Miracle-dz/UniFAR-FTUs huggingface dataset:
High Na+ Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils

Infection and inflammation can augment local Na+ abundance. These increases in local Na+ levels boost proinflammatory and antimicrobial macrophage activity and can favor polarization of T cells towards a proinflammatory Th17 phenotype. Although neutrophils play an important role in fighting intruding invaders, the impact of increased Na+ on the antimicrobial activity of neutrophils remains elusive. Here we show that, in neutrophils, increases in Na+ (high salt, HS) impair the ability of human and murine neutrophils to eliminate Escherichia coli and Staphylococcus aureus. High salt caused reduced spontaneous movement, degranulation and impaired production of reactive oxygen species (ROS) while leaving neutrophil viability unchanged. High salt enhanced the activity of the p38 mitogen-activated protein kinase (p38/MAPK) and increased the interleukin (IL)-8 release in a p38/MAPK-dependent manner. Whereas inhibition of p38/MAPK did not result in improved neutrophil defense, pharmacological blockade of the phagocyte oxidase (PHOX) or its genetic ablation mimicked the impaired antimicrobial activity detected under high salt conditions. Stimulation of neutrophils with phorbol-12-myristate-13-acetate (PMA) overcame high salt-induced impairment in ROS production and restored antimicrobial activity of neutrophils. Hence, we conclude that high salt-impaired PHOX activity results in diminished antimicrobial activity. Our findings suggest that increases in local Na+ represent an ionic checkpoint that prevents excessive ROS production of neutrophils, which decreases their antimicrobial potential and could potentially curtail ROS-mediated tissue damage.
Efficacy and safety of secukinumab in patients with psoriatic arthritis: A meta-analysis of different dosing regimens

The appropriate dosing regimens of secukinumab for psoriatic arthritis (PsA) are not well defined. We performed a meta-analysis to evaluate the efficacy and safety of different dosing regimens of secukinumab in the treatment of PsA. A systematic search was conducted using major electronic databases to identify relevant randomized controlled trials (RCTs) comparing secukinumab 300 mg versus secukinumab 150 mg in patients with PsA. Meta-analysis was performed using Review Manager software (version 5.3). Six studies with a total of 1141 patients were included. At week 24, secukinumab 300 mg was associated with a higher American College of Rheumatology 20% response (ACR 20), ACR 50, PASI 75 response rate, and dactylitis resolution rate than secukinumab 150 mg, especially in the anti-TNF-IR subgroup. At week 52, secukinumab 300 mg was associated with a higher psoriasis area and severity index (PASI) 75 and PASI 90 response rate than secukinumab 150 mg. There was no significant difference between secukinumab 300 mg and secukinumab 150 mg in the risk of any adverse events (AEs) and serious AEs at either week 24 or week 52. Secukinumab 300 mg was significantly more effective than 150 mg, especially for patients with PsA who have failed TNF therapy, and it was well tolerated.
Frequency‐based analysis of random fatigue loads: Models, hypotheses, reality

Spectral methods use analytical expressions to estimate the fatigue damage in vibrating structures subjected to uniaxial or multiaxial random stresses. They exploit the random vibration theory which idealizes the random stress as a random process characterized by a power spectral density (PSD) in the frequency‐domain. The random process is hypothesized to be stationary or non‐stationary, Gaussian or non‐Gaussian, and with narrow‐band or wide‐band power spectral density. The accuracy of analytical spectral solutions depends on whether such hypotheses are fulfilled by actual random time‐histories encountered in practice. Knowing the range of applicability of each spectral method is then of utmost importance to avoid estimation errors. After a short account on the frequency‐domain description of random processes, this paper presents a brief survey on selected spectral methods for uniaxial and multiaxial random loading. It then analyzes when the hypotheses behind each spectral method are not verified in reality, with the purpose to provide recommendations for a safe use of frequency‐based methods.
Association of multiple preventive therapies postdischarge and long-term health outcomes after acute myocardial infarction

Background: Statins, beta-blockers, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers have been advocated by guidelines as secondary prevention medications to improve the long-term outcomes of post-acute myocardial infarction (AMI) patients. However, adequate drug adherence has always been challenging, and different treatment regimens may lead to divergent outcomes that remain unclear under current myocardial infarction (MI) care standards. This study investigated the association between use of different preventive regimens post-AMI and patients’ long-term outcomes. Methods: This cohort study used data files from the Taiwan National Health Insurance Research Database. A total of 77 520 people who were hospitalized with AMI between 2002 and 2015 were assessed. On the basis of medication possession ratio (MPR) to individual medications, eight treatment groups were examined in this study. Receiving therapy was defined as MPR ≥40%. We investigated the association between different treatment groups and all-cause mortality in 24 months. Results: Overall, 51 322 patients with ST-elevation MI and 26 198 with non-ST-elevation MI were included in the study. Patients received all three preventive medications show the lowest mortality in 24 months follow-up periods among all treatment groups. Patients who did not usage of any of these three preventive medications had the highest mortality in 24 months (adjusted hazard ratio, 1.78; 95% CI, 1.64-1.93). This mortality rate had the same pattern across the three cohort generations (2002-2005, 2006-2010, and 2011-2015). Conclusion: In this large population-based real-world study, usage of three preventive therapies post-MI was associated with the lowest rate of all-cause mortality.
Endurance Exercise Training reduces Blood Pressure according to the Wilder’s Principle

Abstract The effect of antihypertensive medicine (AHM) is larger the higher the pre-treatment blood pressure level. It is unknown whether this Wilder’s principle, also applies for the exercise-training blood pressure (BP) lowering effect. One hundred seventy-eight (n=178) middle-aged individuals (55±8 y) with metabolic syndrome (MetS), underwent high intensity interval training (3 days·week–1) for 16 weeks. Participants were divided into medicated (Med; n=103) or not medicated (No Med; n=75) with AHM. Office BP was evaluated before and after the exercise-training. Correlations and stepwise regression analysis were used to determine which variable better predicted the reductions in systolic BP (SBP) with training. After training, participants with hypertension lowered SBP by a similar magnitude regardless of if they were in the Med (–15 mmHg, 95% CI–12,–19; P<0.001) or No Med group (–13 mmHg, 95% CI–9,–16; P<0.001). However, SBP did not decrease among normotensive groups (P=0.847 for Med and P=0.937 for No Med). Pre-treatment SBP levels was the best predictor of exercise-training lowering effect (r=–0.650; β=–0.642; P<0.001). For each 10 mmHg higher pre-training SBP there were a 5 mmHg deeper SBP reduction (Wilder principle). Furthermore, AHM does not interfere with exercise-training BP-lowering effect.
Gene expression network related to DNA methylation and miRNA regulation during the process of aflatoxin B1‐induced malignant transformation of L02 cells

Aflatoxin is a secondary metabolite secreted by Aspergillus flavus, parasitic Aspergillus, and other fungi through the polyketone pathway, and it can be detected in many foods. Aflatoxin has strong toxicity and carcinogenicity, and many studies have shown that aflatoxin is highly associated with liver cancer. In the present study, malignant transformation of L02 cells was induced by aflatoxin B1 (AFB1), and the gene expression, miRNA expression, and methylation level were detected by high‐throughput sequencing. The gene and miRNA expression results showed that 2547 genes and 315 miRNAs were changed in the AFB1‐treated group compared with the DMSO group. Among them, RSAD2 and SCIN were significantly upregulated, whereas TRAPPC3L and UBE2L6 were significantly downregulated. Has‐miR‐33b‐3p was significantly upregulated, whereas Has‐miR‐3613‐5p was significantly downregulated. The methylation results showed that 2832 CpG sites were methylated on the promoter or coding DNA sequence (CDS) of the gene, whereas the expression of DNMT3a and DNMT3b was significantly upregulated. Moreover, hypermethylation occurred in TRAPPC3L, CDH13, and SPINK13. The results of GO and KEGG pathway analyses showed that significantly changed genes and miRNAs were mainly involved in tumor formation, proliferation, invasion, and migration. The results of network map analysis showed that Hsa‐miR‐3613‐5p, Hsa‐miR‐615‐5p, Hsa‐miR‐615‐3p, and Hsa‐miR‐3158‐3p were the key miRNAs for malignant transformation of L02 cells induced by AFB1. In addition, the expression of ONECUT2, RAP1GAP2, and FSTL4 was regulated by DNA methylation and miRNAs. These results suggested that the gene expression network regulated by DNA methylation and miRNAs may play a vital role in AFB1‐induced hepatocellular carcinoma.
GigaMVS: A Benchmark for Ultra-Large-Scale Gigapixel-Level 3D Reconstruction

Multiview stereopsis (MVS) methods, which can reconstruct both the 3D geometry and texture from multiple images, have been rapidly developed and extensively investigated from the feature engineering methods to the data-driven ones. However, there is no dataset containing both the 3D geometry of large-scale scenes and high-resolution observations of small details to benchmark the algorithms. To this end, we present GigaMVS, the first gigapixel-image-based 3D reconstruction benchmark for ultra-large-scale scenes. The gigapixel images, with both wide field-of-view and high-resolution details, can clearly observe both the <italic>Palace</italic>-scale scene structure and <italic>Relievo</italic>-scale local details. The ground-truth geometry is captured by the laser scanner, which covers ultra-large-scale scenes with an average area of 8667 m<inline-formula><tex-math notation="LaTeX">$^2$</tex-math><alternatives><mml:math><mml:msup><mml:mrow/><mml:mn>2</mml:mn></mml:msup></mml:math><inline-graphic xlink:href="fang-ieq1-3115028.gif"/></alternatives></inline-formula> and a maximum area of 32007 m<inline-formula><tex-math notation="LaTeX">$^2$</tex-math><alternatives><mml:math><mml:msup><mml:mrow/><mml:mn>2</mml:mn></mml:msup></mml:math><inline-graphic xlink:href="fang-ieq2-3115028.gif"/></alternatives></inline-formula>. Owing to the extremely large scale, complex occlusion, and gigapixel-level images, GigaMVS exposes problems that emerge from the poor scalability and efficiency of the existing MVS algorithms. We thoroughly investigate the state-of-the-art methods in terms of geometric and textural measurements, which point to the weakness of the existing methods and promising opportunities for future works. We believe that GigaMVS can benefit the community of 3D reconstruction and support the development of novel algorithms balancing robustness, scalability and accuracy.
How top-down and bottom-up attention modulate risky choice

Significance How much are we in control of our decisions? The current study explores how goal-relevant (top-down) and perceptual features (bottom-up) govern the distribution of attention in risky choice. Findings from participants’ choices, eye movements, and computational modeling analysis show that while salient perceptual features can influence the acquisition of information, their influence on choice is limited to situations in which those features are tied to potential outcomes of the decision. When such features are not tied to outcomes, their influence is suppressed by top-down control. These results suggest, contrary to popular accounts, that perceptual salience can induce bottom-up effects of overt selection, but the perceived value of information is the crucial arbiter of intentional control over choice. We examine how bottom-up (or stimulus-driven) and top-down (or goal-driven) processes govern the distribution of attention in risky choice. In three experiments, participants chose between a certain payoff and the chance of receiving a payoff drawn randomly from an array of eight numbers. We tested the hypothesis that initial attention is driven by perceptual properties of the stimulus (e.g., font size of the numbers), but subsequent choice is goal-driven (e.g., win the best outcome). Two experiments in which task framing (goal driven) and font size (stimulus driven) were manipulated demonstrated that payoffs with the highest values and the largest font sizes had the greatest impact on choice. The third experiment added a number in large font to the array, which could not be an outcome of the gamble (i.e., a distractor). Eye movement and choice data indicated that although the distractor attracted attention, it had no influence on option selection. Together with computational modeling analyses, the results suggest that perceptual salience can induce bottom-up effects of overt selection but that the perceived value of information is the crucial arbiter of intentional control over risky choice.
The CO2 record at the Amazon Tall Tower Observatory: A new opportunity to study processes on seasonal and inter‐annual scales

High‐quality atmospheric CO2 measurements are sparse in Amazonia, but can provide critical insights into the spatial and temporal variability of sources and sinks of CO2. In this study, we present the first 6 years (2014–2019) of continuous, high‐precision measurements of atmospheric CO2 at the Amazon Tall Tower Observatory (ATTO, 2.1°S, 58.9°W). After subtracting the simulated background concentrations from our observational record, we define a CO2 regional signal ( ΔCO2obs ) that has a marked seasonal cycle with an amplitude of about 4 ppm. At both seasonal and inter‐annual scales, we find differences in phase between ΔCO2obs and the local eddy covariance net ecosystem exchange (EC‐NEE), which is interpreted as an indicator of a decoupling between local and non‐local drivers of ΔCO2obs . In addition, we present how the 2015–2016 El Niño‐induced drought was captured by our atmospheric record as a positive 2σ anomaly in both the wet and dry season of 2016. Furthermore, we analyzed the observed seasonal cycle and inter‐annual variability of ΔCO2obs together with net ecosystem exchange (NEE) using a suite of modeled flux products representing biospheric and aquatic CO2 exchange. We use both non‐optimized and optimized (i.e., resulting from atmospheric inverse modeling) NEE fluxes as input in an atmospheric transport model (STILT). The observed shape and amplitude of the seasonal cycle was captured neither by the simulations using the optimized fluxes nor by those using the diagnostic Vegetation and Photosynthesis Respiration Model (VPRM). We show that including the contribution of CO2 from river evasion improves the simulated shape (not the magnitude) of the seasonal cycle when using a data‐driven non‐optimized NEE product (FLUXCOM). The simulated contribution from river evasion was found to be 25% of the seasonal cycle amplitude. Our study demonstrates the importance of the ATTO record to better understand the Amazon carbon cycle at various spatial and temporal scales.
Alpha‐arrestins Aly1/Art6 and Aly2/Art3 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis

Phosphatidylinositol (PI) is an essential phospholipid, critical to membrane bilayers. The complete deacylation of PI by B‐type phospholipases produces intracellular and extracellular glycerophosphoinositol (GPI). Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters at the yeast plasma membrane. Internalized GPI is degraded to produce inositol, phosphate and glycerol, thereby contributing to these pools. GIT1 gene expression is controlled by nutrient balance, with phosphate or inositol starvation increasing GIT1 expression to stimulate GPI uptake. However, less is known about control of Git1 protein levels or localization.
Exposure to Systemic Immunosuppressive Ultraviolet Radiation Alters T Cell Recirculation through Sphingosine-1-Phosphate

Systemic suppression of adaptive immune responses is a major way in which UV radiation contributes to skin cancer development. Immune suppression is also likely to explain how UV protects from some autoimmune diseases, such as multiple sclerosis. However, the mechanisms underlying UV-mediated systemic immune suppression are not well understood. Exposure of C57BL/6 mice to doses of UV known to suppress systemic autoimmunity led to the accumulation of cells within the skin-draining lymph nodes and away from non–skin-draining lymph nodes. Transfer of CD45.1+ cells from nonirradiated donors into CD45.2+ UV-irradiated recipients resulted in preferential accumulation of donor naive T cells and a decrease in activated T cells within skin-draining lymph nodes. A single dose of immune-suppressive UV was all that was required to cause a redistribution of naive and central memory T cells from peripheral blood to the skin-draining lymph nodes. Specifically, CD69-independent increases in sphingosine-1-phosphate (S1P) receptor 1–negative naive and central memory T cells occurred in these lymph nodes. Mass spectrometry analysis showed UV-mediated activation of sphingosine kinase 1 activity, resulting in an increase in S1P levels within the lymph nodes. Topical application of a sphingosine kinase inhibitor on the skin prior to UV irradiation eliminated the UV-induced increase in lymph node S1P and T cell numbers. Thus, exposure to immunosuppressive UV disrupts T cell recirculation by manipulating the S1P pathway. Visual Abstract Key Points UV redistributes T cells from blood to skin-draining lymph nodes by increasing lymph node S1P. Sphingosine kinase inhibitors prevent UV increases in lymph node S1P and T cells.
Test-Retest Reliability of Short-Interval Intracortical Inhibition Assessed by Threshold-Tracking and Automated Conventional Techniques

Abstract Two novel short-interval intracortical inhibition (SICI) protocols, assessing SICI across a range of interstimulus intervals (ISIs) using either parallel threshold-tracking transcranial magnetic stimulation (TT-TMS) or automated conventional TMS (cTMS), were recently introduced. However, the test-retest reliability of these protocols has not been investigated, which is important if they are to be introduced in the clinic. SICI was recorded in 18 healthy subjects using TT-TMS (T-SICI) and cTMS (A-SICI). All subjects were examined at four identical sessions, i.e., morning and afternoon sessions on 2 d, 5–7 d apart. Both SICI protocols were performed twice at each session by the same observer. In one of the sessions, another observer performed additional examinations. Neither intraobserver nor interobserver measures of SICI differed significantly between examinations, except for T-SICI at ISI 3 ms (p = 0.00035) and A-SICI at ISI 2.5 ms (p = 0.0103). Intraday reliability was poor-to-good for A-SICI and moderate-to-good for T-SICI. Interday and interobserver reliabilities of T-SICI and A-SICI were moderate-to-good. Although between-subject variation constituted most of the total variation, SICI repeatability in an individual subject was poor. The two SICI protocols showed no considerable systematic bias across sessions and had a comparable test-retest reliability profile. Findings from the present study suggest that both SICI protocols may be reliably and reproducibly employed in research studies, but should be used with caution for individual decision-making in clinical settings. Studies exploring reliability in patient cohorts are warranted to investigate the clinical utility of these two SICI protocols.
Effects of a Written Expression-Based Positive Psychological Intervention on the Psychological Status of Patients With Inflammatory Bowel Disease

This prospective parallel-group controlled trial explored the effects of a written expression-based positive psychological intervention on the psychological status of patients with inflammatory bowel disease. Primary outcomes were anxiety, depression, hope, optimism, and subjective well-being, assessed at 8 weeks. Secondary outcomes were coping mode, quality of life at 8 weeks, and patient feedback. Sixty-eight volunteer patients meeting inclusion criteria were recruited from a hospital in China and randomized into the intervention group (positive psychological intervention+care as usual = 33) and the control group (care as usual = 35). The intervention group showed significantly greater improvements in anxiety, depression, hope, and quality of life (p > .05). The intervention group scored the feasibility, simplicity, and applicability of the positive psychological intervention themes at more than 6.5 for all measures. The study concludes that written expression-based positive psychological interventions alleviate negative emotions in inflammatory bowel disease patients and enhance their positive psychological characteristics. This approach also promotes a positive coping mode in inflammatory bowel disease patients, and the intervention measures devised are convenient, feasible, and well-accepted by patients.
Association of vaginal dysbiosis and gestational diabetes mellitus with adverse perinatal outcomes

Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes and is an independent risk factor for vaginal dysbiosis. Understanding the vaginal microbiota in health and disease is essential to screen, detect, and manage complications of pregnancy. Therefore, the aims of the present study were to assess and compare vaginal dysbiosis in pregnancy in women with and without GDM and examine its impact on perinatal outcomes in our population.
Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor

Abstract BACKGROUND Dentato-rubro-thalamic tract (DRT) deep brain stimulation (DBS) suppresses tremor in essential tremor (ET) patients. However, DRT depiction through tractography can vary depending on the included brain regions. Moreover, it is unclear which section of the DRT is optimal for DBS. OBJECTIVE To evaluate deterministic DRT tractography and tremor control in DBS for ET. METHODS After DBS surgery, DRT tractography was conducted in 37 trajectories (20 ET patients). Per trajectory, 5 different DRT depictions with various regions of interest (ROI) were constructed. Comparison resulted in a DRT depiction with highest correspondence to intraoperative tremor control. This DRT depiction was subsequently used for evaluation of short-term postoperative adverse and beneficial effects. RESULTS Postoperative optimized DRT tractography employing the ROI motor cortex, posterior subthalamic area (PSA), and ipsilateral superior cerebellar peduncle and dentate nucleus best corresponded with intraoperative trajectories (92%) and active DBS contacts (93%) showing optimal tremor control. DRT tractography employing a red nucleus or ventral intermediate nucleus of the thalamus (VIM) ROI often resulted in a more medial course. Optimal stimulation was located in the section between VIM and PSA. CONCLUSION This optimized deterministic DRT tractography strongly correlates with optimal tremor control. This technique is readily implementable for prospective evaluation in DBS target planning for ET.