Miracle-dz/UniFAR-FTUs huggingface dataset:
The Effect of Aging on Resting State Connectivity of Predefined Networks in the Brain

Recent studies have found a deleterious effect of age on a wide variety of measures of functional connectivity, and some hints at a relationship between connectivity at rest and cognitive functioning. However, few studies have combined multiple functional connectivity methods, or examined them over a wide range of adult ages, to try to uncover which metrics and networks seem to be particularly sensitive to age-related decline across the adult lifespan. The present study utilized multiple resting state functional connectivity methods in a sample of adults from 20–80 years old to gain a more complete understanding of the effect of aging on network function and integrity. Whole-brain results showed that aging results in weakening average within-network connectivity, lower system segregation and local efficiency, and higher participation coefficient. Network-level results suggested that nearly every primary sensory and cognitive network faces some degree of age-related decline, including reduced within-network connectivity, higher network-based participation coefficient, and reduced network-level local efficiency. Further, some of these connectivity metrics showed relationships with cognitive performance. Thus, these results suggest that a multi-method analysis of functional connectivity data may be critical to capture the full effect of aging on the health of brain networks.
Effects of Acute Exercise Duration on the Inhibition Aspect of Executive Function in Late Middle-Aged Adults

Objective: This study investigated whether acute exercise duration affects inhibition in late middle-aged adults. Methods: Over four separate days, 40 late middle-aged adults completed, in a counterbalanced order, three exercise sessions consisting of single bouts of moderate-to-vigorous intensity cycling, with the main acute exercise durations being 10, 20, and 45 min, and a control session consisting of 30 min of reading. Their inhibition performance was then evaluated by administration of the Stroop test following each session. Results: The participants had shorter mean response times for both the congruent and neutral conditions of the Stroop following the acute exercise lasting 20 min than they did after the control session. The acute exercise lasting 20 min also resulted in shorter response times for both conditions of the Stroop than the acute exercise lasting only 10 min. Meanwhile, the acute exercise lasting 45 min resulted in a shorter mean response time for the neutral Stroop condition than did the control session. Finally, the acute exercise lasting 20 min resulted in the shortest mean response time of all four sessions for the Stroop incongruent condition. Conclusion: The above findings suggest that the moderate-to-vigorous intensity acute exercise lasting 20 min facilitated multiple cognitive function domains in general, whereas the exercise sessions of shorter and longer duration had negligible effects on executive function in the late middle-aged adults. These results highlight the need to consider the duration of any moderate-to-vigorous intensity exercise when developing acute exercise programs to facilitate executive function in aged populations.
Characterization of a NDM-1- Encoding Plasmid pHFK418-NDM From a Clinical Proteus mirabilis Isolate Harboring Two Novel Transposons, Tn6624 and Tn6625

Acquisition of the blaNDM–1 gene by Proteus mirabilis is a concern because it already has intrinsic resistance to polymyxin E and tigecycline antibiotics. Here, we describe a P. mirabilis isolate that carries a pPrY2001-like plasmid (pHFK418-NDM) containing a blaNDM–1 gene. The pPrY2001-like plasmid, pHFK418-NDM, was first reported in China. The pHFK418-NDM plasmid was sequenced using a hybrid approach based on Illumina and MinION platforms. The sequence of pHFK418-NDM was compared with those of the six other pPrY2001-like plasmids deposited in GenBank. We found that the multidrug-resistance encoding region of pHFK418-NDM contains ΔTn10 and a novel transposon Tn6625. Tn6625 consists of ΔTn1696, Tn6260, In251, ΔTn125 (carrying blaNDM–1), ΔTn2670, and a novel mph(E)-harboring transposon Tn6624. In251 was first identified in a clinical isolate, suggesting that it has been transferred efficiently from environmental organisms to clinical isolates. Genomic comparisons of all these pPrY2001-like plasmids showed that their relatively conserved backbones could integrate the numerous and various accessory modules carrying multifarious antibiotic resistance genes. Our results provide a greater depth of insight into the horizontal transfer of resistance genes and add interpretive value to the genomic diversity and evolution of pPrY2001-like plasmids.
Completing Circular Bacterial Genomes With Assembly Complexity by Using a Sampling Strategy From a Single MinION Run With Barcoding

The Oxford Nanopore MinION is an affordable and portable DNA sequencer that can produce very long reads (tens of kilobase pairs), which enable de novo bacterial genome assembly. Although many algorithms and tools have been developed for base calling, read mapping, de novo assembly, and polishing, an automated pipeline is not available for one-stop analysis for circular bacterial genome reconstruction. In this paper, we present the pipeline CCBGpipe for completing circular bacterial genomes. Raw current signals are demultiplexed and base called to generate sequencing data. Sequencing reads are de novo assembled several times by using a sampling strategy to produce circular contigs that have a sequence in common between their start and end. The circular contigs are polished by using raw signals and sequencing reads; then, duplicated sequences are removed to form a linear representation of circular sequences. The circularized contigs are finally rearranged to start at the start position of dnaA/repA or a replication origin based on the GC skew. CCBGpipe implemented in Python is available at https://github.com/jade-nhri/CCBGpipe. Using sequencing data produced from a single MinION run, we obtained 48 circular sequences, comprising 12 chromosomes and 36 plasmids of 12 bacteria, including Acinetobacter nosocomialis, Acinetobacter pittii, and Staphylococcus aureus. With adequate quantities of sequencing reads (80×), CCBGpipe can provide a complete and automated assembly of circular bacterial genomes.
Androgen Receptor Signaling in the Development of Castration-Resistant Prostate Cancer

Most prostate cancers are androgen-sensitive malignancies whose growths depend on the transcriptional activity of the androgen receptor (AR). In the 1940s, Charles Huggins demonstrated that the surgical removal of testes in men can result in a dramatic improvement in symptoms and can induce prostate cancer regression. Since then, androgen deprivation therapies have been the standard first-line treatment for advanced prostate cancer, including: surgical castration, medical castration, antiandrogens, and androgen biosynthesis inhibitors. These therapies relieve symptoms, reduce tumor burden, and prolong patient survival, while having relatively modest side effects. Unfortunately, hormone deprivation therapy rarely cures the cancer itself. Prostate cancer almost always recurs, resulting in deadly castration-resistant prostate cancer. The underlying escape mechanisms include androgen receptor gene/enhancer amplification, androgen receptor mutations, androgen receptor variants, coactivator overexpression, intratumoral de novo androgen synthesis, etc. Whereas, the majority of the castration-resistant prostate cancers continuously rely on the androgen axis, a subset of recurrent cancers have completely lost androgen receptor expression, undergone divergent clonal evolution or de-differentiation, and become truly androgen receptor-independent small-cell prostate cancers. There is an urgent need for the development of novel targeted and immune therapies for this subtype of prostate cancer, when more deadly small-cell prostate cancers are induced by thorough androgen deprivation and androgen receptor ablation.
Memory Decline and Behavioral Inflexibility in Aged Mice Are Correlated With Dysregulation of Protein Synthesis Capacity

Understanding the molecular mechanisms underlying age-associated cognitive impairments will not only contribute to our general knowledge about “aging” biology, but also provide insights for more effective strategies to prevent and improve the quality of life for both normal aging and pathological aging such as Alzheimer’s disease (AD). Here we first assessed and compared the performance of cognition and synaptic plasticity in young (3–5-month old) and aged c57BL/6J mice (19–21 months old). Findings from behavioral tests demonstrated that old mice, compared to young mice, displayed impairments in spatial learning/memory, working memory, and behavioral flexibility. Further, synaptic electrophysiology experiments on hippocampal slices revealed that the early form of long-term potentiation (LTP, a synaptic model for memory formation) was inhibited in old mice. At the molecular level, biochemical assays on the hippocampus showed dysregulation of signaling pathways controlling protein synthesis capacity including: up-regulation of AKT-mTORC1-p70S6K signaling, which is associated with translation of terminal oligopyrimidine (TOP) class of mRNAs that encode translational machinery; hyper-phosphorylation of mRNA translational elongation factor 2 (eEF2) and its upstream regulator AMP-activated protein kinase (AMPK), indicating repression of general protein synthesis. Moreover, young and old mice exhibited similar brain levels of translational initiation factor 2α (eIF2α) phosphorylation, which is known to be increased in AD and linked to the disease pathophysiology. Thus, our data provide evidence at the molecular level to highlight the similarity and difference between normal and pathological aging, which may contribute to future studies on diagnostic/prognostic biomarkers for aging-related dementia syndromes.
Three-Dimensional Heart Model-Based Screening of Proarrhythmic Potential by in silico Simulation of Action Potential and Electrocardiograms

The proarrhythmic risk is a major concern in drug development. The Comprehensive in vitro Proarrhythmia Assay (CiPA) initiative has proposed the JTpeak interval on electrocardiograms (ECGs) and qNet, an in silico metric, as new biomarkers that may overcome the limitations of the hERG assay and QT interval. In this study, we simulated body-surface ECGs from patch-clamp data using realistic models of the ventricles and torso to explore their suitability as new in silico biomarkers for cardiac safety. We tested seven drugs in this study: dofetilide (high proarrhythmic risk), ranolazine, verapamil (QT increasing, but safe), bepridil, cisapride, mexiletine, and diltiazem. Human ventricular geometry was reconstructed from computed tomography (CT) images, and a Purkinje fiber network was mapped onto the endocardial surface. The electrical wave propagation in the ventricles was obtained by solving a reaction-diffusion equation using finite-element methods. The body-surface ECG data were calculated using a torso model that included the ventricles. The effects of the drugs were incorporated in the model by partly blocking the appropriate ion channels. The effects of the drugs on single-cell action potential (AP) were examined first, and three-dimensional (3D) body-surface ECG simulations were performed at free Cmax values of 1×, 5×, and 10×. In the single-cell and ECG simulations at 5× Cmax, dofetilide, but not verapamil or ranolazine, caused arrhythmia. However, the non-increasing JTpeak caused by verapamil and ranolazine that has been observed in humans was not reproduced in our simulation. Our results demonstrate the potential of 3D body-surface ECG simulation as a biomarker for evaluation of the proarrhythmic risk of candidate drugs.
Plasmacytoid DCs From Patients With Sjögren's Syndrome Are Transcriptionally Primed for Enhanced Pro-inflammatory Cytokine Production

Primary Sjögren's syndrome (pSS) is a systemic auto-immune disease typified by dryness of the mouth and eyes. A majority of patients with pSS have a type-I interferon (IFN)-signature, which is defined as the increased expression of IFN-induced genes in circulating immune cells and is associated with increased disease activity. As plasmacytoid dendritic cells (pDC) are the premier type-I IFN-producing cells and are present at the site of inflammation, they are thought to play a significant role in pSS pathogenesis. Considering the lack of data on pDC regulation and function in pSS patients, we here provided the first in-depth molecular characterization of pSS pDCs. In addition, a group of patients with non-Sjögren's sicca (nSS) was included; these poorly studied patients suffer from complaints similar to pSS patients, but are not diagnosed with Sjögren's syndrome. We isolated circulating pDCs from two independent cohorts of patients and controls (each n = 31) and performed RNA-sequencing, after which data-driven networks and modular analysis were used to identify robustly reproducible transcriptional “signatures” of differential and co-expressed genes. Four signatures were identified, including an IFN-induced gene signature and a ribosomal protein gene-signature, that indicated pDC activation. Comparison with a dataset of in vitro activated pDCs showed that pSS pDCs have higher expression of many genes also upregulated upon pDC activation. Corroborating this transcriptional profile, pSS pDCs produced higher levels of pro-inflammatory cytokines, including type-I IFN, upon in vitro stimulation with endosomal Toll-like receptor ligands. In this setting, cytokine production was associated with expression of hub-genes from the IFN-induced and ribosomal protein gene-signatures, indicating that the transcriptional profile of pSS pDCs underlies their enhanced cytokine production. In all transcriptional analyses, nSS patients formed an intermediate group in which some patients were molecularly similar to pSS patients. Furthermore, we used the identified transcriptional signatures to develop a discriminative classifier for molecular stratification of patients with sicca. Altogether, our data provide in-depth characterization of the aberrant regulation of pDCs from patients with nSS and pSS and substantiate their perceived role in the immunopathology of pSS, supporting studies that target pDCs, type-I IFNs, or IFN-signaling in pSS.
Replacement of Soybean Meal With Soybean Cake Reduces Methane Emissions in Dairy Cows and an Assessment of a Face-Mask Technique for Methane Measurement

The objective of this study was to (a) evaluate the effect of replacing soybean meal (SBM) with soybean cake (SBC) on feeding behavior, rumen fermentation, milk production, nutrient digestibility and CH4 emissions and (b) investigate whether a face-mask technique could be used to predict daily methane (CH4) emissions in dairy cattle. The experiment was conducted as a completely randomized design, with 32 crossbred Holstein × Gyr cows (days in milk (DIM): 112 ± 25.1) randomly assigned to the following treatments (n = 8/group) for 75 days: (1) 0% SBC, (2) 6% SBC, (3) 14% SBC, and (4) 23% SBC, in place of SBM on a dry matter (DM) basis. Across the final 4 weeks of the study, CH4 production was estimated using the proposed face-mask technique subsequent to a respiration chamber measurement for an evaluation of treatment efficacy and face-mask accuracy. There was no effect of SBM replacement by SBC on intake, feeding or drinking behavior (P > 0.21). Total VFA concentration, the individual proportions of VFA and blood metabolites were not altered (P > 0.17) by SBC, however there was a tendency for decreased (P = 0.08) lactate and plasma urea nitrogen (P = 0.07) concentration associated with SBC addition. Fat-corrected milk yield (FCM4%) and composition was not affected (P > 0.27) by SBC; however, there was a tendency for decreased total milk solids (P = 0.07) and milk fat (P = 0.08) associated with 23% SBC treatment. There was no treatment × technique interaction (P > 0.05) effect on gas measurements. A maximum reduction (P = 0.01) in CH4 yield (g/kg DM) and intensity (g/kg milk) of 11 and 20%, respectively, was observed for the 14% SBC inclusion. Compared to the week of mask measurements, chambers decreased (P = 0.01) intake (kg/d, %BW) and increased (P = 0.05) FCM4%. The face-mask method over estimated O2 consumption by 5%. The face-mask method accurately predicted daily CH4 emissions when compared to the chamber at the same time-point. However, there was a linear bias of CH4 outputs so further evaluation of the calculation of total CH4 from a spot measurement is required.
Effect of Radiotherapy Combined With Pembrolizumab on Local Tumor Control in Mucosal Melanoma Patients

Objective: Mucosal melanoma is an aggressive malignancy with a poor response to conventional therapies. The efficacy of radiotherapy (RT), especially combined with immune checkpoint inhibitors (ICIs), for this rare melanoma subtype remains unknown. We investigated the reciprocal effect of RT and ICI on mucosal melanoma patients. Materials and Methods: We identified 23 patients with 31 tumors who were treated with RT between July 2008 and February 2017. All patients received RT for primary or metastatic gross tumor mass with a median dose of 4 Gy per fraction (range 1.8–12 Gy). Eleven patients (14 lesions) were treated with RT alone, whereas 12 (17 lesions) were administered pembrolizumab combined with RT (ICI+RT group). The local control (LC) and adverse event (AE) rates were compared between the groups. Eight patients with metastatic mucosal melanoma treated with ICI alone during the same study period were included as a comparison group. Results: The median follow-up period was 17.4 (range 3.7–95.2) months. The target lesion control rate at 1-year was significantly higher in the ICI+RT group than in the RT-alone group or ICI-alone group (94.1% vs. 57.1% vs. 25%; P < 0.05). No abscopal effect was observed in our cohort. Treatment-related AEs were not significantly increased in the combined treatment group compared with the RT-alone group (P > 0.05). No grade ≥3 AEs occurred in the ICI+RT group. Conclusions: Besides RT acting as an immune adjuvant, ICI might have a radiosensitizing effect and may increase LC without severe toxicity. We have initiated a phase II study to determine the effects of RT in patients with melanoma undergoing anti-PD1 (NCT04017897).
Auditory Stimulation Training With Technically Manipulated Musical Material in Preschool Children With Specific Language Impairments: An Explorative Study

Auditory stimulation training (AST) has been proposed as a potential treatment for children with specific language impairments (SLI). The current study was designed to test this assumption by using an AST with technically modulated musical material (ASTM) in a randomized control group design. A total of 101 preschool children (62 male, 39 females; mean age = 4.52 years, SD = 0.62) with deficits in speech comprehension and poor working memory capacity were randomly allocated into one of two treatment groups or a control group. Children in the ASTM group (n = 40) received three 30-min sessions per week over 12 weeks, whereas children in the comparison group received pedagogical activities during these intervals (n = 24). Children in the control group (n = 37) received no treatment. Working memory, phoneme discrimination and speech perception skills were tested prior to (baseline) and after treatment. Children in the ASTM group showed significantly greater working memory capacity, speech perception, and phoneme discrimination skills after treatment, whereas children in the other groups did not show such improvement. Taken together, these results suggest that ASTM can enhance auditory cognitive performance in children with SLI.
An Empirical Analysis of Data Deletion and Opt-Out Choices on 150 Websites

Many websites offer visitors privacy controls and opt-out choices, either to comply with legal requirements or to address consumer privacy concerns. The way these control mechanisms are implemented can signiﬁcantly affect individuals’ choices and their privacy outcomes. We present an extensive content analysis of a stratiﬁed sample of 150 English-language websites, assessing the usability and interaction paths of their data deletion options and opt-outs for email communications and targeted advertising. This heuristic evaluation identiﬁed substantial issues that likely make exercising these privacy choices on many websites difﬁcult and confusing for US-based consumers. Even though the majority of analyzed websites offered privacy choices, they were located inconsistently across websites. Furthermore, some privacy choices were rendered unusable by missing or unhelpful information, or by links that did not lead to the stated choice. Based on our ﬁndings, we provide insights for addressing usability issues in the end-to-end interaction required to effectively exercise privacy choices and controls.
Contrasting Performance of the Remotely-Derived GPP Products over Different Climate Zones across China

Precise quantification of terrestrial gross primary production (GPP) has been recognized as one of the most important components in understanding the carbon balance between the biosphere and the atmosphere. In recent years, although many large-scale GPP estimates from satellite data and ecosystem models have been generated, few attempts have been made to compare the different GPP products at national scales, particularly for various climate zones. In this study, two of the most widely-used GPP datasets were systematically compared over the eight climate zones across China’s terrestrial ecosystems from 2001 to 2015, which included the moderate resolution imaging spectroradiometer (MODIS) GPP and the breathing Earth system simulator (BESS) GPP products. Additionally, the coarse (0.05o) GPP estimates from the vegetation photosynthesis model (VPM) at the same time scale were used for auxiliary analysis with the two products. Both MODIS and BESS products exhibited a decreasing trend from the southeast region to the northwest inland. The largest GPP was found in the tropical humid region with 5.49 g C m−2 d−1 and 5.07 g C m−2 d−1 for MODIS and BESS, respectively, while the lowest GPP was distributed in the warm temperate arid region, midtemperate semiarid region and plateau zone. Meanwhile, the work confirmed that all these GPP products showed apparent seasonality with the peaks in the summertime. However, large differences were found in the interannual variations across the three GPP products over different climate regions. Generally, the BESS GPP agreed better than the MODIS GPP when compared to the seasonal and interannual variations of VPM GPP. Furthermore, the spatial correlation analysis between terrestrial GPP and the climatic factors, including temperature and precipitation, indicated that natural rainfall dominated the variability in GPP of Northern China, such as the midtemperate semiarid region, while temperature was a key controlling factor in the Southern China and the Tibet Plateau area.