Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular Endothelial Function as a Valid Predictor of Variations in Pulmonary Function in T2DM Patients Without Related Complications

To assess the variations in pulmonary function and vascular endothelial function in their early stages (without related complications). A total of 162 type 2 diabetes mellitus (T2DM) patients without diabetes complications and 55 healthy people were selected, comprising the T2DM group and the control group, respectively, to evaluate changes in vascular endothelial function and lung function and determine the correlation between them. In this study, the T2DM group exhibited significantly lower pulmonary function than that of the control group (P < 0.05). The T2DM group also showed significantly lower flow-mediated dilation (FMD) and nitric oxide (NO) (P < 0.05) than those of the control group. Pulmonary functional indexes correlated positively with FMD and NO (P < 0.05) and correlated negatively with endothelin-1 (ET-1) (P < 0.05). FMD and NO correlated negatively with diabetes duration/HbA1c (P < 0.05), whereas ET-1 correlated positively with glycosylated hemoglobinA1c (HbA1c)/diabetes duration (P < 0.05). Pulmonary functional indexes negatively correlated with HbA1c/diabetes duration (P < 0.05). Multiple linear regression was used to analyze the relationship between vascular endothelial function indexes (FMD, ET-1, and NO) and pulmonary functional indexes. The results indicated that each vascular endothelial function index (FMD, ET-1, and NO) was significantly correlated with the pulmonary functional index (P < 0.05). The patients with T2DM presented changes in the subclinical vascular endothelial and pulmonary function. They also had impaired vascular endothelial functions, which were characterized by reduced vascular endothelial function relative to those of healthy people. Regulating glycemia may improve vascular endothelial and pulmonary functions. Moreover, microvascular lesions in preclinical stages, vascular endothelial function indexes (FMD, ET-1, and NO) were valid predictors of alterations in pulmonary function in T2DM patients without related complications. Clinical Trial Registration ClinicalTrials.gov, identifier NCT03575988.
Prognosis and Genomic Landscape of Liver Metastasis in Patients With Breast Cancer

Objective The prognosis of breast cancer liver metastasis (BCLM) is poor, and its molecular mechanism is unclear. We aimed to determine the factors that affect the prognosis of patients with BCLM and investigate the genomic landscape of liver metastasis (LM). Methods We described the prognosis of patients with BCLM and focused on prognosis prediction for these patients based on clinicopathological factors. Nomogram models were constructed for progression-free survival (PFS) and overall survival (OS) by using a cohort of 231 patients with BCLM who underwent treatment at Shandong Cancer Hospital and Institute (SCHI). We explored the molecular mechanism of LM and constructed driver genes, mutation signatures by using a targeted sequencing dataset of 217 samples of LM and 479 unpaired samples of primary breast cancer (pBC) from Memorial Sloan Kettering Cancer Center (MSKCC). Results The median follow-up time for 231 patients with BCLM in the SCHI cohort was 46 months. The cumulative incidence of LM at 1, 2, and 5 years was 17.5%, 45.0%, and 86.8%, respectively. The median PFS and OS were 7 months (95% CI, 6–8) and 22 months (95% CI, 19–25), respectively. The independent factors that increased the progression risk of patients with LM were Karnofsky performance status (KPS) ≤ 80, TNBC subtype, grade III, increasing trend of CA153, and disease-free interval (DFS) ≤ 1 year. Simultaneously, the independent factors that increased the mortality risk of patients with LM were Ki-67 ≥ 30%, grade III, increasing trend of CA153, pain with initial LM, diabetes, and DFI ≤ 1 year. In the MSKCC dataset, the LM driver genes were ESR1, AKT1, ERBB2, and FGFR4, and LM matched three prominent mutation signatures: APOBEC cytidine deaminase, ultraviolet exposure, and defective DNA mismatch repair. Conclusion This study systematically describes the survival prognosis and characteristics of LM from the clinicopathological factors to the genetic level. These results not only enable clinicians to assess the risk of disease progression in patients with BCLM to optimize treatment options, but also help us better understand the underlying mechanisms of tumor metastasis and evolution and provide new therapeutic targets with potential benefits for drug-resistant patients.
Will Phosphate Bio-Solubilization Stimulate Biological Nitrogen Fixation in Grain Legumes?

Biological nitrogen fixation (BNF) refers to a bacterially mediated process by which atmospheric N2 is reduced, either symbiotically or non-symbiotically, into ammonia (NH3) in the presence of the enzyme complex nitrogenase. In N2-fixing grain legumes, BNF is often hampered under low phosphorus (P) availability. The P status of legumes, particularly nodules, as well as P availability in the rhizosphere, play a vital role in regulating BNF. Aside from increasing P availability via fertilization, other plant traits (i.e., extensive rooting system and their spatial distribution, hyper-nodulation, root exudates, rhizosphere acidification, and heterogeneity) contribute to greater P uptake and hence more effective BNF. The positive interaction between P availability and BNF can be exploited through beneficial soil P solubilizing microorganisms (PSM). These microorganisms can increase plant-available P by modifying either rhizosphere soil processes or promoting plant traits, which lead to increased P uptake by the production of plant growth-promoting substances, both of which could indirectly influence the efficiency of BNF in legumes. In this review, we report on the importance of microbial P bio-solubilization as a pathway for improving BNF in grain legumes via PSM and P solubilizing bacteria (PSB). Because BNF in legumes is a P-requiring agro-ecological process, the ability of soil PSB to synergize with the rhizobial strains is likely a key belowground process worth investigating for advanced research aiming to improve rhizosphere biological functions necessary for sustainable legume-based cropping systems.
Multifaceted Interaction Between Hepatitis B Virus Infection and Lipid Metabolism in Hepatocytes: A Potential Target of Antiviral Therapy for Chronic Hepatitis B

Hepatitis B virus (HBV) is considered a “metabolic virus” and affects many hepatic metabolic pathways. However, how HBV affects lipid metabolism in hepatocytes remains uncertain yet. Accumulating clinical studies suggested that compared to non-HBV-infected controls, chronic HBV infection was associated with lower levels of serum total cholesterol and triglycerides and a lower prevalence of hepatic steatosis. In patients with chronic HBV infection, high ALT level, high body mass index, male gender, or old age was found to be positively correlated with hepatic steatosis. Furthermore, mechanisms of how HBV infection affected hepatic lipid metabolism had also been explored in a number of studies based on cell lines and mouse models. These results demonstrated that HBV replication or expression induced extensive and diverse changes in hepatic lipid metabolism, by not only activating expression of some critical lipogenesis and cholesterolgenesis-related proteins but also upregulating fatty acid oxidation and bile acid synthesis. Moreover, increasing studies found some potential targets to inhibit HBV replication or expression by decreasing or enhancing certain lipid metabolism-related proteins or metabolites. Therefore, in this article, we comprehensively reviewed these publications and revealed the connections between clinical observations and experimental findings to better understand the interaction between hepatic lipid metabolism and HBV infection. However, the available data are far from conclusive, and there is still a long way to go before clarifying the complex interaction between HBV infection and hepatic lipid metabolism.
Thuricin17 Production and Proteome Differences in Bacillus thuringiensis NEB17 Cell-Free Supernatant Under NaCl Stress

Bacillus thuringiensis strain NEB17, produces a bacteriocin, thuricin17 (Th17) and is known to promote the growth more effectively under salt stress conditions. In this study, bacterial salt stress tolerance screening and the possible changes in its secretome under two levels of NaCl stress was evaluated. The salt tolerance screening suggested that the bacterium is able to grow and survive in up to 900 mM NaCl. Thuricin17 production at salt levels from 100 to 500 mM NaCl was quantified using High Performance Liquid Chromatography (HPLC). Salt stress adversely affected the production of Th17 at levels as low as 100 mM NaCl; and the production stopped at 500 mM NaCl, despite the bacterium thriving at these salt levels. Hence, a comparative proteomic study was conducted on the supernatant of the bacterium after 42 h of growth, when Th17 production peaked in the control culture, as determined by Liquid Chromatography - Tandem Mass Spectrometry (LC-MS/MS). Optimal (salt free) bacterial culture served as a control and 200 and 500 mM NaCl as stress conditions. As salt levels increased, the major enzyme classes, transferases, hydrolases, lyases, and ligases showed increased abundance as compared to the control, mostly related to molecular function mechanisms. Some of the notable up-regulated proteins in 500 mM NaCl stress conditions included an S-layer protein, chitin binding domain 3 protein, enterotoxins, phosphopentomutase, glucose 6-phosphate isomerase and bacterial translation initiation factor; while notable down-regulated proteins included hemolytic enterotoxin, phospholipase, sphingomyelinase C, cold shock DNA-binding protein family and alcohol dehydrogenase. These results indicate that, as the salt stress levels increase, the bacterium probably shuts down the production of Th17 and regulates its molecular functional mechanisms to overcome stress. This study indicates that end users have the option of using Th17 as a biostimulant or the live bacterial inoculum depending on the soil salt characteristics, for crop production. The mass spectrometry proteomics data have been deposited to Mass Spectrometry Interactive Virtual Environment (MassIVE) with the dataset identifier PXD024069, and doi: 10.25345/C5RB8T.
Following Guidelines for Drug-Resistant Tuberculosis: “Yes, it’s a challenge”

Background Drug-resistant tuberculosis (DR-TB) is a major contributor to antimicrobial resistance (AMR) globally and is projected to be responsible for up to a quarter of AMR-associated deaths in the future. Management of DR-TB is increasingly decentralised to primary healthcare settings, and simultaneously becoming more complex due to a growing range of treatment options (e.g. novel agents, shorter regimens). This is reflected in the numerous recent updates to international guidelines and as such understanding the barriers and enablers to how healthcare workers access and use guidelines is vital. Materials and Methods We used an established psychological framework – the theoretical domains framework (TDF) – to construct and analyse an online survey and focus groups to explore healthcare workers current use of DR-TB guidelines in South Africa. We aimed to identify barriers and enablers with which to direct future attempts at improving guideline use. Results There were 19 responses to the online survey and 14 participants in two focus groups. 28% used the most up-to-date national guidelines, 79% accessed guidelines primarily on electronic devices. The TDF domains of ‘Social Influences’ (mean Likert score = 4.3) and ‘Beliefs about Consequences’ (4.2) were key enablers, with healthcare workers encouraged to use guidelines and also recognising the value in doing so. ‘Environmental Resources’ (3.7) and ‘Knowledge’ (3.3) were key barriers with limited, or variable access to guidelines and lack of confidence using them being notable issues. This was most noted for certain subgroups: children, HIV co-infected, pregnant women (2.7). Discussion Current use of DR-TB guidelines in South Africa is suboptimal. Planned interventions should focus on overcoming the identified key barriers and might include an increased use of digital tools.
The Prognostic Value of Plasma Cell-Free DNA Concentration in the Prostate Cancer: A Systematic Review and Meta-Analysis

Objective By virtue of largely disparate clinical outcomes of prostate cancer (PCA), there is a pressing need to search for useful biomarkers for PCA prognosis. Cell-free DNA (cfDNA) is a promising biomarker for detecting, monitoring, and predicting survival of prostate cancer (PCA). However, the utility of total cfDNA quantitation in PCA in clinical setting remains elusive. Here, we performed a thorough meta-analysis to assess the prognostic value of cfDNA concentration for patients with PCA. In addition, we tested the possibility of the combination of PSA and cfDNA test results to improve the prediction power in PCA prognosis. Method and Materials More than six databases, including PubMed, Web of Science, Medline, PMC, EMBASE and the Cochrane Library were searched. Results yielded all eligible articles from the date of inception to June 30, 2020. Continuous, diagnostic, and prognostic variables in cfDNA in PCA were included in the meta-analysis by STATA. Results A total of 23 articles were enrolled in our meta-analysis: 69.6% (16/23) were related to diagnosis, and 56.5% (13/23) were related to prognosis. The pooled concentration of cfDNA in PCA patients was significantly higher than in the control group (SMD = 0.89, 95%CI = 0.53, 1.26), mirroring results for the prostate-specific antigen (PSA). For the detection test variables, the SROC with 95%CI was 0.87 (0.84–0.90) for cfDNA concentration. In terms of prognostic variables, the concentrations of cfDNA were significantly related with progression-free survival (PFS, logHR = 0.84 (95%CI0.39, 1.28) and overall survival [OS, log HR = 0.60 (95%CI0.29, 0.90)]. Lastly, the test showed no significant publication bias in the present meta-analysis, excluding the diagnostic meta-analysis. Conclusions The concentration of cell-free DNA is high in the prostate cancer patients. The present study substantiates the prognostic value of the cfDNA concentration. High concentration cfDNA correlates with poor disease outcome of CRPC. The study cohort with large sample size is needed to evaluate the prognosis value of cfDNA in the future. We also emphasized that combination of PSA and cf DNA quantitation is important in future large individual meta study.
The Frequent Sampling of Wound Scratch Assay Reveals the “Opportunity” Window for Quantitative Evaluation of Cell Motility-Impeding Drugs

Wound healing assay performed with automated microscopy is widely used in drug testing, cancer cell analysis, and similar approaches. It is easy to perform, and the results are reproducible. However, it is usually used as a semi-quantitative approach because of inefficient image segmentation in transmitted light microscopy. Recently, several algorithms for wound healing quantification were suggested, but none of them was tested on a large dataset. In the current study, we develop a pipeline allowing to achieve correct segmentation of the wound edges in >95% of pictures and extended statistical data processing to eliminate errors of cell culture artifacts. Using this tool, we collected data on wound healing dynamics of 10 cell lines with 10 min time resolution. We determine that the overall kinetics of wound healing is non-linear; however, all cell lines demonstrate linear wound closure dynamics in a 6-h window between the fifth and 12th hours after scratching. We next analyzed microtubule-inhibiting drugs’, nocodazole, vinorelbine, and Taxol, action on the kinetics of wound healing in the drug concentration-dependent way. Within this time window, the measurements of velocity of the cell edge allow the detection of statistically significant data when changes did not exceed 10–15%. All cell lines show decrease in the wound healing velocity at millimolar concentrations of microtubule inhibitors. However, dose-dependent response was cell line specific and drug specific. Cell motility was completely inhibited (edge velocity decreased 100%), while in others, it decreased only slightly (not more than 50%). Nanomolar doses (10–100 nM) of microtubule inhibitors in some cases even elevated cell motility. We speculate that anti-microtubule drugs might have specific effects on cell motility not related to the inhibition of the dynamic instability of microtubules.
Brain Structural and Functional Reorganization in Tinnitus Patients Without Hearing Loss After Sound Therapy: A Preliminary Longitudinal Study

Sound therapy is one of the most common first-line treatments for idiopathic tinnitus. We aimed to investigate the brain structural and functional alterations between patients with idiopathic tinnitus without hearing loss (HL) and healthy controls (HCs) and between patients before and after sound therapy (narrow band noise). Structural and resting-state functional images were acquired from 13 tinnitus patients without HL and 18 HCs before and after 6 months of narrow band sound therapy (only patients received the treatment). Voxel-based morphometry (VBM) and independent component analysis (ICA) were conducted to separately investigate the brain structural and functional changes. Associations between brain changes and clinical variables were also performed. After the treatment, the % improvement of THI score was −1.30% (± 63.40%). Compared with HCs, tinnitus patients showed gray matter and white matter atrophy in the left middle temporal gyrus at baseline, and the gray matter volume was further reduced after the treatment. The patients also showed increased white matter volume in the cingulum (cingulate), right calcarine, left rolandic operculum, and left parietal and frontal lobes. Additionally, compared with HCs, tinnitus patients exhibited positive [medial visual network (mVN) and sensorimotor network (SMN), mVN and auditory network (AN)] and negative [mVN and lateral visual network (lVN)] internetwork functional connectivity (FC) at baseline and negative [left frontoparietal network (LFPN) and dorsal attention network (DAN), AN and posterior default mode network (pDMN)] internetwork FC after the narrow band sound therapy. The patients also showed negative [LFPN and right frontoparietal network (RFPN), LFPN and RFPN, anterior default mode network (aDMN) and AN, aDMN and DAN] internetwork FC after the treatment when compared with baseline. Our findings suggest that although the outcomes of idiopathic tinnitus patients without HL were not very good when the improvement of THI scores was used as an evaluation indicator, the patients experienced significant differences in auditory-related and non-auditory-related brain reorganization before and after the narrow band sound therapy, that is, sound therapy may have a significant effect on brain reorganization in patients with idiopathic tinnitus. This study may provide some new useful information for the understanding of mechanisms underlying idiopathic tinnitus.
Spiking Neural Network (SNN) With Memristor Synapses Having Non-linear Weight Update

Among many artificial neural networks, the research on Spike Neural Network (SNN), which mimics the energy-efficient signal system in the brain, is drawing much attention. Memristor is a promising candidate as a synaptic component for hardware implementation of SNN, but several non-ideal device properties are making it challengeable. In this work, we conducted an SNN simulation by adding a device model with a non-linear weight update to test the impact on SNN performance. We found that SNN has a strong tolerance for the device non-linearity and the network can keep the accuracy high if a device meets one of the two conditions: 1. symmetric LTP and LTD curves and 2. positive non-linearity factors for both LTP and LTD. The reason was analyzed in terms of the balance between network parameters as well as the variability of weight. The results are considered to be a piece of useful prior information for the future implementation of emerging device-based neuromorphic hardware.
Measuring Online Wellbeing: A Scoping Review of Subjective Wellbeing Measures

With the increasing importance of the internet to our everyday lives, questions are rightly being asked about how its' use affects our wellbeing. It is important to be able to effectively measure the effects of the online context, as it allows us to assess the impact of specific online contexts on wellbeing that may not apply to offline wellbeing. This paper describes a scoping review of English language, peer-reviewed articles published in MEDLINE, EMBASE, and PsychInfo between 1st January 2015 and 31st December 2019 to identify what measures are used to assess subjective wellbeing and in particular to identify any measures used in the online context. Two hundred forty studies were identified; 160 studies were removed by abstract screening, and 17 studies were removed by full-text screening, leaving 63 included studies. Fifty-six subjective wellbeing scales were identified with 18 excluded and 38 included for further analysis. Only one study was identified researching online wellbeing, and no specific online wellbeing scale was found. Therefore, common features of the existing scales, such as the number and type of questions, are compared to offer recommendations for building an online wellbeing scale. Such a scale is recommended to be between 3 and 20 questions, using mainly 5-point Likert or Likert-like scales to measure at least positive and negative affect, and ideally life satisfaction, and to use mainly subjective evaluation. Further research is needed to establish how these findings for the offline world effectively translate into an online measure of wellbeing.
The Untapped Potential of Virtual Reality in Rehabilitation of Balance and Gait in Neurological Disorders

Dynamic systems theory transformed our understanding of motor control by recognizing the continual interaction between the organism and the environment. Movement could no longer be visualized simply as a response to a pattern of stimuli or as a demonstration of prior intent; movement is context dependent and is continuously reshaped by the ongoing dynamics of the world around us. Virtual reality is one methodological variable that allows us to control and manipulate that environmental context. A large body of literature exists to support the impact of visual flow, visual conditions, and visual perception on the planning and execution of movement. In rehabilitative practice, however, this technology has been employed mostly as a tool for motivation and enjoyment of physical exercise. The opportunity to modulate motor behavior through the parameters of the virtual world is often ignored in practice. In this article we present the results of experiments from our laboratories and from others demonstrating that presenting particular characteristics of the virtual world through different sensory modalities will modify balance and locomotor behavior. We will discuss how movement in the virtual world opens a window into the motor planning processes and informs us about the relative weighting of visual and somatosensory signals. Finally, we discuss how these findings should influence future treatment design.