Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of key pathways and genes in different types of chronic kidney disease based on WGCNA

Chronic kidney disease (CKD) is a highly heterogeneous nephrosis that occurs when the structure and function of the kidney is damaged. Gene expression studies have been widely used to elucidate various biological processes; however, the gene expression profile of CKD is currently unclear. The present study aimed to identify diagnostic biomarkers and therapeutic targets using renal biopsy sample data from patients with CKD. Gene expression data from 30 patients with CKD and 21 living donors were analyzed by weighted gene co-expression network analysis (WGCNA), in order to identify gene networks and profiles for CKD, as well as its specific characteristics, and to potentially uncover diagnostic biomarkers and therapeutic targets for patients with CKD. In addition, functional enrichment analysis was performed on co-expressed genes to determine modules of interest. Four co-expression modules were constructed from the WGCNA. The number of genes in the constructed modules ranged from 269 genes in the Turquoise module to 60 genes in the Yellow module. All four co-expression modules were correlated with CKD clinical traits (P<0.05). For example, the Turquoise module, which mostly contained genes that were upregulated in CKD, was positively correlated with CKD clinical traits, whereas the Blue, Brown and Yellow modules were negatively correlated with clinical traits. Functional enrichment analysis revealed that the Turquoise module was mainly enriched in genes associated with the ‘defense response’, ‘mitotic cell cycle’ and ‘collagen catabolic process’ Gene Ontology (GO) terms, implying that genes involved in cell cycle arrest and fibrogenesis were upregulated in CKD. Conversely, the Yellow module was mainly enriched in genes associated with ‘glomerulus development’ and ‘kidney development’ GO terms, indicating that genes associated with renal development and damage repair were downregulated in CKD. The hub genes in the modules were acetyl-CoA carboxylase α, cyclin-dependent kinase 1, Wilm's tumour 1, NPHS2 stomatin family member, podocin, JunB proto-oncogene, AP-1 transcription factor subunit, activating transcription factor 3, forkhead box O1 and v-abl Abelson murine leukemia viral oncogene homolog 1, which were confirmed to be significantly differentially expressed in CKD biopsies. Combining the eight hub genes enabled a high capacity for discrimination between patients with CKD and healthy subjects, with an area under the receiver operating characteristic curve of 1.00. In conclusion, this study provided a framework for co-expression modules of renal biopsy samples from patients with CKD and living donors, and identified several potential diagnostic biomarkers and therapeutic targets for CKD.
Defocused Image Changes Signaling of Ganglion Cells in the Mouse Retina

Myopia is a substantial public health problem worldwide. Although it is known that defocused images alter eye growth and refraction, their effects on retinal ganglion cell (RGC) signaling that lead to either emmetropization or refractive errors have remained elusive. This study aimed to determine if defocused images had an effect on signaling of RGCs in the mouse retina. ON and OFF alpha RGCs and ON–OFF RGCs were recorded from adult C57BL/6J wild-type mice. A mono green organic light-emitting display presented images generated by PsychoPy. The defocused images were projected on the retina under a microscope. Dark-adapted mouse RGCs were recorded under different powers of projected defocused images on the retina. Compared with focused images, defocused images showed a significantly decreased probability of spikes. More than half of OFF transient RGCs and ON sustained RGCs showed disparity in responses to the magnitude of plus and minus optical defocus (although remained RGCs we tested exhibited similar response to both types of defocus). ON and OFF units of ON–OFF RGCs also responded differently in the probability of spikes to defocused images and spatial frequency images. After application of a gap junction blocker, the probability of spikes of RGCs decreased with the presence of optical defocused image. At the same time, the RGCs also showed increased background noise. Therefore, defocused images changed the signaling of some ON and OFF alpha RGCs and ON–OFF RGCs in the mouse retina. The process may be the first step in the induction of myopia development. It appears that gap junctions also play a key role in this process.
Flowering Stage and Daytime Affect Scent Emission of Malus ioensis “Prairie Rose”

Flowering crabapple is an important ornamental flower. It is vital to understand the floral scent properties and the associated release dynamics for carrying out fragrant flower breeding or floral regulation of crabapple. Static headspace solid-phase microextraction coupled with gas chromatography-mass spectrometry was used to detect the volatile compounds in Malus ioensis “Prairie Rose” flowers at different flowering stages and at different day-night time. The results showed that methylheptenone, phenylethanol, geranylacetone, 2-(4-methoxyphenyl)ethanol, α-cedrene were the major compounds in M. ioensis “Prairie Rose”, but the compounds released during different stages and different day-night time were significantly different (P < 0.0001). A total of 25 volatile compounds were identified from the four flowering stages. The floral scents in the initial and flowering stages were the most similar (dissimilarity 0.21). The main compounds in these two stages were geranylacetone and methylheptenone, and the contents of geranylacetone and phenylethanol were positively correlated with the flowering stages. From the bud stage to the end of flowering, the total amount of volatile compounds released showed an initial increase followed by a decrease and the amounts of compounds released during the initial flowering stage were the highest. The aliphatic and benzenoids content was significant higher in the daytime than at night. A total of 15 compounds were detected in the five time periods. Methylheptenone and phenylethanol were particularly released in the 10:00–12:00 and 15:00–17:00 time periods. There were only three common compounds among the five time periods and the types of flower volatiles released during the daytime were obviously higher than those released at night. From the nocturnal to diurnal, the amount of flower volatiles released first increased, then decreased, and the release reached a peak between 10 am and 12 noon, which was consistent with the pollination biological characteristics of Malus flowers. Our findings are important for understanding the mechanism of insect visits to crabapple and the regulation of crabapple flower scent.
Connective Tissue Ultrastructure: A Direct Comparison between Conventional Specimen Preparation and High‐Pressure Freezing/Freeze‐Substitution

It is generally agreed within the microscopy community that the quality of ultrastructure within the connective tissue matrix resulting from high‐pressure freezing followed by freeze‐substitution (HPF/FS) far exceeds that gained following the “conventional” preparation method, which includes aqueous fixation, dehydration, and embedding. Exposure to cryogen at high pressure is the only cryopreservation method capable of vitrifying tissue structure to a depth exceeding 200 μm. Cells within connective tissues prepared by HPF/FS are universally larger, filling the commonly seen void at the juncture between cell and matrix. Without significant shrinkage of cells and the coincident extraction of the cytosolic components, well‐resolved organelles are less clustered within an expanded cytosol. Much of the artifact from “conventional” methods occurs as large space filling and also smaller fibril‐associated proteoglycans are extracted during fixation. However, the visualization of some matrix features by electron microscopy is actually dependent on the collapse or extraction of these “masking” components. Herein, we argue that an impression of ultrastructure within commonly studied matrices, in particular skin, is best gained following the evaluation of both conventional preparations and tissue prepared by HPF/FS. Anat Rec, 2019. © 2019 American Association for Anatomy
Using blended instruction to teach academic vocabulary collocations: A case study

Using Blended Instruction to Teach Academic Vocabulary Collocations: A Case Study M. Teresa das Neves Seesink Learning second language vocabulary has always been a challenge for second language (L2) learners. Transferring new vocabulary to an active stage has been an even greater challenge. In the 1990s, Lewis (2002a) proposed the Lexical Approach as a means to help L2 learners with vocabulary acquisition. This approach encouraged the teaching of vocabulary in chunks, or in other words, putting emphasis on collocations. Focus on vocabulary collocations was suggested by several researchers (Brown, 1974; Hinkel, 2004; Lewis, 2001). They supported the teaching of collocations via in-class exercises. Cobb (1999) and Kaur and Hegelheimer (2005) showed that the use of a concordancer–an online resource which provides information on collocation–was beneficial to learners’ development of active vocabulary. However, studies focusing on explicit teaching of academic vocabulary collocation via blended instruction, which consists of a combination of in-class and online instruction, were not found. This case study examined how teaching academic vocabulary collocations affected the writing development of six students in an Intensive English Program (IEP). Collocation was presented and taught both in-class and via Moodle, the course management software used as the online environment. The study also looked at how these learners perceived blended instruction. These learners came from various language backgrounds. Data were collected via a questionnaire, in-class observations, and learners’ journals, writing samples, mid-course reflections, online logs, and interviews. The class instructor also provided data in the form of instructor’s journals and an interview. The results demonstrated that prior to teaching collocations, the teacher needed to clarify the concept and its importance to learners. Moreover, the results showed that learners benefited from explicit teaching of vocabulary collocations. Regarding blended instruction, the learners perceived the online component as a review/practice tool rather than an integral part of the course. The study also revealed a certain lack of commitment with the online exercises, especially when these exercises were not directly affecting the learners’ grades.
Microbiome Signatures Associated with Steatohepatitis and Moderate to Severe Fibrosis in Children With Nonalcoholic Fatty Liver Disease.

BACKGROUND & AIMS The intestinal microbiome might affect development and severity of nonalcoholic fatty liver disease (NAFLD). We analyzed microbiomes of children with and without NAFLD. METHODS We performed a prospective, observational, cross-sectional study of 87 children (8-17 years old) with biopsy-proven NAFLD and 37 children with obesity without NAFLD (controls). Fecal samples were collected and microbiome composition and functions were assessed using 16S rRNA amplicon sequencing and metagenomic shotgun sequencing. Microbial taxa were identified using zero-inflated negative binomial modeling. Genes contributing to bacterial pathways were identified using gene set enrichment analysis. RESULTS Fecal microbiomes of children with NAFLD had lower α-diversity than controls (3.32 vs 3.52; P=.016). Fecal microbiomes from children with nonalcoholic steatohepatitis (NASH) had lowest α-diversity (controls, 3.52; NAFLD, 3.36; borderline NASH, 3.37; NASH 2.97; P= .001). High abundance of Prevotella copri was associated with more severe fibrosis (P=.036). Genes for lipopolysaccharide biosynthesis were enriched in microbiomes from children NASH (P<.001). Classification and regression tree model with level of alanine aminotransferase and relative abundance of the lipopolysaccharide pathway gene encoding 3-deoxy-D-manno-octulosonate 8-phosphate-phosphatase identified patients with NASH with an area under the receiver operating characteristic curve value of 0.92. Genes involved in flagellar assembly were enriched in fecal microbiomes of patients with moderate to severe fibrosis (P<.001). Classification and regression tree models based on level of alanine aminotransferase and abundance of genes encoding flagellar biosynthesis protein had good accuracy for identifying cases with moderate to severe fibrosis (area under the receiver operating characteristic curve, 0.87). CONCLUSIONS In an analysis of fecal microbiomes of children with NAFLD, we associated NAFLD and NASH with intestinal dysbiosis. NAFLD and its severity were associated with greater abundance of genes encoding inflammatory bacterial products. Alterations to the intestinal microbiome might contribute to pathogenesis of NAFLD and be used as markers of disease or severity.
The Significance of Chirality in Drug Design and Synthesis of Bitopic Ligands as D3 Receptor (D3R) Selective Agonists.

Because of the large degree of homology among dopamine D2-like receptors, discovering ligands capable of discriminating between the D2, D3, and D4 receptor subtypes remains a significant challenge. Previous work has exemplified the use of bitopic ligands as a powerful strategy in achieving subtype selectivity for agonists and antagonists alike. Inspired by the potential for chemical modification of the D3 preferential agonists (+)-PD128,907 (1) and PF592,379 (2), we synthesized bitopic structures to further improve their D3R selectivity. We found that the (2 S,5 S) conformation of scaffold 2 resulted in a privileged architecture with increased affinity and selectivity for the D3R. In addition, a cyclopropyl moiety incorporated into the linker and full resolution of the chiral centers resulted in lead compound 53 and eutomer 53a that demonstrate significantly higher D3R binding selectivities than the reference compounds. Moreover, the favorable metabolic stability in rat liver microsomes supports future studies in in vivo models of dopamine system dysregulation.
Mapping Variation in Breast Cancer Screening: Where to Intervene?

Small geographic areas with lower mammography screening participation rates may reflect gaps in screening efforts. Our objective was to use spatial analyses to understand disparities in mammography screening use and to identify factors to increase its uptake in areas that need it in Lyon metropolitan area, France. Data for screened women between the ages of 50 and 74 were analyzed. Census blocks of screened and non screened women were extracted from the mammography screening programme 2015–2016 dataset. We used spatial regression models, within a generalized additive framework to determine clusters of census blocks with significantly higher prevalence of non-participation of mammography screening. Smoothed risk maps were crude and adjusted on the following covariates: deprivation index and opportunistic screening. Among 178,002 women aged 50 to 74, 49.9% received mammography screening. As hypothesized, women living in highly deprived census blocks had lower participation rates compared to less deprived blocks, 45.2% vs. 51.4% p < 0.001. Spatial analyses identified four clusters, one located in an urban area and three in suburban areas. Moreover, depending on the location of the cluster, the influence came from different variables. Knowing the impact of site-specific risk factors seems to be important for implementing an appropriate prevention intervention.
Gadolinium Retention in the Brain: An MRI Relaxometry Study of Linear and Macrocyclic Gadolinium-Based Contrast Agents in Multiple Sclerosis

BACKGROUND AND PURPOSE: Brain gadolinium retention is consistently reported for linear gadolinium-based contrast agents, while the results for macrocyclics are contradictory and potential clinical manifestations remain controversial. Furthermore, most previous studies are based on conventional T1-weighted MR imaging. We therefore aimed to quantitatively investigate longitudinal and transversal relaxation in the brain in relation to previous gadolinium-based contrast agent administration and explore associations with disability in multiple sclerosis. MATERIALS AND METHODS: Eighty-five patients with MS and 21 healthy controls underwent longitudinal and transverse relaxation rate (R1 and R2) relaxometry. Patients were divided into linear, mixed, and macrocyclic groups based on previous gadolinium-based contrast agent administration. Neuropsychological testing was performed in 53 patients. The dentate nucleus, globus pallidus, caudate nucleus, and thalamus were manually segmented. Repeatability measures were also performed. RESULTS: The relaxometry was robust (2.0% scan-rescan difference) and detected higher R1 (dentate nucleus, globus pallidus, caudate nucleus, thalamus) and R2 (globus pallidus, caudate nucleus) in patients receiving linear gadolinium-based contrast agents compared with controls. The number of linear gadolinium-based contrast agent administrations was associated with higher R1 and R2 in all regions (except R2 in the thalamus). No similar differences and associations were found for the macrocyclic group. Higher relaxation was associated with lower information-processing speed (dentate nucleus, thalamus) and verbal fluency (caudate nucleus, thalamus). No associations were found with physical disability or fatigue. CONCLUSIONS: Previous linear, but not macrocyclic, gadolinium-based contrast agent administration is associated with higher relaxation rates in a dose-dependent manner. Higher relaxation in some regions is associated with cognitive impairment but not physical disability or fatigue in MS. The findings should be interpreted with care but encourage studies into gadolinium retention and cognition.
Estimating historical forest density from land-survey data: A response to Baker and Williams (2018).

In the Western United States, historical forest conditions are used to inform land management and ecosystem restoration goals (North et al. 2009, Stephens et al. 2016). This interest is based on the premise that historical forests were resilient to ecological disturbances (Keane et al. 2018). Researchers throughout the US have used the General Land Office (GLO) surveys of the late 19th and early 20th centuries to estimate historical forest conditions (Bourdo 1956, Schulte and Mladenoff 2001, Cogbill et al. 2002, Paciorek et al. 2016). These surveys were conducted throughout the US and represent a systematic, historical sample of trees across a broad geographic area. This article is protected by copyright. All rights reserved.
3D printed microstructures for flexible electronic devices

Flexible and stretchable electronics have attracted increasing attention and been widely used in wearable devices and electronic skins, where the circuits for flexible and stretchable electronics are typically in-plane-based 2D geometries. Here, we introduce a 3D microprinting technology that can expand one more dimension of the circuit in flexible electronics. We fabricated three-dimensional serpentine microstructures based on direct laser writing. These microstructures with a thin metal coated layer can be used as stretchable conducting meshes. Soft silicone serving as a substrate and encapsulations for these 3D microstructures enables great light transmittance (>90% in visible light range) and flexibility with 114° bending and 24° twisting. Further optimization of the mechanical design of the 3D microstructures can also enhance the stretchability up to 13.8%. These results indicate 3D flexible electronics can be realized by simple microprinting methods. Furthermore, 3D microprinting would also allow for the precise fabrication of other 3D structures, such as mechanically active 3D mesostructures, for the function of mechanical and electrical testing.
Moringa Extract Attenuates Inflammatory Responses and Increases Gene Expression of Casein in Bovine Mammary Epithelial Cells

Simple Summary Bovine mastitis, an inflammatory disease in the udder of dairy cows, is a common disease that causes low quantity and quality of bovine milk. Treatment and prevention of bovine mastitis still rely on antibiotics. However, concerns about excessive use of antibiotics have been raised due to the development of antibiotic-resistant bacteria. Therefore, natural products possessing protective effects in bovine udder have gained a lot of interests. Our objective was to investigate the possibility of Moringa oleifera extract (ME) in protecting bovine epithelial mammary cells. Our results demonstrated that methanol extract of Moringa oleifera leaves has beneficial effects in bovine mammary epithelial cells through its anti-inflammatory, antioxidant, and casein production properties. Data suggest that moringa extract could be a good feed supplement for protecting the udder of cows from inflammatory responses due to mastitis. Abstract Bovine mastitis is a common inflammatory disease in the udder of dairy cows that causes economic loss to dairy industries. The development of alternative strategies, especially the utilization of natural products, e.g., Moringa oleifera, has gained a lot of interests. The objective of the current study was to investigate the protective effects of moringa extract (ME) in bovine mammary epithelial cells (MAC-T) in in vitro settings. Radical scavenging capacities and anti-inflammatory properties of ME were examined using lipopolysaccharide (LPS)-challenged MAC-T cells. ME showed significant radical scavenging activities. In addition, ME decreased reactive oxygen species produced by LPS in cells. ME also attenuated inflammatory cyclooxygenase-2 expression induced by LPS by down-regulating NF-κB signaling cascade. Moreover, ME ameliorated LPS-induced pro-inflammatory cytokines including tumor necrosis factor-α, interleukin-1β, and interleukin-6. Furthermore, ME up-regulated mRNA expression levels of heme oxygenase-1, NAD(P)H: quinone oxidoreductase-1, and thioredoxin reductase 1. Importantly, ME promoted differentiated MAC-T cells by increasing mRNA expression levels of α-casein S1, α-casein S2, and β-casein. In conclusion, ME has beneficial effects in bovine mammary epithelial cells through its anti-inflammatory, antioxidant, and casein production properties. Our study provides evidence that ME could be a good candidate for a feed supplement to decrease inflammatory responses due to bovine mastitis.
Real Time Estimation of the Pose of a Lower Limb Prosthesis from a Single Shank Mounted IMU

The command of a microprocessor-controlled lower limb prosthesis classically relies on the gait mode recognition. Real time computation of the pose of the prosthesis (i.e., attitude and trajectory) is useful for the correct identification of these modes. In this paper, we present and evaluate an algorithm for the computation of the pose of a lower limb prosthesis, under the constraints of real time applications and limited computing resources. This algorithm uses a nonlinear complementary filter with a variable gain to estimate the attitude of the shank. The trajectory is then computed from the double integration of the accelerometer data corrected from the kinematics of a model of inverted pendulum rolling on a curved arc foot. The results of the proposed algorithm are evaluated against the optoelectronic measurements of walking trials of three people with transfemoral amputation. The root mean square error (RMSE) of the estimated attitude is around 3°, close to the Kalman-based algorithm results reported in similar conditions. The real time correction of the integration of the inertial measurement unit (IMU) acceleration decreases the trajectory error by a factor of 2.5 compared to its direct integration which will result in an improvement of the gait mode recognition.