bluuebunny/crossref_metadata_2025 huggingface dataset:
The Direct Semi-Quantitative Detection of 18 Pathogens and Simultaneous Screening for Nine Resistance Genes in Clinical Urine Samples by a High-Throughput Multiplex Genetic Detection System
Authors: Sun Zhaoyang , Liu Wenjian , Zhang Jinghao , Wang Su , Yang Feng , Fang Yi , Jiang Wenrong , Ding Li , Zhao Hu , Zhang Yanmei
Published: April 2021

Background

Urinary tract infections (UTIs) are one the most common infections. The rapid and accurate identification of uropathogens, and the determination of antimicrobial susceptibility, are essential aspects of the management of UTIs. However, existing detection methods are associated with certain limitations. In this study, a new urinary tract infection high-throughput multiplex genetic detection system (UTI-HMGS) was developed for the semi-quantitative detection of 18 pathogens and the simultaneously screening of nine resistance genes directly from the clinical urine sample within 4 hours.

Methods

We designed and optimized a multiplex polymerase chain reaction (PCR) involving fluorescent dye-labeled specific primers to detect 18 pathogens and nine resistance genes. The specificity of the UTI-HMGS was tested using standard strains or plasmids for each gene target. The sensitivity of the UTI-HMGS assay was tested by the detection of serial tenfold dilutions of plasmids or simulated positive urine samples. We also collected clinical urine samples and used these to perform urine culture and antimicrobial susceptibility testing (AST). Finally, all urine samples were detected by UTI-HMGS and the results were compared with both urine culture and Sanger sequencing.

Results

UTI-HMGS showed high levels of sensitivity and specificity for the detection of uropathogens when compared with culture and sequencing. In addition, ten species of bacteria and three species of fungi were detected semi-quantitatively to allow accurate discrimination of significant bacteriuria and candiduria. The sensitivity of the UTI-HMGS for the all the target genes could reach 50 copies per reaction. In total, 531 urine samples were collected and analyzed by UTI-HMGS, which exhibited high levels of sensitivity and specificity for the detection of uropathogens and resistance genes when compared with Sanger sequencing. The results from UTI-HMGS showed that the detection rates of 15 pathogens were significantly higher (P<0.05) than that of the culture method. In addition, there were 41(7.72%, 41/531) urine samples were positive for difficult-to-culture pathogens, which were missed detected by routine culture method.

Conclusions

UTI-HMGS proved to be an efficient method for the direct semi-quantitative detection of 18 uropathogens and the simultaneously screening of nine antibiotic resistance genes in urine samples. The UTI-HMGS could represent an alternative method for the clinical detection and monitoring of antibiotic resistance.
Spatio-Temporal Downscaling of Climate Data Using Convolutional and Error-Predicting Neural Networks
Authors: Serifi Agon , Günther Tobias , Ban Nikolina
Published: April 2021

Numerical weather and climate simulations nowadays produce terabytes of data, and the data volume continues to increase rapidly since an increase in resolution greatly benefits the simulation of weather and climate. In practice, however, data is often available at lower resolution only, for which there are many practical reasons, such as data coarsening to meet memory constraints, limited computational resources, favoring multiple low-resolution ensemble simulations over few high-resolution simulations, as well as limits of sensing instruments in observations. In order to enable a more insightful analysis, we investigate the capabilities of neural networks to reconstruct high-resolution data from given low-resolution simulations. For this, we phrase the data reconstruction as a super-resolution problem from multiple data sources, tailored toward meteorological and climatological data. We therefore investigate supervised machine learning using multiple deep convolutional neural network architectures to test the limits of data reconstruction for various spatial and temporal resolutions, low-frequent and high-frequent input data, and the generalization to numerical and observed data. Once such downscaling networks are trained, they serve two purposes: First, legacy low-resolution simulations can be downscaled to reconstruct high-resolution detail. Second, past observations that have been taken at lower resolutions can be increased to higher resolutions, opening new analysis possibilities. For the downscaling of high-frequent fields like precipitation, we show that error-predicting networks are far less suitable than deconvolutional neural networks due to the poor learning performance. We demonstrate that deep convolutional downscaling has the potential to become a building block of modern weather and climate analysis in both research and operational forecasting, and show that the ideal choice of the network architecture depends on the type of data to predict, i.e., there is no single best architecture for all variables.
Speech Anxiety in the Communication Classroom During the COVID-19 Pandemic: Supporting Student Success
Authors: Prentiss Suzy
Published: April 2021

A wealth of literature clearly supports the presence of speech anxiety in the communication classroom, especially in those classes with a focus on public speaking and/or presentations. Over the years, much work has been done on intentional approaches to empowering students to effectively manage their speech anxiety in face-to-face, hybrid, and online communication courses. These research-based findings have led to best practices and strong pedagogical approaches that create a supportive classroom culture and foster engaged learning. Then COVID-19 appeared, and things changed. In an effort to keep campuses safe and save the spring semester, everyone jumped online. Many instructors and students were experiencing online education for the first time and, understandably, anxiety exploded. Between the uncertainty of a global pandemic, the unchartered territory of a midterm pivot to fully online education, and the unknown effects of the situation on our educational system, our stress levels grew. Public speaking and presentations took on new meaning with Zoom sessions and webcams and our speech anxiety, undoubtedly, grew, as well. Reflecting upon the scholarship of the past with an appreciation of our present situation and looking toward the future, we will curate a list of best practices to prepare students to effectively manage their speech anxiety with agency, ability, and confidence.
Monazite Microstructures and Their Interpretation in Petrochronology
Authors: Schulz Bernhard
Published: April 2021

The phosphate mineral monazite (LREE,Y,Th,Ca,Si)PO4 occurs as an accessory phase in peraluminous granites and Ca-poor meta-psammopelites. Due to negligible common Pb and very low Pb diffusion rates at high temperatures, monazite has received increasing attention in geochronology. As the monazite grain sizes are mostly below 100 μm in upper greenschist to amphibolite facies meta-psammopelites, and rarely exceed 250 μm in granulite facies gneisses and in migmatites, microstructural observation and mineral chemical analysis need the investigation by scanning electron microscope and electron probe microanalyzer, with related routines of automated mineralogy. Not only the microstructural positions, sizes and contours of the grains, but also their internal structures in backscattered electron imaging gray tones, mainly controlled by the Th contents, can be assessed by this approach. Monazite crystallizes mostly euhedral to anhedral with more or less rounded crystal corners. There are transitions from elliptical over amoeboid to strongly emarginated grain shapes. The internal structures of the grains range from single to complex concentric over systematic oszillatory zonations to turbulent and cloudy, all with low to high contrast in backscattered electron imaging gray tones. Fluid-mediated partial alteration and coupled dissolution-reprecipitation can lead to Th-poor and Th-rich rim zones with sharp concave boundaries extending to the interior. Of particular interest is the corona structure with monazite surrounded by apatite and allanite, which is interpreted to result from a replacement during retrogression. The satellite structure with an atoll-like arrangement of small monazites may indicate re-heating after retrogression. Cluster structures with numerous small monazite grains, various aggregation structures and coating suggest nucleation and growth along heating or/and enhanced fluid activity. Microstructures of monazite fluid-mediated alteration, decomposition and replacement are strongly sutured grain boundaries and sponge-like porosity and intergrowth with apatite. Garnet-bearing assemblages allow an independent reconstruction of the pressure-temperature evolution in monazite-bearing meta-psammopelites. This provides additional potential for evaluation of the monazite microstructures, mineral chemistry and Th-U-Pb ages in terms of clockwise and counterclockwise pressure-temperature-time-deformation paths of anatectic melting, metamorphism and polymetamorphism. That way, monazite microstructures serve as unique indicators of tectonic and geodynamic scenarios.
The Evaluation of Social and Professional Life Competences of University Students Through Service-Learning
Authors: Santos Rego Miguel A. , Mella Núñez Ígor , Naval Concepción , Vázquez Verdera Victoria
Published: April 2021

The view previously held in the university regarding teaching-learning processes has changed significantly over the past few years. Undoubtedly, in the case of Europe, this change of pedagogical model has gone hand in hand with the creation of the European Higher Education Area (EHEA). Some of the pivotal areas of EHEA are the independent work of the individual student, the social dimension of learning, and the acquiring of skills, which are not reduced to the mere technical and/or subject matter knowledge. Generic competences and the so-called “soft skills” have also become important, given their significant contribution to the students’ academic, personal, social, and professional development. Predictably, within this framework, new methodologies appear, in line with this educational focus on competences; among these new methodologies include service-learning (SL). It basically consists of introducing a community service into the traditional academic and curricular tasks thereby seeking a better relevance and applicability in the learning processes. This article analyzes the way in which SL contributes to the acquisition, by university students, of a certain skill set which is useful for their social and professional life. To this end, we used a quasi-experimental design, which included pretest and posttest assessments based on a total sample of 1,153 students (789 SL students and 364 non-SL students). The used questionnaire evaluates three important components relevant for the purpose of the present article (perception of the university education, social participation and civic-social competences). The conclusion is that students involved in SL not only show a more positive evolution, but also obtain better results after the projects are completed (regarding satisfaction with the training, and social participation). By the same token, not all students included in the experimental group achieve homogeneous results; the differences are according to variables such as gender, the cycle/year they are enrolled in, area of study or whether or not they previously participated in university service activities. Finally, we observe that this methodology is capable of approaching university education in a holistic way by asserting cross-section type learning processes likely to be useful in the transition from the students’ academic to their professional life.
Analyzing Relationships Between Causal and Assessment Factors of Cognitive Load: Associations Between Objective and Subjective Measures of Cognitive Load, Stress, Interest, and Self-Concept
Authors: Minkley Nina , Xu Kate M. , Krell Moritz
Published: April 2021

The present study is based on a theoretical framework of cognitive load that distinguishes causal factors (learner characteristics affecting cognitive load e.g., self-concept; interest; perceived stress) and assessment factors (indicators of cognitive load e.g., mental load; mental effort; task performance) of cognitive load. Various assessment approaches have been used in empirical research to measure cognitive load during task performance. The most common methods are subjective self-reported questionnaires; only occasionally objective physiological measures such as heart rates are used. However, the convergence of subjective and objective approaches has not been extensively investigated yet, leaving unclear the meaning of each kind of measure and its validity. This study adds to this body of research by analyzing the relationship between these causal and assessment (subjective and objective) factors of cognitive load. The data come from three comparable studies in which high school students (N = 309) participated in a one-day out of school molecular biology project and completed different tasks about molecular biology structures and procedures. Heart rate variability (objective cognitive load) was measured via a chest belt. Subjective cognitive load (i.e., mental load and mental effort) and causal factors including self-concept, interest, and perceived stress were self-reported by participants on questionnaires. The findings show that a) objective heart rate measures of cognitive load are related to subjective measures of self-reported mental effort but not of mental load; b) self-reported mental effort and mental load are better predictors of task performance than objective heart rate measures of cognitive load; c) self-concept, interest and perceived stress are associated with self-reported measures of mental load and mental effort, and self-concept is associated with one of the objective heart rate measures. The findings are discussed based on the theoretical framework of cognitive load and implications for the validity of each measure are proposed.
Endocrine Disruptor Compounds—A Cause of Impaired Immune Tolerance Driving Inflammatory Disorders of Pregnancy?
Authors: Schjenken John E. , Green Ella S. , Overduin Tenuis S. , Mah Chui Yan , Russell Darryl L. , Robertson Sarah A.
Published: April 2021

Endocrine disrupting compounds (EDCs) are prevalent and ubiquitous in our environment and have substantial potential to compromise human and animal health. Amongst the chronic health conditions associated with EDC exposure, dysregulation of reproductive function in both females and males is prominent. Human epidemiological studies demonstrate links between EDC exposure and infertility, as well as gestational disorders including miscarriage, fetal growth restriction, preeclampsia, and preterm birth. Animal experiments show EDCs administered during gestation, or to either parent prior to conception, can interfere with gamete quality, embryo implantation, and placental and fetal development, with consequences for offspring viability and health. It has been presumed that EDCs operate principally through disrupting hormone-regulated events in reproduction and fetal development, but EDC effects on maternal immune receptivity to pregnancy are also implicated. EDCs can modulate both the innate and adaptive arms of the immune system, to alter inflammatory responses, and interfere with generation of regulatory T (Treg) cells that are critical for pregnancy tolerance. Effects of EDCs on immune cells are complex and likely exerted by both steroid hormone-dependent and hormone-independent pathways. Thus, to better understand how EDCs impact reproduction and pregnancy, it is imperative to consider how immune-mediated mechanisms are affected by EDCs. This review will describe evidence that several EDCs modify elements of the immune response relevant to pregnancy, and will discuss the potential for EDCs to disrupt immune tolerance required for robust placentation and optimal fetal development.
Maternal Vitamin B12 Status During Pregnancy and Its Association With Outcomes of Pregnancy and Health of the Offspring: A Systematic Review and Implications for Policy in India
Authors: Behere Rishikesh V. , Deshmukh Anagha S. , Otiv Suhas , Gupte Mohan D. , Yajnik Chittaranjan S.
Published: April 2021

Background

Vitamins B12 and folate participate in the one-carbon metabolism cycle and hence regulate fetal growth. Though vitamin B12 deficiency is widely prevalent, the current public health policy in India is to supplement only iron and folic acid for the prevention of anaemia. Prompted by our research findings of the importance of maternal vitamin B12 status for a healthy pregnancy, birth and offspring health outcomes, we evaluated available literature evidence using a systematic review approach, to inform policy.

Methods

A systematic search was performed for relevant Indian studies in the MEDLINE/PubMed and IndMed databases. We selected studies reporting maternal vitamin B12 status (dietary intake or blood concentrations), and/or metabolic markers of vitamin B12 deficiency (homocysteine, methylmalonic acid) or haematological indices during pregnancy and their associations with outcomes of pregnancy, infancy or in later life. Intervention trials of vitamin B12 during pregnancy were also included. Quality of evidence was assessed on the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Results

Of the 635 articles identified, 46 studies met the inclusion criteria (cohort studies-26, case-control studies-13, RCT’s -7). There is a high prevalence of vitamin B12 deficiency in Indian women during pregnancy (40-70%) (3 studies). Observational studies support associations (adjusted for potential sociodemographic confounders, maternal body size, postnatal factors) of lower maternal B12, higher homocysteine or an imbalance between vitamin B12-folate status with a higher risk of NTDs (6 studies), pregnancy complications (recurrent pregnancy losses, gestational diabetes, pre-eclampsia) (9 studies), lower birth weight (10 studies) and adverse longer-term health outcomes in the offspring (cognitive functions, adiposity, insulin resistance) (11 studies). Vitamin B12 supplementation (7 RCT’s) in pregnancy showed a beneficial effect on offspring neurocognitive development and an effect on birth weight was inconclusive. There is a high quality evidence to support the role of low maternal vitamin B12 in higher risk for NTD and low birth weight and moderate-quality evidence for higher risk of gestational diabetes and later life adverse health outcomes (cognitive functions, risk for diabetes) in offspring.

Conclusion

In the Indian population low maternal vitaminB12 status, is associated with adverse maternal and child health outcomes. The level of evidence supports adding vitamin B12 to existing nutritional programs in India for extended benefits on outcomes in pregnancy and offspring health besides control of anaemia.

Systematic Review Registration

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Decreased Treg Cell and TCR Expansion Are Involved in Long-Lasting Graves’ Disease
Authors: Chen Ziyi , Liu Yufeng , Hu Shiqian , Zhang Meng , Shi Bingyin , Wang Yue
Published: April 2021

Graves’ disease (GD) is a T cell-mediated organ-specific autoimmune disorder. GD patients who have taken anti-thyroid drugs (ATDs) for more than 5 years with positive anti-thyroid stimulating hormone receptor autoantibodies value were defined as persistent GD (pGD). To develop novel immunotherapies for pGD, we investigated the role of T cells in the long-lasting phase of GD. Clinical characteristics were compared between the pGD and newly diagnosed GD (nGD) (N = 20 respectively). Flow cytometric analysis was utilized to determine the proportions of Treg and Th17 cells (pGD, N = 12; nGD, N = 14). T cell receptor sequencing (TCR-seq) and RNA sequencing (RNA-seq) were also performed (pGD, N = 13; nGD, N = 20). Flow cytometric analysis identified lower proportions of Th17 and Treg cells in pGD than in nGD (P = 0.0306 and P = 0.0223). TCR-seq analysis revealed a lower diversity (P = 0.0025) in pGD. Specifically, marked clonal expansion, represented by an increased percentage of top V-J recombination, was observed in pGD patients. Interestingly, pGD patients showed more public T cell clonotypes than nGD patients (2,741 versus 966). Meanwhile, RNA-seq analysis revealed upregulation of the inflammation and chemotaxis pathways in pGD. Specifically, the expression of pro-inflammatory and chemotactic genes (IL1B, IL13, IL8, and CCL4) was increased in pGD, whereas Th17 and Treg cells associated genes (RORC, CARD9, STAT5A, and SATB1) decreased in pGD. Additionally, TCR diversity was negatively correlated with the expression of pro-inflammatory or chemotactic genes (FASLG, IL18R1, CCL24, and CCL14). These results indicated that Treg dysregulation and the expansion of pathogenic T cell clones might be involved in the long-lasting phase of GD via upregulating chemotaxis or inflammation response. To improve the treatment of pGD patients, ATDs combined therapies, especially those aimed at improving Treg cell frequencies or targeting specific expanded pathogenic TCR clones, are worth exploring in the future.
Should Adrenal Venous Sampling Be Performed in PA Patients Without Apparent Adrenal Tumors?
Authors: Okamoto Kentaro , Ohno Youichi , Sone Masakatsu , Inagaki Nobuya , Ichijo Takamasa , Yoneda Takashi , Tsuiki Mika , Wada Norio , Oki Kenji , Tamura Kouichi , Kobayashi Hiroki , Izawa Shoichiro , Tanabe Akiyo , Naruse Mitsuhide
Published: April 2021

Introduction

Some aldosterone-producing micro-adenomas cannot be detected through image inspection. Therefore, adrenal venous sampling (AVS) is often performed, even in primary aldosteronism (PA) patients who have no apparent adrenal tumors (ATs) on imaging. In most of these cases, however, the PA is bilateral.

Objective

To clarify the clinical need for AVS in PA patients without apparent ATs, taking into consideration the rates of adrenalectomy.

Methods

This is a retrospective cross-sectional study assessing 1586 PA patients without apparent ATs in the multicenter Japan PA study (JPAS). We analyzed which parameters could be used to distinguish unilateral PA patients without apparent ATs from bilateral patients. We also analyzed the prevalences of adrenalectomy in unilateral PA patients.

Results

The unilateral subtype without an apparent AT was diagnosed in 200 (12.6%) of 1586 PA patients. Being young and female with a short hypertension duration, normokalemia, low creatinine level, low plasma aldosterone concentration, and low aldosterone-to-renin ratio (ARR) was significantly more common in bilateral than unilateral PA patients. If PA patients without apparent ATs were female and normokalemic with a low ARR (<560 pg/ml per ng/ml/h), the rate of unilateral PA was only 5 (1.1%) out of 444. Moreover, 77 (38.5%) of the 200 did not receive adrenalectomy, despite being diagnosed with the unilateral subtype based on AVS.

Conclusion

The low prevalence of the unilateral subtype in PA patients without apparent ATs suggests AVS is not indicated for all of these patients. AVS could be skipped in female normokalemic PA patients without apparent ATs if their ARRs are not high. However, AVS should be considered for male hypokalemic PA patients with high ARRs because the rates of the unilateral subtype are high in these patients.
Process Systems Engineering Evaluation of Prospective Working Fluids for Organic Rankine Cycles Facilitated by Biogas Combustion Flue Gases
Authors: Qyyum Muhammad Abdul , Naquash Ahmad , Ali Wahid , Haider Junaid , Noon Adnan Aslam , Rehan Mohammad , Nizami Abdul-Sattar , Yasin Muhammad , Lee Moonyong
Published: April 2021

The organic Rankine cycle (ORC) has recently emerged as a practical approach for generating electricity from low-to-high-temperature waste industrial streams. Several ORC-based waste heat utilization plants are already operational; however, improving plant cost-effectiveness and competitiveness is challenging. The use of thermally efficient and cost-competitive working fluids (WFs) improves the overall efficiency and economics of ORC systems. This study evaluates ORC systems, facilitated by biogas combustion flue gases, using n-butanol, i-butanol, and methylcyclohexane, as WFs technically and economically, from a process system engineering perspective. Furthermore, the performance of the aforementioned WFs is compared with that of toluene, a well-known WF, and it is concluded that i-butanol and n-butanol are the most competitive alternatives in terms of work output, exergy efficiency, thermal efficiency, total annual cost, and annual profit. Moreover, the i-butanol and n-butanol-based ORC systems yielded 24.4 and 23.4% more power, respectively, than the toluene-based ORC system; in addition, they exhibited competitive thermal (18.4 and 18.3%, respectively) and exergy efficiencies (38 and 37.7%, respectively). Moreover, economically, i-butanol and n-butanol showed the potential of generating 48.7 and 46% more profit than that of toluene. Therefore, this study concludes that i-butanol and n-butanol are promising WFs for high-temperature ORC systems, and their technical and economic performance compares with that of toluene. The findings of this study will lead to energy efficient ORC systems for generating power.
Heavy Metals in Soils and the Remediation Potential of Bacteria Associated With the Plant Microbiome
Authors: González Henao Sarah , Ghneim-Herrera Thaura
Published: April 2021

High concentrations of non-essential heavy metals/metalloids (arsenic, cadmium, and lead) in soils and irrigation water represent a threat to the environment, food safety, and human and animal health. Microbial bioremediation has emerged as a promising strategy to reduce the concentration of heavy metals in the environment due to the demonstrated ability of microorganisms, especially bacteria, to sequester and transform these compounds. Although several bacterial strains have been reported to be capable of remediation of soils affected by heavy metals, published information has not been comprehensively analyzed to date to recommend the most efficient microbial resources for application in bioremediation or bacterial-assisted phytoremediation strategies that may help improve plant growth and yield in contaminated soils. In this study, we critically analyzed eighty-five research articles published over the past 15 years, focusing on bacteria-assisted remediation strategies for the non-essential heavy metals, arsenic, cadmium, and lead, and selected based on four criteria: i) The bacterial species studied are part of a plant microbiome, i.e., they interact closely with a plant species ii) these same bacterial species exhibit plant growth-promoting characteristics, iii) bacterial resistance to the metal(s) is expressed in terms of the Minimum Inhibitory Concentration (MIC), and iv) metal resistance is related to biochemical or molecular mechanisms. A total of sixty-two bacterial genera, comprising 424 bacterial species/strains associated with fifty plant species were included in our analysis. Our results showed a close relationship between the tolerance level exhibited by the bacteria and metal identity, with lower MIC values found for cadmium and lead, while resistance to arsenic was widespread and significantly higher. In-depth analysis of the most commonly evaluated genera, Agrobacterium, Bacillus, Klebsiella, Enterobacter, Microbacterium, Pseudomonas, Rhodococcus, and Mesorhizobium showed significantly different tolerance levels among them and highlighted the deployment of different biochemical and molecular mechanisms associated with plant growth promotion or with the presence of resistance genes located in the cad and ars operons. In particular, the genera Klebsiella and Enterobacter exhibited the highest levels of cadmium and lead tolerance, clearly supported by molecular and biochemical mechanisms; they were also able to mitigate plant growth inhibition under phytotoxic metal concentrations. These results position Klebsiella and Enterobacter as the best potential candidates for bioremediation and bacteria-assisted phytoremediation strategies in soils contaminated with arsenic, cadmium, and lead.
Polycyclic Aromatic Hydrocarbons Have Adverse Effects on Benthic Communities in the Baltic Sea: Implications for Environmental Status Assessment
Authors: Raymond Caroline , Gorokhova Elena , Karlson Agnes ML
Published: April 2021

Changes in benthic macrofaunal communities are indicative of environmental stressors, including eutrophication and hypoxia. However, some species are sensitive not only to hypoxia but also to various environmental contaminants. We tested which of the environmental predictors (sediment organic carbon, sediment concentrations of metals and polyaromatic hydrocarbons [PAHs], bottom water oxygen, salinity, temperature, and surface chlorophyll-a concentration) that best explained the following response variables: (1) macrofauna community composition, (2) abundance of a benthic sentinel species, the amphipod Monoporeia affinis; and (3) the Benthic Quality Index (BQI). All data originated from 29 reference monitoring stations in the Baltic Sea and the statistical tests included both uni- and multivariate analyses. The community composition and BQI were best explained by the same combination of salinity, depth, temperature and PAH concentrations. The abundance of M. affinis, which is sensitive to hypoxia and chemical exposure, was best explained by PAHs as a single predictor. Our findings suggest that benthic communities in the Baltic Sea are influenced by anthropogenic contaminants, which should be taken into account when benthos is used for eutrophication status assessment.
Ecological Correlates of Elevational Range Shifts in Tropical Birds
Authors: Neate-Clegg Montague H. C. , Jones Samuel E. I. , Tobias Joseph A. , Newmark William D. , Şekercioǧlu Çaǧan H.
Published: April 2021

Globally, birds have been shown to respond to climate change by shifting their elevational distributions. This phenomenon is especially prevalent in the tropics, where elevational gradients are often hotspots of diversity and endemism. Empirical evidence has suggested that elevational range shifts are far from uniform across species, varying greatly in the direction (upslope vs. downslope) and rate of change (speed of elevational shift). However, little is known about the drivers of these variable responses to climate change, limiting our ability to accurately project changes in the future. Here, we compile empirical estimates of elevational shift rates (m/yr) for 421 bird species from eight study sites across the tropics. On average, species shifted their mean elevations upslope by 1.63 ± 0.30 m/yr, their upper limits by 1.62 m ± 0.38 m/yr, and their lower limits by 2.81 ± 0.42 m/yr. Upslope shift rates increased in smaller-bodied, less territorial species, whereas larger species were more likely to shift downslope. When considering absolute shift rates, rates were fastest for species with high dispersal ability, low foraging strata, and wide elevational ranges. Our results indicate that elevational shift rates are associated with species’ traits, particularly body size, dispersal ability, and territoriality. However, these effects vary substantially across sites, suggesting that responses of tropical montane bird communities to climate change are complex and best predicted within the local or regional context.
Intersecting Ecosystem Services Across the Aquatic Continuum: From Global Change Impacts to Local, and Biologically Driven, Synergies and Trade-Offs
Authors: D’Alelio Domenico , Russo Luca , Hay Mele Bruno , Pomati Francesco
Published: April 2021

The study of ecosystem services requires the integration of different observational points. This is particularly true in Water, as this element continuously cycles, increasing chances of interaction among services originating in different ecosystems. However, aquatic scientists historically approached the study of inland/freshwater and open/marine waters in different ways and this cultural division potentially hampers integrative approaches. Herein, we explored the literature pertaining to ecosystem services across the last 23 years, analysing 4,590 aquatic papers. By aggregating and intersecting topics included in this papers’ collection using text-mining and topical network approaches, we saw that the study of local environmental conditions (e.g., river estuary management) and synergies and trade-offs between services (e.g., carbon sequestration and water purification) can display several potential conceptual links between freshwater and marine sciences. Our analyses suggest that to intersect ecosystem services across the aquatic continuum, the conceptual integration between marine and freshwater science must be reinforced, especially at the interface between different “salinity realms.” Such integration should adopt a “system thinking” perspective, in which the focus is on multiple socio-ecological processes giving rise to interactions that are (i) biologically mediated, (ii) potentially conflicting, and (iii) entangled within networks.
Intelligent Health Care: Applications of Deep Learning in Computational Medicine
Authors: Yang Sijie , Zhu Fei , Ling Xinghong , Liu Quan , Zhao Peiyao
Published: April 2021

With the progress of medical technology, biomedical field ushered in the era of big data, based on which and driven by artificial intelligence technology, computational medicine has emerged. People need to extract the effective information contained in these big biomedical data to promote the development of precision medicine. Traditionally, the machine learning methods are used to dig out biomedical data to find the features from data, which generally rely on feature engineering and domain knowledge of experts, requiring tremendous time and human resources. Different from traditional approaches, deep learning, as a cutting-edge machine learning branch, can automatically learn complex and robust feature from raw data without the need for feature engineering. The applications of deep learning in medical image, electronic health record, genomics, and drug development are studied, where the suggestion is that deep learning has obvious advantage in making full use of biomedical data and improving medical health level. Deep learning plays an increasingly important role in the field of medical health and has a broad prospect of application. However, the problems and challenges of deep learning in computational medical health still exist, including insufficient data, interpretability, data privacy, and heterogeneity. Analysis and discussion on these problems provide a reference to improve the application of deep learning in medical health.
Dysregulation of MicroRNAs in Hypertrophy and Ossification of Ligamentum Flavum: New Advances, Challenges, and Potential Directions
Authors: Zhang Baoliang , Chen Guanghui , Yang Xiaoxi , Fan Tianqi , Chen Xi , Chen Zhongqiang
Published: April 2021

Pathological changes in the ligamentum flavum (LF) can be defined as a process of chronic progressive aberrations in the nature and structure of ligamentous tissues characterized by increased thickness, reduced elasticity, local calcification, or aggravated ossification, which may cause severe myelopathy, radiculopathy, or both. Hypertrophy of ligamentum flavum (HLF) and ossification of ligamentum flavum (OLF) are clinically common entities. Though accumulated evidence has indicated both genetic and environmental factors could contribute to the initiation and progression of HLF/OLF, the definite pathogenesis remains fully unclear. MicroRNAs (miRNAs), one of the important epigenetic modifications, are short single-stranded RNA molecules that regulate protein-coding gene expression at posttranscriptional level, which can disclose the mechanism underlying diseases, identify valuable biomarkers, and explore potential therapeutic targets. Considering that miRNAs play a central role in regulating gene expression, we summarized current studies from the point of view of miRNA-related molecular regulation networks in HLF/OLF. Exploratory studies revealed a variety of miRNA expression profiles and identified a battery of upregulated and downregulated miRNAs in OLF/HLF patients through microarray datasets or transcriptome sequencing. Experimental studies validated the roles of specific miRNAs (e.g., miR-132-3p, miR-199b-5p in OLF, miR-155, and miR-21 in HLF) in regulating fibrosis or osteogenesis differentiation of LF cells and related target genes or molecular signaling pathways. Finally, we discussed the perspectives and challenges of miRNA-based molecular mechanism, diagnostic biomarkers, and therapeutic targets of HLF/OLF.
GADTI: Graph Autoencoder Approach for DTI Prediction From Heterogeneous Network
Authors: Liu Zhixian , Chen Qingfeng , Lan Wei , Pan Haiming , Hao Xinkun , Pan Shirui
Published: April 2021

Identifying drug–target interaction (DTI) is the basis for drug development. However, the method of using biochemical experiments to discover drug-target interactions has low coverage and high costs. Many computational methods have been developed to predict potential drug-target interactions based on known drug-target interactions, but the accuracy of these methods still needs to be improved. In this article, a graph autoencoder approach for DTI prediction (GADTI) was proposed to discover potential interactions between drugs and targets using a heterogeneous network, which integrates diverse drug-related and target-related datasets. Its encoder consists of two components: a graph convolutional network (GCN) and a random walk with restart (RWR). And the decoder is DistMult, a matrix factorization model, using embedding vectors from encoder to discover potential DTIs. The combination of GCN and RWR can provide nodes with more information through a larger neighborhood, and it can also avoid over-smoothing and computational complexity caused by multi-layer message passing. Based on the 10-fold cross-validation, we conduct three experiments in different scenarios. The results show that GADTI is superior to the baseline methods in both the area under the receiver operator characteristic curve and the area under the precision–recall curve. In addition, based on the latest Drugbank dataset (V5.1.8), the case study shows that 54.8% of new approved DTIs are predicted by GADTI.
Genome-Wide Association Mapping of Seedling Biomass and Root Traits Under Different Water Conditions in Wheat
Authors: Fatima Iza , Gao Yutian , Xu Xiangru , Jin Jingjing , Duan Shuonan , Zhen Wenchao , Xie Chaojie , Ma Jun
Published: April 2021

Drought is a major threat to global wheat production. In this study, an association panel containing 200 Chinese wheat germplasms was used for genome-wide association studies (GWASs) of genetic loci associated with eight root and seedling biomass traits under normal water and osmotic stress conditions. The following traits were investigated in wheat seedlings at the four-leaf stage: root length (RL), root number (RN), root fresh weight (RFW), root dry weight (RDW), shoot fresh weight (SFW), shoot dry weight (SDW), total fresh weight (TFW), and total dry weight (TDW). A total of 323 and 286 SNPs were detected under two water environments, respectively. Some of these SNPs were near known loci for root traits. Eleven SNPs on chromosomes 1B, 2B, 4B, and 2D had pleiotropic effects on multiple traits under different water conditions. Further analysis indicated that several genes located inside the 4 Mb LD block on each side of these 11 SNPs were known to be associated with plant growth and development and thus may be candidate genes for these loci. Results from this study increased our understanding of the genetic architecture of root and seedling biomass traits under different water conditions and will facilitate the development of varieties with better drought tolerance.
Post-Translational Regulations of Foxp3 in Treg Cells and Their Therapeutic Applications
Authors: Dong Yi , Yang Cuiping , Pan Fan
Published: April 2021

Regulatory T (Treg) cells are indispensable for immune homeostasis due to their roles in peripheral tolerance. As the master transcription factor of Treg cells, Forkhead box P3 (Foxp3) strongly regulates Treg function and plasticity. Because of this, considerable research efforts have been directed at elucidating the mechanisms controlling Foxp3 and its co-regulators. Such work is not only advancing our understanding on Treg cell biology, but also uncovering novel targets for clinical manipulation in autoimmune diseases, organ transplantation, and tumor therapies. Recently, many studies have explored the post-translational regulation of Foxp3, which have shown that acetylation, phosphorylation, glycosylation, methylation, and ubiquitination are important for determining Foxp3 function and plasticity. Additionally, some of these targets have been implicated to have great therapeutic values. In this review, we will discuss emerging evidence of post-translational regulations on Foxp3 in Treg cells and their exciting therapeutic applications.
Regulation of B Lymphocyte Development by Histone H2A Deubiquitinase BAP1
Authors: Lin Yun Hsiao , Liang Yue , Wang HanChen , Tung Lin Tze , Förster Michael , Subramani Poorani Ganesh , Di Noia Javier M. , Clare Simon , Langlais David , Nijnik Anastasia
Published: April 2021

BAP1 is a deubiquitinase (DUB) of the Ubiquitin C-terminal Hydrolase (UCH) family that regulates gene expression and other cellular processes,viadeubiquitination of histone H2AK119ub and other substrates. BAP1 is an important tumor suppressor in human, expressed and functional across many cell-types and tissues, including those of the immune system. B lymphocytes are the mediators of humoral immune response, however the role of BAP1 in B cell development and physiology remains poorly understood. Here we characterize a mouse line with a selective deletion of BAP1 within the B cell lineage (Bap1fl/flmb1-Cre) and establish a cell intrinsic role of BAP1 in the regulation of B cell development. We demonstrate a depletion of large pre-B cells, transitional B cells, and mature B cells inBap1fl/flmb1-Cremice. We characterize broad transcriptional changes in BAP1-deficient pre-B cells, map BAP1 binding across the genome, and analyze the effects of BAP1-loss on histone H2AK119ub levels and distribution. Overall, our work establishes a cell intrinsic role of BAP1 in B lymphocyte development, and suggests its contribution to the regulation of the transcriptional programs of cell cycle progression,viathe deubiquitination of histone H2AK119ub.
A Mouse Model of PPRV Infection for Elucidating Protective and Pathological Roles of Immune Cells
Authors: Sharma Yashu , Sarkar Roman , Jain Ayush , Singh Sudhakar , Shekhar Chander , Shanmugam Chandrasekar , Dhanavelu Muthuchelvan , Tembhurne Prabhakar , Kaul Rajeev , Sehrawat Sharvan
Published: April 2021

The study was aimed at developing an accessible laboratory animal model to elucidate protective and pathological roles of immune mediators during Peste des petits ruminants virus (PPRV) infection. It is because of the critical roles of type I IFNs in anti-viral defense, we assessed the susceptibility of IFN receptor knock out (IFNR KO) mice to PPRV infection. IFNR KO mice were exceedingly susceptible to the infection but WT animals efficiently controlled PPRV. Accordingly, the PPRV infected IFNR KO mice gradually reduced their body weights and succumbed to the infection within 10 days irrespective of the dose and route of infection. The lower infecting doses predominantly induced immunopathological lesions. The viral antigens as well as the replicating PPRV were abundantly present in most of the critical organs such as brain, lungs, heart and kidneys of IFNR KO mice infected with high dose of the virus. Neutrophils and macrophages transported the replicating virus to central nervous system (CNS) and contributed to pathology while the elevated NK and T cell responses directly correlated with the resolution of PPRV infection in WT animals. Using an array of fluorescently labeled H-2Kb tetramers, we discovered four immunogenic epitopes of PPRV. The PPRV-peptides interacted well with H-2Kb in acellular and cellular assay as well as expanded the virus-specific CD8+ T cells in immunized or infected mice. Adoptively transferred CD8+ T cells helped control PPRV in infected mice. Our study therefore established and employed a mouse model for investigating the pathogenesis of PPRV. The model could be useful for elucidating the contribution of immune cells in disease progression as well as to test anti-viral agents.
Higher Risk for Sjögren’s Syndrome in Patients With Fibromyalgia: A Nationwide Population-Based Cohort Study
Authors: Gau Shuo-Yan , Leong Pui-Ying , Lin Cheng-Li , Tsou Hsi-Kai , Wei James Cheng-Chung
Published: April 2021

Objectives

Clinically, associations have been observed between Sjögren’s syndrome and fibromyalgia. Nonetheless, population-based evidence evaluating the risk of Sjögren’s syndrome in fibromyalgia patients is lacking. The main purpose of this retrospective cohort study was to determine the association between fibromyalgia and subsequent development of Sjögren’s syndrome.

Methods

This retrospective cohort study extracted data from the Longitudinal Health Insurance Database (LHID) of the Taiwan National Health Insurance (NHI). During 2000-2012, patients with newly-diagnosed fibromyalgia (International Classification of Diseases, Ninth Revision, Clinical Modification code 729.1) were defined as the exposure cohort. Age- and gender-matched individuals without fibromyalgia were used as the comparison cohort. The adjusted hazard ratios (aHR) for the occurrence of Sjögren’s syndrome in those with fibromyalgia were evaluated along with stratified analyses of different subgroups.

Results

Of the 149,706 subjects whose data were extracted from the LHID, 74,853 subjects had coded fibromyalgia and 74,853 control subjects were without fibromyalgia. Compared to the control group, patients with fibromyalgia had an aHR of 2.00 (95% Confidence Interval [CI], 1.52-2.61) for developing Sjögren’s syndrome. In fibromyalgia patients aged 20-49 years, the aHR for future Sjögren’s syndrome was 3.07 (95% CI, 1.92-4.89).

Conclusion

Patients with fibromyalgia, both males and females, have a higher risk for developing Sjögren’s syndrome than those without fibromyalgia, especially those aged 20-49 years. While managing patients, clinicians should be aware of the bidirectional association between the two diseases, which helps to understand the impact of the association on disease activity and diagnosis.