bluuebunny/crossref_metadata_2025 huggingface dataset:
Roles of Cardiometabolic Factors in Mediating the Causal Effect of Type 2 Diabetes on Cardiovascular Diseases: A Two-Step, Two-Sample Multivariable Mendelian Randomization Study
Authors: Chen Ken , Zhuang Zhenhuang , Shao Chunli , Zheng Jilin , Zhou Qing , Dong Erdan , Huang Tao , Tang Yi-Da
Published: February 2022

Objective

The objective of this study is to investigate the roles of cardiometabolic factors (including blood pressure, blood lipids, thyroid function, body mass, and insulin sensitivity) in mediating the causal effect of type 2 diabetes (T2DM) on cardiovascular disease (CVD) outcomes.

Design

Two-step, two-sample multivariable Mendelian randomization (MVMR) study.

Setting

International genome-wide association study (GWAS) consortia data.

Exposure

Type 2 diabetes, blood pressure: systolic blood pressure (SBP), diastolic blood pressure (DBP); blood lipids: low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG); thyroid function: hyperthyroidism, hypothyroidism; body mass index (BMI), waist-hip-ratio (WHR), and insulin sensitivity.

Main Outcomes

Cardiovascular disease includes coronary heart disease (CHD), myocardial infarction (MI), and stroke.

Methods

Summary-level data for exposures and main outcomes were extracted from GWAS consortia. We used two-sample MR to illustrate the causal effect of T2DM on CVD subtypes and regression-based MVMR to quantify the possible mediation effects of cardiometabolic factors on CVD.

Results

Each additional unit of log odds of T2DM increased 16% risk of CHD [odds ratio (OR): 1.16, 95% CI: 1.12–1.21], 15% risk of myocardial infarction (MI) (OR: 1.15, 95% CI: 1.10–1.20), and 10% risk of stroke (OR: 1.10, 95% CI: 1.06–1.13). In mediation analysis, SBP, DBP, and TG were found as main mediators, while the mediation effects of other cardiometabolic factors were not significant. The proportion of total effect of T2DM on CHD mediated by SBP, DBP, and TG was 16% (95% CI: 8–24%), 7% (95% CI: 1–13%) and 10% (95% CI: 2–18%), respectively. Mediation effect of SBP and DBP on MI and stroke, TG on MI was also prominent, while mediation effect of TG on stroke was not significant. The combined mediation effect of all the three mediators accounted for 29%, 26%, and 13% of the total effect of T2DM on CHD, MI, and stroke, respectively.

Conclusion

Systolic blood pressure, DBP, and TG mediate a substantial proportion of the causal effect of T2DM on CVD and thus interventions on these factors might reduce the considerable excess risk of CVD among patients with T2DM.
Left Ventricular Strain Is Associated With Myocardial Recovery Following ST-Elevation Myocardial Infarction, a Prospective Longitudinal CMR Study
Authors: Taha Mohamad B. , Jeng Eric I. , Salerno Michael , Moguillansky Diego , Keeley Ellen C. , Al-Ani Mohammad A.
Published: February 2022

Background

Infarct size following ST-elevation myocardial infarction (STEMI) is an important determinate of left ventricular (LV) dysfunction and cardiovascular morbidity and mortality. Cardiac magnetic resonance feature tracking (CMR-FT) is a technique that allows for the assessment of myocardial function via quantification of longitudinal, radial, and circumferential strain. We investigated the association between CMR-FT-derived myocardial global strain and myocardial recovery.

Methods

A prospective study on patients presenting with STEMI treated with primary percutaneous coronary intervention (PCI) was conducted. CMR imaging was obtained at two interval time points, the baseline within 2 weeks of hospital discharge and follow-up at 6 months. Strain analysis was performed via FT-CMR, and recovery was quantified by the area of late gadolinium enhancement (LGE).

Results

A total of n = 14 patients met inclusion and exclusion criteria and were analyzed. There was a significant reduction in the infarct size, as measured by LGE mass percentage of the left ventricular muscle mass, between the initial and follow-up CMR (19.7%, IQR 12.2–23.9 vs. 17.1%, IQR 8.3–22.5, p = 0.04). Initial strain parameters were inversely correlated with the initial edema mass and the decrease in LGE mass between the initial and follow-up CMR. All LV global strains had high accuracy for the prediction of a reduction in LGE mass by 50% or more.

Conclusions

LV global strains measured after primary PCI can predict the extent of myocardial recovery.
Mobility Signatures: A Tool for Characterizing Cities Using Intercity Mobility Flows
Authors: Astero Maryam , Huang Zhiren , Saramäki Jari
Published: February 2022

Understanding the patterns of human mobility between cities has various applications from transport engineering to spatial modeling of the spreading of contagious diseases. We adopt a city-centric, data-driven perspective to quantify such patterns and introduce the mobility signature as a tool for understanding how a city (or a region) is embedded in the wider mobility network. We demonstrate the potential of the mobility signature approach through two applications that build on mobile-phone-based data from Finland. First, we use mobility signatures to show that the well-known radiation model is more accurate for mobility flows associated with larger Finnish cities, while the traditional gravity model appears a better fit for less populated areas. Second, we illustrate how the SARS-CoV-2 pandemic disrupted the mobility patterns in Finland in the spring of 2020. These two cases demonstrate the ability of the mobility signatures to quickly capture features of mobility flows that are harder to extract using more traditional methods.
Volcanic Ash and Small Uncrewed Aerial Vehicle (sUAV) Interaction: In-situ Observations and Laboratory Experiments on Aircraft Failure
Authors: Brosch Ermanno
Published: February 2022

The deployment of small uncrewed aerial vehicles (sUAVs) for volcanological applications has grown over the last decade, mainly attributed to the development of affordable, smaller, and versatile platforms. However, the use of sUAVs in active volcanic regions is a challenging operation conducted under extreme environmental conditions. The here reported unsuccessful deployment of an sUAV at Stromboli volcano shows that the aircraft functionality was impaired by airborne volcanic ash, which led to an uncontrolled landing of the aircraft. Laboratory analyses confirmed the presence of volcanic material inside the motors, which is attributed to have caused motor blockage of the sUAV on Stromboli volcano while the aircraft was engulfed by a rising ash plume. Laboratory experiments were conducted to investigate the interaction between volcanic ash and an sUAV motor-propeller assemble. The experiments reproduced the incorporation of ash-sized particles into the motor, proving that volcanic ash can enter the rotating motor while the sUAV is airborne. This shows that ash ingestion into the sUAV at Stromboli volcano resulted in operational failure. These findings shall aid in developing advanced and reliable sUAVs that can extend current deployment opportunities in volcanic environments.
Community-Anchored Assessment of Indigenous Second Language Learning in K-12 Schools
Authors: Tulloch Shelley , Moore Sylvia , Lane Jodie , Townley Sarah , Dicker Joan , Boase Doris , Adams Ellen
Published: February 2022

Indigenous second language programs in K-12 schools contribute to culturally nourishing education and to the revitalization of Indigenous languages. Assessing Indigenous second language learning presents particular opportunities and challenges based on the linguistic, historical, political, cultural, and social contexts in and for which the Indigenous language is being taught and learned. The self-governing Inuit region of Nunatsiavut is concerned with developing effective and appropriate tools for assessing students’ Inuttitut in order to evaluate how well K-12 programs are working so far, identify the basis on which future K-12 Inuttitut curriculum may be developed, and support ongoing assessment of learning and for learning in Inuttitut classrooms. This article discusses ways in which Inuit teachers in Nunatsiavut and a curriculum evaluation team have developed and implemented assessment tools and practices to evaluate Inuttitut learning in Nunatsiavut area K-12 schools. We discuss how Indigenous language learning and assessment, even when it occurs as part of an official school program, can be anchored in families and community. Families and communities need to be part of establishing language learning goals. Inuit teachers are drawing in full community resources and building a community of practice including Elders, other language speakers, leaders, principals, and teachers, to support and create contexts for community-anchored Inuttitut learning and assessment.
Research on Technological Pedagogical and Content Knowledge: A Bibliometric Analysis From 2011 to 2020
Authors: Lee Hung-Ying , Chung Chi-Yang , Wei Ge
Published: February 2022

This study was to explore the bibliometric characteristics of TPACK from 2011 to 2020. By using the keyword “TPACK,” the bibliographic references have been retrieved from the Scopus databases (date of search: March 7, 2021). The VOSviewr software tool and Bibliometrix R package were used for information analysis. The results confirmed that there are 700 articles, representing 63 countries and 159 journals scanned. Articles in 2013 were cited the most times, and since 2016, the number of articles is on the rise every year. The United States, Turkey, and Australia were the three leading countries in this field. Most of the articles were published in educational technology journals. The total articles published by American institutions are more than the others, followed by Asian institutions. The most prolific authors are all Asians, followed by Americans. Core themes from the highly cited articles have been surrounding PCK, teacher education, skill, and pedagogy. The development of TPACK has gradually turned to practical strategies and tried to find strategic ways to facilitate teachers to implement technology-assisted teaching.
Water Extract of Rhizoma Drynaria Selectively Exerts Estrogenic Activities in Ovariectomized Rats and Estrogen Receptor-Positive Cells
Authors: Zhou Liping , Wong Ka-Ying , Poon Christina Chui-Wa , Yu Wenxuan , Xiao Huihui , Chan Chi-On , Mok Daniel Kam-Wah , Wong Man-Sau
Published: February 2022

Our previous study demonstrated that the bone protective actions of herbal medicine Rhizoma Drynariae (Gusuibu, RD) were mainly mediated by flavonoid phytoestrogens via estrogen receptors, raising concerns about the safety of using RD as it may induce estrogen-like risk-benefit profile and interact with other ER ligands, such as selective estrogen receptor modulators (SERMs), when coadministered. The present study evaluated the estrogenic activities of RD and its potential interaction with tamoxifen, a SERM, in estrogen-sensitive tissues by using mature ovariectomized (OVX) rats and ER-positive cells. Similar to but weaker than tamoxifen, RD at its clinical dose dramatically ameliorated OVX-induced changes in bone and dopamine metabolism-related markers in OVX rats. However, tamoxifen, but not RD, induced uterotrophic effects. No significant alteration in mammary gland was observed in OVX rats treated with RD, which was different from the inhibitory actions of tamoxifen. The two-way ANOVA results indicated the interactions between RD and tamoxifen in the bone, brain, and uterus of OVX rats while RD did not alter their responses to tamoxifen. Our results demonstrate that RD selectively exerts estrogenic actions in a different manner from tamoxifen. Moreover, RD interacts with tamoxifen without altering its effects in OVX rats.
Intelligent Online Health Estimation for Lithium-Ion Batteries Based on a Parallel Attention Network Combining Multivariate Time Series
Authors: Tan Xiaojun , Liu Xiaoxi , Wang Huanyu , Fan Yuqian , Feng Guodong
Published: February 2022

With the development of cloud and edge computing, data-driven methods for estimating a Li-ion battery’s state of health are becoming increasingly attractive. However, existing data-driven estimation methods have problems of low accuracy and weak robustness that need to be solved. Focusing on these points, this paper proposes a parallel attention network combining multivariate time series to extract the mapping relationship between the selected health features and the state of health. First, multivariate time series are extracted, which can describe battery aging characteristics at different scales. Then, a novel parallel learning framework is designed by integrating long short-term memory cells and an attention mechanism, which can make full use of the health features and help to solve the challenging issues of estimation accuracy and robustness. Experimental results show that the proposed model is able to obtain estimation results for different batteries with a mean absolute percentage error of less than 1%. Compared with existing methods, the maximum error of the proposed model is 38% lower on average. Furthermore, even under measurement noise injections of 50 dB, a preferable estimation result (maximum error of 3.36%) can still be achieved.
How Arsenic, an Inorganic Pollutant, is Involved in the Physiology of Biomolecular Condensates in the Cell
Authors: Udagawa Osamu , Hirano Seishiro
Published: February 2022

The existence of membrane-less organelles in the cells has been known for a relatively long time. Of the membrane-less organelles, stress granules, processing bodies, and PML-NBs have been intensively investigated in relation to arsenic. The membrane-less organelles, which concentrate biomolecules (proteins, nucleic acids), have recently been shown to self-organize by means of phase separation/transition. These biomolecular condensates (membrane-less organelles) can provide local enhancement of the efficiency of specific reactions. The biomolecular condensates have attracted dramatic attention over the last decade because highly organized biochemical complexes in the cell have long been understood by the membrane-dependent compartmentalization. In this mini review, we highlight the initiation of phase separation for each biomolecular condensate in which arsenic could be involved. We further reflect on the adequacy of the arsenic-dependent ROS levels for the formation of biomolecular condensates. These perspectives led us to re-evaluate the biological action of arsenic from a biophysical and bio-rheological point of view.
Detecting Tuberculosis-Consistent Findings in Lateral Chest X-Rays Using an Ensemble of CNNs and Vision Transformers
Authors: Rajaraman Sivaramakrishnan , Zamzmi Ghada , Folio Les R. , Antani Sameer
Published: February 2022

Research on detecting Tuberculosis (TB) findings on chest radiographs (or Chest X-rays: CXR) using convolutional neural networks (CNNs) has demonstrated superior performance due to the emergence of publicly available, large-scale datasets with expert annotations and availability of scalable computational resources. However, these studies use only the frontal CXR projections, i.e., the posterior-anterior (PA), and the anterior-posterior (AP) views for analysis and decision-making. Lateral CXRs which are heretofore not studied help detect clinically suspected pulmonary TB, particularly in children. Further, Vision Transformers (ViTs) with built-in self-attention mechanisms have recently emerged as a viable alternative to the traditional CNNs. Although ViTs demonstrated notable performance in several medical image analysis tasks, potential limitations exist in terms of performance and computational efficiency, between the CNN and ViT models, necessitating a comprehensive analysis to select appropriate models for the problem under study. This study aims to detect TB-consistent findings in lateral CXRs by constructing an ensemble of the CNN and ViT models. Several models are trained on lateral CXR data extracted from two large public collections to transfer modality-specific knowledge and fine-tune them for detecting findings consistent with TB. We observed that the weighted averaging ensemble of the predictions of CNN and ViT models using the optimal weights computed with the Sequential Least-Squares Quadratic Programming method delivered significantly superior performance (MCC: 0.8136, 95% confidence intervals (CI): 0.7394, 0.8878, p < 0.05) compared to the individual models and other ensembles. We also interpreted the decisions of CNN and ViT models using class-selective relevance maps and attention maps, respectively, and combined them to highlight the discriminative image regions contributing to the final output. We observed that (i) the model accuracy is not related to disease region of interest (ROI) localization and (ii) the bitwise-AND of the heatmaps of the top-2-performing models delivered significantly superior ROI localization performance in terms of mean average precision [mAP@(0.1 0.6) = 0.1820, 95% CI: 0.0771,0.2869, p < 0.05], compared to other individual models and ensembles. The code is available at https://github.com/sivaramakrishnan-rajaraman/Ensemble-of-CNN-and-ViT-for-TB-detection-in-lateral-CXR.
The Interactions Between Autoinflammation and Type 2 Immunity: From Mechanistic Studies to Epidemiologic Associations
Authors: Sylvester McKella , Son Aran , Schwartz Daniella M.
Published: February 2022

Autoinflammatory diseases are a group of clinical syndromes characterized by constitutive overactivation of innate immune pathways. This results in increased production of or responses to monocyte- and neutrophil-derived cytokines such as interleukin-1β (IL-1β), Tumor Necrosis Factor-α (TNF-α), and Type 1 interferon (IFN). By contrast, clinical allergy is caused by dysregulated type 2 immunity, which is characterized by expansion of T helper 2 (Th2) cells and eosinophils, as well as overproduction of the associated cytokines IL-4, IL-5, IL-9, and IL-13. Traditionally, type 2 immune cells and autoinflammatory effectors were thought to counter-regulate each other. However, an expanding body of evidence suggests that, in some contexts, autoinflammatory pathways and cytokines may potentiate type 2 immune responses. Conversely, type 2 immune cells and cytokines can regulate autoinflammatory responses in complex and context-dependent manners. Here, we introduce the concepts of autoinflammation and type 2 immunity. We proceed to review the mechanisms by which autoinflammatory and type 2 immune responses can modulate each other. Finally, we discuss the epidemiology of type 2 immunity and clinical allergy in several monogenic and complex autoinflammatory diseases. In the future, these interactions between type 2 immunity and autoinflammation may help to expand the spectrum of autoinflammation and to guide the management of patients with various autoinflammatory and allergic diseases.
Estradiol Ameliorates Acute Kidney Ischemia-Reperfusion Injury by Inhibiting the TGF-βRI-SMAD Pathway
Authors: Ren Lian , Li Fang , Di Ziyang , Xiong Yan , Zhang Shichen , Ma Qing , Bian Xiaoen , Lang Zhiquan , Ye Qifa , Wang Yanfeng
Published: February 2022

Renal ischemia–reperfusion injury (IRI) is less extensive in females than males in both animals and humans; however, this protection diminishes after menopause, suggesting that estrogen plays a pivotal role in IRI, but the underlying mechanism remains largely unknown. Our study found that 45 min of warm ischemia was sufficient to induce significant pathological changes without causing death in model animals. Compared with male rats, female rats exhibited less extensive apoptosis, kidney injury, and fibrosis; these effects were worsened in ovariectomized (OVX) rats and ameliorated upon estradiol (E2) supplementation. Furthermore, the levels of TGF-βRI, but not TGF-βRII or TGF-β1, were significantly increased in OVX rats, accompanied by phosphorylated SMAD2/3 activation. Interestingly, the alteration trend of the nuclear ERα level was opposite that of TGF-βRI. Furthermore, dual luciferase reporter and chromatin immunoprecipitation assays showed that ERα could bind to the promoter region of TGF-βRI and negatively regulate its mRNA expression. Moreover, an in vitro study using NRK-52E cells showed that ERα knockdown blocked E2-mediated protection, while TGF-βRI knockdown protected cells against hypoxic insult. The findings of this study suggest that renal IRI is closely related to the TGF-βRI-SMAD pathway in females and that E2 exert its protective effect via the ERα-mediated transcriptional inhibition of TGF-βRI expression.
Low-Molecular-Weight Heparin Versus Aspirin in Early Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis
Authors: Xia Hui , Wang Ziyao , Tian Min , Liu Zunjing , Zhou Zhenhua
Published: February 2022

Objectives

To evaluate the difference between low-molecular-weight heparin (LMWH) and aspirin in preventing early neurological deterioration (END) and recurrent ischemic stroke (RIS), post-recovery independence, and safety outcomes in acute ischemic stroke.

Materials and Methods

We performed systematic searches of the PubMed, Embase, Web of Science, and Cochrane Library databases for full-text articles of randomized controlled trials (RCTs) of LMWH vs. aspirin in the early management of acute ischemic stroke. Information on study design, eligibility criteria, baseline information, and outcomes was extracted. Synthesized relative risks (RRs) with 95% confidence intervals (CIs) are used to present the differences between the two treatments based on fixed-effects models.

Results

Five RCTs were retrieved from the online databases. The results showed no significant difference in efficacy outcomes between the two groups among unselected patients. Subgroup analysis showed that LMWH was significantly related to a lower incidence of END events [relative risk (RR): 0.44, 95% confidence interval (CI): 0.35–0.56] and reduced occurrence of RIS during treatment (OR: 0.34, 95% CI: 0.16–0.75) in non-cardioembolic stroke. LMWH significantly increased the number of patients with a modified Rankin scale (mRS) score of 0–1 at 6 months in patients with large-artery occlusive disease (LAOD) (RR: 0.50, 95% CI: 0.27–0.91). LMWH had a similar effect on symptomatic intracranial hemorrhage (sICH) and major extracranial hemorrhage during treatment to that of aspirin, except that LMWH was related to an increased likelihood of extracranial hemorrhage.

Conclusions

In patients with acute non-cardioembolic ischemic stroke, especially that with large-artery stenosis, LMWH treatment significantly reduced the incidence of END and RIS, and improved the likelihood of independence (mRS 0–1) at 6 months compared with those with aspirin treatment. LMWH was related to an increased likelihood of extracranial hemorrhage among all patients; however, the difference in major extracranial hemorrhage and sICH was not significant. Choosing the appropriate patients and paying attention to the start time and duration of treatment are very important in the use of anticoagulation.

Systematic Review Registration

http://www.crd.york.ac.uk/PROSPERO, identifier CRD42020185446.
Microbiome Resilience and Health Implications for People in Half-Year Travel
Authors: Cheng Mingyue , Liu Hong , Han Maozhen , Li Shuai Cheng , Bu Dongbo , Sun Shiwei , Hu Zhiqiang , Yang Pengshuo , Wang Rui , Liu Yawen , Chen Feng , Peng Jianjun , Peng Hong , Song Hongxing , Xia Yang , Chu Liqun , Zhou Quan , Guan Feng , Wu Jing , Tan Guangming , Ning Kang
Published: February 2022

Travel entail change in geography and diet, both of which are known as determinant factors in shaping the human gut microbiome. Additionally, altered gut microbiome modulates immunity, bringing about health implications in humans. To explore the effects of the mid-term travel on the gut microbiome, we generated 16S rRNA gene and metagenomic sequencing data from longitudinal samples collected over six months. We monitored dynamic trajectories of the gut microbiome variation of a Chinese volunteer team (VT) in their whole journey to Trinidad and Tobago (TAT). We found gut microbiome resilience that VT’s gut microbial compositions gradually transformed to the local TAT’s enterotypes during their six-month stay in TAT, and then reverted to their original enterotypes after VT’s return to Beijing in one month. Moreover, we identified driven species in this bi-directional plasticity that could play a role in immunity modulation, as exemplified by Bacteroides dorei that attenuated atherosclerotic lesion formation and effectively suppressed proinflammatory immune response. Another driven species P. copri could play a crucial role in rheumatoid arthritis pathogenesis, a chronic autoimmune disease. Carbohydrate-active enzymes are often implicated in immune and host-pathogen interactions, of which glycoside hydrolases were found decreased but glycosyltransferases and carbohydrate esterases increased during the travel; these functions were then restored after VT’ returning to Beijing. Furthermore, we discovered these microbial changes and restoration were mediated by VT people’s dietary changes. These findings indicate that half-year travel leads to change in enterotype and functional patterns, exerting effects on human health. Microbial intervention by dietary guidance in half-year travel would be conducive to immunity modulation for maintaining health.
Nocturnal Eyes in Slipper Lobsters (Decapoda Scyllaridae): Physiological and Ecological Implications of Habitat Depths for Visual Traits
Authors: Hayasaka Oki , Chang Hao-Yi , Li Li-Chun , Tseng Yung-Che , Shao Yi Ta
Published: February 2022

The light characteristics of an ecosystem drive evolutionary adaptations in visual traits, enhancing the diversity and abundance of species living there. The visual systems of crustaceans are highly diverse and often correspond to the optical properties of their preferred environments. Although habitat depth is known to greatly influence visual specialization in marine crustaceans, it remains unclear whether depth drives visual adaptions in nocturnal species. Slipper lobsters (Scyllaridae) are nocturnal benthic marine crustaceans distributed throughout a wide range of depths. In order to understand the visual adaptive capabilities of slipper lobsters inhabiting different depths, we characterized the eye structures of a shallow-water species (Parribacus japonicas), an intermediate-depth species (Scyllarides squammosus) and a deep-water species (Ibacus novemdentatus). Moreover, we measured by electroretinogram (ERG) the spectral sensitivities and temporal resolutions for each species using the following light stimuli: UV (λmax 386 nm), blue (λmax 462 nm), green (λmax 518 nm), yellow (λmax 590 nm), and red (λmax 632 nm). Our histological experiments show that all three species possess a typical superposition compound eye with square facets, and their ERG measurements revealed a single sensitivity peak for each species. Notably, peak spectral sensitivity corresponded to habitat depth, with the estimated peak for I. novemdentatus (493.0 ± 9.8 nm) being similar to that of S. squammosus (517.4 ± 2.1 nm), but lower than that of P. japonicus (537.5 ± 9.9 nm). Additionally, the absolute sensitivities at respective peak wavelengths for I. novemdentatus and P. japonicus were higher than that of S. squammosus. No differences were observed among the three species for maximum critical flicker fusion frequency (CFFmax) across light stimuli. However, P. japonicus had lower CFFmax values than the other two species. These data suggest that all three nocturnal slipper lobsters are likely monochromatic and well adapted to dim light environments. Significantly, the deep-water slipper lobster displayed higher spectral sensitivities at shorter wavelengths than the shallow water species, but temporal resolution was not compromised.
Incident Gout: Risk of Death and Cause-Specific Mortality in Western Sweden: A Prospective, Controlled Inception Cohort Study
Authors: Dehlin Mats , Sandström Tatiana Zverkova , Jacobsson Lennart TH
Published: February 2022

Background

Excess mortality in gout has been attributed to cardiovascular diseases (CVD). Considering the decline in CVD mortality in the general population, we wanted to evaluate overall mortality in gout and cause-specific contributions to mortality beyond CVD and temporal trends.

Methods

All incident cases of gout between 2006 and 2015 in western Sweden and 5 population controls per case matched for age, sex, and county were identified. Comorbidities were identified for 5 years preceding the index date. Follow-up ended at death, migration, or end of study on December 2017. Effect of gout on death risk was calculated using COX regression on the whole population and stratified by sex, adjusted for demographics, and comorbidities. Death incidence rates were compared between the two time periods, 2006–2010 and 2011–2015.

Results

We identified 22,055 cases of incident gout and 98,946 controls, median age (Q1, Q3) 69–68 (57, 79/56, 78) years and 67.6–66.5% males. Except for dementia, all comorbidities were significantly more common at baseline among gout cases. Overall, the risk for death in incident gout was neither increased overall nor in men, but women had a 10% elevated risk. In adjusted models for cause-specific mortality, death from CVD, renal disease, and digestive system diseases were significantly increased in the total gout population while death from dementia, cancer, and lung diseases were significantly decreased. There were no significant differences in overall incident death rate ratios between cases and controls in the two time periods examined.

Conclusions

An increased risk for CVD, renal disease, and diseases of the digestive system in patients with gout highlights the importance of addressing CVD risk factors in gout management. Gout was associated with reduced mortality from dementia, which may have implications on urate lowering therapy and possible effects on dementia risk.
Progression-Free Survival Prediction in Small Cell Lung Cancer Based on Radiomics Analysis of Contrast-Enhanced CT
Authors: Chen Ningxin , Li Ruikun , Jiang Mengmeng , Guo Yixian , Chen Jiejun , Sun Dazhen , Wang Lisheng , Yao Xiuzhong
Published: February 2022

Purposes and Objectives

The aim of this study was to predict the progression-free survival (PFS) in patients with small cell lung cancer (SCLC) by radiomic signature from the contrast-enhanced computed tomography (CT).

Methods

A total of 186 cases with pathological confirmed small cell lung cancer were retrospectively assembled. First, 1,218 radiomic features were automatically extracted from tumor region of interests (ROIs) on the lung window and mediastinal window, respectively. Then, the prognostic and robust features were selected by machine learning methods, such as (1) univariate analysis based on a Cox proportional hazard (CPH) model, (2) redundancy removing using the variance inflation factor (VIF), and (3) multivariate importance analysis based on random survival forests (RSF). Finally, PFS predictive models were established based on RSF, and their performances were evaluated using the concordance index (C-index) and the cumulative/dynamic area under the curve (C/D AUC).

Results

In total, 11 radiomic features (6 for mediastinal window and 5 for lung window) were finally selected, and the predictive model constructed from them achieved a C-index of 0.7531 and a mean C/D AUC of 0.8487 on the independent test set, better than the predictions by single clinical features (C-index = 0.6026, mean C/D AUC = 0.6312), and single radiomic features computed in lung window (C-index = 0.6951, mean C/D AUC = 0.7836) or mediastinal window (C-index = 0.7192, mean C/D AUC = 0.7964).

Conclusion

The radiomic features computed from tumor ROIs on both lung window and mediastinal window can predict the PFS for patients with SCLC by a high accuracy, which could be used as a useful tool to support the personalized clinical decision for the diagnosis and patient management of patients with SCLC.
Understanding the Unique Microenvironment in the Aging Liver
Authors: Zhao Yalei , Yang Ya , Li Qian , Li Jianzhou
Published: February 2022

In the past decades, many studies have focused on aging because of our pursuit of longevity. With lifespans extended, the regenerative capacity of the liver gradually declines due to the existence of aging. This is partially due to the unique microenvironment in the aged liver, which affects a series of physiological processes. In this review, we summarize the related researches in the last decade and try to highlight the aging-related alterations in the aged liver.
Diversity Among Cyanobacterial Photosystem I Oligomers
Authors: Chen Ming , Liu Xuan , He Yujie , Li Ningning , He Jun , Zhang Ying
Published: February 2022

Unraveling the oligomeric states of the photosystem I complex is essential to understanding the evolution and native mechanisms of photosynthesis. The molecular composition and functions of this complex are highly conserved among cyanobacteria, algae, and plants; however, its structure varies considerably between species. In cyanobacteria, the photosystem I complex is a trimer in most species, but monomer, dimer and tetramer arrangements with full physiological function have recently been characterized. Higher order oligomers have also been identified in some heterocyst-forming cyanobacteria and their close unicellular relatives. Given technological progress in cryo-electron microscope single particle technology, structures of PSI dimers, tetramers and some heterogeneous supercomplexes have been resolved into near atomic resolution. Recent developments in photosystem I oligomer studies have largely enriched theories on the structure and function of these photosystems.
Internal pH and Acid Anion Accumulation in Listeria monocytogenes and Escherichia coli Exposed to Lactic or Acetic Acids at Mildly Acidic pH
Authors: Branson Savannah R. , Broadbent Jeff R. , Carpenter Charles E.
Published: February 2022

Organic acids are widely employed in the food industry to control growth of microbial pathogens such as Listeria monocytogenes and Escherichia coli. There is substantial evidence that intracellular accumulation of acid anions is a major inhibitor to cell viability, and that some bacteria are able to combat the toxic effects of anion accumulation via their ability to continue active metabolism at a lower intracellular pH (pHi). This study followed the accumulation of acid anion into the cell pellet and parallel changes in pHi in two human pathogenic strains of L. monocytogenes (N1-227 and R2-499) and in E. coli O157:H7 after exposure to sub-bacteriostatic levels of lactic and acetic acids at mildly acidic pH 6. The methodology employed in these studies included independent measures of pHi and intracellular anion accumulation. For the latter work, cells were pelleted through bromododecane to strip off extracellular water and solutes. Listeria strains accumulated 1.5-fold acetate or 2.5-fold lactate as compared to the external environment while mounting a defense against anion accumulation that included up to a 1-unit pHi drop from 7.5 to 6.5 for strain R2-499. E. coli accumulated 2.5-fold acetate but not lactate and apparently made use of combat mechanisms other than lowering pHi not explored in this study. Inulin was employed to estimate the fractional volume of cell pellet present as intracellular space. That intracellular fraction was 0.24 for E. coli, which infers that acid accumulation into the intercellular space was minimally 4 × that measured for the entire pellet. An intercellular fraction of pellet was not measurable for strains of L. monocytogenes. The data also bring into question the efficacy across bacterial species of the common, but confounding, practice of using intracellular anion accumulation as a measure of pHi, and vice versa.
Property and Function of a Novel Chitinase Containing Dual Catalytic Domains Capable of Converting Chitin Into N-Acetyl-D-Glucosamine
Authors: Wang Chengyong , Chen Xueman , Zhou Ning , Chen Yan , Zhang Alei , Chen Kequan , Ouyang Pingkai
Published: February 2022

A novel multifunctional chitinase (CmChi3)-encoding gene was cloned from Chitinolyticbacter meiyuanensis and actively expressed in Escherichia coli. Sequence analysis showed that CmChi3 contains two glycoside hydrolase family 18 (GH18) catalytic domains and exhibited low identity with well-characterized chitinases. The optimum pH and temperature of purified recombinant CmChi3 were 6.0 and 50°C, respectively. CmChi3 exhibited strict substrate specificity of 4.1 U/mg toward colloidal chitin (CC) and hydrolyzed it to yield N-acetyl-D-glucosamine (GlcNAc) as the sole end product. An analysis of the hydrolysis products toward N-acetyl chitooligosaccharides (N-acetyl COSs) and CC substrates revealed that CmChi3 exhibits endochitinase, N-acetyl-β-d-glucosaminidase (NAGase), and transglycosylase (TGase) activities. Further studies revealed that the N-terminal catalytic domain of CmChi3 exhibited endo-acting and NAGase activities, while the C-terminal catalytic domain showed exo-acting and TGase activities. The hydrolytic properties and favorable environmental adaptations indicate that CmChi3 holds potential for commercial GlcNAc production from chitin.
Homogeneous Selection and Dispersal Limitation Dominate the Effect of Soil Strata Under Warming Condition
Authors: Wang Zhujun , Feng Kai , Lu Guangxin , Yu Hao , Wang Shang , Wei Ziyan , Dang Ning , Wang Yingcheng , Deng Ye
Published: February 2022

Global warming is likely to affect the underground microbial communities in various ecosystems, but the response of soil microbial communities along a vertical depth profile to global warming has been elusive. Herein, we leveraged a warming field experiment in Qinghai-Tibet Plateau grassland and investigated the community structure of prokaryotes and fungi from the upper (0–15 cm) and lower (15–30 cm) strata under ambient and elevated temperature treatments. Three-years continual warming only significantly shifted the prokaryotic community within the upper strata and there was no significant effect observed for the fungal community. Additionally, under ambient temperature, there were significant differences between the two strata in both the prokaryotic and fungal communities, but under warming, this effect was alleviated. Next, the prokaryotic and fungal community assembly processes were measured by a phylogenetic-bin-based null approach (iCAMP). Though deterministic and stochastic processes dominated the assembly of prokaryotic and fungal communities, respectively, the deterministic processes were strengthened under warming for both communities. Specifically, the increased portion of homogeneous selection, contributing to a homogenous state, led to a smaller difference between prokaryotic communities of the two soil strata under warming. The smaller difference in the stochastic process component, i.e., dispersal limitation, contributed to the similar fungal community structures between the two strata under warming. This study deepens our understanding of warming effects on grassland microbial communities and gives greater insights on the underlying mechanisms for microbial assembly between upper and lower soil strata under warming scenarios.
Bacterial Species Associated With Human Inflammatory Bowel Disease and Their Pathogenic Mechanisms
Authors: Zhang Li , Liu Fang , Xue Jessica , Lee Seul A. , Liu Lu , Riordan Stephen M.
Published: February 2022

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with unknown etiology. The pathogenesis of IBD results from immune responses to microbes in the gastrointestinal tract. Various bacterial species that are associated with human IBD have been identified. However, the microbes that trigger the development of human IBD are still not clear. Here we review bacterial species that are associated with human IBD and their pathogenic mechanisms to provide an updated broad understanding of this research field. IBD is an inflammatory syndrome rather than a single disease. We propose a three-stage pathogenesis model to illustrate the roles of different IBD-associated bacterial species and gut commensal bacteria in the development of human IBD. Finally, we recommend microbe-targeted therapeutic strategies based on the three-stage pathogenesis model.
The in situ Production of Aquatic Fluorescent Organic Matter in a Simulated Freshwater Laboratory Model
Authors: Perrin Eva M. , Thorn Robin M. S. , Sargeant Stephanie L. , Attridge John W. , Reynolds Darren M.
Published: February 2022

Dissolved organic matter (DOM) is ubiquitous throughout aquatic systems. Fluorescence techniques can be used to characterize the fluorescing proportion of DOM, aquatic fluorescent organic matter (AFOM). AFOM is conventionally named in association with specific fluorescence “peaks,” which fluoresce in similar optical regions as microbially-derived proteinaceous material (Peak T), and terrestrially-derived humic-like compounds (Peaks C/C+), with Peak T previously being investigated as a tool for bacterial enumeration within freshwaters. The impact of anthropogenic nutrient loading on the processing of DOM by microbial communities is largely unknown. Previous laboratory studies utilizing environmental freshwater have employed growth media with complex background fluorescence, or very high nutrient concentrations, preventing the investigation of AFOM production under a range of more representative nutrient concentrations within a matrix exhibiting very low background fluorescence. We describe a laboratory-based model with Pseudomonas aeruginosa that incorporates a low fluorescence growth matrix consisting of a simulated freshwater (SFW), representative of low-hardness freshwater systems allowing controlled nutrient conditions to be studied. The effects of microbial processing of DOM as a function of available nitrogen, phosphorous, and dissolved organic carbon (DOC) in the form of glucose were investigated over 48 h at highly resolved time increments. The model system demonstrates the production of a range of complex AFOM peaks in the presence and absence of DOC, revealing no linear relationship between cell numbers and any of the peaks for the bacterial species studied, with AFOM peaks increasing with microbial cell number, ranging from 55.2 quinine sulfate units (QSU) per 106 cells to 155 QSU per 106 cells (p < 0.05) for Peak T during the exponential growth phase of P. aeruginosa under high nutrient conditions with 5 mg L−1 DOC. Nutrient and DOC concentration was found to cause differential production of autochthonous- or allochthonous-like AFOM, with lower DOC concentrations resulting in higher Peak T production relative to Peaks C/C+ upon the addition of nutrients, and high DOC concentrations resulting in higher Peak C/C+ production relative to Peak T. Our results show the production of allochthonous-like AFOM from a simple and non-fluorescent carbon source, and provide uncertainty in the use of Peak T as a reliable surrogate for specific bacterial enumeration, particularly in dynamic or nutrient-impacted environments, pointing toward the use of fluorescence as an indicator for microbial metabolism.
Survivability of Kluyveromyces marxianus Isolated From Korean Kefir in a Simulated Gastrointestinal Environment
Authors: Youn Hye-Young , Kim Dong-Hyeon , Kim Hyeon-Jin , Bae Dongryeoul , Song Kwang-Young , Kim Hyunsook , Seo Kun-Ho
Published: February 2022

Kluyveromyces marxianus accounts for > 90% of the yeast population of kefir, and recently, its probiotic potential has been actively explored with a focus on its health benefits and safety. Herein, the survivability of five kefir-isolated K. marxianus strains (Km A1–A5) in a simulated gastrointestinal (GI) environment was evaluated and compared with those of commercial probiotic yeast, Saccharomyces boulardii MYA-796. To further explore the potential to survive in the host GI tract, biochemical activities, hydrophobicity assay, biofilm formation, auto-aggregation analysis, and phenol tolerance of the strains were assessed. K. marxianus A4 exhibited the best survivability among all tested strains, including the clinically proven probiotic yeast strain S. boulardii MYA-796 (p = 0.014) in the artificial GI tract ranging from pH 2.0 to 7.5. In addition, the five K. marxianus strains and S. boulardii MYA-796 displayed different assimilation of lactose, xylitol, D-sorbitol, and DL-lactate, indicating that K. marxianus metabolized a wide range of substances and, thus, might be more feasible to nourish themselves in the host GI tract for survival. K. marxianus strains showed a greater hydrophobicity of cell surface, abilities to biofilm formation and auto-aggregation, and phenol tolerance than S. boulardii MYA-796, suggesting greater potential for survival in the host GI tract.
Extracytoplasmic Function Sigma Factors Governing Production of the Primary Siderophores in Pathogenic Burkholderia Species
Authors: Grove Anne
Published: February 2022

Bacteria respond to changing environments by modulating their gene expression programs. One of the mechanisms by which this may be accomplished is by substituting the primary σ factor with an alternative σ factor belonging to the family of extracytoplasmic function (ECF) σ factors. ECF σ factors are activated only in presence of specific signals, and they direct the RNA polymerase (RNAP) to transcribe a defined subset of genes. One condition, which may trigger the activation of an ECF σ factor, is iron limitation. To overcome iron starvation, bacteria produce and secrete siderophores, which chelate iron and facilitate its cellular uptake. In the genus Burkholderia, which includes several serious human pathogens, uptake of iron is critical for virulence, and expression of biosynthetic gene clusters encoding proteins involved in synthesis and transport of the primary siderophores are under control of an ECF σ factor. This review summarizes mechanisms involved in regulation of these gene clusters, including the role of global transcriptional regulators. Since siderophore-mediated iron acquisition is important for virulence, interference with this process constitutes a viable approach to the treatment of bacterial infections.
Leveraging Factors of Self-Efficacy and Motivation to Optimize Stroke Recovery
Authors: Gangwani Rachana , Cain Amelia , Collins Amy , Cassidy Jessica M.
Published: February 2022

The International Classification of Functioning, Disability and Health framework recognizes that an individual's functioning post-stroke reflects an interaction between their health condition and contextual factors encompassing personal and environmental factors. Personal factors significantly impact rehabilitation outcomes as they determine how an individual evaluates their situation and copes with their condition in daily life. A key personal factor is self-efficacy—an individual's belief in their capacity to achieve certain outcomes. Self-efficacy influences an individual's motivational state to execute behaviors necessary for achieving desired rehabilitation outcomes. Stroke rehabilitation practice and research now acknowledge self-efficacy and motivation as critical elements in post-stroke recovery, and increasing evidence highlights their contributions to motor (re)learning. Given the informative value of neuroimaging-based biomarkers in stroke, elucidating the neurological underpinnings of self-efficacy and motivation may optimize post-stroke recovery. In this review, we examine the role of self-efficacy and motivation in stroke rehabilitation and recovery, identify potential neural substrates underlying these factors from current neuroimaging literature, and discuss how leveraging these factors and their associated neural substrates has the potential to advance the field of stroke rehabilitation.