bluuebunny/crossref_metadata_2025 huggingface dataset:
Passivity Enhancement Strategy of Grid-Connected Inverter System Based on the Adaptive Active Damper
Authors: Shi Chen , Zhao Jianfeng
Published: May 2022

The grid-connected inverter system may be unstable when connected to a weak grid, and installing an active damper as a virtual resistor at the PCC is convenient for stabilizing the system. This article proposes a passivity enhancement strategy for the grid-connected inverter system via the adaptive active damper. Furthermore, the admittances of the grid-connected inverter system with the active damper are derived, and the real parts of the admittances of the whole system have been calculated. And the admittance measurement results obtained by the frequency scanning method approximately match the theoretical results. Additionally, the virtual resistor’s stability region is discussed, the bandwidth of the phase-locked loop is recommended, ensuring the stabilizing effect of the active damper under the weak grid. And the online resonance frequency detection algorithm guarantees the passivity enhancement of the active damper when grid impedance changes. Finally, controller hardware-in-the-loop tests validate the theoretical analysis of passivity enhancement based on the active damper.
Rainwater Harvesting Systems That Reduce Water Consumption With Optimal Locations of Solar Concentration Power Plants
Authors: Murillo-Alvarado Pascual Eduardo , Cárdenas Gil Marco Antonio
Published: May 2022

At present, the increase in population has caused an increase in the demand for electrical energy, which creates saturation in the national electrical system. In addition to this, the main source of energy for the generation of electricity is fossil fuels, which causes environmental pollution problems due to the increase in the concentration of greenhouse gases. To counteract the negative environmental impact, new energy sources that are friendlier to the environment have been sought, such as solar energy through power generation plants using solar concentrators. In this sense, this research proposes a mathematical optimization model to determine the feasibility of installing electric power generation plants through solar concentrators, to satisfy the energy demand in cities with the highest demand for electric power in the state of Michoacán. The proposed model considers the availability of water resources, the demand for energy, the costs involved for the installation of power generation plants, and the sizing of water collection systems to reduce the consumption of fresh water that is extracted from natural sources. It is a linear integer mixed programming model, where two scenarios are analyzed, considering variation in the operating time of the thermal storage system and the incorporation of the rainwater harvesting system to reduce freshwater consumption. The results show that 237,600 MW can be produced by installing three of the six power generation plants considered and considering a 19 h operation with thermal storage, generating a profit from the sales of the energy produced of 6,326,700 USD/year. Likewise, with the sizing of the rainwater harvesting system, it is possible to collect 1,678 m3 for the operation of the three determined power generation plants.
Urban Climate Informatics: An Emerging Research Field
Authors: Middel Ariane , Nazarian Negin , Demuzere Matthias , Bechtel Benjamin
Published: May 2022

The scientific field of urban climatology has long investigated the two-way interactions between cities and their overlying atmosphere through in-situ observations and climate simulations at various scales. Novel research directions now emerge through recent advancements in sensing and communication technologies, algorithms, and data sources. Coupled with rapid growth in computing power, those advancements augment traditional urban climate methods and provide unprecedented insights into urban atmospheric states and dynamics. The emerging field introduced and discussed here as Urban Climate Informatics (UCI) takes on a multidisciplinary approach to urban climate analyses by synthesizing two established domains: urban climate and climate informatics. UCI is a rapidly evolving field that takes advantage of four technological trends to answer contemporary climate challenges in cities: advances in sensors, improved digital infrastructure (e.g., cloud computing), novel data sources (e.g., crowdsourced or big data), and leading-edge analytical algorithms and platforms (e.g., machine learning, deep learning). This paper outlines the history and development of UCI, reviews recent technological and methodological advances, and highlights various applications that benefit from novel UCI methods and datasets.
Analyzing the Spatial Distribution of LST and Its Relationship With Underlying Surfaces in Different Months by Classification and Intersection
Authors: Wei Xiao , Wang Xiao-Jun
Published: May 2022

Urban heat islands (UHIs) have become one of the most critical issues around the world, especially in the context of rapid urbanization and global climate change. Extensive research has been conducted across disciplines on the factors related to land surface temperature (LST) and how to mitigate the UHI effect. However, there remain deficiencies in the exploration of LST changes across time and their relationship with underlying surfaces in different temperature ranges. In order to fill the gap, this study compared the LST of each month by using the quantile classification method taking the Landsat 8 images of Nanjing on May 18th, July 21st, and October 9th in 2017 as the subject and then calculated the differences between July and May as well as that between July and October by an intersection tool taking the LST classes of July as the baseline. Additionally, the spatial pattern of each temperature class and intersection area was analyzed with the help of several landscape metrics, and the land contribution index (LCI) was utilized to better quantify the thermal contribution of each underlying surface to the area. The results indicated that the difference between months mainly reflected in the medium temperature area, especially between July and October, in which landscape patterns illustrated a trend of fragmentation and decentralization. The proportions of underlying surfaces in different types of intersection revealed the distinction of their warming and cooling degrees over time, in which the warming degree of other rigid pavement was higher in the warming process from May to July, and the cooling degree of buildings was greater in the cooling process from July to October. The LCI of each underlying surface in the entire study area was different from that in each temperature class, indicating that underlying surfaces had distinguished thermal contributions in different temperature ranges. This study is expected to fill the gap in previous studies and provide a new perspective on the mitigation of UHI.
TGF-β Signaling Pathway-Based Model to Predict the Subtype and Prognosis of Head and Neck Squamous Cell Carcinoma
Authors: Zheng Lian , Guan Zhenjie , Xue Miaomiao
Published: May 2022

Background: Although immunotherapy with immune checkpoint therapy has been used to treat head and neck squamous cell carcinoma (HNSCC), response rates and treatment sensitivity remain limited. Recent studies have indicated that transforming growth factor-β (TGF-β) may be an important target for novel cancer immunotherapies.

Materials and methods: We collected genomic profile data from The Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator method and Cox regression were used to establish a prognostic model. Gene set enrichment analysis was applied to explore biological functions. Tracking of indels by decomposition and subclass mapping algorithms were adopted to evaluate immunotherapy efficiency.

Result: We established a seven TGF-β pathway-associated gene signature with good prediction efficiency. The high-risk score subgroup mainly showed enrichment in tumor-associated signaling such as hypoxia and epithelial-mesenchymal transition (EMT) pathways; This subgroup was also associated with tumor progression. The low-risk score subgroup was more sensitive to immunotherapy and the high-risk score subgroup to cisplatin, erlotinib, paclitaxel, and crizotinib.

Conclusion: The TGF-β pathway signature gene model provides a novel perspective for evaluating effectiveness pre-immunotherapy and may guide further studies of precision immuno-oncology.
Mechanisms of Kwashiorkor-Associated Immune Suppression: Insights From Human, Mouse, and Pig Studies
Authors: Michael Husheem , Amimo Joshua O. , Rajashekara Gireesh , Saif Linda J. , Vlasova Anastasia N.
Published: May 2022

Malnutrition refers to inadequate energy and/or nutrient intake. Malnutrition exhibits a bidirectional relationship with infections whereby malnutrition increases risk of infections that further aggravates malnutrition. Severe malnutrition (SM) is the main cause of secondary immune deficiency and mortality among children in developing countries. SM can manifest as marasmus (non-edematous), observed most often (68.6% of all malnutrition cases), kwashiorkor (edematous), detected in 23.8% of cases, and marasmic kwashiorkor, identified in ~7.6% of SM cases. Marasmus and kwashiorkor occur due to calorie-energy and protein-calorie deficiency (PCD), respectively. Kwashiorkor and marasmic kwashiorkor present with reduced protein levels, protein catabolism rates, and altered levels of micronutrients leading to uncontrolled oxidative stress, exhaustion of anaerobic commensals, and proliferation of pathobionts. Due to these alterations, kwashiorkor children present with profoundly impaired immune function, compromised intestinal barrier, and secondary micronutrient deficiencies. Kwashiorkor-induced alterations contribute to growth stunting and reduced efficacy of oral vaccines. SM is treated with antibiotics and ready-to-use therapeutic foods with variable efficacy. Kwashiorkor has been extensively investigated in gnotobiotic (Gn) mice and piglet models to understand its multiple immediate and long-term effects on children health. Due to numerous physiological and immunological similarities between pigs and humans, pig represents a highly relevant model to study kwashiorkor pathophysiology and immunology. Here we summarize the impact of kwashiorkor on children’s health, immunity, and gut functions and review the relevant findings from human and animal studies. We also discuss the reciprocal interactions between PCD and rotavirus—a highly prevalent enteric childhood pathogen due to which pathogenesis and immunity are affected by childhood SM.
T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis
Authors: Costa-Madeira Juliana C. , Trindade Gabrielly B. , Almeida Paulo H. P. , Silva João S. , Carregaro Vanessa
Published: May 2022

A key point of immunity against protozoanLeishmaniaparasites is the development of an optimal T cell response, which includes a low apoptotic rate, high proliferative activity and polyfunctionality. During acute infection, antigen-specific T cells recognize the pathogen resulting in pathogen control but not elimination, promoting the development and the maintenance of a population of circulating effector cells that mount rapid response quickly after re-exposure to the parasite. However, in the case of visceral disease, the functionality of specific T cells is lost during chronic infection, resulting in inferior effector functions, poor response to specific restimulation, and suboptimal homeostatic proliferation, a term referred to as T cell exhaustion. Multiple factors, including parasite load, infection duration and host immunity, affect T lymphocyte exhaustion. These factors contribute to antigen persistence by promoting inhibitory receptor expression and sustained production of soluble mediators, influencing suppressive cell function and the release of endogenous molecules into chronically inflamed tissue. Together, these signals encourage several changes, reprogramming cells into a quiescent state, which reflects disease progression to more severe forms, and development of acquired resistance to conventional drugs to treat the disease. These points are discussed in this review.
NK Cells Equipped With a Chimeric Antigen Receptor That Overcomes Inhibition by HLA Class I for Adoptive Transfer of CAR-NK Cells
Authors: Zhuang Xiaoxuan , Long Eric O.
Published: May 2022

Dominant inhibitory receptors for HLA class I (HLA-I) endow NK cells with high intrinsic responsiveness, a process termed licensing or education, but hinder their ability to kill HLA-I+ tumor cells. Cancer immunotherapy with adoptive transfer of NK cells must overcome inhibitory signals by such receptors to promote elimination of HLA-I+ tumor cells. As proof of concept, we show here that a chimeric antigen receptor (CAR) can be engineered to overcome inhibition by receptors for HLA-I and to promote lysis of HLA-I+ tumor cells by CAR-NK cells. The design of this NK-tailored CAR (NK-CAR) relied on the potent NK cell activation induced by the synergistic combination of NK receptors CD28H (CD28 homolog, TMIGD2) and 2B4 (CD244, SLAMF4). An NK-CAR consisting of the single-chain fragment variable (scFv) of a CD19 antibody, the CD28H transmembrane domain, and the fusion of CD28H, 2B4, and TCRζ signaling domains was compared to a third-generation T-cell CAR with a CD28-41BB-TCRζ signaling domain. The NK-CAR delivered stronger activation signals to NK cells and induced more robust tumor cell lysis. Furthermore, such CAR-NK cells could overcome inhibition by HLA-E or HLA-C expressed on tumor cells. Therefore, engineering of CAR-NK cells that could override inhibition by HLA-I in patients undergoing cancer immunotherapy is feasible. This approach offers an attractive alternative to more complex strategies, such as genetic editing of inhibitory receptors in CAR-NK cells or treatment of patients with a combination of CAR-NK cells and checkpoint blockade with antibodies to inhibitory receptors. A significant benefit of inhibition-resistant NK-CARs is that NK cell inhibition would be overcome only during contact with targeted tumor cells and that HLA-I on healthy cells would continue to maintain NK cell responsiveness through licensing.
Fitness of B-Cell Responses to SARS-CoV-2 WT and Variants Up to One Year After Mild COVID-19 – A Comprehensive Analysis
Authors: Meyer Benjamin , Martinez-Murillo Paola Andrea , Lemaitre Barbara , Blanchard-Rohner Géraldine , Didierlaurent Arnaud M. , Fontannaz Paola , Eugercios Manzanas Chloé , Lambert Paul-Henri , Loevy Natasha , Kaiser Laurent , Sartoretti Julie , Tougne Chantal , Villard Jean , Huttner Angela , Siegrist Claire-Anne , Eberhardt Christiane S.
Published: May 2022

Objective

To comprehensively evaluate SARS-CoV-2 specific B-cell and antibody responses up to one year after mild COVID-19.

Methods

In 31 mildly symptomatic COVID-19 participants SARS-CoV-2-specific plasmablasts and antigen-specific memory B cells were measured by ELISpot. Binding antibodies directed against the proteins spike (S), domain S1, and nucleocapsid (N) were estimated using rIFA, ELISA, and commercially available assays, and avidity measured using thiocyanate washout. Neutralizing antibodies against variants of concern were measured using a surrogate-neutralization test.

Results

Plasmablast responses were assessed in all participants who gave sequential samples during the first two weeks after infection; they preceded the rise in antibodies and correlated with antibody titers measured at one month. S1 and N protein-specific IgG memory B-cell responses remained stable during the first year, whereas S1-specific IgA memory B-cell responses declined after 6 months. Antibody titers waned over time, whilst potent affinity maturation was observed for anti-RBD antibodies. Neutralizing antibodies against wild-type (WT) and variants decayed during the first 6 months but titers significantly increased for Alpha, Gamma and Delta between 6 months and one year. Therefore, near-similar titers were observed for WT and Alpha after one year, and only slightly lower antibody levels for the Delta variant compared to WT. Anti-RBD antibody responses correlated with the neutralizing antibody titers at all time points, however the predicted titers were 3-fold lower at one year compared to one month.

Conclusion

In mild COVID-19, stable levels of SARS-CoV-2 specific memory B cells and antibodies neutralizing current variants of concern are observed up to one year post infection. Care should be taken when predicting neutralizing titers using commercial assays that measure binding antibodies.
The Effects of Free Heme on Functional and Molecular Changes During Ex Vivo Normothermic Machine Perfusion of Human Kidneys
Authors: Hosgood Sarah A. , Elliott Tegwen R. , Jordan Nina P. , Nicholson Michael L.
Published: May 2022

Normothermic machine perfusion (NMP) is a technique of kidney preservation designed to restore cellular metabolism after cold ischemia. Kidneys are perfused with an oxygenated banked red blood cell (RBC) based solution for 1h at 36°C. During NMP, RBCs can become damaged, releasing free heme into the perfusate. This can act as a damage-associated molecular pattern (DAMP) activating inflammatory signalling pathways. The aim of this study was to measure the levels of free heme during NMP, assess the effect on kidney function and determine any association with inflammatory and stress related gene expression. Levels of free heme were measured in perfusate samples from a series of donation after circulatory death (DCD) kidneys undergoing NMP as part of a randomised controlled trial (RCT). The age of RBCs and levels of free heme were correlated with perfusion parameters. Changes in gene expression were analysed in a series of kidneys declined for transplantation using the NanoString nCounter Organ Transplant Panel and qRT-PCR. Older units of RBCs were associated with higher levels of free heme and levels increased significantly during NMP (Pre 8.56 ± 7.19µM vs 26.29 ± 15.18µM, P<0.0001). There was no association with levels of free heme and perfusion parameters during NMP (P > 0.05). Transcriptional and qPCR analysis demonstrated the upregulation of differentially expressed genes associated with apoptosis (FOS and JUN), inflammatory cytokines (IL-6, SOCS3, ATF3), chemokines (CXCL8, CXCL2, CC3/L1) and oxidative stress (KLF4) after NMP. However, these did not correlate with levels of free heme (P >0.05). A significant amount of free heme can be detected in the perfusate before and after NMP particularly when older units of red cells are used. Although transcriptional analysis demonstrated significant upregulation of genes involved with apoptotic, inflammatory and oxidative pathways these were not associated with high levels of free heme.
Effector Memory T Cells and CD45RO+ Regulatory T Cells in Metastatic vs. Non-Metastatic Lymph Nodes in Lung Cancer Patients
Authors: Kwiecień Iwona , Rutkowska Elżbieta , Sokołowski Rafał , Bednarek Joanna , Raniszewska Agata , Jahnz-Różyk Karina , Rzepecki Piotr , Domagała-Kulawik Joanna
Published: May 2022

Lymphocytes play a leading role in regulation of the immune system in lung cancer patients. The recognition of T cells profile may help in prediction of effectiveness of anticancer immunotherapy. The aim of the study was to determine the dominant subpopulation of CD4+ and CD8+ lymphocytes in metastatic and non-metastatic lymph nodes (LNs) of lung cancer patients. LNs aspirates were obtained during EBUS/TBNA procedure and cells were analyzed by flow cytometry. We showed a higher percentage of CD4+ and CD8+ effector memory T cells in the metastatic than in the non-metastatic LNs (28.6 vs. 15.3% and 28.6 vs. 14.0%, p< 0.05). The proportion of CD45RO+ T regulatory cells (CD45RO+ Tregs) was higher in the metastatic LNs than in the non-metastatic ones (65.6 vs. 31%, p< 0.05). We reported the significant differences in T cell subsets depending on the lung cancer metastatic process. We observed that the effector memory T cells were predominant subpopulations in metastatic LNs. Lymphocyte profile in LNs is easy to evaluate by flow cytometry of EBUS/TBNA samples and may reflect the immune status in lung cancer.
Furin and TMPRSS2 Resistant Spike Induces Robust Humoral and Cellular Immunity Against SARS-CoV-2 Lethal Infection
Authors: Lin Jhe-Jhih , Tien Chih-Feng , Kuo Yi-Ping , Lin En-Ju , Tsai Wei-Hsiang , Chen Ming-Yu , Tsai Pei-Ju , Su Yu-Wen , Pathak Nikhil , Yang Jinn-Moon , Yu Chia-Yi , Chuang Zih-Shiuan , Wu Han-Chieh , Tsai Wan-Ting , Dai Shih-Syong , Liao Hung-Chun , Chai Kit Man , Su Yu-Siang , Chuang Tsung-Hsien , Liu Shih-Jen , Chen Hsin-Wei , Dou Horng-Yunn , Chen Feng-Jui , Chen Chiung-Tong , Liao Chin-Len , Yu Guann-Yi
Published: May 2022

An effective COVID-19 vaccine against broad SARS-CoV-2 variants is still an unmet need. In the study, the vesicular stomatitis virus (VSV)-based vector was used to express the SARS-CoV-2 Spike protein to identify better vaccine designs. The replication-competent of the recombinant VSV-spike virus with C-terminal 19 amino acid truncation (SΔ19 Rep) was generated. A single dose of SΔ19 Rep intranasal vaccination is sufficient to induce protective immunity against SARS-CoV-2 infection in hamsters. All the clones isolated from the SΔ19 Rep virus contained R682G mutation located at the Furin cleavage site. An additional S813Y mutation close to the TMPRSS2 cleavage site was identified in some clones. The enzymatic processing of S protein was blocked by these mutations. The vaccination of the R682G-S813Y virus produced a high antibody response against S protein and a robust S protein-specific CD8+ T cell response. The vaccinated animals were protected from the lethal SARS-CoV-2 (delta variant) challenge. The S antigen with resistance to enzymatic processes by Furin and TMPRSS2 will provide better immunogenicity for vaccine design.
Extracellular Vesicles From TNFα Preconditioned MSCs: Effects on Immunomodulation and Bone Regeneration
Authors: Kang Miya , Huang Chun-Chieh , Gajendrareddy Praveen , Lu Yu , Shirazi Sajjad , Ravindran Sriram , Cooper Lyndon F.
Published: May 2022

Mesenchymal stem cells show remarkable versatility and respond to extracellular and micro environmental cues by altering their phenotype and behavior. In this regard, the MSC’s immunomodulatory properties in tissue repair are well documented. The paracrine effects of MSCs in immunomodulation are, in part, attributable to their secreted extracellular vesicles (EVs). When MSCs migrate to the wound bed, they are exposed to a myriad of inflammatory signals. To understand their response to an inflammatory environment from an EV perspective, we sought to evaluate the effects of the inflammatory cytokine TNFα on MSC EV mediated immunomodulation. Our results indicate that while the physical characteristics of the EVs remain unchanged, the TNFα preconditioned MSC EVs possess enhanced immunomodulatory properties. In vitro experiments using polarized (M1 and M2) primary mouse macrophages indicated that the preconditioned MSC EVs suppressed pro-inflammatory (M1) markers such as IL-1β and iNOS and elevated reparatory (M2) markers such as Arg1 and CD206. When evaluated in vivo in a rat calvarial defect model, the TNFα preconditioned MSC EVs reduced inflammation at 1-, 3- and 7-days post wounding resulting in the subsequent enhanced bone formation at 4- and 8-weeks post wounding possibly by modulation of oncostatin M (OSM) expression. An analysis of EV miRNA composition revealed significant changes to anti-inflammatory miRNAs in the preconditioned MSC EVs hinting at a possible role for EV derived miRNA in the enhanced immunomodulatory activity. Overall, these results indicate that MSC exposure to inflammatory signals influence the MSC EV’s immunomodulatory function in the context of tissue repair. The specific function of TNFα preconditioned MSC EV miRNAs in immunomodulatory control of bone regeneration merits further investigation.
Humoral Response to BNT162b2 Vaccine Against SARS-CoV-2 Variants Decays After Six Months
Authors: Lopera Tulio J. , Chvatal-Medina Mateo , Flórez-Álvarez Lizdany , Zapata-Cardona Maria I. , Taborda Natalia A. , Rugeles Maria T. , Hernandez Juan C.
Published: May 2022

SARS-CoV-2 vaccines have shown very high effectiveness in real-world scenarios. However, there is compelling evidence for a fast-paced waning of immunity. The increasing number of new variants that could alter the severity, transmissibility, and potential to evade the immune response raised significant concern. Therefore, elucidating changes in the humoral immune response against viral variants induced by vaccines over time is crucial for improving immunization protocols. We carried out a 6-month longitudinal prospective study in which 60 individuals between 21 and 71 years of age who have received the complete scheme of the BNT162b2 vaccine were followed to determine titers of serum neutralizing activity. The neutralizing capacity was measured at one, three, and six-months post-vaccination by plaque reduction neutralization assay using SARS-CoV-2 B.1 (D614G) and the Gamma, Alpha, Delta, and Mu variants. Data were analyzed using GraphPad 5.0. Neutralizing activity against five different SARS-CoV-2 variants was detected in the serum samples of all vaccinated participants to a different extent after one month, with a progressive decrease according to age and gender. Overall, after one month of vaccination, the neutralizing titer was lower for all evaluated variants when compared to B.1, most remarkable against Delta and Mu, with a reduction of 83.1% and 92.3%, respectively. In addition, the Titer at 3- or 6-months follow-up decreased dramatically for all variants. Our results support the decaying of serum neutralizing activity, both over time and across SARS-CoV-2 variants, being more significant in older men. Since Delta and Mu appear to evade the neutralizing activity, these and further new variants of immune escape mutations should be considered for novel vaccine formulations.
Serial Analysis of the T-Cell Receptor β-Chain Repertoire in People Living With HIV Reveals Incomplete Recovery After Long-Term Antiretroviral Therapy
Authors: Towlerton Andrea M. H. , Ravishankar Shashidhar , Coffey David G. , Puronen Camille E. , Warren Edus H.
Published: May 2022

Long-term antiretroviral therapy (ART) in people living with HIV (PLHIV) is associated with sustained increases in CD4+ T-cell count, but its effect on the peripheral blood T-cell repertoire has not been comprehensively evaluated. In this study, we performed serial profiling of the composition and diversity of the T-cell receptor β-chain (TRB) repertoire in 30 adults with HIV infection before and after the initiation of ART to define its long-term impact on the TRB repertoire. Serially acquired blood samples from 30 adults with HIV infection collected over a mean of 6 years (range, 1-12) years, with 1-4 samples collected before and 2-8 samples collected after the initiation of ART, were available for analysis. TRB repertoires were characterized via high-throughput sequencing of the TRB variable region performed on genomic DNA extracted from unsorted peripheral blood mononuclear cells. Additional laboratory and clinical metadata including serial measurements of HIV viral load and CD4+ T-cell count were available for all individuals in the cohort. A previously published control group of 189 TRB repertoires from peripheral blood samples of adult bone marrow transplant donors was evaluated for comparison. ART initiation in PLHIV was associated with a sustained reduction in viral load and a significant increase in TRB repertoire diversity. However, repertoire diversity in PLHIV remained significantly lower than in the control group even after long-term ART. The composition of TRB repertoires of PLHIV after ART also remained perturbed compared to the control cohort, as evidenced by large persistent private clonal expansions, reduced efficiency in the generation of TRB CDR3 amino acid sequences, and a narrower range of CDR3 lengths. Network analysis revealed an antigen-experienced structure in the TRB repertoire of PLHIV both before and after ART initiation that was quite distinct from the structure of control repertoires, with a slight shift toward a more naïve structure observed after ART initiation. Though we observe significant improvement in TRB repertoire diversity with durable viral suppression in PLHIV on long-term ART, the composition and structure of these repertoires remain significantly perturbed compared to the control cohort of adult bone marrow transplant donors.
The Diel and Seasonal Heterogeneity of Carbonate Chemistry and Dissolved Oxygen in Three Types of Macroalgal Habitats
Authors: Li Huiru , Moon Hanbi , Kang Eun Ju , Kim Ja-Myung , Kim Miok , Lee Kitack , Kwak Cheol-Woo , Kim Haryun , Kim Il-Nam , Park Ki Yeol , Lee Young Kweon , Jin Ji Woong , Edwards Matthew S. , Kim Ju-Hyoung
Published: May 2022

As concerns about ocean acidification continue to grow, the importance of macroalgal communities in buffering coastal seawater biogeochemistry through their metabolisms is gaining more attention. However, studies on diel and seasonal fluctuations in seawater chemistry within these communities are still rare. Here, we characterized the spatial and temporal heterogeneity in diel and seasonal dynamics of seawater carbonate chemistry and dissolved oxygen (DO) in three types of macroalgal habitats (UAM: ulvoid algal mat dominated, TAM: turf algal mat dominated, and SC: Sargassum horneri and coralline algae dominated). Our results show that diel fluctuations in carbonate parameters and DO varied significantly among habitat types and seasons due to differences in their biological metabolisms (photosynthesis and calcification) and each site’s hydrological characteristics. Specifically, carbonate parameters were most affected by biological metabolisms at the SC site, and by environmental variables at the UAM site. Also, we demonstrate that macroalgal communities reduced ocean acidification conditions when ocean temperatures supported photosynthesis and thereby the absorption of dissolved inorganic carbon. However, once temperatures exceeded the optimum ranges for macroalgae, respiration within these communities exceeded photosynthesis and increased CO2 concentrations, thereby exacerbating ocean acidification conditions. We conclude that the seawater carbonate chemistry is strongly influenced by the metabolisms of the dominant macroalgae within these different habitat types, which may, in turn, alter their buffering capacity against ocean acidification.
Modeling Coastal Environmental Change and the Tsunami Hazard
Authors: Weiss Robert , Dura Tina , Irish Jennifer L.
Published: May 2022

The hazard from earthquake-generated tsunami waves is not only determined by the earthquake’s magnitude and mechanisms, and distance to the earthquake area, but also by the geomorphology of the nearshore and onshore areas, which can change over time. In coastal hazard assessments, a changing coastal environment is commonly taken into account by increasing the sea-level to projected values (static). However, sea-level changes and other climate-change impacts influence the entire coastal system causing morphological changes near- and onshore (dynamic). We compare the run-up of the same suite of earthquake-generated tsunamis to a barrier island-marsh-lagoon-marsh system for statically adjusted and dynamically adjusted sea level and bathymetry. Sea-level projections from 2000 to 2100 are considered. The dynamical adjustment is based on a morphokinetic model that incorporates sea-level along with other climate-change impacts. We employ Representative Concentration Pathways 2.6 and 8.5 without and with treatment of Antarctic Ice-sheet processes (known as K14 and K17) as different sea-level projections. It is important to note that we do not account for the occurrence probability of the earthquakes. Our results indicate that the tsunami run-up hazard for the dynamic case is approximately three times larger than for the static case. Furthermore, we show that nonlinear and complex responses of the barrier island-marsh-lagoon-marsh system to climate change profoundly impacts the tsunami hazard, and we caution that the tsunami run-up is sensitive to climate-change impacts that are less well-studied than sea-level rise.
Rapid and Sensitive Assay of Helicobacter pylori With One-Tube RPA-CRISPR/Cas12 by Portable Array Detector for Visible Analysis of Thermostatic Nucleic Acid Amplification
Authors: Dai Bing , Xiang An , Qu Di , Chen Guo , Wang Li , Wang Wenwen , Zhai Dongsheng , Wang Lei , Lu Zifan
Published: May 2022

Helicobacter pylori (H. pylori) has infected more than half of the world’s population and is still a threat to human health. The urea breath test, despite being widely used in clinical diagnosis, still faces huge challenges in the immediate detection of H. pylori. Thus, a rapid, sensitive, and highly specific point of care diagnosis is particularly important for preventing the further transmission of H. pylori and for real-time monitoring of the disease in a given population. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostics have been applied to various types of nucleic acid testing; however, there are often shortcomings of complex operation and high signal transmission background. In this study, we proposed a new platform for the assay of H. pylori using one-tube-based CRISPR/Cas12a diagnostic methods and designed a detector for this platform, which is a portable array detector for visible analysis of thermostatic nucleic acid amplification (Pad-VATA). By incorporating isothermal recombinase polymerase amplification, our platform could detect the conserved gene fragments of H. pylori with a constant low as 2 copies/μl. The assay process can be performed at a single temperature in about 30 min and integrated into the reactor in the palm-sized Pad-VATA to facilitate rapid diagnosis of H. pylori. We also verified the accuracy of our platform using 10 clinical samples and found that the platform can quickly detect H. pylori infection in a given population. We believe that this fast, convenient, efficient, and inexpensive screening and diagnostic platform can be widely used in various settings, including homes and clinics.
The Xanthomonas citri Reverse Fitness Deficiency by Activating a Novel β-Glucosidase Under Low Osmostress
Authors: Li Kaihuai , Liao Jinxing , Wei Ming , Qiu Shanxu , Wu Weiyin , Zhao Yancun , Wang Haihong , Liu Qiongguang , Liu Fengquan , Chang Changqing
Published: May 2022

Bacteria can withstand various types of environmental osmostress. A sudden rise in osmostress affects bacterial cell growth that is countered by activating special genes. The change of osmostress is generally a slow process under the natural environment. However, the collective response of bacteria to low osmostress remains unknown. This study revealed that the deletion of phoP (ΔphoP) from X. citri significantly compromised the growth and virulence as compared to the wild-type strain. Interestingly, low osmostress reversed physiological deficiencies of X. citri phoP mutant related to bacterial growth and virulence. The results also provided biochemical and genetic evidence that the physiological deficiency of phoP mutant can be reversed by low osmostress induced β-glucosidase (BglS) expression. Based on the data, this study proposes a novel regulatory mechanism of a novel β-glucosidase activation in X. citri through low osmostress to reverse the fitness deficiency.
The Brazilian Rare Genomes Project: Validation of Whole Genome Sequencing for Rare Diseases Diagnosis
Authors: Coelho Antonio Victor Campos , Mascaro-Cordeiro Bruna , Lucon Danielle Ribeiro , Nóbrega Maria Soares , Reis Rodrigo de Souza , de Alexandre Rodrigo Bertollo , Moura Livia Maria Silva , Oliveira Gustavo Santos de , Guedes Rafael Lucas Muniz , Caraciolo Marcel Pinheiro , Zurro Nuria Bengala , Cervato Murilo Castro , Oliveira João Bosco
Published: May 2022

Rare diseases affect up to 13.2 million individuals in Brazil. The Brazilian Rare Genomes Project is envisioned to further the implementation of genomic medicine into the Brazilian public healthcare system. Here we report the validation results of a whole genome sequencing (WGS) procedure for implementation in clinical laboratories. In addition, we report data quality for the first 1,200 real-world patients sequenced. We sequenced a well-characterized group of 76 samples, including seven gold standard genomes, using a PCR-free WGS protocol on Illumina Novaseq 6,000 equipment. We compared the observed variant calls with their expected calls, observing good concordance for single nucleotide variants (SNVs; mean F-measure = 99.82%) and indels (mean F-measure = 99.57%). Copy number variants and structural variants events detection performances were as expected (F-measures 96.6% and 90.3%, respectively). Our WGS protocol presented excellent intra-assay reproducibility (coefficients of variation ranging between 0.03% and 0.20%) and inter-assay reproducibility (coefficients of variation ranging between 0.02% and 0.09%). Limitations of the WGS protocol include the inability to confidently detect variants such as uniparental disomy, balanced translocations, repeat expansion variants, and low-level mosaicism. In summary, the observed performance of the WGS protocol was in accordance with that seen in the best centers worldwide. The Rare Genomes Project is an important initiative to bring pivotal improvements to the quality of life of the affected individuals.
Conventional and Nonconventional Sources of Exosomes–Isolation Methods and Influence on Their Downstream Biomedical Application
Authors: Janouskova Olga , Herma Regina , Semeradtova Alena , Poustka David , Liegertova Michaela , Malinska Hana Auer , Maly Jan
Published: May 2022

Despite extensive study of extracellular vesicles (EVs), specifically exosomes (EXs) as biomarkers, important modulators of physiological or pathological processes, or therapeutic agents, relatively little is known about nonconventional sources of EXs, such as invertebrate or plant EXs, and their uses. Likewise, there is no clear information on the overview of storage conditions and currently used isolation methods, including new ones, such as microfluidics, which fundamentally affect the characterization of EXs and their other biomedical applications. The purpose of this review is to briefly summarize conventional and nonconventional sources of EXs, storage conditions and typical isolation methods, widely used kits and new “smart” technologies with emphasis on the influence of isolation techniques on EX content, protein detection, RNA, mRNA and others. At the same time, attention is paid to a brief overview of the direction of biomedical application of EXs, especially in diagnostics, therapy, senescence and aging and, with regard to the current situation, in issues related to Covid-19.
eRNAs Identify Immune Microenvironment Patterns and Provide a Novel Prognostic Tool in Acute Myeloid Leukemia
Authors: Jiang Ziming , Long Junyu , Deng Kaige , Zheng Yongchang , Chen Miao
Published: May 2022

Background: Enhancer RNAs (eRNAs) play an essential role in tumorigenesis as non-coding RNAs transcribed from enhancer regions. However, the landscape of eRNAs in acute myeloid leukemia (AML) and the potential roles of eRNAs in the tumor microenvironment (TME) remain unclear.

Method: Gene expression data collected from The Cancer Genome Atlas (TCGA) project were combined with Histone ChIP-seq so as to reveal the comprehensive landscape of eRNAs. Single-sample gene set enrichment analysis algorithm (ssGSEA) and ESTIMATE were employed to enumerate immune cell infiltration and tumor purity.

Results: Most prognostic eRNAs were enriched in immune-related pathways. Two distinct immune microenvironment patterns, the immune-active subtype and the immune-resistant subtype, were identified in AML. We further developed an eRNA-derived score (E-score) that could quantify immune microenvironment patterns and predict the response to immune checkpoint inhibitor (ICI) treatment. Finally, we established a prognostic nomogram combining E-score and other clinical features, which showed great discriminative power in both the training set [Harrell’s concordance index (C index): 0.714 (0.651–0.777), p < 0.0001] and validation set [C index: 0.684 (0.614–0.755), p < 0.0001]. Calibration of the nomogram was also validated independently.

Conclusion: In this study, we systematically understood the roles of eRNAs in regulating TME diversity and complexity. Moreover, our E-score model provided the first predictive model for ICI treatment in AML.
Structural MRI Reveals Cervical Spinal Cord Atrophy in the P301L Mouse Model of Tauopathy: Gender and Transgene-Dosing Effects
Authors: Sartoretti Thomas , Ganley Robert P. , Ni Ruiqing , Freund Patrick , Zeilhofer Hanns Ulrich , Klohs Jan
Published: May 2022

In primary tauopathies, the deposition of tau neurofibrillary tangles and threads as well as neurodegenerative changes have been found within the brain and spinal cord. While degenerative changes have been intensively studied in the brain using structural magnetic resonance imaging (MRI), MRI studies investigating the spinal cord are still scarce. In the present study, we acquired ex vivo high resolution structural MRI of the cervical spinal cord of 8.5–9 month old hemizygous and homozygous P301L mice and non-transgenic littermates of both genders. We assessed the total cross-sectional area, and the gray and white matter anterior-posterior width and left-right width that are established imaging marker of spinal cord degeneration. We observed significant tissue-specific reductions in these parameters in female P301L mice that were stronger in homozygous than in hemizygous P301L mice, indicating both an effect of gender and transgene expression on cervical spinal cord atrophy. Moreover, atrophy was stronger in the gray matter than in the white matter. Immunohistochemical analysis revealed neurodegenerative and neuroinflammatory changes in the cervical spinal cord in both the gray and white matter of P301L mice. Collectively, our results provide evidence for cervical spinal cord atrophy that may directly contribute to the motor signs associated with tauopathy.
Correlation Between Chronic Tinnitus Distress and Symptoms of Depression: A Systematic Review
Authors: Meijers Sebastiaan M. , Rademaker Maaike , Meijers Rutger L. , Stegeman Inge , Smit Adriana L.
Published: May 2022

Objectives

In this systematic review, we aim to evaluate the evidence regarding the correlation between tinnitus distress and the severity of depressive symptoms in patients with chronic tinnitus. Also, the prevalence of clinically relevant depressive symptoms scores in patients with chronic tinnitus was evaluated.

Methods

We performed a systematic review in PubMed, EMBASE, and the Cochrane library in June 2021 using the terms “depression” and “tinnitus,” and their synonyms, following PRISMA guidelines. Studies were selected on relevance and critically appraised regarding risk of bias using the Newcastle–Ottowa Quality Assessment Scale.

Results

A total of 1,912 articles were screened on title and abstract after the removal of the duplicates. Eventually, 33 (1.5%) articles were included for the final analysis. Only cross-sectional cohort studies and case–control studies with a low level of evidence and a high risk of bias due to the study design and patient selection were found. Statistically significant correlations between the experienced tinnitus distress and depressive symptoms were reported in 31 out of 33 studies. Clinically relevant depression scores had a prevalence of 4.6–41.7%.

Conclusions

In this systematic review, in which mostly cross-sectional studies were included, a statistically significant correlation was found between the experienced tinnitus distress and the reported severity of symptoms of depression in patients with chronic tinnitus. A wide range of clinically relevant depression scores were reported in included studies. Due to the high risk of bias of included studies it is not possible to provide a definite answer on the existence of this relationship. Future population-based studies are necessary to provide more clarity.
First Pass Effect and Location of Occlusion in Recanalized MCA M1 Occlusions
Authors: Salahuddin Hisham , Rao Rahul R. , Zaidi Syed F. , Prologo-Richardson Paige , Khalid Fatima , Saju Linda , Taqi Muhammad Asif , Burgess Richard R. , Jumaa Mouhammad A.
Published: May 2022

Background

The first pass effect has been shown to improve clinical outcomes in patients with middle cerebral artery (MCA) M1 occlusions.

Objective

To determine the rates of first pass effect in MCA M1 occlusions and determine if proximal or distal location of occlusion modified clinical outcomes.

Methods

Patients with recanalized MCA M1 occlusions who underwent endovascular thrombectomy (EVT) were reviewed to determine the effect of first pass effect (FPE) and location of occlusion on clinical outcomes. MCA occlusions were classified as proximal if they included the first two thirds of the MCA and involved the lenticulostriate vessels, or distal if they did not.

Results

We included 261 patients of which 27% achieved FPE. Of the cohort, there were 91 (35%) proximal MCA occlusions and 170 (65%) distal MCA occlusions. Baseline demographics and treatment time metrics were comparable across both groups. There was a trend toward good clinical outcome in patients with or without a FPE (60 vs. 46%; p = 0.06), however a higher rate of excellent clinical outcome was noted in patients with FPE (46 vs. 30%; p = 0.02). When compared by location, patients with distal MCA occlusions had a higher rate of excellent clinical outcome (40 vs. 25%; p = 0.02). Multivariable analysis showed that distal MCA occlusion was the strongest predictor of an excellent clinical outcome and first pass effect.

Conclusion

Patients with MCA M1 occlusions with FPE have a higher rate of excellent clinical outcomes compared to those who did not. Location of MCA occlusion appears to modify rates of first pass effect and excellent clinical outcomes.
Role of Teneurin C-Terminal Associated Peptides (TCAP) on Intercellular Adhesion and Communication
Authors: Dodsworth Thomas L. , Lovejoy David A.
Published: May 2022

The teneurin C-terminal associated peptides (TCAP) are encoded by the terminal exon of all metazoan teneurin genes. Evidence supports the liberation of a soluble TCAP peptide either by proteolytic cleavage from the mature transmembrane teneurin protein or by a separately transcribed mRNA. Synthetic versions of TCAP, based on its genomic structure, are efficacious at regulating intercellular communication by promoting neurite outgrowth and increasing dendritic spine density in vitro and in vivo in rodent models. This is achieved through cytoskeletal re-arrangement and metabolic upregulation. The putative receptors for TCAPs are the latrophilin (LPHN) family of adhesion G-protein coupled receptors, which facilitate TCAP’s actions through G-proteins associated with cAMP and calcium-regulating signalling pathways. The teneurin/TCAP and latrophilin genes are phylogenetically ancient, likely serving primitive functions in cell adhesion and energy regulation which have been since adapted for a more complex role in synaptogenesis in vertebrate nervous systems.