bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of Carbapenem-Resistant Klebsiella pneumoniae Co-Harboring blaKPC-Carrying Plasmid and pLVPK-Like Virulence Plasmid in Bloodstream Infections
Authors: Du Fang-ling , Huang Qi-sen , Wei Dan-dan , Mei Yan-fang , Long Dan , Liao Wen-jian , Wan La-gen , Liu Yang , Zhang Wei
Published: March 2021

This study aimed to characterize carbapenem-resistant Klebsiella pneumoniae (CR-KP) co-harboring blaKPC-2-carrying plasmid and pLVPK-like virulence plasmid. Between December 2017 and April 2018, 24 CR-KP isolates were recovered from 24 patients with bacteremia. The mortality was 66.7%. Pulsed-field gel electrophoresis and multilocus sequence typing results indicated four clusters, of which cluster A (n = 21, 87.5%) belonged to ST11 and the three remaining isolates (ST412, ST65, ST23) had different pulsotypes (cluster B, C, D). The blaKPC-2-carrying plasmids all belonged to IncFIIK type, and the size ranged from 100 to 390 kb. Nineteen strains (79.2%) had a 219-kb virulence plasmid possessed high similarity to pLVPK from CG43 with serotype K2. Two strains had a 224-kb virulence plasmid resembled plasmid pK2044 from K. pneumoniae NTUH-K2044(ST23). Moreover, three strains carried three different hybrid resistance- and virulence-encoding plasmids. Conjugation assays showed that both blaKPC-2 and rmpA2 genes could be successfully transferred to E. coli J53 in 62.5% of the strains at frequencies of 4.5 × 10−6 to 2.4 × 10−4, of which three co-transferred blaKPC-2 along with rmpA2 in large plasmids. Infection assays in the Galleria mellonella model demonstrated the virulence level of these isolates was found to be consistently higher than that of classic Klebsiella pneumoniae. In conclusion, CR-KP co-harboring blaKPC-2-carrying plasmid and pLVPK-like virulence plasmid were characterized by multi-drug resistance, enhanced virulence, and transferability, and should, therefore, be regarded as a real superbug that could pose a serious threat to public health. Hence, heightened efforts are urgently needed to avoid its co-transmission of the virulent plasmid (gene) and resistant plasmid (gene) in clinical isolates.
Murine Model of Sinusitis Infection for Screening Antimicrobial and Immunomodulatory Therapies
Authors: Alford Morgan A. , Choi Ka-Yee G. , Trimble Michael J. , Masoudi Hamid , Kalsi Pavneet , Pletzer Daniel , Hancock Robert E. W.
Published: March 2021

The very common condition of sinusitis is characterized by persistent inflammation of the nasal cavity, which contributes to chronic rhinosinusitis and morbidity of cystic fibrosis patients. Colonization by opportunistic pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa triggers inflammation that is exacerbated by defects in the innate immune response. Pathophysiological mechanisms underlying initial colonization of the sinuses are not well established. Despite their extensive use, current murine models of acute bacterial rhinosinusitis have not improved the understanding of early disease stages due to analytical limitations. In this study, a model is described that is technically simple, allows non-invasive tracking of bacterial infection, and screening of host-responses to infection and therapies. The model was modified to investigate longer-term infection and disease progression by using a less virulent, epidemic P. aeruginosa cystic fibrosis clinical isolate LESB65. Tracking of luminescent bacteria was possible after intranasal infections, which were sustained for up to 120 h post-infection, without compromising the overall welfare of the host. Production of reactive oxidative species was associated with neutrophil localization to the site of infection in this model. Further, host-defense peptides administered by Respimat® inhaler or intranasal instillation reduced bacterial burden and impacted disease progression as well as cytokine responses associated with rhinosinusitis. Thus, future studies using this model will improve our understanding of rhinosinusitis etiology and early stage pathogenesis, and can be used to screen for the efficacy of emerging therapies pre-clinically.
Harnessing Colon Chip Technology to Identify Commensal Bacteria That Promote Host Tolerance to Infection
Authors: Gazzaniga Francesca S. , Camacho Diogo M. , Wu Meng , Silva Palazzo Matheus F. , Dinis Alexandre L. M. , Grafton Francis N. , Cartwright Mark J. , Super Michael , Kasper Dennis L. , Ingber Donald E.
Published: March 2021

Commensal bacteria within the gut microbiome contribute to development of host tolerance to infection, however, identifying specific microbes responsible for this response is difficult. Here we describe methods for developing microfluidic organ-on-a-chip models of small and large intestine lined with epithelial cells isolated from duodenal, jejunal, ileal, or colon organoids derived from wild type or transgenic mice. To focus on host-microbiome interactions, we carried out studies with the mouse Colon Chip and demonstrated that it can support co-culture with living gut microbiome and enable assessment of effects on epithelial adhesion, tight junctions, barrier function, mucus production, and cytokine release. Moreover, infection of the Colon Chips with the pathogenic bacterium, Salmonella typhimurium, resulted in epithelial detachment, decreased tight junction staining, and increased release of chemokines (CXCL1, CXCL2, and CCL20) that closely mimicked changes previously seen in mice. Symbiosis between microbiome bacteria and the intestinal epithelium was also recapitulated by populating Colon Chips with complex living mouse or human microbiome. By taking advantage of differences in the composition between complex microbiome samples cultured on each chip using 16s sequencing, we were able to identify Enterococcus faecium as a positive contributor to host tolerance, confirming past findings obtained in mouse experiments. Thus, mouse Intestine Chips may represent new experimental in vitro platforms for identifying particular bacterial strains that modulate host response to pathogens, as well as for investigating the cellular and molecular basis of host-microbe interactions.
Vasodilator Myocardial Perfusion Cardiac Magnetic Resonance Imaging Is Superior to Dobutamine Stress Echocardiography in the Detection of Relevant Coronary Artery Stenosis: A Systematic Review and Meta-Analysis on Their Diagnostic Accuracy
Authors: Haberkorn Sebastian M. , Haberkorn Sandra I. , Bönner Florian , Kelm Malte , Hopkin Gareth , Petersen Steffen E.
Published: March 2021

Objectives: Guideline recommendations for patients with either a high or a low risk of obstructive coronary artery disease (CAD) are clear. However, the evidence for initial risk stratification in patients with an intermediate risk of CAD is still unclear, despite the availability of multiple non-invasive assessment strategies. The aim of this study was to synthesize the evidence for this population to provide more informed recommendations.

Background: A meta-analysis was performed to systematically assess the diagnostic accuracy of vasodilator myocardial perfusion cardiovascular magnetic resonance imaging (pCMR) and dobutamine stress echocardiography (DSE) for the detection of relevant CAD. In contrast to previous work, this meta-analysis follows rigorous selection criteria in regards to the risk stratification and a narrowly prespecified definition of their invasive reference tests, resulting in unprecedentedly informative results for this reference group.

Data Collection and Analysis: From the 5,634 studies identified, 1,306 relevant articles were selected after title screening and further abstract screening left 865 studies for full-text review. Of these, 47 studies fulfilled all inclusion criteria resulting in a total sample size of 4,742 patients.

Results: pCMR studies showed a superior sensitivity [0.88 (95% confidence interval (CI): 0.85–0.90) vs. 0.72 (95% CI: 0.61–0.81)], diagnostic odds ratio (DOR) [38 (95% CI: 29–49) vs. 20 (95% CI: 9–46)] and an augmented post-test probability [negative likelihood ratio (LR) of 0.14 (95% CI: 0.12–0.18) vs. 0.31 (95% CI: 0.21, 0.46)] as compared to DSE. Specificity was statistically indifferent [0.84 (95% CI: 0.81–0.87) vs. 0.89 (95% CI: 0.83–0.93)].

Conclusion: The results of this systematic review and meta-analysis suggest that pCMR has a superior diagnostic test accuracy for relevant CAD compared to DSE. In patients with intermediate risk of CAD only pCMR can reliably rule out relevant stenosis. In this risk cohort, pCMR can be offered for initial risk stratification and guidance of further invasive treatment as it also rules in relevant CAD.
School Counselor Preparation to Support Inclusivity, Equity and Access for Students of Color With Disabilities
Authors: Reese Diane M.
Published: March 2021

The effective implementation of comprehensive school counseling services to all students is premised on the ASCA National Model framework themes of leadership, advocacy, collaboration, and systemic change. The school counselor’s role is to support the academic, career and social-emotional development of all students. From a school counselor advocacy and social justice perspective, school counselors engage in practices that will support all students and create opportunities for equal access and success through their leadership and service as collaborators, consultants and change agents. School counselor leadership results in positive changes within the school community. Using the ASCA Model Framework themes, school counselors can integrate these themes to support inclusivity, equity and access for students of color with disabilities, to the general education curriculum. In order to better prepare school counselor trainees to provide culturally appropriate support and services for students of color with disabilities, school counselor education programs must be more intentional in providing graduate-level course work that introduces trainees to best practices in their work with students with disabilities. First, this writer will discuss the ethical imperative for school counselor educators to be intentional in integrating special education curriculum in preparation programs and how school counselor education programs can use the ASCA Model framework themes in preparing school counselor trainees to engage in best practices to encourage, support, and ensure that students of color with disabilities have access and inclusion in the general education settings. Secondly, this writer will also discuss the incorporation of interactive related ASCA theme activities as preparation for school counselor trainees, in a special topics course as well as during practicum and internship and future professional school counselor opportunities.
Exploitation Histories of Pangolins and Endemic Pheasants on Hainan Island, China: Baselines and Shifting Social Norms
Authors: Wang Yifu , Leader-Williams Nigel , Turvey Samuel T.
Published: March 2021

Overexploitation is a critical threat to the survival of many species. The global demand for wildlife products has attracted considerable research attention, but regional species exploitation histories are more rarely investigated. We interviewed 169 villagers living around seven terrestrial nature reserves on Hainan Island, China, with the aim of reconstructing historical patterns of hunting and consumption of local wildlife, including the globally threatened Chinese pangolin (Manis pentadactyla) and Hainan peacock-pheasant (Polyplectron katsumatae), from the mid-20th century onwards. We aimed to better understand the relationship between these past activities and current consumption patterns. Our findings suggest that eating pangolin meat was not a traditional behaviour in Hainan, with past consumption prohibited by local myths about pangolins. In contrast, local consumption of peacock-pheasant meat was a traditional activity. However, later attitudes around hunting pangolins and peacock-pheasants in Hainan were influenced by pro-hunting policies and a state-run wildlife trade from the 1960s to the 1980s. These new social norms still shape the daily lifestyles and perceptions of local people towards wildlife consumption in Hainan today. Due to these specific historical patterns of wildlife consumption, local-adapted interventions such as promoting substitute meat choices and alternative livelihoods might be effective at tackling local habits of consuming wild meat. Our study highlights the importance of understanding the local historical contexts of wildlife use for designing appropriate conservation strategies.
The Impacts of Recolonisation of an Urbanised River by Native and Non-native Species
Authors: Rotherham Ian D.
Published: March 2021

The roles of native and non-native species in the recolonisation of the River Don in South Yorkshire, England, are considered through the lens of environmental history. Notable as one of the most polluted river systems in Western Europe, the Don-Dearne-Rother catchment runs west to east from South Yorkshire and North Derbyshire and drains a significance part of middle England. However, from their origins in the foothills of the high Pennine hills with peat-bogs and heather moorland, the constituent rivers run through upland-fringe farmland and then into the major urban and industrial centres of the region. By the mid-twentieth century the reaches of these watercourses were grossly polluted and physically degraded too. However, from the 1970s onward there began a slow recovery in environmental quality and this has continued to the present day. This paper focuses on the ecological changes in the main urban zones of the River Don catchment and includes the constituent rivers namely the Sheaf, the Porter, the Rother, the Dearne, the Rivelin, and the Loxley. Importantly, though conservationists may be reluctant to accept it, the new ecology which has emerged throughout the catchment is irreparably changed from that of the seventeenth and eighteenth centuries. That landscape itself was already majorly altered from the countryside described in the Domesday account of 1086, and that too was much changed from the Romano-British landscape of a millennium earlier. The landscape is changing and is permanently changed and so too is the ecology that it now supports. In this context, a hybrid or recombinant ecology has been observed to develop through the process of eco-fusion and is made up of an intimate mix of native and non-native species.
Deep Learning Reveals Key Immunosuppression Genes and Distinct Immunotypes in Periodontitis
Authors: Ning Wanchen , Acharya Aneesha , Sun Zhengyang , Ogbuehi Anthony Chukwunonso , Li Cong , Hua Shiting , Ou Qianhua , Zeng Muhui , Liu Xiangqiong , Deng Yupei , Haak Rainer , Ziebolz Dirk , Schmalz Gerhard , Pelekos George , Wang Yang , Hu Xianda
Published: March 2021

Background

Periodontitis is a chronic immuno-inflammatory disease characterized by inflammatory destruction of tooth-supporting tissues. Its pathogenesis involves a dysregulated local host immune response that is ineffective in combating microbial challenges. An integrated investigation of genes involved in mediating immune response suppression in periodontitis, based on multiple studies, can reveal genes pivotal to periodontitis pathogenesis. Here, we aimed to apply a deep learning (DL)-based autoencoder (AE) for predicting immunosuppression genes involved in periodontitis by integrating multiples omics datasets.

Methods

Two periodontitis-related GEO transcriptomic datasets (GSE16134 and GSE10334) and immunosuppression genes identified from DisGeNET and HisgAtlas were included. Immunosuppression genes related to periodontitis in GSE16134 were used as input to build an AE, to identify the top disease-representative immunosuppression gene features. Using K-means clustering and ANOVA, immune subtype labels were assigned to disease samples and a support vector machine (SVM) classifier was constructed. This classifier was applied to a validation set (Immunosuppression genes related to periodontitis in GSE10334) for predicting sample labels, evaluating the accuracy of the AE. In addition, differentially expressed genes (DEGs), signaling pathways, and transcription factors (TFs) involved in immunosuppression and periodontitis were determined with an array of bioinformatics analysis. Shared DEGs common to DEGs differentiating periodontitis from controls and those differentiating the immune subtypes were considered as the key immunosuppression genes in periodontitis.

Results

We produced representative molecular features and identified two immune subtypes in periodontitis using an AE. Two subtypes were also predicted in the validation set with the SVM classifier. Three “master” immunosuppression genes, PECAM1, FCGR3A, and FOS were identified as candidates pivotal to immunosuppressive mechanisms in periodontitis. Six transcription factors, NFKB1, FOS, JUN, HIF1A, STAT5B, and STAT4, were identified as central to the TFs-DEGs interaction network. The two immune subtypes were distinct in terms of their regulating pathways.

Conclusion

This study applied a DL-based AE for the first time to identify immune subtypes of periodontitis and pivotal immunosuppression genes that discriminated periodontitis from the healthy. Key signaling pathways and TF-target DEGs that putatively mediate immune suppression in periodontitis were identified. PECAM1, FCGR3A, and FOS emerged as high-value biomarkers and candidate therapeutic targets for periodontitis.
A Next Generation Formulation of Curcumin Ameliorates Experimentally Induced Osteoarthritis in Rats via Regulation of Inflammatory Mediators
Authors: Yabas Mehmet , Orhan Cemal , Er Besir , Tuzcu Mehmet , Durmus Ali Said , Ozercan Ibrahim Hanifi , Sahin Nurhan , Bhanuse Prakash , Morde Abhijeet Ashok , Padigaru Muralidhara , Sahin Kazim
Published: March 2021

Osteoarthritis (OA) is a chronic and debilitating disease of the knee joint. OA of the knee is initiated by physical damage and accumulated oxidative stress, followed by an exaggerated inflammation leading to cartilage damage. Currently, no effective and safe therapeutic option capable of restoring articular cartilage tissue and joint architecture is available. We here report a novel and highly bioavailable formulation of curcumin, labeled as Next Generation Ultrasol Curcumin (NGUC), which was 64.7 times more bioavailable than natural 95% curcumin extract as demonstrated in rat bioavailability studies. We further investigated the protective effect of NGUC against monosodium iodoacetate (MIA)‐induced knee OA in rats. Analysis of X-ray and histopathological images revealed that NGUC supplementation restored joint architecture and reduced swelling of joints induced by MIA. NGUC treatment caused a significant reduction in the levels of inflammatory mediators such as TNF-α, IL-1β, IL-6, COMP, and CRP, and expressions of MMP-3, 5-LOX, COX-2, and NFκB in synovial tissue of rats with MIA-induced OA. NGUC also decreased serum MDA level and increased the levels of antioxidant enzymes SOD, CAT, and GPX. Thus, our results indicate that a novel formulation of curcumin with enhanced bioavailability effectively ameliorates the pathophysiology of OA.
TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis
Authors: Gagelmann Nico , Wolschke Christine , Klyuchnikov Evgeny , Christopeit Maximilian , Ayuk Francis , Kröger Nicolaus
Published: March 2021

This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; P < 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37–0.61; P < 0.001) and 0.48 (95% CI, 0.36–0.64; P < 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with FLT3-ITD positive AML.
Single-Pulse TMS to the Temporo-Occipital and Dorsolateral Prefrontal Cortex Evokes Lateralized Long Latency EEG Responses at the Stimulation Site
Authors: Jarczok Tomasz A. , Roebruck Friederike , Pokorny Lena , Biermann Lea , Roessner Veit , Klein Christoph , Bender Stephan
Published: March 2021

Introduction

Transcranial magnetic stimulation (TMS)–evoked potentials (TEPs) allow for probing cortical functions in health and pathology. However, there is uncertainty whether long-latency TMS-evoked potentials reflect functioning of the targeted cortical area. It has been suggested that components such as the TMS-evoked N100 are stereotypical and related to nonspecific sensory processes rather than transcranial effects of the changing magnetic field. In contrast, TEPs that vary according to the targeted brain region and are systematically lateralized toward the stimulated hemisphere can be considered to reflect activity in the stimulated brain region resulting from transcranial electromagnetic induction.

Methods

TMS with concurrent 64-channel electroencephalography (EEG) was sequentially performed in homologous areas of both hemispheres. One sample of healthy adults received TMS to the dorsolateral prefrontal cortex; another sample received TMS to the temporo-occipital cortex. We analyzed late negative TEP deflections corresponding to the N100 component in motor cortex stimulation.

Results

TEP topography varied according to the stimulation target site. Long-latency negative TEP deflections were systematically lateralized (higher in ipsilateral compared to contralateral electrodes) in electrodes over the stimulated brain region. A calculation that removes evoked components that are not systematically lateralized relative to the stimulated hemisphere revealed negative maxima located around the respective target sites.

Conclusion

TEPs contain long-latency negative components that are lateralized toward the stimulated hemisphere and have their topographic maxima at the respective stimulation sites. They can be differentiated from co-occurring components that are invariable across different stimulation sites (probably reflecting coactivation of peripheral sensory afferences) according to their spatiotemporal patterns. Lateralized long-latency TEP components located at the stimulation site likely reflect activity evoked in the targeted cortex region by direct transcranial effects and are therefore suitable for assessing cortical functions.
Modular Neurodynamics and Its Classification by Synchronization Cores
Authors: Pasemann Frank
Published: March 2021

It is assumed that the cause of cognitive and behavioral capacities of living systems is to be found in the complex structure-function relationship of their brains; a property that is still difficult to decipher. Based on a neurodynamics approach to embodied cognition this paper introduces a method to guide the development of modular neural systems into the direction of enhanced cognitive abilities. It uses formally the synchronization of subnetworks to split the dynamics of coupled systems into synchronized and asynchronous components. The concept of a synchronization core is introduced to represent a whole family of parameterized neurodynamical systems living in a synchronization manifold. It is used to identify those coupled systems having a rich spectrum of dynamical properties. Special coupling structures—called generative—are identified which allow to make the synchronized dynamics more “complex” than the dynamics of the isolated parts. Furthermore, a criterion for coupling structures is given which, in addition to the synchronized dynamics, allows also for an asynchronous dynamics by destabilizing the synchronization manifold. The large class of synchronization equivalent systems contains networks with very different coupling structures and weights allsharing the same dynamical properties. To demonstrate the method a simple example is discussed in detail.
Postoperative Concurrent Chemoradiotherapy Versus Radiotherapy Alone for Advanced Oral Cavity Cancer in the Era of Modern Radiation Techniques
Authors: Kim Tae Hyung , Cha In-Ho , Choi Eun Chang , Kim Hye Ryun , Kim Hyung Jun , Kim Se-Heon , Keum Ki Chang , Lee Chang Geol
Published: March 2021

Background/Purpose

Surgery followed by postoperative radiotherapy (RT) has been considered the standard treatment for oral cavity squamous cell carcinoma (OCSCC) of advanced stages or with adverse prognostic factors. In this study, we compared the outcomes in patients with OCSCC who received postoperative concurrent chemoradiotherapy (CCRT) or postoperative RT alone using modern RT techniques.

Methods

A total of 275 patients with OCSCC treated between 2002 and 2018 were retrospectively analyzed. Adverse prognostic factor was defined as extranodal extension (ENE), microscopically involved surgical margin, involvement of ≥2 lymph nodes, perineural disease, and/or lymphovascular invasion (LVI). In total, 148 patients (54%) received CCRT and 127 patients (46%) received RT alone. More patients in the CCRT group had N3 disease and stage IVB disease (46.6% vs. 10.2%, p<0.001), ENE (56.1% vs. 15.7%, p<0.001), LVI (28.4% vs. 13.4%, p=0.033).

Results

With a median follow-up of 40 (range, 5–203) months, there were no significant differences in the 5-year overall survival (OS) and PFS between treatment groups. In the subgroup analysis according to high risk, the concurrent use of chemotherapy showed significantly improved OS in patients with ENE (HR 0.39, p=0.003).

Conclusion

Our retrospective study showed that postoperative CCRT group had comparable survival outcomes to those in the RT alone group for advanced OCSCC in the era of modern RT techniques and indicated that concurrent chemotherapy should be administered to patients with ENE. Prospective randomized studies for confirmation are needed.
E3 Ubiquitin Ligase UBR5 Promotes the Metastasis of Pancreatic Cancer via Destabilizing F-Actin Capping Protein CAPZA1
Authors: Li Jin , Zhang Wei , Gao Jian , Du Min , Li Huimin , Li Mengge , Cong Hui , Fang Yuan , Liang Yiyi , Zhao Dan , Xiang Gang , Ma Xiaojing , Yao Ming , Tu Hong , Gan Yu
Published: March 2021

The ubiquitin-proteasome system (UPS) is a regulated mechanism of intracellular protein degradation and turnover, and its dysfunction is associated with various diseases including cancer. UBR5, an E3 ubiquitin ligase, is emerging as an important regulator of the UPS in cancers, but its role in pancreatic cancer is poorly understood. Here, we show that UBR5 is significantly upregulated in pancreatic cancer tissues. High UBR5 expression is correlated with increased lymph node metastasis and poor survival of patients. The loss-of-function and gain-of-function studies demonstrated that UBR5 substantially enhanced the in vitro migratory and invasive ability of pancreatic cancer cells. UBR5 knockdown also markedly inhibited in vivo cancer metastasis in the liver metastatic model of pancreatic cancer in nude mice, suggesting UBR5 as a potent metastatic promoter in pancreatic cancer. Furthermore, using co-immunoprecipitation combined with mass spectrometry analyses, CAPZA1, a member of F-actin capping protein α subunit family, was identified as a novel substrate of UBR5. UBR5 overexpression could promote the degradation of CAPZA1 via the UPS and induce the accumulation of F-actin, which has been described as an essential molecular event during the process of CAPZA1 deficiency-induced cancer cells migration and invasion. UBR5 knockdown significantly increased the intracellular level of CAPZA1 and CAPZA1 downregulation largely reversed the UBR5 knockdown-induced suppression of cell migration and invasion in pancreatic cancer cells. Collectively, our findings unveil UBR5 as a novel and critical regulator of pancreatic cancer metastasis and highlight the potential for UBR5-CAPZA1 axis as a therapeutic target for preventing metastasis in pancreatic cancer patients, especially in those with increased UBR5 expression.
Probiotics in Cancer
Authors: Lu Ke , Dong Shanwu , Wu Xiaoyan , Jin Runming , Chen Hongbo
Published: March 2021

In recent years, the consumption of over-the-counter probiotics to promote health has grown rapidly worldwide and become an independent industry. In medicine, various studies have demonstrated that probiotics can help improve the immune system and intestinal health. They are usually safe, but in some rare cases, they may cause concerning adverse reactions. Although the use of probiotics has been widely popularized in the public, the results of many probiotic clinical trials are contradictory. Particularly in cancer patients, the feasibility of probiotic management providing benefits by targeting cancer and lessening anticancer side effects requires further investigation. This review summarizes the interactions between probiotics and the host as well as current knowledge on the pros and cons of utilizing probiotics in cancer patients.
Metabolic Profile, Bioactivities, and Variations in the Chemical Constituents of Essential Oils of the Ferula Genus (Apiaceae)
Authors: Sonigra Priyankaraj , Meena Mukesh
Published: March 2021

The genusFerulais the third largest and a well-known genus of the Apiaceae family. It is categorized in the Peucedaneae tribe and Ferulinae subtribe of the Apiaceae family. At present, about 180Ferulaspecies have been reported. The genus is mainly distributed throughout central and South-West Asia (especially Iran and Afghanistan), the far-East, North India, and the Mediterranean. The genusFerulais characterized by the presence of oleo-gum-resins (asafoetida, sagapenum, galbanum, and ammoniacum) and their use in natural and conventional pharmaceuticals. The main phytochemicals present in the genusFerulaare as follows: coumarin, coumarin esters, sesquiterpenes, sesquiterpene lactones, monoterpene, monoterpene coumarins, prenylated coumarins, sulfur-containing compounds, phytoestrogen, flavonoids and carbohydrates. This genus is considered to be a valuable group of medicinal plants due to its many different biological and pharmacological uses as volatile oils (essential oils). Numerous biological activities are shown by the chemical components of the essential oils obtained from differentFerulaspecies. Because this genus includes many bioactivities such as antimicrobial, insecticidal, antioxidant, cytotoxic, etc., researchers are now focusing on this genus. Several reviews are already available on this particular genus, including information about the importance and the uses of all the phytochemicals found in the species ofFerula. Despite this, no review that specifically provides information about the biological activities ofFerula-derived essential oils, has been published yet. Therefore, the present review has been conducted to provide important information about the chemical profile, factors affecting the chemical composition, and biological activities of essential oils of theFerulaspecies.
BAY 60-6583 Enhances the Antitumor Function of Chimeric Antigen Receptor-Modified T Cells Independent of the Adenosine A2b Receptor
Authors: Tang Jiaxing , Zou Yan , Li Long , Lu Fengping , Xu Hongtao , Ren Pengxuan , Bai Fang , Niedermann Gabriele , Zhu Xuekai
Published: March 2021

Chimeric antigen receptor (CAR) T cells are powerful in eradicating hematological malignancies, but their efficacy is limited in treating solid tumors. One of the barriers is the immunosuppressive response induced by immunomodulatory signaling pathways. Pharmacological targeting of these immunosuppressive pathways may be a simple way to improve the efficacy of CAR T cells. In this study, anti-CD133 and anti-HER2 CAR T cells were generated from healthy donors, and combination therapy using CAR T cells and small molecules targeting adenosine receptors was performed in vitro and in vivo with the goal of probing for potential synergistic antitumor activities. The adenosine A2b receptor agonist, BAY 60-6583, was found to significantly increase cytokine secretion of CD133-or HER2-specific CAR T cells when co-cultured with the respective target tumor cells. The in vitro cytotoxicity and proliferation of CAR T cells were also enhanced when supplied with BAY 60-6583. Furthermore, the combination with this small molecule facilitated the anti-HER2 CAR T cell-mediated elimination of tumor cells in a xenograft mouse model. However, the enhanced antitumor activities could not be suppressed by knockout of the adenosine A2b receptor in CAR T cells. Furthermore, mass spectrometry and computational methods were used to predict several potential alternative targets. Four potential targets (pyruvate kinase M (PKM), Talin-1, Plastin-2, and lamina-associated polypeptide 2) were captured by a photo-affinity probe, of which PKM and Talin-1 were predicted to interact with BAY 60-6583. Overall, our data suggest that BAY 60-6583 upregulates T cell functions through a mechanism independent of the adenosine A2b receptor.
In vitro Regeneration of Clematis Plants in the Nikita Botanical Garden via Somatic Embryogenesis and Organogenesis
Authors: Mitrofanova Irina , Ivanova Natalia , Kuzmina Tatyana , Mitrofanova Olga , Zubkova Natalya
Published: March 2021

The effects of growth regulators, namely, 6-benzylaminopurine (BAP) and thidiazuron (TDZ), on the morphogenic capacity of 13 cultivars of clematis plants, in terms of their morphological structure formation, shoot regeneration, and somatic embryo development, are presented. The clematis cultivars ‘Alpinist,’ ‘Ay-Nor,’ ‘Bal Tsvetov,’ ‘Crimson Star,’ ‘Crystal Fountain,’ ‘Kosmicheskaya Melodiya,’ ‘Lesnaya Opera,’ ‘Madame Julia Correvon,’ ‘Nevesta,’ ‘Nikitsky Rosovyi,’ ‘Nikolay Rubtsov,’ ‘Serenada Kryma,’ and ‘Vechniy Zov’ were taken in collection plots of the Nikita Botanical Gardens for use in study. After explant sterilization with 70% ethanol (1 min), 0.3–0.4% Cl2 (15 min), and 1% thimerosal (10 min), 1-cm long segments with a single node were introduced to an in vitro culture. The explants were established on the basal MS medium supplemented with BAP (2.20–8.90 μM) and 0.049 μM NAA, or TDZ (3.0; 6.0, and 9.0 μM) with 30 g/L sucrose and 9 g/L agar. The medium with 0.89 μM BAP served as the control. Culture vessels and test tubes with the explants were maintained in plant growth chamber-controlled conditions: with a 16-h photoperiod, under cool-white light fluorescent lamps with a light intensity of 37.5 μmol m–2 s–1, at a temperature of 24 ± 1°C. Histological analysis demonstrated that adventitious bud and somatic embryo formation in studied clematis cultivars occurred at numerous areas of active meristematic cell zones. The main role of plant growth regulators and its concentrations were demonstrated. It was determined that maximum adventitious microshoot regeneration without any morphological abnormalities formed on the media supplemented with BAP or TDZ. 4.40 μM BAP, or 6.0 μM TDZ were optimal cytokinin concentrations for micropropagation. The explants of ‘Alpinist,’ ‘Ay-Nor,’ ‘Crimson Star,’ ‘Crystal Fountain,’ ‘Nevesta,’ and ‘Serenada Kryma’ cultivars displayed high morphogenetic capacity under in vitro culturing. During indirect somatic embryogenesis, light intensity 37.5 μmol m–2 s–1 stimulated a higher-number somatic embryo formation and a temperature of 26°C affected somatic embryo development. Active formation of primary and secondary somatic embryos was also demonstrated. 2.20 μM BAP with 0.09 μM IBA affected the high-number somatic embryo formation for eight cultivars. Secondary somatic embryogenesis by the same concentration of BAP was induced. The frequency of secondary somatic embryogenesis was higher in ‘Crystal Fountain’ (100%), ‘Crimson Star’ (100%), ‘Nevesta’ (97%), and ‘Ay-Nor’ (92%) cultivars. Based on these results, the methodology for direct somatic embryogenesis and organogenesis of studied clematis cultivars has been developed.
Cost-Benefit Analysis of the Upland-Rice Root Architecture in Relation to Phosphate: 3D Simulations Highlight the Importance of S-Type Lateral Roots for Reducing the Pay-Off Time
Authors: Gonzalez Daniel , Postma Johannes , Wissuwa Matthias
Published: March 2021

The rice root system develops a large number of nodal roots from which two types of lateral roots branch out, large L-types and fine S-types, the latter being unique to the species. All roots including S-types are covered by root hairs. To what extent these fine structures contribute to phosphate (P) uptake under P deficiency was investigated using a novel 3-D root growth model that treats root hairs as individual structures with their own Michaelis-Menten uptake kinetics. Model simulations indicated that nodal roots contribute most to P uptake followed by L-type lateral roots and S-type laterals and root hairs. This is due to the much larger root surface area of thicker nodal roots. This thickness, however, also meant that the investment in terms of P needed for producing nodal roots was very large. Simulations relating P costs and time needed to recover that cost through P uptake suggest that producing nodal roots represents a considerable burden to a P-starved plant, with more than 20 times longer pay-off time compared to S-type laterals and root hairs. We estimated that the P cost of these fine root structures is low enough to be recovered within a day of their formation. These results expose a dilemma in terms of optimizing root system architecture to overcome P deficiency: P uptake could be maximized by developing more nodal root tissue, but when P is growth-limiting, adding more nodal root tissue represents an inefficient use of the limiting factor P. In order to improve adaption to P deficiency in rice breeding two complementary strategies seem to exist: (1) decreasing the cost or pay-off time of nodal roots and (2) increase the biomass allocation to S-type roots and root hairs. To what extent genotypic variation exists within the rice gene pool for either strategy should be investigated.
Incremental Validity of Character Strengths as Predictors of Job Performance Beyond General Mental Ability and the Big Five
Authors: Harzer Claudia , Bezuglova Natalia , Weber Marco
Published: March 2021

Over the last decades, various predictors have proven relevant for job performance [e.g., general mental ability (GMA), broad personality traits, such as the Big Five]. However, prediction of job performance is far from perfect, and further potentially relevant predictors need to be investigated. Narrower personality traits, such as individuals' character strengths, have emerged as meaningfully related to different aspects of job performance. However, it is still unclear whether character strengths can explain additional variance in job performance over and above already known powerful predictors. Consequently, the present study aimed at (1) examining the incremental validity of character strengths as predictors of job performance beyond GMA and/or the Big Five traits and (2) identifying the most important predictors of job performance out of the 24 character strengths, GMA, and the Big Five. Job performance was operationalized with multidimensional measures of both productive and counterproductive work behavior. A sample of 169 employees from different occupations completed web-based self-assessments on character strengths, GMA, and the Big Five. Additionally, the employees' supervisors provided web-based ratings of their job performance. Results showed that character strengths incrementally predicted job performance beyond GMA, the Big Five, or GMA plus the Big Five; explained variance increased up to 54.8, 43.1, and 38.4%, respectively, depending on the dimension of job performance. Exploratory relative weight analyses revealed that for each of the dimensions of job performance, at least one character strength explained a numerically higher amount of variance than GMA and the Big Five, except for individual task proactivity, where GMA exhibited the numerically highest amount of explained variance. The present study shows that character strengths are relevant predictors of job performance in addition to GMA and other conceptualizations of personality (i.e., the Big Five). This also highlights the role of socio-emotional skills, such as character strengths, for the understanding of performance outcomes above and beyond cognitive ability.
Four-Year-Old's Online Versus Face-to-Face Word Learning via eBooks
Authors: Escudero Paola , Pino Escobar Gloria , Casey Charlotte G. , Sommer Kristyn
Published: March 2021

Developmental research typically relies on face-to-face testing at laboratories, childcare centers, museums or playgroups. Current social distancing measures have led to a halt in research. Although face-to-face interaction is considered essential for research involving young children, current technology provides viable alternatives. This paper introduces an accessible, replicable and easy to follow method to conduct online developmental research with young children employing a word-learning task as an exemplar, including a detailed workflow and step-by-step guide to using easily accessible programs and platforms. Four-year-old children's (N = 56) performance on a word-learning task delivered online vs. face-to-face is provided as a method validation. Children's performance on the word-learning task was predominantly consistent across delivery modes, with only slight variation in performance between modes. The implications of these similar results across face-to-face and online methods are discussed alongside avenues for further research. Importantly, this paper presents an emerging methodological approach for the online administration of developmental science both within and beyond the COVID-19 pandemic, adding a new tool to current and future developmental scientist's toolkits.
Are Your Muscles or Your Brain Making You Feel Tired After Exercise?
Authors: Zhang Derek , Li Juana , Miller Ryan , Batraka Marina , Effing Sophie Marie Anne , Hossain Fahmida , Bernard Anne-Catherine , Marillier Mathieu , Domnik Nicolle J.
Published: March 2021

Did you know your muscles can feel exhausted without actually being exhausted? It turns out that your brain is just as important as your muscles when it comes to fatigue, or physical tiredness. You can experience “peripheral” fatigue, which is fatigue originating from the muscles, or you can experience central fatigue, which originates from the brain and central nervous system. By studying both the brain and the muscles, scientists can examine which is causing your fatigue. But how? Do we need to perform brain surgery to get answers? Luckily, special techniques involving stimulation of the nerves and muscles can be used instead! In this article, we illustrate how scientists determine if the tiredness you feel after exercising is caused by central or peripheral fatigue or maybe both. We will also explore the differences between the two.
Climate Change Effects on Aquaculture Production: Sustainability Implications, Mitigation, and Adaptations
Authors: Maulu Sahya , Hasimuna Oliver J. , Haambiya Lloyd H. , Monde Concillia , Musuka Confred G. , Makorwa Timothy H. , Munganga Brian P. , Phiri Kanyembo J. , Nsekanabo Jean DaMascene
Published: March 2021

Aquaculture continues to significantly expand its production, making it the fastest-growing food production sector globally. However, the sustainability of the sector is at stake due to the predicted effects of climate change that are not only a future but also a present reality. In this paper, we review the potential effects of climate change on aquaculture production and its implications on the sector's sustainability. Various elements of a changing climate, such as rising temperatures, sea-level rise, diseases and harmful algal blooms, changes in rainfall patterns, the uncertainty of external inputs supplies, changes in sea surface salinity, and severe climatic events have been discussed. Furthermore, several adaptation options have been presented as well as some gaps in existing knowledge that require further investigations. Overall, climate change effects and implications on aquaculture production sustainability are expected to be both negative and positive although, the negative effects outweigh the positive ones. Adapting to the predicted changes in the short-term while taking mitigation measures in the long-term could be the only way toward sustaining the sector's production. However, successful adaptation will depend on the adaptive capacity of the producers in different regions of the world.
Alternative Winemaking Techniques to Improve the Content of Phenolic and Aromatic Compounds in Wines
Authors: Dumitriu (Gabur) Georgiana-Diana , Teodosiu Carmen , Gabur Iulian , Cotea Valeriu V. , Peinado Rafael A. , López de Lerma Nieves
Published: March 2021

In this study, a complete physical–chemical analysis was performed for Fetească neagră wine, aged with oak staves. Red wine samples were taken from grape varieties grown in Northeast Romania and produced during 2013 vintage. At the end of the fermentation process, four oak mini staves (1 cm width × 10 cm length × 1 cm thickness) from heavy toasted French oak were added to 5 L of red wine. Samples were aged using two time periods, respectively at 1.5 and 3 months, in a room at 14–16 °C. Results showed that the initial content of total phenolic decreased during ageing, from 931.1 mg catechin/L at 1.5 months to 775.4 mg catechin/L at 3 months. In contrast, the initial content of total antioxidant activity increased after the same period of ageing to 13.3 mM Trolox as compared to the aged wines for 1.5 months, at 12.8 mM Trolox. The corregram representing the relationship between the total phenols, total antioxidant activity (TAA) and their fractions and CieLab parameters was performed. Thirty-seven minor volatile compounds were quantified by stir bars sorptive extraction and gas chromatography coupled with mass spectrometry (SBSE-GC-MS). An increase in odor activity value (OAV) with ageing time was observed, especially for fruity, fatty and woody series. The oak staves used in ageing processes can contribute positively to the aromatic profile of wines and could be considered a good choice for producing short-aged wines.
Relationship between Plant Roots, Rhizosphere Microorganisms, and Nitrogen and Its Special Focus on Rice
Authors: Xiong Qiangqiang , Hu Jinlong , Wei Haiyan , Zhang Hongcheng , Zhu Jinyan
Published: March 2021

Fertilization is an important practical measure in agricultural production. As an important nutrient element of plants, nitrogen (N) has a significant impact on the plant productivity and microbial function. Rhizosphere microorganisms affect plant growth and development, nitrogen uptake and utilization, and ecological adaptability. The interaction mechanism between plant and rhizosphere microorganisms is one of the hotspots in life science research and the key program of agricultural microorganism utilization. In this article, the relationship among plant root morphology and physiology, rhizosphere microorganisms, and nitrogen is reviewed, summarized, and prospected.