Miracle-dz/UniFAR-FTUs huggingface dataset:
Foot and Ankle Somatosensory Deficits Affect Balance and Motor Function in Children With Cerebral Palsy

Sensory dysfunction is prevalent in cerebral palsy (CP). Evidence suggests that sensory deficits can contribute to manual ability impairments in children with CP, yet it is still unclear how they contribute to balance and motor performance. Therefore, the objective of this study was to investigate the relationship between lower extremity (LE) somatosensation and functional performance in children with CP. Ten participants with spastic diplegia (Gross Motor Function Classification Scale: I-III) and who were able to stand independently completed the study. Threshold of light touch pressure, two-point discriminatory ability of the plantar side of the foot, duration of cutaneous vibration sensation, and error in the joint position sense of the ankle were assessed to quantify somatosensory function. The balance was tested by the Balance Evaluation System Test (BESTest) and postural sway measures during a standing task. Motor performance was evaluated by using a battery of clinical assessments: (1) Gross Motor Function Measure (GMFM-66-IS) to test gross motor ability; (2) spatiotemporal gait characteristics (velocity, step length) to evaluate walking ability; (3) Timed Up and Go (TUG) and 6 Min Walk (6MWT) tests to assess functional mobility; and (4) an isokinetic dynamometer was used to test the Maximum Volitional Isometric Contraction (MVIC) of the plantar flexor muscles. The results showed that the light touch pressure measure was strongly associated only with the 6MWT. Vibration and two-point discrimination were strongly related to balance performance. Further, the vibration sensation of the first metatarsal head demonstrated a significantly strong relationship with motor performance as measured by GMFM-66-IS, spatiotemporal gait parameters, TUG, and ankle plantar flexors strength test. The joint position sense of the ankle was only related to one subdomain of the BESTest (Postural Responses). This study provides preliminary evidence that LE sensory deficits can possibly contribute to the pronounced balance and motor impairments in CP. The findings emphasize the importance of developing a thorough LE sensory test battery that can guide traditional treatment protocols toward a more holistic therapeutic approach by combining both motor and sensory rehabilitative strategies to improve motor function in CP.
Exploratory Analysis of Behavioral Impulsivity, Pro-inflammatory Cytokines, and Resting-State Frontal EEG Activity Associated With Non-suicidal Self-Injury in Patients With Mood Disorder

Introduction: Non-suicidal self-injury (NSSI) is a rapidly increasing mental health problem that requires more clinical attention. In this study, we aimed to explore the biobehavioral markers of NSSI in participants with mood disorders. Methods: A total of 45 participants with mood disorders (bipolar I, II, and major depressive disorder) were included in the study. Behavioral impulsivity was measured using the immediate memory task (IMT)/delayed memory task (DMT) and the go-no-go (GNG) tests. Plasma levels of tumor necrosis factor-α (TNF-α), interleukin 1 beta (IL-1 β), and interleukin 6 (IL-6) and resting-state quantitative electroencephalography (qEEG) were measured. Results: The NSSI group had shorter GNG reaction time (GNG-RT) and higher TNF-α levels compared to the non-NSSI group. TNF-α was positively correlated with frontal theta power. In addition, GNG-RT showed a significant positive association with frontal alpha activity. Conclusion: NSSI in mood disorders was associated with increased behavioral impulsivity and greater inflammation. Increased pro-inflammatory cytokines were associated with frontal theta power. Increased inflammation might change major neurotransmitter metabolism, which eventually affects frontal function and decreases response inhibition. Further studies to explore their causal relationship are warranted.
Serum Fibroblast Growth Factor 19 and Total Bile Acid Concentrations Are Potential Biomarkers of Hepatocellular Carcinoma in Patients with Type 2 Diabetes Mellitus

Purpose Type 2 diabetes mellitus (T2DM) carries a high risk of hepatocellular carcinoma (HCC). Both serum fibroblast growth factor 19 (FGF19) and bile acid concentrations are associated with T2DM and HCC. We aimed at evaluating the relationships between FGF19 and bile acid concentrations and HCC in patients with T2DM. Methods Twenty-seven healthy volunteers (control group), 27 patients with T2DM (T2DM group), 16 patients with newly diagnosed HCC (HCC group), and 10 T2DM patients with newly diagnosed HCC (T2DM-HCC group) were studied at the Affiliated Hospital of Nantong University between June 2016 and June 2017. The serum concentrations of serum FGF19 and total bile acids (TBA) were measured in all the participants. Correlation analysis and multiple stepwise regression analysis of the FGF19 and TBA concentrations were performed in all the participants and in the four groups. Results The concentrations of FGF19 were 220.5 pg/ml, 185.1 pg/ml, 115.8 pg/ml, and 70.4 pg/ml in the HCC, T2DM-HCC, control, and T2DM groups, respectively (p < 0.001), and the TBA concentrations were 21.75 μmol/l, 14.25 μmol/l, 14.25 μmol/l, 14.25 μmol/l, 14.25 p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 r = 0.777; p < 0.001), and the TBA concentrations were 21.75 Conclusions Simultaneous increase of serum FGF19 and TBA levels may be used as indicators of HCC screening at early stage in patients with T2DM.
Serum Levels of Autoantibodies Against Extracellular Antigens and Neutrophil Granule Proteins Increase in Patients with COPD Compared to Non-COPD Smokers

Background Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease leading to irreversible airflow limitation and is characterized by chronic pulmonary inflammation, obstructive bronchiolitis and emphysema. Etiologically, COPD is mediated by toxic gases and particles, eg, cigarette smoke, while the pathogenesis of the disease is largely unknown. Several lines of evidence indicate a link between COPD and autoimmunity but comprehensive studies are lacking. Methods By using a protein microarray assaying more than 19,000 human proteins we determined in this study the autoantibody profiles of COPD and non-COPD smokers. The discovery cohort included 5 COPD patients under acute exacerbation (AECOPD) and 5 age- and gender-matched non-COPD smokers. One putative candidate autoantibody, anti-lactoferrin IgG, was further investigated by using immunoblotting with a large validation cohort containing 124 healthy controls, 92 patients with AECOPD and 52 patients with stable COPD. Results We show that i) autoantigens targeted by autoantibodies with higher titers in COPD patients were enriched in extracellular regions, while those with lower titers in COPD patients were enriched in intracellular compartments. ii) levels of IgG autoantibodies against many neutrophil granule proteins were significantly higher in COPD patients than in non-COPD smokers. Furthermore, increased levels of anti-lactoferrin antibodies in COPD patients were confirmed in a cohort with a large number of samples. Conclusion The comprehensive autoantibody profiles from COPD patients established in this study demonstrated for the first time a shift in the cellular localization of antigens targeted by autoantibodies in COPD.
Intramyocellular Lipids, Insulin Resistance, and Functional Performance in Patients with Severe Obstructive Sleep Apnea

Purpose An increasing number of studies have linked the severity of obstructive sleep apnea (OSA) with metabolic dysfunction. However, little is known about the lipid compartments (intramyocellular [IMCL] and extramyocellular [EMCL] lipids) inside the musculature in these patients. The present study was designed to investigate the IMCL and EMCL, biochemical data, and functional performance in patients with severe OSA, and to examine the correlations between intramuscular lipid contents and test variables. Participants and Methods Twenty patients with severe OSA (apnea-hypopnea index [AHI]: ≥30/h; body mass index [BMI]: 26.05±2.92) and 20 age- and BMI-matched controls (AHI <5/h) were enrolled. Proton magnetic resonance spectroscopy was used to measure the IMCL and EMCL of the right vastus lateralis muscle. Biochemical data, including levels of fasting plasma glucose, insulin, lipid profiles, and high-sensitivity C-reactive protein (hsCRP), were measured. Insulin resistance index (IR) was calculated using the homeostasis model assessment method. Performance tests included a cardiopulmonary exercise test and knee extension strength and endurance measurements. Results Patients with severe OSA had significantly (P<0.05) lower values of IMCL (14.1±5.4 AU) and EMCL (10.3±5.8 AU) compared to the control group (25.2±17.6 AU and 14.3±11.1 AU, respectively). Patients with severe OSA had significantly higher hsCRP, IR, and dyslipidemia compared with controls (all P<0.05). Furthermore, IMCL was negatively correlated with AHI, cumulative time with nocturnal pulse oximetric saturation lower than 90% (TSpO2<90%) (ρ=−0.35, P<0.05), IR (ρ=−0.40, P<0.05), glucose (ρ=−0.33, P<0.05), and insulin (ρ=−0.36, P<0.05), and positively correlated with lowest oximetric saturation (ρ=0.33, P<0.01). Conclusion Skeletal muscle dysfunction and metabolic abnormalities were observed in patients with OSA that did not have obesity. IMCL was positively correlated with aerobic capacity and muscular performance, but negatively correlated with AHI and IR. Large-scale clinical trials are required to explore the complicated mechanism among OSA, intramuscular metabolism, and insulin action. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00813852.
Invisible oil beyond the Deepwater Horizon satellite footprint

A portion of the Deepwater Horizon oil spill extended beyond the satellite footprint and contained toxic oil concentrations. Major oil spills are catastrophic events that immensely affect the environment and society, yet determining their spatial extent is a highly complex task. During the Deepwater Horizon (DWH) blowout, ~149,000 km2 of the Gulf of Mexico (GoM) was covered by oil slicks and vast areas of the Gulf were closed for fishing. Yet, the satellite footprint does not necessarily capture the entire oil spill extent. Here, we use in situ observations and oil spill transport modeling to examine the full extent of the DWH spill, focusing on toxic-to-biota (i.e., marine organisms) oil concentration ranges. We demonstrate that large areas of the GoM were exposed to invisible and toxic oil that extended beyond the boundaries of the satellite footprint and the fishery closures. With a global increase in petroleum production–related activities, a careful assessment of oil spills’ full extent is necessary to maximize environmental and public safety.
Deep Reinforcement Learning for Strategic Bidding in Electricity Markets

Bi-level optimization and reinforcement learning (RL) constitute the state-of-the-art frameworks for modeling strategic bidding decisions in deregulated electricity markets. However, the former neglects the market participants’ physical non-convex operating characteristics, while conventional RL methods require discretization of state and/or action spaces and thus suffer from the curse of dimensionality. This paper proposes a novel deep reinforcement learning (DRL) based methodology, combining a deep deterministic policy gradient (DDPG) method with a prioritized experience replay (PER) strategy. This approach sets up the problem in multi-dimensional continuous state and action spaces, enabling market participants to receive accurate feedback regarding the impact of their bidding decisions on the market clearing outcome, and devise more profitable bidding decisions by exploiting the entire action domain, also accounting for the effect of non-convex operating characteristics. Case studies demonstrate that the proposed methodology achieves a significantly higher profit than the alternative state-of-the-art methods, and exhibits a more favourable computational performance than benchmark RL methods due to the employment of the PER strategy.
A Simple Method for the Design and Development of Flavivirus NS1 Recombinant Proteins Using an In Silico Approach

Even in countries that are currently not facing a flavivirus epidemic, the spread of mosquito-borne flaviviruses presents an increasing public threat, owing to climate change, international travel, and other factors. Many of these countries lack the resources (viral strains, clinical specimens, etc.) needed for the research that could help cope with the threat imposed by flaviviruses, and therefore, an alternative approach is needed. Using an in silico approach to global databases, we aimed to design and develop flavivirus NS1 recombinant proteins with due consideration towards antigenic variation. NS1 genes analyzed in this study included a total of 6,823 sequences, from Dengue virus (DENV), Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), and Yellow fever virus (YKV). We extracted and analyzed 316 DENV NS1 sequence types (STs), 59 JEV STs, 75 WNV STs, 30 YFV STs, and 43 ZIKV STs using a simple algorithm based on phylogenetic analysis. STs were reclassified according to the variation of the major epitope by MHC II binding. 78 DENV epitope type (EpT), 29 JEV EpTs, 29 WNV EpTs, 12 YFV EpTs, and 5 ZIKV EpTs were extracted according to their major epitopes. Also, frequency results showed that there were dominant EpTs in all flavivirus. Fifteen STs were selected and purified for the expression of recombinant antigen in Escherichia coli by sodium dodecyl sulfate extraction. Our study details a novel in silico approach for the development of flavivirus diagnostics, including a simple way to screen the important peptide regions.
Identification of the Different Roles and Potential Mechanisms of T Isoforms in the Tumor Recurrence and Cell Cycle of Chordomas

Purpose The roles of T (brachyury) isoforms in chordomas remain unclear. This study aimed to investigate the different roles and mechanisms of them in chordomas. Patients and methods The expression of T isoforms mRNAs in 57 chordomas was assessed, and a prognosis analysis was conducted. Cell apoptosis, proliferation and cell cycle assays were performed after specific T isoform mRNA knockdown. Whole-transcriptome sequencing, Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis and competing endogenous RNA (ceRNA) analysis were conducted. Results As revealed in this study, the T-long isoform was a significant risk factor (hazard ratio [HR], 1.09; P=0.018) and the T-short isoform was a protective factor (HR, 0.24; P=0.012) associated with tumor recurrence. After T-long isoform knockdown, the cell cycle was arrested at G0/G1 phase and cell proliferation was significantly inhibited. A bioinformatic analysis revealed that the upregulation of H19, P21 and GADD45B; downregulation of SKP2 and CDK2; and accompanying changes in the P53 signaling pathway consistently contributed to G0/G1 arrest. After T-short isoform knockdown, the cell cycle was arrested at G2/M phase and cell apoptosis tended to increase slightly (P=0.067). The upregulation of YWHAZ and downregulation of E2F1 and its target genes might contribute to cell cycle arrest in G2/M phase and apoptosis. In addition, the ceRNA network, consisting of long noncoding RNAs, mRNAs and microRNAs, was established. Conclusion The T-long isoform was a risk factor and the T-short isoform was a protective factor for chordoma recurrence. In addition, the cell cycle was the main target of T isoforms knockdown, and the changes in the downstream transcriptome may contribute to the different effects of specific T isoform knockdown on the changes in the cell cycle distributions and apoptosis and proliferation of chordoma cells.
Uric Acid and Arterial Stiffness

Abstract Hyperuricemia is usually associated with hypertension, diabetes mellitus, metabolic syndrome and chronic kidney disease. Accumulating data from epidemiological studies indicate an association of increased uric acid (UA) with cardiovascular diseases. Possible pathogenic mechanisms include enhancement of oxidative stress and systemic inflammation caused by hyperuricemia. Arterial stiffness may be one of the possible pathways between hyperuricemia and cardiovascular disease, but a clear relationship between increased UA and vascular alterations has not been confirmed. The review summarizes the epidemiological studies investigating the relationship between UA and arterial stiffness and highlights the results of interventional studies evaluating arterial stiffness parameters in patients treated with UA-lowering drugs.
Effects of Ambient Temperature on Acute Exacerbations of Chronic Obstructive Pulmonary Disease: Results from a Time-Series Analysis of 143318 Hospitalizations

Purpose To evaluate the associations between acute exacerbations of chronic obstructive pulmonary disease (AECOPD) hospitalizations and daily mean temperature (Tmean) as well as daily apparent temperature (AT), and to explore the practical values of these two indices in policymaking and patient education. Methods Daily AECOPD hospitalizations and Meteorological data in Beijing were obtained between 2013 and 2016. Distributed lag non-linear model was adopted to investigate the association between daily ambient temperature and AECOPD hospitalizations. The cumulative effects of cold/hot temperature were abstracted. For the extreme and moderate low-temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 1st and 10th percentiles of temperature in comparison with that at the 25th percentile of temperature. For the extreme and moderate high temperature effect estimates, we, respectively, computed the RR of AECOPD hospitalizations at the 99th and 90th percentiles of temperature in comparison with that at the 75th percentile of temperature. Results During the study period, 143, 318 AECOPD hospitalizations were collected. A reverse J-shape relationship was found between temperature and AECOPD hospitalizations. When comparing the effect of Tmean, higher RRs were associated with increases in AT on AECOPD hospitalizations but a lower value of Akaike’s Information Criterion for quasi-Poisson (Q-AIC). The RR of extremely low temperature of Tmean and AT were 1.55 (95% CI: 1.21,2.00) and 2.08 (95% CI: 1.44,3.01), respectively. Moderate low temperature also had an adverse impact on AECOPD hospitalizations. No associations were found between high temperature and AECOPD risk. We found the females and those aged <65 years to be more susceptible to temperature change. Conclusion Lower temperature is associated with a higher risk for AECOPD hospitalizations. Ambient temperature is probably a better predictor in terms of quantifying risk than mean temperature when studying temperature impact on health.
Routing Nanomolar Protein Cargoes to Lipid Raft‐Mediated/Caveolar Endocytosis through a Ganglioside GM1‐Specific Recognition Tag

There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. Certain viral and bacterial proteins are readily internalized in functional form through lipid raft‐mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis. A pentapeptide sequence WYKYW is presented, which specifically captures the glycan moiety of GM1 (KD = 24 nm). The WYKYW‐tag facilitates the GM1‐dependent endocytosis of proteins in which the cargo‐loaded caveosomes do not fuse with lysosomes. A structurally intact immunoglobulin G complex (580 kDa) is successfully delivered into live HeLa cells at extracellular concentrations ranging from 20 to 160 nm, and escape of the cargo proteins to the cytosol is observed. The short peptidic WYKYW‐tag is an advantageous endocytosis routing sequence for lipid raft‐mediated/caveolar cell delivery of therapeutic macromolecules, especially for cancer cells that overexpress GM1.
Portal Venous Metabolite Profiling After RYGB in Male Rats Highlights Changes in Gut-Liver Axis

Abstract After Roux-en-Y gastric bypass (RYGB) surgery, the intestine undergoes structural and metabolic reprogramming and appears to enhance use of energetic fuels including glucose and amino acids (AAs), changes that may be related to the surgery’s remarkable metabolic effects. Consistently, RYGB alters serum levels of AAs and other metabolites, perhaps reflecting mechanisms for metabolic improvement. To home in on the intestinal contribution, we performed metabolomic profiling in portal venous (PV) blood from lean, Long Evans rats after RYGB vs sham surgery. We found that one-carbon metabolism (OCM), nitrogen metabolism, and arginine and proline metabolism were significantly enriched in PV blood. Nitrogen, OCM, and sphingolipid metabolism as well as ubiquinone biosynthesis were also overrepresented among metabolites uniquely affected in PV vs peripheral blood in RYGB-operated but not sham-operated animals. Peripheral blood demonstrated changes in AA metabolism, OCM, sphingolipid metabolism, and glycerophospholipid metabolism. Despite enrichment for many of the same pathways, the overall metabolite fingerprint of the 2 compartments did not correlate, highlighting a unique role for PV metabolomic profiling as a window into gut metabolism. AA metabolism and OCM were enriched in peripheral blood both from humans and lean rats after RYGB, demonstrating that these conserved pathways might represent mechanisms for clinical improvement elicited by the surgery in patients. Together, our data provide novel insight into RYGB’s effects on the gut-liver axis and highlight a role for OCM as a key metabolic pathway affected by RYGB.