and programmed death ligand-1 (PD-L1), have dramatically improved the survival and quality of life of a subset of non-small cell lung cancer (NSCLC) patients. Multiple predictive biomarkers have been proposed to select the patients who may benefit from the immune checkpoint inhibitors. EGFR-mutant NSCLC is the most prevalent molecular subtype in Asian lung cancer patients. However, patients with EGFR-mutant NSCLC show poor response to anti-PD-1/PD-L1 treatment. While small-molecule EGFR tyrosine kinase inhibitors (TKIs) are the preferred initial treatment for EGFR-mutant NSCLC, acquired drug resistance is severely limiting the long-term efficacy. However, there is currently no further effective treatment option for TKIs-refractory EGFR-mutant NSCLC patients. The reasons mediating the poor response of EGFR-mutated NSCLC patients to immunotherapy are not clear. Initial investigations revealed that EGFR-mutated NSCLC has lower PD-L1 expression and a low tumor mutational burden, thus leading to weak immunogenicity. Moreover, the use of PD-1/PD-L1 blockade prior to or concurrent with osimertinib has been reported to increase the risk of pulmonary toxicity. Furthermore, emerging evidence shows that PD-1/PD-L1 blockade in NSCLC patients can lead to hyperprogressive disease associated with dismal prognosis. However, it is difficult to predict the treatment toxicity. New biomarkers are urgently needed to predict response and toxicity associated with the use of PD-1/PD-L1 immunotherapy in EGFR-mutated NSCLC. Recently, promising data have emerged to suggest the potentiation of PD-1/PD-L1 blockade therapy by anti-angiogenic agents and a few other novel therapeutic agents. This article reviews the current investigations about the poor response of EGFR-mutated NSCLC to anti-PD-1/PD-L1 therapy, and discusses the new strategies that may be adopted in the future.
Post-Transformation IGHV-IGHD-IGHJ Mutations in Chronic Lymphocytic Leukemia B Cells: Implications for Mutational Mechanisms and Impact on Clinical Course
Authors: Bagnara Davide , Tang Catherine , Brown Jennifer R. , Kasar Siddha , Fernandes Stacey , Colombo Monica , Vergani Stefano , Mazzarello Andrea N. , Ghiotto Fabio , Bruno Silvia , Morabito Fortunato , Rai Kanti R. , Kolitz Jonathan E. , Barrientos Jacqueline C. , Allen Steven L. , Fais Franco , Scharff Matthew D. , MacCarthy Thomas , Chiorazzi Nicholas
Published: May 2021

Analyses of IGHV gene mutations in chronic lymphocytic leukemia (CLL) have had a major impact on the prognostication and treatment of this disease. A hallmark of IGHV-mutation status is that it very rarely changes clonally over time. Nevertheless, targeted and deep DNA sequencing of IGHV-IGHD-IGHJ regions has revealed intraclonal heterogeneity. We used a DNA sequencing approach that achieves considerable depth and minimizes artefacts and amplification bias to identify IGHV-IGHD-IGHJ subclones in patients with prolonged temporal follow-up. Our findings extend previous studies, revealing intraclonal IGHV-IGHD-IGHJ diversification in almost all CLL clones. Also, they indicate that some subclones with additional IGHV-IGHD-IGHJ mutations can become a large fraction of the leukemic burden, reaching numerical criteria for monoclonal B-cell lymphocytosis. Notably, the occurrence and complexity of post-transformation IGHV-IGHD-IGHJ heterogeneity and the expansion of diversified subclones are similar among U-CLL and M-CLL patients. The molecular characteristics of the mutations present in the parental, clinically dominant CLL clone (CDC) differed from those developing post-transformation (post-CDC). Post-CDC mutations exhibit significantly lower fractions of mutations bearing signatures of activation induced deaminase (AID) and of error-prone repair by Polη, and most of the mutations were not ascribable to those enzymes. Additionally, post-CDC mutations displayed a lower percentage of nucleotide transitions compared with transversions that was also not like the action of AID. Finally, the post-CDC mutations led to significantly lower ratios of replacement to silent mutations in VH CDRs and higher ratios in VH FRs, distributions different from mutations found in normal B-cell subsets undergoing an AID-mediated process. Based on these findings, we propose that post-transformation mutations in CLL cells either reflect a dysfunctional standard somatic mutational process or point to the action of another mutational process not previously associated with IG V gene loci. If the former option is the case, post-CDC mutations could lead to a lesser dependence on antigen dependent BCR signaling and potentially a greater influence of off-target, non-IG genomic mutations. Alternatively, the latter activity could add a new stimulatory survival/growth advantage mediated by the BCR through structurally altered FRs, such as that occurring by superantigen binding and stimulation.
FLASH Radiotherapy: History and Future
Authors: Lin Binwei , Gao Feng , Yang Yiwei , Wu Dai , Zhang Yu , Feng Gang , Dai Tangzhi , Du Xiaobo
Published: May 2021

The biological effects of radiation dose to organs at risk surrounding tumor target volumes are a major dose-limiting constraint in radiotherapy. This can mean that the tumor cannot be completely destroyed, and the efficacy of radiotherapy will be decreased. Thus, ways to reduce damage to healthy tissue has always been a topic of particular interest in radiotherapy research. Modern radiotherapy technologies such as helical tomotherapy (HT), intensity-modulated radiation therapy (IMRT), and proton radiotherapy can reduce radiation damage to healthy tissues. Recent outcomes of animal experiments show that FLASH radiotherapy (FLASH-RT) can reduce radiation-induced damage in healthy tissue without decreasing antitumor effectiveness. The very short radiotherapy time compared to that of conventional dose-rate radiotherapy is another advantage of FLASH-RT. The first human patient received FLASH-RT in Switzerland in 2018. FLASH-RT may become one of the main radiotherapy technologies in clinical applications in the future. We summarize the history of the development of FLASH-RT, its mechanisms, its influence on radiotherapy, and its future.
Differential Impact of TGFB1 Variation by Metastatic Status in Androgen-Deprivation Therapy for Prostate Cancer
Authors: Shiota Masaki , Fujimoto Naohiro , Matsumoto Takashi , Tsukahara Shigehiro , Nagakawa Shohei , Ueda Shohei , Ushijima Miho , Kashiwagi Eiji , Takeuchi Ario , Inokuchi Junichi , Uchiumi Takeshi , Eto Masatoshi
Published: May 2021

Transforming growth factor-β1 (TGF-β1) plays a dual role in cancer, acting as a tumor suppressor in the early stage of cancer development and as a tumor promoter in the later stage of cancer progression in various cancers. In this study, we investigated the association between genetic polymorphisms inTGFB1and clinicopathological characteristics or oncological outcome in prostate cancer cases treated with androgen-deprivation therapy (ADT) according to metastasis status. Japanese male patients with hormone-sensitive prostate cancer treated with ADT from 1993 to 2005 were included in this study. Genomic DNA was obtained from whole blood samples, and genotyping ofTGFB1(rs2241716 and rs4803455) was performed by PCR-based technique. No significant association between genetic polymorphisms inTGFB1(rs2241716 and rs4803455) and clinicopathological parameters or prognosis was observed in patients with non-metastatic disease. In patients with metastatic disease, Gleason score in CT/TT carriers (rs2241716) and CA/AA carriers (rs4803455) was unfavorable compared with CC carriers. In addition, the CT/TT alleles in rs2241716 (hazard ratio, 1.82; 95% confidence interval, 1.12–2.94; P = 0.015) and the CA/AA alleles in rs4803455 (hazard ratio, 1.75; 95% confidence interval, 1.03–2.98; P = 0.040) were associated with a higher risk of progression during ADT compared with the CC allele in patients with metastatic disease.TGFB1genetic variations were associated with adverse characteristics and progression risk in ADT among patients with metastatic disease, but not those with non-metastatic disease, supporting a distinct role of TGF-β signaling between non-metastatic and metastatic prostate cancer.
“Poor Effort” Does Not Account for Reduced Forced Vital Capacity in Asthmatic Children
Authors: Feng Yong , Yang Que , Shang Yunxiao
Published: May 2021

Purpose: Poor forced vital capacity (FVC) effort has been considered to be the main reason for FVC reduction by the ATS/ERS guideline; however, this has rarely been mentioned in previous studies. The present study aims to determine whether reduced FVC in asthmatic children is correlated to poor FVC effort.

Methods: A total of 209 asthmatic children within 5–13 years old were included and divided into reduced FVC (“restricted,” n = 66) and typical obstruction group (“obstructed,” n = 143). Forced expiratory flows before and after bronchodilation were recorded in asthmatic children. The differences in clinical characteristics, spirometric results, FVC effort, and bronchodilator response were compared between two groups. Exhalation time (ET) was divided into effective ET (ETe) and plateau ET (ETp) by the start point of exhalation plateau on the time-volume curve. FVC effort was assessed by ET, ETp, and back extrapolated volume (EV)/FVC (%).

Results: Asthmatic children in the restricted group had significantly higher slow vital capacity (SVC)/FVC (%), higher EV/FVC (%), shorter ET, shorter ETe, and longer ETp, when compared with those with obstructed. In the obstructed group, ET (r = 0.201, P = 0.016) and ETe (r = 0.496, P < 0.001) positively correlated with FVC, and ETp (r = −0.224, P = 0.007) negatively correlated with FVC. In the restricted group, FVC positively correlated with ETe (r = 0.350, P = 0.004) but not ET and ETp. FVC z-score significantly correlated with total IgE (n = 51, r = −0.349, P = 0.012) and with FEF25−75% z-score (n = 66, r = 0.531, P < 0.001) in the restricted group. The further logistic regression revealed that the risk of restricted increased by 1.12 (95% CI, 1.04–1.22, P = 0.005) with every 1% increase in %ΔFVC. In subjects with restricted and bronchodilation tests, %ΔFVC was significantly associated with FeNO (n = 29, r = 0.386, P = 0.039), FEF25−75% z-score (n = 29, r = −0.472, P = 0.010), and SVC/FVC (%) (n = 19, r = 0.477, P = 0.039) but not with EV/FVC (%), ET, ETe, or ETp (P > 0.05).

Conclusion: These findings suggested that “poor FVC effort” does not account for the FVC reduction in asthmatic children. Short ET and high SVC/FVC (%) are characteristics of reduced FVC.
Efficacy of Short Course of Preksha Dhyana for Functional Abdominal Pain Disorder in a Busy Pediatric Clinic
Authors: Mehta Vijay , Mehta Akshay , Patel Samit , Irastorza Laura , Rizvi Syed Ahsan , Abomoelak Bassam , Mehta Naina , Mehta Devendra
Published: May 2021

Introduction: Mind body techniques such as meditation improve symptoms in children and adults with IBS. Typical courses, however, are lengthy and difficult to administer. We report our experience with a short course of Preksha Dhyana (PD), a child-friendly focused meditation with yoga.

Method: Physicians deliver focused meditation while medical assistants taught yoga. Three sessions were administered biweekly with recommendations for daily practice. Pain severity Likert scores were compared with a treatment as usual (TAU) historical control. Anxiety scores were compared from baseline in the PD group.

Results: Thirty PD patients aged 9–17 (20 female) and 52 consecutive TAU group aged 5–17 (33 female) were reviewed. The biweekly sessions had high (71%) completion rates. Utilization rates of PD were similar to TAU despite added sessions. The PD group had an average time of follow-up of 8.9 ± 9.4 vs. 6.0 ± 3.9 months in the TAU group (p = 0.522). Changes in pain scores from baseline showed improvement in the PD group, 0.67 ± 0.13 vs. TAU 1.39 ± 0.11 (p = 0.0003). In the PD group, anxiety scores improved significantly from baseline (0.5 vs. 1, P < 0.001). Pain improved in 93% (28/30) and resolved in 47% (14/30).

Conclusion: A short course of PD was successfully embedded in a busy pediatric office without additional staffing. The approach proved cost-effective without increasing overall healthcare utilization and showed significant benefits over TAU. Pending RCT confirmation, this offers a cost-effective method to incorporate mind–body techniques into a pediatric office practice.
Traditional Chinese Medicine Qingre Huoxue Treatment vs. the Combination of Methotrexate and Hydroxychloroquine for Active Rheumatoid Arthritis: A Multicenter, Double-Blind, Randomized Controlled Trial
Authors: Gong Xun , Liu Wei-Xiang , Tang Xiao-Po , Wang Jian , Liu Jian , Huang Qing-Chun , Liu Wei , Fang Yong-Fei , He Dong-Yi , Liu Ying , Gao Ming-Li , Wu Qing-Jun , Chen Shi , Li Zhen-Bin , Wang Yue , Xie Yan-Ming , Zhang Jun-Li , Zhou Cai-Yun , Ma Li , Wang Xin-Chang , Zhang Chi , Jiang Quan
Published: May 2021

Traditional Chinese medicine (TCM) has been used successfully to treat rheumatoid arthritis (RA). Qingre Huoxue treatment (Qingre Huoxue decoction (QRHXD)/Qingre Huoxue external preparation (QRHXEP)) is a therapeutic scheme of TCM for RA. To date, there have been few studies comparing the efficacy and safety of QRHXD and conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for the treatment of active RA. This was investigated in a multicenter, double-blind, randomized controlled trial involving 468 Chinese patients with active RA [disease activity score (DAS)-28 > 3.2] treated with QRHXD/QRHXEP (TCM group), methotrexate plus hydroxychloroquine [Western medicine (WM) group], or both [integrative medicine (IM) group]. Patients were followed up for 24 weeks. The primary outcome measure was the change in DAS-28 from baseline to 24 weeks. The secondary outcome measures were treatment response rate according to American College of Rheumatology 20, 50, and 70% improvement criteria (ACR-20/50/70) and the rate of treatment-related adverse events (TRAEs). The trial was registered at ClinicalTrials.gov (NCT02551575). DAS-28 decreased in all three groups after treatment (p < 0.0001); the score was lowest in the TCM group (p < 0.05), while no difference was observed between the WM and IM groups (p > 0.05). At week 24, ACR-20 response was 73.04% with TCM, 80.17% with WM, and 73.95% with IM (based on the full analysis set [FAS], p > 0.05); ACR-50 responses were 40.87, 47.93, and 51.26%, respectively, (FAS, p > 0.05); and ACR-70 responses were 20.87, 22.31, and 25.21%, respectively, (FAS, p > 0.05). Thus, treatment efficacy was similar across groups based on ACR criteria. On the other hand, the rate of TRAEs was significantly lower in the TCM group compared to the other groups (p < 0.05). Thus, QRHXD/QRHXEP was effective in alleviating the symptoms of active RA—albeit to a lesser degree than csDMARDs—with fewer side effects. Importantly, combination with QRHXD enhanced the efficacy of csDMARDs. These results provide evidence that QRHXD can be used as an adjunct to csDMARDs for the management of RA, especially in patients who experience TRAEs with standard drugs.

Clinical Trial Registration: ClinicalTrials.gov, identifier NCTNCT025515.
A Flexible Microdevice for Mechanical Cell Stimulation and Compression in Microfluidic Settings
Authors: Onal Sevgi , Alkaisi Maan M. , Nock Volker
Published: May 2021

Evidence continues to emerge that cancer is a disease not only of genetic mutations, but also of altered mechanobiological profiles of the cells and microenvironment. This mutation-independent element might be a key factor in promoting development and spread of cancer. Biomechanical forces regulate tumor microenvironment by solid stress, matrix mechanics, interstitial pressure, and flow. Compressive stress by tumor growth and stromal tissue alters cell deformation and recapitulates the biophysical properties of cells to grow, differentiate, spread, or invade. Such solid stress can be introduced externally to change the cell response and to mechanically induce cell lysis by dynamic compression. In this work, we report a microfluidic cell culture platform with an integrated, actively modulated actuator for the application of compressive forces on cancer cells. Our platform is composed of a control microchannel in a top layer for introducing external force and a polydimethylsiloxane (PDMS) membrane with monolithically integrated actuators. The integrated actuator, herein called micro-piston, was used to apply compression on SKOV-3 ovarian cancer cells in a dynamic and controlled manner by modulating applied gas pressure, localization, shape, and size of the micro-piston. We report fabrication of the platform, characterization of the mechanical actuator experimentally and computationally, and cell loading and culture in the device. We further show the use of the actuator to perform both repeated dynamic cell compression at physiological pressure levels and end point mechanical cell lysis, demonstrating suitability for mechanical stimulation to study the role of compressive forces in cancer microenvironments. Finally, we extend cell compression applications in our device to investigating mechanobiologically related protein and nuclear profiles in cyclically compressed cells.
Melissa officinalis L. as a Nutritional Strategy for Cardioprotection
Authors: Draginic Nevena , Jakovljevic Vladimir , Andjic Marijana , Jeremic Jovana , Srejovic Ivan , Rankovic Marina , Tomovic Marina , Nikolic Turnic Tamara , Svistunov Andrey , Bolevich Sergey , Milosavljevic Isidora
Published: May 2021

This review aimed to provide a summary on the traditional uses, phytochemistry, and pharmacological activities in the cardiovascular system and cardiotoxicity of Melissa officinalis (MO), with the special emphasis on the protective mechanisms in different cardiovascular pathologies. MO is a perennial aromatic herb commonly known as lemon balm, honey balm, or bee balm, which belongs to Lamiaceae family. Active components are mainly located in the leaves or essential oil and include volatile compounds, terpenoid (monoterpenes, sesquiterpenes, triterpenes), and polyphenolic compounds [rosmarinic acid (RA), caffeic acid, protocatechuic acid, quercitrin, rhamnocitrin, luteolin]. For centuries, MO has been traditionally used as a remedy for memory, cognition, anxiety, depression, and heart palpitations. Up until now, several beneficial cardiovascular effects of MO, in the form of extracts (aqueous, alcoholic, and hydroalcoholic), essential oil, and isolated compounds, have been confirmed in preclinical animal studies, such as antiarrhythmogenic, negative chronotropic and dromotropic, hypotensive, vasorelaxant, and infarct size–reducing effects. Nonetheless, MO effects on heart palpitations are the only ones confirmed in human subjects. The main mechanisms proposed for the cardiovascular effects of this plant are antioxidant free radical–scavenging properties of MO polyphenols, amelioration of oxidative stress, anti-inflammatory effects, activation of M2 and antagonism of β1 receptors in the heart, blockage of voltage-dependent Ca2+ channels, stimulation of endothelial nitric oxide synthesis, prevention of fibrotic changes, etc. Additionally, the main active ingredient of MO-RA, per se, has shown substantial cardiovascular effects. Because of the vastness of encouraging data from animal studies, this plant, as well as the main ingredient RA, should be considered and investigated further as a tool for cardioprotection and adjuvant therapy in patients suffering from cardiovascular diseases.
Consequences of Mixotrophy on Cell Energetic Metabolism in Microchloropsis gaditana Revealed by Genetic Engineering and Metabolic Approaches
Authors: Bo Davide Dal , Magneschi Leonardo , Bedhomme Mariette , Billey Elodie , Deragon Etienne , Storti Mattia , Menneteau Mathilde , Richard Christelle , Rak Camille , Lapeyre Morgane , Lembrouk Mehdi , Conte Melissa , Gros Valérie , Tourcier Guillaume , Giustini Cécile , Falconet Denis , Curien Gilles , Allorent Guillaume , Petroutsos Dimitris , Laeuffer Frédéric , Fourage Laurent , Jouhet Juliette , Maréchal Eric , Finazzi Giovanni , Collin Séverine
Published: May 2021

Algae belonging to the Microchloropsis genus are promising organisms for biotech purposes, being able to accumulate large amounts of lipid reserves. These organisms adapt to different trophic conditions, thriving in strict photoautotrophic conditions, as well as in the concomitant presence of light plus reduced external carbon as energy sources (mixotrophy). In this work, we investigated the mixotrophic responses of Microchloropsis gaditana (formerly Nannochloropsis gaditana). Using the Biolog growth test, in which cells are loaded into multiwell plates coated with different organic compounds, we could not find a suitable substrate for Microchloropsis mixotrophy. By contrast, addition of the Lysogeny broth (LB) to the inorganic growth medium had a benefit on growth, enhancing respiratory activity at the expense of photosynthetic performances. To further dissect the role of respiration in Microchloropsis mixotrophy, we focused on the mitochondrial alternative oxidase (AOX), a protein involved in energy management in other algae prospering in mixotrophy. Knocking-out the AOX1 gene by transcription activator-like effector nuclease (TALE-N) led to the loss of capacity to implement growth upon addition of LB supporting the hypothesis that the effect of this medium was related to a provision of reduced carbon. We conclude that mixotrophic growth in Microchloropsis is dominated by respiratory rather than by photosynthetic energetic metabolism and discuss the possible reasons for this behavior in relationship with fatty acid breakdown via β-oxidation in this oleaginous alga.
Improving the Fertigation of Soilless Urban Vertical Agriculture Through the Combination of Struvite and Rhizobia Inoculation in Phaseolus vulgaris
Authors: Arcas-Pilz Verónica , Parada Felipe , Villalba Gara , Rufí-Salis Martí , Rosell-Melé Antoni , Gabarrell Durany Xavier
Published: May 2021

Soilless crop production is a viable way to promote vertical agriculture in urban areas, but it relies extensively on the use of mineral fertilizer. Thus, the benefits of fresher, local food and avoiding the transportation and packaging associated with food import could be counteracted by an increase in nutrient-rich wastewater, which could contribute to freshwater and marine eutrophication. The present study aimed to explore the use of mineral fertilizer substitutes in soilless agriculture. Phaseolus vulgaris (common bean) was fertilized with a combination of slow-releasing fertilizer struvite (a source of N, P, and Mg), which is a byproduct of wastewater treatment plants, and inoculation with Rhizobium (a N2-fixing soil bacteria). The experiment included three bean-production lines: (A) 2 g/plant of struvite and rhizobial inoculation; (B) 5 g/plant of struvite and rhizobial inoculation, both irrigated with a Mg-, P-, and N-free nutrient solution; and (C) a control treatment that consisted of irrigation with a full nutrient solution and no inoculation. Plant growth, development, yields, and nutrient contents were determined at 35, 62, and 84 days after transplanting as well as biological N2 fixation, which was determined using the 15N natural abundance method. Treatments A and B resulted in lower total yields per plant than the control C treatment (e.g., 59.35 ± 26.4 g plant–1 for A, 74.2 ± 23.0 g plant–1 for B, and 147.71 ± 45.3 g plant–1 for C). For A and B, the nodulation and N2 fixation capacities appeared to increase with the amount of initially available struvite, but, over time, deficient levels of Mg were reached as well as nearly deficient levels of P, which could explain the lower yields. Nevertheless, we conclude that the combination of struvite and N2-fixing bacteria covered the N needs of plants throughout the growth cycle. However, further studies are needed to determine the optimal struvite quantities for vertical agriculture systems that can meet the P and Mg requirements throughout the lifetime of the plants.
Relationship Between Proactive Personality and Job Performance of Chinese Nurses: The Mediating Role of Competency and Work Engagement
Authors: Hu Xuehui , Zhao Rong , Gao Jing , Li Jianzhen , Yan Pei , Yan Xiaofei , Shao Shuai , Su Jingkuan , Li Xiaokang
Published: May 2021

Background: As one of the main participants in health care, nurses are esteemed an important driving force for the vigorous health care development. Studies report that nurses’ proactive personality has positive effects on their job performance; however, this relationship acquires further understanding.

Objective: A cross-sectional study was performed to explore the relationship between nurses’ proactive personality and job performance; the mediating role of nurses’ competency and work engagement in this relationship was also evaluated.

Methods: The study was performed in a large third-degree general hospital in October 2019, Xi’an, PR, China. A sample of 246 nurses participated in this cross-sectional study. Proactive personality was assessed with the Proactive Personality Questionnaire (PPS), job performance was assessed by Heilman three-item measurements, nurse competence was estimated with Nurse Competency Scale (NCS), and work engagement was assessed with the Utrecht Work Engagement Scale (UWES). The structural equation model was used to test the main hypotheses.

Results: Structural equation model analysis revealed that work engagement partially mediated the association between proactive personality and job performance. The serial two-mediator model which was used to explore the association between proactive personality and job performance through competency and work engagement, in sequence, was demonstrated.

Conclusion: This study demonstrates that work engagement partially mediated the association between nurses’ proactive personality and their job performance. The serial two-mediator model demonstrated that proactive personality was associated with job performance via competency and work engagement. This study also revealed the critical role of nursing managers in understanding the nurses’ proactive personality, which would facilitate them to enhance the latter’s competency and promote their work engagement. All these will in turn constantly improve the overall quality of nursing and advance professional development of nursing and benefits for patients.
The Influence of Social Support and Ability Perception on Coping Strategies for Competitive Stress in Soccer Players: The Mediating Role of Cognitive Assessment
Authors: Dai Zhao , Liu Qiang , Ma Wenhui , Yang Chengwei
Published: May 2021

Objectives: To explore the effect of social support and ability perception on stress coping strategies for competitive stress, and to reveal the mediating effects of primary and secondary evaluation, so as to further improve the theoretical model of stress coping in soccer players.

Methods: A total of 331 male athletes from 22 teams in the Chengdu Middle School Campus Football League were taken as survey samples, and surveys were conducted on their stress experience, social support, ability perception, cognitive assessment, and coping strategies for competition stress. SPSS 21.0 and AMOS 21.0 statistical analysis software were used. Descriptive statistics, correlation analysis, exploratory factor analysis (EFA), and confirmatory factor analysis (CFA) were used to process the obtained data.

Results: (1) Positive primary assessment acted as a full mediator in the relationship between social support and secondary assessments, and negative primary assessment acted as a partial mediator in the relationship between competence perception and secondary assessments; (2) Secondary assessment played a partial mediating role between positive primary assessment and positive coping strategies, and a full mediating role between negative primary assessment and positive coping strategies; (3) Secondary assessments played the mediator neither between social support and a coping strategy for stress nor competence perception and a coping strategy for stress; (4) Positive primary assessment, positive negative assessment, and secondary assessment all had significant positive benefits for positive coping. Still, the impact of positive primary assessment on positive coping was significantly better than negative primary assessment and secondary assessment.

Conclusion: The coping strategy for the competitive stress model proposed by this study has a very good fit for the causal model. It can be used to explain the observed data from soccer players in middle schools. The primary and secondary assessments play different roles in the model. The combination of problem focuses and emotional focus on the positive stress coping strategy is suitable in the field of competitive sports. Still, the relevant research results need to be further explored and verified in the future.
Prevalence of Risk Factors Associated With Mental Health Symptoms Among the Outpatient Psychiatric Patients and Their Family Members in China During the Coronavirus Disease 2019 Pandemic
Authors: Qiu Yan , Huang Jing , Sun Jinghui , Zhao Jiaxu , Chen Apian , Chen Jindong , Wu Renrong , Li Sujuan , Teng Ziwei , Tan Yuxi , Wang Bolun , Wu Haishan
Published: May 2021

Objective: To investigate the prevalence of and risk factors associated with mental health symptoms in psychiatric outpatients and their family members in China during the COVID-19 pandemic.

Methods: This cross-sectional, survey-based, region-stratified study collected demographic data and mental health measurements for depression, anxiety and acute stress from 269 psychiatric patients and 231 family members in the Second Xiangya Hospital in China from April 27, 2020 to May 8, 2020. Binary logistic regression analysis was performed to identify risk factors associated with mental health outcomes.

Result: The results of this survey revealed that symptoms of depression, anxiety, and acute stress were highly prevalent symptoms in the psychiatric patient group. Respondents who were female, unmarried or highly educated were significantly more likely to have the above symptoms. In the family member group, more than half of them felt that the burden of nursing had increased during the epidemic. Subjects with a high degree of burden of care were significantly more likely to exhibit the above mental health symptoms, while females were significantly more likely to have acute stress.

Conclusions: The results of this survey revealed a high prevalence of mental health disorder symptoms among psychiatric patients and an increased burden of nursing among their family members after the COVID-19 outbreak in China. Understanding the risk factors in those particular groups of people help improve the public health service system for mental health problems during public health events. For further study, exploration of the needs of mental health services and dynamic change tracking will be needed.
“It's Like a Kick in the Teeth”: The Emergence of Novel Predictors of Burnout in Frontline Workers During Covid-19
Authors: Sumner Rachel C. , Kinsella Elaine L.
Published: May 2021

The context of Covid-19 has offered an unusual cultural landscape for examining how workers view their own position relative to others, and how individuals respond to prolonged exposure to workplace stress across different sectors and cultures. Through our recent work tracking the well-being of frontline workers in the UK and Ireland (the CV19 Heroes project), we have uncovered additional psychological factors that have not been accounted for in previous models of occupational stress or burnout. In recent months, frontline workers have worked to protect the community from the threat of SARS-CoV-2 and, simultaneously, have evaluated their perceptions of collective efforts of others as either congruent or incongruent with collective goals (e.g., lowered mortality and morbidity): we call this novel aspect solidarity appraisal. These frontline workers have been hailed as heroes, which we argue has led to the creation of an implicit psychological contract (the hero contract) between frontline workers and the public. Here, the heroes are willing to “go above and beyond” for the greater good, with the expectation that we (the public) do our part by adhering to public health guidelines. Where frontline workers perceive incongruence between the words and actions of others in working toward collective goals this drives negative affect and subsequent burnout. In this perspective article, we evaluate the cultural context of the pandemic in the UK and Ireland and suggest important socio-cultural factors that contribute to perceptions of solidarity, and how this may relate to burnout and worker welfare during and beyond the pandemic context.
The Effect of Vocabulary Depth and Breadth on English Listening Comprehension Can Depend on How Comprehension Is Measured
Authors: Luo Yuzhi , Song Hongwen , Wan Li , Zhang Xiaochu
Published: May 2021

This study examines the relative contribution of vocabulary breadth (VB) and vocabulary depth (VD) to three different listening comprehension measures. One hundred and thirteen English majors were given VB and VD tests, and three listening comprehension tests. Based on three pairs of hierarchical multiple regression analyses, we found that the relative contribution of VB and VD varied across the three listening comprehension tests. Specifically, for the listening test with an expository text dictation to assess integrative skills, both VB and VD made a unique positive contribution to comprehension, but this was greater in the case of depth. For the listening test involving narrative conversations to assess literal comprehension, neither VB nor VD (after controlling for each other) could independently predict comprehension, whereas for the listening test that comprises expository passages to assess inferential comprehension, VD could separately predict comprehension but VB could not. These findings suggest that the relative contribution of VD and VB to listening comprehension may depend on how a listening test is constructed. Therefore, the findings will contribute to listening comprehension and vocabulary knowledge research, and vocabulary teaching and learning.