Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-Modality Imaging for the Identification of Arrhythmogenic Substrates Prior to Electrophysiology Studies

Noninvasive cardiac imaging is crucial for the characterization of patients who are candidates for cardiac ablations, for both procedure planning and long-term management. Multimodality cardiac imaging can provide not only anatomical parameters but even more importantly functional information that may allow a better risk stratification of cardiac patients. Moreover, fusion of anatomical and functional data derived from noninvasive cardiac imaging with the results of endocavitary mapping may possibly allow a better identification of the ablation substrate and also avoid peri-procedural complications. As a result, imaging-guided electrophysiological procedures are associated with an improved outcome than traditional ablation procedures, with a consistently lower recurrence rate.
Characteristics of Idiopathic Sensory Processing Disorder in Young Children

This study described the developmental and behavioral characteristics of children identified with idiopathic sensory processing disorder (SPD) as well as the relations among specific types of SPD as proposed by the nosology presented by Miller et al. (2007), adaptive behavior profiles, and behaviors associated with mental functioning. A retrospective, non-experimental design applying descriptive and correlational analyses was used. Data were obtained from clinic medical records of 78 children ages 2 to 7 years who were identified with sensory processing problems affecting daily life, but who did not meet criteria for any other neurodevelopmental or mental disorders following a comprehensive diagnostic evaluation. Results revealed that all SPD types as described by current typologies were well represented with the most common being the over-responsivity sensory modulation subtype. Within the sample, 53% of the children displayed more than one SPD type. Atypical externalizing and internalizing behavior scores associated with various mental disorders as measured by the child behavior checklist (CBCL) fell in the borderline dysfunctional range. Adaptive behavior for all developmental domains was below average, and the severity of SPD symptoms moderately and positively correlated with behaviors associated with mental disorders, and with lower adaptive behavior performance. It was concluded that symptoms characteristic of the various types of idiopathic SPD overlap substantially suggesting that current typologies may include more types/subtypes than are necessary or clinically useful. Children with SPD share similar, but often less severe pathological behaviors associated with other mental or related neurodevelopmental disorders. Psychometrically sound measures of SPD are needed, and further study of the neural mechanisms involved in sensory processing deficits is vital for validating idiopathic SPD as its own diagnostic entity.
Echinacea purpurea Ethanol Extract Improves Male Reproductive Dysfunction With Streptozotocin–Nicotinamide-Induced Diabetic Rats

As lifestyle changes, the prevalence of diabetes increases every year. Diabetes-induced male reproductive dysfunction is predominantly due to increased oxidative stress and then results in sperm damage and infertility. Echinacea purpurea is a traditional medicinal herb and is well-known for its immune-modulatory, antioxidative, anti-inflammatory, anticancer, and antiviral activities. The Toll-like receptor 4 (TLR4) plays a critical role in innate immune responses leading to nuclear factor (NF)-κB phosphorylation and release of proinflammatory cytokines including nitric oxide (NO), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α. However, the relation between Echinacea purpurea extract and TLR4 remains unclear. This study aimed to investigate the protective effects on male reproduction of Echinacea purpurea ethanol extract (EPE) against diabetic rats and whether the anti-inflammatory effects were through the TLR4 pathway. Diabetic male Sprague–Dawley (SD) rats were induced by streptozotocin (65 mg/kg) and nicotinamide (230 mg/kg). EPE was tested in three doses (93, 279, and 465 mg/kg p.o. daily) for 4 weeks. Besides, metformin administration (100 mg/kg/day) was treated as a positive control. Results indicated that EPE administration for about 4 weeks improved hyperglycemia and insulin resistance. Additionally, EPE increased sperm motility, protected sperm morphology and mitochondrial membrane potential, as well as protein for testosterone synthesis enzyme. In sperm superoxide dismutase, catalase, and glutathione antioxidants were increased, whereas proinflammatory cytokines, such as NO, IL-1β, and TNF-α were decreased. The testis protein content of TLR4 and downstream phospho-NF-κB p65 also were reduced. The EPE might reduce the production of proinflammatory cytokines via TLR4 pathways and improve diabetes-induced male infertility.
Cross-Whisker Adaptation of Neurons in Layer 2/3 of the Rat Barrel Cortex

Neurons in the barrel cortex respond preferentially to stimulation of one principal whisker and weakly to several adjacent whiskers. Such integration exists already in layer 4, the pivotal recipient layer of thalamic inputs. Previous studies show that cortical neurons gradually adapt to repeated whisker stimulations and that layer 4 neurons exhibit whisker specific adaptation and no apparent interactions with other whiskers. This study aimed to study the specificity of adaptation of layer 2/3 cortical cells. Towards this aim, we compared the synaptic response of neurons to either repetitive stimulation of one of two responsive whiskers or when repetitive stimulation of the two whiskers was interleaved. We found that in most layer 2/3 cells adaptation is whisker-specific. These findings indicate that despite the multi-whisker receptive fields in the cortex, the adaptation process for each whisker-pathway is mostly independent of other whiskers. A mechanism allowing high responsiveness in complex environments.
Decoding Multiple Sound-Categories in the Auditory Cortex by Neural Networks: An fNIRS Study

This study aims to decode the hemodynamic responses (HRs) evoked by multiple sound-categories using functional near-infrared spectroscopy (fNIRS). The six different sounds were given as stimuli (English, non-English, annoying, nature, music, and gunshot). The oxy-hemoglobin (HbO) concentration changes are measured in both hemispheres of the auditory cortex while 18 healthy subjects listen to 10-s blocks of six sound-categories. Long short-term memory (LSTM) networks were used as a classifier. The classification accuracy was 20.38 ± 4.63% with six class classification. Though LSTM networks’ performance was a little higher than chance levels, it is noteworthy that we could classify the data subject-wise without feature selections.
A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level

Whilst the impact of hypoxia and ionizing radiations on gene expression is well-understood, the interplay of these two effects is not. To better investigate this aspect at the gene level human bladder, brain, lung and prostate cancer cell lines were irradiated with photons (6 Gy, 6 MV LINAC) in hypoxic and normoxic conditions and prepared for the whole genome analysis at 72 h post-irradiation. The analysis was performed on the obtained 20,000 genes per cell line using PCA and hierarchical cluster algorithms to extract the most dominant genes altered by radiation and hypoxia. With the help of the introduced novel radiation-in-hypoxia and oxygen-impact profiles, it was possible to overcome cell line specific gene regulation patterns. Based on that, 37 genes were found to be consistently regulated over all studied cell lines. All DNA-repair related genes were down-regulated after irradiation, independently of the oxygen state. Cell cycle-dependent genes showed up-regulation consistent with an observed change in cell population in the S and G2/M phases of the cell cycle after irradiation. Genes behaving oppositely in their regulation behavior when changing the oxygen concentration and being irradiated, were immunoresponse and inflammation related genes. The novel analysis method, and by consequence, the results presented here have shown how it is important to consider the two effects together (oxygen and radiation) when analyzing gene response upon cancer radiation treatment. This approach might help to unrevel new gene patterns responsible for cancer radioresistance in patients.
Association of Myopia and Genetic Variants of TGFB2-AS1 and TGFBR1 in the TGF-β Signaling Pathway: A Longitudinal Study in Chinese School-Aged Children

Background Myopia is a complex multifactorial condition which involves several overlapping signaling pathways mediated by distinct genes. This prospective cohort study evaluated the associations of two genetic variants in the TGF-β signaling pathway with the onset and progression of myopia and ocular biometric parameters in Chinese school-aged children. Methods A total of 556 second grade children were examined and followed up for 3.5 years. Non-cycloplegic refraction and ocular biometric parameters were measured annually. Multivariate regression analysis was used to assess the effect of the TGFBR1 rs10760673 and TGFB2-AS1 rs7550232 variants on the occurrence and progression of myopia. A 10,000 permutations test was used to correct for multiple testing. Functional annotation of single nucleotide polymorphisms (SNPs) was performed using RegulomeDB, HaploReg, and rVarBase. Results A total of 448 children were included in the analysis. After adjustments for gender, age, near work time and outdoor time with 10,000 permutations, the results indicated that the C allele and the AC or CC genotypes of rs7550232 adjacent to TGFB2-AS1 were associated with a significantly increased risk of the onset of myopia in two genetic models (additive: P’ = 0.022; dominant: P’ = 0.025). Additionally, the A allele and the AA or AG genotypes of rs10760673 of TGFBR1 were associated with a significant myopic shift (additive: P’ = 0.008; dominant: P’ = 0.028; recessive: P’ = 0.027). Furthermore, rs10760673 was associated with an increase in axial length (AL) (P’ = 0.013, β = 0.03) and a change in the ratio of AL to the corneal radius of curvature (AL/CRC) (P’ = 0.031, β = 0.003). Analysis using RegulomeDB, HaploReg, and rVarBase indicated that rs7550232 is likely to affect transcription factor binding, any motif, DNase footprint, and DNase peak. Conclusion The present study indicated that rs10760673 and rs7550232 may represent susceptibility loci for the progression and onset of myopia, respectively, in school-aged children. Associations of the variants of the TGFBR1 and TGFB2-AS1 genes with myopia may be mediated by the TGF-β signaling pathway; this hypothesis requires validation in functional studies. This trial was registered as ChiCTR1900020584 at www.Chictr. org.cn.
An Overview on Identification and Regulatory Mechanisms of Long Non-coding RNAs in Fungi

For decades, more and more long non-coding RNAs (lncRNAs) have been confirmed to play important functions in key biological processes of different organisms. At present, most identified lncRNAs and those with known functional roles are from mammalian systems. However, lncRNAs have also been found in primitive eukaryotic fungi, and they have different functions in fungal development, metabolism, and pathogenicity. In this review, we highlight some recent researches on lncRNAs in the primitive eukaryotic fungi, particularly focusing on the identification of lncRNAs and their regulatory roles in diverse biological processes.
Exosome: The Regulator of the Immune System in Sepsis

Sepsis is a syndrome comprised of a series of life-threatening organ dysfunctions caused by a maladjusted body response to infection with no effective treatment. There is growing evidence that the immune system plays a core role in sepsis. Pathogens cause abnormal host immune response and eventually lead to immunosuppression, which is an important cause of death in patients with sepsis. Exosomes are vesicles derived from double invagination of plasma membrane, associating with immune responses closely. The cargos delivered by exosomes into recipient cells, especially immune cells, effectively alter their response and functions in sepsis. In this review, we focus on the effects and mechanisms of exosomes on multiple immune cells, as well as the role of immune cell-derived exosomes in sepsis. This is helpful for us to have an in-depth understanding of the mechanism of immune disorders in sepsis. Exosomes is also expected to become a novel target and therapeutic approach for sepsis.
Individualized Prediction of Colorectal Cancer Metastasis Using a Radiogenomics Approach

Objectives: To evaluate whether incorporating the radiomics, genomics, and clinical features allows prediction of metastasis in colorectal cancer (CRC) and to develop a preoperative nomogram for predicting metastasis. Methods: We retrospectively analyzed radiomics features of computed tomography (CT) images in 134 patients (62 in the primary cohort, 28 in the validation cohort, and 44 in the independent-test cohort) clinicopathologically diagnosed with CRC at Dazhou Central Hospital from February 2018 to October 2019. Tumor tissues were collected from all patients for RNA sequencing, and clinical data were obtained from medical records. A total of 854 radiomics features were extracted from enhanced venous-phase CT of CRC. Least absolute shrinkage and selection operator regression analysis was utilized for data dimension reduction, feature screen, and radiomics signature development. Multivariable logistic regression analysis was performed to build a multiscale predicting model incorporating the radiomics, genomics, and clinical features. The receiver operating characteristic curve, calibration curve, and decision curve were conducted to evaluate the performance of the nomogram. Results: The radiomics signature based on 16 selected radiomics features showed good performance in metastasis assessment in both primary [area under the curve (AUC) = 0.945, 95% confidence interval (CI) 0.892–0.998] and validation cohorts (AUC = 0.754, 95% CI 0.570–0.938). The multiscale nomogram model contained radiomics features signatures, four-gene expression related to cell cycle pathway, and CA 19-9 level. The multiscale model showed good discrimination performance in the primary cohort (AUC = 0.981, 95% CI 0.953–1.000), the validation cohort (AUC = 0.822, 95% CI 0.635–1.000), and the independent-test cohort (AUC = 0.752, 95% CI 0.608–0.896) and good calibration. Decision curve analysis confirmed the clinical application value of the multiscale model. Conclusion: This study presented a multiscale model that incorporated the radiological eigenvalues, genomics features, and CA 19-9, which could be conveniently utilized to facilitate the individualized preoperatively assessing metastasis in CRC patients.
ACCEPTED AUTHOR VERSION OF THE MANUSCRIPT: The influence of a diet supplemented with 20% rye and xylanase in different housing systems on the occurrence of pathogenic bacteria in broiler chickens

Sanitary conditions and diet are important elements determining the occurrence of pathogens in animals. The aim of the research was to assess the effect of an experimental diet with rye and xylanase for broiler chickens in cages and in a free-range system on the intestinal microbiome. The study was carried out in two experimental stages, the first on 224 1-d-old male Ross 308 chickens with an initial weight of 41 g, and the second on 2000 1-d-old male chickens with an initial weight of 42 g. All birds were reared to 42 d of age and fed crumbled starter (1 to 21 d) and pelleted grower–finisher (22 to 42 d) isonitrogenous and isoenergetic diets, supplemented with 20% rye and/or 200 mg/kg xylanase. Directly after slaughter, bacteria were isolated from the cloaca of birds and identified using classical microbiological methods and MALDI-TOF mass spectrometry. The antibiotic susceptibility of the bacteria was assessed by the disc diffusion method. The study showed the presence of abundant bacteria in the gut microbiome of chickens kept in both housing systems. The most frequently isolated bacteria were Escherichia coli , Enterococcus spp. , Proteus spp. , Campylobacter spp. , and Staphylococcus spp. Antibiotic resistance was significantly higher in E. coli , Proteus spp. , and Campylobacter spp. obtained from chickens from the free-range farm, but in the case of Enterococcus and Staphylococcus , resistance was higher in bacteria from caged birds. The high antibiotic resistance among pathogens of the gastrointestinal tract necessitates the search for means to control the microbiome in favour of beneficial bacteria. The significant influence of rye and xylanase on the bacterial content may be the basis for the introduction of this method to support the control of pathogens.
Force Field Parameters for Fe2+4S2−4 Clusters of Dihydropyrimidine Dehydrogenase, the 5-Fluorouracil Cancer Drug Deactivation Protein: A Step towards In Silico Pharmacogenomics Studies

The dimeric dihydropyrimidine dehydrogenase (DPD) metalloenzyme, an adjunct anti-cancer drug target contains highly specialized 4 × Fe2+4S2-4 clusters per chain. These clusters facilitate the catalysis of the rate-limiting step in the pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers a redox catabolic reaction. In the process, majority of administered 5-fluorouracil (5-FU) cancer drug is inactivated while a small proportion is activated to nucleic acid antimetabolites. The occurrence of missense mutations in DPD protein within the general population, including those of African descent, has adverse toxicity effects due to altered 5-FU metabolism. Thus, deciphering mutation effects on protein structure and function is vital, especially for precision medicine purposes. We previously proposed combined molecular dynamics (MD) and dynamic residue network (DRN) analysis to decipher the molecular mechanisms of missense mutations in other proteins. However, the presence of Fe2+4S2-4 clusters in DPD poses a challenge for such in silico studies. The existing AMBER force field parameters cannot accurately describe the Fe2+ center coordination exhibited by this enzyme. Therefore, this study aimed to derive AMBER force field parameters for DPD enzyme Fe2+ centers, using the original Seminario method and collation features Visual Force Field Derivation Toolkit as a supportive approach. All-atom MD simulations were performed to validate the results. Both approaches generated similar force field parameters which accurately described the human DPD protein Fe2+4S2-4 clusters architecture. This information is crucial and opens new avenues for in silico cancer pharmacogenomics and drug discovery related research on 5-FU drug efficacy and toxicity issues.
An Artificial-Intelligence- and Telemedicine-Based Screening Tool to Identify Glaucoma Suspects from Color Fundus Imaging

Backgrounds & Objective Glaucomatous vision loss may be preceded by an enlargement of the cup-to-disc ratio (CDR). We propose to develop and validate an artificial intelligence based CDR grading system that may aid in effective glaucoma-suspect screening. Design, Setting & Participants 1546 disc-centered fundus images were selected including all 457 images from the Retinal Image Database for Optic Nerve Evaluation dataset, and images randomly selected from the Age-Related EyeDisease Study, and Singapore Malay Eye Study to develop the system. First, a proprietary semi-automated software was used by an expert grader to quantify vertical CDR. Then, using CDR below 0.5 (not suspect) and CDR above 0.5 (glaucoma-suspect), deep learning architectures were used to train and test a binary classifier system. Measurements The binary classifier, with glaucoma-suspect as positive, is measured using sensitivity, specificity, accuracy, and AUC. Results The system achieved an accuracy of 89.67% (sensitivity, 83.33%; specificity, 93.89%; AUC, 0.93). For external validation, the Retinal Fundus Image database for Glaucoma Analysis dataset, which has 638 gradable quality images, was used. Here the model achieved an accuracy of 83.54% (sensitivity, 80.11%; specificity, 84.96%; AUC, 0.85). Conclusions Having demonstrated an accurate and fully automated glaucoma-suspect screening system that can be deployed on telemedicine platforms, we plan prospective trials to determine the feasibility of the system in primary care settings.
Dravet Variant SCN1AA1783V Impairs Interneuron Firing Predominantly by Altered Channel Activation

Dravet syndrome (DS) is a developmental epileptic encephalopathy mainly caused by functional NaV1.1 haploinsufficiency in interneurons (IN). Recently, a new conditional mouse model expressing the recurrent human p.A1783V missense variant has become available. Here we provide an electrophysiological characterization of this variant in tsA201 cells, revealing both altered voltage-dependence of activation and slow inactivation without reduced sodium peak current density. Simulating IN excitability in a Hodgkin-Huxley one-compartment model suggested surprisingly similar firing deficits for Scn1aA1783V and full haploinsufficiency as caused by heterozygous truncation variants. Impaired NaVA1783V channel activation was predicted to have a significantly larger impact on channel function than altered slow inactivation and is therefore proposed as the main mechanism underlying IN dysfunction. The computational model was validated in cortical organotypic slice cultures derived from conditional Scn1aA1783V mice. Pan-neuronal activation of the p.A1783V variant in vitro confirmed the predicted IN firing deficit while demonstrating normal excitability of pyramidal neurons. Taken together these data demonstrate that despite maintained physiological peak currents density LOF gating properties may match effects of full haploinsufficiency on neuronal level, thereby causing DS. Highlights NaV1.1A1783V alters voltage-dependence of activation and slow inactivation while not affecting fast inactivation. Depolarizing and hyperpolarizing shifts of activation and slow inactivation curves result in combined channel loss of function (LOF). Simulations of NaV1.1A1783V interneuronal properties indicate reduced action potential firing rates comparable to full SCN1A haploinsufficiency, which is often found in Dravet syndrome. In silico modelling identifies impaired channel activation as the predominant mechanism of channel LOF. Panneuronal induction of Scn1a+/A1783V in a cortical slice culture model confirms restriction of loss of function and its restriction to interneurons.