bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of Machine Learning Classifier to Candida auris Drug Resistance Analysis
Authors: Li Dingchen , Wang Yaru , Hu Wenjuan , Chen Fangyan , Zhao Jingya , Chen Xia , Han Li
Published: October 2021

Candida auris (C. auris) is an emerging fungus associated with high morbidity. It has a unique transmission ability and is often resistant to multiple drugs. In this study, we evaluated the ability of different machine learning models to classify the drug resistance and predicted and ranked the drug resistance mutations of C. auris. Two C. auris strains were obtained. Combined with other 356 strains collected from the European Bioinformatics Institute (EBI) databases, the whole genome sequencing (WGS) data were analyzed by bioinformatics. Machine learning classifiers were used to build drug resistance models, which were evaluated and compared by various evaluation methods based on AUC value. Briefly, two strains were assigned to Clade III in the phylogenetic tree, which was consistent with previous studies; nevertheless, the phylogenetic tree was not completely consistent with the conclusion of clustering according to the geographical location discovered earlier. The clustering results of C. auris were related to its drug resistance. The resistance genes of C. auris were not under additional strong selection pressure, and the performance of different models varied greatly for different drugs. For drugs such as azoles and echinocandins, the models performed relatively well. In addition, two machine learning algorithms, based on the balanced test and imbalanced test, were designed and evaluated; for most drugs, the evaluation results on the balanced test set were better than on the imbalanced test set. The mutations strongly be associated with drug resistance of C. auris were predicted and ranked by Recursive Feature Elimination with Cross-Validation (RFECV) combined with a machine learning classifier. In addition to known drug resistance mutations, some new resistance mutations were predicted, such as Y501H and I466M mutation in the ERG11 gene and R278H mutation in the ERG10 gene, which may be associated with fluconazole (FCZ), micafungin (MCF), and amphotericin B (AmB) resistance, respectively; these mutations were in the “hot spot” regions of the ergosterol pathway. To sum up, this study suggested that machine learning classifiers are a useful and cost-effective method to identify fungal drug resistance-related mutations, which is of great significance for the research on the resistance mechanism of C. auris.
Leishmania Parasites Differently Regulate Antioxidant Genes in Macrophages Derived From Resistant and Susceptible Mice
Authors: Bichiou Haifa , Rabhi Sameh , Ben Hamda Cherif , Bouabid Cyrine , Belghith Meriam , Piquemal David , Trentin Bernadette , Rabhi Imen , Guizani-Tabbane Lamia
Published: October 2021

Macrophage–Leishmania interactions are central to parasite growth and disease outcome. Macrophages have developed various strategies to fight invaders, including oxidative burst. While some microorganisms seem to survive and even thrive in an oxidative environment, others are susceptible and get killed. To counter oxidative stress, macrophages switch the expressions of cytoprotective and detoxifying enzymes, which are downstream targets of the nuclear factor erythroid 2-related factor 2 (Nrf2), to enhance cell survival. We have explored the transcription of NRF2 and of its target genes and compared the effect of the parasite on their transcription in bone marrow-derived macrophages (BMdMs) from Leishmania-resistant and Leishmania-susceptible mice. While heme oxygenase 1 (HO-1) transcription is independent of the genetic background, the transcription of glutathione reductase (Gsr) and of cysteine/glutamate exchange transporter (Slc7a11), involved in glutathione accumulation, was differentially regulated in BMdMs from both mouse strains. We also show that, except for HO-1, known to favor the survival of the parasite, the transcription of the selected genes, including Gsr, CD36, and catalase (CAT), was actively repressed, if not at all time points at least at the later ones, by the parasite, especially in Balb/c BMdMs. Consistent with these results, we found that the silencing of NRF2 in this study increases the survival and multiplication of the parasite.
Donor-Derived Human Parvovirus B19 Infection in Kidney Transplantation
Authors: Yu Yedong , Wei Chunchun , Lyu Junhao , Wu Xiaoliang , Wang Rending , Huang Hongfeng , Wu Jianyong , Chen Jianghua , Peng Wenhan
Published: October 2021

Background

Donor-derived human parvovirus B19 (B19V) infections are rarely reported. Thus, its incidence in kidney transplantation is still unknown due to lack of surveillance studies. Similarly, whether the donor needs to be routinely screened for B19V and whether the kidneys from those with B19V DNAemia could be accepted also remain unknown.

Methods

This retrospective study aims to evaluate the donor-derived B19V infections occurring in 823 living and 1,225 deceased donor kidney transplantations from January 2016 to December 2020. The serum viral load of living donors and their corresponding recipients was evaluated before and after transplantation. Meanwhile, for the deceased donor kidney transplantation, the serum viral load of recipients was only tested after transplantation; if recipients of a deceased donor subsequently developed B19V infection, the serum viral load of recipients and their corresponding donors before transplantation would then be further traced.

Results

A total of 15 living donors were B19V DNAemia positive before the donation, of which B19V DNAemia occurred in three corresponding recipients. In deceased donor kidney transplantation, DNAemia occurred simultaneously in 18 recipients and their corresponding nine donors. A progressive decline in hemoglobin and reticulocyte count could be observed in one living donor recipient and other 11 deceased donor recipients, which were all well controlled by treatment eventually.

Conclusion

The incidence of donor-derived B19V infection was 0.4% and 1.5% in living and deceased kidney transplantations, respectively. B19V was seemingly unnecessary to be routinely screened for the donor. Moreover, kidneys of the donors with B19V infection were acceptable.
The Development of Preschool Children’s Awareness of Semantic Radicals in Chinese Characters
Authors: Li Mengna , Chen Suiqing , Wu Shaomin
Published: October 2021

The present study investigated the development of Chinese preschool children’s awareness of semantic radicals in Chinese characters. The two specific areas of focus were the development of awareness of the category consistency of the semantic radical and awareness of the semantic radical. A sample of 55 four-year-old children and 61 five-year-old children were randomly selected from a public preschool that did not include formal literacy education in its curriculum. Experiment 1 found that the children’s awareness of the category consistency of semantic radicals had not yet developed, regardless of the configuration of characters. Experiment 2 found that the children showed no obvious awareness of the semantic radical and had a strong bias toward using phonetic radicals rather than semantic radicals to classify characters, with the bias being significant for characters of left-right configuration. The current findings suggest that Chinese preschool children have an awareness of radicals in Chinese characters and they are more sensitive to the phonetic radical than to the semantic radical and, consequently, prioritize the former.
Diagnostic Value of Angiography-Derived IMR for Coronary Microcirculation and Its Prognostic Implication After PCI
Authors: Dai Neng , Che Wenliang , Liu Lu , Zhang Wen , Yin Guoqing , Xu Bin , Xu Yawei , Duan Shaofeng , Yu Haojun , Li Chenguang , Yao Kang , Huang Dong , Ge Junbo
Published: October 2021

Background: Angiography-derived index of microcirculatory resistance (angio-IMR) is an emerging pressure-wire-free index to assess coronary microvascular function, but its diagnostic and prognostic value remains to be elucidated.

Methods and Results: The study population consisted of three independent cohorts. The internal diagnostic cohort enrolled 53 patients with available hyperemic microcirculatory resistance (HMR) calculated from myocardial blood flow and pressure. The external diagnostic cohort included 35 ischemia and no obstructive coronary artery disease (INOCA) patients and 45 controls. The prognostic cohort included 138 coronary artery disease (CAD) patients who received PCI. Angio-IMR was calculated after the estimation of angiography-derived fractional flow reserve (angio-FFR) using the equation of angio-IMR = estimated hyperemic Pa × angio-FFR × [vessel length/(K × Vdiastole)]. The primary outcome was a composite of cardiac death or readmission due to heart failure at 28 months after index procedure. Angio-IMR demonstrated a moderate correlation with HMR (R = 0.74, p < 0.001) and its diagnostic accuracy, sensitivity, specificity, and area under the curve to diagnose INOCA were 79.8, 83.1, 78.0, and 0.84, respectively, with a best cut-off of 25.1. Among prognostic cohort, patients with angio-IMR ≥25.1 showed a significantly higher risk of cardiac death or readmission due to heart failure than those with an angio-IMR <25.1 (18.6 vs. 5.4%, adjusted HR 9.66, 95% CI 2.04–45.65, p = 0.004). Angio-IMR ≥25.1 was an independent predictor for cardiac death or readmission due to heart failure (HR 11.15, 95% CI 1.76–70.42, p = 0.010).

Conclusions: Angio-IMR showed a moderate correlation with HMR and high accuracy to predict microcirculatory dysfunction. Angio-IMR measured after PCI predicts the risk of cardiac death or readmission due to heart failure in patients with CAD.

Clinical Trial Registration: Diagnostic and Prognostic Value of Angiography-derived IMR (CHART-MiCro), NCT04825028.
Additional Value of Non-contrast Chest CT in the Prediction of Adverse Cardiovascular Events in Patients With Novel Coronavirus Disease 2019 (COVID-19)
Authors: Li Shuang , Wang Xiaojun , Hu Hongyao , Xu Jing , He Jian , Yang Wenjing , He Bin , Liu Yanmei , Yu Huidan , Zhou Quan , Zhang Haijun , Liu Tingting , Hu Ke , Zhao Yang , Huang Zhixin , Zhu Hengcheng , Zhang Bicheng , Zhao Shihua , Sirajuddin Arlene , Arai Andrew E. , Chen Jun , Zhou Xiaoyang , Lu Minjie
Published: October 2021

Background: Coronavirus disease 2019 (COVID-19) has outbroken in China and subsequently spread worldwide since the end of 2019. Chest computed tomography (CT) plays an important role in the diagnosis of lung diseases, but its value in the diagnosis of cardiac injury remains unknown.

Methods: We enrolled 241 consecutive hospitalized patients (aged 61 ± 16 years, 115 males) with laboratory-confirmed COVID-19 at Renmin Hospital of Wuhan University from January 11 to March 2, 2020. They were divided into two groups according to whether major adverse cardiovascular events (MACEs) occurred during the follow-up. The anteroposterior diameter of the left atrium (LAD), the length of the left ventricle (LV), and cardiothoracic ratio (CTR) were measured. The values of myocardial CT were also recorded.

Results: Of 241 patients, 115 patients (47.7%) had adverse cardiovascular events. Compared with no MACEs, patients with MACEs were more likely to have bilateral lesions (95.7% vs. 86.5%, p = 0.01). In multivariable analysis, bronchial wall thickening would increase the odds of MACEs by 13.42 (p = 0.01). LAD + LV and CTR was the best predictor for MACEs (area under the curve = 0.88, p < 0.001) with a sensitivity of 82.6% and a specificity of 80.2%. Plasma high-sensitivity troponin I levels in patients with cardiac injury showed a moderate negative correlation with minimum CT value (R2 = −0.636, p < 0.001).

Conclusions: Non-contrast chest CT can be a useful modality for detection cardiac injury and provide additional value to predict MACEs in COVID-19 patients.
When Aortic Stenosis Is Not Alone: Epidemiology, Pathophysiology, Diagnosis and Management in Mixed and Combined Valvular Disease
Authors: Mantovani Francesca , Fanti Diego , Tafciu Elvin , Fezzi Simone , Setti Martina , Rossi Andrea , Ribichini Flavio , Benfari Giovanni
Published: October 2021

Aortic stenosis (AS) may present frequently combined with other valvular diseases or mixed with aortic regurgitation, with peculiar physio-pathological and clinical implications. The hemodynamic interactions between AS in mixed or combined valve disease depend on the specific combination of valve lesions and may result in diagnostic pitfalls at echocardiography; other imaging modalities may be helpful. Indeed, diagnosis is challenging because several echocardiographic methods commonly used to assess stenosis or regurgitation have been validated only in patients with the single-valve disease. Moreover, in the developed world, patients with multiple valve diseases tend to be older and more fragile over time; also, when more than one valvular lesion needs to address the surgical risk rises together with the long-term risk of morbidity and mortality associated with multiple valve prostheses, and the likelihood and risk of reoperation. Therefore, when AS presents mixed or combined valve disease, the heart valve team must integrate various parameters into the diagnosis and management strategy, including suitability for single or multiple transcatheter valve procedures. This review aims to summarize the most critical pathophysiological mechanisms underlying AS when associated with mitral regurgitation, mitral stenosis, aortic regurgitation, and tricuspid regurgitation. We will focus on echocardiography, clinical implications, and the most important treatment strategies.
Quantitative Analysis of Phase Separation Using the Lattice Boltzmann Method
Authors: Li Xiaoqi , Fang Jichao , Ji Bingyu
Published: October 2021

Phase separation is widely observed in multiphase systems. In this study, it has been investigated using Shan–Chen lattice Boltzmann method. The adhesion parameter in SC model leads to the desired fluid–fluid phenomenon, which was varied to specify the strength of separation between two phases to present emulsified performance in oil production. In order to describe such behaviors quantitatively, graphical distributions were described with time and were corresponded with a statistical index–Fourier structure factor that is able to predict complex phase separation behaviors, thereby providing a measurement for calculating such random distribution during the process of separation as well as evaluating heterogeneous degrees of the entire domain. The repulsive interactions are specified as low, intermediate, and high values. Phase separations with clear boundaries have been observed and each stage of separation evolvement has been discussed in this study. Magnitudes of structure factors are increased with higher degrees of fluctuations.
Enhancing Diversity in STEMM
Authors: Haddad Mary Alice , Jenkins Tyler , Solivan Bonnie , Williams Alison
Published: October 2021

Professional and scientific societies can foster inclusive environments that can enhance the diversity of their respective fields and disciplines, but some associations are doing a better job than others. This paper reviewed more than a dozen professional associations and their efforts to support diversity as reported online in an effort to identify successful examples. It finds that resources generally fall into two categories: 1) Websites highlighting the accomplishments of specific individuals, which raise the profile of diverse practitioners in the field. 2) Membership associations that support under-represented communities within a particular field. This article will offer a review of the resources available and some recommendations for how professional associations can better enhance their support for diversity and inclusion in their fields.
Influence of the Lignin Extraction Methods on the Content of Tricin in Grass Lignins
Authors: Xie Minting , Chen Zhendong , Xia Yue , Lin Minsheng , Li Jiaqi , Lan Wu , Zhang Liming , Yue Fengxia
Published: October 2021

Tricin as a monomer of grass lignin with unique biological properties is beneficial to human health with the potential for various applications. The abundant grass lignin could be an alternative source for tricin if an effective separation method is available. In this study, we used different lignin preparations, including alkali lignin (AL), mild acidolysis lignin (MAL), cellulase enzymatic lignin (CEL), γ-valerolactone lignin (GVL), and organosolv lignin (OL), to investigate the effect of different fractionation methods on the tricin content of the wheat straw lignin. The tricin signal of different lignins can be clearly identified by 2D heteronuclear singular quantum correlation (HSQC) spectra. GVL showed the highest tricin level among these lignin samples as the tricin content of GVL was accounted to be 8.6% by integrals. The tricin content was carefully determined using thioacidolysis combined with high-performance liquid chromatography-mass spectrometric (HPLC-MS), and the quantitative results of tricin by HPLC-MS were basically consistent with that of 2D HSQC integrals. Both methods have proved that the tricin contents of lignins isolated under acid conditions were significantly higher than that of AL. In addition, the determination of the sun protection factors (SPF) of lignin-based sunscreen and antioxidant activity of lignin preparations indicated that reserving more tricin was beneficial to the UV resistance of lignin samples. Therefore, this study not only provides new insights for the extraction methods of lignin with high tricin content but also is beneficial to the future study on the application of tricin and tricin-lignin.
Simulation Study on the Development Process and Phase Interface Structure of Gas-Liquid Slug Flow in a Horizontal Pipe
Authors: Wu Xiao , Wang Zhaoting , Dong Mei , Ge Quan , Dong Longfei
Published: October 2021

Here, a unified 3D numerical model of gas-liquid two-phase flow in a horizontal pipe was established using the interface capture method based on the open source software package OpenFOAM. Through numerical simulation of the natural slugging and development process of slug flow under different working conditions, the motion, phase interface structure, pressure and velocity field distributions of the liquid slug were fully developed and analyzed. The simulation results are consistent with the experiment. The results showed that during the movement of the slug head, there is a throwing phenomenon and a wave-like motion of the liquid slug. In addition, the slug tail and body area have very similar velocity profiles, and the overall velocity field distribution becomes more uniform with the development of liquid slug. Moreover, there are sudden pressure fluctuations at the head and tail of the liquid slug.
Evaluation of Tannery Wastewater Treatment by Integrating Vesicular Basalt With Local Plant Species in a Constructed Wetland System
Authors: Alemu Agegnehu , Gabbiye Nigus , Lemma Brook
Published: October 2021

Tannery wastewater is composed of a complex mixture of organic and inorganic components from various processes that can critically pollute the environment, especially water bodies if discharged without treatment. In this study, integrated vesicular basalt rock and local plant species were used to establish a horizontal subsurface flow constructed wetland system and to investigate the treatment efficiency of tannery wastewater. Four pilot units were vegetated with P. purpureum, T. domingensis, C. latifolius, and E. pyramidalis, and a fifth unit was left unvegetated (control). The constructed wetland units in horizontal subsurface flow systems were effective in removing total chromium (Cr), chemical oxygen demand (COD), and 5-day biological oxygen demand (BOD5) from the inflow tannery wastewater. The removal efficiency reached up to 99.38, 84.03, and 80.32% for total Cr, COD, and BOD5, respectively, in 6 days of hydraulic retention time (HRT). The removal efficiency of total suspended solid (TSS), total phosphorus (TP), and nitrate (NO3−) of the constructed wetland units reached a maximum of 70.59, 62.32, and 71.23%, respectively. This integrated system was effective for treating tannery wastewater, which is below the Ethiopian surface water standard discharge limit set to BOD5 (200 mg L−1), COD (500 mg L−1), total Cr (2 mg L−1), NO3− (20 mg L−1), TSS (50 mg L−1), and TP (10 mg L−1).
Spatial Variability of Soil Organic Carbon and Total Nitrogen in Desert Steppes of China’s Hexi Corridor
Authors: Wang Xuyang , Li Yuqiang , Duan Yulong , Wang Lilong , Niu Yayi , Li Xiaohui , Yan Meng
Published: October 2021

Stock estimates are critical to quantifying carbon and nitrogen sequestration, quantifying greenhouse gas emissions, and understanding key biogeochemical processes (i.e., soil carbon and nutrient cycling). Many studies have assessed soil organic matter and nutrients in different ecosystems. However, the spatial distribution of carbon and nitrogen and the key influencing factors in arid desert steppe remain unclear. Here, we investigated the soil organic carbon (SOC) and soil total nitrogen (STN) to a depth of 100 cm at 126 sites in a desert steppe in northwestern China.SOCandSTNcontents decreased with increasing depth; the highest averageSOCandSTNcontents were 12.70 and 0.65 g kg−1in the surface 5 cm, and the lowest were from 80 to 100 cm (4.49 and 0.16 g kg−1, respectively).SOCdensity (SOCD) andSTNdensity (STND) to a depth of 100 cm averaged 8.94 and 0.45 kg m−2, respectively. The top 1 m of the soils stored approximately 1,041 TgSOCand 52 TgSTNin the study area. Geostatistical analysis showed strong and moderate spatial autocorrelation forSOCDin different soil layers, but the autocorrelation forSTNDgradually weakened with increasing depth.SOCDandSTNDdecreased from southwest to northeast in the study area, along an elevation gradient. Both were significantly positively correlated with topographic variables, precipitation, and the normalized-difference vegetation index, but negatively correlated with temperature and aridity. More than 40% of theSOCDandSTNDspatial variation was explained by elevation, which was the dominant factor. The data and high-resolution maps from this study will support future soil carbon and nitrogen analyses.
Comprehensive Insights Into Forensic Features and Genetic Background of Chinese Northwest Hui Group Using Six Distinct Categories of 231 Molecular Markers
Authors: Chen Chong , Jin Xiaoye , Zhang Xingru , Zhang Wenqing , Guo Yuxin , Tao Ruiyang , Chen Anqi , Xu Qiannan , Li Min , Yang Yue , Zhu Bofeng
Published: October 2021

The Hui minority is predominantly composed of Chinese-speaking Islamic adherents distributed throughout China, of which the individuals are mainly concentrated in Northwest China. In the present study, we employed the length and sequence polymorphisms-based typing system of 231 molecular markers, i.e., amelogenin, 22 phenotypic-informative single nucleotide polymorphisms (PISNPs), 94 identity-informative single nucleotide polymorphisms (IISNPs), 24 Y-chromosomal short tandem repeats (Y-STRs), 56 ancestry-informative single nucleotide polymorphisms (AISNPs), 7 X-chromosomal short tandem repeats (X-STRs), and 27 autosomal short tandem repeats (A-STRs), into 90 unrelated male individuals from the Chinese Northwest Hui group to comprehensively explore its forensic characteristics and genetic background. Total of 451 length-based and 652 sequence-based distinct alleles were identified from 58 short tandem repeats (STRs) in 90 unrelated Northwest Hui individuals, denoting that the sequence-based genetic markers could pronouncedly provide more genetic information than length-based markers. The forensic characteristics and efficiencies of STRs and IISNPs were estimated, both of which externalized high polymorphisms in the Northwest Hui group and could be further utilized in forensic investigations. No significant departure from the Hardy–Weinberg equilibrium (HWE) expectation was observed after the Bonferroni correction. Additionally, four group sets of reference population data were exploited to dissect the genetic background of the Northwest Hui group separately from different perspectives, which contained 26 populations for 93 IISNPs, 58 populations for 17 Y-STRs, 26 populations for 55 AISNPs (raw data), and 109 populations for 55 AISNPs (allele frequencies). As a result, the analyses based on the Y-STRs indicated that the Northwest Hui group primarily exhibited intimate genetic relationships with reference Hui groups from Chinese different regions except for the Sichuan Hui group and secondarily displayed close genetic relationships with populations from Central and West Asia, as well as several Chinese groups. However, the AISNP analyses demonstrated that the Northwest Hui group shared more intimate relationships with current East Asian populations apart from reference Hui group, harboring the large proportion of ancestral component contributed by East Asia.
A Novel Homozygous Missense Mutation in the Zinc Finger DNA Binding Domain of GLI1 Causes Recessive Post-Axial Polydactyly
Authors: Umair Muhammad , Ahmad Farooq , Ahmad Saeed , Alam Qamre , Rehan Mohd , Alqosaibi Amany I. , Alnamshan Mashael M. , Rafeeq Misbahuddin M , Haque Shahnaz , Sain Ziaullah M , Ismail Muhammad , Alfadhel Majid
Published: October 2021

Background: Polydactyly is a prevalent digit abnormality characterized by having extra digits/toes. Mutations in eleven known genes have been associated to cause nonsyndromic polydactyly: GLI3, GLI1, ZRS regulating LMBR1, IQCE, ZNF141, PITX1, MIPOL1, FAM92A, STKLD1, KIAA0825, and DACH1.

Method: A single affected family member (IV-4) was subjected to whole-exome sequencing (WES) to identify the causal gene. Bi-directional Sanger sequencing was performed to segregate the identified variant within the family. In silico analysis was performed to investigate the effect of the variant on DNA binding properties.

Results: whole-exome sequencing identified a bi-allelic missense variant (c.1010C > T; p. Ser337Leu) in exon nine of GLI1 gene located on chromosome 12q13.3. With the use of Sanger sequencing, the identified variant segregated perfectly with the disease phenotype. Furthermore, in silico analysis of this DNA binding protein revealed that the variant weakened the DNA binding interaction, resulting in indecorous GLI1 function.

Conclusion: Herein, we report a novel variant in GLI1 gene, causing autosomal recessive post-axial polydactyly type A (PAPA) type 8. This confirms the critical role of GLI1 in digit development and might help in genotype–phenotype correlation in the future.
A Systematic Review of Transcriptional Dysregulation in Huntington’s Disease Studied by RNA Sequencing
Authors: Malla Bimala , Guo Xuanzong , Senger Gökçe , Chasapopoulou Zoi , Yildirim Ferah
Published: October 2021

Huntington’s disease (HD) is a chronic neurodegenerative disorder caused by an expansion of polyglutamine repeats in exon 1 of the Huntingtin gene. Transcriptional dysregulation accompanied by epigenetic alterations is an early and central disease mechanism in HD yet, the exact mechanisms and regulators, and their associated gene expression programs remain incompletely understood. This systematic review investigates genome-wide transcriptional studies that were conducted using RNA sequencing (RNA-seq) technology in HD patients and models. The review protocol was registered at the Open Science Framework (OSF). The biomedical literature and gene expression databases, PubMed and NCBI BioProject, Array Express, European Nucleotide Archive (ENA), European Genome-Phenome Archive (EGA), respectively, were searched using the defined terms specified in the protocol following the PRISMA guidelines. We conducted a complete literature and database search to retrieve all RNA-seq-based gene expression studies in HD published until August 2020, retrieving 288 articles and 237 datasets from PubMed and the databases, respectively. A total of 27 studies meeting the eligibility criteria were included in this review. Collectively, comparative analysis of the datasets revealed frequent genes that are consistently dysregulated in HD. In postmortem brains from HD patients, DNAJB1, HSPA1B and HSPB1 genes were commonly upregulated across all brain regions and cell types except for medium spiny neurons (MSNs) at symptomatic disease stage, and HSPH1 and SAT1 genes were altered in expression in all symptomatic brain datasets, indicating early and sustained changes in the expression of genes related to heat shock response as well as response to misfolded proteins. Specifically in indirect pathway medium spiny neurons (iMSNs), mitochondria related genes were among the top uniquely dysregulated genes. Interestingly, blood from HD patients showed commonly differentially expressed genes with a number of brain regions and cells, with the highest number of overlapping genes with MSNs and BA9 region at symptomatic stage. We also found the differential expression and predicted altered activity of a set of transcription factors and epigenetic regulators, including BCL6, EGR1, FOSL2 and CREBBP, HDAC1, KDM4C, respectively, which may underlie the observed transcriptional changes in HD. Altogether, our work provides a complete overview of the transcriptional studies in HD, and by data synthesis, reveals a number of common and unique gene expression and regulatory changes across different cell and tissue types in HD. These changes could elucidate new insights into molecular mechanisms of differential vulnerability in HD.

Systematic Review Registration:https://osf.io/pm3wq
Whole-Transcriptome Sequence of Degenerative Meniscus Cells Unveiling Diagnostic Markers and Therapeutic Targets for Osteoarthritis
Authors: Jiang Zongrui , Du Xue , Wen Xingzhao , Li Hongyi , Zeng Anyu , Sun Hao , Hu Shu , He Qing , Liao Weiming , Zhang Zhiqi
Published: October 2021

Meniscus plays an important role in joint homeostasis. Tear or degeneration of meniscus might facilitate the process of knee osteoarthritis (OA). Hence, to investigate the transcriptome change during meniscus degeneration, we reveal the alterations of messenger RNA (mRNA), microRNA (miRNA), long noncoding RNA (lncRNA), and circular RNA (circRNA) in meniscus during OA by whole-transcriptome sequence. A total of 375 mRNAs, 15 miRNAs, 56 lncRNAs, and 90 circRNAs were significantly altered in the degenerative meniscus treated with interleukin-1β (IL-1β). More importantly, highly specific co-expression RNA (ceRNA) networks regulated by lncRNA LOC107986251-miR-212-5p-SESN3 and hsa_circ_0018069-miR-147b-3p-TJP2 were screened out during IL-induced meniscus degeneration, unveiling potential therapeutic targets for meniscus degeneration during the OA process. Furthermore, lipocalin-2 (LCN2) and RAB27B were identified as potential biomarkers in meniscus degeneration by overlapping three previously constructed databases of OA menisci. LCN2 and RAB27B were both upregulated in osteoarthritic menisci and IL-1β-treated menisci and were highly associated with the severity of OA. This could introduce potential novel molecules into the database of clinical diagnostic biomarkers and possible therapeutic targets for early-stage OA treatment.
dFRAME: A Video Recording-Based Analytical Method for Studying Feeding Rhythm in Drosophila
Authors: Niu Mengxia , Zhang Xiaohang , Li Weihan , Wang Jianxun , Li Yan
Published: October 2021

Animals, from insects to humans, exhibit obvious diurnal rhythmicity of feeding behavior. Serving as a genetic animal model, Drosophila has been reported to display feeding rhythms; however, related investigations are limited due to the lack of suitable and practical methods. Here, we present a video recording-based analytical method, namely, Drosophila Feeding Rhythm Analysis Method (dFRAME). Using our newly developed computer program, FlyFeeding, we extracted the movement track of individual flies and characterized their food-approaching behavior. To distinguish feeding and no-feeding events, we utilized high-magnification video recording to optimize our method by setting cut-off thresholds to eliminate the interference of no-feeding events. Furthermore, we verified that this method is applicable to both female and male flies and for all periods of the day. Using this method, we analyzed long-term feeding status of wild-type and period mutant flies. The results recaptured previously reported feeding rhythms and revealed detailed profiles of feeding patterns in these flies under either light/dark cycles or constant dark environments. Together, our dFRAME method enables a long-term, stable, reliable, and subtle analysis of feeding behavior in Drosophila. High-throughput studies in this powerful genetic animal model will gain great insights into the molecular and neural mechanisms of feeding rhythms.
Hypertension-Related Drug Activity Identification Based on Novel Ensemble Method
Authors: Yang Bin , Bao Wenzheng , Wang Jinglong
Published: October 2021

Hypertension is a chronic disease and major risk factor for cardiovascular and cerebrovascular diseases that often leads to damage to target organs. The prevention and treatment of hypertension is crucially important for human health. In this paper, a novel ensemble method based on a flexible neural tree (FNT) is proposed to identify hypertension-related active compounds. In the ensemble method, the base classifiers are Multi-Grained Cascade Forest (gcForest), support vector machines (SVM), random forest (RF), AdaBoost, decision tree (DT), Gradient Boosting Decision Tree (GBDT), KNN, logical regression, and naïve Bayes (NB). The classification results of nine classifiers are utilized as the input vector of FNT, which is utilized as a nonlinear ensemble method to identify hypertension-related drug compounds. The experiment data are extracted from hypertension-unrelated and hypertension-related compounds collected from the up-to-date literature. The results reveal that our proposed ensemble method performs better than other single classifiers in terms of ROC curve, AUC, TPR, FRP, Precision, Specificity, and F1. Our proposed method is also compared with the averaged and voting ensemble methods. The results reveal that our method could identify hypertension-related compounds more accurately than two classical ensemble methods.
The HHV-6A Proteins U20 and U21 Target NKG2D Ligands to Escape Immune Recognition
Authors: Chaouat Abigael Eva , Seliger Barbara , Mandelboim Ofer , Schmiedel Dominik
Published: October 2021

The coevolution of the human immune system and herpesviruses led to the emergence and diversification of both cellular danger molecules recognized by immune cells on the one hand and viral countermeasures that prevent the expression of these proteins on infected cells on the other. There are eight ligands for the activating receptor NKG2D in humans – MICA, MICB, ULBP1-6. Several of them are induced and surface-expressed on herpesvirus-infected cells to serve as danger signals to activate the immune system. Therefore, these ligands are frequently targeted for suppression by viral immune evasion mechanisms. Mechanisms to downregulate NKG2D ligands and thereby escape immune recognition have been identified in all other human herpesviruses (HHV), except for HHV-6A. In this study, we identify two HHV-6A encoded immunoevasins, U20 and U21, which suppress the expression of the NKG2D ligands ULBP1 and ULBP3, respectively, during infection. Additionally, MICB is targeted by a so far unexplored viral protein. Due to the diminished NKG2D ligand surface expression on infected cells, recognition of HHV-6A infected cells by innate immune cells is impaired. Importantly, our study indicates that immune escape mechanisms between the related herpesviruses HHV-6A and HHV-6B are evolutionary conserved as the same NKG2D ligands are targeted. Our data contribute an additional piece of evidence for the importance of the NKG2D receptor – NKG2D ligand axis during human herpesvirus infections and sheds light on immune evasion mechanisms of HHV-6A.
RNA-Containing Immune Complexes Formed by Anti-Melanoma Differentiation Associated Gene 5 Autoantibody Are Potent Inducers of IFN-α
Authors: Wang Kaiwen , Zhao Jiangfeng , Wu Wanlong , Xu Wenwen , Sun Shuhui , Chen Zhiwei , Fu Yakai , Guo Li , Du Hui , Ye Shuang
Published: October 2021

Objective

Anti-melanoma differentiation-associated gene 5 (MDA5) autoantibody is a distinctive serology hallmark of dermatomyositis (DM). As an autoantigen, MDA5 is a cytoplasmic RNA recognition receptor. The aim of this study was to address the question of whether the RNA-containing immune complex (IC) formed by MDA5 and anti-MDA5 could activate type I interferon (IFN) response.

Method

Patients with anti-MDA5+ DM (n = 217), anti-MDA5− DM (n = 68), anti-synthase syndrome (ASyS, n = 57), systemic lupus erythematosus (SLE, n = 245), rheumatoid arthritis (RA, n = 89), and systemic sclerosis (SSc, n = 30) and healthy donors (HD, n = 94) were enrolled in our studies. Anti-MDA5 antibody was detected by line blotting, enzyme-linked immunosorbent assay (ELISA), immunoprecipitation, and Western blotting. Cytokine profiling was determined by multiplex flow cytometry, and IFN-α was further measured by ELISA. Type I IFN-inducible genes were detected by quantitative PCR (qPCR). RNA–IC binding was analyzed by RNA immunoprecipitation. Plasmacytoid dendritic cells (pDCs) derived from healthy donors were cultivated and stimulated with MDA5 ICs with or without RNase and Toll-like receptor 7 (TLR-7) agonist. The interaction between MDA5 ICs and TLR7 was evaluated by immunoprecipitation and confocal microscopy.

Results

According to our in-house ELISA, the presence of anti-MDA5 antibody in 76.1% of DM patients, along with 14.3% of SLE patients who had a lower titer yet positive anti-MDA5 antibody, was related to the high level of peripheral IFN-α. ICs formed by MDA5 and anti-MDA5 were potent inducers of IFN-α via TLR-7 in an RNA-dependent manner in vitro.

Conclusion

Our data provided evidence of the mechanistic relevance between the anti-MDA5 antibody and type I IFN pathway.
Lactobacillus plantarum CCFM1143 Alleviates Chronic Diarrhea via Inflammation Regulation and Gut Microbiota Modulation: A Double-Blind, Randomized, Placebo-Controlled Study
Authors: Yang Bo , Yue Yue , Chen Yang , Ding Mengfan , Li Bowen , Wang Linlin , Wang Qun , Stanton Catherine , Ross R. Paul , Zhao Jianxin , Zhang Hao , Chen Wei
Published: October 2021

Irritable bowel syndrome with diarrhea and functional diarrhea are both functional bowel disorders that cause chronic diarrhea. Chronic diarrhea is closely related to daily life and the psychological condition of diarrhea in patients, and probiotics can play a significant role in alleviating chronic diarrhea in some research. Lactobaccilus plantarum CCFM1143 can relieve diarrhea in mice caused by enterotoxigenic Escherichia coli (ETEC); however, its clinical effects remain unclear. This study aimed to assess the effects of CCFM1143 as a therapy for chronic diarrhea patients. Fifty-five patients with chronic diarrhea were randomly assigned into the probiotic group (n = 28) and the placebo group (n = 27), receiving the routine regimen with or without probiotics for 4 weeks, respectively. CCFM1143 can mitigate the apparent clinical symptoms and improve the health status and quality of life of patients. In addition, it could inhibit the increase in interleukin 6 (IL-6) and the decrease in motilin; modulate the short-chain fatty acids, especially acetic and propionic acids; and regulate the gut microbiota, particularly reducing the abundance of Bacteroides and Eggerthella and enriching the abundance of Akkermansia, Anaerostipes, and Terrisporobacter. In addition, treatment with probiotics showed clinical effectiveness in managing chronic diarrhea when compared with the placebo group. The findings could help to develop and further the application of probiotics for chronic diarrhea.
Virus Infection Is an Instigator of Intestinal Dysbiosis Leading to Type 1 Diabetes
Authors: Morse Zachary J. , Horwitz Marc S.
Published: October 2021

In addition to genetic predisposition, environmental determinants contribute to a complex etiology leading to onset of type 1 diabetes (T1D). Multiple studies have established the gut as an important site for immune modulation that can directly impact development of autoreactive cell populations against pancreatic self-antigens. Significant efforts have been made to unravel how changes in the microbiome function as a contributor to autoimmune responses and can serve as a biomarker for diabetes development. Large-scale longitudinal studies reveal that common environmental exposures precede diabetes pathology. Virus infections, particularly those associated with the gut, have been prominently identified as risk factors for T1D development. Evidence suggests recent-onset T1D patients experience pre-existing subclinical enteropathy and dysbiosis leading up to development of diabetes. The start of these dysbiotic events coincide with detection of virus infections. Thus viral infection may be a contributing driver for microbiome dysbiosis and disruption of intestinal homeostasis prior to T1D onset. Ultimately, understanding the cross-talk between viral infection, the microbiome, and the immune system is key for the development of preventative measures against T1D.
Integrating Serum Metabolome and Gut Microbiome to Evaluate the Benefits of Lauric Acid on Lipopolysaccharide- Challenged Broilers
Authors: Wu Yanping , Li Qing , Liu Jinsong , Liu Yulan , Xu Yinglei , Zhang Ruiqiang , Yu Yang , Wang Yongxia , Yang Caimei
Published: October 2021

Lauric acid (LA) is a crucial medium-chain fatty acid (MCFA) that has many beneficial effects on humans and animals. This study aimed to investigate the effects of LA on the intestinal barrier, immune functions, serum metabolism, and gut microbiota of broilers under lipopolysaccharide (LPS) challenge. A total of 384 one-day-old broilers were randomly divided into four groups, and fed with a basal diet, or a basal diet supplemented with 75 mg/kg antibiotic (ANT), or a basal diet supplemented with 1000 mg/kg LA. After 42 days of feeding, three groups were intraperitoneally injected with 0.5 mg/kg Escherichia coli- derived LPS (LPS, ANT+LPS and LA+LPS groups) for three consecutive days, and the control (CON) group was injected with the same volume of saline. Then, the birds were sacrificed. Results showed that LA pretreatment significantly alleviated the weight loss and intestinal mucosal injuries caused by LPS challenge. LA enhanced immune functions and inhibited inflammatory responses by upregulating the concentrations of immunoglobulins (IgA, IgM, and IgY), decreasing IL-6 and increasing IL-4 and IL-10. Metabolomics analysis revealed a significant difference of serum metabolites by LA pretreatment. Twenty-seven serum metabolic biomarkers were identified and mostly belong to lipids. LA also markedly modulated the pathway for sphingolipid metabolism, suggesting its ability to regulate lipid metabolism. Moreover,16S rRNA analysis showed that LA inhibited LPS-induced gut dysbiosis by altering cecal microbial composition (reducing Escherichia-Shigella, Barnesiella and Alistipes, and increasing Lactobacillus and Bacteroides), and modulating the production of volatile fatty acids (VFAs). Pearson’s correlation assays showed that alterations in serum metabolism and gut microbiota were strongly correlated to the immune factors; there were also strong correlations between serum metabolites and microbiota composition. The results highlight the potential of LA as a dietary supplement to combat bacterial LPS challenge in animal production and to promote food safety.
Leukemic Stem Cells: From Leukemic Niche Biology to Treatment Opportunities
Authors: Marchand Tony , Pinho Sandra
Published: October 2021

Acute myeloid leukemia (AML) is one of the most common types of leukemia in adults. While complete remission can be obtained with intensive chemotherapy in young and fit patients, relapse is frequent and prognosis remains poor. Leukemic cells are thought to arise from a pool of leukemic stem cells (LSCs) which sit at the top of the hierarchy. Since their discovery, more than 30 years ago, LSCs have been a topic of intense research and their identification paved the way for cancer stem cell research. LSCs are defined by their ability to self-renew, to engraft into recipient mice and to give rise to leukemia. Compared to healthy hematopoietic stem cells (HSCs), LSCs display specific mutations, epigenetic modifications, and a specific metabolic profile. LSCs are usually considered resistant to chemotherapy and are therefore the drivers of relapse. Similar to their HSC counterpart, LSCs reside in a highly specialized microenvironment referred to as the “niche”. Bidirectional interactions between leukemic cells and the microenvironment favor leukemic progression at the expense of healthy hematopoiesis. Within the niche, LSCs are thought to be protected from genotoxic insults. Improvement in our understanding of LSC gene expression profile and phenotype has led to the development of prognosis signatures and the identification of potential therapeutic targets. In this review, we will discuss LSC biology in the context of their specific microenvironment and how a better understanding of LSC niche biology could pave the way for new therapies that target AML.
The Prospect of Global Coral Reef Bathymetry by Combining Ice, Cloud, and Land Elevation Satellite-2 Altimetry With Multispectral Satellite Imagery
Authors: Gleason Arthur C. R. , Smith Ross , Purkis Sam J. , Goodrich Kyle , Dempsey Alexandra , Mantero Alejandro
Published: October 2021

Empirical methods for estimating shallow-water bathymetry using passive multispectral satellite imagery are robust and globally applicable, in theory, but they require copious local measurements of water depth for algorithm calibration. Such calibration data have historically been unavailable for most locations, but NASA’s Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2), a satellite-based LiDAR, might hold unique promise to fill this critical data gap. Although ICESat-2 was not designed as a marine altimeter, its ATLAS sensor consists of six green (532 nm) lasers that can penetrate a water surface and return photons reflected by the seabed, thereby generating bathymetric profiles. Utilizing TCarta’s NSF SBIR-funded Space-Based Laser Bathymetry Extraction Tool and ICESat-2’s ATL03 geolocated photon data product, we have compared ICESat-2 bathymetric retrievals with a portfolio of soundings acquired in situ using a vessel-mounted single-beam echosounder. This analysis demonstrated very high correlation (R2 = 0.96) between the field and space-based bathymetry data. The comparisons were made at multiple Caribbean and Pacific coral reef sites over water depths ranging from 1 to 20 m. Results suggest that ICESat-2 could be an effective approach for calibrating and validating empirical and radiative transfer methods, alike, for estimating shallow-water bathymetry from remote sensing imagery, thereby enabling the immediate potential for shallow-water bathymetric mapping of Earth’s reefs.