bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Procalcitonin to Guide Antibiotic Escalation in Patients With Suspected Bacterial Infection: A New Application of Procalcitonin in the Intensive Care Unit
Authors: Wang Xu , Long Yun , Su Longxiang , Zhang Qing , Shan Guangliang , He Huaiwu
Published: March 2022

Background

Procalcitonin (PCT) is efficient in reducing antibiotic usage without increasing complications for its sensitivity and specificity in detecting bacterial infection. However, its role in guiding antibiotic-spectrum escalation has not been studied. This study was performed to validate the role of PCT in indicating antibiotic spectrum escalation when pathogen results are unknown for ICU patients of suspected bacterial infections.

Methods

This was a single-center retrospective study including patients who were admitted to Peking Union Medical College Hospital from January 2014 to June 2018 for suspected bacterial infections. Patients were divided into “escalation” or “non-escalation” groups according to the change of employed antibiotic spectrum before and after the occurrence of “PCT alert”. The main study endpoint was the length of ICU stay (LIS), and LIS longer than 7 days was defined as “prolonged-ICU-stay (PIS)” while LIS equal to or shorter than 7 days was defined as “non-prolonged-ICU-stay(nPIS)”. Demographics, clinical characteristics, and infection characteristics were compared between patients in the “nPIS” and “PIS” groups. Multivariable logistic regression was used to evaluate independent risk factors for PIS.

Results

Totally, 1109 patients were included, and 654 in the PIS group, other 455 in the nPIS group. Respiratory infection was the main cause in both groups. Patients were older in PIS group than in nPIS group(PIS vs. nPIS: 58.99 ± 16.30 vs. 56.12 ± 15.93 years, P=0.002). The baseline Sequential Organ Failure Assessment (SOFA) score was 11.16 ± 7.33 and 9.73 ± 3.70 in PIS and nPIS groups. Fewer patients received antibiotic escalation in face of “PCT alert” in PIS group (PIS vs. nPIS: 27.68 vs.35.38%, P=0.014). In the multivariable logistic regression model, older age, higher heart rate, not undergoing surgery, higher baseline SOFA score, and not escalating antibiotics in face of “PCT alert” were associated with a prolonged ICU stay. The odds ratio of antibiotic escalation for PIS was 0.582 (95% CI: 0.365, 0.926, P=0.022).

Conclusions

Using PCT to guide antibiotic escalation when pathogen evidence is unavailable could be associated with a shorter length of ICU stay for ICU patients of suspected bacterial infection.
Prediction of Myocardial Infarction From Patient Features With Machine Learning
Authors: Chen Zhihao , Shi Jixi , Pommier Thibaut , Cottin Yves , Salomon Michel , Decourselle Thomas , Lalande Alain , Couturier Raphaël
Published: March 2022

This study proposes machine learning-based models to automatically evaluate the severity of myocardial infarction (MI) from physiological, clinical, and paraclinical features. Two types of machine learning models are investigated for the MI assessment: the classification models classify the presence of the infarct and the persistent microvascular obstruction (PMO), and the regression models quantify the Percentage of Infarcted Myocardium (PIM) of patients suspected of having an acute MI during their reception in the emergency department. The ground truth labels for these supervised models are derived from the corresponding Delayed Enhancement MRI (DE-MRI) exams and manual annotations of the myocardium and scar tissues. Experiments were conducted on 150 cases and evaluated with cross-validation. Results showed that for the MI (PMO inclusive) and the PMO (infarct exclusive), the best models obtained respectively a mean error of 0.056 and 0.012 for the quantification, and 88.67 and 77.33% for the classification accuracy of the state of the myocardium. The study of the features' importance also revealed that the troponin value had the strongest correlation to the severity of the MI among the 12 selected features. For the proposal's translational perspective, in cardiac emergencies, qualitative and quantitative analysis can be obtained prior to the achievement of MRI by relying only on conventional tests and patient features, thus, providing an objective reference for further treatment by physicians.
Prevalence of Metabolic Syndrome in Women After Maternal Complications of Pregnancy: An Observational Cohort Analysis
Authors: Aldridge Emily , Pathirana Maleesa , Wittwer Melanie , Sierp Susan , Leemaqz Shalem Y. , Roberts Claire T. , Dekker Gustaaf A. , Arstall Margaret A.
Published: March 2022

Introduction

Certain complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, spontaneous preterm birth, and placental abruption, are established independent risk factors for premature cardiovascular disease in women. Metabolic syndrome, which is associated with an increased risk of cardiovascular disease, may be a suitable alternative to traditional cardiovascular risk calculators that underestimate risk in young women. This study aimed to investigate the prevalence of metabolic syndrome in women who experienced a complicated pregnancy 6 months earlier.

Methods

This observational study investigated the prevalence of metabolic syndrome as defined by the International Diabetes Federation in all eligible participants (n = 247) attending a postpartum lifestyle intervention clinic from August 2018 to June 2021 at the Lyell McEwin Hospital in Adelaide, South Australia.

Results

A total of 89 (36%) participants met the criteria for metabolic syndrome at a mean follow up time of 7 months postpartum. Almost 90% of the cohort were abdominally obese, and over two thirds of the total cohort met at least two of the criteria for metabolic syndrome.

Conclusions

Women with a prior history of one of the common major pregnancy complications are at high risk of future cardiovascular and metabolic disease, with many showing either metabolic syndrome or multiple risk factors at only 7 months postpartum. The results indicate that follow-up within 1 year postpartum is an appropriate time to commence preventative strategies, as many women are already showing early signs of disease.
Changes in Specific Biomarkers Indicate Cardiac Adaptive and Anti-inflammatory Response of Repeated Recreational SCUBA Diving
Authors: Dumić Jerka , Cvetko Ana , Abramović Irena , Šupraha Goreta Sandra , Perović Antonija , Njire Bratičević Marina , Kifer Domagoj , Sinčić Nino , Gornik Olga , Žarak Marko
Published: March 2022

Objective

Recreational SCUBA (rSCUBA) diving has become a highly popular and widespread sport. Yet, information on molecular events underlying (patho)physiological events that follow exposure to the specific environmental conditions (hyperbaric conditions, coldness, immersion, and elevated breathing pressure), in which rSCUBA diving is performed, remain largely unknown. Our previous study suggested that repeated rSCUBA diving triggers an adaptive response of cardiovascular and immune system. To elucidate further molecular events underlying cardiac and immune system adaptation and to exclude possible adverse effects we measured blood levels of specific cardiac and inflammation markers.

Methods

This longitudinal intervention study included fourteen recreational divers who performed five dives, one per week, on the depth 20–30 m that lasted 30 min, after the non-dive period of 5 months. Blood samples were taken immediately before and after the first, third, and fifth dives. Copeptin, immunoglobulins A, G and M, complement components C3 and C4, and differential blood count parameters, including neutrophil-to-lymphocyte ratio (NLR) were determined using standard laboratory methods. Cell-free DNA was measured by qPCR analysis and N-glycans released from IgG and total plasma proteins (TPP), were analyzed by hydrophilic interaction ultra-performance liquid chromatography.

Results

Copeptin level increased after the first dive but decreased after the third and fifth dive. Increases in immunoglobulins level after every dive and during whole studied period were observed, but no changes in C3, C4, and cfDNA level were detected. NLR increased only after the first dive. IgG and TPP N-glycosylation alterations toward anti-inflammatory status over whole studied period were manifested as an increase in monogalyctosylated and core-fucosylated IgG N-glycans and decrease in agalactosylated TPP N-glycans.

Conclusion

rSCUBA diving practiced on a regular basis promotes anti-inflammatory status thus contributing cardioprotection and conferring multiple health benefits.
Gas Monitoring of Volcanic-Hydrothermal Plumes in a Tropical Environment: The Case of La Soufrière de Guadeloupe Unrest Volcano (Lesser Antilles)
Authors: Moune Severine , Moretti Roberto , Burtin Arnand , Jessop David Edward , Didier Tristan , Robert Vincent , Bonifacie Magali , Tamburello Giancarlo , Komorowski J-Christophe. , Allard Patrick , Buscetti Margaux
Published: March 2022

Fumarolic gas survey of dormant volcanoes in hydrothermal activity is crucial to detect compositional and mass flux changes in gas emissions that are potential precursors of violent phreatic or even magmatic eruptions. Here we report on new data for the chemical compositions (CO2, H2S, SO2) and fluxes of fumarolic gas emissions (97–104°C) from La Soufrière volcano in Guadeloupe (Lesser Antilles) obtained from both mobile MultiGas measurements and permanent MultiGas survey. This paper covers the period 2016–2020, encompassing a period of enhanced hydrothermal unrest including an abrupt seismic energy release (M 4.1) on April 27, 2018. Our dataset reveals fumarolic CO2/H2S and SO2/H2S gas trends correlated to the evolution of surface activity and to other geochemical and geophysical parameters. We demonstrate that, even under tropical conditions (high humidity and rainfall), MultiGas surveys of low-T fumarolic emissions permit to distinguish deeply sourced signals of volcanic unrest from secondary changes in degassing due to shallow forcing processes such as water-gas-rock interactions in the hydrothermal system and meteorological effects.
Late Holocene Orbital Forcing and Solar Activity on the Kuroshio Current of Subtropical North Pacific at Different Timescales
Authors: Ding Xue , Hu Bangqi , Li Jun , Zhao Jingtao , Yao Yue , Li Qing , Lan Jianghu , Zheng Xufeng , Yi Liang
Published: March 2022

The North Pacific subtropical gyre (NPSTG) redistributes heat and moisture between low and high latitudes and plays a key role in modulating the global climate change and ecosystem. Recent evidence suggests intensification and poleward shift of the subtropical gyres over the last decades due to global warming, but insufficient observations have hampered insight into the integrated effects of ocean-atmosphere interactions at longer timescales. Here we present the first high-resolution (∼12 years) grain-size record from Core CF1 in the Okinawa Trough, western subtropical North Pacific, to reconstruct the evolution of the western boundary Kuroshio Current (KC) of NPSTG during the Late Holocene. Our results indicate the KC slow-down during 4.6–2.0 ka, followed by quick enhancement after 2.0 ka, with centennial-scale variabilities (500–700 years) superimposed on the long-term trend. Over millennial timescales, gradually increased pole-to-equator thermal gradient, due to orbital forcing mechanisms, resulted in long-term enhanced KC, whereas solar activity triggered phase changes in the tropical Pacific mean state and controlled KC anomalies on centennial timescales. We suggest that both forcing mechanisms resulted in ocean-atmosphere feedback provoking concurrent changes in mid-latitude westerly and subtropical easterly winds over the North Pacific, alternating their dominance as source regions causing the dynamic changes of KC at different timescales. Our findings offer insight into the role of external forcing mechanisms in the NPSTG changes before the Anthropocene, which have profound implications for the deeper understanding of changes in ocean gyres under global warming scenarios.
A Convolutional Neural Network Bird Species Recognizer Built From Little Data by Iteratively Training, Detecting, and Labeling
Authors: Eichinski Philip , Alexander Callan , Roe Paul , Parsons Stuart , Fuller Susan
Published: March 2022

Automatically detecting the calls of species of interest in audio recordings is a common but often challenging exercise in ecoacoustics. This challenge is increasingly being tackled with deep neural networks that generally require a rich set of training data. Often, the available training data might not be from the same geographical region as the study area and so may contain important differences. This mismatch in training and deployment datasets can impact the accuracy at deployment, mainly due to confusing sounds absent from the training data generating false positives, as well as some variation in call types. We have developed a multiclass convolutional neural network classifier for seven target bird species to track presence absence of these species over time in cotton growing regions. We started with no training data from cotton regions but we did have an unbalanced library of calls from other locations. Due to the relative scarcity of calls in recordings from cotton regions, manually scanning and labeling the recordings was prohibitively time consuming. In this paper we describe our process of overcoming this data mismatch to develop a recognizer that performs well on the cotton recordings for most classes. The recognizer was trained on recordings from outside the cotton regions and then applied to unlabeled cotton recordings. Based on the resulting outputs a verification set was chosen to be manually tagged and incorporated in the training set. By iterating this process, we were gradually able to build the training set of cotton audio examples. Through this process, we were able to increase the average class F1 score (the harmonic mean of precision and recall) of the recognizer on target recordings from 0.45 in the first iteration to 0.74.
Males Are Capable of Long-Distance Dispersal in a Social Bee
Authors: Garcia Bulle Bueno Francisco , Garcia Bulle Bueno Bernardo , Buchmann Gabriele , Heard Tim , Latty Tanya , Oldroyd Benjamin P. , Hosoi Anette E. , Gloag Rosalyn
Published: March 2022

Pollinator conservation is aided by knowledge of dispersal behavior, which shapes gene flow and population structure. In many bees, dispersal is thought to be male-biased, and males’ movements may be critical to maintaining gene flow in disturbed and fragmented habitats. Yet male bee movements are challenging to track directly and male dispersal ability remains poorly understood in most species. Here, we combine field manipulations and models to assess male dispersal ability in a stingless bee (Tetragonula carbonaria). We placed colonies with virgin queens at varying distances apart (1–48 km), genotyped the males that gathered at mating aggregations outside each colony, and used pairwise sibship assignment to determine the distribution of likely brothers across aggregations. We then compared simulations of male dispersal to our observed distributions and found best-fit models when males dispersed an average of 2–3 km (>2-fold female flight ranges), and maximum of 20 km (30-fold female flight ranges). Our data supports the view that male bee dispersal can facilitate gene flow over long-distances, and thus play a key role in bee populations’ resilience to habitat loss and fragmentation. In addition, we show that the number of families contributing to male aggregations can be used to estimate local stingless bee colony densities, allowing population monitoring of these important tropical pollinators.
Impacts of Future Climate and Land Use/Cover Changes on Water-Related Ecosystem Services in Changbai Mountains, Northeast China
Authors: Wang Hebin , Wang Wen J. , Wang Lei , Ma Shuang , Liu Zhihua , Zhang Wenguang , Zou Yuanchun , Jiang Ming
Published: March 2022

Sustaining ecosystem services in alpine regions is a pressing global challenge given future accelerating environmental changes. Understanding how future climate change and land use/cover change (LUCC) drive ecosystem service will be important in this challenge. However, few studies have considered the combined effects of future climate change and LUCC on ecosystem services. We assessed water yield and soil retention services and their drivers in the Changbai mountains region (CBMR) from the 2020 to 2050s using the Integrated Valuation of Ecosystem Services and Trade-offs (InVEST) model and factor control experiments. Water yield decreased by 2.80% and soil retention increased by 6.14% over the 30 years. Climate change decreased water yield and increased soil retention, while LUCC decreased both water yield and soil retention. The interactive effects between climate change and LUCC had relatively small inhibitory effects on water yield and large facilitation effects on soil retention. Changes in water yield were mainly attributed to climate change, while soil retention was largely influenced by interaction. Our study highlights the individual and interactive contributions of future climate change and land use to ecosystem service in the mountains region, which can provide important information for informed future land management and policy making for sustaining diverse ecosystem services.
Identifying Membrane Protein Types Based on Lifelong Learning With Dynamically Scalable Networks
Authors: Lu Weizhong , Shen Jiawei , Zhang Yu , Wu Hongjie , Qian Yuqing , Chen Xiaoyi , Fu Qiming
Published: March 2022

Membrane proteins are an essential part of the body’s ability to maintain normal life activities. Further research into membrane proteins, which are present in all aspects of life science research, will help to advance the development of cells and drugs. The current methods for predicting proteins are usually based on machine learning, but further improvements in prediction effectiveness and accuracy are needed. In this paper, we propose a dynamic deep network architecture based on lifelong learning in order to use computers to classify membrane proteins more effectively. The model extends the application area of lifelong learning and provides new ideas for multiple classification problems in bioinformatics. To demonstrate the performance of our model, we conducted experiments on top of two datasets and compared them with other classification methods. The results show that our model achieves high accuracy (95.3 and 93.5%) on benchmark datasets and is more effective compared to other methods.
Knowledge Graphs for Indication Expansion: An Explainable Target-Disease Prediction Method
Authors: Gurbuz Ozge , Alanis-Lobato Gregorio , Picart-Armada Sergio , Sun Miao , Haslinger Christian , Lawless Nathan , Fernandez-Albert Francesc
Published: March 2022

Indication expansion aims to find new indications for existing targets in order to accelerate the process of launching a new drug for a disease on the market. The rapid increase in data types and data sources for computational drug discovery has fostered the use of semantic knowledge graphs (KGs) for indication expansion through target centric approaches, or in other words, target repositioning. Previously, we developed a novel method to construct a KG for indication expansion studies, with the aim of finding and justifying alternative indications for a target gene of interest. In contrast to other KGs, ours combines human-curated full-text literature and gene expression data from biomedical databases to encode relationships between genes, diseases, and tissues. Here, we assessed the suitability of our KG for explainable target-disease link prediction using a glass-box approach. To evaluate the predictive power of our KG, we applied shortest path with tissue information- and embedding-based prediction methods to a graph constructed with information published before or during 2010. We also obtained random baselines by applying the shortest path predictive methods to KGs with randomly shuffled node labels. Then, we evaluated the accuracy of the top predictions using gene-disease links reported after 2010. In addition, we investigated the contribution of the KG’s tissue expression entity to the prediction performance. Our experiments showed that shortest path-based methods significantly outperform the random baselines and embedding-based methods outperform the shortest path predictions. Importantly, removing the tissue expression entity from the KG severely impacts the quality of the predictions, especially those produced by the embedding approaches. Finally, since the interpretability of the predictions is crucial in indication expansion, we highlight the advantages of our glass-box model through the examination of example candidate target-disease predictions.
Explanation-Driven Deep Learning Model for Prediction of Brain Tumour Status Using MRI Image Data
Authors: Gaur Loveleen , Bhandari Mohan , Razdan Tanvi , Mallik Saurav , Zhao Zhongming
Published: March 2022

Cancer research has seen explosive development exploring deep learning (DL) techniques for analysing magnetic resonance imaging (MRI) images for predicting brain tumours. We have observed a substantial gap in explanation, interpretability, and high accuracy for DL models. Consequently, we propose an explanation-driven DL model by utilising a convolutional neural network (CNN), local interpretable model-agnostic explanation (LIME), and Shapley additive explanation (SHAP) for the prediction of discrete subtypes of brain tumours (meningioma, glioma, and pituitary) using an MRI image dataset. Unlike previous models, our model used a dual-input CNN approach to prevail over the classification challenge with images of inferior quality in terms of noise and metal artifacts by adding Gaussian noise. Our CNN training results reveal 94.64% accuracy as compared to other state-of-the-art methods. We used SHAP to ensure consistency and local accuracy for interpretation as Shapley values examine all future predictions applying all possible combinations of inputs. In contrast, LIME constructs sparse linear models around each prediction to illustrate how the model operates in the immediate area. Our emphasis for this study is interpretability and high accuracy, which is critical for realising disparities in predictive performance, helpful in developing trust, and essential in integration into clinical practice. The proposed method has a vast clinical application that could potentially be used for mass screening in resource-constraint countries.
Novel Insight Into Nutritional Regulation in Enhancement of Immune Status and Mediation of Inflammation Dynamics Integrated Study In Vivo and In Vitro of Teleost Grass Carp (Ctenopharyngodon idella): Administration of Threonine
Authors: Dong Yu-Wen , Jiang Wei-Dan , Wu Pei , Liu Yang , Kuang Sheng-Yao , Tang Ling , Tang Wu-Neng , Zhou Xiao-Qiu , Feng Lin
Published: March 2022

This study aims to investigate the effects of threonine (Thr) on immunoregulation in vivo and in vitro of teleost grass carp (Ctenopharyngodon idella). Juveniles (9.53 ± 0.02 g) were reared for 8 weeks with respective Thr diet (3.99, 7.70, 10.72, 14.10, 17.96, and 21.66 g/kg) and then challenged with Aeromonas hydrophila for in vivo study. Macrophages isolated from head kidney were treated in vitro for 48 h with L-Thr (0, 0.5, 1.0, 2.0, 4.0, and 8.0 mM) after 6 h of lipopolysaccharide induction. The results showed that, compared with Thr deficiency (3.99 g/kg), the optimal dietary Thr (14.10g/kg) affected the immunocyte activation in the head kidney (HK) and spleen (SP) by downregulating the mRNA expressions of MHC-II and upregulating CD4 (not CD8), and it mediated the innate immune by enhancing the activities of lysozyme (LZ), acid phosphatase content of complement 3 (C3) and C4, increasing the mRNA abundances of hepcidin, liver expressed antimicrobial peptide-2A (LEAP-2A), LEAP-2B, β-defensin1, downregulating tumor necrosis factor α (TNF-α), IL-6, IL-1β, IL-12p35, IL-12p40, IL-17AF1, and IL-17D partly by attenuating RORγ1 transcriptional factor and nuclear factor kappa B p65 (NF-κBp65) signaling cascades [IKKβ/IκBα/NF-κBp65] and upregulating transforming growth factor β1 (TGF-β1), IL-4/13A, -4/13B, IL-10, and IL-22 partly by GATA-3. Besides these, the optimal dietary Thr regulated the adaptive immune by upregulating the mRNAs of immunoglobulin M (IgM) and IgZ (not IgD). Moreover, 2 mM Thr downregulated in vitro the mRNA abundances of colony stimulating factor-1, inducible nitric oxide synthase, mannose receptor 1, matrix metalloproteinase2 (MMP-2), and MMP-9 significantly (P < 0.05), indicating that Thr could attenuate the M1-type macrophages’ activation. Moreover, L-Thr downregulated the mRNA transcripts of TNF-α, IL-6, and IL-1β associated with impairing the SOCS1/STAT1 signaling and upregulated IL-10 and TGF-β1 partly by accentuating the SOCS3/STAT3 pathway. The above-mentioned observations suggested that Thr improved the immune status in the immune organs of fish by enhancing the immune defense and mediating the inflammation process. Finally, based on the immune indices of LZ activity in HK and C3 content in SP, the optimal Thr for immune enhancement in juvenile grass carp (9.53–53.43 g) was determined to be 15.70 g/kg diet (4.85 g/100 g protein) and 14.49 g/kg diet (4.47 g/100 g protein), respectively.
Porcine Gasdermin D Is a Substrate of Caspase-1 and an Executioner of Pyroptosis
Authors: Song Yueyang , Song Jiameng , Wang Meng , Wang Junwei , Ma Bo , Zhang Wenlong
Published: March 2022

Gasdermin (GSDM) family proteins were recently identified as the executioner of pyroptosis. The mechanism of pyroptosis mediated by gasdermin D (GSDMD) (a member of GSDM family) in humans and mice is well understood. In pyroptosis, mouse and human GSDMDs are cleaved by activated proinflammatory caspases (caspase-1, 4, 5, or 11) to produce anamino-terminal domain (GSDMD-NT) and a carboxyl-terminal domain (GSDMD-CT). The GSDMD-NT drives cell membrane rupture, which leads to the pyroptotic death of the cells. The expression of porcine GSDMD (pGSDMD) has recently been determined, but the activation and regulation mechanism of pGSDMD and its ability to mediate pyroptosis are largely unknown. In the present study, the activation of porcine caspase-1 (pcaspase-1) and cleavage of pGSDMD occurred in the duodenum and jejunum of a piglet challenged with enterotoxigenic Escherichia coli were first determined. Then the capability of pcaspase-1 to cleave pGSDMD was determined in a cell-free system and in human embryonic kidney cells. The pGSDMD cleavage by pcaspase-1 occurred after the pGSDMD molecule’s 276Phenylalanine-Glutamine-Serine-Aspartic acid279 motif. The pGSDMD-NT generated from the pGSDMD cleavage by pcaspase-1 showed the ability to drive cell membrane rupture in eukaryotic cells. When expressed in E. coli competent cells, pGSDMD-NT showed bactericidal activity. These results suggest that pGSDMD is a substate of pcaspase-1 and an executioner of pyroptosis. Our work sheds light on pGSDMD’s activation mechanisms and functions.
Can CD200R1 Agonists Slow the Progression of Osteoarthritis Secondary to Injury?
Authors: Vachhani Kathak , Prodeus Aaron , Nakamura Sayaka , Rockel Jason S. , Hopfgartner Adam , Kapoor Mohit , Gariépy Jean , Whyne Cari , Nam Diane
Published: March 2022

Post-traumatic knee osteoarthritis is characterized by cartilage degeneration, subchondral bone remodeling, osteophyte formation, and synovial changes. Therapeutic targeting of inflammatory activity in the knee immediately post injury may alter the course of osteoarthritis development. This study aimed to determine whether CD200R1 agonists, namely the protein therapeutic CD200Fc or the synthetic DNA aptamer CCS13, both known to act as anti-inflammatory agents, are able to delay the pathogenesis of injury-associated knee osteoarthritis in a murine model. Ten week old male C57BL/6 mice were randomized and surgical destabilization of the medial meniscus (DMM) to induce knee arthritis or sham surgery as a control were performed. CCS13 was evaluated as a therapeutic treatment along with CD200Fc and a phosphate-buffered saline vehicle control. Oligonucleotides were injected intra-articularly beginning one week after surgery, with a total of six injections administered prior to sacrifice at 12 weeks post-surgery. Histopathological assessment was used as the primary outcome measure to assess cartilage and synovial changes, while µCT imaging was used to compare the changes to the subchondral bone between untreated and treated arthritic groups. We did not find any attenuation of cartilage degeneration or synovitis in DMM mice with CD200Fc or CCS13 at 12 weeks post-surgery, nor stereological differences in the properties of subchondral bone. The use of CD200R1 agonists to blunt the inflammatory response in the knee are insufficient to prevent disease progression in the mouse DMM model of OA without anatomical restoration of the normal joint biomechanics.
Maltodextrin Consumption Impairs the Intestinal Mucus Barrier and Accelerates Colitis Through Direct Actions on the Epithelium
Authors: Zangara Megan T. , Ponti András K. , Miller Noah D. , Engelhart Morgan J. , Ahern Philip P. , Sangwan Naseer , McDonald Christine
Published: March 2022

Food additives are common components of processed foods consumed in a Western diet. In inflammatory bowel disease patients, some diets that exclude food additives improved clinical disease parameters, suggesting a link between food additives and disease pathogenesis. Food additives also enhanced disease severity in mouse colitis models through incompletely described mechanisms. This study examined the mechanisms by which the food additive maltodextrin (MDX) alters the development of colitis in a murine model. Interleukin-10 knockout (IL10KO) mice were fed diets supplemented with MDX or carboxymethyl cellulose (CMC) to determine their impact on colitis onset and severity; microbiome composition, function, and location; colonic immune cell infiltrates; and mucus layer integrity. Primary IL10KO colonic epithelial monolayers were used to dissect the impact of MDX directly on epithelial differentiation and mucus production. MDX or CMC consumption increased the incidence and severity of colitis, as well as decreased microbiome diversity, altered microbial composition, and decreased fecal acetic acid levels. The number of mucus producing cells were decreased in food additive fed mice and resulted in increased microbial proximity to the intestinal epithelium. Additionally, MDX supplementation resulted in crypt hyperplasia and expansion of the HopX+ injury renewal stem cell niche. In primary intestinal epithelial-derived monolayers devoid of microbes and immune cells, MDX exposure decreased goblet cell number and mucus production in association with downregulated expression of the transcription factor Klf4, a marker of terminally differentiated goblet cells. These results suggest MDX disrupts the balance of epithelial cell differentiation and proliferation to contribute to disease pathogenesis through direct and indirect actions on the intestinal epithelial barrier.
Activated CD8+CD38+ Cells Are Associated With Worse Clinical Outcome in Hospitalized COVID-19 Patients
Authors: Bobcakova Anna , Barnova Martina , Vysehradsky Robert , Petriskova Jela , Kocan Ivan , Diamant Zuzana , Jesenak Milos
Published: March 2022

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), that spread around the world during the past 2 years, has infected more than 260 million people worldwide and has imposed an important burden on the healthcare system. Several risk factors associated with unfavorable outcome were identified, including elderly age, selected comorbidities, immune suppression as well as laboratory markers. The role of immune system in the pathophysiology of SARS-CoV-2 infection is indisputable: while an appropriate function of the immune system is important for a rapid clearance of the virus, progression to the severe and critical phases of the disease is related to an exaggerated immune response associated with a cytokine storm. We analyzed differences and longitudinal changes in selected immune parameters in 823 adult COVID-19 patients hospitalized in the Martin University Hospital, Martin, Slovakia. Examined parameters included the differential blood cell counts, various parameters of cellular and humoral immunity (serum concentration of immunoglobulins, C4 and C3), lymphocyte subsets (CD3+, CD4+, CD8+, CD19+, NK cells, CD4+CD45RO+), expression of activation (HLA-DR, CD38) and inhibition markers (CD159/NKG2A). Besides already known changes in the differential blood cell counts and basic lymphocyte subsets, we found significantly higher proportion of CD8+CD38+ cells and significantly lower proportion of CD8+NKG2A+ and NK NKG2A+ cells on admission in non-survivors, compared to survivors; recovery in survivors was associated with a significant increase in the expression of HLA-DR and with a significant decrease of the proportion of CD8+CD38+cells. Furthermore, patients with fatal outcome had significantly lower concentrations of C3 and IgM on admission. However, none of the examined parameters had sufficient sensitivity or specificity to be considered a biomarker of fatal outcome. Understanding the dynamic changes in immune profile of COVID-19 patients may help us to better understand the pathophysiology of the disease, potentially improve management of hospitalized patients and enable proper timing and selection of immunomodulator drugs.
Progress in the Use of Biosourced Phenolic Molecules for Electrode Manufacturing
Authors: Quílez-Bermejo Javier , Pérez-Rodríguez Sara , Celzard Alain , Fierro Vanessa
Published: March 2022

In the era of renewable technologies and clean processes, carbon science must adapt to this new model of a green society. Carbon materials are often obtained from petroleum precursors through polluting processes that do not meet the requirements of sustainable and green chemistry. Biomass is considered the only renewable source for the production of carbon materials, as the carbon in biomass comes from the consumption of carbon dioxide from the atmosphere, resulting in zero net carbon dioxide emissions. In addition to being a green source of carbon materials, biomass has many advantages such as being a readily available, large and cheap feedstock, as well as the ability to create unique carbon-derived structures with well-developed porosity and heteroatom doping. All these positive aspects position biomass-derived carbon materials as attractive alternatives in multiple applications, from energy storage to electrocatalysis, via adsorption and biosensors, among others. This review focuses on the application of phenolic resins to the production of electrodes for energy storage and the slow but inexorable movement from petroleum-derived phenolic compounds to biosourced molecules (i.e., lignins, tannins, etc.) as precursors for these carbon materials. Important perspectives and challenges for the design of these biosourced electrodes are discussed.
Comparative Study on the Effect of Ultrasonic Power on the Microstructure and Mechanical Properties of 2195 Aluminum Alloy Ingot
Authors: Hu Yuqi , Jiang Ripeng , Li Xiaoqian
Published: March 2022

High-intensity ultrasound was introduced for the casting of 2195 aluminum–lithium alloy ingots. The shape of the ingots was a cylinder with a length of 650 mm and a radius of 30 mm. In this study, the effects of different ultrasonic powers were applied in the melt. The grain shape, α-Al grain size, the size of the precipitated phase, and the mechanical properties of the ingots were compared. The results showed that when the power of the ultrasonic system was maintained at 1,600 W, an ingot with a more uniformly dispersed precipitation phase and grain refinement structure was formed. It can be concluded that the coarse eutectic structure in the ingot is effectively reduced when the power is around 1,600 W, and the mechanical properties of the ingot reach the best value.
Bacterial Recruitment to Carnivorous Pitcher Plant Communities: Identifying Sources Influencing Plant Microbiome Composition and Function
Authors: Grothjan Jacob J. , Young Erica B.
Published: March 2022

Processes influencing recruitment of diverse bacteria to plant microbiomes remain poorly understood. In the carnivorous pitcher plantSarracenia purpureamodel system, individual pitchers open to collect rainwater, invertebrates and a diverse microbial community, and this detrital food web is sustained by captured insect prey. This study examined how potential sources of bacteria affect the development of the bacterial community within pitchers, how the host plant tissue affects community development and how established vs. assembling communities differ. In a controlled greenhouse experiment, seven replicate pitchers were allocated to five treatments to exclude specific bacterial sources or host tissue: milliQ water only, milliQ + insect prey, rainwater + prey, established communities + prey, artificial pitchers with milliQ + prey. Community composition and functions were examined over 8–40 weeks using bacterial gene sequencing and functional predictions, measurements of cell abundance, hydrolytic enzyme activity and nutrient transformations. Distinct community composition and functional differences between artificial and real pitchers confirm an important influence of host plant tissue on community development, but also suggest this could be partially related to host nutrient uptake. Significant recruitment of bacteria to pitchers from air was evident from many taxa common to all treatments, overlap in composition between milliQ, milliQ + prey, and rainwater + prey treatments, and few taxa unique to milliQ only pitchers. Community functions measured as hydrolytic enzyme (chitinase, protease) activity suggested a strong influence of insect prey additions and were linked to rapid transformation of insect nutrients into dissolved and inorganic sources. Bacterial taxa found in 6 of 7 replicate pitchers within treatments, the “core microbiome” showed tighter successional trajectories over 8 weeks than all taxa. Established pitcher community composition was more stable over 8 weeks, suggesting a diversity-stability relationship and effect of microinvertebrates on bacteria. This study broadly demonstrates that bacterial composition in host pitcher plants is related to both stochastic and specific bacterial recruitment and host plants influence microbial selection and support microbiomes through capture of insect prey.
Adapting to Novel Environments Together: Evolutionary and Ecological Correlates of the Bacterial Microbiome of the World’s Largest Cavefish Diversification (Cyprinidae, Sinocyclocheilus)
Authors: Zhou Shipeng , Rajput Amrapali P. , Mao Tingru , Liu Yewei , Ellepola Gajaba , Herath Jayampathi , Yang Jian , Meegaskumbura Madhava
Published: March 2022

The symbiosis between a host and its microbiome is essential for host fitness, and this association is a consequence of the host’s physiology and habitat. Sinocyclocheilus, the largest cavefish diversification of the world, an emerging multi-species model system for evolutionary novelty, provides an excellent opportunity for examining correlates of host evolutionary history, habitat, and gut-microbial community diversity. From the diversification-scale patterns of habitat occupation, major phylogenetic clades (A–D), geographic distribution, and knowledge from captive-maintained Sinocyclocheilus populations, we hypothesize habitat to be the major determinant of microbiome diversity, with phylogeny playing a lesser role. For this, we subject environmental water samples and fecal samples (representative of gut-microbiome) from 24 Sinocyclocheilus species, both from the wild and after being in captivity for 6 months, to bacterial 16S rRNA gene profiling using Illumina sequencing. We see significant differences in the gut microbiota structure of Sinocyclocheilus, reflective of the three habitat types; gut microbiomes too, were influenced by host-related factors. There is no significant association between the gut microbiomes and host phylogeny. However, there is some microbiome related structure at the clade level, with the most geographically distant clades (A and D) being the most distinct, and the two overlapping clades (B and C) showing similarities. Microbes inhabiting water were not a cause for significant differences in fish-gut microbiota, but water quality parameters were. Transferring from wild to captivity, the fish microbiomes changed significantly and became homogenized, signifying plastic changes and highlighting the importance of environmental factors (habitat) in microbiome community assembly. The core microbiome of this group, at higher taxonomic scale, resembled that of other teleost fishes. Our results suggest that divergent natural environments giving rise to evolutionary novelties underlying host adaptations, also includes the microbiome of these fishes.
Biochar-Mediated Degradation of Roxarsone by Shewanella oneidensis MR-1
Authors: Wengang Li , Fang Chen , Rong Zhong , Cuihong Chen
Published: March 2022

It is widely believed that biochar plays an essential role in sequestrating pollutants. The impacts of biochar on microbial growth, and consequently on the environmental fate of pollutants, however, remains poorly understood. In this study, wheat-straw-derived biochar was used to investigate how biochar amendment affected Shewanella oneidensis MR-1 growth and roxarsone transformation in water under anaerobic conditions. Three biochar with different physicochemical properties were used to mediate the roxarsone degradation. The results showed that the degradation rate of roxarsone could be accelerated by the increase of biochar pyrolysis temperature. From the characterization of biochar, the total specific surface area, micropore surface area and micropore volume of biochar increase, but the average pore diameter decreases as the pyrolysis temperature increases. Through infrared spectroscopy analysis, it was found that as the pyrolysis temperature increases, the degree of condensation of biochar increases, thereby increasing the pollutant removal rate. From the changes of the relative concentration of MR-1 and its secreted extracellular polymer content, the growth promotion ability of biochar also increases as the pyrolysis temperature increases. These results suggest that wheat-straw-derived biochar may be an important agent for activating microbial growth and can be used to accelerate the transformation of roxarsone, which could be a novel strategy for roxarsone remediation.
Long-Term Expansion of Porcine Intestinal Organoids Serves as an in vitro Model for Swine Enteric Coronavirus Infection
Authors: Zhang Min , Lv Lilei , Cai Hongming , Li Yanhua , Gao Fei , Yu Lingxue , Jiang Yifeng , Tong Wu , Li Liwei , Li Guoxin , Tong Guangzhi , Liu Changlong
Published: March 2022

A reliable and reproducible model in vitro for swine enteric coronaviruses infection would be intestinal models that support virus replication and can be long-term cultured and manipulated experimentally. Here, we designed a robust long-term culture system for porcine intestinal organoids from the intestinal crypt or single LGR5+ stem cell by combining previously defined insights into the growth requirements of the intestinal epithelium of humans. We showed that long-term cultured swine intestinal organoids were expanded in vitro for more than 6 months and maintained the potential to differentiate into different types of cells. These organoids were successfully infected with porcine enteric coronavirus, including porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), and were capable of supporting virus replication and progeny release. RNA-seq analysis showed robust induction of transcripts associated with antiviral signaling in response to enteric coronavirus infection, including hundreds of interferon-stimulated genes and cytokines. Moreover, gene set enrichment analysis indicated that PEDV infection could suppress the immune response in organoids. This 3D intestinal organoid model offers a long-term, renewable resource for investigating porcine intestinal infections with various pathogens.
Gene Expression-Based Signature Can Predict Sorafenib Response in Kidney Cancer
Authors: Gudkov Alexander , Shirokorad Valery , Kashintsev Kirill , Sokov Dmitriy , Nikitin Daniil , Anisenko Andrey , Borisov Nicolas , Sekacheva Marina , Gaifullin Nurshat , Garazha Andrew , Suntsova Maria , Koroleva Elena , Buzdin Anton , Sorokin Maksim
Published: March 2022

Sorafenib is a tyrosine kinase inhibitory drug with multiple molecular specificities that is approved for clinical use in second-line treatments of metastatic and advanced renal cell carcinomas (RCCs). However, only 10–40% of RCC patients respond on sorafenib-containing therapies, and personalization of its prescription may help in finding an adequate balance of clinical efficiency, cost-effectiveness, and side effects. We investigated whether expression levels of known molecular targets of sorafenib in RCC can serve as prognostic biomarker of treatment response. We used Illumina microarrays to profile RNA expression in pre-treatment formalin-fixed paraffin-embedded (FFPE) samples of 22 metastatic or advanced RCC cases with known responses on next-line sorafenib monotherapy. Among them, nine patients showed partial response (PR), three patients—stable disease (SD), and 10 patients—progressive disease (PD) according to Response Evaluation Criteria In Solid Tumors (RECIST) criteria. We then classified PR + SD patients as “responders” and PD patients as “poor responders”. We found that gene signature including eight sorafenib target genes was congruent with the drug response characteristics and enabled high-quality separation of the responders and poor responders [area under a receiver operating characteristic curve (AUC) 0.89]. We validated these findings on another set of 13 experimental annotated FFPE RCC samples (for 2 PR, 1 SD, and 10 PD patients) that were profiled by RNA sequencing and observed AUC 0.97 for 8-gene signature as the response classifier. We further validated these results in a series of qRT-PCR experiments on the third experimental set of 12 annotated RCC biosamples (for 4 PR, 3 SD, and 5 PD patients), where 8-gene signature showed AUC 0.83.