Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-Term Use of a Sensory Prosthesis Improves Function in a Patient With Peripheral Neuropathy: A Case Report

Background: Peripheral neuropathy (PN) can result in either partial or complete loss of distal sensation resulting in an increased fall risk. Walkasins® uses a shoe insert to detect the magnitude and direction of sway and sends signals to a leg unit that provides sensory balance cues. The objective of this case report is to describe the long-term influence of the Walkasins® lower limb sensory neuroprosthesis on balance and gait for an individual with diabetic PN. Case Description: A 51-year-old male with a 3-year history of PN and a 10-year history of type II diabetes mellitus was fitted bilaterally with Walkasins® and utilized them 8–10 hours/day for more than 2 years. Although, vibration and tactile sensation thresholds were severely impaired at his 1st metatarsophalangeal joint and the lateral malleolus bilaterally he could perceive tactile stimuli from the Walkasins® above the ankles. Outcomes: Following Walkasins® use, his Activities-specific Balance Confidence Scale (ABC) scores improved from 33 to 80%. His mean Vestibular Activities of Daily Living (VADL) scores decreased from 3.54 to 1. His Functional Gait Assessment (FGA) scores increased from 13/30 to 28/30 and his miniBESTest scores improved from 15/28 to 26/28. Gait speed increased from 0.23 to 1.5 m/s. The patient described a decrease in pain and cramping throughout his lower extremities and an increase in function. Discussion: Gait and balance improved with the use of the Walkasins® and participation in a wellness program. This improvement suggests that the use of sensory substitution devices, such as the Walkasins®, may replace sensory deficits related to gait and balance dysfunction experienced by patients with PN. Further research is needed to determine if other patients will have a similar response and what the necessary threshold of sensory function is to benefit from use of the Walkasins®.
The Cerebellum Is Related to Cognitive Dysfunction in White Matter Hyperintensities

Objective White matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) is frequently presumed to be secondary to cerebral small vessel disease (CSVD) and associated with cognitive decline. The cerebellum plays a key role in cognition and has dense connections with other brain regions. Thus, the aim of this study was to investigate if cerebellar abnormalities could occur in CSVD patients with WMHs and the possible association with cognitive performances. Methods A total of 104 right-handed patients with WMHs were divided into the mild WMHs group (n = 39), moderate WMHs group (n = 37), and severe WMHs group (n = 28) according to the Fazekas scale, and 36 healthy controls were matched for sex ratio, age, education years, and acquired resting-state functional MRI. Analysis of voxel-based morphometry of gray matter volume (GMV) and seed-to-whole-brain functional connectivity (FC) was performed from the perspective of the cerebellum, and their correlations with neuropsychological variables were explored. Results The analysis revealed a lower GMV in the bilateral cerebellum lobule VI and decreased FC between the left- and right-sided cerebellar lobule VI with the left anterior cingulate gyri in CSVD patients with WMHs. Both changes in structure and function were correlated with cognitive impairment in patients with WMHs. Conclusion Our study revealed damaged GMV and FC in the cerebellum associated with cognitive impairment. This indicates that the cerebellum may play a key role in the modulation of cognitive function in CSVD patients with WMHs.
miRNA-Based Signature Associated With Tumor Mutational Burden in Colon Adenocarcinoma

Colon adenocarcinoma (COAD) is one of the most common malignant tumors. Tumor mutation burden (TMB) has become an independent biomarker for predicting the response to immune checkpoint inhibitors (ICIs). miRNAs play an important role in cancer-related immune regulation. However, the relationship between miRNA expression and TMB in COAD remains unclear. Therefore, the transcriptome profiling data, clinical data, mutation annotation data, and miRNA expression profiles for cases of COAD were downloaded from the TCGA database. Subsequently, 323 COAD cases were randomly divided into training and test sets. The differential expression of miRNAs in the high and low TMB groups in the training set was obtained as a signature using the least absolute shrinkage and selection operator (LASSO) logistic regression and verified in the test set. Based on the LASSO method, principal component analysis (PCA), and ROC, we found that the signature was credible because it can discriminate between high and low TMB levels. In addition, the correlation between the 18-miRNA-based signature and immune checkpoints was performed, followed by qRT-PCR, to measure the relative expression of 18 miRNAs in COAD patients. The miRNA-based model had a strong positive correlation with TMB and a weak positive correlation with CTLA4 and CD274 (PD-L1). However, no correlation was observed between the model and SNCA (PD-1). Finally, enrichment analysis of the 18 miRNAs was performed to explore their biological functions. The results demonstrated that 18 miRNAs were involved in the process of immunity and cancer pathways. In conclusion, the 18-miRNA-based signature can effectively predict and discriminate between the different TMB levels of COAD and provide a guide for its treatment with ICIs.
In vivo Inhibition of the 3-Dehydroquinate Synthase by 7-Deoxysedoheptulose Depends on Promiscuous Uptake by Sugar Transporters in Cyanobacteria

7-Deoxysedoheptulose (7dSh) is a bioactive deoxy-sugar actively excreted by the unicellular cyanobacterium Synechococcus elongatus PCC 7942 (S. elongatus) but also Streptomyces setonensis. In our previous publications we have shown that in S. elongatus, 7dSh is exclusively synthesized by promiscuous enzyme activity from an inhibitory by-product of radical SAM enzymes, without a specific gene cluster being involved. Additionally, we showed that 7dSh inhibits the growth of cyanobacteria, but also the growth of plants and fungi, presumably by inhibiting the 3-dehydroquinate synthase (DHQS), the second enzyme of the shikimate pathway, as the substrate of this enzyme strongly accumulates in cells treated with 7dSh. In this study, by using purified DHQS of Anabaena variabilis ATCC 29413 (A. variabilis) we biochemically confirmed that 7dSh is a competitive inhibitor of this enzyme. By analyzing the effect of 7dSh on a subset of cyanobacteria from all the five subsections, we identified different species whose growth was inhibited by 7dSh. We also found that in some of the susceptible cyanobacteria import of 7dSh is mediated by structurally different and promiscuous transporters: 7dSh can be taken up by the fructose ABC-transporter in A. variabilis and via the glucose permease in Synechocystis sp. PCC 6803 (Synechocystis sp.). In both cases, an effective uptake and thereby intracellular enrichment of 7dSh was essential for the inhibitory activity. Importantly, spontaneous mutations in the sugar transporters of A. variabilis and Synechocystis sp. not only disabled growth of the two strains on fructose and glucose, respectively, but also almost abolished their sensitivity to 7dSh. Although we have clearly shown in these examples that the effective uptake plays an essential role in the inhibitory effect of 7dSh, questions remain about how 7dSh resistance works in other (cyano)bacteria. Also, the involvement of a putative ribokinase in 7dSh resistance in the producer strain S. elongatus remained to be further investigated. Overall, these data establish 7dSh as the first allelochemical targeting the shikimate pathway in other cyanobacteria and plants and suggest a role of 7dSh in niche competition.
Integrated Analysis of Microarray and RNA-Seq Data for the Identification of Hub Genes and Networks Involved in the Pancreatic Cancer

Pancreatic cancer (PaCa) is the seventh most fatal malignancy, with more than 90% mortality rate within the first year of diagnosis. Its treatment can be improved the identification of specific therapeutic targets and their relevant pathways. Therefore, the objective of this study is to identify cancer specific biomarkers, therapeutic targets, and their associated pathways involved in the PaCa progression. RNA-seq and microarray datasets were obtained from public repositories such as the European Bioinformatics Institute (EBI) and Gene Expression Omnibus (GEO) databases. Differential gene expression (DE) analysis of data was performed to identify significant differentially expressed genes (DEGs) in PaCa cells in comparison to the normal cells. Gene co-expression network analysis was performed to identify the modules co-expressed genes, which are strongly associated with PaCa and as well as the identification of hub genes in the modules. The key underlaying pathways were obtained from the enrichment analysis of hub genes and studied in the context of PaCa progression. The significant pathways, hub genes, and their expression profile were validated against The Cancer Genome Atlas (TCGA) data, and key biomarkers and therapeutic targets with hub genes were determined. Important hub genes identified included ITGA1, ITGA2, ITGB1, ITGB3, MET, LAMB1, VEGFA, PTK2, and TGFβ1. Enrichment analysis characterizes the involvement of hub genes in multiple pathways. Important ones that are determined are ECM–receptor interaction and focal adhesion pathways. The interaction of overexpressed surface proteins of these pathways with extracellular molecules initiates multiple signaling cascades including stress fiber and lamellipodia formation, PI3K-Akt, MAPK, JAK/STAT, and Wnt signaling pathways. Identified biomarkers may have a strong influence on the PaCa early stage development and progression. Further, analysis of these pathways and hub genes can help in the identification of putative therapeutic targets and development of effective therapies for PaCa.
A Random Forest and Current Fault Texture Feature–Based Method for Current Sensor Fault Diagnosis in Three-Phase PWM VSR

Three-phase PWM voltage-source rectifier (VSR) systems have been widely used in various energy conversion systems, where current sensors are the key component for state monitoring and system control. The current sensor faults may bring hidden danger or damage to the whole system; therefore, this paper proposed a random forest (RF) and current fault texture feature–based method for current sensor fault diagnosis in three-phase PWM VSR systems. First, the three-phase alternating currents (ACs) of the three-phase PWM VSR are collected to extract the current fault texture features, and no additional hardware sensors are needed to avoid causing additional unstable factors. Then, the current fault texture features are adopted to train the random forest current sensor fault detection and diagnosis (CSFDD) classifier, which is a data-driven CSFDD classifier. Finally, the effectiveness of the proposed method is verified by simulation experiments. The result shows that the current sensor faults can be detected and located successfully and that it can effectively provide fault locations for maintenance personnel to keep the stable operation of the whole system.
Human D-aspartate Oxidase: A Key Player in D-aspartate Metabolism

In recent years, the D-enantiomers of amino acids have been recognized as natural molecules present in all kingdoms, playing a variety of biological roles. In humans, d-serine and d-aspartate attracted attention for their presence in the central nervous system. Here, we focus on d-aspartate, which is involved in glutamatergic neurotransmission and the synthesis of various hormones. The biosynthesis of d-aspartate is still obscure, while its degradation is due to the peroxisomal flavin adenine dinucleotide (FAD)-containing enzyme d-aspartate oxidase. d-Aspartate emergence is strictly controlled: levels decrease in brain within the first days of life while increasing in endocrine glands postnatally and through adulthood. The human d-aspartate oxidase (hDASPO) belongs to the d-amino acid oxidase-like family: its tertiary structure closely resembles that of human d-amino acid oxidase (hDAAO), the enzyme that degrades neutral and basic d-amino acids. The structure-function relationships of the physiological isoform of hDASPO (named hDASPO_341) and the regulation of gene expression and distribution and properties of the longer isoform hDASPO_369 have all been recently elucidated. Beyond the substrate preference, hDASPO and hDAAO also differ in kinetic efficiency, FAD-binding affinity, pH profile, and oligomeric state. Such differences suggest that evolution diverged to create two different ways to modulate d-aspartate and d-serine levels in the human brain. Current knowledge about hDASPO is shedding light on the molecular mechanisms underlying the modulation of d-aspartate levels in human tissues and is pushing novel, targeted therapeutic strategies. Now, it has been proposed that dysfunction in NMDA receptor-mediated neurotransmission is caused by disrupted d-aspartate metabolism in the nervous system during the onset of various disorders (such as schizophrenia): the design of suitable hDASPO inhibitors aimed at increasing d-aspartate levels thus represents a novel and useful form of therapy.
A Comparison of Closed Loop vs. Fixed Frequency tACS on Modulating Brain Oscillations and Visual Detection

Transcranial alternating current stimulation has emerged as an effective tool for the exploration of brain oscillations. By applying a weak alternating current between electrodes placed on the scalp matched to the endogenous frequency, tACS enables the specific modulation of targeted brain oscillations This results in alterations in cognitive functions or persistent physiological changes. Most studies that utilize tACS determine a fixed stimulation frequency prior to the stimulation that is kept constant throughout the experiment. Yet it is known that brain rhythms can encounter shifts in their endogenous frequency. This could potentially move the ongoing brain oscillations into a frequency region where it is no longer affected by the stimulation, thereby decreasing or negating the effect of tACS. Such an effect of a mismatch between stimulation frequency and endogenous frequency on the outcome of stimulation has been shown before for the parietal alpha-activity. In this study, we employed an intermittent closed loop stimulation protocol, where the stimulation is divided into short epochs, between which an EEG is recorded and rapidly analyzed to determine a new stimulation frequency for the next stimulation epoch. This stimulation protocol was tested in a three-group study against a classical fixed stimulation protocol and a sham-treatment. We targeted the parietal alpha rhythm and hypothesized that this setup will ensure a constant close match between the frequencies of tACS and alpha activity. This closer match should lead to an increased modulation of detection of visual luminance changes depending on the phase of the tACS and an increased rise in alpha peak power post stimulation when compared to a protocol with fixed pre-determined stimulation frequency. Contrary to our hypothesis, our results show that only a fixed stimulation protocol leads to a persistent increase in post-stimulation alpha power as compared to sham. Furthermore, in none of the stimulated groups significant modulation of detection performance occurred. While the lack of behavioral effects is inconclusive due to the short selection of different phase bins and trials, the physiological results suggest that a constant stimulation with a fixed frequency is actually beneficial, when the goal is to produce persistent synaptic changes.
Blood Pressure Changes After a Health Promotion Program Among Mexican Workers

Background: Cardiovascular disease is becoming increasingly prevalent in low and middle-income countries (LMIC), and high blood pressure (BP) is one of the main risk factors. The efficacy and sustainability of worksite health promotion (WHP) programs for BP reduction in LMIC have yet to be determined. Methods: This non-randomized company-based trial evaluated 6- and 12-months effects of a WHP intervention on BP among 2,002 participating workers from seven Mexican companies. Intervention and control groups were assigned at the company level. The intervention included nutrition counseling, physical exercise, and stress management components. Mixed models assessed differences in BP change between intervention and control companies in intent-to-treat (ITT), per-protocol (PerP), and as-treated (AsTr) analyses, and also within-group changes stratified by company, intervention component, and baseline cardiovascular risk factor levels. All analyses were adjusted for potential confounders. We accounted for missing data and loss to follow-up using inverse probability of censoring weighting. Results: ITT analyses revealed mean BP change differences of −1.1 mmHg at 12 months (95% CI: −2.9; 0.6) in intervention companies relative to control companies. PerP and AsTr analyses confirmed this finding. Within-group analyses showed consistent BP reductions at both 6 and 12 months. Substantial differences in BP changes ranging from diastolic −6.1 mmHg, (95% CI: −11.2; −1.2) to systolic −13.0 mmHg (95% CI: −16.0; −10.1) were found among individuals with diabetes at baseline in intervention companies relative to control companies. Conclusion: After 1 year, WHP was associated with modest but uncertain BP reductions. Substantial reductions were mainly observed among diabetic workers.
STAT3 Partly Inhibits Cell Proliferation via Direct Negative Regulation of FST Gene Expression

Follistatin (FST) is a secretory glycoprotein and belongs to the TGF-β superfamily. Previously, we found that two single nucleotide polymorphisms (SNPs) of sheep FST gene were significantly associated with wool quality traits in Chinese Merino sheep (Junken type), indicating that FST is involved in the regulation of hair follicle development and hair trait formation. The transcription regulation of human and mouse FST genes has been widely investigated, and many transcription factors have been identified to regulate FST gene. However, to date, the transcriptional regulation of sheep FST is largely unknown. In the present study, genome walking was used to close the genomic gap upstream of the sheep genomic FST gene and to obtain the FST gene promoter sequence. Transcription factor binding site analysis showed sheep FST promoter region contained a conserved putative binding site for signal transducer and activator of transcription 3 (STAT3), located at nucleotides −423 to −416 relative to the first nucleotide (A, +1) of the initiation codon (ATG) of sheep FST gene. The dual-luciferase reporter assay demonstrated that STAT3 inhibited the FST promoter activity and that the mutation of the putative STAT3 binding site attenuated the inhibitory effect of STAT3 on the FST promoter activity. Additionally, chromatin immunoprecipitation assay (ChIP) exhibited that STAT3 is directly bound to the FST promoter. Cell proliferation assay displayed that FST and STAT3 played opposite roles in cell proliferation. Overexpression of sheep FST significantly promoted the proliferation of sheep fetal fibroblasts (SFFs) and human keratinocyte (HaCaT) cells, and overexpression of sheep STAT3 displayed opposite results, which was accompanied by a significantly reduced expression of FST gene (P < 0.05). Taken together, STAT3 directly negatively regulates sheep FST gene and depresses cell proliferation. Our findings may contribute to understanding molecular mechanisms that underlie hair follicle development and morphogenesis.
Screening of Filamentous fungi for xylanases and cellulases not inhibited by xylose and glucose

Aims: Screening different filamentous fungi for thermostable xylanases and cellulases that would not be inhibited by xylose and glucose, respectively. Methodology: Samples of fungi collected in the Atlantic forest region, Minas Gerais, Brazil, and some fungi from our Culture Collection were used in this screening. All fungi were grown in liquid media containing 1% sugar cane bagasse (SCB). After that, an aliquot of the crude broth was incubated at different temperatures (from 4 to 60 °C) in carboxymethyl cellulose (CMC) or xylan-media plates, for 12 hours. After this period, the plates were stained with Congo Red. Fungi that presented the best results (larger halos) were tested for the effect of adding xylose and glucose in the xylanase and cellulases activities, respectively. Crude extracts obtained from fungi grown in SCB were used for laccase and lichenase assay. Results: The screening on agar plates with CMC/xylan presented halos of different sizes. From all tested fungi, the best cellulase producer was Malbranchea pulchella, which also Original Research Article British Biotechnology Journal, 4(1): 30-39, 2014 31 presented the most thermostable xylanase. Penicillium griseofulvum presented bigger halos at all temperatures tested, but the xylanase lost almost 14% of its stability in higher temperatures. The effect of xylose and glucose on the enzymatic activities recorded dosedependent. It was observed that 20% activation of the enzymes produced by M. pulchella with 30 mM glucose or 20 mM xylose to cellulase and xylanase, respectively. It was observed a loss of less than 20% for P. griseofulvum xylolytic activity using 50 mM xylose. Lichenase was detected in some fungi prospected but laccase was not detected. Conclusion: Malbranchea pulchella was a good producer of xylanase and cellulase tolerant to xylose and glucose, respectively. Other studies must be performed with this fungus so that it can be used in the future for biotechnological purposes.
Wheat Rhizosphere Metagenome Reveals Newfound Potential Soil Zn-Mobilizing Bacteria Contributing to Cultivars’ Variation in Grain Zn Concentration

An effective solution to global human zinc (Zn) deficiency is Zn biofortification of staple food crops, which has been hindered by the low available Zn in calcareous soils worldwide. Many culturable soil microbes have been reported to increase Zn availability in the laboratory, while the status of these microbes in fields and whether there are unculturable Zn-mobilizing microbes remain unexplored. Here, we use the culture-independent metagenomic sequencing to investigate the rhizosphere microbiome of three high-Zn (HZn) and three low-Zn (LZn) wheat cultivars in a field experiment with calcareous soils. The average grain Zn concentration of HZn was higher than the Zn biofortification target 40 mg kg–1, while that of LZn was lower than 40 mg kg–1. Metagenomic sequencing and analysis showed large microbiome difference between wheat rhizosphere and bulk soil but small difference between HZn and LZn. Most of the rhizosphere-enriched microbes in HZn and LZn were in common, including many of the previously reported soil Zn-mobilizing microbes. Notably, 30 of the 32 rhizosphere-enriched species exhibiting different abundances between HZn and LZn possess the functional genes involved in soil Zn mobilization, especially the synthesis and exudation of organic acids and siderophores. Most of the abundant potential Zn-mobilizing species were positively correlated with grain Zn concentration and formed a module with strong interspecies relations in the co-occurrence network of abundant rhizosphere-enriched microbes. The potential Zn-mobilizing species, especially Massilia and Pseudomonas, may contribute to the cultivars’ variation in grain Zn concentration, and they deserve further investigation in future studies on Zn biofortification.