bluuebunny/crossref_metadata_2025 huggingface dataset:
Humans Are More Influential Than Coyotes on Mammalian Mesopredator Spatiotemporal Activity Across an Urban Gradient
Authors: Moura Chad W. , Clucas Barbara , Furnas Brett J.
Published: June 2022

For mammalian mesopredators, human-dominated landscapes offer a mosaic of risk and reward. While the reward of anthropogenic food resources may attract mesopredators to human-dominated areas, increased mesopredator activity and abundance in these areas may cause interspecific conflict. For smaller-bodied mesopredators, the perceived risk of intraguild predation by larger mesopredators may be enough to drive spatial and temporal avoidance strategies to reduce risk while still benefiting from anthropogenic resources. We evaluated how the spatiotemporal activity of four non-canid mammalian mesopredators – raccoon (Procyon lotor), striped skunk (Mephitis mephitis), opossum (Didelphis virginiana), and domestic cat (Felis catus) – might change in the presence of an intraguild predator, the coyote (Canis latrans), and a “super predator,” humans. We quantified mesopredator activity by deploying camera traps at 110 sites across an urban gradient in the Sacramento Metropolitan Area in central California, USA. We hypothesized that mesopredators would likely change their spatiotemporal activity in response to urban intensity (H1), coyotes (H2), human presence (H3), and if urban intensity might mediate the response to humans and coyotes (H4). We used single-species occupancy models to test how mesopredators responded to different spatial scales of urbanization, as well as the temporal presence of coyotes and humans. Top single-species models then informed two-species conditional occupancy models to evaluate how mesopredators responded to “dominant” coyotes. Finally, we used temporal overlap analyzes to evaluate whether activity patterns of mesopredators changed in response to humans and coyotes across three levels of urban intensity. Mesopredators did not change their spatial or temporal activity across the urban gradient when coyotes were present. Additionally, coyotes did not influence mesopredator temporal activity at 1-3-day scales; however, raccoons and cats may avoid coyotes at finer scales. Humans influenced mesopredator detectability, as cats and coyotes avoided humans after 1 and 2 days respectively, and opossums avoided urban areas when humans were present within 3 days. Coyotes may play a limited role in altering smaller-bodied mesopredator activity, especially when humans are present. While the impacts of human presence and urban features are often linked, mesopredators may perceive the risk each poses differently, and adjust their activity accordingly.
Harmonizing and Searching Macroinvertebrate Trait Information in Alpine Streams: Method and Application–A Case Study in the Three Parallel Rivers Region, China
Authors: Ao Sicheng , Li Xianfu , Tian Zhen , Hu Jiancheng , Cai Qinghua
Published: June 2022

The traits of organisms provide critical information for understanding changes in biodiversity and ecosystem function at large scales. In recent years, trait databases of macroinvertebrates have been developed across continents. Anyone using different databases to search for traits will encounter a series of problems that lead to uncertain results due to the inconsistency of the trait information. For example, traits for a particular macroinvertebrate taxon may be inconsistent across databases, coded in inconsistent ways, or cannot be found. However, most of the current studies do not clearly state their solutions, which seriously hinders the accuracy and comparability of global trait studies. To solve these problems, we collected representative databases from several continents, including the United States, Europe, South Africa, Bolivia, Australia, and New Zealand. By comparing the inconsistency of similar trait classifications in the nine databases, we harmonized 41 of these grouping features. We found that these databases differed widely in terms of the range and category of traits. And the method of coding traits also varies from database to database. Moreover, we showed a set of trait searching rules that integrate trait databases from different regions of the world, allowing traits to be identified more easily and uniformly using different trait databases worldwide. We also applied this method to determine the traits of 155 macroinvertebrate taxa in the Three Parallel Rivers Region (TPRR). The results showed that among a total of 155 macroinvertebrate taxa, the 41 grouping features of all genera were not fully identified, and 32 genera were not recorded (thus using family-level data). No trait information was found at all for two families, which contain two genera. This suggests that many macroinvertebrate taxa and their traits have not been fully studied, especially in those regions, including China, where macroinvertebrate trait studies are lagging. This inadequacy and unevenness have seriously hindered the study and development of macroinvertebrate trait and functional diversity worldwide. Our results complement the information on stream macroinvertebrate traits in the TPRR, a global biodiversity hotspot, and greatly promote the uniformity of global trait research and the accuracy and comparability of trait research in different regions.
Systemic Candidiasis in Mice: New Insights From an Old Model
Authors: Jungnickel Berit , Jacobsen Ilse D.
Published: June 2022

Animal models are essential to understand the pathophysiology of infections, to test novel antifungal compounds, and to determine the potential of adjunctive therapies, e.g. immune modulation. The murine model of systemic candidiasis induced by intravenous infection is technically straightforward, highly reproducible, and well-characterized. However, intravenous inoculation circumvents the necessity for the fungus to translocate across mucosal barriers, and the use of SPF mice that are immunologically naïve to Candida does not reflect the situation in human patients, in whom adaptive immune responses have been induced by mucosal colonization prior to infection. Therefore, mouse models that combine intestinal colonization and systemic infection have been developed, resulting in novel insights into host-fungal interactions and immunity. In this review, we summarize the main findings, current questions, and discuss how these might impact the translatability of results from mice to humans.
CRISPR-Based Approaches for Gene Regulation in Non-Model Bacteria
Authors: Call Stephanie N. , Andrews Lauren B.
Published: June 2022

CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) have become ubiquitous approaches to control gene expression in bacteria due to their simple design and effectiveness. By regulating transcription of a target gene(s), CRISPRi/a can dynamically engineer cellular metabolism, implement transcriptional regulation circuitry, or elucidate genotype-phenotype relationships from smaller targeted libraries up to whole genome-wide libraries. While CRISPRi/a has been primarily established in the model bacteriaEscherichia coliandBacillus subtilis, a growing numbering of studies have demonstrated the extension of these tools to other species of bacteria (here broadly referred to as non-model bacteria). In this mini-review, we discuss the challenges that contribute to the slower creation of CRISPRi/a tools in diverse, non-model bacteria and summarize the current state of these approaches across bacterial phyla. We find that despite the potential difficulties in establishing novel CRISPRi/a in non-model microbes, over 190 recent examples across eight bacterial phyla have been reported in the literature. Most studies have focused on tool development or used these CRISPRi/a approaches to interrogate gene function, with fewer examples applying CRISPRi/a gene regulation for metabolic engineering or high-throughput screens and selections. To date, most CRISPRi/a reports have been developed for common strains of non-model bacterial species, suggesting barriers remain to establish these genetic tools in undomesticated bacteria. More efficient and generalizable methods will help realize the immense potential of programmable CRISPR-based transcriptional control in diverse bacteria.
Construction and Comprehensive Analysis of the ceRNA Network to Reveal Key Genes for Benign Tracheal Stenosis
Authors: He Yanpeng , Zou Chunyan , Cai Zhigang
Published: June 2022

Objective: To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis.

Method: Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. Differentially expressed mRNA, lncRNA, and circRNA were analyzed using the DESeq2 package. The protein interaction networks for differentially expressed mRNAs were constructed by STRING. The results of gene co-expression network analysis, Starbase database prediction, and differential gene expression were combined to construct a competing endogenous RNA network. The transcription factors of key genes were predicted using the Network Analyst database and a transcription factor-mRNA regulatory network was constructed. The classical pathways, intermolecular interaction networks, and upstream regulatory components of key genes were analyzed using Ingenuity Pathway Analysis (IPA). Finally, the DGIDB database was used to predict the potential therapeutic drugs to target the identified key genes.

Result: Based on mRNA, lncRNA and circRNA expression data, we found that differentially expressed mRNAs were enriched in oxygen transport, neutrophil activation, immune response, and oxygen binding. Then the pearson correlation between mRNAs of 46 key genes and lncRNAs and cricRNAs were calculated, and the correlation greater than 0.9 were selected to construct the co-expression network of “mRNA-lncRA” and “mRNA-cricRNA.” Moreover, a “lncRNA-miRNA-mRNA” network and a “circRNA-miRNA-mRNA” network were constructed. IPA analysis showed that the 46 key genes were significantly associated with inflammatory activation and acute respiratory distress syndrome. The constructed TF-mRNA regulatory network was composed of 274 nodes and 573 interacting pairs. 251 potential therapeutic drugs were identified from the DGIDB database.

Conclusion: This study analyzed the differential genes associated with benign tracheal stenosis and explored the potential regulatory mechanisms, providing a scientific reference for further studies on the pathogenesis of benign tracheal stenosis.
Multi-Modal Medical Image Fusion With Geometric Algebra Based Sparse Representation
Authors: Li Yanping , Fang Nian , Wang Haiquan , Wang Rui
Published: June 2022

Multi-modal medical image fusion can reduce information redundancy, increase the understandability of images and provide medical staff with more detailed pathological information. However, most of traditional methods usually treat the channels of multi-modal medical images as three independent grayscale images which ignore the correlation between the color channels and lead to color distortion, attenuation and other bad effects in the reconstructed image. In this paper, we propose a multi-modal medical image fusion algorithm with geometric algebra based sparse representation (GA-SR). Firstly, the multi-modal medical image is represented as a multi-vector, and the GA-SR model is introduced for multi-modal medical image fusion to avoid losing the correlation of channels. Secondly, the orthogonal matching pursuit algorithm based on geometric algebra (GAOMP) is introduced to obtain the sparse coefficient matrix. The K-means clustering singular value decomposition algorithm based on geometric algebra (K-GASVD) is introduced to obtain the geometric algebra dictionary, and update the sparse coefficient matrix and dictionary. Finally, we obtain the fused image by linear combination of the geometric algebra dictionary and the coefficient matrix. The experimental results demonstrate that the proposed algorithm outperforms existing methods in subjective and objective quality evaluation, and shows its effectiveness for multi-modal medical image fusion.
Future of Colorectal Cancer Screening: From One-Size-FITs-All to Tailor-Made
Authors: Kortlever Tim , van der Vlugt Manon , Dekker Evelien
Published: June 2022

Screening for colorectal cancer (CRC) and its precursor lesions, advanced adenomas (AA), has been shown to effectively reduce CRC-related mortality. However, the method of CRC screening varies among countries. Primary colonoscopy screening is the most effective screening option from an individual point of view, but it is costly and population-wide participation rates are relatively low. Repeated screening with a fecal immunochemical test (FIT) is a non-invasive and inexpensive way to select individuals at high risk for CRC for colonoscopy. Despite its widespread use and mostly high participation rates, FIT is not perfect. Its sensitivity for advanced neoplasia (AN) is low. Besides, the false positivity rate of FIT is relatively high. This leads to unnecessary colonoscopies, anxiety, and risks among FIT-positives. New strategies need to be developed to improve CRC screening. In the past years, much research has been undertaken on risk-based screening or risk models. These include tests consisting of multiple risk factors and/or biomarkers that either assess the risk of disease at a single point in time (cross-sectional risk models) or predict the risk of developing CRC in the future (longitudinal risk models). We provide an overview of the developments on risk models for CRC screening and discuss some of the obstacles that need to be overcome to enable widespread implementation in existing CRC screening programs.
External Assessment of the Anti-N-Methyl-D-Aspartate Receptor Encephalitis One-Year Functional Status Score in Chinese Pediatric Patients
Authors: Luo Hanyu , Li Yuhang , Zheng Yaxin , Zhou Lvli , Yang Jiaxin , Fang Zhixu , Jiang Yan , Wang Juan , Yao Zhengxiong , Chen Min , Jiang Li
Published: June 2022

Objective

to assess the performance of the Anti-N-Methyl-D-Aspartate Receptor encephalitis (NMDAR) One-Year Functional Status (NEOS) score in predicting one-year functional outcome in Chinese children with anti-NMDAR encephalitis.

Methods

children with anti-NMDAR encephalitis at the Children’s Hospital of Chongqing Medical University were retrospectively enrolled from January 2014 to December 2020. Patients were categorized into two groups based on the modified Rankin Scale (mRS) at one-year follow-up. Discrimination of the NEOS score was assessed by the area under curve (AUC) of the receiver operating characteristic curve. Calibration of the NEOS score was assessed by comparing predicted probabilities with observed probabilities using a calibration curve and the Hosmer-Lemeshow test. The clinical practicability of the NEOS score was evaluated by performing a decision curve analysis.

Results

one hundred seventy-five children (101 females and 74 males) with anti-NMDAR encephalitis and a median age of 7.7 years were enrolled. Of those, 149 (85.1%) had a good outcome at 1 year (mRS ≤ 2), and the remaining 26 (14.9%) had a poor outcome (mRS > 2). Patients with a higher NEOS score had a significantly higher mRS at one-year follow-up [Spearman r = 0.3878, 95% confidence interval (CI): 0.2500-0.5103, P < 0.001]. The AUC of the NEOS score was 0.870 (95% CI: 0.801-0.938, P < 0.001). The observed probability and predicted probability showed moderate consistency in the calibration curve and the Hosmer-Lemeshow test (P = 0.912). The decision curve analysis showed that using the NEOS score to predict one-year outcomes could provide additional net benefit during clinical practice.

Conclusions

the NEOS score is a potentially reliable model to predict the one-year functional outcome in Chinese children with anti-NMDAR encephalitis.
Identification of a Disease-Associated Network of Intestinal Immune Cells in Treatment-Naive Inflammatory Bowel Disease
Authors: van Unen Vincent , Ouboter Laura F. , Li Na , Schreurs Mette , Abdelaal Tamim , Kooy-Winkelaar Yvonne , Beyrend Guillaume , Höllt Thomas , Maljaars P. W. Jeroen , Mearin M. Luisa , Mahfouz Ahmed , Witte Anne M. C. , Clemens Cornelis H. M. , Abraham Sunje , Escher Johanna C. , Lelieveldt Boudewijn P. F. , Pascutti M. Fernanda , van der Meulen – de Jong Andrea E. , Koning Frits
Published: June 2022

Chronic intestinal inflammation underlies inflammatory bowel disease (IBD). Previous studies indicated alterations in the cellular immune system; however, it has been challenging to interrogate the role of all immune cell subsets simultaneously. Therefore, we aimed to identify immune cell types associated with inflammation in IBD using high-dimensional mass cytometry. We analyzed 188 intestinal biopsies and paired blood samples of newly-diagnosed, treatment-naive patients (n=42) and controls (n=26) in two independent cohorts. We applied mass cytometry (36-antibody panel) to resolve single cells and analyzed the data with unbiased Hierarchical-SNE. In addition, imaging-mass cytometry (IMC) was performed to reveal the spatial distribution of the immune subsets in the tissue. We identified 44 distinct immune subsets. Correlation network analysis identified a network of inflammation-associated subsets, including HLA-DR+CD38+ EM CD4+ T cells, T regulatory-like cells, PD1+ EM CD8+ T cells, neutrophils, CD27+ TCRγδ cells and NK cells. All disease-associated subsets were validated in a second cohort. This network was abundant in a subset of patients, independent of IBD subtype, severity or intestinal location. Putative disease-associated CD4+ T cells were detectable in blood. Finally, imaging-mass cytometry revealed the spatial colocalization of neutrophils, memory CD4+ T cells and myeloid cells in the inflamed intestine. Our study indicates that a cellular network of both innate and adaptive immune cells colocalizes in inflamed biopsies from a subset of patients. These results contribute to dissecting disease heterogeneity and may guide the development of targeted therapeutics in IBD.
Risks of SARS-CoV-2 Infection and Immune Response to COVID-19 Vaccines in Patients With Inflammatory Bowel Disease: Current Evidence
Authors: Esposito Susanna , Caminiti Caterina , Giordano Rosanna , Argentiero Alberto , Ramundo Greta , Principi Nicola
Published: June 2022

Inflammatory bowel diseases (IBD), including Crohn’s disease, ulcerative colitis, and unclassified inflammatory bowel disease, are a group of chronic, immune mediated conditions that are presumed to occur in genetically susceptible individuals because of a dysregulated intestinal immune response to environmental factors. IBD patients can be considered subjects with an aberrant immune response that makes them at increased risk of infections, particularly those due to opportunistic pathogens. In many cases this risk is significantly increased by the therapy they receive. Aim of this narrative review is to describe the impact of SARS-CoV-2 infection and the immunogenicity of COVID-19 vaccines in patients with IBD. Available data indicate that patients with IBD do not have an increased susceptibility to infection with SARS-CoV-2 and that, if infected, in the majority of the cases they must not modify the therapy in place because this does not negatively affect the COVID-19 course. Only corticosteroids should be reduced or suspended due to the risk of causing severe forms. Furthermore, COVID-19 seems to modify the course of IBD mainly due to the impact on intestinal disease of the psychological factors deriving from the measures implemented to deal with the pandemic. The data relating to the immune response induced by SARS-CoV-2 or by COVID-19 vaccines can be considered much less definitive. It seems certain that the immune response to disease and vaccines is not substantially different from that seen in healthy subjects, with the exception of patients treated with anti-tumor necrosis factor alone or in combination with other immunosuppressants who showed a reduced immune response. How much, however, this problem reduces induced protection is not known. Moreover, the impact of SARS-CoV-2 variants on IBD course and immune response to SARS-CoV-2 infection and COVID-19 vaccines has not been studied and deserves attention. Further studies capable of facing and solving unanswered questions are needed in order to adequately protect IBD patients from the risks associated with SARS-CoV-2 infection.
Predicting and Scoring Estuary Ecological Health Using a Bayesian Belief Network
Authors: Zeldis John R. , Plew David R.
Published: June 2022

Excessive nutrient and sediment inputs threaten ecological condition in many estuaries. We describe a Bayesian Belief Network (BBN) that calculates an Estuary Trophic Index (ETI) score ranging between 0 (no symptoms of eutrophication) to 1 (grossly eutrophic) for estuaries in Aotearoa New Zealand (NZ). The ETI BBN includes estuary physiographic characteristics (estuary type, flushing time, intertidal area, estuary closure state, water column stratification) and nutrient and sediment loads available from existing geospatial tools and databases, that drive responses of ‘primary’ indicators (macroalgae and phytoplankton biomass) and ‘secondary’ indicators (or symptoms) of estuary ecological impairment (sediment carbon, sediment apparent redox potential discontinuity depth, water column oxygen, macrobenthos and seagrass condition). Relationships between the BBN nodes are based primarily on observational and model-based information from NZ and international studies rather than expert opinion. The model can be used in a purely predictive manner under knowledge-poor situations, using only the physiographic drivers and nutrient/sediment loads, or refined using field-derived observations of indicator values to reduce the uncertainty associated with the probabilistic BBN score. It is designed for shallow tidal lagoons, tidal river estuaries and coastal lakes; systems which are sensitive to eutrophication and sedimentation pressure and are common in NZ and globally. Modelled ETI BBN scores agreed well with ETI scores calculated from observed indicator values for 11 well-studied NZ estuaries. We predict ecological condition of 291 NZ estuaries, most of which have no monitored information on trophic state. We illustrate capabilities of the ETI BBN with two case studies: to evaluate improvements in estuary health arising from diversion of wastewater from an estuary via an ocean outfall, and to estimate catchment diffuse nutrient load reductions required to meet estuary health objectives. The ETI BBN may serve as a template for other agencies wishing to develop similar tools.
Identification of Interacting Proteins of Transcription Factor DpAP2 Related to Carotenoid Biosynthesis From Marine Microalga Dunaliella parva
Authors: Shang Changhua , Pang Bingbing , Zhang Jin , Yu Lihong , Gan Shanling , Li Yujia , Wu Haifeng
Published: June 2022

Carotenoids are widely distributed and structurally diverse, which have significant roles in the photosynthesis of plants. As a precursor of vitamin A, carotenoids are also antioxidants that reduce various chronic diseases, which are beneficial for human health. Currently, the existing studies concerned the biological roles of APETALA2 (AP2)/ethylene-responsive factor (ERF) genes originated from higher plants. The AP2 superfamily of the transcriptional regulator was identified in higher plants, which was related to growth, development, carotenoid metabolism, and responses to various stresses. However, the regulatory mechanisms of the AP2-modulating carotenoid metabolism have not been reported in microalgae, which remain to be elucidated. Dunaliella parva AP2 (i.e., DpAP2), an important transcription factor, promotes carotenoid accumulation by binding to the promoter of target gene. Here, we identified an important AP2/ERF transcription factor, DpAP2, which could promote carotenoid accumulation by binding to the promoter of target gene. To demonstrate the function of DpAP2, the interacting proteins were identified by the yeast two-hybrid system. The results showed that DpAP2 could interact with three proteins with different activities (DNA-binding transcription factor activity, protein kinase activity, and alpha-D-phosphohexomutase activity); these proteins may be associated with multiple biological processes. This paper laid a good foundation for a deep understanding of the regulatory mechanisms of DpAP2 and genetic engineering breeding in D. parva.
Bioplastics in the Sea: Rapid In-Vitro Evaluation of Degradability and Persistence at Natural Temperatures
Authors: Miksch Lukas , Köck Matthias , Gutow Lars , Saborowski Reinhard
Published: June 2022

The progressive substitution of petroleum-based polymers, such as polyethylene, polyvinylchloride, or polyethylene terephtalate, by so-called bioplastics facilitated the development and production of many new materials. The continuously refined properties of bioplastic compounds and their blends enable various applications. With growing production and utilization of bioplastic products, these materials are increasingly discarded into the environment. Although many of these materials are labeled biodegradable, there is limited information about their degradability under environmental conditions. We tested the enzymatic degradability of five bioplastic compounds with the rapid pH-Stat titration assay at environmentally relevant seawater temperatures between 5 and 30°C and pH 8.2. These plastics, issued from the European Horizon 2020 Project ´Bioplastics Europe´, are based on polylactic acid (PLA), polybutylene succinate (PBS), and poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV). Suspensions of microparticles (< 200 µm) were incubated with each of the three hydrolytic enzymes, protease, lipase, and esterase. A PLA-based compound blended with polybutylene adipate terephthalate (PBAT) showed the highest hydrolysis rate of 30 nmol·min-1 when incubated with lipase at 30°C. All other materials showed low hydrolysis rates of less than 10 nmol·min-1. Below 20°C, hydrolysis almost ceased. Plate clearing assays with the same enzymes at 37°C and pH 5 and pH 8, respectively, largely confirmed the results of the pH-Stat titration assays. Our findings indicate that there is a potential degradation of most of the materials with at least one of these hydrolytic enzymes. Nonetheless, the rate of enzymatic degradation under environmentally relevant conditions is low, which indicates only a marginal degradability of bioplastics in the marine environment.
Decreased Risk of Low Back Pain During Pregnancy Associated With the Use of Orthopedic Manual Therapy: A Nested Case-Control Study
Authors: Chang Wei-Chiao , Livneh Hanoch , Yen Chieh-Tsung , Hsieh Min-Chih , Lu Ming-Chi , Chen Wei-Jen , Tsai Tzung-Yi
Published: June 2022

Background

Recent evidence suggests that the use of orthopedic manual therapy (OMT) may lessen the subsequent risk of low back pain (LBP), but this association has not been examined among pregnant women who are at higher risk of LBP. This study aims to determine whether the addition of OMT to conventional LBP treatment before pregnancy could decrease the subsequent risk of LBP during pregnancy.

Methods

From Taiwan's National Health Insurance Research Database, we identified 68,960 women, 20–55 years of age, with first pregnancy between 2001 and 2012. We then performed a nested case-control study in which 3,846 women with newly diagnosed LBP were matched to 3,846 controls according to age and cohort entry year. Multivariate conditional logistic regression was employed to estimate the association between OMT use before pregnancy and LBP during pregnancy.

Results

OMT users had a lower risk of LBP than did non-users, with an adjusted OR of 0.86 (95% CI, 0.78–0.93). Subgroup analysis showed that women with high intensity use of OMT treatment prior to pregnancy reported the lowest level of LBP during pregnancy by nearly 30%.

Conclusion

The pre-pregnancy use of OMT treatment significantly decreased LBP risk during pregnancy, especially with high-intensity use. Thus, clinicians may consider recommending OMT for pregnant women to avoid possible obstetric complications during the pregnancy.
Smartphone-Acquired Anterior Segment Images for Deep Learning Prediction of Anterior Chamber Depth: A Proof-of-Concept Study
Authors: Qian Chaoxu , Jiang Yixing , Soh Zhi Da , Sakthi Selvam Ganesan , Xiao Shuyuan , Tham Yih-Chung , Xu Xinxing , Liu Yong , Li Jun , Zhong Hua , Cheng Ching-Yu
Published: June 2022

Purpose

To develop a deep learning (DL) algorithm for predicting anterior chamber depth (ACD) from smartphone-acquired anterior segment photographs.

Methods

For algorithm development, we included 4,157 eyes from 2,084 Chinese primary school students (aged 11–15 years) from Mojiang Myopia Progression Study (MMPS). All participants had with ACD measurement measured with Lenstar (LS 900) and anterior segment photographs acquired from a smartphone (iPhone Xs), which was mounted on slit lamp and under diffuses lighting. The anterior segment photographs were randomly selected by person into training (80%, no. of eyes = 3,326) and testing (20%, no. of eyes = 831) dataset. We excluded participants with intraocular surgery history or pronounced corneal haze. A convolutional neural network was developed to predict ACD based on these anterior segment photographs. To determine the accuracy of our algorithm, we measured the mean absolute error (MAE) and coefficient of determination (R2) were evaluated. Bland Altman plot was used to illustrate the agreement between DL-predicted and measured ACD values.

Results

In the test set of 831 eyes, the mean measured ACD was 3.06 ± 0.25 mm, and the mean DL-predicted ACD was 3.10 ± 0.20 mm. The MAE was 0.16 ± 0.13 mm, andR2was 0.40 between the predicted and measured ACD. The overall mean difference was −0.04 ± 0.20 mm, with 95% limits of agreement ranging between −0.43 and 0.34 mm. The generated saliency maps showed that the algorithm mainly utilized central corneal region (i.e., the site where ACD is clinically measured typically) in making its prediction, providing further plausibility to the algorithm's prediction.

Conclusions

We developed a DL algorithm to estimate ACD based on smartphone-acquired anterior segment photographs. Upon further validation, our algorithm may be further refined for use as a ACD screening tool in rural localities where means of assessing ocular biometry is not readily available. This is particularly important in China where the risk of primary angle closure disease is high and often undetected.
Diagnosis of Idiopathic Pulmonary Fibrosis in High-Resolution Computed Tomography Scans Using a Combination of Handcrafted Radiomics and Deep Learning
Authors: Refaee Turkey , Salahuddin Zohaib , Frix Anne-Noelle , Yan Chenggong , Wu Guangyao , Woodruff Henry C. , Gietema Hester , Meunier Paul , Louis Renaud , Guiot Julien , Lambin Philippe
Published: June 2022

Purpose

To develop handcrafted radiomics (HCR) and deep learning (DL) based automated diagnostic tools that can differentiate between idiopathic pulmonary fibrosis (IPF) and non-IPF interstitial lung diseases (ILDs) in patients using high-resolution computed tomography (HRCT) scans.

Material and Methods

In this retrospective study, 474 HRCT scans were included (mean age, 64.10 years ± 9.57 [SD]). Five-fold cross-validation was performed on 365 HRCT scans. Furthermore, an external dataset comprising 109 patients was used as a test set. An HCR model, a DL model, and an ensemble of HCR and DL model were developed. A virtual in-silico trial was conducted with two radiologists and one pulmonologist on the same external test set for performance comparison. The performance was compared using DeLong method and McNemar test. Shapley Additive exPlanations (SHAP) plots and Grad-CAM heatmaps were used for the post-hoc interpretability of HCR and DL models, respectively.

Results

In five-fold cross-validation, the HCR model, DL model, and the ensemble of HCR and DL models achieved accuracies of 76.2 ± 6.8, 77.9 ± 4.6, and 85.2 ± 2.7%, respectively. For the diagnosis of IPF and non-IPF ILDs on the external test set, the HCR, DL, and the ensemble of HCR and DL models achieved accuracies of 76.1, 77.9, and 85.3%, respectively. The ensemble model outperformed the diagnostic performance of clinicians who achieved a mean accuracy of 66.3 ± 6.7% (p < 0.05) during the in-silico trial. The area under the receiver operating characteristic curve (AUC) for the ensemble model on the test set was 0.917 which was significantly higher than the HCR model (0.817, p = 0.02) and the DL model (0.823, p = 0.005). The agreement between HCR and DL models was 61.4%, and the accuracy and specificity for the predictions when both the models agree were 93 and 97%, respectively. SHAP analysis showed the texture features as the most important features for IPF diagnosis and Grad-CAM showed that the model focused on the clinically relevant part of the image.

Conclusion

Deep learning and HCR models can complement each other and serve as useful clinical aids for the diagnosis of IPF and non-IPF ILDs.
Orthostatic Challenge Causes Distinctive Symptomatic, Hemodynamic and Cognitive Responses in Long COVID and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Vernon Suzanne D. , Funk Sherlyn , Bateman Lucinda , Stoddard Gregory J. , Hammer Sarah , Sullivan Karen , Bell Jennifer , Abbaszadeh Saeed , Lipkin W. Ian , Komaroff Anthony L.
Published: June 2022

Background

Some patients with acute COVID-19 are left with persistent, debilitating fatigue, cognitive impairment (“brain fog”), orthostatic intolerance (OI) and other symptoms (“Long COVID”). Many of the symptoms are like those of other post-infectious fatigue syndromes and may meet criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Common diagnostic laboratory tests are often unrevealing.

Methods

We evaluated whether a simple, standardized, office-based test of OI, the 10-min NASA Lean Test (NLT), would aggravate symptoms and produce objective hemodynamic and cognitive abnormalities, the latter being evaluated by a simple smart phone-based app.

Participants

People with Long COVID (N = 42), ME/CFS (N = 26) and healthy control subjects (N = 20) were studied just before, during, immediately after, 2 and 7 days following completion of the NLT.

Results

The NLT provoked a worsening of symptoms in the two patient groups but not in healthy control subjects, and the severity of all symptoms was similar and significantly worse in the two patient groups than in the control subjects (p < 0.001). In the two patient groups, particularly those with Long COVID, the NLT provoked a marked and progressive narrowing in the pulse pressure. All three cognitive measures of reaction time worsened in the two patient groups immediately following the NLT, compared to the healthy control subjects, particularly in the Procedural Reaction Time (p < 0.01).

Conclusions

A test of orthostatic stress easily performed in an office setting reveals different symptomatic, hemodynamic and cognitive abnormalities in people with Long COVID and ME/CFS, compared to healthy control subjects. Thus, an orthostatic challenge easily performed in an office setting, and the use of a smart phone app to assess cognition, can provide objective confirmation of the orthostatic intolerance and brain fog reported by patients with Long COVID and ME/CFS.
Saccharomyces Boulardii Ameliorates Non-alcoholic Steatohepatitis in Mice Induced by a Methionine-Choline-Deficient Diet Through Gut-Liver Axis
Authors: Yang An-Ming , Lin Chien-Yu , Liu Shih-Hao , Syu Guan-Da , Sun Hao-Jhe , Lee Kuei-Chuan , Lin Han-Chieh , Hou Ming-Chih
Published: June 2022

Non-alcoholic steatohepatitis (NASH) is affecting people worldwide. Changes in the intestinal microbiome are crucial to NASH. A previous study showed that eradicating intestinal fungi ameliorates NASH; however, the role of intestinal fungi in the development of NASH remains unclear. Saccharomyces boulardii (SB), a dietary supplement yeast, has been reported to restore the integrity of the intestine. Here, we tested the effect of SB in the treatment of NASH. For this study, we fed eight-week-old C57/BL6 male mice either a methionine-choline deficient (MCD) diet or a normal chow diet (NCD) for eight weeks. Half of the MCD diet-fed mice were gavaged with SB (5 mg/day) once daily. The remainder of the NCD–fed mice were gavaged with normal saline as a control. The MCD diet-fed mice on SB supplement showed better liver function, less hepatic steatosis, and decreased inflammation. Both hepatic inflammatory gene expression and fibrogenic gene expression were suppressed in mice with SB gavage. Intestinal damage caused by the MCD diet was tampered with, intestine inflammation decreased, and gut permeability improved in mice that had been given the SB supplement. Deep sequencing of the fecal microbiome showed a potentially increased beneficial gut microbiota and increased microbiota diversity in the SB-supplemented mice. The SB supplement maintains gut integrity, increases microbial diversity, and increases the number of potentially beneficial gut microbiota. Thus, the SB supplement attenuates gut leakage and exerts a protective effect against NASH. Our results provide new insight into the prevention of NASH.
Mass Cytometry and Single-Cell Transcriptome Analyses Reveal the Immune Cell Characteristics of Ulcerative Colitis
Authors: Luo Yongxin , Liu Shiying , Li Huibiao , Hou Jiangtao , Lin Wenjia , Xu Zewen , Lu Tianyu , Li Yanwu , Peng Bin , Zhang Shijing , Han Xue , Kuang Zuoliang , Wen Yi , Cai Jiazhong , Liu Fengbin , Chen Xin-Lin
Published: June 2022

Background: The pathogenesis of ulcerative colitis (UC) is closely related to immunity. The immune characteristic differences between active UC (UCa) and inactive UC (UCin) have not been completely explained. Mass cytometry (CyTOF) and single-cell RNA sequencing (scRNA-seq) were used to analyze the immune cells of UCa, UCin and healthy control (HC) subjects to determine the specific immune characteristics.

Methods: The immune cell subsets among UCa, UCin, HC were distinguished using CyTOF analysis. scRNA-seq analysis was used to validate the results of CyTOF. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to understand the roles of differential immune cell subsets.

Results: After CyTOF analysis and validation of scRNA-seq analysis, differential immune cell subsets mainly contained TNF+IL-17A++ effector memory (EM) Tregs, CXCR3+CTLA4+ EM Tregs, CXCR3++CCR7+ B cells, HLA-DR+CCR7+ dendritic cells (DCs) and CTLA-4+ natural killer (NK) cells. In comparison to HC, CCR6+TNF+CD161+ EM T cells were highly enriched in UCa and UCin. Besides, UCa was characterized by an increase in CD38+TNF+ EM Tregs, CXCR3+CCR4+ naïve B cells, HLA-DR+CD14+IL21+ macrophages/monocytes, HLA-DR+CCR7+ DCs, AHR+CD14+ cytotoxic NK (cNK) cells and CD8A+IFNG+ cNK cells. Decreases in CD38+CD27+ plasmablasts, CXCR3+CD38+ regulatory NK cells, and CXCR3+CCR7+ tolerant NK cells in UCa were discovered.

Conclusions: Novel immune cell subsets which was used to distinguish UCa, UCin and HC were identified. This information might be utilized to distinguish the patients with UCa and UCin.
Multi-Timepoint Metabolic Fingerprinting of a Post-Episode Period of Hypoglycemia and Ketoacidosis Among Children With Type 1 Diabetes
Authors: Małachowska Beata , Pietrowska Karolina , Młynarski Wojciech , Szadkowska Agnieszka , Krętowski Adam , Ciborowski Michał , Fendler Wojciech
Published: June 2022

Background: Acute complications of type 1 diabetes mellitus such as diabetes ketoacidosis (DKA) and hypoglycemia (HG) are detrimental in a short- and long-term perspective. Restoration of normoglycemia and correction of pH do not mean that all metabolic disturbances caused by HG or DKA are immediately reversed.

Aim: This study aimed to identify serum metabolic changes caused by an episode of DKA and HG that may indicate the mechanisms contributing to long-term consequences of DKA/HG.

Materials and methods: Four groups of children with type 1 diabetes were recruited. The first two study groups included patients after an episode of DKA or HG, respectively. Additionally, two comparative groups were recruited—children with established type 1 diabetes (EDM) and patients with newly diagnosed diabetes without diabetes ketoacidosis (NDM). Serum samples were collected in three group-specific time points (since the hospital admission): HG 0h-12h–48h; DKA or NDM 0h-24h–72 h; and one random fasting sample from patients with EDM. Two batches of 100 samples each were created: for DKA batch 20 × 3 DKA patients, 10 × 3 NDM and 10 EDM; for HG batch: 10 × 3 HG patients, 25 EDM and 15 × 3 NDM. All patients within the batches were age and sex matched. Metabolic fingerprinting was performed with LC-QTOF-MS.

Results: Four metabolites were associated with a DKA episode occurring in the preceding 72 h: three were found higher after the DKA episode versus comparative groups: lysophosphatidylcholine (LPC) (18:1), sphingomyelins (SM) (34:0 and d18:0/15:0), and one was found lower: LPC (18:0). Similarly, four metabolites were identified for the HG episode in the last 48 h: three were found higher after the HG episode versus comparative groups: two lysophosphatidylethanolamines (LPE) (18:2 and 20:3) and one LPC (18:2); and one was found lower after the HG episode: oxy-phosphatidylocholine (PC O-34:4).

Conclusions: We found eight metabolites whose levels may be traced in the serum, indicating the DKA or HG episode for up to 72 h and 48 h, respectively. Acute complications of diabetes may cause persistent metabolic disturbances long after pH and glucose level normalization.
Thioredoxin Reductase Inhibitors as Potential Antitumors: Mercury Compounds Efficacy in Glioma Cells
Authors: Pires Vanessa , Bramatti Isabella , Aschner Michael , Branco Vasco , Carvalho Cristina
Published: June 2022

Glioblastoma multiforme (GBM) is the most aggressive and common form of glioma. GBM, like many other tumors, expresses high levels of redox proteins, such as thioredoxin (Trx) and thioredoxin reductase (TrxR), allowing tumor cells to cope with high levels of reactive oxygen species (ROS) and resist chemotherapy and radiotherapy. Thus, tackling the activity of these enzymes is a strategy to reduce cell viability and proliferation and most importantly achieve tumor cell death. Mercury (Hg) compounds are among the most effective inhibitors of TrxR and Trx due to their high affinity for binding thiols and selenols. Moreover, organomercurials such as thimerosal, have a history of clinical use in humans. Thimerosal effectively crosses the blood–brain barrier (BBB), thus reaching effective concentrations for the treatment of GBM. Therefore, this study evaluated the effects of thimerosal (TmHg) and its metabolite ethylmercury (EtHg) over the mouse glioma cell line (GL261), namely, the inhibition of the thioredoxin system and the occurrence of oxidative cellular stress. The results showed that both TmHg and EtHg increased oxidative events and triggered cell death primarily by apoptosis, leading to a significant reduction in GL261 cell viability. Moreover, the cytotoxicity of TmHg and ETHg in GL261 was significantly higher when compared to temozolomide (TMZ). These results indicate that EtHg and TmHg have the potential to be used in GBM therapy since they strongly reduce the redox capability of tumor cells at exceedingly low exposure levels.
OOP-ESEEM Spectroscopy: Accuracies of Distances of Spin-Correlated Radical Pairs in Biomolecules
Authors: Al Said Tarek , Weber Stefan , Schleicher Erik
Published: June 2022

In addition to the commonly used electron–electron double resonance (ELDOR) technique, there are several other electron paramagnetic resonance (EPR) methods by which structure information can be obtained by exploiting the dipolar coupling between two radicals based on its characteristic r−3 dependence. In this contribution, we explore the potential of out-of-phase-electron-spin echo envelope modulation (OOP-ESEEM) spectroscopy to collect accurate distance information in photo-sensitive (bio) molecules. Although the method has already been applied to spin-correlated radical pairs in several classes of light-active proteins, the accuracy of the information obtained has not yet been extensively evaluated. To do this in a system-independent fashion, OOP-ESEEM time traces simulated with different values of the dipolar and exchange couplings were generated and analyzed in a best-possible way. Excellent agreement between calculated and numerically fitted values over a wide range of distances (between 15 and 45 Å) was obtained. Furthermore, the limitations of the method and the dependence on various experimental parameters could be evaluated.
Approaches to Using the Chameleon: Robust, Automated, Fast-Plunge cryoEM Specimen Preparation
Authors: Levitz Talya S. , Weckener Miriam , Fong Ivan , Naismith James H. , Drennan Catherine L. , Brignole Edward J. , Clare Daniel K. , Darrow Michele C.
Published: June 2022

The specimen preparation process is a key determinant in the success of any cryo electron microscopy (cryoEM) structural study and until recently had remained largely unchanged from the initial designs of Jacques Dubochet and others in the 1980s. The process has transformed structural biology, but it is largely manual and can require extensive optimisation for each protein sample. The chameleon instrument with its self-wicking grids and fast-plunge freezing represents a shift towards a robust, automated, and highly controllable future for specimen preparation. However, these new technologies require new workflows and an understanding of their limitations and strengths. As early adopters of the chameleon technology, we report on our experiences and lessons learned through case studies. We use these to make recommendations for the benefit of future users of the chameleon system and the field of cryoEM specimen preparation generally.
Opposing Roles of Wild-type and Mutant p53 in the Process of Epithelial to Mesenchymal Transition
Authors: Semenov Oleg , Daks Alexandra , Fedorova Olga , Shuvalov Oleg , Barlev Nickolai A.
Published: June 2022

The central role of an aberrantly activated EMT program in defining the critical features of aggressive carcinomas is well documented and includes cell plasticity, metastatic dissemination, drug resistance, and cancer stem cell-like phenotypes. The p53 tumor suppressor is critical for leashing off all the features mentioned above. On the molecular level, the suppression of these effects is exerted by p53 via regulation of its target genes, whose products are involved in cell cycle, apoptosis, autophagy, DNA repair, and interactions with immune cells. Importantly, a set of specific mutations in the TP53 gene (named Gain-of-Function mutations) converts this tumor suppressor into an oncogene. In this review, we attempted to contrast different regulatory roles of wild-type and mutant p53 in the multi-faceted process of EMT.
Inbred Mice Again at Stake: How the Cognitive Profile of the Wild-Type Mouse Background Discloses Pathogenic Effects of APP Mutations
Authors: Ammassari-Teule Martine
Published: June 2022

Increasing efforts have been made in the last decades to increase the face validity of Alzheimer's disease (AD) mouse models. Main advancements have consisted in generating AD mutations closer to those identified in humans, enhancing genetic diversity of wild-type backgrounds, and choosing protocols much apt to reveal AD-like cognitive dysfunctions. Nevertheless, two aspects remain less considered: the cognitive specialization of inbred strains used as recipient backgrounds of mutations and the heuristic importance of studying destabilization of memory circuits in pre-symptomatic mice facing cognitive challenges. This article underscores the relevance of these behavioral/experimental aspects by reviewing data which show that (i) inbred mice differ in their innate predisposition to rely on episodic vs. procedural memory, which implicates differential sensitivity to mutations aimed at disrupting temporal lobe-dependent memory, and that (ii) investigating training-driven neural alterations in asymptomatic mutants unveils early synaptic damage, which considerably anticipates detection of AD first signs.