bluuebunny/crossref_metadata_2025 huggingface dataset:
Construction and Demolition Waste-Derived Feedstock: Fuel Characterization of a Potential Resource for Sustainable Aviation Fuels Production
Authors: Bach Quang-Vu , Fu Jinxia , Turn Scott
Published: November 2021

Detailed characterization of physical and fuel properties of construction and demolition waste (CDW) can support research and commercial efforts to develop sustainable aviation fuels. The current study reports time-series data for bulk density, mineral composition, reactivity, and fuel properties (proximate analysis, ultimate analysis, heating value and ash fusibility) of the combustible material fraction of samples mined from an active CDW landfill on the island of Oʻahu, Hawaiʻi. The fuel properties are in ranges comparable to other reference solid wastes such as demolition wood, municipal solid wastes, and landfilled materials. Ash fusion temperatures (from initial deformation to fluid deformation) among the samples were found to lie in a narrow range from 1,117 to 1,247°C. Despite higher ash contents, the CDW derived feedstock samples had comparable heating values to reference biomass and construction wood samples, indicating the presence of higher energy content materials (e.g., plastics, roofing material, etc.) in addition to wood. The waste samples show lower reactivity peaks in the devolatilization stage, but higher reactivity peaks (located at lower temperatures) in the gasification and combustion stage, compared with those of reference biomass and construction woods. Mineral elemental analysis revealed that materials from various sources (gypsum, plastic, rust, paint, paint additives, and soils) were present in the samples. Soil recovered from the landfill contained higher Ca, Cu, Fe, K, Mn, Pb, and Zn levels than soil samples from elsewhere on the island. Results from this study can provide insight on variations in the physical and fuel properties of the CDW derived feedstocks, and support the design of conversion systems.
Integration of Active Solar Thermal Technologies in Greenhouses: A Mini Review
Authors: Ding Ding
Published: November 2021

Traditional agricultural greenhouses have been used to grow vegetables in the winter without any auxiliary heating. However, crop production is highly influenced by soil and air temperatures, humidity, and solar radiation. The aim of this paper is to review the recent active solar thermal technologies that help reduce the energy demand for greenhouse climate control and achieve intensive crop production. The review is categorized into the following topics: 1) locations for collector installation; 2) discussion on the different types of solar collectors, which include metal-based, glass-based, ceramic-based, plastic-based, and hybrid photovoltaic/thermal types for greenhouse applications; 3) heat release systems in active greenhouses in terms of basal heating, backwall heating, and air heating systems; and 4) short-term and long-term heat storage systems for greenhouses. Future studies on active solar greenhouses might focus on microclimate prediction, long-term heat storage, and system optimization.
Research on the Hole Length Ratio of Fan-Shaped Holes in Flat Plate Film Cooling
Authors: Zhou Xun , Qin Runxuan , Cai Le
Published: November 2021

To study the influence of different hole length ratios on the flow structure and film cooling efficiency, a calculation model of fan-shaped hole was constructed and numerically studied. The effect of different hole length ratios on the cooling efficiency under different blowing ratios was compared and analyzed. The results showed that as the blowing ratio increases, the overall average efficiency of most of the hole length ratio cases first increases and then decreases. Only in the case with a cylindrical part length/total length ratio of 0.5 did the efficiency continue to increase. When the blowing ratio is small, the spanwise average efficiency of each hole length ratio case is closer, but the flow structure and efficiency distribution are quite different. For the medium blowing ratio, the overall average efficiency of the small hole length ratio case is higher, and the efficiency decreases as the hole length ratio increases. When the cylindrical part length/total length ratio is further increased to 1, the cooling efficiency region basically converges into a spanwise narrow region. For larger blowing ratio conditions, after 10D after the hole outlet, the case with a cylindrical part length/total length of 0.5 is more efficient.
Decoupled Acoustic and Visual Components in the Multimodal Signals of the Common Cuckoo (Cuculus canorus)
Authors: Esposito Martina , Ceraulo Maria , Tuliozi Beniamino , Buscaino Giuseppa , Mazzola Salvatore , Sala Luigi , Dal Zotto Matteo , Campobello Daniela
Published: November 2021

Because of its parasitic habits, reproduction costs of the common cuckoo (Cuculus canorus) are mostly spent in pre-laying activities. Female costs are limited to searching host nests and laying eggs, whereas, males spend time in performing intense vocal displays, possibly with territorial purpose. This last aspect, together with a sexual plumage dimorphism, points to both intra- and inter-sexual selections operating within this species. One element triggering sexual selection is a differential fitness accrued by different phenotypes. Before analyzing possible sexual selection mechanisms operating in cuckoos, it is therefore necessary to verify whether there is a variability among male secondary characters by describing and quantifying them. Here we aimed to quantitatively characterize the main two potential candidates of sexual selection traits, i.e., calls and displays, shown by males at perches. During the 2019 breeding season, in a site within the Po Plain, we both audio and video recorded cuckoo males at five different perches. We analyzed acoustic variables as well as display sequences searching for potential correlations. We found a significant variation among calls that could be clustered into four vocal types. We also found that no visual displays were associated with vocal displays; cuckoo males were either vocal and motionless or soundless and active. We discuss our results under the perspective of the potential value of sexual selection in brood parasites and its role in its parasitic habit.
Species Home-Making in Ecosystems: Toward Place-Based Ecological Metrics of Belonging
Authors: Cordell Susan , Bardwell-Jones Celia , Ostertag Rebecca , Uowolo Amanda , DiManno Nicole
Published: November 2021

Globalization has undeniably impacted the Earth’s ecosystems, but it has also influenced how we think about natural systems. Three fourths of the world’s forests are now altered by human activity, which challenges our concepts of native ecosystems. The dichotomies of pristine vs. disturbed as well as our view of native and non-native species, have blurred; allowing us to acknowledge new paradigms about how humans and nature interact. We now understand that the use of militaristic language to define the perceived role of a plant species is holding us back from the fact that novel systems (new combinations of all species) can often provide valuable ecosystem services (i.e., water, carbon, nutrients, cultural, and recreation) for creatures (including humans). In reality, ecosystems exist in a gradient from native to intensely managed – and “non-nativeness” is not always a sign of a species having negative effects. In fact, there are many contemporary examples of non-native species providing critical habitat for endangered species or preventing erosion in human-disturbed watersheds. For example, of the 8,000–10,000 non-native species introduced to Hawai‘i, less than 10% of these are self-sustaining and 90 of those pose a danger to native biota and are considered invasive. In this paper, we explore the native/non-native binary, the impacts of globalization and the political language of invasion through the lens of conservation biology and sociology with a tropical island perspective. This lens gives us the opportunity to offer a place-based approach toward the use of empirical observation of novel species interactions that may help in evaluating management strategies that support biodiversity and ecosystem services. Finally, we offer a first attempt at conceptualizing a site-specific approach to develop “metrics of belonging” within an ecosystem.
Cell2Fire: A Cell-Based Forest Fire Growth Model to Support Strategic Landscape Management Planning
Authors: Pais Cristobal , Carrasco Jaime , Martell David L. , Weintraub Andres , Woodruff David L.
Published: November 2021

Cell2Fire is a new cell-based wildland fire growth simulator designed to integrate data-driven landscape management planning models. The fire environment is modeled by partitioning the landscape into cells characterized by fuel, weather, moisture content, and topographic attributes. The model can use existing fire spread models such as the Canadian Forest Fire Behavior Prediction System to model fire growth. Cell2Fire is structured to facilitate its use for predicting the growth of individual fires or by embedding it in landscape management simulation models. Decision-making models such as fuel treatment/harvesting plans can be easily integrated and evaluated. It incorporates a series of out-of-the-box planning heuristics that provide benchmarks for comparison. We illustrate their use by applying and evaluating a series of harvesting plans for forest landscapes in Canada. We validated Cell2Fire by using it to predict the growth of both real and hypothetical fires, comparing our predictions with the fire scars produced by a validated fire growth simulator (Prometheus). Cell2Fire is implemented as an open-source project that exploits parallelism to efficiently support the modeling of fire growth across large spatial and temporal scales. Our experiments indicate that Cell2Fire is able to efficiently simulate wildfires (up to 30x faster) under different conditions with similar accuracy as state-of-the-art simulators (above 90% of accuracy). We demonstrate its effectiveness as part of a harvest planning optimization framework, identifying relevant metrics to capture and actions to mitigate the impact of wildfire uncertainty.
Weighted Gene Co-Expression Network Analysis and Treatment Strategies of Tumor Recurrence-Associated Hub Genes in Lung Adenocarcinoma
Authors: Shen Zhengze , Liu Shengwei , Liu Jie , Liu Jingdong , Yao Caoyuan
Published: November 2021

Despite the recent progress of lung adenocarcinoma (LUAD) therapy, tumor recurrence remained to be a challenging factor that impedes the effectiveness of treatment. The objective of the present study was to predict the hub genes affecting LUAD recurrence via weighted gene co-expression network analysis (WGCNA). Microarray samples from LUAD dataset of GSE32863 were analyzed, and the modules with the highest correlation to tumor recurrence were selected. Functional enrichment analysis was conducted, followed by establishment of a protein–protein interaction (PPI) network. Subsequently, hub genes were identified by overall survival analyses and further validated by evaluation of expression in both myeloid populations and tissue samples of LUAD. Gene set enrichment analysis (GSEA) was then carried out, and construction of transcription factors (TF)–hub gene and drug–hub gene interaction network was also achieved. A total of eight hub genes (ACTR3, ARPC5, RAB13, HNRNPK, PA2G4, WDR12, SRSF1, and NOP58) were finally identified to be closely correlated with LUAD recurrence. In addition, TFs that regulate hub genes have been predicted, including MYC, PML, and YY1. Finally, drugs including arsenic trioxide, cisplatin, Jinfukang, and sunitinib were mined for the treatment of the eight hub genes. In conclusion, our study may facilitate the invention of targeted therapeutic drugs and shed light on the understanding of the mechanism for LUAD recurrence.
The Emerging Interplay Between Recirculating and Tissue-Resident Memory T Cells in Cancer Immunity: Lessons Learned From PD-1/PD-L1 Blockade Therapy and Remaining Gaps
Authors: Gitto Silvia , Natalini Ambra , Antonangeli Fabrizio , Di Rosa Francesca
Published: November 2021

Remarkable progress has been made in the field of anti-tumor immunity, nevertheless many questions are still open. Thus, even though memory T cells have been implicated in long-term anti-tumor protection, particularly in prevention of cancer recurrence, the bases of their variable effectiveness in tumor patients are poorly understood. Two types of memory T cells have been described according to their traffic pathways: recirculating and tissue-resident memory T cells. Recirculating tumor-specific memory T cells are found in the cell infiltrate of solid tumors, in the lymph and in the peripheral blood, and they constantly migrate in and out of lymph nodes, spleen, and bone marrow. Tissue-resident tumor-specific memory T cells (TRM) permanently reside in the tumor, providing local protection.

Anti-PD-1/PD-L1, a type of immune checkpoint blockade (ICB) therapy, can considerably re-invigorate T cell response and lead to successful tumor control, even in patients at advanced stages. Indeed, ICB has led to unprecedented successes against many types of cancers, starting a ground-breaking revolution in tumor therapy. Unfortunately, not all patients are responsive to such treatment, thus further improvements are urgently needed. The mechanisms underlying resistance to ICB are still largely unknown. A better knowledge of the dynamics of the immune response driven by the two types of memory T cells before and after anti-PD-1/PD-L1 would provide important insights on the variability of the outcomes. This would be instrumental to design new treatments to overcome resistance.

Here we provide an overview of T cell contribution to immunity against solid tumors, focusing on memory T cells. We summarize recent evidence on the involvement of recirculating memory T cells and TRM in anti-PD-1/PD-L1-elicited antitumor immunity, outline the open questions in the field, and propose that a synergic action of the two types of memory T cells is required to achieve a full response. We argue that a T-centric vision focused on the specific roles and the possible interplay between TRM and recirculating memory T cells will lead to a better understanding of anti-PD-1/PD-L1 mechanism of action, and provide new tools for improving ICB therapeutic strategy.
Development of a Flow Cytometry Assay to Predict Immune Checkpoint Blockade-Related Complications
Authors: Schilling Hannah-Lou , Glehr Gunther , Kapinsky Michael , Ahrens Norbert , Riquelme Paloma , Cordero Laura , Bitterer Florian , Schlitt Hans J. , Geissler Edward K. , Haferkamp Sebastian , Hutchinson James A. , Kronenberg Katharina
Published: November 2021

Treatment of advanced melanoma with combined immune checkpoint inhibitor (ICI) therapy is complicated in up to 50% of cases by immune-related adverse events (irAE) that commonly include hepatitis, colitis and skin reactions. We previously reported that pre-therapy expansion of cytomegalovirus (CMV)-reactive CD4+ effector memory T cells (TEM) predicts ICI-related hepatitis in a subset of patients with Stage IV melanoma given αPD-1 and αCTLA-4. Here, we develop and validate a 10-color flow cytometry panel for reliably quantifying CD4+ TEM cells and other biomarkers of irAE risk in peripheral blood samples. Compared to previous methods, our new panel performs equally well in measuring CD4+ TEM cells (agreement = 98%) and is superior in resolving CD4+ CD197+ CD45RA- central memory T cells (TCM) from CD4+ CD197+ CD45RA+ naive T cells (Tnaive). It also enables us to precisely quantify CD14+ monocytes (CV = 6.6%). Our new “monocyte and T cell” (MoT) assay predicts immune-related hepatitis with a positive predictive value (PPV) of 83% and negative predictive value (NPV) of 80%. Our essential improvements open the possibility of sharing our predictive methods with other clinical centers. Furthermore, condensing measurements of monocyte and memory T cell subsets into a single assay simplifies our workflows and facilitates computational analyses.
A New Formulation of Probiotics Attenuates Calcipotriol-Induced Dermatitis by Inducing Regulatory Dendritic Cells
Authors: Xu Beilei , Ling Shiqi , Xu Xiaoqiang , Liu Xiaochun , Wang Ao , Zhou Yuan , Luo Yang , Li Wei , Yao Xu
Published: November 2021

Atopic dermatitis (AD) is a recurrent chronic inflammatory skin disease affecting up to 30% of the children population, and immuno-regulatory therapy that could modify the course of disease is urgently needed. Probiotics have demonstrated therapeutic effects on AD and could potentially regulate the disease process. However, the efficacy of probiotics for AD is inconsistent among different studies, which is mainly due to the elusive mechanism and different species and (or) strains used. In this study, we designed a mixture of five strains of probiotics (named IW5) and analyzed the effect and mechanism of IW5 on calcipotriol (MC903)-induced AD-like dermatitis. We found that IW5 significantly alleviated skin inflammation of the MC903-induced AD in mice. Administration with IW5 induced increased production of regulatory T cells and regulatory dendritic cells (DCregs) in the mesenteric lymph nodes. We also found that the diversity of the gut microbiota in the mice with MC903-induced dermatitis was increased after IW5 administration, and the level of butyrate in the gut was elevated. In cell culture, butyrate induced the production of DCregs. Our study revealed the therapeutic effects of a newly designed probiotics mixture and uncovered a possible mechanism, providing a foundation for future clinical studies.
Air Pollution Particulate Matter Amplifies White Matter Vascular Pathology and Demyelination Caused by Hypoperfusion
Authors: Huuskonen Mikko T. , Liu Qinghai , Lamorie-Foote Krista , Shkirkova Kristina , Connor Michelle , Patel Arati , Montagne Axel , Baertsch Hans , Sioutas Constantinos , Morgan Todd E. , Finch Caleb E. , Zlokovic Berislav V. , Mack William J.
Published: November 2021

Cerebrovascular pathologies are commonly associated with dementia. Because air pollution increases arterial disease in humans and rodent models, we hypothesized that air pollution would also contribute to brain vascular dysfunction. We examined the effects of exposing mice to nanoparticulate matter (nPM; aerodynamic diameter ≤200 nm) from urban traffic and interactions with cerebral hypoperfusion. C57BL/6 mice were exposed to filtered air or nPM with and without bilateral carotid artery stenosis (BCAS) and analyzed by multiparametric MRI and histochemistry. Exposure to nPM alone did not alter regional cerebral blood flow (CBF) or blood brain barrier (BBB) integrity. However, nPM worsened the white matter hypoperfusion (decreased CBF on DSC-MRI) and exacerbated the BBB permeability (extravascular IgG deposits) resulting from BCAS. White matter MRI diffusion metrics were abnormal in mice subjected to cerebral hypoperfusion and worsened by combined nPM+BCAS. Axonal density was reduced equally in the BCAS cohorts regardless of nPM status, whereas nPM exposure caused demyelination in the white matter with or without cerebral hypoperfusion. In summary, air pollution nPM exacerbates cerebrovascular pathology and demyelination in the setting of cerebral hypoperfusion, suggesting that air pollution exposure can augment underlying cerebrovascular contributions to cognitive loss and dementia in susceptible elderly populations.
Geographic Variation of Particle Size Distribution in the Kuroshio Region: Possible Causes in the Upper Water Column
Authors: Yamada Yosuke , Fukuda Hideki , Umezawa Yu , Nagata Toshi
Published: November 2021

Particle size distribution (PSD) in the ocean is a fundamental property that influences carbon export and food webs; however, PSD variation and its causes in oligotrophic oceans are not entirely clear. Here, we used Laser In-Situ Scattering and Transmissometry to investigate PSD (size range 5.2–119 μm) and related variables at 11 stations in the surface layer (0–20 m) of the Kuroshio region of the western North Pacific, where strong current causes dynamic hydrographic and ecological conditions. PSD slopes (range –3.2 to –4.2), derived from the power law model, were steeper at onshore stations and flatter at oligotrophic stations located offshore and at lower latitudes. Notably, slopes tended to become steeper with increasing chlorophyll a concentration, opposing the generally observed relationship between the two variables, whereas they became flatter with increasing transparent exopolymer particle (TEP) concentration. Possible explanations of the above results are localized occurrence of nanophytoplankton and TEP facilitation of particle aggregation. The results support the hypothesis that PSD slopes are controlled by a multitude of factors, including phytoplankton community dynamics and aggregation processes. To determine whether TEP-induced particle aggregation enhances or suppresses carbon export, we need a better understanding of the nature (porosity, density, and sinking velocity) of aggregates in oligotrophic oceans.
The Pilling-Bedworth Ratio of Oxides Formed From the Precipitated Phases in Magnesium Alloys
Authors: Jiang Quantong , Lu Dongzhu , Liu Chang , Liu Nazhen , Hou Baorong
Published: November 2021

The Pilling-Bedworth ratio of oxides preferentially formed from the precipitated phases in magnesium alloys were calculated. The results showed that the PBR value of Nd2O3 preferentially formed from Mg12Nd was 1.0584, and the PBR value of Y2O3 preferentially formed from Mg24Y5 was 1.1923. Both the Nd2O3 and Y2O3 would provide a good protection to the Mg matrix. The Gd2O3 preferentially formed from Mg3Gd, whereas the MgO preferentially formed from MgNi2. The PBR value of these two oxides were both larger than 2. The corresponding oxides formed from the common precipitated phases Mg17Al12, MgZn2, MgCu2, Mg2Ca, Mg12Ce, and MgAg were all less than 1. The oxide films formed on surfaces of pure Mg and Mg-xY (x = 3, 5, 7 wt.%) alloys at high temperatures were analyzed. The results showed that the oxide films were composed of a Y2O3/MgO outer layer and an inner layer rich with Y2O3. The formation of Y2O3 was mainly caused by the oxidation of Mg24Y5. The more Y2O3 existed in the composite oxidation film, the better corrosion resistance of the Mg-Y samples.
Machine Learning Approach to Predict Positive Screening of Methicillin-Resistant Staphylococcus aureus During Mechanical Ventilation Using Synthetic Dataset From MIMIC-IV Database
Authors: Hirano Yohei , Shinmoto Keito , Okada Yohei , Suga Kazuhiro , Bombard Jeffrey , Murahata Shogo , Shrestha Manoj , Ocheja Patrick , Tanaka Aiko
Published: November 2021

Background: Mechanically ventilated patients are susceptible to nosocomial infections such as ventilator-associated pneumonia. To treat ventilated patients with suspected infection, clinicians select appropriate antibiotics. However, decision-making regarding the use of antibiotics for methicillin-resistant Staphylococcus aureus (MRSA) is challenging, because of the lack of evidence-supported criteria. This study aims to derive a machine learning model to predict MRSA as a possible pathogen responsible for infection in mechanically ventilated patients.

Methods: Data were collected from the Medical Information Mart for Intensive Care (MIMIC)-IV database (an openly available database of patients treated at the Beth Israel Deaconess Medical Center in the period 2008–2019). Of 26,409 mechanically ventilated patients, 809 were screened for MRSA during the mechanical ventilation period and included in the study. The outcome was positivity to MRSA on screening, which was highly imbalanced in the dataset, with 93.9% positive outcomes. Therefore, after dividing the dataset into a training set (n = 566) and a test set (n = 243) for validation by stratified random sampling with a 7:3 allocation ratio, synthetic datasets with 50% positive outcomes were created by synthetic minority over-sampling for both sets individually (synthetic training set: n = 1,064; synthetic test set: n = 456). Using these synthetic datasets, we trained and validated an XGBoost machine learning model using 28 predictor variables for outcome prediction. Model performance was evaluated by area under the receiver operating characteristic (AUROC), sensitivity, specificity, and other statistical measurements. Feature importance was computed by the Gini method.

Results: In validation, the XGBoost model demonstrated reliable outcome prediction with an AUROC value of 0.89 [95% confidence interval (CI): 0.83–0.95]. The model showed a high sensitivity of 0.98 [CI: 0.95–0.99], but a low specificity of 0.47 [CI: 0.41–0.54] and a positive predictive value of 0.65 [CI: 0.62–0.68]. Important predictor variables included admission from the emergency department, insertion of arterial lines, prior quinolone use, hemodialysis, and admission to a surgical intensive care unit.

Conclusions: We were able to develop an effective machine learning model to predict positive MRSA screening during mechanical ventilation using synthetic datasets, thus encouraging further research to develop a clinically relevant machine learning model for antibiotics stewardship.
Simple Self-Assessment Tool to Predict Osteoporosis in Taiwanese Men
Authors: Liu Dung-Huan , Hsu Chung-Yuan , Wu Pei-Ching , Chen Ying-Chou , Chen You-Yin , Chen Jia-Feng , Yu Shan-Fu , Cheng Tien-Tsai
Published: November 2021

Background: Although the self-assessment tools for predicting osteoporosis are convenient for clinicians, they are not commonly used among men. We developed the Male Osteoporosis Self-Assessment Tool for Taiwan (MOSTAi) to identify the patients at risk of osteoporosis.

Methods: All the participants completed a questionnaire on the clinical risk factors for the fracture risk assessment tool. The risk index was calculated by the multivariate regression model through the item reduction method. The receiver operating characteristic (ROC) curve was used to analyze its sensitivity and specificity, and MOSTAi was developed and validated.

Results: A total of 2,290 men participated in the bone mineral density (BMD) survey. We chose a model that considered two variables (age and weight). The area under the curve (AUC) of the model was 0.700. The formula for the MOSTAi index is as follows: 0.3 × (weight in kilograms) – 0.1 × (years). We chose 11 as the appropriate cut-off value for the MOSTAi index to identify the subjects at the risk of osteoporosis.

Conclusions: The MOSTAi is a simple, intuitive, and country-specific tool that can predict the risk of osteoporosis in Taiwanese men. Due to different demographic characteristics, each region of the world can develop its own model to identify patients with osteoporosis more effectively.
Risk Factors for Invasive Aspergillosis in Patients Admitted to the Intensive Care Unit With Coronavirus Disease 2019: A Multicenter Retrospective Study
Authors: Xu Jiqian , Yang Xiaobo , Lv Zheng , Zhou Ting , Liu Hong , Zou Xiaojing , Cao Fengsheng , Zhang Lu , Liu Boyi , Chen Wei , Yu Yuan , Shu Huaqing , Yuan Shiying , Hu Ming , Huang Chaolin , Shang You
Published: November 2021

Background: Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in coronavirus disease 2019 (COVID-19) patients admitted to intensive care units (ICUs), but risk factors for COVID-19-associated IPA (CAPA) have not been fully characterized. The aim of the current study was to identify factors associated with CAPA, and assess long-term mortality.

Methods: A retrospective cohort study of adult COVID-19 patients admitted to ICUs from six hospitals was conducted in Hubei, China. CAPA was diagnosed via composite clinical criteria. Demographic information, clinical variables, and 180-day outcomes after the diagnosis of CAPA were analyzed.

Results: Of 335 critically ill patients with COVID-19, 78 (23.3%) developed CAPA within a median of 20.5 days (range 13.0–42.0 days) after symptom onset. Compared to those without CAPA, CAPA patients were more likely to have thrombocytopenia (50 vs. 19.5%, p < 0.001) and secondary bacterial infection prior to being diagnosed with CAPA (15.4 vs. 6.2%, p = 0.013), and to receive vasopressors (37.2 vs. 8.6%, p < 0.001), higher steroid dosages (53.9 vs. 34.2%, p = 0.002), renal replacement therapy (37.2 vs. 13.6%, p < 0.001), and invasive mechanical ventilation (57.7 vs. 35.8%, p < 0.001). In multivariate analysis incorporating hazard ratios (HRs) and confidence intervals (CIs), thrombocytopenia (HR 1.98, 95% CI 1.16–3.37, p = 0.012), vasopressor use (HR 3.57, 95% CI 1.80–7.06, p < 0.001), and methylprednisolone use at a daily dose ≥ 40 mg (HR 1.69, 95% CI 1.02–2.79, p = 1.02–2.79) before CAPA diagnosis were independently associated with CAPA. Patients with CAPA had longer median ICU stays (17 days vs. 12 days, p = 0.007), and higher 180-day mortality (65.4 vs. 33.5%, p < 0.001) than those without CAPA.

Conclusions: Thrombocytopenia, vasopressor use, and corticosteroid treatment were significantly associated with increased risk of incident IPA in COVID-19 patients admitted to ICUs. The occurrence of CAPA may increase the likelihood of long-term COVID-19 mortality.
Comparison of the New Viscoelastic Coagulation Analyzer ClotPro® With ROTEM® Delta and Conventional Coagulation Tests in Critically Ill Patients With COVID-19
Authors: Infanger Lukas , Dibiasi Christoph , Schaden Eva , Ulbing Stefan , Wiegele Marion , Lacom Conrad , Gratz Johannes
Published: November 2021

Background: Viscoelastic coagulation testing has been suggested to help manage coagulopathy in critically ill patients with COVID-19. However, results from different viscoelastic devices are not readily comparable. ClotPro® is a novel thromboelastometry analyzer offering a wider range of commercially available assays.

Methods: We compared the results from ClotPro with results from the well-established ROTEM® Delta device and conventional coagulation tests in critically ill patients with COVID-19.

Results: Viscoelastic parameters indicated the presence of a potentially hypercoagulable state in the majority of patients. In up to 95 paired measurements, we found strong correlations between several parameters routinely used in clinical practice: (i) EX test vs. EXTEM CT, A5, A10, MCF, (ii) IN test vs. INTEM A5, A10, MCF, and (iii) FIB test vs. FIBTEM A5, A10, MCF (all R > 0.7 and p < 0.001). In contrast, IN test CT vs. INTEM CT showed only a moderate correlation (R = 0.53 and p < 0.001). Clot strength parameters of both devices exhibited strong correlations with platelet counts and fibrinogen levels (all R > 0.7 and p < 0.001). Divergent correlations of intrinsically activated assays with aPTT and anti-factor Xa activity were visible. Regarding absolute differences of test results, considerable delta occurred in CT, CFT, and clot strength parameters (all p < 0.001) between both devices.

Conclusions: Several parameters obtained by ClotPro show strong correlations with ROTEM Delta. Due to weak correlations of intrinsically activated clotting times and considerable absolute differences in a number of parameters, our findings underline the need for device-specific algorithms in this patient cohort.
Improving Chicken Responses to Glycoconjugate Vaccination Against Campylobacter jejuni
Authors: Nothaft Harald , Perez-Muñoz Maria Elisa , Yang Tianfu , Murugan Abarna V. M. , Miller Michelle , Kolarich Daniel , Plastow Graham S. , Walter Jens , Szymanski Christine M.
Published: November 2021

Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.
Antifungal Effect of Antimicrobial Photodynamic Therapy Mediated by Haematoporphyrin Monomethyl Ether and Aloe Emodin on Malassezia furfur
Authors: Cui Zixin , Zhang Miaomiao , Geng Songmei , Niu Xinwu , Wang Xiaopeng , Zhu Yanyan , Ye Feng , Liu Chengcheng
Published: November 2021

Infectious dermatological diseases caused by Malassezia furfur are often chronic, recurrent, and recalcitrant. Current therapeutic options are usually tedious, repetitive, and associated with adverse effects. Alternatives that broaden the treatment options and reduce side effects for patients are needed. Antimicrobial photodynamic therapy (aPDT) is an emerging approach that is quite suitable for superficial infections. The aim of this study is to investigate the antimicrobial efficacy and effect of aPDT mediated by haematoporphyrin monomethyl ether (HMME) and aloe emodin (AE) on clinical isolates of M. furfur in vitro. The photodynamic antimicrobial efficacy of HMME and AE against M. furfur was assessed by colony forming unit (CFU) assay. The uptake of HMME and AE by M. furfur cells was investigated by fluorescence microscopy. Reactive oxygen species (ROS) probe and flow cytometry were employed to evaluate the intracellular ROS level. The effect of HMME and AE-mediated aPDT on secreted protease and lipase activity of M. furfur was also investigated. The results showed that HMME and AE in the presence of light effectively inactivated M. furfur cells in a photosensitizer (PS) concentration and light energy dose-dependent manner. AE exhibited higher antimicrobial efficacy against M. furfur than HMME under the same irradiation condition. HMME and AE-mediated aPDT disturbed the fungal cell envelop, significantly increased the intracellular ROS level, and effectively inhibited the activity of secreted protease and lipase of M. furfur cells. The results suggest that HMME and AE have potential to serve as PSs in the photodynamic treatment of dermatological diseases caused by M. furfur, but further ex vivo or in vivo experiments are needed to verify that they can meet the requirements for clinical practice.
Unveiling Endophytic Bacterial Community Structures of Different Rice Cultivars Grown in a Cadmium-Contaminated Paddy Field
Authors: Chu Chaoqun , Fan Meiyu , Song Chongyang , Li Ni , Zhang Chao , Fu Shaowei , Wang Weiping , Yang Zhiwei
Published: November 2021

Endophytic bacteria play potentially important roles in the processes of plant adaptation to the environment. Understanding the composition and dynamics of endophytic bacterial communities under heavy metal (HM) stress can reveal their impacts on host development and stress tolerance. In this study, we investigated root endophytic bacterial communities of different rice cultivars grown in a cadmium (Cd)-contaminated paddy field. These rice cultivars are classified into low (RBQ, 728B, and NX1B) and high (BB and S95B) levels of Cd-accumulating capacity. Our metagenomic analysis targeting 16S rRNA gene sequence data reveals thatProteobacteria,Firmicutes,Actinobacteria,Acidobacteria,Bacteroidetes, andSpirochaetesare predominant root endophytic bacterial phyla of the five rice cultivars that we studied. Principal coordinate analysis shows that the developmental stage of rice governs a larger source of variation in the bacterial communities compared to that of any specific rice cultivar or of the root Cd content. Endophytic bacterial communities during the reproductive stage of rice form a more highly interconnected network and exhibit higher operational taxonomic unit numbers, diversities, and abundance than those during the vegetative stage. Forty-five genera are significantly correlated with Cd content in rice root, notably including positive-correlatingGeobacterandHaliangium; and negative-correlatingPseudomonasandStreptacidiphilus. Furthermore, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis shows that functional pathways, such as biosynthesis of siderophore and type II polyketide products, are significantly enhanced during the reproductive stage compared to those during the vegetative stage under Cd stress. The isolated endophytic bacteria from the Cd-contaminated rice roots display high Cd resistance and multiple traits that may promote plant growth, suggesting their potential application in alleviating HM stress on plants. This study describes in detail for the first time the assemblage of the bacterial endophytomes of rice roots under Cd stress and may provide insights into the interactions among endophytes, plants, and HM contamination.
Dual-Transcriptomic, Microscopic, and Biocontrol Analyses of the Interaction Between the Bioeffector Pythium oligandrum and the Pythium Soft-Rot of Ginger Pathogen Pythium myriotylum
Authors: Daly Paul , Chen Siqiao , Xue Taiqiang , Li Jingjing , Sheikh Taha Majid Mahmood , Zhang Qimeng , Wang Xuehai , Zhang Jinfeng , Fitzpatrick David A. , McGowan Jamie , Shi Xiujuan , Deng Sheng , Jiu Min , Zhou Dongmei , Druzhinina Irina S. , Wei Lihui
Published: November 2021

Biological control is a promising approach to suppress diseases caused by Pythium spp. such as Pythium soft rot of ginger caused by P. myriotylum. Unusually for a single genus, it also includes species that can antagonize Pythium plant pathogens, such as Pythium oligandrum. We investigated if a new isolate of P. oligandrum could antagonize P. myriotylum, what changes occurred in gene expression when P. oligandrum (antagonist) and P. myriotylum (host) interacted, and whether P. oligandrum could control soft-rot of ginger caused by P. myriotylum. An isolate of P. oligandrum, GAQ1, recovered from soil could antagonize P. myriotylum in a plate-based confrontation assay whereby P. myriotylum became non-viable. The loss of viability of P. myriotylum coupled with how P. oligandrum hyphae could coil around and penetrate the hyphae of P. myriotylum, indicated a predatory interaction. We investigated the transcriptional responses of P. myriotylum and P. oligandrum using dual-RNAseq at a stage in the confrontation where similar levels of total transcripts were measured from each species. As part of the transcriptional response of P. myriotylum to the presence of P. oligandrum, genes including a subset of putative Kazal-type protease inhibitors were strongly upregulated along with cellulases, elicitin-like proteins and genes involved in the repair of DNA double-strand breaks. In P. oligandrum, proteases, cellulases, and peroxidases featured prominently in the upregulated genes. The upregulation along with constitutive expression of P. oligandrum proteases appeared to be responded to by the upregulation of putative protease inhibitors from P. myriotylum, suggesting a P. myriotylum defensive strategy. Notwithstanding this P. myriotylum defensive strategy, P. oligandrum had a strong disease control effect on soft-rot of ginger caused by P. myriotylum. The newly isolated strain of P. oligandrum is a promising biocontrol agent for suppressing the soft-rot of ginger. The dual-RNAseq approach highlights responses of P. myriotylum that suggests features of a defensive strategy, and are perhaps another factor that may contribute to the variable success and durability of biological attempts to control diseases caused by Pythium spp.
Activity of PD-1 Inhibitor Combined With Anti-Angiogenic Therapy in Advanced Sarcoma: A Single-Center Retrospective Analysis
Authors: You Yang , Guo Xi , Zhuang Rongyuan , Zhang Chenlu , Wang Zhiming , Shen Feng , Wang Yan , Liu Wenshuai , Zhang Yong , Lu Weiqi , Hou Yingyong , Wang Jing , Zhang Xuan , Lu Minzhi , Zhou Yuhong
Published: November 2021

Background: Immune checkpoint inhibitors (ICIs) are employed to treat various cancers, including soft tissue sarcomas (STSs), and less than 20% of patients benefit from this treatment. Vascular endothelial growth factor (VEGF) promotes the immunosuppressive tumor microenvironment and contributes to ICI-resistant therapy. Anti-VEGF receptor tyrosine-kinase inhibitors (TKIs) combined with ICIs have shown antitumor activity in patients with alveolar soft-part sarcoma (ASPS). However, they have not been extensively studied to treat other STS subtypes, such as leiomyosarcoma (LMS), dedifferentiated liposarcoma (DDLPS), undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), and angiosarcoma (AS).

Methods: In this retrospective study, we collected data from 61 patients who were diagnosed with advanced STS based on imaging and histology, including LMS, DDLPS, and UPS. Among them, 41 patients were treated with ICIs combined with TKIs and 20 patients received ICI therapy. The endpoints of progression-free survival (PFS) and overall response rate (ORR) were analyzed in the two groups, and the overall response [partial response (PR), stable disease (SD), and progressive disease (PD)] of each patient was determined using RECIST 1.1 evaluation criteria.

Results: In total, 61 STS patients had the following subtypes: LMS (n = 20), DDLPS (n = 17), UPS (n = 8), ASPS (n = 7), MFS (n = 7), and AS (n = 2). The median PFS (mPFS) was significantly prolonged after ICI treatment in combination with TKIs (11.74 months, 95% CI 4.41–14.00) compared to ICI treatment alone (6.81 months, 95% CI 5.43–NA) (HR 0.5464, p = 0.043). The 12-month PFS rates of patients who received ICI–TKI treatment were increased from 20.26% (95% CI 0.08–0.53) to 42.90% (95% CI 0.27–0.68). In the combination therapy group, 12 patients (30%) achieved PR, 25 patients (62.5%) achieved SD, and 3 patients (7.5%) achieved PD for 3 months or longer. In the non-TKI-combination group, 2 patients (9.5%) achieved PR, 14 patients (66.7%) achieved SD, and 5 patients (23.8%) achieved PD within 3 months. The ORRs in the two groups were 30.0% (ICI–TKI combination) and 9.5% (ICI only), respectively. A notable ORR was observed in the ICI–TKI combination group, especially for subtypes ASPS (66.7%), MFS (42.9%), and UPS (33.3%). The PD-L1 expression (n = 33) and tumor mutation burden (TMB, n = 27) were determined for each patient. However, our results showed no significant difference in PFS or response rates between the two groups.

Conclusion: This study suggests that ICI–TKI treatment has antitumor activity in patients with STS, particularly the ASPS and MFS subtypes. Moreover, effective biomarkers to predict clinical outcomes are urgently needed after combination therapy in the STS subtypes.
Atheroprotective Effects and Molecular Mechanism of Berberine
Authors: Xing Lu , Zhou Xin , Li Ai-Hong , Li Hui-Jin , He Chun-Xia , Qin Wei , Zhao Dong , Li Peng-Quan , Zhu Li , Cao Hui-Ling
Published: November 2021

Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. Atherosclerosis is the main pathological basis of cardiovascular diseases and it is closely associated with hyperlipidemia, endothelial injury, macrophage-derived foam cells formation, proliferation and migration of vascular smooth muscle cells (VSMCs), platelet aggregation, and altered gut microbiota. Various symptomatic treatments, that are currently used to inhibit atherosclerosis, need to be administered in long term and their adverse effects cannot be ignored. Berberine (BBR) has beneficial effects on atherosclerosis through regulating multiple aspects of its progression. This review highlights the recent advances in understanding the anti-atherosclerosis mechanism of BBR. BBR alleviated atherosclerosis by attenuation of dyslipidemia, correction of endothelial dysfunction, inhibition of macrophage inflammation and foam cell formation, activation of macrophage autophagy, regulation of the proliferation and migration of VSMCs, attenuation of platelet aggregation, and modulation of gut microbiota. This review would provide a modern scientific perspective to further understanding the molecular mechanism of BBR attenuating atherosclerosis and supply new ideas for atherosclerosis management.
Role of G Protein-Coupled Receptors in Microglial Activation: Implication in Parkinson’s Disease
Authors: Gu Chao , Chen Yajing , Chen Yan , Liu Chun-Feng , Zhu Zengyan , Wang Mei
Published: November 2021

Parkinson’s disease (PD) is one of the prevalent neurodegenerative diseases associated with preferential loss of dopaminergic (DA) neurons in the substantia nigra compacta (SNc) and accumulation of α-synuclein in DA neurons. Even though the precise pathogenesis of PD is not clear, a large number of studies have shown that microglia-mediated neuroinflammation plays a vital role in the process of PD development. G protein-coupled receptors (GPCRs) are widely expressed in microglia and several of them act as regulators of microglial activation upon corresponding ligands stimulations. Upon α-synuclein insults, microglia would become excessively activated through some innate immune receptors. Presently, as lack of ideal drugs for treating PD, certain GPCR which is highly expressed in microglia of PD brain and mediates neuroinflammation effectively could be a prospective source for PD therapeutic intervention. Here, six kinds of GPCRs and two types of innate immune receptors were introduced, containing adenosine receptors, purinergic receptors, metabotropic glutamate receptors, adrenergic receptors, cannabinoid receptors, and melatonin receptors and their roles in neuroinflammation; we highlighted the relationship between these six GPCRs and microglial activation in PD. Based on the existing findings, we tried to expound the implication of microglial GPCRs-regulated neuroinflammation to the pathophysiology of PD and their potential to become a new expectation for clinical therapeutics.