bluuebunny/crossref_metadata_2025 huggingface dataset:
Mangrove Trace Metal Biogeochemistry Response to Global Climate Change
Authors: de Lacerda Luiz Drude , Ward Raymond D. , Borges Rebecca , Ferreira Alexander Cesar
Published: April 2022

This review discusses observed impacts from different climate change-driven pressures on mangrove's role in modulating trace metal transfer at the land-ocean interface. It contributes to the literature in a global context and shows mangroves as mitigators or providing positive feedback to metal mobilization. Most chalcophile metals2+ accumulate in mangrove soils associated with sulfides while high sedimentation rates avoid their oxidation. Exudation of oxygen by roots fixates Fe, which co-precipitates metals as oxyhydroxides in the rhizosphere. These two biogeochemical processes reduce trace metal availability to plants and their mobility within estuaries. However, climate change-driven pressures alter this geochemical equilibrium. Increasing atmospheric CO2 and temperature, and the intensity and frequency of extreme climatic events, have proved to affect mangrove functioning and cover, but no direct observation on the impact on metal biogeochemistry is presently available, whereas sea level rise and saline intrusion impacts on the fate of metals have already been observed. Sea level rise increases erosion, that dissociates deposited sulfides releasing metals to the water column. Released metals adsorb onto suspended particles and can re-deposit in the estuary or are exported to continental shelf sediments. Saline intrusion may oxidize deeper sediment layers releasing metals to porewaters. Part of the mobilized metals may remain in solution complexed with DOM and have their bioavailability increased, as shown by high bioaccumulation factors and biomagnification and high metal concentrations in the estuarine biota, which results in higher human exposure through fisheries consumption. Since erosion occurs preferentially at the sea border and higher sedimentation at the higher reaches of the estuary, triggering mangroves migration landward, spatial gradients are formed, and shall be taken into consideration when planning mitigation or adaptation strategies. These observations suggest disruption of traditional humans dwelling in mangrove dominated coastlines by increasing contamination of coastal fisheries, often the principal protein source for those groups and an important source of income. Further research into the environmental and socioeconomic impacts of climate change driven alterations to metal biogeochemical processes in mangroves as contaminant levels are expected to increase.
Ensemble Models of For-Hire Vehicle Trips
Authors: Wu Hao , Levinson David
Published: April 2022

Ensemble forecasting is class of modeling approaches that combines different data sources, models of different types, with different assumptions, and/or pattern recognition methods. By comprehensively pooling information from multiple sources, analyzed with different techniques, ensemble models can be more accurate, and can better account for different sources of real-world uncertainties. The share of for-hire vehicle (FHV) trips increased rapidly in recent years. This paper applies ensemble models to predicting for-hire vehicle (FHV) trips in Chicago and New York City, showing that properly applied ensemble models can improve forecast accuracy beyond the best single model.
A Pyroptosis-Related Gene Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer Based on Computational Biology Techniques
Authors: Wang Zitao , Bao Anyu , Liu Shiyi , Dai Fangfang , Gong Yiping , Cheng Yanxiang
Published: April 2022

Breast cancer (BC) is a malignant tumor with high morbidity and mortality, which seriously threatens women’s health worldwide. Pyroptosis is closely correlated with immune landscape and the tumorigenesis and development of various cancers. However, studies about pyroptosis and immune microenvironment in BC are limited. Therefore, our study aimed to investigate the potential prognostic value of pyroptosis-related genes (PRGs) and their relationship to immune microenvironment in BC. First, we identified 38 differentially expressed PRGs between BC and normal tissues. Further on, the least absolute shrinkage and selection operator (LASSO) Cox regression and computational biology techniques were applied to construct a four-gene signature based on PRGs and patients in The Cancer Genome Atlas (TCGA) cohort were classified into high- and low-risk groups. Patients in the high-risk group showed significantly lower survival possibilities compared with the low-risk group, which was also verified in an external cohort. Furthermore, the risk model was characterized as an independent factor for predicting the overall survival (OS) of BC patients. What is more important, functional enrichment analyses demonstrated the robust correlation between risk score and immune infiltration, thereby we summarized genetic mutation variation of PRGs, evaluated the relationship between PRGs, different risk group and immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint blockers (ICB), which indicated that the low-risk group was enriched in higher TMB, more abundant immune cells, and subsequently had a brighter prognosis. Except for that, the lower expression of PRGs such as GZMB, IL18, IRF1, and GZMA represented better survival, which verified the association between pyroptosis and immune landscape. In conclusion, we performed a comprehensive bioinformatics analysis and established a four-PRG signature consisting of GZMB, IL18, IRF1, and GZMA, which could robustly predict the prognosis of BC patients.
Stemness Subtypes and Scoring System Predict Prognosis and Efficacy of Immunotherapy in Soft Tissue Sarcoma
Authors: Gu Hui-Yun , Qu Wen-Qiang , Peng Hai-Heng , Yu Yi-Feng , Jiang Zhe-Zhen , Qi Bai-Wen , Yu Ai-Xi
Published: April 2022

Tumor stemness has been reported to play important roles in cancers. However, a comprehensive analysis of tumor stemness remains to be performed to investigate the specific mechanisms and practical values of stemness in soft tissue sarcomas (STS). Here, we applied machine learning to muti-omic data of patients from TCGA-SARC and GSE21050 cohorts to reveal important roles of stemness in STS. We demonstrated limited roles of existing mRNAsi in clinical application. Therefore, based on stemness-related signatures (SRSs), we identified three stemness subtypes with distinct stemness, immune, and metabolic characteristics using consensus clustering. The low-stemness subtype had better prognosis, activated innate and adaptive immunity (e.g., infiltrating B, DC, Th1, CD8+ T, activated NK, gamma delta T cells, and M1 macrophages), more enrichment of metabolic pathways, more sites with higher methylation level, higher gene mutations, CNA burdens, and immunogenicity indicators. Furthermore, the 16 SRS-based stemness prognostic index (SPi) was developed, and we found that low-SPi patients with low stemness had better prognosis and other characteristics similar to those in the low-stemness subtype. Besides, low-stemness subtype and low-SPi patients could benefit from immunotherapy. The predictive value of SPi in immunotherapy was more accurate after the addition of MSI into SPi. MSIlowSPilow patients might be more sensitive to immunotherapy. In conclusion, we highlighted mechanisms and practical values of the stemness in STS. We also recommended the combination of MSI and SPi which is a promising tool to predict prognosis and achieve precise treatments of immunotherapy in STS.
Rotavirus-Induced Expansion of Antigen-Specific CD8 T Cells Does Not Require Signaling via TLR3, MyD88 or the Type I Interferon Receptor
Authors: Muleta Konjit Getachew , Ulmert Isabel , Hamza Kedir Hussen , van Dijl Sharné , Nakawesi Joy , Lahl Katharina
Published: April 2022

Rotavirus (RV) infection induces strong adaptive immunity. While protection from reinfection requires humoral immunity, initial clearance of infection depends on cytotoxic CD8 T cells. Type I classical dendritic cells (cDC1) excel at CD8 T cell induction through cross-presentation and are essential for optimal cytotoxicity towards RV. Upon sensing of infection-induced innate immune signals through pattern recognition receptors (PRRs), cumulating in autocrine type I interferon (IFN) signaling, cDC1 mature and migrate to the draining lymph nodes (LNs), where they prime adaptive immune cells. To analyze which PRR pathways lead to robust cytotoxicity in the context of RV infection, we measured RV-specific CD8 T cell priming in mice deficient for Toll-like receptor 3 (TLR3), recognizing double-stranded RNA, or for MyD88, the adapter for all other TLRs and IL-1 family cytokines. Individual TLR3- and MyD88-mediated signaling was not required for the priming of CD8 T cell responses to RV and neither deficiency impacted on RV clearance. Surprisingly, the accumulation of RV-specific CD8 T cells was also not altered in the absence of type I IFN signaling, while their ability to produce IFNγ and granzyme were blunted. Together, this suggests a substantial level of redundancy in the sensing of RV infection and the translation of signals into protective CD8 T cell immunity.
Dichotomy in Neutralizing Antibody Induction to Peptide-Conjugated Vaccine in Squalene Emulsion Contrast With Aluminum Hydroxide Formulation
Authors: Bonduelle Olivia , Chaudesaigues Chloé , Tolazzi Monica , Suleiman Ehsan , de Bernard Simon , Alves Karine , Nourikyan Julien , Bohec Mylene , Baudrin Laura G. , Katinger Dietmar , Debré Patrice , Scarlatti Gabriella , Vieillard Vincent , Combadière Behazine
Published: April 2022

W614A-3S peptide is a modified 3S motif of the HIV-gp41 (mutation W614A). We previously detected the presence of natural neutralizing antibodies directed against W614A-3S peptide (NAbs) in long-term non-progressor HIV+patients. Here, we compared the efficacy of W614A-3S peptide formulated in either squalene emulsion (SQE) or in aluminum hydroxide (Alum) in inducing broadly-NAbs (bNAbs). Rabbit and mouse models were used to screen the induction of bNAbs following 4 immunizations. SQE was more efficient than Alum formulation in inducing W614A-3S-specific bNAbs with up to 67%–93% of HIV strains neutralized. We then analyzed the quality of peptide-specific murine B cells by single-cell gene expression by quantitative reverse transcription-PCR and single-cell V(D)J sequencing. We found more frequent germinal center B cells in SQE than in Alum, albeit with a different gene expression profile. The V(D)J sequencing of W614A-3S-specific BCR showed significant differences in BCR sequences and validates the dichotomy between adjuvant formulations. All sixteen BCR sequences which were cloned were specific of peptide. Adjuvant formulations of W614A-3S-peptide-conjugated immunogen impact the quantity and quality of B cell immune responses at both the gene expression level and BCR sequence.
Bioinformatics and System Biology Approach to Identify the Influences of COVID-19 on Rheumatoid Arthritis
Authors: Hu Huan , Tang Nana , Zhang Facai , Li Li , Li Long
Published: April 2022

Background

Severe coronavirus disease 2019 (COVID -19) has led to a rapid increase in mortality worldwide. Rheumatoid arthritis (RA) was a high-risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, whereas the molecular mechanisms underlying RA and CVOID-19 are not well understood. The objectives of this study were to analyze potential molecular mechanisms and identify potential drugs for the treatment of COVID-19 and RA using bioinformatics and a systems biology approach.

Methods

Two Differentially expressed genes (DEGs) sets extracted from GSE171110 and GSE1775544 datasets were intersected to generate common DEGs, which were used for functional enrichment, pathway analysis, and candidate drugs analysis.

Results

A total of 103 common DEGs were identified in the two datasets between RA and COVID-19. A protein-protein interaction (PPI) was constructed using various combinatorial statistical methods and bioinformatics tools. Subsequently, hub genes and essential modules were identified from the PPI network. In addition, we performed functional analysis and pathway analysis under ontological conditions and found that there was common association between RA and progression of COVID-19 infection. Finally, transcription factor-gene interactions, protein-drug interactions, and DEGs-miRNAs coregulatory networks with common DEGs were also identified in the datasets.

Conclusion

We successfully identified the top 10 hub genes that could serve as novel targeted therapy for COVID-19 and screened out some potential drugs useful for COVID-19 patients with RA.
Cryopreserved PM21-Particle-Expanded Natural Killer Cells Maintain Cytotoxicity and Effector Functions In Vitro and In Vivo
Authors: Oyer Jeremiah L. , Croom-Perez Tayler J. , Dieffenthaller Thomas A. , Robles-Carillo Liza D. , Gitto Sarah B. , Altomare Deborah A. , Copik Alicja J.
Published: April 2022

There is a great interest in developing natural killer (NK) cells as adoptive cancer immunotherapy. For off-the-shelf approaches and to conduct multicenter clinical trials, cryopreserved NK cells are the preferred product. However, recent studies reported that cryopreservation of NK cells results in loss of cell motility and, as a consequence, cytotoxicity which limits the clinical utility of such products. This study assessed the impact of cryopreservation on the recovery and function of PM21-particle expanded NK cells (PM21-NK cells) as well as their antitumor activity in vitro using 2D and 3D cancer models and in vivo in ovarian cancer models, including patient-derived xenografts (PDX). Viable PM21-NK cells were consistently recovered from cryopreservation and overnight rest with a mean recovery of 73 ± 22% (N = 19). Thawed and rested NK cells maintained the expression of activating receptors when compared to expansion-matched fresh NK cells. Cryopreserved NK cells that were thawed and rested showed no decrease in cytotoxicity when co-incubated with tumor cells at varying effector-to-target (NK:T) ratios compared to expansion-matched fresh NK cells. Moreover, no differences in cytotoxicity were observed between expansion-matched cryopreserved and fresh NK cells in 3D models of tumor killing. These were analyzed by kinetic, live-cell imaging assays co-incubating NK cells with tumor spheroids. When exposed to tumor cells, or upon cytokine stimulation, cryopreserved NK cells that were thawed and rested showed no significant differences in surface expression of degranulation marker CD107a or intracellular expression of TNFα and IFNγ. In vivo antitumor activity was also assessed by measuring the extension of survival of SKOV-3-bearing NSG mice treated with fresh vs. cryopreserved NK cells. Cryopreserved NK cells caused a statistically significant survival extension of SKOV-3-bearing NSG mice that was comparable to that observed with fresh NK cells. Additionally, treatment of NSG mice bearing PDX tumor with cryopreserved PM21-NK cells resulted in nearly doubling of survival compared to untreated mice. These data suggest that PM21-NK cells can be cryopreserved and recovered efficiently without appreciable loss of viability or activity while retaining effector function both in vitro and in vivo. These findings support the use of cryopreserved PM21-NK cells as a cancer immunotherapy treatment.
Arbovirus Surveillance in Field-Collected Mosquitoes From Pernambuco-Brazil, During the Triple Dengue, Zika and Chikungunya Outbreak of 2015-2017
Authors: Krokovsky Larissa , Paiva Marcelo H. S. , Guedes Duschinka R. D. , Barbosa Rosângela M. R. , de Oliveira André L. S. , Anastácio Daniela B. , Pontes Claudenice Ramos , Ayres Constância F. J.
Published: April 2022

The (re) emergence of arboviruses around the world is a public health concern once severe outbreaks are usually associated with these infections. The co-circulation of Dengue (DENV), Zika (ZIKV) and Chikungunya (CHIKV) viruses in the past few years has caused a unique epidemic situation in Brazil. The northeast region of the country was the most affected by clinical complications from such arboviruses’ infections, including neurological disorders caused by ZIKV. In this particular region, Aedes mosquitoes are the main vectors of DENV, ZIKV and CHIKV, with Culex quinquefasciatus also considered as a potential vector of ZIKV. Therefore, virological surveillance in mosquitoes contributes to understanding the epidemiological profile of these diseases. Here, we report the circulation of DENV, ZIKV and CHIKV in Aedes spp. and Cx. quinquefasciatus female mosquitoes collected in areas with a high arbovirus circulation in humans in the Metropolitan Region of Recife, Pernambuco, Brazil, during the triple-epidemics of 2015-17. All the field-caught mosquitoes were sent to the laboratory for arbovirus screening after RNA extraction and RT-PCR/RT-qPCR. A total of 6,227 females were evaluated and, as a result, DENV, ZIKV and CHIKV were identified in Ae. aegypti, Ae. taeniorhynchus and Cx. quinquefasciatus mosquito pools. In addition, DENV and ZIKV were isolated in C6/36 cells. In conclusion, it is important to highlight that arbovirus surveillance performed in mosquitoes from DENV-ZIKV-CHIKV hotspots areas can serve as an early-warning system to target vector control actions more efficiently in each studied area.
Eutrophication Amplifies the Diel Variability of Carbonate Chemistry in an Equatorial, Semi-Arid, and Negative Estuary
Authors: Cotovicz Luiz C. , Marins Rozane V. , da Silva Agda Raquel Facundo
Published: April 2022

This study presents high-resolution data on diel variations of carbonate chemistry in a semi-arid estuary (Jaguaribe River) in NE Brazil, which has witnessed decreasing annual rainfall and freshwater inputs due to climate change and river damming. In addition, the estuary has been suffering with increasing discharges from shrimp farm and urban effluents. We monitored surface water and atmospheric CO2 partial pressure (pCO2), temperature, salinity, and wind speed with continuous real-time measurements during two eulerian surveys in October 2017 (33 h) and September 2018 (44 h), during spring tides in the dry season. Additionally, pH, total alkalinity (TA), dissolved inorganic carbon (DIC), carbonate (CO32–), and saturation state of calcite (Ωcal) and aragonite (Ωara) were monitored hourly. Higher salinity (>38) during ebb tides confirmed the hypersalinity and negative estuarine circulation. TA and DIC concentrations in the estuary were higher than in the adjacent coastal ocean due to evaporation, showing positive correlation with salinity and negative correlation with tidal height. Measured TA and DIC concentrations were slightly higher than those calculated by the conservative evaporation model, suggesting their production in the estuary by aerobic and anaerobic processes. CO32–, Ωcal, and Ωara showed a clear semi-diurnal (tidal-driven) and diel (24 h; biological-driven) patterns: lowest values occurred at flood tide during night-time (respectively, 185 μmol kg–1, 4.3 and 2.8), whereas highest occurred during ebb tide and daytime (respectively, 251 μmol kg–1, 5.7 and 3.8). DIC/TA ratios were higher at night-time supporting a diel control (linked to solar irradiance) of the carbonate buffering capacity. pCO2 was oversaturated comparing to the atmosphere (512–860 μatm) and the estuary was a source of CO2, with fluxes ranging from 2.2 to 200.0 mmol C m–2 d–1 (51.9 ± 26.7 mmol C m–2 d–1), which are higher than emissions normally found in low-inflow, marine-dominated estuaries. The diel variability of DIC indicated a net heterotrophic metabolism averaging −5.17 ± 7.39 mmol C m–2 h–1. Eutrophication amplifies the diel variability of the CO2 system generating large differences between daytime and night-time. The results highlight the importance of considering diel variability when estimating CO2 fluxes and carbonate chemistry in eutrophic, semi-arid, and tidally dominated estuaries under rapid environmental changes, and may represent future conditions in estuaries worldwide experiencing warming, increasing aridity and eutrophication.
Prediction of Long-Term Beach Profile Evolution Due to Episodic Wave Incidence Under Tidal Environment
Authors: Lee Sahong , Lim Changbin , Lee Jung-Lyul
Published: April 2022

Recently, studies have been conducted that long-term changes in shoreline position can be sufficiently interpreted using an ordinary differential equation that includes only erosion and recovery processes. Here, the erosion process term is given as a function of the breaking wave energy, which causes the shoreline to retreat to the ultimate erosion position by the incoming wave energy. The recovery process term is given as a function of the concentration of suspended sediment and allows it to recover to its shoreline position. Therefore, in this study, we propose a numerical technique that simulates long-term changes in the beach profile by extending the ordinary differential equation to be applied to the change in seabed constituting the beach profile by applying the parabolic equation of the equilibrium beach profile of the surf zone. This model also consists of a term that allows the beach profile to converge to the equilibrium beach profile due to the breaking wave energy and another term that allows it to converge back to the linear shoaling profile when the wave is extinguished. Therefore, it is possible to simulate the repeated formation and disappearance of scarp and berm whenever a storm wave passes, and it can also be applied to the morphological change at the beach with a large tidal range. The validity of the proposed methodology was verified by comparing the long-term shoreline observation data of Tairua Beach, New Zealand, where the tidal difference is about 2 m, with the results of the long-term beach section convergence model of this study. In addition, short-term observation data were also compared and analyzed to investigate the ability to simulate morphological changes due to episodic erosion and recovery processes. The results of this study are expected to be applied not only to the beach profile but also to the three-dimensional morphology change of the beach, and it is expected that it will serve as a cornerstone for a more detailed topographic change prediction study due to sea level rise.
Influence of an Offshore Mussel Aquaculture Site on the Distribution of Epibenthic Macrofauna in Îles de la Madeleine, Eastern Canada
Authors: Sean Anne-Sara , Drouin Annick , Archambault Philippe , McKindsey Christopher W.
Published: April 2022

Mussel farming influences benthic environments by organic loading and the addition of physical structure within aquaculture leases. This study evaluated near-field (distance to mussel aquaculture structures, line-scale) and bay-scale (inside vs. outside a blue mussel, Mytilius edulis, farm) effects of an offshore mussel farm in Îles de la Madeleine (Canada) on epibenthic macrofaunal communities. Benthic communities were evaluated by underwater visual counts using SCUBA in June and July 2014. The mussel farm influenced benthic communities at line- and bay-scales. Overall, crabs (Cancer irroratus, Pagarus pubecsens, Pagarus acadianus), sea stars (Asterias rubens), Northern moon snails (Polinices heros), and American lobsters (Homarus americanus) were more abundant in farm sites than outside of farm sites and ocean quahogs (Arctica islandica) were more abundant outside. No clear spatial trend was observed for winter flounder (Pseudopleuronectes americanus) and the sand dollar (Echinarachnius parma) but both species differed (flounder) or showed a trend to differ (sand dollar) between sampling dates. Spatial structure in the distribution of macrofauna was evident within the aquaculture lease as most species were more abundant directly below and close to mussel lines and anchor blocks. There was no spatial structure in non-farm sites. Further investigation is needed to evaluate if mussel farms serve as ecological traps for the species that congregate within them. The long-term effects of the observed spatial effects of offshore mussel culture on macrofauna fitness remains unknown.
Three Distinct Views of Deep Pelagic Community Composition Based on Complementary Sampling Approaches
Authors: Hetherington Elizabeth D. , Choy C. Anela , Thuesen Erik V. , Haddock Steven H. D.
Published: April 2022

Our perception of deep-sea communities has evolved as various sampling approaches have captured different components of deep-sea habitats. We sampled midwater zooplankton assemblages in Monterey Bay, California to quantify community composition (abundance and biomass) and biodiversity (at the Order level) across three depth ranges, and the effects of sampling methodology on community parameters. We collected zooplankton using two types of opening-closing trawls [Tucker Trawl and Multiple Opening/Closing Net and Environmental Sensing System (MOCNESS)] and video recordings from a remotely operated vehicle (ROV). We quantified the relative contributions of microbes to community biomass using synoptic water-bottle casts and flow cytometry. Overall, the pelagic community was most similar between the Tucker trawl and ROV (dissimilarity = 52.4%) and least similar between the MOCNESS and ROV (dissimilarity = 65.8%). Dissimilarity between sampling methods was driven by the relative abundances of crustaceans and gelatinous taxa, where gelatinous animals (cnidarians, ctenophores, tunicates) were more abundant in ROV surveys (64.2%) and Tucker trawls (46.8%) compared to MOCNESS samples (14.5%). ROV surveys were the only method that sufficiently documented the most physically delicate taxa (e.g., physonect siphonophores, lobate ctenophores, and larvaceans). Biomass was also one order of magnitude lower in MOCNESS trawls compared to Tucker trawls. Due to these large differences, the relative contributions of microbes to total biomass were substantially lower in Tucker trawl samples (mean = 7.5%) compared to MOCNESS samples (mean = 51%). These results illustrate that our view of planktonic composition and community biomass is strongly dependent on sampling methodology.
Analytical Model of Crack Width in Hogging Moment Regions of Steel–Concrete Composite Beams Under Fatigue Loading
Authors: Song Aiming , Xu Hongtao , Wan Shui , Luo Qi
Published: April 2022

A modified formula for average crack spacing and a numerical model for crack width in hogging moment regions of steel–concrete composite beams under fatigue loading are proposed in this article. First, the existing calculation formulas and test data of average crack spacing are discussed and summarized. By introducing the factor of transverse reinforcement spacing, a modified formula of crack spacing is suggested based on the method of non-linear fitting. Then, a numerical model for crack width in negative moment regions under fatigue loading is proposed. In the analytical model, the explicit formulations of slip occurring at both the beam–slab interface and the reinforcement–concrete interface are included by considering fatigue effects, as well as the stress of reinforcement in the cracked section. Finally, a fatigue test on two steel–concrete composite plate beams subjected to hogging moment is designed and conducted. Compared with the crack width evaluation methods in the existing literature, the analysis results of the numerical model show more reasonable agreement with the data of the experimental beams performed in this study.
Association Between Platelet Levels and 28-Day Mortality in Patients With Sepsis: A Retrospective Analysis of a Large Clinical Database MIMIC-IV
Authors: Wang Danni , Wang Suning , Wu Hao , Gao Jiansheng , Huang Kairong , Xu Danhong , Ru Huangyao
Published: April 2022

Background

This research focused on evaluating the correlation between platelet count and sepsis prognosis, and even the dose-response relationship, in a cohort of American adults.

Method

Platelet counts were recorded retrospectively after hospitalization for patients admitted to Beth Israel Deaconess Medical Center’s intensive care unit between 2008 and 2019. On admission to the intensive care unit, sepsis patients were divided into four categories based on platelet counts (very low < 50 × 109/L, intermediate-low 50 × 109–100 × 109/L, low 100 × 109–150 × 109/L, and normal ≥ 150 × 109/L). A multivariate Cox proportional risk model was used to calculate the 28-day risk of mortality in sepsis based on baseline platelet counts, and a two-piece linear regression model was used to calculate the threshold effect.

Results

The risk of 28-day septic mortality was nearly 2-fold higher in the platelet very low group when compared to the low group (hazard ratios [HRs], 2.24; 95% confidence interval [CI], 1.92–2.6). Further analysis revealed a curvilinear association between platelets and the sepsis risk of death, with a saturation effect predicted at 100 × 109/L. When platelet counts were below 100 × 109/L, the risk of sepsis 28-day death decreased significantly with increasing platelet count levels (HR, 0.875; 95% CI, 0.84–0.90).

Conclusion

When platelet count was less than 100 × 109/L, it was a strong predictor of the potential risk of sepsis death, which is declined by 13% for every 10 × 109/L growth in platelets. When platelet counts reach up to 100 × 109/L, the probability of dying to sepsis within 28 days climbs by 1% for every 10 × 109/L increase in platelet count.
The Role of the Two-Component QseBC Signaling System in Biofilm Formation and Virulence of Hypervirulent Klebsiella pneumoniae ATCC43816
Authors: Lv Jingnan , Zhu Jie , Wang Ting , Xie Xiaofang , Wang Tao , Zhu Zhichen , Chen Liang , Zhong Fengyun , Du Hong
Published: April 2022

Hypervirulent Klebsiella pneumoniae (hvKP) is an evolving infectious pathogen associated with high mortality. The convergence of hypervirulence and multidrug resistance further challenges the clinical treatment options for K. pneumoniae infections. The QseBC two-component system (TCS) is a component of quorum-sensing regulatory cascade and functions as a global regulator of biofilm growth, bacterial motility, and virulence in Escherichia coli. However, the functional mechanisms of QseBC in hvKP have not been reported, and we aim to examine the role of QseBC in regulating virulence in hvKP strain ATCC43816. The CRISPR-Cas9 system was used to construct qseB, qseC, and qseBC knockout in ATCC43816. No significant alterations in the growth and antibiotic susceptibility were detected between wild-type and mutants. The deletion of qseC led to an increase of biofilm formation, resistance to serum killing, and high mortality in the G. mellonella model. RNAseq differential gene expression analysis exhibited that gene-associated biofilm formation (glgC, glgP, glgA, gcvA, bcsA, ydaM, paaF, ptsG), bacterial type VI secretion system (virB4, virB6, virB10, vgrG, hcp), and biosynthesis of siderophore (entC, entD, entE) were significantly upregulated in comparison with the wild-type control. In addition, qseB, ygiW (encode OB-family protein), and AraC family transcriptional regulator IT767_23090 genes showed highest expressions in the absence of QseC, which might be related to increased virulence. The study provided new insights into the functional importance of QseBC in regulating the virulence of hvKP.
Isolation and Characterization of a Lytic Vibriophage OY1 and Its Biocontrol Effects Against Vibrio spp.
Authors: Gao Lu , Ouyang Min , Li Yi , Zhang Hui , Zheng Xiang-Feng , Li Hua-Xiang , Rao Sheng-Qi , Yang Zhen-Quan , Gao Song
Published: April 2022

Vibrio species are important pathogens of marine animals and aquaculture populations and some of them can cause serious infections in humans through consumption of contaminated seafood and aquaculture products. Lytic bacteriophages can potentially alleviate Vibrio contamination in the aquaculture organisms and in the processing of aquatic products and have gained significant scientific attention in recent years. In the present study, bacteriophages were isolated from sewage of local aquatic products markets and grown using Vibrio mimicus CICC 21613 as host cells. The lytic vibriophage OY1 belonging to the newly proposed family Autographiviridae and the genus Maculvirus was identified by observation under electron microscope and comparative genomic analysis. The phage OY1 showed lytic activity against 24 among 32 tested strains belonging to eight Vibrio species. The complete phage OY1 genome consists of a single circular double-stranded DNA of 43,479 bp with a total GC content of 49.27% and was predicted to encode 40 open reading frames (ORFs). To evaluate its potential against vibrios, the one-step growth curve, thermal and pH stability, host range, and lytic activity of the OY1 phage against Vibrio species were evaluated. The results showed that phage OY1 had a range of thermal and pH tolerance, and exhibited a significant inhibitory effect on the growth of tested Vibrio species. Bacterial growth in the fish muscle extract juice (FMEJ) inoculated with Vibrio mimicus CICC 21613, Vibrio parahaemolyticus CICC 21617, Vibrio alginolyticus VJ14, and the mixed bacterial culture was reduced by 2.65 log CFU/ml, 2.42 log CFU/ml, 1.93 log CFU/ml, and 2.01 log CFU/ml, respectively, by incubation with phage OY1 at 25°C for 36 h. Phage OY1 also showed a strong ability to prevent biofilm formation and destroy formed Vibrio species biofilms. These results indicate that phage OY1 is a potential biocontrol agent against Vibrio species in the aquaculture industry and in food safety control.
RdsA Is a Global Regulator That Controls Cell Shape and Division in Rhizobium etli
Authors: Martínez-Absalón Sofía , Guadarrama Carmen , Dávalos Araceli , Romero David
Published: April 2022

Unlike other bacteria, cell growth in rhizobiales is unipolar and asymmetric. The regulation of cell division, and its coordination with metabolic processes is an active field of research. In Rhizobium etli, gene RHE_PE00024, located in a secondary chromosome, is essential for growth. This gene encodes a predicted hybrid histidine kinase sensor protein, participating in a, as yet undescribed, two-component signaling system. In this work, we show that a conditional knockdown mutant (cKD24) in RHE_PE00024 (hereby referred as rdsA, after rhizobium division and shape) generates a striking phenotype, where nearly 64% of the cells present a round shape, with stochastic and uncoordinated cell division. For rod-shaped cells, a large fraction (12 to 29%, depending on their origin) present growth from the old pole, a sector that is normally inactive for growth in a wild-type cell. A fraction of the cells (1 to 3%) showed also multiple ectopic polar growths. Homodimerization of RdsA appears to be required for normal function. RNAseq analysis of mutant cKD24 reveals global changes, with downregulated genes in at least five biological processes: cell division, wall biogenesis, respiration, translation, and motility. These modifications may affect proper structuring of the divisome, as well as peptidoglycan synthesis. Together, these results indicate that the hybrid histidine kinase RdsA is an essential global regulator influencing cell division and cell shape in R. etli.
In vivo Functional Characterization of Hydrophilic X2 Modules in the Cellulosomal Scaffolding Protein
Authors: Tao Xuanyu , Liu Jiantao , Kempher Megan L. , Xu Tao , Zhou Jizhong
Published: April 2022

As part of free cellulases or scaffolding proteins in cellulosomes, the hydrophilic non-catalytic X2 module is widely distributed in cellulolytic Clostridia or other Firmicutes bacteria. Previous biochemical studies suggest that X2 modules might increase the solubility and substrate binding affinity of X2-bearing proteins. However, their in vivo biological functions remain elusive. Here we employed CRISPR-Cas9 editing to genetically modify X2 modules by deleting the conserved motif (NGNT) from the CipC scaffoldin. Both single and double X2 mutants (X2-N: near the N terminus of CipC; X2-C: near the C terminus of CipC) presented similar stoichiometric compositions in isolated cellulosomes as the wildtype strain (WT). These X2 mutants had an elongated adaptation stage during growth on cellulose compared to cellobiose. Compared to WT, the double mutant ΔX2-NC reduced cellulose degradation by 15% and the amount of released soluble sugars by 63%. Since single X2 mutants did not present such obvious physiological changes as ΔX2-NC, there seems to be a functional redundancy between X2 modules in CipC. The in vivo adhesion assay revealed that ΔX2-NC decreased cell attachment to cellulose by 70% but a weaker effect was also overserved in single X2 mutants. These results highlight the in vivo biological role of X2 in increasing cellulose degradation efficiency by enhancing the binding affinity between cells and cellulose, which provides new perspectives for microbial engineering.
A Novel Loop-Mediated Isothermal Amplification Assay for Rapid Detection of Yersinia pestis
Authors: Bai Ying , Rizzo Maria Rosales , Parise Christina , Maes Sarah , Eisen Rebecca J.
Published: April 2022

Rapid detection of Yersinia pestis, the causative agent of plague, is essential during field investigations to enable prompt control measures for prevention of the spread of the disease. Affordable, efficient, reliable, and simple detection assays are extremely useful, particularly in plague-endemic regions with limited resources. We developed a loop-mediated isothermal amplification (LAMP) assay that detects Y. pestis within 30 min by simply incubating at 65°C on a dry bath heater. The assay targeted the caf1A gene that is situated on the pMT1 plasmid using six specific primers. Y. pestis presence is visually detected based on the color change in the reactions. For comparison of the assay performance, a real-time LAMP with fluorescent dye detection was conducted on a real-time PCR instrument using the same six primers. Sensitivity assessment showed that the limit of detection (LOD) was 0.2 and 0.03 pg when performed on the dry bath heater and on the real-time PCR instrument, respectively. The assay was 100% specific, having no cross-reactivity with closely related Yersinia spp. and other bacterial species. We tested the LAMP assay on field-collected fleas and showed that it successfully detected Y. pestis with identical results to that of a previously published pentaplex real-time PCR assay. These findings suggest that the relatively inexpensive and simpler LAMP assay could be used to support field investigations, yielding comparable results to more expensive and complex PCR assays.
The Effect of Early and Delayed Harvest on Dynamics of Fermentation Profile, Chemical Composition, and Bacterial Community of King Grass Silage
Authors: Long Shihe , Li Xuefeng , Yuan Xianjun , Su Rina , Pan Junxin , Chang Ye , Shi Mengli , Cui Zhihai , Huang Naixin , Wang Jian
Published: April 2022

The objective of this study was to assess the effect of harvesting time on the fermentation characteristics, chemical composition, and microbial community of king grass silage. King grass was harvested at three growth periods of 90 days (KN90S), 110 days (KN110S), and 130 days (KN130S); chopped into 2–3-cm particle size; and ensiled in polyethylene bags (20 × 30 cm). The fermentation quality and chemical composition of silages were analyzed after 1, 3, 7, 14, 30, and 60 days of ensiling. Bacterial community of silage ensiled for 60 days was profiled using next generation sequencing (NGS) technology. The KN110S showed the most extensive lactic acid (LA) fermentation during 7 days of fermentation compared to KN90S and KN130S. After 60 days of fermentation, the KN110S showed the lowest pH and the highest lactic acid content among the three treatments. The butyric acid and ammonia nitrogen contents of KN90S and KN130S were significantly greater than those of KN110S (p < 0.05). After a timespan of 60 days of ensiling, the bacterial community of king grass silage was predominantly populated by Proteobacteria in phylum level, whereas unclassified Enterobacteriaceae genus remained dominant in all silages. A higher relative abundance of Clostridium was observed in KN90S and KN130S, but not in KN110S, and greater abundance of Lactococcus appeared in KN110S and KN130S silages than KN90S. It is concluded that harvesting time had an important effect on the fermentation quality and microbial community of king grass silage.
Comparative Assessment of the Efficacy of Commercial Hand Sanitizers Against Human Norovirus Evaluated by an in vivo Fingerpad Method
Authors: Escudero-Abarca Blanca I. , Goulter Rebecca M. , Manuel Clyde S. , Leslie Rachel A. , Green Kristen , Arbogast James W. , Jaykus Lee-Ann
Published: April 2022

Human noroviruses (hNoV) are the leading cause of acute non-bacterial gastroenteritis worldwide and contaminated hands play a significant role in the spread of disease. Some hand sanitizers claim to interrupt hNoV transmission, but their antiviral efficacy on human hands is poorly characterized. The purpose of this work was to characterize the efficacy of representative commercial hand sanitizers against hNoV using an in vivo fingerpad method (ASTM E1838-17). Eight products [seven ethanol-based and one benzalkonium chloride (BAK)-based], and a benchmark 60% ethanol solution, were each evaluated on 10 human volunteers using the epidemic GII.4 hNoV strain. Virus titers before and after treatment were evaluated by RT-qPCR preceded by RNase treatment; product efficacy was characterized by log10 reduction (LR) in hNoV genome equivalent copies after treatment. The benchmark treatment produced a 1.7 ± 0.5 LR, compared with Product A (containing 85% ethanol) which produced a 3.3 ± 0.3 LR and was the most efficacious (p < 0.05). Product B (containing 70% ethanol), while less efficacious than Product A (p < 0.05), performed better than the benchmark with a LR of 2.4 ± 0.4. Five of the other ethanol-based products (labeled ethanol concentration ranges of 62–80%) showed similar efficacy to the 60% ethanol benchmark with LR ranging from 1.3 to 2.0 (p > 0.05). Product H (0.1% BAK) was less effective than the benchmark with a LR of 0.3 ± 0.2 (p < 0.05). None of the products screened were able to completely eliminate hNoV (maximum assay resolution 5.0 LR). Product performance was variable and appears driven by overall formulation. There remains a need for more hand sanitizer formulations having greater activity against hNoV, a virus that is comparatively recalcitrant relative to other pathogens of concern in community, healthcare, and food preparation environments.
INPP5E and Coordination of Signaling Networks in Cilia
Authors: Zhang Renshuai , Tang Jianming , Li Tianliang , Zhou Jun , Pan Wei
Published: April 2022

Primary cilia are ubiquitous mechanosensory organelles that specifically coordinate a series of cellular signal transduction pathways to control cellular physiological processes during development and in tissue homeostasis. Defects in the function or structure of primary cilia have been shown to be associated with a large range of diseases called ciliopathies. Inositol polyphosphate-5-phosphatase E (INPP5E) is an inositol polyphosphate 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety and hydrolyzes both phosphatidylinositol-4, 5-bisphosphate (PtdIns(4,5)P2) and PtdIns(3,4,5)P3, leading to changes in the phosphoinositide metabolism, thereby resulting in a specific phosphoinositide distribution and ensuring proper localization and trafficking of proteins in primary cilia. In addition, INPP5E also works synergistically with cilia membrane-related proteins by playing key roles in the development and maintenance homeostasis of cilia. The mutation of INPP5E will cause deficiency of primary cilia signaling transduction, ciliary instability and ciliopathies. Here, we present an overview of the role of INPP5E and its coordination of signaling networks in primary cilia.
Complications After Deep Brain Stimulation: A 21-Year Experience in 426 Patients
Authors: Jung In-Ho , Chang Kyung Won , Park So Hee , Chang Won Seok , Jung Hyun Ho , Chang Jin Woo
Published: April 2022

Background

Deep brain stimulation is an established treatment for movement disorders such as Parkinson’s disease, essential tremor, and dystonia. However, various complications that occur after deep brain stimulation are a major concern for patients and neurosurgeons.

Objective

This study aimed to analyze various complications that occur after deep brain stimulation.

Methods

We reviewed the medical records of patients with a movement disorder who underwent bilateral deep brain stimulation between 2000 and 2020. Among them, patients requiring revision surgery were analyzed.

Results

A total of 426 patients underwent bilateral deep brain stimulation for a movement disorder. The primary disease was Parkinson’s disease in 315 patients, followed by dystonia in 71 patients and essential tremor in 40 patients. Twenty-six (6.1%) patients had complications requiring revision surgery; the most common complication was infection (12 patients, 2.8%).

Conclusion

Various complications may occur after deep brain stimulation, and patient prognosis should be improved by reducing complications.
The Role of Inhibitory Interneurons in Circuit Assembly and Refinement Across Sensory Cortices
Authors: Ferrer Camilo , De Marco García Natalia V.
Published: April 2022

Sensory information is transduced into electrical signals in the periphery by specialized sensory organs, which relay this information to the thalamus and subsequently to cortical primary sensory areas. In the cortex, microcircuits constituted by interconnected pyramidal cells and inhibitory interneurons, distributed throughout the cortical column, form the basic processing units of sensory information underlying sensation. In the mouse, these circuits mature shortly after birth. In the first postnatal week cortical activity is characterized by highly synchronized spontaneous activity. While by the second postnatal week, spontaneous activity desynchronizes and sensory influx increases drastically upon eye opening, as well as with the onset of hearing and active whisking. This influx of sensory stimuli is fundamental for the maturation of functional properties and connectivity in neurons allocated to sensory cortices. In the subsequent developmental period, spanning the first five postnatal weeks, sensory circuits are malleable in response to sensory stimulation in the so-called critical periods. During these critical periods, which vary in timing and duration across sensory areas, perturbations in sensory experience can alter cortical connectivity, leading to long-lasting modifications in sensory processing. The recent advent of intersectional genetics, in vivo calcium imaging and single cell transcriptomics has aided the identification of circuit components in emergent networks. Multiple studies in recent years have sought a better understanding of how genetically-defined neuronal subtypes regulate circuit plasticity and maturation during development. In this review, we discuss the current literature focused on postnatal development and critical periods in the primary auditory (A1), visual (V1), and somatosensory (S1) cortices. We compare the developmental trajectory among the three sensory areas with a particular emphasis on interneuron function and the role of inhibitory circuits in cortical development and function.