bluuebunny/crossref_metadata_2025 huggingface dataset:
Elucidation of the Host Bronchial Lymph Node miRNA Transcriptome Response to Bovine Respiratory Syncytial Virus
Authors: Johnston Dayle , Earley Bernadette , McCabe Matthew S. , Kim Jaewoo , Taylor Jeremy F. , Lemon Ken , McMenamy Michael , Duffy Catherine , Cosby S. Louise , Waters Sinéad M.
Published: April 2021

Bovine respiratory disease (BRD) causes substantial morbidity and mortality, affecting cattle of all ages. One of the main causes of BRD is an initial inflammatory response to bovine respiratory syncytial virus (BRSV). MicroRNAs are novel and emerging non-coding small RNAs that regulate many biological processes and are implicated in various inflammatory diseases. The objective of the present study was to elucidate the changes in the bovine bronchial lymph node miRNA transcriptome in response to BRSV following an experimental viral challenge. Holstein-Friesian calves were either administered a challenge dose of BRSV (103.5 TCID50/ml × 15 ml) (n = 12) or were mock inoculated with sterile phosphate buffered saline (n = 6). Daily scoring of clinical signs was performed and calves were euthanized at day 7 post-challenge. Bronchial lymph nodes were collected for subsequent RNA extraction and sequencing (75 bp). Read counts for known miRNAs were generated using the miRDeep2 package using the UMD3.1 reference genome and the bovine mature miRNA sequences from the miRBase database (release 22). EdgeR was used for differential expression analysis and Targetscan was used to identify target genes for the differentially expressed (DE) miRNAs. Target genes were examined for enriched pathways and gene ontologies using Ingenuity Pathway Analysis (Qiagen). Multi-dimensional scaling (MDS) based on miRNA gene expression changes, revealed a clearly defined separation between the BRSV challenged and control calves, although the clinical manifestation of disease was only mild. One hundred and nineteen DE miRNAs (P < 0.05, FDR < 0.1, fold change > 1.5) were detected between the BRSV challenged and control calves. The DE miRNAs were predicted to target 465 genes which were previously found to be DE in bronchial lymph node tissue, between these BRSV challenged and control calves. Of the DE predicted target genes, 455 had fold changes that were inverse to the corresponding DE miRNAs. There were eight enriched pathways among the DE predicted target genes with inverse fold changes to their corresponding DE miRNA including: granulocyte and agranulocyte adhesion and diapedesis, interferon signalling and role of pathogen recognition receptors in recognition of bacteria and viruses. Functions predicted to be increased included: T cell response, apoptosis of leukocytes, immune response of cells and stimulation of cells. Pathogen recognition and proliferation of cytotoxic T cells are vital for the recognition of the virus and its subsequent elimination.
The Role of Antibodies Against the Crude Capsular Extract in the Immune Response of Porcine Alveolar Macrophages to In Vitro Infection of Various Serovars of Glaesserella (Haemophilus) parasuis
Authors: Matiašková Katarína , Kavanová Lenka , Kulich Pavel , Gebauer Jan , Nedbalcová Kateřina , Kudláčková Hana , Tesařík Radek , Faldyna Martin
Published: April 2021

In Glässer’s disease outbreaks,Glaesserella (Haemophilus) parasuishas to overcome the non-specific immune system in the lower respiratory tract, the alveolar macrophages. Here we showed that porcine alveolar macrophages (PAMs) were able to recognize and phagocyteG. parasuiswith strain-to-strain variability despite the presence of the capsule in virulent (serovar 1, 5, 12) as well in avirulent strains (serovar 6 and 9). The capsule, outer membrane proteins, virulence-associated autotransporters, cytolethal distending toxins and many other proteins have been identified as virulence factors of this bacterium. Therefore, we immunized pigs with the crude capsular extract (cCE) from the virulentG. parasuisCAPM 6475 strain (serovar 5) and evaluated the role of the anti-cCE/post-vaccinal IgG in the immune response of PAMs toin vitroinfection with variousG. parasuisstrains. We demonstrated the specific binding of the antibodies to the cCE by Western-blotting assay and immunoprecipitation as well as the specific binding to the strain CAPM 6475 in transmission electron microscopy. In the cCE, we identified several virulence-associated proteins that were immunoreactive with IgG isolated from sera of immunized pigs. Opsonization ofG. parasuisstrains by post-vaccinal IgG led to enhanced phagocytosis ofG. parasuisby PAMs at the first two hours of infection. Moreover, opsonization increased the oxidative burst and expression/production of both pro- and anti-inflammatory cytokines. The neutralizing effects of these antibodies on the antioxidant mechanisms ofG. parasuismay lead to attenuation of its virulence and pathogenicityin vivo. Together with opsonization of bacteria by these antibodies, the host may eliminateG. parasuisin the infection site more efficiently. Based on these results, the crude capsular extract is a vaccine candidate with immunogenic properties.
Zika Virus Infection of Human Iris Pigment Epithelial Cells
Authors: Ryan Feargal J. , Carr Jillian M. , Furtado João M. , Ma Yuefang , Ashander Liam M. , Simões Milena , Oliver Genevieve F. , Granado G. Bracho , Dawson Abby C. , Michael Michael Z. , Appukuttan Binoy , Lynn David J. , Smith Justine R.
Published: April 2021

During recent Zika epidemics, adults infected with Zika virus (ZIKV) have developed organ-specific inflammatory complications. The most serious Zika-associated inflammatory eye disease is uveitis, which is commonly anterior in type, affecting both eyes and responding to corticosteroid eye drops. Mechanisms of Zika-associated anterior uveitis are unknown, but ZIKV has been identified in the aqueous humor of affected individuals. The iris pigment epithelium is a target cell population in viral anterior uveitis, and it acts to maintain immune privilege within the anterior eye. Interactions between ZIKV and human iris pigment epithelial cells were investigated with infectivity assays and RNA-sequencing. Primary cell isolates were prepared from eyes of 20 cadaveric donors, and infected for 24 hours with PRVABC59 strain ZIKV or incubated uninfected as control. Cytoimmunofluorescence, RT-qPCR on total cellular RNA, and focus-forming assays of culture supernatant showed cell isolates were permissive to infection, and supported replication and release of infectious ZIKV. To explore molecular responses of cell isolates to ZIKV infection at the whole transcriptome level, RNA was sequenced on the Illumina NextSeq 500 platform, and results were aligned to the human GRCh38 genome. Multidimensional scaling showed clear separation between transcriptomes of infected and uninfected cell isolates. Differential expression analysis indicated a vigorous molecular response of the cell to ZIKV: 7,935 genes were differentially expressed between ZIKV-infected and uninfected cells (FDR < 0.05), and 99% of 613 genes that changed at least two-fold were up-regulated. Reactome and KEGG pathway and Gene Ontology enrichment analyses indicated strong activation of viral recognition and defense, in addition to biosynthesis processes. A CHAT network included 6275 molecular nodes and 24 contextual hubs in the cell response to ZIKV infection. Receptor-interacting serine/threonine kinase 1 (RIPK1) was the most significantly connected contextual hub. Correlation of gene expression with read counts assigned to the ZIKV genome identified a negative correlation between interferon signaling and viral load across isolates. This work represents the first investigation of mechanisms of Zika-associated anterior uveitis using an in vitro human cell model. The results suggest the iris pigment epithelium mounts a molecular response that limits intraocular pathology in most individuals.
Humanized Mouse Models for the Advancement of Innate Lymphoid Cell-Based Cancer Immunotherapies
Authors: Horowitz Nina B. , Mohammad Imran , Moreno-Nieves Uriel Y. , Koliesnik Ievgen , Tran Quan , Sunwoo John B.
Published: April 2021

Innate lymphoid cells (ILCs) are a branch of the immune system that consists of diverse circulating and tissue-resident cells, which carry out functions including homeostasis and antitumor immunity. The development and behavior of human natural killer (NK) cells and other ILCs in the context of cancer is still incompletely understood. Since NK cells and Group 1 and 2 ILCs are known to be important for mediating antitumor immune responses, a clearer understanding of these processes is critical for improving cancer treatments and understanding tumor immunology as a whole. Unfortunately, there are some major differences in ILC differentiation and effector function pathways between humans and mice. To this end, mice bearing patient-derived xenografts or human cell line-derived tumors alongside human genes or human immune cells represent an excellent tool for studying these pathways in vivo. Recent advancements in humanized mice enable unparalleled insights into complex tumor-ILC interactions. In this review, we discuss ILC behavior in the context of cancer, the humanized mouse models that are most commonly employed in cancer research and their optimization for studying ILCs, current approaches to manipulating human ILCs for antitumor activity, and the relative utility of various mouse models for the development and assessment of these ILC-related immunotherapies.
Chimerism, the Microenvironment and Control of Leukemia
Authors: Deeg H. Joachim
Published: April 2021

Transplantation of allogeneic hematopoietic cells faces two barriers: failure of engraftment due to a host versus graft reaction, and the attack of donor cells against the patient, the graft versus host (GVH) reaction. This reaction may lead to GVH disease (GVHD), but in patients transplanted due to leukemia or other malignant disorders, this may also convey the benefit of a graft versus leukemia (GVL) effect. The interplay of transplant conditioning with donor and host cells and the environment in the patient is complex. The microbiome, particularly in the intestinal tract, profoundly affects these interactions, directly and via soluble mediators, which also reach other host organs. The microenvironment is further altered by the modifying effect of malignant cells on marrow niches, favoring the propagation of the malignant cells. The development of stable mixed donor/host chimerism has the potential of GVHD prevention without necessarily increasing the risk of relapse. There has been remarkable progress with novel conditioning regimens and selective T-cell manipulation aimed at securing engraftment while preventing GVHD without ablating the GVL effect. Interventions to alter the microenvironment and change the composition of the microbiome and its metabolic products may modify graft/host interactions, thereby further reducing GVHD, while enhancing the GVL effect. The result should be improved transplant outcome.
The Fate of Activated Group 2 Innate Lymphoid Cells
Authors: Mathä Laura , Martinez-Gonzalez Itziar , Steer Catherine A. , Takei Fumio
Published: April 2021

Group 2 innate lymphoid cells (ILC2s) reside in both mucosal and non-mucosal tissues and play critical roles in the first line of defense against parasites and irritants such as allergens. Upon activation by cytokines released from epithelial and stromal cells during tissue damage or stimulation, ILC2s produce copious amounts of IL-5 and IL-13, leading to type 2 inflammation. Over the past 10 years, ILC2 involvement in a variety of human diseases has been unveiled. However, questions remain as to the fate of ILC2s after activation and how that might impact their role in chronic inflammatory diseases such as asthma and fibrosis. Here, we review studies that have revealed novel properties of post-activation ILC2s including the generation of immunological memory, exhausted-like phenotype, transdifferentiation and activation-induced migration.
Downscaling With an Unstructured Coastal-Ocean Model to the Goro Lagoon and the Po River Delta Branches
Authors: Maicu Francesco , Alessandri Jacopo , Pinardi Nadia , Verri Giorgia , Umgiesser Georg , Lovo Stefano , Turolla Saverio , Paccagnella Tiziana , Valentini Andrea
Published: April 2021

The Goro Lagoon Finite Element Model (GOLFEM) presented in this paper concentrates on the high-resolution downscaled model of the Goro Lagoon, along with five Po river branches and the coastal area of the Po delta in the northern Adriatic Sea (Italy) where crucial socio-economic activities take place. GOLFEM was validated by means of validation scores (bias – BIAS, root mean square error – RMSE, and mean absolute error – MAE) for the water level, current velocity, salinity and temperature measured at several fixed stations in the lagoon. The range of scores at the stations are: for temperature between −0.8 to +1.2°C, for salinity from −0.2 to 5 PSU, for sea level 0.1 m. The lagoon is dominated by an estuarine vertical circulation due to a double opening at the lagoon mouth and sustained by multiple sources of freshwater inputs. The non-linear interactions among the tidal forcing, the wind and the freshwater inputs affect the lagoon circulation at both seasonal and daily time scales. The sensitivity of the circulation to the forcings was analyzed with several sensitivity experiments done with the exclusion of the tidal forcing and different configurations of the river connections. GOLFEM was designed to resolve the lagoon dynamics at high resolution in order to evaluate the potential effects on the clam farming of two proposed scenarios of human intervention on the morphology of the connection with the sea. We calculated the changes of the lagoon current speed and salinity, and using opportune fitness indexes related to the clams physiology, we quantified analytically the effects of the interventions in terms of extension and persistence of areas of the clams optimal growth. The results demonstrate that the correct management of this kind of fragile environment relies on both long-term (intervention scenarios) and short-term (coastal flooding forecasts and potential anoxic conditions) modeling, based on a flexible tool that is able to consider all the recorded human interventions on the river connections. This study also demonstrates the importance of designing a seamless chain of models that are capable of integrating local effects into the coarser operational oceanographic models.
Ultrasound-Guided Synovial Biopsy: A Review
Authors: Saraiva Fernando
Published: April 2021

Ultrasound-guided synovial biopsy is a safe, well-tolerated, and effective method to collect good-quality synovial tissue from all types of joints for clinical and research purposes. Although synovial biopsy cannot be used to distinguish between types of inflammatory rheumatic disease, analysis of synovial tissue has led to remarkable advances in the understanding of the pathobiology of rheumatoid arthritis and other inflammatory rheumatic diseases. Synovitis is the hallmark of these diseases; hence, accessing the core of the pathological process, synovial tissue, provides an opportunity to gather information with potential diagnostic and prognostic utility.
MD Simulations on a Well-Built Docking Model Reveal Fine Mechanical Stability and Force-Dependent Dissociation of Mac-1/GPIbα Complex
Authors: Jiang Xiaoyan , Sun Xiaoxi , Lin Jiangguo , Ling Yingchen , Fang Ying , Wu Jianhua
Published: April 2021

Interaction of leukocyte integrin macrophage-1 antigen (Mac-1) to platelet glycoprotein Ibα (GPIbα) is critical for platelet–leukocyte crosstalk in hemostasis and inflammatory responses to vessel injuries under hemodynamic environments. The mechano-regulation and its molecular basis for binding of Mac-1 to GPIbα remain unclear, mainly coming from the lack of crystal structure of the Mac-1/GPIbα complex. We herein built a Mac-1/GPIbα complex model through a novel computer strategy, which included a flexible molecular docking and system equilibrium followed by a “force-ramp + snapback” molecular dynamics (MD) simulation. With this model, a series of “ramp-clamp” steered molecular dynamics (SMD) simulations were performed to examine the GPIbα–Mac-1 interaction under various loads. The results demonstrated that the complex was mechano-stable for both the high rupture force (>250 pN) at a pulling velocity of 3 Å/ns and the conformational conservation under various constant tensile forces (≤75 pN); a catch-slip bond transition was predicted through the dissociation probability, examined with single molecular AFM measurements, reflected by the interaction energy and the interface H-bond number, and related to the force-induced allostery of the complex; besides the mutation-identified residues D222 and R218, the residues were also dominant in the binding of Mac-1 to GPIbα. This study recommended a valid computer strategy for building a likely wild-type docking model of a complex, provided a novel insight into the mechanical regulation mechanism and its molecular basis for the interaction of Mac-1 with GPIbα, and would be helpful for understanding the platelet–leukocyte interaction in hemostasis and inflammatory responses under mechano-microenvironments.
Long Non-coding RNA DLEU2L Targets miR-210-3p to Suppress Gemcitabine Resistance in Pancreatic Cancer Cells via BRCA2 Regulation
Authors: Xu Fei , Wu Heshui , Xiong Jiongxin , Peng Tao
Published: April 2021

Gemcitabine (GEM) resistance remains a challenging clinical issue to overcome in chemotherapy against pancreatic cancer. We previously demonstrated that miR-210 derived from pancreatic cancer stem cells enhanced the GEM-resistant properties of pancreatic cancer cells, thus identifying miR-210 as an oncogenic miRNA. Herein, we report the existence of an upstream effector that acts as a competing endogenous RNA (ceRNA) to miR-210. Bioinformatic screening was performed to identify lncRNAs with a binding relationship to miR-210. Overexpression and interference vectors were constructed to demonstrate the effect of ceRNA activity in pancreatic cell behavior, both in vitro and in vivo. DLEU2L (deleted in lymphocytic leukemia 2-like), which is expressed at low levels in pancreatic cancer tissues, was shown to exhibit a binding relationship with miR-210-3p. Overexpression of DLEU2L and silencing of miR-210-3p suppressed the proliferation, migration, and invasion of pancreatic cancer cells while promoting apoptosis. These effects occurred via the inhibition of the Warburg effect (aerobic glycolysis) and AKT/mTOR signaling. In addition, we showed that BRCA2 is a target gene of miR-210-3p, and the downregulation of miR-210-3p by DLEU2L effectively induced an upregulation of BRCA2 via the ceRNA mechanism. In vivo, DLEU2L overexpression and miR-210-3p interference suppressed pancreatic tumor progression, consistent with the results of in vitro studies. The findings of our study establish DLEU2L as a ceRNA to miR-210-3p and reveal the critical role of the DLEU2L/miR-210-3p crosstalk in targeting GEM resistance.
Asymmetric Influence of Vocalic Context on Mandarin Sibilants: Evidence From ERP Studies
Authors: Meng Yaxuan , Kotzor Sandra , Xu Chenzi , S. Z. Wynne Hilary , Lahiri Aditi
Published: April 2021

In the present study, we examine the interactive effect of vowels on Mandarin fricative sibilants using a passive oddball paradigm to determine whether theHEIGHTfeatures of vowels can spread on the surface and influence preceding consonants with unspecified features. The stimuli are two pairs of Mandarin words ([sa] ∼ [ʂa] and [su] ∼ [ʂu]) contrasting in vowelHEIGHT([LOW] vs. [HIGH]). Each word in the same pair was presented both as standard and deviant, resulting in four conditions (/standard/[deviant]: /sa/[ʂa]∼ /ʂa/[sa]and /su/[ʂu]∼ /ʂu/[su]). In line with the Featurally Underspecified Lexicon (FUL) model, asymmetric patterns of processing were found in the [su] ∼ [ʂu] word pair where both the MMN (mismatch negativity) and LDN (late discriminative negativity) components were more negative in /su/[ʂu](mismatch) than in /ʂu/[su](no mismatch), suggesting the spreading of the feature [HIGH] from the vowel [u] to [ʂ] on the surface. In the [sa] ∼ [ʂa] pair, however, symmetric negativities (for both MMN and LDN) were observed as there is no conflict between the surface feature [LOW] from [a] to [ʂ] and the underlying specified feature [LOW] of [s]. These results confirm that not all features are fully specified in the mental lexicon: features of vowels can spread on the surface and influence surrounding unspecified segments.
Blinking Networks of Memristor Oscillatory Circuits in the Flux-Charge Domain
Authors: Lanza Valentina , Secco Jacopo , Corinto Fernando
Published: April 2021

Multistability phenomena and complex nonlinear dynamics in memristor oscillators pave the way to obtain efficient solutions to optimization problems by means of novel computational architectures based on the interconnection of single–device oscillators. It is well-known that topological properties of interconnections permit to control synchronization and spatio–temporal patterns in oscillatory networks. When the interconnections can change in time with a given probability to connect two oscillators, the whole network acts as a complex network with blinking couplings. The work of has shown that a particular class of blinking complex networks are able to completely synchronize in a faster fashion with respect to other coupling strategies. This work focuses on the specific class of blinking complex networks made of Memristor–based Oscillatory Circuits (MOCs). By exploiting the recent Flux–Charge Analysis Method, we make clear that synchronization phenomena in blinking networks of memristor oscillators having stochastic couplings, i.e., Blinking Memristor Oscillatory Networks (BMONs), correspond to global periodic oscillations on invariant manifolds and the effect of a blinking link is to shift the nonlinear dynamics through the infinite (invariant) manifolds. Numerical simulations performed on MOCs prove that synchronization phenomena can be controlled just by changing the coupling amongst them.
DDX19A Promotes Metastasis of Cervical Squamous Cell Carcinoma by Inducing NOX1-Mediated ROS Production
Authors: Jiang Yanhui , Wang Baibin , Li Yongliang , Shen Jiahui , Wei Yutao , Li Hanjie , Chen Shangqiu , Yang Hua , Zeng Famin , Liu Changqing , Wang Feng , He Huanhuan , Chen Yong , Liu Jihong
Published: April 2021

The major obstacle to treat cervical squamous cell carcinoma (CSCC) is the high prevalence of metastasis, which severely affects 5-year survival rate and quality of life for cancer patients. The DEAD-box helicase family has been reported to be a critical mediator in the development and metastasis of various cancers. DEAD-box helicase 19A (DDX19A) is a member of the DEAD-box helicase family; however, its functional role in CSCC is unclear. In this study, bioinformatics analysis of clinical samples from public databases demonstrated that the expression of DDX19A was elevated in CSCC tissues and that high expression of DDX19A was positively correlated with metastasis and poor clinical outcome. Functionally, we found that DDX19A promoted CSCC cell migration and invasion in vitro and lung metastasis in vivo. Mechanistically, overexpression of DDX19A increased NADPH oxidase 1 (NOX1) expression, enhanced reactive oxygen species (ROS) production, and induced the migration and invasion of CSCC cells. Rescue experiments revealed that DDX19A-induced CSCC functional alterations were dependent on NOX1 and that DDX19A-promoted CSCC metastasis was abrogated upon the inhibition of ROS. Our results demonstrated that DDX19A could promote CSCC metastasis by inducing NOX1-mediated ROS production and that blockage of the NOX1/ROS axis might serve as a potential therapeutic target for patients with DDX19A-overexpressed CSCC.
Co-Occurring Alteration of NOTCH and DDR Pathways Serves as Novel Predictor to Efficacious Immunotherapy in NSCLC
Authors: Zhang Zhimin , Gu Yanyan , Su Xiaona , Bai Jing , Guan Wei , Ma Jungang , Luo Jia , He Juan , Zhang Bicheng , Geng Mingying , Xia Xuefeng , Guan Yanfang , Shen Cheng , Chen Chuan
Published: April 2021

Although immune checkpoint inhibitors (ICIs) have shown remarkable benefit for treatment of advanced non-small lung cancer (NSCLC), only a minority of patients can achieve durable responses and the most patients produce an ultra-rapid progressive disease. Here, we collected the availably published datasets and mined the determinants of response to immunotherapy on pathway levels. One hundred six NSCLC patients treated with immunotherapy were combined from Rizvi et al. and Hellman et al. studies (whole exon sequencing). Two independent validation datasets consisted of the MSKCC cohort (targeted sequencing) and data by Anagnostou and colleagues (whole exon sequencing). The Cancer Genome Atlas (TCGA) somatic mutation and gene expression data were applied to explore the immunobiology features. In the first combined cohort, we detected NOTCH pathway altered in 71% patients with durable clinical benefit (DCB) while only 36% among no durable benefit (NDB) (p = 0.005). Compared to NDB group, co-occurrence of NOTCH and at least two DDR (co-DDR) pathway was discovered in DCB group and contributed to a prolonged progression-free survival (PFS) [22.1 vs 3.6 months, p < 0.0001, HR, 0.34, 95% confidence interval (CI), 0.2–0.59]. In two independent datasets, co-occurrence of NOTCH+/co-DDR+ was also validated to be a better immunotherapy efficacy [Cohort 2: 13 vs 6 months, p = 0.034, HR, 0.55, 95% CI, 0.31–0.96; Cohort 3: 21 vs 11 months, p = 0.067, HR, 0.45, 95% CI, 0.18–1.1]. By analyzing TCGA cohort, we found patients with coexisting NOTCH+/co-DDR+ pathway had a higher TMB, more infiltration of CD4+T cells. Overall, co-occurrence of NOTCH and co-DDR pathway reflect a better immunotherapy efficacy in advanced NSCLC. This genomic predictor show promise in stratifying patients that suit for immunotherapy for future clinical practice.
An Effective Workflow for Differentiating the Same Genus Herbs of Chrysanthemum morifolium Flower and Chrysanthemum Indicum Flower
Authors: He Jiao , Zhang Qian , Ma Cuiying , Giancaspro Gabriel I. , Bi Kaishun , Li Qing
Published: April 2021

C. morifolium flower and C. indicum flower are two closely related herbal species with similar morphological and microscopic characteristics but are discriminated in edible and medicinal purpose. However, there is no effective approach to distinguish the two herbs. A novel workflow for quickly differentiating C. morifolium flower and C. indicum flower was developed. Firstly, the difference in anti-inflammatory effects for C. morifolium flower and C. indicum flower was characterized using lipopolysaccharide-treated rats. Then HPLC fingerprint analysis for 53 batches of C. morifolium flowers and 33 batches of C. indicum flower was carried out to deep profile the chemical components. The preliminary markers were screened out by OPLS-DA, identified by HPLC-ESI-QTOF-MS, and quantified by the improved SSDMC (single reference standard to determine multiple compounds) approach. Finally, multiple statistical data mining was performed to confirm the markers and a binary logistic regression equation was built to differentiate C. morifolium flower and C. indicum flower successfully. In general, the established workflow was rapid, effective and highly feasible, which would provide a powerful tool for herb identification.
Prevalence of Chemotherapy-Induced Peripheral Neuropathy in Multiple Myeloma Patients and its Impact on Quality of Life: A Single Center Cross-Sectional Study
Authors: Selvy Marie , Kerckhove Nicolas , Pereira Bruno , Barreau Fantine , Nguyen Daniel , Busserolles Jérôme , Giraudet Fabrice , Cabrespine Aurélie , Chaleteix Carine , Soubrier Martin , Bay Jacques-Olivier , Lemal Richard , Balayssac David
Published: April 2021

Bortezomib is a pivotal drug for the management of multiple myeloma. However, bortezomib is a neurotoxic anticancer drug responsible for chemotherapy-induced peripheral neuropathy (CIPN). CIPN is associated with psychological distress and a decrease of health-related quality of life (HRQoL), but little is known regarding bortezomib-related CIPN. This single center, cross-sectional study assessed the prevalence and severity of sensory/motor CIPN, neuropathic pain and ongoing pain medications, anxiety, depression, and HRQoL, in multiple myeloma patients after the end of bortezomib treatment. Paper questionnaires were sent to patients to record the scores of sensory and motor CIPNs (QLQ-CIPN20), neuropathic pain (visual analogue scale and DN4 interview), anxiety and depression (HADS), the scores of HRQoL (QLQ-C30 and QLQ-MY20) and ongoing pain medications. Oncological data were recorded using chemotherapy prescription software and patient medical records. The prevalence of sensory CIPN was 26.9% (95% CI 16.7; 39.1) among the 67 patients analyzed and for a mean time of 2.9 ± 2.8 years since the last bortezomib administration. The proportion of sensory CIPN was higher among patients treated by intravenous and subcutaneous routes than intravenous or subcutaneous routes (p = 0.003). QLQ-CIPN20 motor scores were higher for patients with a sensory CIPN than those without (p < 0.001) and were correlated with the duration of treatment and the cumulative dose of bortezomib (coefficient: 0.31 and 0.24, p = 0.01 and 0.0475, respectively), but not sensory scores. Neuropathic pain was screened in 44.4% of patients with sensory CIPN and 66.7% of them had ongoing pain medications, but none were treated with duloxetine (recommended drug). Multivariable analysis revealed that thalidomide treatment (odds-ratio: 6.7, 95% CI 1.3; 35.5, p = 0.03) and both routes of bortezomib administration (odds-ratio: 13.4, 95% CI 1.3; 139.1, p = 0.03) were associated with sensory CIPN. Sensory and motor CIPNs were associated with anxiety, depression, and deterioration of HRQoL. Sensory CIPN was identified in a quarter of patients after bortezomib treatment and associated with psychological distress that was far from being treated optimally. There is a need to improve the management of patients with CIPN, which may include better training of oncologists regarding its diagnosis and pharmacological treatment.
Bibliometric Analysis of Global Research Trends on Ultrasound Microbubble: A Quickly Developing Field
Authors: Wu Haiyang , Tong Linjian , Wang Yulin , Yan Hua , Sun Zhiming
Published: April 2021

Background: Microbubbles are widely used as highly effective contrast agents to improve the diagnostic capability of ultrasound imaging. Mounting evidence suggests that ultrasound coupled with microbubbles has promising therapeutic applications in cancer, cardiovascular, and neurological disorders by acting as gene or drug carriers. The aim of this study was to identify the scientific output and activity related to ultrasound microbubble through bibliometric approaches.

Methods: The literature related to ultrasound microbubble published between 1998 and 2019 was identified and selected from the Science Citation Index Expanded of Web of Science Core Collection on February 21, 2021. The Scopus database was also searched to validate the results and provided as supplementary material. Quantitative variables including number of publications and citations, H-index, and journal citation reports were analyzed by using Microsoft Excel 2019 and GraphPad Prism 8.0 software. VOS viewer and CiteSpace V were used to perform coauthorship, citation, co-citation, and co-occurrence analysis for countries/regions, institutions, authors, and keywords.

Results: A total of 6088 publications from the WoSCC were included. The United States has made the largest contribution in this field, with the majority of publications (2090, 34.3%), citations (90,741, 46.6%), the highest H-index (138), and close collaborations with China and Canada. The most contributive institution was the University of Toronto. Professors De Jong N and Dayton P A have made great achievements in this field. However, the research cooperation between institutions and authors was relatively weak. All the studies could be divided into four clusters: “ultrasound diagnosis study,” “microbubbles’ characteristics study,” “gene therapy study,” and “drug delivery study.” The average appearing years (AAY) of keywords in the cluster “drug delivery study” was more recent than other clusters. For promising hot spots, “doxorubicin” showed a relatively latest AAY of 2015.49, followed by “nanoparticles” and “breast cancer.”

Conclusion: There has been an increasing amount of scientific output on ultrasound microbubble according to the global trends, and the United States is staying ahead in this field. Collaboration between research teams still needs to be strengthened. The focus gradually shifts from “ultrasound diagnosis study” to “drug delivery study.” It is recommended to pay attention to the latest hot spots, such as “doxorubicin,” “nanoparticles,” and “breast cancer.”
Association of 5-Hydroxytryptamine 3 Receptor Antagonists With the Prognosis of Liver Failure
Authors: Chen Yuting , Sun Jingkang , Fan Xiude , Wang Xiaoyun , Zeng Lu , Zhang Xiaoge , Zhang Kun , Li Na , Han Qunying , Liu Zhengwen
Published: April 2021

Liver failure is a severe clinical syndrome with high mortality. 5-Hydroxytryptamine 3 receptor antagonists (5-HT3RAs) can reduce liver damage in animal models. We investigated whether 5-HT3RAs may improve the prognosis of liver failure. We analyzed the 28 and 90 days mortality of liver failure patients in relation to the use of 5-HT3RAs using data from a tertiary hospital in northwest China. According to the use of 5-HT3RAs, 419 patients with liver failure (46 acute, 93 sub-acute, 44 chronic, 236 acute on chronic) were divided into 5-HT3RA group (n = 105) and control group (n = 314). 5-HT3RAs were associated with decreased 28 days (HR 0.18, 95% CI 0.10-0.34, p < 0.001) and 90 days (HR 0.21, 95% CI 0.13-0.33, p < 0.001) mortality. After propensity score matching (PSM) (n = 67 in each group), 5-HT3RAs were still significantly associated with reduced 28 days (HR 0.10, 95%CI 0.04-0.26, p < 0.001) and 90 days (HR 0.16, 95%CI 0.08-0.31, p < 0.001) mortality. 5-HT3RA group patients had significantly higher 28 and 90 days survivals than controls both before and after PSM (all p < 0.001). This study shows that 5-HT3RAs are associated with increased survival of liver failure patients and thus may be used to treat liver failure if the findings are confirmed by additional studies.
Application of Antibody Fragments Against Aβ With Emphasis on Combined Application With Nanoparticles in Alzheimer’s Disease
Authors: Sun Zhi-Ting , Ma Chi , Li Guang-Jian , Zheng Xiang-Yu , Hao Yi-Tong , Yang Yu , Wang Xu
Published: April 2021

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases and accumulating evidences suggest a key role of amyloid-β (Aβ) peptide in the pathogenesis of AD. According to the amyloid cascade hypothesis, the imbalance of producing and clearing Aβ is the beginning of neurodegeneration and dementia. Consequently, immunotherapy becomes popular through using antibodies against Aβ. However, many studies of monoclonal antibodies were stopped because adverse effects appeared or there were no evident benefits observed. Some antibody fragments have many advantages over monoclonal antibodies, such as small sizes, lack of the crystallizable fraction (Fc) and so on. There are three main antibody fragments, including single chain variable fragments (scFvs), Fab fragments and single-domain antibody fragments. Nanoparticles can facilitate the entry of drug molecules across the blood-brain barrier, making them become excellent carriers. Various kinds of nanoparticles have been applied in the treatment of AD. The combination of nanoparticles and antibody fragments against amyloid-β can be used in the diagnosis and treatment of Alzheimer’s disease. In this review, we summarize the progress of antibody fragments against amyloid-β in AD, focusing on the combined application with nanoparticles in the diagnosis and treatment of AD.
On the Time Transition Between Short- and Long-Time Regimes of Colloidal Particles in External Periodic Potentials
Authors: Pérez-Guerrero Daniela , Arauz-Lara José Luis , Sarmiento-Gómez Erick , Guerrero-García Guillermo Iván
Published: April 2021

The dynamics of colloidal particles at infinite dilution, under the influence of periodic external potentials, is studied hereviaexperiments and numerical simulations for two representative potentials. From the experimental side, we analyzed the motion of a colloidal tracer in a one-dimensional array of fringes produced by the interference of two coherent laser beams, providing in this way an harmonic potential. The numerical analysis has been performedviaBrownian dynamics (BD) simulations. The BD simulations correctly reproduced the experimental position- and time-dependent density of probability of the colloidal tracer in the short-times regime. The long-time diffusion coefficient has been obtained from the corresponding numerical mean square displacement (MSD). Similarly, a simulation of a random walker in a one dimensional array of adjacent cages with a probability of escaping from one cage to the next cage is one of the most simple models of a periodic potential, displaying two diffusive regimes separated by a dynamical caging period. The main result of this study is the observation that, in both potentials, it is seen that the critical timet*, defined as the specific time at which a change of curvature in the MSD is observed, remains approximately constant as a function of the height barrierU0of the harmonic potential or the associated escape probability of the random walker. In order to understand this behavior, histograms of the first passage time of the tracer have been calculated for several height barriersU0or escape probabilities. These histograms display a maximum at the most likely first passage timet′, which is approximately independent of the height barrierU0, or the associated escape probability, and it is located very close to the critical timet*. This behavior suggests that the critical timet*, defining the crossover between short- and long-time regimes, can be identified as the most likely first passage timet′as a first approximation.
A Transgenic Mouse Model of Eccentric Left Ventricular Hypertrophy With Preserved Ejection Fraction Exhibits Alterations in the Autophagy-Lysosomal Pathway
Authors: Wenzel Kristin , Krämer Elisabeth , Geertz Birgit , Carrier Lucie , Felix Stephan B. , Könemann Stephanie , Schlossarek Saskia
Published: April 2021

The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are the main proteolytic systems involved in cellular homeostasis. Since cardiomyocytes, as terminally differentiated cells, lack the ability to share damaged proteins with their daughter cells, they are especially reliant on these protein degradation systems for their proper function. Alterations of the UPS and ALP have been reported in a wide range of cardiac diseases, including cardiomyopathies. In this study, we determined whether the UPS and ALP are altered in a mouse model of eccentric left ventricular (LV) hypertrophy expressing both cyclin T1 and Gαq under the control of the cardiac-specific α-myosin heavy chain promoter (double transgenic; DTG). Compared to wild-type (WT) littermates, DTG mice showed higher end-diastolic (ED) LV wall thicknesses and diameter with preserved ejection fraction (EF). The cardiomyopathic phenotype was further confirmed by an upregulation of the fetal gene program and genes associated with fibrosis as well as a downregulation of genes involved in Ca2+ handling. Likewise, higher NT-proBNP levels were detected in DTG mice. Investigation of the UPS showed elevated steady-state levels of (poly)ubiquitinated proteins without alterations of all proteasomal activities in DTG mice. Evaluation of ALP key marker revealed a mixed pattern with higher protein levels of microtubule-associated protein 1 light chain 3 beta (LC3)-I and lysosomal-associated membrane protein-2, lower protein levels of beclin-1 and FYVE and coiled-coil domain-containing protein 1 (FYCO1) and unchanged protein levels of p62/SQSTM1 in DTG mice when compared to WT. At transcriptional level, a > 1.2-fold expression was observed for Erbb2, Hdac6, Lamp2, Nrg1, and Sqstm1, while a < 0.8-fold expression was revealed for Fyco1 in DTG mice. The results related to the ALP suggested overall a repression of the ALP during the initiation process, but an induction of the ALP at the level of autophagosome-lysosome fusion and the delivery of ubiquitinated cargo to the ALP for degradation.
High-Resolution Measurement of Local Activation Time Differences From Bipolar Electrogram Amplitude
Authors: Gaeta Stephen , Bahnson Tristram D. , Henriquez Craig
Published: April 2021

Localized changes in myocardial conduction velocity (CV) are pro-arrhythmic, but high-resolution mapping of local CV is not yet possible during clinical electrophysiology procedures. This is in part because measurement of local CV at small spatial scales (1 mm) requires accurate annotation of local activation time (LAT) differences with very high temporal resolution (≤1 ms), beyond that of standard clinical methods. We sought to develop a method for high-resolution measurement of LAT differences and validate against existing techniques. First, we use a simplified theoretical model to identify a quantitative relationship between the LAT difference of a pair of electrodes and the peak amplitude of the bipolar EGM measured between them. This allows LAT differences to be calculated from bipolar EGM peak amplitude, by a novel “Determination of EGM Latencies by Transformation of Amplitude” (DELTA) method. Next, we use simulated EGMs from a computational model to validate this method. With 1 kHz sampling, LAT differences less than 4 ms were more accurately measured with DELTA than by standard LAT annotation (mean error 3.8% vs. 22.9%). In a 1-dimensional and a 2-dimension model, CV calculations were more accurate using LAT differences found by the DELTA method than by standard LAT annotation (by unipolar dV/dt timing). DELTA-derived LAT differences were more accurate than standard LAT annotation in simulated complex fractionated EGMs from a model incorporating fibrosis. Finally, we validated the DELTA method in vivo using 18,740 bipolar EGMs recorded from the left atrium of 10 atrial fibrillation patients undergoing catheter ablation. Using clinical EGMs, there was agreement in LAT differences found by DELTA, standard LAT annotation, and unipolar waveform cross-correlation. These results demonstrate an underlying relationship between a bipolar EGM’s peak amplitude and the activation time difference between its two electrodes. Our computational modeling and clinical results suggest this relationship can be leveraged clinically to improve measurement accuracy for small LAT differences, which may improve CV measurement at small spatial scales.
Microenvironment Influences Odontogenic Mesenchymal Stem Cells Mediated Dental Pulp Regeneration
Authors: Huang Xiaoyao , Li Zihan , Liu Anqi , Liu Xuemei , Guo Hao , Wu Meiling , Yang Xiaoxue , Han Bing , Xuan Kun
Published: April 2021

Dental pulp as a source of nutrition for the whole tooth is vulnerable to trauma and bacterial invasion, which causes irreversible pulpitis and pulp necrosis. Dental pulp regeneration is a valuable method of restoring the viability of the dental pulp and even the whole tooth. Odontogenic mesenchymal stem cells (MSCs) residing in the dental pulp environment have been widely used in dental pulp regeneration because of their immense potential to regenerate pulp-like tissue. Furthermore, the regenerative abilities of odontogenic MSCs are easily affected by the microenvironment in which they reside. The natural environment of the dental pulp has been proven to be capable of regulating odontogenic MSC homeostasis, proliferation, and differentiation. Therefore, various approaches have been applied to mimic the natural dental pulp environment to optimize the efficacy of pulp regeneration. In addition, odontogenic MSC aggregates/spheroids similar to the natural dental pulp environment have been shown to regenerate well-organized dental pulp both in preclinical and clinical trials. In this review, we summarize recent progress in odontogenic MSC-mediated pulp regeneration and focus on the effect of the microenvironment surrounding odontogenic MSCs in the achievement of dental pulp regeneration.
Beneficial Relationships Between Endophytic Bacteria and Medicinal Plants
Authors: Wu Wei , Chen Wenhua , Liu Shiyu , Wu Jianjun , Zhu Yeting , Qin Luping , Zhu Bo
Published: April 2021

Plants benefit extensively from endophytic bacteria, which live in host plant tissues exerting no harmful effects. Bacterial endophytes promote the growth of host plants and enhance their resistance toward various pathogens and environmental stresses. They can also regulate the synthesis of secondary metabolites with significant medicinal properties and produce various biological effects. This review summarizes recent studies on the relationships between bacterial endophytes and medicinal plants. Endophytic bacteria have numerous applications in agriculture, medicine, and other industries: improving plant growth, promoting resistance toward both biotic and abiotic stresses, and producing metabolites with medicinal potential. Their distribution and population structure are affected by their host plant’s genetic characteristics and health and by the ecology of the surrounding environment. Understanding bacterial endophytes can help us use them more effectively and apply them to medicinal plants to improve yield and quality.
Coronavirus Awareness and Mental Health: Clinical Symptoms and Attitudes Toward Seeking Professional Psychological Help
Authors: Landa-Blanco Miguel , Landa-Blanco Ana , Mejía-Suazo Claudio J. , Martínez-Martínez Carlos A.
Published: April 2021

The current study analyzed the relationship between Coronavirus (COVID-19) Awareness, mental health, and willingness to seek professional psychological help. This was made through a quantitative approach, using online questionnaires to collect data from 855 subjects. The questionnaires included the Brief Symptom Inventory (BSI-53) to measure mental health indicators, the Attitudes Toward Seeking Professional Psychological Help Scale–Short Form, and the Coronavirus Awareness Scale-10 (CAS-10). An Exploratory Factor Analysis suggests that three factors underlie the CAS-10: Coronavirus Concern, Exaggerated Perception, and Immunity Perception. Results indicate a significant positive correlation between Coronavirus Concern and both general anxiety and phobic anxiety symptoms. Immunity Perception is positively related to paranoid ideation and psychotic symptoms. A Mediation Analysis determined that Coronavirus Concern has a significant positive direct effect on Openness to Seeking Psychological Treatment (OSPT), while Exaggerated Perception and Immunity Perception scores have significant direct negative effects on the Value and Need in Seeking Treatment (VNST) scores. Indirectly, the relationship between Coronavirus Concern and OPST is significantly mediated by anxiety symptoms. Similar results were found for the VNST subscale. There is a negative significant effect of Immunity Perception over OSPT mediated by Paranoid Ideation. However, the overall model only achieved small r2 coefficients for the OSPT (0.060) and VNST (0.095) scores. Comparisons in Coronavirus Awareness between sex, age, and the presence of children and older adults at home were also made. These results are discussed regarding their practical implications for mental health providers and policymakers.