bluuebunny/crossref_metadata_2025 huggingface dataset:
An Experimental Study on Effusion Film Cooling Performance of Sand Dune-Inspired Hole Under Swirling Flow Condition
Authors:   School of Mechanical Engineering, Shanghai Jiao Tong University, Zhao Shengwei , Zhang Xu ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Wang Kechen ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Zhou* Wenwu ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Peng Di ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Liu Yingzheng ,   School of Mechanical Engineering, Shanghai Jiao Tong University
Published: March 2023

Effusion film cooling is an essential technology applied to protect the aero-engine combustion chambers. In this study, a sand dune-inspired effusion cooling configuration under swirling flow was studied and compared with cylinder effusion cooling plate. The adiabatic film cooling effectiveness was measured by applying PSP (Pressure Sensitive Paint) technique and the flow field in the midplane was obtained by using PIV (Particle Image Velocimetry) technique. Four cases were studied for each configuration: when the pressure drop of the slot coolant was 3%, the pressure drop of the plate was set to 1%, 2% and 3% separately, and when the slot coolant was turned off, the pressure drop of the plate was set to 3%. With the slot on, the film effectiveness of the dune-inspired design increases about 20% in the upstream zone (x/D < 24) and 90% in the downstream zone (x/D > 24) compared to the circular hole. If the slot coolant is off, the film cooling effectiveness increases about 140% in both upstream and downstream zone. Based on the PIV results, the dune shells prevent the jets lifting-off thus the coolant film is better attached to the cooled wall.
The Influence of the Slot on The Effusion Cooling Performance with the Simulated Swirling Flow
Authors:   School of Mechanical Engineering, Shanghai Jiao Tong University, Jiang Jian , Shao Hongyi ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Wang Kechen ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Zhou* Wenwu ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Peng Di ,   School of Mechanical Engineering, Shanghai Jiao Tong University, Liu Yingzheng ,   School of Mechanical Engineering, Shanghai Jiao Tong University
Published: March 2023

An experimental study was conducted to investigate the influence of the slot jet on the cooling performance of a slot-effusion combined cooling scheme with a simulated swirling flow of the lean-burn combustor. PIV (particle image velocimetry) results show the slot jet reshapes the large-scale vortex structure and changes the lift-up effect of effusion jets. PSP (pressure-sensitive paint) results show there is still a region lacking the coverage of the slot coolant with an active slot, and here adiabatic cooling effectiveness ηad decreases downstream of holes. This phenomenon is enhanced by the lower effusion pressure drop. Consequently, the laterally averaged ηad shows an increase of 27% in the downstream of effusion plate when ΔP= 3%. While for ΔP=1% and 2%, the introduction of slot jet leads to an unchanged or slightly declined laterally averaged ηad in the region of 40<x / D<60. Moreover, the slot jet inhibits the lift-up effect of effusion jets when ΔP=3% resulting in a maximum rise of 180.0% for the area-averaged ηad. PIV and PSP results indicate the importance of the match for the pressure drops of the slot jet ΔW and effusion jetsΔP. From the present study, the same pressure drop (3%) for slot and effusion jet shows better cooling performance.
Isotropic and Anisotropic Mesh Adaptation for Rans Simulations of a Nacelle Under Crosswind Conditions
Authors:   Safran Tech, Digital Sciences & Technologies, Papadogiannis Dimitrios , Billon Laure ,   Safran Tech, Digital Sciences & Technologies, Alauzet Frédéric ,   Inria Saclay Ile-de-France
Published: March 2023

Mesh adaptation of unstructured meshes for aerodynamic simulations, that typically resolve the Reynolds Averaged Navier-Stokes (RANS) equations, is a promising approach to enable high numerical precision on complex geometries. Its objective is to minimize the discretization error without using empirical meshing guidelines. The most common approach of mesh adaptation is the “feature-based” isotropic mesh adaptation: from an initial flow prediction on an isotropic unstructured mesh, a local error estimator is computed using a flow variable. It is then used to adapt the mesh using isotropic tetras. Additional near-wall resolution can be achieved by extracting prism layers from the walls. A more efficient approach is to use anisotropic mesh adaptation purely with tetras that are stretched to follow the flow’s preferential directions. In this work, we demonstrate the abilities of feature-based isotropic and anisotropic mesh adaptation on a complex flow phenomenon of importance for jet engines: flow separation in a nacelle under crosswind conditions. Two different solvers, adapted for either isotropic or anisotropic meshes, are employed. Results are compared with standard unstructured simulations with user-imposed mesh refinements and highlight the ability of mesh adaptation to automatically capture all the relevant flow phenomena without any user input and at reduced cell counts.
An innovative prediction strategy for the compressor fouling effects during an airline mission
Authors:   University of Ferrara, Friso Riccardo , Suman Alessio ,   University of Ferrara, Zanini Nicola ,   University of Ferrara, Pinelli Michele ,   University of Ferrara
Published: March 2023

Solid particles ingestion is one of the main causes of performance degradation in gas turbine engine compressors. Particles that enter the engine can stick to the internal surfaces and then form deposits. These, in turn, involve a variation of blade surface roughness and geometry and then performance deterioration. In this work, a strategy for predicting the effects of compressor fouling on the engine performance during a complete airline mission is proposed. The mission analysis has been conducted by discretizing the altitude profile, then locally performing a force balance on a reference aircraft. Particles deposition is accounted for by modifying the compressor maps by means of appropriate degradation coefficients. Finally, engine performance has been computed by using an in-house 0D gas-path code. A predicted fuel consumption profile along the mission has been proposed to evaluate the effects of compressor fouling. In particular, a rise in this quantity in time has been encountered. The presented approach enables the prediction of the fouling effects on gas turbine engines, and then optimize their maintenance scheduling.
Cellular cartography: Towards an atlas of the neuronal microtubule cytoskeleton
Authors: Iwanski Malina K. , Kapitein Lukas C.
Published: March 2023

Microtubules, one of the major components of the cytoskeleton, play a crucial role during many aspects of neuronal development and function, such as neuronal polarization and axon outgrowth. Consequently, the microtubule cytoskeleton has been implicated in many neurodevelopmental and neurodegenerative disorders. The polar nature of microtubules is quintessential for their function, allowing them to serve as tracks for long-distance, directed intracellular transport by kinesin and dynein motors. Most of these motors move exclusively towards either the plus- or minus-end of a microtubule and some have been shown to have a preference for either dynamic or stable microtubules, those bearing a particular post-translational modification or those decorated by a specific microtubule-associated protein. Thus, it becomes important to consider the interplay of these features and their combinatorial effects on transport, as well as how different types of microtubules are organized in the cell. Here, we discuss microtubule subsets in terms of tubulin isotypes, tubulin post-translational modifications, microtubule-associated proteins, microtubule stability or dynamicity, and microtubule orientation. We highlight techniques used to study these features of the microtubule cytoskeleton and, using the information from these studies, try to define the composition, role, and organization of some of these subsets in neurons.
Efficacy of chlorin dioxide wipes in disinfecting airway devices contaminated with Covid-19
Authors: Albaharna Hussain , Almubiereek Hassan , Almualim Mohammed , Bukhamsin Rehab , Abdelfattah Ahmed , Buohliqah Lamia
Published: March 2023

Background

Reprocessing and disinfecting endoscopes is a routine practice in otolaryngology. An effective, safe, and rapid disinfection technique is essential during the COVID-19 pandemic

Objective

To validate the efficacy of chlorine dioxide wipes in disinfecting three types of airway endoscopes contaminated with COVID-19-positive patient secretions.

Methods

Chlorine dioxide wipes were tested on rigid nasal endoscopes, laryngoscope blades, and flexible bronchoscopes. The endoscopes were disinfected using the wipes after exposure to COVID-19-positive patients. The tested scope was included in the study if the post procedure pre disinfection swab was positive for COVID-19 virus using RT-PCR. We analyzed 38 samples for 19 subjects (scopes) pre and post disinfection with chlorine dioxide wipes from July 2021 to February 2022.

Results

A total of four rigid endoscopes, four flexible bronchoscopes, and four laryngoscopes were included in the study which represent 24 pre and post disinfection swabs. The others were excluded because of negative pre disinfection swab. All the post disinfection PCR swab results were negative.

Conclusion

Chlorine dioxide is a convenient, fast, and effective disinfection technique for COVID-19-contaminated airway endoscopes.
Evaluating the moderating role of information seeking platforms on university students' risk perception and anxiety during the COVID-19 pandemic in Ghana
Authors: Hagan John Elvis , Quansah Frank , Ankomah Francis , Agormedah Edmond Kwesi , Srem-Sai Medina , Schack Thomas
Published: March 2023

Introduction

The emergence of COVID-19 resulted in heightened usage of online information seeking platforms among students aimed at obtaining information about the virus. This situation further increased the levels of risk perception and anxiety levels as students managed to stay safe. This study examined the roles of information seeking platforms; specifically, social media platforms and professional platforms as moderators of the link between risk perception and anxiety among university students in Ghana.

Methods

Participants were recruited from two universities in Ghana; namely, University of Education, Winneba (UEW) and University of Cape Coast (UCC) through a survey approach. The study conveniently sampled 778 participants who completed a set of questionnaires.

Results

The study results revealed that COVID-19 risk perception was positively related to anxiety. Further, the use of specific online information platforms significantly moderated the link between risk perception and anxiety. Specifically, social media platforms significantly moderated the relationship between COVID-19 risk perception and anxiety level. Primarily, students who utilized social media as a COVID-19 information source reported high anxiety levels in the presence of high-risk perception compared to those who did not use social media. Additionally, professional platform usage acted as a buffer in the positive link between COVID-19 risk perception and anxiety levels. In the presence of high risk perception, students who used professional platforms, compared to those who did not use professional platforms, showed significantly low anxiety levels.

Conclusions

The findings suggest the key role social media and professional platforms played in shaping students' perceptions of COVID-19. These outcomes call for the swift scrutiny of health-related information obtained from social media platforms. Both users and disseminators of health-related information on social media platforms have the responsibility of verifying the credibility of whichever information they post and/or access. Risk perception should also be an integral part of effective risk communication planning in educational institutions during outbreak of diseases.
Mapping the helix model of innovation influence on education: A bibliometric review
Authors: Zakaria Haziman , Kamarudin Diyana , Fauzi Muhammad Ashraf , Wider Walton
Published: March 2023

As a direct result of the increased significance of knowledge in the various endeavours attempting to implement the triple helix model, higher education institutions have assumed a more prominent position in the processes involved in regional innovation and development. Expanding study on the helix model is currently examining the underlying causes and consequences of the evolution of the helix model in education. This research examines the relationship between the triple helix model and education by using bibliometric analysis on 227 articles subjected to peer review between 1970 and 2022. This investigation concentrated on three aspects of analysis: (1) document citationviathe use of co-citation analysis that produce 4 clusters; (2) document cited reference through the utilisation of bibliographic coupling that generates 5 clusters; and (3) document keyword through the utilisation of co-word analysis with 4 clusters. These results are essential for academics, practitioners, and other interested parties working to improve the helix model for policymakers by putting it into an education strategy.
Extracellular vesicles rejuvenate the microenvironmental modulating function of recipient tissue-specific mesenchymal stem cells in osteopenia treatment
Authors: Sonoda Soichiro , Yamaza Takayoshi
Published: March 2023

Systemic transplantation of mesenchymal stem cells (MSCs), such as bone marrow MSCs (BMMSCs) and stem cells from human exfoliated deciduous teeth (SHED), is considered a prominent treatment for osteopenia. However, the mechanism of action of the transplanted MSCs has been poorly elucidated. In the recipient target tissue, including bone and bone marrow, only a few donor MSCs can be detected, suggesting that the direct contribution of donor MSCs may not be expected for osteopenia treatment. Meanwhile, secretomes, especially contents within extracellular vesicles (EVs) released from donor MSCs (MSC-EVs), play key roles in the treatment of several diseases. In this context, administrated donor MSC-EVs may affect bone-forming function of recipient cells. In this review, we discuss how MSC-EVs contribute to bone recovery recipient tissue in osteopenia. We also summarize a novel mechanism of action of systemic administration of SHED-derived EVs (SHED-EVs) in osteopenia. We found that reduced telomerase activity in recipient BMMSCs caused the deficiency of microenvironmental modulating function, including bone and bone marrow-like niche formation and immunomodulation in estrogen-deficient osteopenia model mice. Systemic administration of SHED-EVs could exert therapeutic effects on bone reduction via recovering the telomerase activity, leading to the rejuvenation of the microenvironmental modulating function in recipient BMMSCs, as seen in systemic transplantation of SHED. RNase-preconditioned donor SHED-EVs diminished the therapeutic benefits of administrated SHED-EVs in the recipient osteopenia model mice. These facts suggest that MSC-EV therapy targets the recipient BMMSCs to rejuvenate the microenvironmental modulating function via telomerase activity, recovering bone density. We then introduce future challenges to develop the reproducible MSC-EV therapy in osteopenia.
A systematic review of social equity in FEWS analyses
Authors: Stone Tiffanie F. , Dickey Loulou C. , Summers Haleigh , Thompson Janette R. , Rehmann Chris R. , Zimmerman Emily , Tyndall John
Published: March 2023

Integrating social equity considerations into analyses of the food-energy-water systems nexus (FEWS) could improve understanding of how to meet increasing resource demands without impacting social vulnerabilities. Effective integration requires a robust definition of equity and an enhanced understanding of reliable FEWS analysis methods. By exploring how equity has been incorporated into FEWS research in the United States and countries with similar national development, this systematic literature review builds a knowledge base to address a critical research need. Our objectives were to 1) catalog analysis methods and metrics relevant to assessing FEWS equity at varying scales; 2) characterize current studies and interpret shared themes; and 3) identify opportunities for future research and the advancement of equitable FEWS governance. FEWS equity definitions and metrics were categorized by respective system (food, energy, water, overall nexus) and common governance scales (local, regional, national, global). Two central issues were climate change, which increases FEWS risks for vulnerable populations, and sustainable development, which offers a promising framework for integrating equity and FEWS in policy-making contexts. Social equity in FEWS was integrated into studies through affordability, access, and sociocultural elements. This framework could support researchers and practitioners to include equity in FEWS analysis tools based on study scale, purpose, and resource availability. Research gaps identified during the review included a lack of studies effectively integrating all three systems, a need for publicly available datasets, omission of issues related to energy conversion facilities, and opportunities for integration of environmental justice modalities into FEWS research. This paper synthesized how social equity has previously been incorporated into FEWS and outlines pathways for further consideration of equity within nexus studies. Our findings suggested that continued exploration of connections between FEWS, equity, and policy development across scales could reduce social risks and vulnerabilities associated with these systems.
Research on network capacity, absorptive capacity and service innovation performance of technology business incubators—based on PLS-SEM and fsQCA methods
Authors: Dong Hao , Murong Ruiyi , Li Jian
Published: March 2023

Introduction: In the new economic normal, technology incubators are an important support to achieve the growth of strategic emerging enterprises. On the basis of resource based theory, organizational learning theory, inter-organizational relationship theory, and network capability theory, this study constructs a theoretical framework and hypotheses of the impact of network capability within the “resource-capability-relationship” perspective, absorptive capacity on service innovation performance of technology business incubators.

Methods: This study uses 234 Chinese incubators in the incubator network as samples and applies partial least squares structural equation modeling (PLS-SEM) and fuzzy-set qualitative comparative analysis (fsQCA) to explore the questions mentioned above.

Results: The results verify the relationship between network capacity, absorptive capacity, and service innovation performance. Furthermore, the results yield four paths that lead to high service innovation performance, such as “network capability orientation” and “high absorption orientation”, which are different combinations of network capacity and absorptive capacity.

Discussion: The research results are important for improving the innovation performance of technology incubator services and ensuring the stable and effective operation of incubated enterprises.
Clinical and genetic analysis in Chinese families with synpolydactyly, and cellular localization of HOXD13 with different length of polyalanine tract
Authors: Chen Xiumin , Zhao Feiyue , Xu Yiming , Cao Yixuan , Li Shan , Zhang Xue , Zhao Xiuli
Published: March 2023

Synpolydactyly (SPD) is caused by mutations in the transcription factor gene HOXD13. Such mutations include polyalanine expansion (PAE), but further study is required for the phenotypic spectrum characteristics of HOXD13 PAE. We investigated four unrelated Chinese families with significant limb malformations. Three PAEs were found in the HOXD13 polyalanine coding region: c.172_192dup (p.Ala58_Ala64dup) in Family 1, c.169_192dup (p.Ala57_Ala64dup) in Family 2, and c.183_210dup (p.Ala62_Ala70dup) in Family 3 and Family 4. Interestingly, we identified a new manifestation of preaxial polydactyly in both hands in a pediatric patient with an expansion of seven alanines, a phenotype not previously noted in SPD patients. Comparing with the wild-type cells and mutant cells with polyalanine contractions (PACs), the HOXD13 protein with a PAE of nine-alanine or more was difficult to enter the nucleus, and easy to form inclusion bodies in the cytoplasm, and with the increase of PAE, the more inclusion bodies were formed. This study not only expanded the phenotypic spectrum of SPD, but also enriched our understanding of its pathogenic mechanisms.
Case Report: The compound heterozygotes variants in FLT4 causes autosomal recessive hereditary lymphedema in a Chinese family
Authors: Xiang Qinqin , Chen Jing , Xiao Xiao , Xu Bocheng , Xie Hanbing , Wang He , Yang Mei , Liu Shanling
Published: March 2023

Background: Lymphedema is a local form of tissue swelling, which is caused by excessive retention of lymph fluid in interstitial compartment caused by impaired lymphatic drainage damage. Primary lymphedema is caused by developmental lymphatic vascular abnormalities. Most cases are inherited as autosomal dominant, with incomplete penetrance and variable expression. Here we report compound heterozygotes variants in FLT4 of a Chinese family associated with primary lymphedema display autosomal recessive inheritance.

Case presentation: Trio-whole-exome sequencing (Trio-WES) was performanced to analyse the underlying genetic cause of a proband with primary lymphedema in a Chinese family. Sanger sequencing was used to validate the variants in proband with primary lymphedema and members of the family with no clinical signs and symptoms. We reported compound heterozygotes for the Fms Related Receptor Tyrosine Kinase 4 (FLT4) gene detected in the proband, who carrying two different point variants. One was a missense variant (NM_182925.5; c.1504G>A, p.Glu502Lys), and the other was a recurrent variant (NM_182925.5; c.3323_3325del, p.Phe1108del). The missense variant c.1504G>A was detected in the proband, unaffected father, and unaffected paternal grandmother but not detected in unaffected paternal grandfather. The recurrent variant c.3323_3325del was detected in the proband, unaffected mother, and unaffected maternal grandfather but not detected in unaffected maternal grandmother. Our results suggests the possibility of an autosomal recessive inherited form of primary lymphedema resulting from variants of FLT4 encoding the vascular endothelial growth factor receptor-3.

Conclusion: The results of the present study identifed compound heterozygotes FLT4 variants in a family with primary lymphedema which provides more information for autosomal recessive primary lymphedema caused by FLT4.
An updated review of the immunological mechanisms of keloid scars
Authors: Lee Chih-Chun , Tsai Chia-Hsuan , Chen Chih-Hao , Yeh Yuan-Chieh , Chung Wen-Hung , Chen Chun-Bing
Published: March 2023

Keloid is a type of disfiguring pathological scarring unique to human skin. The disorder is characterized by excessive collagen deposition. Immune cell infiltration is a hallmark of both normal and pathological tissue repair. However, the immunopathological mechanisms of keloid remain unclear. Recent studies have uncovered the pivotal role of both innate and adaptive immunity in modulating the aberrant behavior of keloid fibroblasts. Several novel therapeutics attempting to restore regulation of the immune microenvironment have shown variable efficacy. We review the current understanding of keloid immunopathogenesis and highlight the potential roles of immune pathway-specific therapeutics.
Analyzing efficiency measurement and influencing factors of China’s marine green economy: Based on a two-stage network DEA model
Authors: Zou Wenjie , Yang Yuping , Yang Mengting , Zhang Xiaoyan , Lai Shennan , Chen Huangxin
Published: March 2023

This research adopts a two-stage network DEA model to measure marine green economy efficiency from 2006 to 2018 and employs the panel Tobit model to analyze the influencing factors. The results indicate that total efficiency and production efficiency of China’s marine green economy generally show a fluctuating downward trend. Further investigation of influencing factors shows that foreign direct investment and opening up have a significantly positive effect on total efficiency of the marine green economy, while industrial development level and marine economy development level have a negative effect on it. Additionally, these variables have varying impacts on different stages of the marine green economy. Our findings help identify the operational characteristics of the marine green economy at different stages and can assist policymakers in optimizing the development pattern of the marine economy.
Newly detected, virulent Toxoplasma gondii COUG strain causing fatal steatitis and toxoplasmosis in southern sea otters (Enhydra lutris nereis)
Authors: Miller Melissa Ann , Newberry Cara A. , Sinnott Devinn M. , Batac Francesca Irene , Greenwald Katherine , Reed Angelina , Young Colleen , Harris Michael D. , Packham Andrea E. , Shapiro Karen
Published: March 2023

From February 2020 to March 2022, four southern sea otters (Enhydra lutris nereis) stranded in California with severe protozoal steatitis and systemic toxoplasmosis. Three of the infected otters stranded within 26 km of each other, and all four animals died during periods of increased rainfall-driven surface water runoff. High parasite burdens were observed in all tissues except the central nervous system, and toxoplasmosis with severe protozoal steatitis was the primary cause of death for all cases. This lesion pattern differs substantially from all prior reports of toxoplasmosis in sea otters. All cases were T. gondii-positive via serology, immunohistochemistry, and PCR. Multilocus sequence typing at 13 loci revealed that all were infected with the same strain of T. gondii, previously characterized as an atypical and rare genotype in North America (TgCgCa1, or COUG). The COUG genotype was first isolated from mountain lions in British Columbia, Canada during investigation of a waterborne outbreak of toxoplasmosis in humans. This genotype has not been previously reported from sea otters, nor any aquatic species. All prior T. gondii strains obtained from >140 southern sea otters represent Type II or Type X strains, or variants of these genotypes. Archival necropsy data (>1,000 animals over 24 years) were negative for prior cases of severe T. gondii-associated steatitis prior to the cases described herein, and no sublethal COUG T. gondii infections have been previously indentified in sea otters. According to prior studies, the T. gondii COUG genotype is highly virulent in mice and is unusual among T. gondii isolates in eliciting a Type I interferon response in murine and human cells in vitro; this unusual immunomodulatory response could explain the apparent high virulence of this atypical T. gondii strain. Our findings reveal a novel and concerning lesion pattern for sea otters with toxoplasmosis. Due to high zoonotic potential and the risk of infection via shared marine food resources, these findings may also indicate potential health threats for other animals and humans.
Sensitivity optical non-linear measurement based on wide-band phase objects
Authors: Shao Zhangyang , Yang Yong , Yang Junyi , Zhou Wenfa , Liu Kun , Li Zhongguo , Fang Yu , Wu Xingzhi , Song Yinglin
Published: March 2023

On the basic that the phase object (PO) is the key optical device in the 4f imaging system, a modified high sensitivity optical nonlinear measurement technique with an absorptive homemade phase object (HPO) is reported in order to characterize the value of weak nonlinear refraction material. The absorptive HPO used in this technique is two transparent glass plates on which a liquid film between two pieces of transparent glasses is deposited and added a rotating object at the below HPO to modulate the phase of a PO. The measuring sensitivity can be improved by changing the transmittance of the absorptive HPO. Meanwhile, because the phase retardation of HPO can be continuously adjustable by modulate the rotating object, it makes the sensitivity of measurement at different wavelengths of laser optimal. Results show that the measuring sensitivity is improved 2-4 times compare with the conventional 4f imaging technique. Furthermore, the modified technique can be used to measure the spectrum of nonlinear refraction coefficients of materials at the continuous wavelength. This method further expands the 4f phase coherent imaging measurement technology, not only solves the deficiencies of the conventional phase object, but also improves the accuracy of the measurement. Experiment and theoretical analysis results are presented to validate our technique.
Upper airway disease diagnosis as a predictive biomarker of therapeutic response to biologics in severe asthma
Authors: Cottin Sophie , Doyen Virginie , Pilette Charles
Published: March 2023

Asthma is a heterogeneous disease sharing airway instability but with different biology, risk factors, and response-to-therapy patterns. Biologics have revolutionized the one-size-fits-to-all approach to personalized medicine in severe asthma (SA), which relies on the identification of biomarkers that define distinct endotypes. Thus, blood eosinophils and, to some extent, exhaled nitric oxide (FeNO) can predict the response to approved anti-type 2 (T2) biologics (anti-IgE, anti–IL-5, and anti–IL-4R alpha), whereas age at onset and comorbidities such as anxiety/depression, obesity, reflux, and upper airway disease (UAD) also influence therapeutic responses in SA. In this article, focusing on the predictive value of biomarkers for the therapeutic response to biologics in SA, we first summarize the level of prediction achieved by T2 biomarkers (blood eosinophils, FeNO) and then review whether data support the predictive value of upper airway diagnosis on such outcomes. Post hoc analysis of most studies with T2 biologics suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) and, to a lower extent, allergic rhinitis may help in predicting clinical response. Considering that T2 biologics are now also approved for the treatment of severe CRSwNP, diagnosis of upper airway disease is a key step in determining eligibility for such therapy.
Transcriptome analysis of Lr19-virulent mutants provides clues for the AvrLr19 of Puccinia triticina
Authors: Cui Zhongchi , Wu Wenyue , Fan Fan , Wang Fei , Liu Daqun , Di Dianping , Wang Haiyan
Published: March 2023

Introduction

Wheat leaf rust caused by Puccinia triticina (Pt) remains one of the most destructive diseases of common wheat worldwide. Understanding the pathogenicity mechanisms of Pt is important to control wheat leaf rust.

Methods

The urediniospores of Pt race PHNT (wheat leaf rust resistance gene Lr19-avirulent isolate) were mutagenized with ethyl methanesulfonate (EMS), and two Lr19-virulent mutants named M1 and M2 were isolated. RNA sequencing was performed on samples collected from wheat cultivars Chinese Spring and TcLr19 infected with wild-type (WT) PHNT, M1, and M2 isolates at 14 days post-inoculation (dpi), respectively. Screening AvrLr19 candidates by quantitative reverse transcription PCR (qPCR) and Agrobacterium-mediated transient assays in Nicotiana benthamiana.

Results

560 genes with single nucleotide polymorphisms (SNPs) and insertions or deletions (Indels) from non-differentially expressed genes were identified. Among them, 10 secreted proteins were screened based on their fragments per kilobase of exon model per million mapped reads (FPKM) values in the database. qPCR results showed that the expression profiles of 7 secreted proteins including PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, and PTTG_03570 among 10 secreted proteins in mutants were significantly different with that in wild-type isolate after infection wheat TcLr19 and might be related to the recognition between Lr19 and AvrLr19. In addition, a total of 216 differentially expressed genes (DEGs) were obtained from three different sample comparisons including M1-vs-WT, M2-vs-WT, and M1-vs-M2. Among 216 DEGs, 15 were predicted to be secreted proteins. One secreted protein named PTTG_04779 could inhibit programmed progress of cell death (PCD) induced by apoptosis-controlling genes B-cell lymphoma-2 associated X protein (BAX) on Nicotiana benthamiana, indicating that it might play a virulence function in plant. Taken together, total 8 secreted proteins, PTTG_04779, PTTG_27471, PTTG_12441, PTTG_28324, PTTG_26499, PTTG_06910, PTTG_26516, PTTG_03570 are identified as AvrLr19 candidates.

Discussion

Our results showed that a large number of genes participate in the interaction between Pt and TcLr19, which will provide valuable resources for the identification of AvrLr19 candidates and pathogenesis-related genes.
Characterization of cephalosporin and fluoroquinolone resistant Enterobacterales from Irish farm waste by whole genome sequencing
Authors: Prendergast Deirdre M. , Slowey Rosemarie , Burgess Catherine M. , Murphy Declan , Johnston Dayle , Morris Dearbháile , O’ Doherty Áine , Moriarty John , Gutierrez Montserrat
Published: March 2023

Background

The Enterobacterales are a group of Gram-negative bacteria frequently exhibiting extended antimicrobial resistance (AMR) and involved in the transmission of resistance genes to other bacterial species present in the same environment. Due to their impact on human health and the paucity of new antibiotics, the World Health Organization (WHO) categorized carbapenem resistant and ESBL-producing as critical. Enterobacterales are ubiquitous and the role of the environment in the transmission of AMR organisms or antimicrobial resistance genes (ARGs) must be examined in tackling AMR in both humans and animals under the one health approach. Animal manure is recognized as an important source of AMR bacteria entering the environment, in which resistant genes can accumulate.

Methods

To gain a better understanding of the dissemination of third generation cephalosporin and fluoroquinolone resistance genes between isolates in the environment, we applied whole genome sequencing (WGS) to Enterobacterales (79 E. coli, 1 Enterobacter cloacae, 1 Klebsiella pneumoniae, and 1 Citrobacter gillenii) isolated from farm effluents in Ireland before (n = 72) and after (n = 10) treatment by integrated constructed wetlands (ICWs). DNA was extracted using the MagNA Pure 96 system (Roche Diagnostics, Rotkreuz, Switzerland) followed by WGS on a MiSeq platform (Illumina, Eindhoven, Netherlands) using v3 chemistry as 300-cycle paired-end runs. AMR genes and point mutations were identified and compared to the phenotypic results for better understanding of the mechanisms of resistance and resistance transmission.

Results

A wide variety of cephalosporin and fluoroquinolone resistance genes (mobile genetic elements (MGEs) and chromosomal mutations) were identified among isolates that mostly explained the phenotypic AMR patterns. A total of 31 plasmid replicon types were identified among the 82 isolates, with a subset of them (n = 24), identified in E. coli isolates. Five plasmid replicons were confined to the Enterobacter cloacae isolate and two were confined to the Klebsiella pneumoniae isolate. Virulence genes associated with functions including stress, survival, regulation, iron uptake secretion systems, invasion, adherence and toxin production were identified.

Conclusion

Our study showed that antimicrobial resistant organisms (AROs) can persist even following wastewater treatment and could transmit AMR of clinical relevance to the environment and ultimately pose a risk to human or animal health.
Bacterial and fungal diversities examined through high-throughput sequencing in response to lead contamination of tea garden soil
Authors: Zhang Ziyan , Deng Qingmei , Ye Hui , Ge Gaofei
Published: March 2023

Several studies have indicated that the heavy-metal content in tea is increasing gradually. Researchers examining the soil of more than 100 tea gardens in China have observed that lead content was higher in some soils. The effect of lead contamination on soil microorganisms in tea gardens was studied to determine the effect of lead on the essential functions of microorganisms in a tea garden soil ecosystem. Previous studies on pot experiments adopted the method of adding a single instance of pollution, which failed to comprehensively simulate the characteristics of the slow accumulation of heavy metals in soil. This study designed with two pollution modes (multistage and single instance) determined the content of soil lead in different forms according to the European Community Bureau of Reference extraction procedure. The community structure, species diversity and functional abundance of soil bacteria and fungi were examined by high-throughput sequencing. We observed that the content of four forms of lead was higher in the multistage contamination mode than in the single instance contamination mode. The effects of lead contamination on bacteria differed significantly (p < 0.05), and the abundance and diversity of bacteria were higher in the multistage contamination mode than in the single instance contamination mode. The community structure of fungi was more affected by lead than was that of bacteria. The content of each lead form was the environmental factor most strongly affecting soil bacteria and fungi. The predicted main function of the bacterial community was amino acid transport and metabolism, and the trophic mode of the fungal community was mainly pathotroph–saprotroph. This study revealed changes in soil microorganisms caused by different forms of lead and contamination methods in tea garden soil and provide a theoretical basis for examining the effects of lead contamination on soil microorganisms.
The differences between broad bean koji fermented in laboratory and factory conditions by an efficient Aspergillus oryzae
Authors: Li Heng , Lu Zhen-Ming , Deng Wei-Qin , Zhang Qi-Sheng , Chen Gong , Li Qi , Xu Zheng-Hong , Ma Yan-He
Published: March 2023

Broad bean paste-meju was fermented by a mixture of broad bean koji and saline; koji fermentation is an essential process for the production of broad bean paste-meju. Aspergillus oryzae was the most widely used in sauce fermentation. The purpose of this study was to research the factory adaptability of the highly efficient A. oryzae PNM003 and further evaluate the effect of fermentation conditions and fermentation strains on koji. A. oryzae PNM003 was compared with the widely used strain HN 3.042 not only in the laboratory but also in factory conditions (large scale). Results showed that the koji made with the same starter in the factory had a greater amount of fungi than that in the laboratory. Bacteria and yeast levels in HN_L koji were higher than in PN_L koji. As for fungi constitution, almost only Aspergillus survived in the end through the microorganism self-purification process during koji fermentation. As for the bacterial constitution, koji was grouped by fermentation conditions instead of fermentation starter. PN koji had higher protease activity and a higher content of total acids, amino acid nitrogen, amino acids, and organic acids in the laboratory conditions. Nevertheless, in factory conditions, PN koji and HN koji had similar indexes. As for volatile flavor compounds, koji made with the two starters in the same condition was grouped together. As for the same starter, there were more flavor compounds metabolized in the factory condition than in the laboratory condition, especially esters and alcohols. The results showed PN was a highly efficient strain to ferment koji, but the advantages were expressed more remarkably in laboratory conditions. In brief, the fermented condition had a greater influence than the fermentation starter for broad bean koji.
Minocycline prevents hypoxia-induced seizures
Authors: Fukushi Isato , Ikeda Keiko , Takeda Kotaro , Yoshizawa Masashi , Kono Yosuke , Hasebe Yohei , Pokorski Mieczyslaw , Okada Yasumasa
Published: March 2023

Severe hypoxia induces seizures, which reduces ventilation and worsens the ictal state. It is a health threat to patients, particularly those with underlying hypoxic respiratory pathologies, which may be conducive to a sudden unexpected death in epilepsy (SUDEP). Recent studies provide evidence that brain microglia are involved with both respiratory and ictal processes. Here, we investigated the hypothesis that microglia could interact with hypoxia-induced seizures. To this end, we recorded electroencephalogram (EEG) and acute ventilatory responses to hypoxia (5% O2 in N2) in conscious, spontaneously breathing adult mice. We compared control vehicle pre-treated animals with those pre-treated with minocycline, an inhibitory modulator of microglial activation. First, we histologically confirmed that hypoxia activates microglia and that pre-treatment with minocycline blocks hypoxia-induced microglial activation. Then, we analyzed the effects of minocycline pre-treatment on ventilatory responses to hypoxia by plethysmography. Minocycline alone failed to affect respiratory variables in room air or the initial respiratory augmentation in hypoxia. The comparative results showed that hypoxia caused seizures, which were accompanied by the late phase ventilatory suppression in all but one minocycline pre-treated mouse. Compared to the vehicle pre-treated, the minocycline pre-treated mice showed a delayed occurrence of seizures. Further, minocycline pre-treated mice tended to resist post-ictal respiratory arrest. These results suggest that microglia are conducive to seizure activity in severe hypoxia. Thus, inhibition of microglial activation may help suppress or prevent hypoxia-induced ictal episodes.
Dityrosine cross-linking and its potential roles in Alzheimer’s disease
Authors: Maina Mahmoud B. , Al-Hilaly Youssra K. , Serpell Louise C.
Published: March 2023

Oxidative stress is a significant source of damage that accumulates during aging and contributes to Alzheimer’s disease (AD) pathogenesis. Oxidation of proteins can give rise to covalent links between adjacent tyrosines known as dityrosine (DiY) cross-linking, amongst other modifications, and this observation suggests that DiY could serve as a biomarker of accumulated oxidative stress over the lifespan. Many studies have focused on understanding the contribution of DiY to AD pathogenesis and have revealed that DiY crosslinks can be found in both Aβ and tau deposits – the two key proteins involved in the formation of amyloid plaques and tau tangles, respectively. However, there is no consensus yet in the field on the impact of DiY on Aβ and tau function, aggregation, and toxicity. Here we review the current understanding of the role of DiY on Aβ and tau gathered over the last 20 years since the first observation, and discuss the effect of this modification for Aβ and tau aggregation, and its potential as a biomarker for AD.
Multimodality liver directed treatment for colorectal liver metastasis: Array of complementary options can improve outcomes - A single centre experience from India
Authors: Patkar Shraddha , Chopde Amit , Shetty Nitin , Kulkarni Suyash , Gala Kunal Bharat , Chandra Daksh , Ramaswamy Anant , Ostwal Vikas , Goel Mahesh
Published: March 2023

AIM

Complimentary use of Liver directed therapies (LDTs) with systemic chemotherapy has improved oncologic outcomes in colorectal liver metastasis (CRLM). We analysed institutional results of multimodality management.

Methods

Retrospective analysis of prospectively maintained database of CRLM patients managed with LDT including surgical resection, Ablation, Transarterial chemoembolization (TACE) or Transarterial radioembolization (TARE) between November 2011 to March 2020. Management plan was decided in multidisciplinary meeting. Resectable tumours underwent surgical resection or ablation or both in some cases. Borderline resectable or unresectable disease was treated with down staging chemotherapy or TACE/TARE followed by resection or ablation. All patients received adjuvant chemotherapy. Factors influencing survival were analysed.

Results

Out of total 375 patients, surgery alone was done in 191 (50.93%) patients while surgery with other LDT in 26 patients (6.93%). Ablation alone was done in 100 (26.66%) whereas TACE/TARE were done as standalone treatment in 21 (5.6%) and 7 (1.86%) patients respectively. TACE + ablation was done in 28 (7.46%) and TARE + ablation was done in 2(0.53%) patients.5-year Overall Survival(OS) was 49.8% while Event free survival(EFS) was 21.4%. The median OS and EFS for surgical group was significantly better than non-surgical group (78 V/s 39 months; p<0.05 and 20 V/s 15 months p <0.005). The resectable (78 months) group had better median OS as compared to borderline resectable and Unresectable group (39 months and 29 months). Male gender, resectable disease and surgical intervention were associated with improved OS.

Conclusion

Although surgery remains the mainstay of treatment, complementary use of non-surgical LDT with systemic therapy offers possibility of good outcomes in advanced liver limited disease. Our experience highlights the impact of multidisciplinary care in optimizing CRLM treatment.
Risk factors of temperature increase after cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy
Authors: Kang Hui-xia , Ma Jun-ying , Su Yan-yan , Kang Shan , Feng Bao-jie , Feng Xiao-bei , Wang Xu-sha , Lu Yun-yun
Published: March 2023

Background

Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is the standard treatment for patients with peritoneal cancer (PC). Following CRS-HIPEC, patients may also face risks caused by whole body hyperthermia. This study analyzed the incidence of temperature increases following CRS-HIPEC and identified the attendant risk factors.

Methods

A retrospective analysis was carried out among 458 patients who received CRS-HIPEC at the Fourth Hospital of Hebei Medical University between August 2018 and January 2021. The patients were divided into two groups according to post-HIPEC axillary temperature (≥38°C), with the demographics and the laboratory test results subsequently analyzed and compared, and the risk factors pertaining to temperature increases analyzed using univariate and multivariate logistic regression.

Results

During CRS-HIPEC, 32.5% (149/458) of the patients with a temperature increase had an axillary temperature of not lower than 38°C, and 8.5% (39/458) of the patients with hyperpyrexia had an axillary temperature of not lower than 39°C. Female gender, gynecological malignancies, type of chemotherapy drug, increased postoperative neutrophil percentage, and a sharp drop in postoperative prealbumin were associated with the incidence of a temperature increase and axillary temperatures of >38°C. Among these factors, the type of chemotherapy drug was identified as an independent risk factor for a temperature increase during CRS-HIPEC.

Conclusion

By determining the risk factors pertaining to temperature increases during CRS-HIPEC, medical staff can identify the attendant risks among the patients and thus take preventive measures in a timely manner to maintain the patient’s body temperature at a stable level. This suggests that further clinical research should be conducted to build a risk-prediction model for temperature increases following CRS-HIPEC.