bluuebunny/crossref_metadata_2025 huggingface dataset:
COP 26 Futures We Want - India Country Profile
Authors: Debnath Ramit , Sagar Ambuj , Babu Suresh
Published: October 2021

This regional profile for India was developed in the context of the BEIS COP26 Futures We Want project. It has been developed with input from in-country academic experts Professor Ambuj Sagar (Indian Institute of Technology, India) and Dr Suresh Babu (Dr B R Ambedkar University, India). It sets out a synthesis of the available evidence base on regional challenges and opportunities for mitigation, adaptation, and resilience measures for India associated with climate change and a global transition to an inclusive, desirable, and resilient net-zero future.
Havalandırma Kanalı Tasarımında Malzeme Seçimi ve Tasarımına Bağlı Ağırlık Optimizasyonu
Authors: Altuncu Ekrem , Eker Cem , Kırmızıtepe Samet
Published: October 2021

Günümüz yolcu otobüsü imalatı endüstrisinde hafifletme ile yakıt tasarrufunu artırmak için birçok çalışma yapılmaktadır. Bu çalışmalar ışığında otobüs hava kanalı profili (1000X320mm) tasarımında ağırlık optimizasyonu ihtiyacı doğmuştur. Gerek malzeme seçimi ve tasarımı, gerekse malzeme optimizasyonu kapsamında, alüminyum alaşımı ve ABS malzeme kullanım oranına bağlı tasarımlar karşılıklı değerlendirilmiştir. Araç içi yolcu yükü taşıma bölümü (12m boy) tasarımlarında kullanılan malzemelerin mevcut taşıma yükü ve tasarım geometrisine bağlı detaylar incelenmiş ve analiz edilmiştir. ANSYS yapısal analiz (CAE) modülünü kullanarak 1 metre üründe 60 kg yük kaldırabilecek şekilde gerilmeler hesaplanarak ABS ile alüminyum profil özellikleri teknoekonomik açıdan karşılaştırılmıştır. Yapılan analiz sonucunda ABS malzemenin kullanımı ile tasarımda hafiflik optimizasyonu sağlanabilmiş, araç yakıt tasarrufu içi 22 kg /araç hafifletme ve tasarım esnekliği sağlanabilmiştir.
Thermal Analysis of Thermal Spray Coated Gray Cast Iron Brake Rotor
Authors: Akyüz Recep , Altuncu Ekrem , Demirdalmiş Ozan , Çengelli Bilgi
Published: October 2021

Braking is a process which transform the kinetic energy of the rotor into heat energy. During the braking phase, the frictional heat generated at the interface rotor–pad can lead to high temperatures (> 600 oC). In long-term frequent use of braking, increased temperature causes disc distortions, heat cracks, and causes degradation of the pad material. This creates a risk in the reduction of rotor-pad interface friction and loss of brake performance under safe driving conditions. In this study, the thermal monitoring of the thermal spray coated rotor was investigated and the variation of the friction coefficient and wear related thickness were measured. In addition, changes in torque forces at increasing temperatures were also evaluated.
A Novel Real-Time Reverse Transcription Loop-Mediated Isothermal Amplification Detection Platform: Application to Diagnosis of COVID-19
Authors: Wang Yi , Wang Xiaoxia , Chen Hai , Han Limei , Wang Licheng , Chen Ting , Li Sha , Li Huan , Li Yuanli , Li Zhengkun , Fu Xiaoying , Chen Shaojin , Xing Mei , Tai Jun , Zhu Xiong
Published: October 2021

The ongoing Corona virus disease (COVID-19) outbreak has become a huge global health concern. Here, we reported a novel detection platform based on the loop-mediated isothermal amplification (LAMP), termed real-time reverse transcription LAMP (rRT-LAMP) and applied it for the diagnosis of COVID-19 (COVID-19 rRT-LAMP). rRT-LAMP integrates reverse transcription, LAMP amplification, restriction endonuclease cleavage and real-time fluorescence detection into one-pot reaction, and facilitates the diagnosis of COVID-19 at 64°C for only 35 min. The ORF1ab (opening reading frame 1a/b) and NP (nucleoprotein) genes of SARS-CoV-2 were detected for diagnosing COVID-19. The limit of detection (LoD) of COVID-19 rRT-LAMP assay was 14 copies (for each marker) per vessel, and no positive results were obtained from non-SARS-CoV-2 templates. To demonstrate its feasibility, a total of 33 oropharynx swab samples collected from COVID-19 patients also were diagnosed as SARS-CoV-2 infection using COVID-19 rRT-LAMP protocol. No cross-reactivity was yielded from 41 oropharynx swab samples collected from non-COVID-19 patients. These data suggesting that the COVID-19 rRT-LAMP assay is a potential detection tool for the diagnosis of SARS-CoV-2 infection in clinical, field and disease control laboratories, and will be valuable for controlling the COVID-19 epidemic.
Advances and Prospects in Biomaterials for Intervertebral Disk Regeneration
Authors: Li Chunxu , Bai Qiushi , Lai Yuxiao , Tian Jingjing , Li Jiahao , Sun Xiaodan , Zhao Yu
Published: October 2021

Low-back and neck-shoulder pains caused by intervertebral disk degeneration are highly prevalent among middle-aged and elderly people globally. The main therapy method for intervertebral disk degeneration is surgical intervention, including interbody fusion, disk replacement, and diskectomy. However, the stress changes caused by traditional fusion surgery are prone to degeneration of adjacent segments, while non-fusion surgery has problems, such as ossification of artificial intervertebral disks. To overcome these drawbacks, biomaterials that could endogenously regenerate the intervertebral disk and restore the biomechanical function of the intervertebral disk is imperative. Intervertebral disk is a fibrocartilaginous tissue, primarily comprising nucleus pulposus and annulus fibrosus. Nucleus pulposus (NP) contains high water and proteoglycan, and its main function is absorbing compressive forces and dispersing loads from physical activities to other body parts. Annulus fibrosus (AF) is a multilamellar structure that encloses the NP, comprises water and collagen, and supports compressive and shear stress during complex motion. Therefore, different biomaterials and tissue engineering strategies are required for the functional recovery of NP and AF based on their structures and function. Recently, great progress has been achieved on biomaterials for NP and AF made of functional polymers, such as chitosan, collagen, polylactic acid, and polycaprolactone. However, scaffolds regenerating intervertebral disk remain unexplored. Hence, several tissue engineering strategies based on cell transplantation and growth factors have been extensively researched. In this review, we summarized the functional polymers and tissue engineering strategies of NP and AF to endogenously regenerate degenerative intervertebral disk. The perspective and challenges of tissue engineering strategies using functional polymers, cell transplantation, and growth factor for generating degenerative intervertebral disks were also discussed.
Long Non-coding RNAs LOC100126784 and POM121L9P Derived From Bone Marrow Mesenchymal Stem Cells Enhance Osteogenic Differentiation via the miR-503-5p/SORBS1 Axis
Authors: Xu Yiyang , Xin Ruobing , Sun Hong , Long Dianbo , Li Zhiwen , Liao Hongyi , Xue Ting , Zhang Ziji , Kang Yan , Mao Guping
Published: October 2021

Long non-coding RNAs (lncRNAs) play pivotal roles in mesenchymal stem cell differentiation. However, the mechanisms by which non-coding RNA (ncRNA) networks regulate osteogenic differentiation remain unclear. Therefore, our aim was to identify RNA-associated gene and transcript expression profiles during osteogenesis in bone marrow mesenchymal stem cells (BMSCs). Using transcriptome sequencing for differentially expressed ncRNAs and mRNAs between days 0 and 21 of osteogenic differentiation of BMSCs, we found that the microRNA (miRNA) miR-503-5p was significantly downregulated. However, the putative miR-503-5p target, sorbin and SH3 domain containing 1 (SORBS1), was significantly upregulated in osteogenesis. Moreover, through lncRNA-miRNA-mRNA interaction analyses and loss- and gain-of-function experiments, we discovered that the lncRNAs LOC100126784 and POM121L9P were abundant in the cytoplasm and enhanced BMSC osteogenesis by promoting SORBS1 expression. In contrast, miR-503-5p reversed this effect. Ago2 RNA-binding protein immunoprecipitation and dual-luciferase reporter assays further validated the direct binding of miR-503-5p to LOC100126784 and POM121L9P. Furthermore, SORBS1 knockdown suppressed early osteogenic differentiation in BMSCs, and co-transfection with SORBS1 small interfering RNAs counteracted the BMSCs’ osteogenic capacity promoted by LOC100126784- and POM121L9P-overexpressing lentivirus plasmids. Thus, the present study demonstrated that the lncRNAs LOC100126784 and POM121L9P facilitate the osteogenic differentiation of BMSCs via the miR-503-5p/SORBS1 axis, providing potential therapeutic targets for treating osteoporosis and bone defects.
ID2 Inhibits Bladder Cancer Progression and Metastasis via PI3K/AKT Signaling Pathway
Authors: Mao Weipu , Wang Keyi , Sun Si , Wu Jianping , Chen Ming , Geng Jiang , Luo Ming
Published: October 2021

Background: Inhibitors of DNA-binding (ID) proteins are important regulators of cell proliferation and differentiation. The aim of this study was to evaluated the role of ID proteins in bladder cancer (BCa) and related molecular mechanisms.

Methods: The TCGA database was analyzed for the expression and clinical significance of ID proteins. The expression of ID2 was determined by qRT-PCR, immunohistochemical staining and western blot. The role of ID2 was determined by CCK-8, colony formation, wound healing, transwell and xenograft tumor assays, and the potential mechanism of ID2 in BCa was investigated by RNA sequencing.

Results: ID2 expression was significantly downregulated in TCGA database and clinical samples, and high ID2 expression was associated with low-grade tumor staging and correlated with better overall survival, disease specific survival (DSS) and progress free interval (PFI). In vivo and in vitro experiments showed that knockdown of ID2 promoted proliferation, migration, invasion and metastasis of BCa cells, while overexpression of ID2 significantly inhibited cell proliferation, migration, invasion and metastasis. Mechanistically, ID2 acts as a tumor suppressor through PI3K/AKT signaling pathway to inhibit the progression and metastasis of BCa.

Conclusion: Our results suggest that ID2 exerts tumor suppressive effects in BCa through PI3K/AKT signaling pathway, and altered ID2 expression can be used as a biomarker of BCa progression and metastasis.
Pancreatic Ductal Adenocarcinoma: Preclinical in vitro and ex vivo Models
Authors: Gündel Beate , Liu Xinyuan , Löhr Matthias , Heuchel Rainer
Published: October 2021

Pancreatic ductal adenocarcinoma (PDAC) is one of the most overlooked cancers despite its dismal median survival time of 6 months. The biggest challenges in improving patient survival are late diagnosis due to lack of diagnostic markers, and limited treatment options due to almost complete therapy resistance. The past decades of research identified the dense stroma and the complex interplay/crosstalk between the cancer- and the different stromal cells as the main culprits for the slow progress in improving patient outcome. For better ex vivo simulation of this complex tumor microenvironment the models used in PDAC research likewise need to become more diverse. Depending on the focus of the investigation, several in vitro and in vivo models for PDAC have been established in the past years. Particularly, 3D cell culture such as spheroids and organoids have become more frequently used. This review aims to examine current PDAC in vitro models, their inherent limitations, and their successful implementations in research.
Fusing NIR and Process Sensors Data for Polymer Production Monitoring
Authors: Strani Lorenzo , Mantovani Erik , Bonacini Francesco , Marini Federico , Cocchi Marina
Published: October 2021

Process analytical technology and multivariate process monitoring are nowadays the most effective approaches to achieve real-time quality monitoring/control in production. However, their use is not yet a common practice, and industries benefit much less than they could from the outcome of the hundreds of sensors that constantly monitor production in industrial plants. The huge amount of sensor data collected are still mostly used to produce univariate control charts, monitoring one compartment at a time, and the product quality variables are generally used to monitor production, despite their low frequency (offline measurements at analytical laboratory), which is not suitable for real-time monitoring. On the contrary, it would be extremely advantageous to benefit from predictive models that, based on online sensors, will be able to return quality parameters in real time. As a matter of fact, the plant setup influences the product quality, and process sensors (flow meters, thermocouples, etc.) implicitly register process variability, correlation trends, drift, etc. When the available spectroscopic sensors, reflecting chemical composition and structure, consent to monitor the intermediate products, coupling process, and spectroscopic sensor and extracting/fusing information by multivariate analysis from this data would enhance the evaluation of the produced material features allowing production quality to be estimated at a very early stage. The present work, at a pilot plant scale, applied multivariate statistical process control (MSPC) charts, obtained by data fusion of process sensor data and near-infrared (NIR) probes, on a continuous styrene-acrylonitrile (SAN) production process. Furthermore, PLS regression was used for real-time prediction of the Melt Flow Index and percentage of bounded acrylonitrile (%AN). The results show that the MSPC model was able to detect deviations from normal operative conditions, indicating the variables responsible for the deviation, be they spectral or process. Moreover, predictive regression models obtained using the fused data showed better results than models computed using single datasets in terms of both errors of prediction and R2. Thus, the fusion of spectra and process data improved the real-time monitoring, allowing an easier visualization of the process ongoing, a faster understanding of possible faults, and real-time assessment of the final product quality.
Site-Specific Protein Modifications by an Engineered Asparaginyl Endopeptidase from Viola canadensis
Authors: Chen Yu , Zhang Dingpeng , Zhang Xiaohong , Wang Zhen , Liu Chuan-Fa , Tam James P.
Published: October 2021

Asparaginyl endopeptidases (AEPs) or legumains are Asn/Asp (Asx)-specific proteases that break peptide bonds, but also function as peptide asparaginyl ligases (PALs) that make peptide bonds. This ligase activity can be used for site-specific protein modifications in biochemical and biotechnological applications. Although AEPs are common, PALs are rare. We previously proposed ligase activity determinants (LADs) of these enzymes that could determine whether they catalyze formation or breakage of peptide bonds. LADs are key residues forming the S2 and S1′ substrate-binding pockets flanking the S1 active site. Here, we build on the LAD hypothesis with the engineering of ligases from proteases by mutating the S2 and S1′ pockets of VcAEP, an AEP from Viola canadensis. Wild type VcAEP yields <5% cyclic product from a linear substrate at pH 6.5, whereas the single mutants VcAEP-V238A (Vc1a) and VcAEP-Y168A (Vc1b) targeting the S2 and S1′ substrate-binding pockets yielded 34 and 61% cyclic products, respectively. The double mutant VcAEP-V238A/Y168A (Vc1c) targeting both the S2 and S1′ substrate-binding pockets yielded >90% cyclic products. Vc1c had cyclization efficiency of 917,759 M−1s−1, which is one of the fastest rates for ligases yet reported. Vc1c is useful for protein engineering applications, including labeling of DARPins and cell surface MCF-7, as well as producing cyclic protein sfGFP. Together, our work validates the importance of LADs for AEP ligase activity and provides valuable tools for site-specific modification of proteins and biologics.
Phylogenetic Analysis Indicates That Evasin-Like Proteins of Ixodid Ticks Fall Into Three Distinct Classes
Authors: Bhattacharya Shoumo , Nuttall Patricia Anne
Published: October 2021

Chemokines are structurally related proteins that activate leucocyte migration in response to injury or infection. Tick saliva contains chemokine-binding proteins or evasins which likely neutralize host chemokine function and inflammation. Biochemical characterisation of 50 evasins fromIxodes,AmblyommaandRhipicephalusshows that they fall into two functional classes, A and B, with exclusive binding to either CC- or CXC- chemokines, respectively. Class A evasins, EVA1 and EVA4 have a four-disulfide-bonded core, whereas the class B evasin EVA3 has a three-disulfide-bonded “knottin” structure. All 29 class B evasins have six cysteine residues conserved with EVA3, arrangement of which defines a Cys6-motif. Nineteen of 21 class A evasins have eight cysteine residues conserved with EVA1/EVA4, the arrangement of which defines a Cys8-motif. Two class A evasins fromIxodes(IRI01, IHO01) have less than eight cysteines. Many evasin-like proteins have been identified in tick salivary transcriptomes, but their phylogenetic relationship with respect to biochemically characterized evasins is not clear. Here, using BLAST searches of tick transcriptomes with biochemically characterized evasins, we identify 292 class A and 157 class B evasins and evasin-like proteins from Prostriate (Ixodes), and Metastriate (Amblyomma, Dermacentor, Hyalomma,Rhipicephalus) ticks. Phylogenetic analysis shows that class A evasins/evasin-like proteins segregate into two classes, A1 and A2. Class A1 members are exclusive to Metastriate ticks and typically have a Cys8-motif and include EVA1 and EVA4. Class A2 members are exclusive to Prostriate ticks, lack the Cys8-motif, and include IHO01 and IRI01. Class B evasins/evasin-like proteins are present in both Prostriate and Metastriate lineages, typically have a Cys6-motif, and include EVA3. Most evasins/evasin-like proteins in Metastriate ticks belong to class A1, whereas in Prostriate species they are predominantly class B. In keeping with this, the majority of biochemically characterized Metastriate evasins bind CC-chemokines, whereas the majority of Prostriate evasins bind CXC-chemokines. While the origin of the structurally dissimilar classes A1 and A2 is yet unresolved, these results suggest that class B evasin-like proteins arose before the divergence of Prostriate and Metastriate lineages and likely functioned to neutralize CXC-chemokines and support blood feeding.
The Depletion of Carbohydrate Metabolic Genes in the Gut Microbiome Contributes to the Transition From Central Obesity to Type 2 Diabetes
Authors: Jia Ruikai , Huang Min , Qian Lichun , Yan Xiaoye , Lv Qing , Ye Hua , Ye Li , Wu Xin , Chen Weizhi , Chen Ye , Jia Yankai , Huang Yueqing , Wu Huihui
Published: October 2021

Obesity, especially central obesity, is a strong risk factor for developing type 2 diabetes (T2D). However, the mechanism underlying the progression from central obesity to T2D remains unknown. Therefore, we analyzed the gut microbial profiles of central obese individuals with or without T2D from a Chinese population. Here we reported both the microbial compositional and gene functional alterations during the progression from central obesity to T2D. Several opportunistic pathogens were enriched in obese T2D patients. We also characterized thousands of genes involved in sugar and amino acid metabolism whose abundance were significantly depleted in obese T2D group. Moreover, the abundance of those genes was negatively associated with plasma glycemia level and percentage of individuals with impaired plasma glucose status. Therefore, our study indicates that the abundance of those depleted genes can be used as a potential biomarker to identify central obese individuals with high risks of developing T2D.
Power Consumption Predicting and Anomaly Detection Based on Transformer and K-Means
Authors: Zhang Junfeng , Zhang Hui , Ding Song , Zhang Xiaoxiong
Published: October 2021

With the advancement of technology and science, the power system is getting more intelligent and flexible, and the way people use electric energy in their daily lives is changing. Monitoring the condition of electrical energy loads, particularly in the early detection of aberrant loads and behaviors, is critical for power grid maintenance and power theft detection. In this paper, we combine the widely used deep learning model Transformer with the clustering approach K-means to estimate power consumption over time and detect anomalies. The Transformer model is used to forecast the following hour’s power usage, and the K-means clustering method is utilized to optimize the prediction results, finally, the anomalies is detected by comparing the predicted value and the test value. On real hourly electric energy consumption data, we test the proposed model, and the results show that our method outperforms the most commonly used LSTM time series model.
When and Why Did Human Brains Decrease in Size? A New Change-Point Analysis and Insights From Brain Evolution in Ants
Authors: DeSilva Jeremy M. , Traniello James F. A. , Claxton Alexander G. , Fannin Luke D.
Published: October 2021

Human brain size nearly quadrupled in the six million years sinceHomolast shared a common ancestor with chimpanzees, but human brains are thought to have decreased in volume since the end of the last Ice Age. The timing and reason for this decrease is enigmatic. Here we use change-point analysis to estimate the timing of changes in the rate of hominin brain evolution. We find that hominin brains experienced positive rate changes at 2.1 and 1.5 million years ago, coincident with the early evolution ofHomoand technological innovations evident in the archeological record. But we also find that human brain size reduction was surprisingly recent, occurring in the last 3,000 years. Our dating does not support hypotheses concerning brain size reduction as a by-product of body size reduction, a result of a shift to an agricultural diet, or a consequence of self-domestication. We suggest our analysis supports the hypothesis that the recent decrease in brain size may instead result from the externalization of knowledge and advantages of group-level decision-making due in part to the advent of social systems of distributed cognition and the storage and sharing of information. Humans live in social groups in which multiple brains contribute to the emergence of collective intelligence. Although difficult to study in the deep history ofHomo, the impacts of group size, social organization, collective intelligence and other potential selective forces on brain evolution can be elucidated using ants as models. The remarkable ecological diversity of ants and their species richness encompasses forms convergent in aspects of human sociality, including large group size, agrarian life histories, division of labor, and collective cognition. Ants provide a wide range of social systems to generate and test hypotheses concerning brain size enlargement or reduction and aid in interpreting patterns of brain evolution identified in humans. Although humans and ants represent very different routes in social and cognitive evolution, the insights ants offer can broadly inform us of the selective forces that influence brain size.
miRNA Expression Profiling Uncovers a Role of miR-139-5p in Regulating the Calcification of Human Aortic Valve Interstitial Cells
Authors: Zhang Fan , Cheng Naixuan , Han Yingchun , Zhang Congcong , Zhang Haibo
Published: October 2021

Calcific aortic valve disease (CAVD) is the most common structural heart disease, and the morbidity is increased with elderly population. Several microRNAs (miRNAs) have been identified to play crucial roles in CAVD, and numerous miRNAs are still waiting to be explored. In this study, the miRNA expression signature in CAVD was analyzed unbiasedly by miRNA-sequencing, and we found that, compared with the normal control valves, 152 miRNAs were upregulated and 186 miRNAs were downregulated in calcified aortic valves. The functions of these differentially expressed miRNAs were associated with cell differentiation, apoptosis, adhesion and immune response processes. Among downregulated miRNAs, the expression level of miR-139-5p was negatively correlated with the osteogenic gene RUNX2, and miR-139-5p was also downregulated during the osteogenic differentiation of primary human aortic valve interstitial cells (VICs). Subsequent functional studies revealed that miR-139-5p overexpression inhibited the osteogenic differentiation of VICs by negatively modulating the expression of pro-osteogenic gene FZD4 and CTNNB1. In conclusion, these results suggest that miR-139-5p plays an important role in osteogenic differentiation of VICs via the Wnt/β-Catenin pathway, which may further provide a new therapeutic target for CAVD.
Human Organoid and Supporting Technologies for Cancer and Toxicological Research
Authors: Sekine Keisuke
Published: October 2021

Recent progress in the field of organoid-based cell culture systems has enabled the use of patient-derived cells in conditions that resemble those in cancer tissue, which are better than two-dimensional (2D) cultured cell lines. In particular, organoids allow human cancer cells to be handled in conditions that resemble those in cancer tissue, resulting in more efficient establishment of cells compared with 2D cultured cell lines, thus enabling the use of multiple patient-derived cells with cells from different genetic background, in keeping with the heterogeneity of the cells. One of the most valuable points of using organoids is that human cells from either healthy or cancerous tissue can be used. Using genome editing technology such as clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein, organoid genomes can be modified to, for example, cancer-prone genomes. The normal, cancer, or genome-modified organoids can be used to evaluate whether chemicals have genotoxic or non-genotoxic carcinogenic activity by evaluating the cancer incidence, cancer progression, and cancer metastasis. In this review, the organoid technology and the accompanying technologies were summarized and the advantages of organoid-based toxicology and its application to pancreatic cancer study were discussed.
Structural Insights on the SARS-CoV-2 Variants of Concern Spike Glycoprotein: A Computational Study With Possible Clinical Implications
Authors: Cueno Marni E. , Imai Kenichi
Published: October 2021

Coronavirus disease 2019 (COVID-19) pandemic has been attributed to SARS-CoV-2 (SARS2) and, consequently, SARS2 has evolved into multiple SARS2 variants driving subsequent waves of infections. In particular, variants of concern (VOC) were identified to have both increased transmissibility and virulence ascribable to mutational changes occurring within the spike protein resulting to modifications in the protein structural orientation which in-turn may affect viral pathogenesis. However, this was never fully elucidated. Here, we generated spike models of endemic HCoVs (HCoV 229E, HCoV OC43, HCoV NL63, HCoV HKU1, SARS CoV, MERS CoV), original SARS2, and VOC (alpha, beta, gamma, delta). Model quality check, structural superimposition, and structural comparison based on RMSD values, TM scores, and contact mapping were all performed. We found that: 1) structural comparison between the original SARS2 and VOC whole spike protein model have minor structural differences (TM > 0.98); 2) the whole VOC spike models putatively have higher structural similarity (TM > 0.70) to spike models from endemic HCoVs coming from the same phylogenetic cluster; 3) original SARS2 S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM = 1.0) and S1-NTD (TM > 0.96); and 4) endemic HCoV S1-CTD and S1-NTD models are structurally comparable to VOC S1-CTD (TM > 0.70) and S1-NTD (TM > 0.70) models belonging to the same phylogenetic cluster. Overall, we propose that structural similarities (possibly ascribable to similar conformational epitopes) may help determine immune cross-reactivity, whereas, structural differences (possibly associated with varying conformational epitopes) may lead to viral infection (either reinfection or breakthrough infection).
The Tonsil Lymphocyte Landscape in Pediatric Tonsil Hyperplasia and Obstructive Sleep Apnea
Authors: Carrasco Anna , Sjölander Isabella , Van Acker Aline , Dernstedt Andy , Fehrm Johan , Forsell Mattias , Friberg Danielle , Mjösberg Jenny , Rao Anna
Published: October 2021

Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27-CD21hi B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.
Associations of Serum S100A12 With Severity and Prognosis in Patients With Community-Acquired Pneumonia: A Prospective Cohort Study
Authors: Jiang Xiao , Huang Chun-Mei , Feng Chun-Mei , Xu Zheng , Fu Lin , Wang Xin-Ming
Published: October 2021

Background

Previous studies indicated the calcium-binding protein S100A12 to be involved in the pathophysiology of pulmonary inflammatory diseases. However, the role of S100A12 has remained elusive in patients with community-acquired pneumonia (CAP). Therefore, the purpose of this prospective cohort study was to evaluate the association between serum S100A12 with severity and prognosis in CAP patients.

Methods

Two groups with either 239 CAP patients or 239 healthy controls were enrolled in our study. Fasting blood and clinical characteristics were collected. On admission, serum S100A12 was measured using enzyme-linked immunosorbent assay (ELISA).

Results

Serum S100A12 was increased in CAP patients compared to control subjects. Furthermore, serum S100A12 was elevated according to the severity of CAP. Correlative analysis suggested that the level of serum S100A12 was associated with blood routine indices, renal function markers, inflammatory cytokines and other clinical parameters among CAP patients. Additionally, linear and logistical regression analyses indicated that serum S100A12 was positively associated with CAP severity scores in CAP patients. In addition, the association of high serum S100A12 and prognosis was accessed using a follow-up research. Elevated serum S100A12 on admission increased the risk of death and hospital stay in CAP patients during hospitalization.

Conclusions

Elevated serum S100A12 on admission is positively associated with the severity and adverse prognosis in CAP patients, suggesting that S100A12 may involve in the pathophysiological process of CAP. The titre of serum S100A12 may be used as a biomarker for diagnosis and prognosis among CAP patients.
International Prognostic Index-Based Immune Prognostic Model for Diffuse Large B-Cell Lymphoma
Authors: Mu Shidai , Shi Deyao , Ai Lisha , Fan Fengjuan , Peng Fei , Sun Chunyan , Hu Yu
Published: October 2021

Background

The International Prognostic Index (IPI) is widely used to discriminate the prognosis of patients with diffuse large B-cell lymphoma (DLBCL). However, there is a significant need to identify novel valuable biomarkers in the context of targeted therapy, such as immune checkpoint blockade (ICB).

Methods

Gene expression data and clinical DLBCL information were obtained from The Cancer Genome Atlas and Gene Expression Omnibus datasets. A total of 371 immune-related genes in DLBCL patients associated with different IPI risk groups were identified by weighted gene co-expression network analysis, and eight genes were selected to construct an IPI-based immune prognostic model (IPI-IPM). Subsequently, we analyzed the somatic mutation and transcription profiles of the IPI-IPM subgroups as well as the potential clinical response to immune checkpoint blockade (ICB) in IPI-IPM subgroups.

Results

The IPI-IPM was constructed based on the expression ofCMBL,TLCD3B,SYNDIG1,ESM1,EPHA3,HUNK,PTX3, andIL12A, where high-risk patients had worse overall survival than low-risk patients, consistent with the results in the independent validation cohorts. The comprehensive results showed that high IPI-IPM risk scores were correlated with immune-related signaling pathways, highKMT2DandCD79Bmutation rates, and upregulation of inhibitory immune checkpoints, includingPD-L1,BTLA, andSIGLEC7, indicating a greater potential response to ICB therapy.

Conclusion

The IPI-IPM has independent prognostic significance for DLBCL patients, which provides an immunological perspective to elucidate the mechanisms of tumor progression and sheds light on the development of immunotherapy for DLBCL.
Bamboo Fences as a Nature-Based Measure for Coastal Wetland Protection in Vietnam
Authors: Mai Van Cong , Ngo Anh , Mai Tri , Dao H. T.
Published: October 2021

Climate change has induced sea-level rise and a high intensity of storms, which create high nearshore waves. These caused severe mangrove degradation and erosion along the coastal wetland areas in the Mekong Delta in Vietnam. Mangroves in the coastal wetland foreshore can withstand only some certain design storm waves and grow under several certain submerged conditions. Therefore, reducing waves and shallowing wetland elevation for recovering mangroves and protecting them in an early birth state is important. Bamboo or melaleuca fences have been used as a nature-based solution to reduce waves and currents approaching the shore for these above purposes along Vietnamese Mekong deltaic coasts. This paper investigates wave transmission through the bamboo fence system and assesses its effectiveness in protecting the mangroves. Waves were simultaneously measured at two locations for comparison: in front of and behind the fences. The result shows that the wave reduction by the fences is considerable, and sedimentation occurs rapidly in the shelter areas behind the fences, which is highly favorable for the recovery and growth of mangroves. Next, the empirical formulae have been proposed for relationships between the wave transmission coefficient of the fence and the dimensionless wave-structures parameters, such as the relative water depth, the wave steepness, and the fence freeboard. The findings create a basic technical reference for designing a naturally friendly-based solution by using bamboo and/or wooden fences in coastal protection generally and protecting mangroves specifically. The outcome of the research contributes to narrowing an existing gap in Vietnamese design guidelines for coastal wetland protection and also facilitates the use of locally available eco-friendly materials for coastal management along the Vietnamese Mekong delta coasts.
Exclusive Enteral Nutrition Plus Immediate vs. Delayed Washed Microbiota Transplantation in Crohn's Disease With Malnutrition: A Randomized Pilot Study
Authors: Xiang Liyuan , Yu Yan , Ding Xiao , Zhang Hui , Wen Quan , Cui Bota , Zhang Faming
Published: October 2021

Background: The potential of washed microbiota transplantation (WMT) in Crohn's disease (CD) has been reported. This study aimed to explore the suitable timing of WMT in patients with CD complicated with malnutrition.

Methods: This is a randomized, open-label study. Patients with active CD complicated with malnutrition were included and 1:1 randomized to undergo WMT at day 1 (group WMT-DAY1) or day 8 (group WMT-DAY8). The observation duration was 15 days. Exclusive enteral nutrition (EEN) was administered in both groups. The primary outcome was the improvement in nutritional parameters at day 8 and day 15 in two groups. The secondary outcome was the rate of clinical remission at day 15 in two groups.

Results: Totally 19 patients completed the trial. At day 8, the lymphocyte count, albumin and prealbumin increased significantly compared to those at day 1 in group WMT-DAY1 (p = 0.018, p = 0.028, p = 0.028, respectively), while no significant increase in any nutritional parameter was shown in group WMT-DAY8. At day 15, albumin increased significantly compared to that at day 1 in both groups (p < 0.05), while significant increase in prealbumin was only shown in group WMT-DAY1 (p = 0.004) compared to that at day 1. The rate of clinical remission at day 15 in group WMT-DAY1 and group WMT-DAY8 was 87.5% (7/8) and 72.7% (8/11), respectively (p = 0.603).

Conclusion: EEN combined with immediate WMT intervention could rapidly improve the nutritional status and induce clinical remission in malnourished patients with CD.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT02897661.
Effects of the Pars Plana Vitrectomy on the Chronic Total Rhegmatogenous Retinal Detachment in the Young Adults
Authors: Yu Jinguo , Hu Xingxing , Zhang Jiangkai , Han Han , Huang Bo , Brant Rodrigo , Zhang Cheng , Yan Hua
Published: October 2021

Objective: To observe the characteristics and evaluate the efficacy and safety of the chronic total rhegmatogenous retinal detachment (RRD) treatment by the 23-gauge pars plana vitrectomy (PPV) in young adults and to analyze the related factors.

Methods: A retrospective chart review was performed for the young adults who underwent the 23-gauge PPV for the chronic total RRD at the Tianjin Medical University General Hospital from 2011 to 2018. A total of 54 eyes of 48 patients were included in this study. The preoperative vision ranged from 2.00 to 1.00. The mean duration of RRD was 9 ± 0.6 months with a range from 4 to 18 months. The proliferative vitreoretinopathy (PVR) grade D1 and grade D2 was diagnosed in 48 eyes and 6 eyes, respectively. About 37 eyes were filled with C3F8 and 17 eyes were filled with silicone oil tamponade. The follow-up ranged from 9 to 78 months with a mean of 23 ± 2.2 months.

Results: The postoperative visual acuity increased in all the eyes at the final observation. The retinal attachment was achieved in 49 eyes (90.7%) in the primary PPV. Five eyes (9.3%) with the failed retinal attachment finally achieved the attachment after the second procedure. The postoperative complications mainly included temporary intraocular pressure (IOP) elevation, hyphema, and retinal redetachment.

Conclusion: Chronic total RRD can be treated via the 23-gauge PPV with a great anatomical and visual prognosis in the young adult. The successful treatment of the chronic total RRD in young adults is mainly associated with the complete dissection of the severe vitreoretinopathy, especially for the epiretinal membrane at the retinal breaks and degenerations and the subretinal proliferation during surgery.
Ewe Vaginal Microbiota: Associations With Pregnancy Outcome and Changes During Gestation
Authors: Koester Lucas R. , Petry Amy L. , Youngs Curtis R. , Schmitz-Esser Stephan
Published: October 2021

Reproductive performance is paramount to the success of livestock production enterprises focused on lamb meat production. Reproductive success is influenced by various factors, possibly including the reproductive tract microbial communities present at the time of copulation and throughout pregnancy. There are few publications that identify the vaginal microbial communities of livestock, and even fewer exist for sheep. To compare ewe vaginal microbial communities, vaginal swabs were taken from 67 Hampshire and Hampshire X Suffolk crossbred ewes from the Iowa State University sheep farm at a pre-breeding time point (S1) and after pregnancy testing (S2). Animals that were determined pregnant were sampled again within a few days of expected parturition (S3). DNA was extracted from these swabs, and 16S rRNA gene Illumina MiSeq amplicon sequencing was conducted to fingerprint the bacterial communities found within this system. Pre-breeding time point samples showed no differences in community structure between animals later found to be pregnant or non-pregnant, but significant changes were detected in species richness (Chao; P < 0.001) and species diversity (Shannon; P < 0.001) at the second sampling time point. A higher microbial diversity within the S2 time point samples may suggest a more stable environment driven by pregnancy, as this increased diversity is maintained in pregnant animals from the S2 to the S3 time point. Additionally, several bacterial phylotypes, such as Mannheimia, Oscillospiraceae-like OTUs and Alistipes, were more abundant at either the S1 or S2 time points in animals that established pregnancy, suggesting a beneficial effect on pregnancy outcome. This study identifies changes within the microbial communities of the ewe vagina before and during gestation and offers inferences on how these changes may impact pregnancy outcome. Information presented herein offers new knowledge about sheep vaginal microbial communities and serves as a starting point to help guide researchers to improve sheep reproductive performance in the future.
Pseudorabies Virus US3 Protein Inhibits IFN-β Production by Interacting With IRF3 to Block Its Activation
Authors: Xie Jingying , Zhang Xiangbo , Chen Lei , Bi Yingjie , Idris Adi , Xu Shujuan , Li Xiangrong , Zhang Yong , Feng Ruofei
Published: October 2021

Pseudorabies virus is a typical swine alphaherpesvirus, which can cause obvious neurological disorders and reproductive failure in pigs. It is capable of evading host antiviral immune response. However, the mechanism by which many PRV proteins assist the virus to evade innate immunity is not fully understood. This study identified PRV US3 protein as a crucial antagonistic viral factor that represses interferon beta (IFN-β) expression. A in-depth study showed that US3 protein restricted type I IFN production by targeting interferon regulatory factor 3 (IRF3), a key molecule required for type I IFN induction. Additionally, US3 protein interacted with IRF3, degraded its protein expression to block the phosphorylation of IRF3. These findings suggested a novel strategy utilized by PRV to inhibit IFN-β production and escape the host innate immunity.
Plasma and CSF Neurofilament Light Chain in Amyotrophic Lateral Sclerosis: A Cross-Sectional and Longitudinal Study
Authors: Vacchiano Veria , Mastrangelo Andrea , Zenesini Corrado , Masullo Marco , Quadalti Corinne , Avoni Patrizia , Polischi Barbara , Cherici Arianna , Capellari Sabina , Salvi Fabrizio , Liguori Rocco , Parchi Piero
Published: October 2021

Background: Neurofilament light chain (NfL) is a validated biofluid marker of neuroaxonal damage with great potential for monitoring patients with neurodegenerative diseases. We aimed to further validate the clinical utility of plasma (p) vs. CSF (c) NfL for distinguishing patients with Amyotrophic Lateral Sclerosis (ALS) from ALS mimics. We also assessed the association of biomarker values with clinical variables and survival and established the longitudinal changes of pNfL during the disease course.

Methods: We studied 231 prospectively enrolled patients with suspected ALS who underwent a standardized protocol including neurological examination, electromyography, brain MRI, and lumbar puncture. Patients who received an alternative clinical diagnosis were considered ALS mimics. We classified the patients based on the disease progression rate (DPR) into fast (DPR > 1), intermediate (DPR 0.5–1), and slow progressors (DPR < 0.5). All patients were screened for the most frequent ALS-associated genes. Plasma and CSF samples were retrospectively analyzed; NfL concentrations were measured with the SIMOA platform using a commercial kit.

Results: ALS patients (n = 171) showed significantly higher pNfL (p < 0.0001) and cNfL (p < 0.0001) values compared to ALS mimics (n = 60). Both cNfL and pNfL demonstrated a good diagnostic value in discriminating the two groups, although cNfL performed slightly better (cNfL: AUC 0.924 ± 0.022, sensitivity 86.8%, specificity 92.4; pNfL: AUC 0.873 ± 0.036, sensitivity 84.7%, specificity 83.3%). Fast progressors showed higher cNfL and pNfL as compared to intermediate (p = 0.026 and p = 0.001) and slow progressors (both p < 0.001). Accordingly, ALS patients with higher baseline cNfL and pNfL levels had a shorter survival (highest tertile of cNfL vs. lowest tertile, HR 4.58, p = 0.005; highest tertile of pNfL vs. lowest tertile, HR 2.59, p = 0.015). Moreover, there were positive associations between cNfL and pNfL levels and the number of body regions displaying UMN signs (rho = 0.325, p < 0.0001; rho = 0.308, p = 0.001). Finally, longitudinal analyses in 57 patients showed stable levels of pNfL during the disease course.

Conclusion: Both cNfL and pNfL have excellent diagnostic and prognostic performance for symptomatic patients with ALS. The stable longitudinal trajectory of pNfL supports its use as a marker of drug effect in clinical trials.
Adolescent Binge-Type Ethanol Exposure in Rats Mirrors Age-Related Cognitive Decline by Suppressing Cholinergic Tone and Hippocampal Neurogenesis
Authors: Reitz Nicole L. , Nunes Polliana T. , Savage Lisa M.
Published: October 2021

Heavy alcohol consumption followed by periods of abstinence (i.e., binge drinking) during adolescence is a concern for both acute and chronic health issues. Persistent brain damage after adolescent intermittent ethanol exposure in rodents, a model of binge drinking, includes reduced hippocampal neurogenesis and a loss of neurons in the basal forebrain that express the cholinergic phenotype. The circuit formed between those regions, the septohippocampal pathway, is critical for learning and memory. Furthermore, this circuit is also altered during the aging process. Thus, we examined whether pathology in septohippocampal circuit and impairments in spatial behaviors are amplified during aging following adolescent intermittent ethanol exposure. Female and male rats were exposed to intermittent intragastric gavage of water (control) or 20% ethanol (dose of 5 g/kg) for a 2 days on/off cycle from postnatal days 25–55. Either 2 (young adult) or 12–14 (middle-age) months post exposure, rats were tested on two spatial tasks: spontaneous alternation and novel object in place. Acetylcholine efflux was assessed in the hippocampus during both tasks. There was no adolescent ethanol-induced deficit on spontaneous alternation, but middle-aged male rats displayed lower alternation rates. Male rats exposed to ethanol during adolescence had blunted behavioral evoked acetylcholine during spontaneous alternation testing. All ethanol-exposed rats displayed suppression of the cholinergic neuronal phenotype. On the novel object in place task, regardless of sex, ethanol-exposed rats performed significantly worse than control-treated rats, and middle aged-rats, regardless of sex or ethanol exposure, were significantly impaired relative to young adult rats. These results indicate that male rats display earlier age-related cognitive impairment on a working memory task. Furthermore, male rats exposed to ethanol during adolescence have blunted behavior-evoked hippocampal acetylcholine efflux. In addition, middle-aged and ethanol-exposed rats, regardless of sex, are impaired at determining discrete spatial relationship between objects. This type of pattern separation impairment was associated with a loss of neurogenesis. Thus, binge-type adolescent ethanol exposure does affect the septohippocampal circuit, and can accelerate age-related cognitive impairment on select spatial tasks.