bluuebunny/crossref_metadata_2025 huggingface dataset:
Combining Earthquake Ground Motion and Ambient Vibration Recordings to Evaluate a Local High-Resolution Amplification Model—Insight From the Lucerne Area, Switzerland
Authors: Janusz Paulina , Perron Vincent , Knellwolf Christoph , Fäh Donat
Published: May 2022

Amplification factors are often estimated using empirical methods based on earthquake ground motion; however, especially in low-seismicity urban areas, recording a statistically representative number of high-quality signals may take years. Hence, the attempts to use ambient vibration instead have progressed. This includes the development of the hybrid site-to-reference spectral ratio (SSRh) method that combines earthquake and ambient vibration recordings. We applied the method in the Lucerne area in central Switzerland that is characterized by low-to-moderate seismicity but was struck by several strong earthquakes in historical times (i.e., Mw 5.9 in 1,601) and is located in a glacial basin filled with unconsolidated deposits prone to significant amplification. To develop the high-resolution local site amplification model for the city of Lucerne using the SSRh method, we took advantage of a small seismic monitoring network installed in the Lucerne area in total for about a year and the stations of the Swiss Strong Motion Network (SSMNet). In addition, we performed two extensive surveys to record ambient vibrations and used dozens of measurements performed in the area since 2001. The resulting amplification model referring to the Swiss reference bedrock conditions indicates high-amplification factors (up to 10-fold) for a broad range of frequencies. The model is consistent with geological data and site response proxies such as f0 values. The direct comparison of our results with the SSR amplification functions for several sites shows good agreement. However, the model is characterized by high uncertainty and influenced by daily variation of the noise wavefield, as well as the spatial distribution of the stations of the seismic network. We also discussed the extent of the applicability of the method, concluding that the main factor influencing its performance is not the distance but the similarity of the site condition between the stations.
Sedimentary Hydrodynamic Processes Under Low-Oxygen Conditions: Implications for Past, Present, and Future Oceans
Authors: Bruni Elena T. , Blattmann Thomas M. , Haghipour Negar , Louw Deon , Lever Mark , Eglinton Timothy I.
Published: May 2022

Continental margin sediments represent a major global sink of organic carbon (OC), and as such exert a key control on Earth’s climate. Today, OC burial in marine sediments mainly takes place under oxygen-rich water columns, where most OC is stabilized through intimate association with sediment grains and biogenic minerals. In prior episodes of Earth’s past, when large parts of the oceans were anoxic, the mode of sedimentary OC burial must have been very different, however. Present-day analogues indicate that surface sediments accumulating under low-oxygen water columns are often “soupy” in texture. Moreover, most OC occurs in large (100–2,000 μm diameter) organic and organo-mineral aggregates which, due to their low density, are prone to wave- and current-induced resuspension. Upon mobilization, these aggregates can undergo lateral transport within so-called nepheloid layers, and may be translocated hundreds of kilometres, and on timescales of thousands of years. Little is known about processes of formation, resuspension and hydrodynamic properties of these aggregates in oxygen-poor waters, or which factors control their eventual breakdown or burial. The goal of this study is to examine the drivers and biogeochemical consequences of this resuspension on OC cycling in modern, oxygen-depleted, “Semi-Liquid Ocean Bottom” (SLOB) regions. We argue that models of sediment and OM hydrodynamics and redistribution that describe sedimentation processes in oxygenated ocean waters of the modern ocean are a poor analogue for equivalent processes occurring under oxygen-deficient conditions. In the latter, we hypothesize that 1) the abundance of low-density organic-rich particles and aggregates leads to a greater propensity for sediment remobilization at low(er) shear stress, and 2) upon resuspension into low-oxygen bottom waters, remobilized OM may be subject to less degradation (less attenuation) during lateral transport, leading to efficient and widespread translocation to distal centres of deposition. We address specific aspects of the SLOB hypothesis utilizing a combination of literature and new data, focussing on the Benguela Upwelling Region as a model system.
Stability Analysis of Shallow Goaf Based on Field Monitoring and Numerical Simulation: A Case Study at an Open-Pit Iron Mine, China
Authors: Jia Hanwen , Yan Baoxu , Guan Kai , Liu Honglei , Wu Qinzheng , Yin Yantian , Liu Huanxin
Published: May 2022

Evaluation of the stability of a shallow goaf in an open-pit iron mine is important for successful mining. Based on the idea of “rock disaster analysis and prediction combining field monitoring and numerical simulation,” a modification of Mathews stability graph is proposed, and a monitoring scheme combing stress, displacement, and surface subsidence is selected per the field geological condition. The displacement monitoring data and numerical model are combined, and the numerical model is corrected per the monitoring data; the time-dependent deformation and damage to the goaf is obtained; and its stability is comprehensively evaluated. Results show that the northern area is in a relatively stable stage, whilst the southern area has a certain risk of collapse. At last, the proposed framework was successfully used in the open-pit iron mine to evaluate the stability of the shallow goaf and can be used for reference to similar geological conditions.
Jordanian University Instructors’ Practices and Perceptions of Online Testing in the COVID-19 Era
Authors: Haider Ahmad S. , Hussein Riyad F. , Saed Hadeel A.
Published: May 2022

It is widely known that exceptional circumstances inevitably call for the use of matching procedures. As there has been a change in face-to-face teaching methods, there have also been parallel changes in student evaluation and assessment plans or strategies during the COVID-19 era. This study investigates how COVID-19 affected online testing in higher education institutions in Jordan. For this purpose, the researchers developed a five-construct Likert-type questionnaire with 20 items and distributed it to a sample of 426 university instructors. The constructs were the internet and technology, technical and logistic issues, types of questions, test design, and students’ awareness. The results showed that the Internet and technology are essential to guarantee the successful performance of online testing. The study also showed that this type of testing affected the test design and types of questions in a way to eliminate or at least reduce the spread of online cheating. The study recommends that higher education institutions provide instructors with on-the-job training, not only in e-learning techniques and procedures but also in preparing and conducting online exams.
Lifelong Learning and Metacognition in the Assessment of Pre-service Teachers in Practice-Based Teacher Education
Authors: Matsumoto-Royo Kiomi , Ramírez-Montoya Maria Soledad , Glasserman-Morales Leonardo David
Published: May 2022

Initial teacher education should prepare pre-service teachers to develop effective teaching and lifelong learning tendencies. This study aimed to identify the component to consider in pre-service teachers’ assessment processes that promote lifelong learning and develop metacognition skills. For this, it analyzed how the planned and implemented actions by the teacher educators in Practice-based Teacher Education programs promoted metacognition and lifelong learning in the pre-service teachers. The method was a mixed explanatory sequential design. Quantitative and qualitative instruments were applied. Information was obtained from the learning and assessment resources (72 syllabi and 14 assessment tasks) and pre-service teachers’ opinions (survey: n = 231, interviews: n = 8). The findings identified three main components: (i) authentic and relevant assessment tasks, (ii) prior communication of instructions and evaluation criteria, and (iii) frequent performance-focused feedback from peers and teacher educators during and at the end of assignments. The study results can be valuable in teacher education programs to strengthen assessment processes, promote lifelong learning tendencies, and develop metacognitive skills among the teachers in training.
The Challenge of Position-Taking in Novice Higher Education Students’ Argumentative Writing
Authors: Kleemola Katri , Hyytinen Heidi , Toom Auli
Published: May 2022

Argumentative writing is the central generic skill in higher education studies. However, students have difficulties in basic argumentation skills. Novice students do not necessarily receive adequate guidance, and their prior education may not have supported the requirements of higher education writing. Position-taking is at the core of argumentation, but students are often hesitant to make their point. Furthermore, they may have an incorrect and one-sided perception about an argument, leading them to avoid alternative positions in their argumentative writing. The study aims to explore starting level skills of novice students’ argumentative writing, namely their position-taking. The participants were 196 first-year students from diverse fields of study in two Finnish higher education institutions. They were required to solve a problem and write an argumentative essay based on five documents that were given to them. The essays were analyzed using qualitative content analysis applying abductive approach. Substantial variation was detected in students’ position-taking. We identified four groups of writers based on their position-taking. First two groups were more or less explicit in their position-taking. Most of the students (72%) belonged to these two groups. However, a minority of them were consistent in their position-taking. Writers in the third group (15%) implied their position, and writers in the fourth group (12%) stuck to summarizing sources without position-taking. The findings invite teachers to support novice students in their basic argumentation. Co-operation between faculty teachers and writing teachers is encouraged.
Review of Mendelian Randomization Studies on Endometrial Cancer
Authors: Guo Jian-Zeng , Wu Qi-Jun , Liu Fang-Hua , Gao Chang , Gong Ting-Ting , Li Gang
Published: May 2022

Endometrial cancer (EC) is a common gynecological cancer. In some parts of the world, the incidence and mortality of EC are on the rise. Understanding the risk factors of EC is necessary to prevent the occurrence of this disease. Observational studies have revealed the association between certain modifiable environmental risk factors and EC risk. However, due to unmeasured confounding, measurement errors, and reverse causality, observational studies sometimes have limited ability to judge robust causal inferences. In recent years, Mendelian randomization (MR) analysis has received extensive attention, providing valuable insights for cancer-related research, and is expected to identify potential therapeutic interventions. In MR analysis, genetic variation (alleles are randomly assigned during meiosis and are usually independent of environmental or lifestyle factors) is used instead of modifiable exposure to study the relationship between risk factors and disease. Therefore, MR analysis can make causal inference about exposure and disease risk. This review briefly describes the key principles and assumptions of MR analysis; summarizes published MR studies on EC; focuses on the correlation between different risk factors and EC risks; and discusses the application of MR methods in EC research. The results of MR studies on EC showed that type 2 diabetes, uterine fibroids, higher body mass index, higher plasminogen activator inhibitor-1 (PAI-1), higher fasting insulin, early insulin secretion, longer telomere length, higher testosterone and higher plasma cortisol levels are associated with increased risk of EC. In contrast, later age of menarche, higher circulatory tumor necrosis factor, higher low-density lipoprotein cholesterol, and higher sex hormone-binding globulin levels are associated with reduced risk of EC. In general, despite some limitations, MR analysis still provides an effective way to explore the causal relationship between different risk factors and EC.
Antithymocyte Globulin as Second-Line Therapy in Graves Orbitopathy—Preliminary Results From a Prospective Single-Center Study
Authors: Sarnat-Kucharczyk Monika , Świerkot Maria , Handzlik Gabriela , Kulawik Grażyna , Jagoda Krystyna , Grochoła-Małecka Iga , Fryżewska Joanna , Mrukwa-Kominek Ewa , Chudek Jerzy
Published: May 2022

Objective

Management of Graves’ orbitopathy remains a challenge. Our previous case report has shown promising results for rabbit antithymocyte globulin (rATG) in the treatment of Graves’ orbitopathy.

Design

We present the response of 7 individuals with active moderate-to-severe steroid-resistant Graves’ orbitopathy to rATG, representing preliminary results from a prospective single-center study.

Methods

rATG was administered intravenously at a dose of 0.8–1.0 mg/kg daily (cumulative dose of 150–200 mg). The primary outcome measures at weeks 24 and 48 were ≥2-point reduction in Clinical Activity Score from baseline, a proptosis response, a diplopia response, and improvement of distant best-corrected visual acuity and mean retinal sensitivity. Key secondary outcomes included stabilization of ganglion cell complex thickness, a decrease of retinal nerve fiber layer in OCT, and a reduction in CD4/CD8 ratio and TRAb at 48 weeks.

Results

An improvement in clinical activity score was observed in all patients, with disease inactivation in 3 cases. Proptosis reduction equal to or greater than 2 mm was noted for 8 of 10 eyes. Diplopia improved in three of 6 patients. There was an improvement in best-corrected visual acuity (from 0.69 to 0.78) and mean retinal sensitivity (from 20.8 to 23.5 dB). In addition, there was a long-lasting improvement in CD4/CD8 ratio in 6 patients. Two patients experienced adverse events (influenza and serum sickness).

Conclusion

rATG therapy offers a long-lasting improvement in moderate-to-severe steroid-resistant Graves’ orbitopathy with improvement in functional vision (reduction of diplopia, improvement of visual acuity, retinal sensitivity, and VEP pattern). The therapy is well-tolerated.

Clinical Trial Registration

ClinicalTrials.gov, identifier NCT05199103.
Technical Performance Optimization of a Novel Geothermal Hybrid Power Generation System
Authors: Zhou Ying , Qin Jiyun , Hu Eric , Zhang Qinglei
Published: May 2022

Geothermal Aided Power Generation (GAPG) technology is a geothermal hybrid power system that geothermal energy has been integrated into the fossil fired plant to preheat the feedwater, and displace the extraction steam of fossil fired plant. In such a power system, the heat exchange process between extraction steam and geo-fluid occurs in a heat exchange between. When the geo-fluid in the heat exchanger quench to lower temperature for heat transfer purpose, silica scaling would occur in the heat exchanger system. The performance of the GAPG plant would be influenced by the configuration of the heat exchanger and silica scaling in the heat exchanger. For a GAPG plant, it has two possible configurations for a heat exchanger system: series arrangement and parallel arrangement. The different configuration also impacts on the technical performance of the GAPG plant. The silica scaling in the heat exchanger system would harm the performance of the GAPG plant. In this study, a GAPG power system from a 300 MW power plant is used as a case study to understand the impact of displacement selections and heat exchanger arrangement on the performance of the GAPG plant. It was found that there is no silica scaling occurring in heat exchangers system if geo-fluid is used to displace to high-grade extraction steam only. Furthermore, the Parallel arrangement is better than the Series arrangement in terms of the additional power output. Moreover, the GAPG plant has protentional to reduce carbon dioxide emissions by 13%.
N6-Methyladenosine-Related lncRNAs Are Novel Prognostic Markers and Predict the Immune Landscape in Acute Myeloid Leukemia
Authors: Zhang Lulu , Ke Wen , Hu Pin , Li Zhangzhi , Geng Wei , Guo Yigang , Song Bin , Jiang Hua , Zhang Xia , Wan Chucheng
Published: May 2022

Background: Acute myelocytic leukemia (AML) is one of the hematopoietic cancers with an unfavorable prognosis. However, the prognostic value of N 6-methyladenosine-associated long non-coding RNAs (lncRNAs) in AML remains elusive.

Materials and Methods: The transcriptomic data of m6A-related lncRNAs were collected from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database. AML samples were classified into various subgroups according to the expression of m6A-related lncRNAs. The differences in terms of biological function, tumor immune microenvironment, copy number variation (CNV), and drug sensitivity in AML between distinct subgroups were investigated. Moreover, an m6A-related lncRNA prognostic model was established to evaluate the prognosis of AML patients.

Results: Nine prognosis-related m6A-associated lncRNAs were selected to construct a prognosis model. The accuracy of the model was further determined by the Kaplan–Meier analysis and time-dependent receiver operating characteristic (ROC) curve. Then, AML samples were classified into high- and low-risk groups according to the median value of risk scores. Gene set enrichment analysis (GSEA) demonstrated that samples with higher risks were featured with aberrant immune-related biological processes and signaling pathways. Notably, the high-risk group was significantly correlated with an increased ImmuneScore and StromalScore, and distinct immune cell infiltration. In addition, we discovered that the high-risk group harbored higher IC50 values of multiple chemotherapeutics and small-molecule anticancer drugs, especially TW.37 and MG.132. In addition, a nomogram was depicted to assess the overall survival (OS) of AML patients. The model based on the median value of risk scores revealed reliable accuracy in predicting the prognosis and survival status.

Conclusion: The present research has originated a prognostic risk model for AML according to the expression of prognostic m6A-related lncRNAs. Notably, the signature might also serve as a novel biomarker that could guide clinical applications, for example, selecting AML patients who could benefit from immunotherapy.
Dynamic Meta-data Network Sparse PCA for Cancer Subtype Biomarker Screening
Authors: Miao Rui , Dong Xin , Liu Xiao-Ying , Lo Sio-Long , Mei Xin-Yue , Dang Qi , Cai Jie , Li Shao , Yang Kuo , Xie Sheng-Li , Liang Yong
Published: May 2022

Previous research shows that each type of cancer can be divided into multiple subtypes, which is one of the key reasons that make cancer difficult to cure. Under these circumstances, finding a new target gene of cancer subtypes has great significance on developing new anti-cancer drugs and personalized treatment. Due to the fact that gene expression data sets of cancer are usually high-dimensional and with high noise and have multiple potential subtypes’ information, many sparse principal component analysis (sparse PCA) methods have been used to identify cancer subtype biomarkers and subtype clusters. However, the existing sparse PCA methods have not used the known cancer subtype information as prior knowledge, and their results are greatly affected by the quality of the samples. Therefore, we propose the Dynamic Metadata Edge-group Sparse PCA (DM-ESPCA) model, which combines the idea of meta-learning to solve the problem of sample quality and uses the known cancer subtype information as prior knowledge to capture some gene modules with better biological interpretations. The experiment results on the three biological data sets showed that the DM-ESPCA model can find potential target gene probes with richer biological information to the cancer subtypes. Moreover, the results of clustering and machine learning classification models based on the target genes screened by the DM-ESPCA model can be improved by up to 22–23% of accuracies compared with the existing sparse PCA methods. We also proved that the result of the DM-ESPCA model is better than those of the four classic supervised machine learning models in the task of classification of cancer subtypes.
Key Molecules of Triglycerides Pathway Metabolism Are Disturbed in Patients With Systemic Lupus Erythematosus
Authors: Quevedo-Abeledo Juan Carlos , Martín-González Candelaria , Ferrer-Moure Carmen , de Armas-Rillo Laura , Hernandez-Hernandez Maria Vanesa , González-Gay Miguel Á. , Ferraz-Amaro Iván
Published: May 2022

Background

Elevated triglycerides or triglyceride-rich lipoproteins are an additional cause of cardiovascular (CV) disease. Given that patients with systemic lupus erythematosus (SLE) have a high prevalence of premature CV disease and show an altered lipid profile, our objective was to study whether three molecules that play a central role in the triglyceride metabolism: apolipoprotein C-III (ApoC3), angiopoietin-like protein 4 (ANGPLT4), and lipoprotein lipase (LPL) differ between SLE patients and controls, and how they are related to disease characteristics, including disease damage.

Methods

Cross-sectional study that included 347 women, 185 of them diagnosed with SLE and 162 age-matched controls. ANGPTL4, ApoC3 and LPL, and standard lipid profiles were analyzed in SLE patients and controls. A multivariable analysis was performed to assess whether ANGPTL4, ApoC3 and LPL molecules differ between patients and controls and to study their relationship with SLE disease damage.

Results

After fully multivariable analysis that included classic CV risk factors, and the modifications that the disease itself produces over the lipid profile, it was found that ApoC3 was significantly lower (beta coef. -1.2 [95%CI -1.6- -0.8) mg/dl, <0.001), and ANGPTL4 (beta coef. 63 [95%CI 35-90] ng/ml, <0.001) and LPL (beta coef. 79 [95%CI 30-128] ng/ml, p=0.002) significantly higher in patients with SLE compared to controls. Disease damage score was significantly and independently associated with higher serum levels of LPL (beta coef. 23 [95%CI 10-35] ng/ml, p=0.001). Mediation analysis suggested that the relationship between disease damage and LPL was direct and not mediated by ApoC3 or ANGPLT4.

Conclusion

The ApoC3, ANGPLT4 and LPL axis is disrupted in patients with SLE. Disease damage explains this disturbance.
Identification of Immune-Related Genes Concurrently Involved in Critical Illnesses Across Different Etiologies: A Data-Driven Analysis
Authors: Peng Yaojun , Wu Qiyan , Zhou Qing , Yang Zhanglin , Yin Fan , Wang Lingxiong , Chen Qi , Feng Cong , Ren Xuewen , Liu Tianyi
Published: May 2022

Severe trauma and sepsis can lead to multiple organ dysfunction syndrome, which is a leading cause of death in intensive care units with mortality rates in excess of 50%. In addition to infection, the degree of immuno-inflammatory response also influences the outcome. The genomic changes observed after a variety of pathophysiological insults, such as trauma, sepsis, burns are similar, and consist of innate immune activation and adaptive immunity suppression. However, the characteristics of the shared mechanisms of aforementioned critical illnesses and the clinical relevance remain less explored. In the present study, we performed a data analysis to identify functional genes concurrently involved in critical illnesses across differing etiologies (trauma and sepsis derived from community-acquired pneumonia/abdominal source) and explored the shared signaling pathways these common genes involved in to gain insight into the underlying molecular mechanisms. A number of immune-related biological functions were found to be dysregulated in both trauma and sepsis in the present study, so we continued to identify immune-related common genes, profiled the immune cell proportion, and explored the relationships between them. The diagnostic and prognostic value of the immune-related common genes was also evaluated to address their potential clinical utilization as novel biomarkers. Notably, we identified a list of 14 immune-related genes concurrently dysregulated in trauma and sepsis showing favorable diagnostic value, among which S100P can predict prognosis of sepsis patients. Moreover, a spectrum of immune cell subsets including naïve B cells, CD8+ T cells, CD4+ memory resting T cells, activated NK cells, resting dendritic cells, plasma cells, Tregs, macrophages M0 and macrophages M1 was found to be concurrently dysregulated in both trauma and sepsis, and a close relation between above identified immune-related genes and immune cell subsets was observed. Our data-driven findings lay a foundation for future research to elucidate the pathophysiology regarding the aspect of inflammatory and immune response in critical illnesses, and suggest future studies focus on interpreting the function roles of the identified immune-related genes, as well as the reactive immune cell subsets.
Rapid Hypermutation B Cell Trajectory Recruits Previously Primed B Cells Upon Third SARS-Cov-2 mRNA Vaccination
Authors: Paschold Lisa , Klee Bianca , Gottschick Cornelia , Willscher Edith , Diexer Sophie , Schultheiß Christoph , Simnica Donjete , Sedding Daniel , Girndt Matthias , Gekle Michael , Mikolajczyk Rafael , Binder Mascha
Published: May 2022

The COVID-19 pandemic shows that vaccination strategies building on an ancestral viral strain need to be optimized for the control of potentially emerging viral variants. Therefore, aiming at strong B cell somatic hypermutation to increase antibody affinity to the ancestral strain - not only at high antibody titers - is a priority when utilizing vaccines that are not targeted at individual variants since high affinity may offer some flexibility to compensate for strain-individual mutations. Here, we developed a next-generation sequencing based SARS-CoV-2 B cell tracking protocol to rapidly determine the level of immunoglobulin somatic hypermutation at distinct points during the immunization period. The percentage of somatically hypermutated B cells in the SARS-CoV-2 specific repertoire was low after the primary vaccination series, evolved further over months and increased steeply after boosting. The third vaccination mobilized not only naïve, but also antigen-experienced B cell clones into further rapid somatic hypermutation trajectories indicating increased affinity. Together, the strongly mutated post-booster repertoires and antibodies deriving from this may explain why the third, but not the primary vaccination series, offers some protection against immune-escape variants such as Omicron B.1.1.529.
From COVID-19 to Sarcoidosis: How Similar Are These Two Diseases?
Authors: Zhao Min , Tian Chang , Cong Shan , Di Xin , Wang Ke
Published: May 2022

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), leads to the dysregulation of the immune system, exacerbates inflammatory responses, and even causes multiple organ dysfunction syndrome in patients with severe disease. Sarcoidosis is an idiopathic granulomatous multisystem disease characterized by dense epithelioid non-necrotizing lesions with varying degrees of lymphocytic inflammation. These two diseases have similar clinical manifestations and may also influence each other and affect their clinical courses. In this study, we analyzed some possible connections between sarcoidosis and COVID-19, including the role of the renin–angiotensin system in the respiratory system, immune response, and cell death pathways, to understand the underlying mechanisms of SARS-CoV-2 infection, predisposing patients to severe forms of COVID-19. This review will provide a new prospect for the treatment of COVID-19 and an opportunity to explore the pathogenesis and development of sarcoidosis.
The Incidence, Outcomes, and Risk Factors of Secondary Poor Graft Function in Haploidentical Hematopoietic Stem Cell Transplantation for Acquired Aplastic Anemia
Authors: Lin Fan , Han Tingting , Zhang Yuanyuan , Cheng Yifei , Xu Zhengli , Mo Xiaodong , Wang Fengrong , Yan Chenhua , Sun Yuqian , Wang Jingzhi , Tang Feifei , Han Wei , Chen Yuhong , Wang Yu , Zhang Xiaohui , Liu Kaiyan , Huang Xiaojun , Xu Lanping
Published: May 2022

Secondary poor graft function (sPGF) increases the risk of life-threatening complications after hematopoietic stem cell transplantation (HSCT). The incidence, clinical outcomes, and risk factors of sPGF have not been elucidated in haploidentical (haplo-) HSCT for acquired aplastic anemia (AA) patients. We retrospectively reviewed 423 consecutive AA patients who underwent haplo-HSCT between January 2006 and December 2020 and report a 3-year cumulative incidence of 4.62% (95% confidence interval [CI]: 3.92%-10.23%) of sPGF. While no primary PGF occurred. The median time to sPGF was 121 days (range 30-626 days) after transplantation. To clarify the risk factors for sPGF, 17 sPGF cases and 382 without PGF were further analyzed. Compared to patients without PGF, the 2-year overall survival was significantly poorer for sPGF patients (67.7% vs 90.8%, p =.002). Twelve sPGF patients were alive until the last follow-up, and 7 achieved transfusion independency. The multivariable analyses revealed that later neutrophil engraftment (OR 2.819, p=.049) and a history of refractory cytomegalovirus viremia (OR=7.038, p=.002) post-transplantation were associated with sPGF. There was weak evidence that a history of grade 3-4 acute graft-versus-host disease increased the risk of sPGF (p=.063). We advocated better post-transplantation strategies to balance the risk of immunosuppression and viral reactivation for haplo-HSCT in AA patients.
Hyperoxia Is Not Associated With 30-day Survival in Out-of-Hospital Cardiac Arrest Patients Who Undergo Extracorporeal Cardiopulmonary Resuscitation
Authors: Kobayashi Mioko , Kashiura Masahiro , Yasuda Hideto , Sugiyama Kazuhiro , Hamabe Yuichi , Moriya Takashi
Published: May 2022

Introduction

The appropriate arterial partial pressure of oxygen (PaO2) in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) remains unclear. The present study aimed to investigate the relationship between hyperoxia and 30-day survival in patients who underwent ECPR.

Materials and Methods

This single-center retrospective cohort study was conducted between January 2010 and December 2018. OHCA patients who underwent ECPR were included in the study. Exclusion criteria were (1) age <18 years, (2) death within 24 h after admission, (3) return of spontaneous circulation at hospital arrival, and (4) hypoxia (PaO2 < 60 mmHg) 24 h after admission. Based on PaO2 at 24 h after admission, patients were classified into normoxia (60 mmHg ≤ PaO2 ≤ 100 mmHg), mild hyperoxia (100 mmHg < PaO2 ≤ 200 mmHg), and severe hyperoxia (PaO2 > 200 mmHg) groups. The primary outcome was 30-day survival after cardiac arrest, while the secondary outcome was 30-day favorable neurological outcome. Multivariate logistic regression analysis for 30-day survival or 30-day favorable neurological outcome was performed using multiple propensity scores as explanatory variables. To estimate the multiple propensity score, we fitted a multinomial logistic regression model using the patients' demographic, pre-hospital, and in-hospital characteristics.

Results

Of the patients who underwent ECPR in the study center, 110 were eligible for the study. The normoxia group included 29 cases, mild hyperoxia group included 46 cases, and severe hyperoxia group included 35 cases. Mild hyperoxia was not significantly associated with survival, compared with normoxia as the reference (adjusted odds ratio, 1.06; 95% confidence interval: 0.30–3.68; p = 0.93). Severe hyperoxia was also not significantly associated with survival compared to normoxia (adjusted odds ratio, 1.05; 95% confidence interval: 0.27–4.12; p = 0.94). Furthermore, no association was observed between oxygenation and 30-day favorable neurological outcomes.

Conclusions

There was no significant association between hyperoxia at 24 h after admission and 30-day survival in OHCA patients who underwent ECPR.
A Porcine Sepsis Model With Numerical Scoring for Early Prediction of Severity
Authors: Rutai Attila , Zsikai Bettina , Tallósy Szabolcs Péter , Érces Dániel , Bizánc Lajos , Juhász László , Poles Marietta Zita , Sóki József , Baaity Zain , Fejes Roland , Varga Gabriella , Földesi Imre , Burián Katalin , Szabó Andrea , Boros Mihály , Kaszaki József
Published: May 2022

Introduction

Sepsis can lead to organ dysfunctions with disturbed oxygen dynamics and life-threatening consequences. Since the results of organ-protective treatments cannot always be transferred from laboratory models into human therapies, increasing the translational potential of preclinical settings is an important goal. Our aim was to develop a standardized research protocol, where the progression of sepsis-related events can be characterized reproducibly in model experiments within clinically-relevant time frames.

Methods

Peritonitis was induced in anesthetized minipigs injected intraperitoneally with autofeces inoculum (n = 27) or with saline (sham operation; n = 9). The microbial colony-forming units (CFUs) in the inoculum were retrospectively determined. After awakening, clinically relevant supportive therapies were conducted. Nineteen inoculated animals developed sepsis without a fulminant reaction. Sixteen hours later, these animals were re-anesthetized for invasive monitoring. Blood samples were taken to detect plasma TNF-α, IL-10, big endothelin (bET), high mobility group box protein1 (HMGB1) levels and blood gases, and sublingual microcirculatory measurements were conducted. Hemodynamic, respiratory, coagulation, liver and kidney dysfunctions were detected to characterize the septic status with a pig-specific Sequential Organ Failure Assessment (pSOFA) score and its simplified version (respiratory, cardiovascular and renal failure) between 16 and 24 h of the experiments.

Results

Despite the standardized sepsis induction, the animals could be clustered into two distinct levels of severity: a sepsis (n = 10; median pSOFA score = 2) and a septic shock (n = 9; median pSOFA score = 8) subgroup at 18 h of the experiments, when the decreased systemic vascular resistance, increased DO2 and VO2, and markedly increased ExO2 demonstrated a compensated hyperdynamic state. Septic animals showed severity-dependent scores for organ failure with reduced microcirculation despite the adequate oxygen dynamics. Sepsis severity characterized later with pSOFA scores was in correlation with the germ count in the induction inoculum (r = 0.664) and CFUs in hemocultures (r = 0.876). Early changes in plasma levels of TNF-α, bET and HMGB1 were all related to the late-onset organ dysfunctions characterized by pSOFA scores.

Conclusions

This microbiologically-monitored, large animal model of intraabdominal sepsis is suitable for clinically-relevant investigations. The methodology combines the advantages of conscious and anesthetized studies, and mimics human sepsis and septic shock closely with the possibility of numerical quantification of host responses.
Multiple Groups of Methanotrophic Bacteria Mediate Methane Oxidation in Anoxic Lake Sediments
Authors: Su Guangyi , Zopfi Jakob , Niemann Helge , Lehmann Moritz F.
Published: May 2022

Freshwater lakes represent an important source of the potent greenhouse gas methane (CH4) to the atmosphere. Methane emissions are regulated to large parts by aerobic (MOx) and anaerobic (AOM) oxidation of methane, which are important CH4 sinks in lakes. In contrast to marine benthic environments, our knowledge about the modes of AOM and the related methanotrophic microorganisms in anoxic lake sediments is still rudimentary. Here, we demonstrate the occurrence of AOM in the anoxic sediments of Lake Sempach (Switzerland), with maximum in situ AOM rates observed within the surface sediment layers in presence of multiple groups of methanotrophic bacteria and various oxidants known to support AOM. However, substrate-amended incubations (with NO2−, NO3−, SO42−, Fe-, and Mn-oxides) revealed that none of the electron acceptors previously reported to support AOM enhanced methane turnover in Lake Sempach sediments under anoxic conditions. In contrast, the addition of oxygen to the anoxic sediments resulted in an approximately 10-fold increase in methane oxidation relative to the anoxic incubations. Phylogenetic and isotopic evidence indicate that both Type I and Type II aerobic methanotrophs were growing on methane under both oxic and anoxic conditions, although methane assimilation rates were an order of magnitude higher under oxic conditions. While the anaerobic electron acceptor responsible for AOM could not be identified, these findings expand our understanding of the metabolic versatility of canonically aerobic methanotrophs under anoxic conditions, with important implications for future investigations to identify methane oxidation processes. Bacterial AOM by facultative aerobic methane oxidizers might be of much larger environmental significance in reducing methane emissions than previously thought.
Engineering Acetogenic Bacteria for Efficient One-Carbon Utilization
Authors: Lee Hyeonsik , Bae Jiyun , Jin Sangrak , Kang Seulgi , Cho Byung-Kwan
Published: May 2022

C1 gases, including carbon dioxide (CO2) and carbon monoxide (CO), are major contributors to climate crisis. Numerous studies have been conducted to fix and recycle C1 gases in order to solve this problem. Among them, the use of microorganisms as biocatalysts to convert C1 gases to value-added chemicals is a promising solution. Acetogenic bacteria (acetogens) have received attention as high-potential biocatalysts owing to their conserved Wood–Ljungdahl (WL) pathway, which fixes not only CO2 but also CO. Although some metabolites have been produced via C1 gas fermentation on an industrial scale, the conversion of C1 gases to produce various biochemicals by engineering acetogens has been limited. The energy limitation of acetogens is one of the challenges to overcome, as their metabolism operates at a thermodynamic limit, and the low solubility of gaseous substrates results in a limited supply of cellular energy. This review provides strategies for developing efficient platform strains for C1 gas conversion, focusing on engineering the WL pathway. Supplying liquid C1 substrates, which can be obtained from CO2, or electricity is introduced as a strategy to overcome the energy limitation. Future prospective approaches on engineering acetogens based on systems and synthetic biology approaches are also discussed.
Acinetobacter baumannii Secretes a Bioactive Lipid That Triggers Inflammatory Signaling and Cell Death
Authors: Tiku Varnesh , Kew Chun , Kofoed Eric M. , Peng Yutian , Dikic Ivan , Tan Man-Wah
Published: May 2022

Acinetobacter baumannii is a highly pathogenic Gram-negative bacterium that causes severe infections with very high fatality rates. A. baumannii infection triggers innate as well as adaptive immunity, however, our understanding of the inflammatory factors secreted by A. baumannii that alarm the immune system remains limited. In this study, we report that the lab adapted and clinical strains of A. baumannii secrete an inflammatory bioactive factor which activates TLR2, leading to canonical IRAK4-dependent NF-κB signaling and production of pro-inflammatory cytokines interleukin (IL)-6 and IL-8 and activation of the inflammasome pathway causing pyroptotic cell death. Biochemical fractionation of the A. baumannii culture filtrate revealed the hydrophobic nature of the inflammatory factor. Concordantly, lipase treatment of the culture filtrate or TLR2 inhibition in macrophages abrogated NF-κB activation and cell death induction. Culture filtrates from the LPS- and lipoprotein-deficient A. baumannii mutants retain immuno-stimulatory properties suggesting that a lipid other than these known stimulatory molecules can trigger inflammation during A. baumannii infection. Our results reveal that A. baumannii secretes a previously unappreciated inflammatory bioactive lipid that activates multiple pro-inflammatory signaling pathways and induces cell death in human and murine macrophages.
A Potential Biofertilizer—Siderophilic Bacteria Isolated From the Rhizosphere of Paris polyphylla var. yunnanensis
Authors: Wang Yihan , Zhang Gongyou , Huang Ya , Guo Min , Song Juhui , Zhang Tingting , Long Yaohang , Wang Bing , Liu Hongmei
Published: May 2022

The increasing demands for crop production have become a great challenge while people also realizing the significance of reductions in synthetic chemical fertilizer use. Plant growth-promoting rhizobacteria (PGPR) are proven biofertilizers for increasing crop yields by promoting plant growthviavarious direct or indirect mechanisms. Siderophilic bacteria, as an important type of PGPR, can secrete siderophores to chelate unusable Fe3+in the soil for plant growth. Siderophilic bacteria have been shown to play vital roles in preventing diseases and enhancing the growth of plants.Paris polyphyllavar.yunnanensis(PPVY) is an important traditional Chinese herb. However, reports about its siderophilic bacteria are still rare. This study firstly isolated siderophilic bacteria from the rhizosphere soil ofPPVY, identified by morphological and physio-biochemical characteristics as well as 16S rRNA sequence analysis. The dominant genus in the rhizobacteria ofPPVYwasBacillus. Among 22 isolates, 21 isolates produced siderophores. The relative amount of siderophores ranged from 4 to 41%. Most of the isolates produced hydroxamate siderophores and some produced catechol. Four isolates belonging toEnterobacterproduced the catechol type, and none of them produced carboxylate siderophores. Intriguingly, 16 strains could produce substances that have inhibitory activity againstCandida albicansonly in an iron-limited medium (SA medium). The effects of different concentrations of Fe3+and three types of synthetic chemical fertilizers on AS19 growth, siderophore production, and swimming motility were first evaluated from multiple aspects. The study also found that the cell-free supernatant (CFS) with high siderophore units (SUs) of AS19 strain could significantly promote the germination of pepper and maize seeds and the development of the shoots and leaves ofGynura divaricata(Linn.). The bacterial solution of AS19 strain could significantly promote the elongation of the roots ofG. divaricata(Linn.). Due to its combined traits promoting plant growth and seed germination, the AS19 has the potential to become a bioinoculant. This study will broaden the application prospects of the siderophilic bacteria-AS19 as biofertilizers for future sustainable agriculture.
Identification of Cytoplasmic Chaperone Networks Relevant for Respiratory Syncytial Virus Replication
Authors: Latorre Victor , Geller Ron
Published: May 2022

RNA viruses have limited coding capacity and must therefore successfully subvert cellular processes to facilitate their replication. A fundamental challenge faced by both viruses and their hosts is the ability to achieve the correct folding and assembly of their proteome while avoiding misfolding and aggregation. In cells, this process is facilitated by numerous chaperone systems together with a large number of co-chaperones. In this work, we set out to define the chaperones and co-chaperones involved in the replication of respiratory syncytial virus (RSV). Using an RNAi screen, we identify multiple members of cellular protein folding networks whose knockdown alters RSV replication. The reduced number of chaperones and co-chaperones identified in this work can facilitate the unmasking of specific chaperone subnetworks required for distinct steps of the RSV life cycle and identifies new potential targets for antiviral therapy. Indeed, we show that the pharmacological inhibition of one of the genes identified in the RNAi screen, valosin-containing protein (VCP/p97), can impede the replication of RSV by interfering with the infection cycle at multiple steps.
SPECT Imaging of Acute Disc Herniation by Targeting Integrin α5β1 in Rat Models
Authors: Guan Jian , Yuan Chenghua , Tian Xin , Cheng Lei , Gao Hannan , Yao Qingyu , Wang Xinyu , Wu Hao , Chen Zan , Jian Fengzeng
Published: May 2022

Objective

Traditional morphological imaging of intervertebral disc herniation (IVDH) is challenging in early disease diagnosis. Aiming at the early diagnosis of IVD by non-invasive molecular imaging targeting of integrin α5β1, we performed novel imaging in rats with acute IVDH for the first time.

Methods

Animal models were prepared by conducting an established needle puncture procedure through the normal intervertebral disc (IVD). The disc-injured rats underwent SPECT/CT imaging of the 99mTc-3PisoDGR2 peptide at 1 day to 2 months postinjury. The expression change of integrin α5β1 was determined by anti-integrin α5 and anti-integrin α5β1 immunohistochemistry (IHC). Magnetic resonance imaging (MRI) was performed for comparison during disease progression. The morphological changes of the disc were determined by safranin-O staining.

Results

Rats with acute IVDH showed gradually increased disc uptake of 99mTc-3PisoDGR2 from 1 to 7 days posttreatment, which was a significantly higher level than that of the normal disks in degenerative diseases. IHC results showed the expression of integrin α5β1 on the surface of annulus fibrosus (AF) cells and nucleus pulposus (NP) cells, which agreed with the uptake data. MRI showed a progressively decreased T2 density and MRI index throughout the investigation. Hematoxylin and eosin (HE) staining and safranin-O staining revealed a disorganized structure of the IVD as well as loss of proteoglycans after puncture.

Conclusions

The present study demonstrated a good correlation between integrin α5β1 expression and acute disc herniation. The SPECT/CT imaging of 99mTc-3PisoDGR2 targeting integrin α5β1 may diagnose IVDH in an acute phase for early disease management.