Miracle-dz/UniFAR-FTUs huggingface dataset:
Aberrant Expression of Intracellular let-7e, miR-146a, and miR-155 Correlates with Severity of Depression in Patients with Major Depressive Disorder and Is Ameliorated after Antidepressant Treatment

Chronic inflammation and abnormalities in Toll-like receptor (TLR) signaling pathways are associated with major depressive disorder (MDD). Our previous work reported that impaired negative regulators for the TLR pathways are associated with MDD. This study aimed to assess the association between the severity of depression and the intracellular microRNAs that regulate TLR4 signaling in both peripheral blood mononuclear cells (PBMCs) and monocytes from MDD patients. The severity of MDD before and after antidepressant treatment was determined by the 17-item Hamilton Depression Rating Scale, and quantitative RT-PCR was used to measure the levels of intracellular regulatory microRNAs, including let-7e, miR-21-5p miR-145, miR-223, miR-146a, and miR-155, in PBMCs and monocytes isolated from 43 healthy controls and 84 patients with MDD before and after treatment with antidepressants. Assays of PBMCs showed that the levels of let-7e, miR-146a, and miR-155 were lower in MDD patients than in healthy controls and were significantly higher after than before treatment in the 69 patients who completed treatment with antidepressants for four weeks. Levels of miR-146a and miR-155 in monocytes were lower in MDD patients than in controls and were increased in the former after antidepressant treatment. Multiple linear regression analyses found that let-7e and miR-146a expression before treatment was inversely correlated with severity of depression, whereas miR-155 before treatment was directly correlated with severity of depression. These findings suggest that intracellular regulatory microRNAs which regulate TLR4 signaling are aberrantly expressed in patients with MDD and that these levels are ameliorated by antidepressant treatment.
Balancing confidence and humility in the diagnostic process

Abstract Humility in medicine can be difficult to achieve, yet arguably is one of the most important competencies to master. Overconfidence, on the contrary, is a natural tendency, having established its roots in evolution where quicker and more confident decisions likely conferred a selective advantage. Moreover, humility may evoke an image of weakness and vulnerability, antithetical to contemporary medicine, whose culture is dominated by overconfidence. Nevertheless, humility can be learned, and is important because overconfident behavior can be detrimental to our patients medically, psychosocially and legally, when it results in delayed or missed diagnoses. To achieve humility requires a great deal of metacognition, normalizing doubt and not being afraid to utilize tools that may feel beneath us. To practice humility requires strength and emotional resilience. In this paper we explore the definitions, roles and implications of humility in medicine, and we pose suggestions of how to accomplish this in the diagnostic process.
A 10 b, 20 Msample/s, 35 mW pipeline A/D converter

This paper describes a 10 b, 20 Msample/s pipeline A/D converter implemented in 1.2 /spl mu/m CMOS technology which achieves a power dissipation of 35 mW at full speed operation. Circuit techniques used to achieve this level of power dissipation include digital correction to allow the use of dynamic comparators, and optimum scaling of capacitor values through the pipeline. Also, to be compatible with low voltage mixed-signal system environments, a switched capacitor (SC) circuit in each pipeline stage is implemented and operated at 3.3 V with a new high-speed, low-voltage operational amplifier and charge pump circuits. Measured performance includes 0.6 LSB of INL, 59.1 dB of SNDR (Signal-to-Noise-plus-Distortion-Ratio) for 100 kHz input at 20 Msample/s. At Nyquist sampling (10 MHz input) SNDR is 55.0 dB. Differential input range is /spl plusmn/1 V, and measured input referred RMS noise is 220 /spl mu/V. The power dissipation at 1 MS/s is below 3 mW with 58 dB of SNDR. >
Exploring Tantalum as a Potential Dopant to Promote the Thermoelectric Performance of Zinc Oxide

Zinc oxide (ZnO) has being recognised as a potentially interesting thermoelectric material, allowing flexible tuning of the electrical properties by donor doping. This work focuses on the assessment of tantalum doping effects on the relevant structural, microstructural, optical and thermoelectric properties of ZnO. Processing of the samples with a nominal composition Zn1−xTaxO by conventional solid-state route results in limited solubility of Ta in the wurtzite structure. Electronic doping is accompanied by the formation of other defects and dislocations as a compensation mechanism and simultaneous segregation of ZnTa2O6 at the grain boundaries. Highly defective structure and partial blocking of the grain boundaries suppress the electrical transport, while the evolution of Seebeck coefficient and band gap suggest that the charge carrier concentration continuously increases from x = 0 to 0.008. Thermal conductivity is almost not affected by the tantalum content. The highest ZT~0.07 at 1175 K observed for Zn0.998Ta0. 002O is mainly provided by high Seebeck coefficient (−464 μV/K) along with a moderate electrical conductivity of ~13 S/cm. The results suggest that tantalum may represent a suitable dopant for thermoelectric zinc oxide, but this requires the application of specific processing methods and compositional design to enhance the solubility of Ta in wurtzite lattice.
The Role of NADPH oxidases in the Etiology of Obesity and Metabolic Syndrome: Contribution of Individual Isoforms and Cell Biology.

SIGNIFICANCE Highly prevalent in Western cultures, obesity, metabolic syndrome, and diabetes increase the risk of cardiovascular morbidity and mortality and cost health care systems billions of dollars annually. At the cellular level, obesity, metabolic syndrome, and diabetes are associated with increased production of reactive oxygen species (ROS). Increased levels of ROS production in key organ systems like adipose tissue, skeletal muscle, and the vasculature causes disruption of tissue homeostasis leading to increased morbidity and risk of mortality. More specifically, growing evidence implicates the NADPH oxidase (Nox) enzymes in these pathologies through impairment of insulin signaling, inflammation, and vascular dysfunction. The Nox family of enzymes is a major driver of redox signaling through its production of superoxide anion, hydrogen peroxide and downstream oxidative metabolites. CRITICAL ISSUES However, due to the short half-lives of individual ROS and/or cellular defense systems, radii of ROS diffusion are commonly short, restricting redox signaling and oxidant stress to often localized events. Thus, special emphasis should be placed on cell type and subcellular location of Nox enzymes to better understand their role in the pathophysiology of metabolic diseases. Recent Advances: The primary goal of this review is to highlight recent advances and survey our current understanding of cell specific Nox enzymes' contributions to metabolic diseases. FUTURE DIRECTIONS We discuss the targeting of Nox enzymes as potential therapy and bring to light potential emerging areas Nox research, microparticles and epigenetics, in the context of metabolic disease.
The Effect of Er,Cr:YSGG and Diode Laser Applications on Dental Implant Surfaces Contaminated with Acinetobacter Baumannii and Pseudomonas Aeruginosa

Treatment of peri-implantitis through several implant surface decontamination techniques have been reported, however, some of them can negatively alter the implant surface or enhance more bacterial resistance. The aim of this in vitro study was to evaluate implant surface decontamination by means of Er,Cr:YSGG and diode lasers. Fifty micro-textured (MTX) dental implants were contaminated with Acinetobacter baumannii (n = 25) and with Pseudomonas aeruginosa (n = 25). All implants were then divided into five groups for the decontamination procedure. In group I (GI), decontamination was done with an Er,Cr:YSGG laser (2780 nm), while in group II (GII) decontamination was performed using photodynamic therapy (a 650 nm diode laser). In Group III (GIII) decontamination was performed with photodynamic therapy (an 808 nm diode laser), and in group IV (GIV) decontamination was performed with 0.12% chlorhexidine. Group V (GV) was the control group with no decontamination. After decontamination, colony forming units (CFU) were counted and implants were prepared for SEM analysis. A significant difference (p < 0.001) was observed for GI compared to the other groups, and also for GIV compared to both GII and GIII. The Er,Cr:YSGG laser (GI) showed the best results in decontaminating the implant surface. Chlorhexidine (GIV), proved to be better in decontaminating the implant surface than photodynamic therapy GII and diode laser GIII. No significant difference was found between group GII and GIII. The SEM analysis showed no significant change in the implant surface topography. The results of this study suggest that the Er,Cr:YSGG laser can be considered as an effective technique for reducing bacteria contamination on implant surfaces.
Sustained Local Delivery of Diclofenac from Three-Dimensional Ultrafine Fibrous Protein Scaffolds with Ultrahigh Drug Loading Capacity

The three-dimensional (3D) ultrafine fibrous scaffolds loaded with functional components can not only provide support to 3D tissue repair, but also deliver the components in-situ with small dosage and low fusion frequency. However, the conventional loading methods possess drawbacks such as low loading capacity or high burst release. In this research, an ultralow concentration phase separation (ULCPS) technique was developed to form 3D ultrafine gelatin fibers and, meanwhile, load an anti-inflammatory drug, diclofenac, with high capacities for the long-term delivery. The developed scaffolds could achieve a maximum drug loading capacity of 12 wt. % and a highest drug loading efficiency of 84% while maintaining their 3D ultrafine fibrous structure with high specific pore volumes from 227.9 to 237.19 cm3/mg. The initial release at the first hour could be reduced from 34.7% to 42.2%, and a sustained linear release profile was observed with a rate of about 1% per day in the following 30 days. The diclofenac loaded in and released from the ULCPS scaffolds could keep its therapeutic molecular structure. The cell viability has not been affected by the release of drug when the loading was less than 12 wt. %. The results proved the possibility to develop various 3D ultrafine fibrous scaffolds, which can supply functional components in-situ with a long-term.
Comparison of Strategies for the Determination of Sterol Sulfates via GC-MS Leading to a Novel Deconjugation-Derivatization Protocol

Sulfoconjugates of sterols play important roles as neurosteroids, neurotransmitters, and ion channel ligands in health and disease. In most cases, sterol conjugate analysis is performed with liquid chromatography-mass spectrometry. This is a valuable tool for routine analytics with the advantage of direct sterol sulfates analysis without previous cleavage and/or derivatization. The complementary technique gas chromatography-mass spectrometry (GC-MS) is a preeminent discovery tool in the field of sterolomics, but the analysis of sterol sulfates is hampered by mandatory deconjugation and derivatization. Despite the difficulties in sample workup, GC-MS is an indispensable tool for untargeted analysis and steroid profiling. There are no general sample preparation protocols for sterol sulfate analysis using GC-MS. In this study we present a reinvestigation and evaluation of different deconjugation and derivatization procedures with a set of representative sterol sulfates. The advantages and disadvantages of trimethylsilyl (TMS), methyloxime-trimethylsilyl (MO-TMS), and trifluoroacetyl (TFA) derivatives were examined. Different published procedures of sterol sulfate deconjugation, including enzymatic and chemical cleavage, were reinvestigated and examined for diverse sterol sulfates. Finally, we present a new protocol for the chemical cleavage of sterol sulfates, allowing for simultaneous deconjugation and derivatization, simplifying GC-MS based sterol sulfate analysis.
Task load modulates tDCS effects on language performance

Transcranial direct current stimulation (tDCS) effects in cognition are inconsistent across studies. This study aimed to discuss why typical models might be insufficient to explain these effects, and to investigate a brain state factor, task load, with behavioral experiments on phonological processing. The motor theory of speech perception states that motor codes for articulation take part in speech perception, a view sharpened by neuroimaging findings, which show that the motor role in phonological processing is weighted by the nature of the tasks. Three groups of 20 participants, each under a different tDCS condition (anodal, cathodal, or sham), performed a categorical perception (CP), a lexical decision (LD), and a word naming (WN) task while stimulated on the pars opercularis of the left inferior frontal gyrus, a language area typically involved with the motor role. These tasks were assumed to be subserved by a network of nodes which included the target, believed to be increasingly relevant for performance from speech perception to speech production. A‐tDCS facilitation and C‐tDCS downregulation should directly increase with the relevance of the target for the task. Downregulation of a low relevance node could result in facilitation by compensation from other nodes. Overall, our brain stimulation findings support the neuroimaging literature in that motor participation in phonological processing depends on task nature and show that tDCS effects are modulated by task load relative to the target. Outcomes such as the improved performance following cathodal tDCS in CP and WN suggest that compensatory mechanisms may take place when the tasks involve more complex neuronal networks.
Bioluminescent Ross River Virus Allows Live Monitoring of Acute and Long-Term Alphaviral Infection by In Vivo Imaging

Arboviruses like chikungunya and Ross River (RRV) are responsible for massive outbreaks of viral polyarthritis. There is no effective treatment or vaccine available against these viruses that induce prolonged and disabling arthritis. To explore the physiopathological mechanisms of alphaviral arthritis, we engineered a recombinant RRV expressing a NanoLuc reporter (RRV-NLuc), which exhibited high stability, near native replication kinetics and allowed real time monitoring of viral spread in an albino mouse strain. During the acute phase of the disease, we observed a high bioluminescent signal reflecting viral replication and dissemination in the infected mice. Using Bindarit, an anti-inflammatory drug that inhibits monocyte recruitment, we observed a reduction in viral dissemination demonstrating the important role of monocytes in the propagation of the virus and the adaptation of this model to the in vivo evaluation of treatment strategies. After resolution of the acute symptoms, we observed an increase in the bioluminescent signal in mice subjected to an immunosuppressive treatment 30 days post infection, thus showing active in vivo replication of remnant virus. We show here that this novel reporter virus is suitable to study the alphaviral disease up to the chronic phase, opening new perspectives for the evaluation of therapeutic interventions.
An Embedded Sensor System for Real-Time Detecting 5-DOF Error Motions of Rotary Stages

The geometric error motions of rotary stages greatly affect the accuracy of constructed machines such as machine tools, measuring instruments, and robots. In this paper, an embedded sensor system for real-time measurement of two radial and three angular error motions of a rotary stage is proposed, which makes use of a rotary encoder with multiple scanning heads to measure the rotational angle and two radial error motions and a miniature autocollimator to measure two tilt angular errors of the axis of rotation. The assembly errors of the grid disc of the encoder and the mirror for autocollimator are also evaluated and compensated. The developed measuring device can be fixed inside the rotary stage. In the experiments, radial error motions of two points on the axis (h = 5 mm and 60 mm) were measured and calibrated with LVDTs, and the data showed that the radial error motions of the axis were less than 20 μm, and the calibration residual errors were less than 2 μm. When intermittent external forces were applied to the stage, the change of the stage’s error motion could also be monitored accurately.
Conserved G-Quadruplexes Regulate the Immediate Early Promoters of Human Alphaherpesviruses

Human Alphaherpesviruses comprise three members, herpes simplex virus (HSV) 1 and 2 and varicella zoster virus (VZV). These viruses are characterized by a lytic cycle in epithelial cells and latency in the nervous system, with lifelong infections that may periodically reactivate and lead to serious complications, especially in immunocompromised patients. The mechanisms that regulate viral transcription have not been fully elucidated, but the master role of the immediate early (IE) genes has been established. G-quadruplexes are non-canonical nucleic-acid structures that control transcription, replication, and recombination in many organisms including viruses and that represent attractive antiviral targets. In this work, we investigate the presence, conservation, folding and activity of G-quadruplexes in the IE promoters of the Alphaherpesviruses. Our analysis shows that all IE promoters in the genome of HSV-1, HSV-2 and VZV contain fully conserved G-quadruplex forming sequences. These comprise sequences with long loops and bulges, and thus deviating from the classic G-quadruplex motifs. Moreover, their location is both on the leading and lagging strand and in some instances they contain exuberant G-tracts. Biophysical and biological analysis proved that all sequences actually fold into G-quadruplex under physiological conditions and can be further stabilized by the G-quadruplex ligand BRACO-19, with subsequent impairment of viral IE gene transcription in cells. These results help shed light on the control of viral transcription and indicate new viral targets to design drugs that impair the early steps of Alphaherpesviruses. In addition, they validate the significance of G-quadruplexes in the general regulation of viral cycles.
Impact of Constant Versus Fluctuating Temperatures on the Development and Life History Parameters of Aldrichina grahami (Diptera: Calliphoridae)

Necrophagous fly species are commonly used as forensic tools to estimate the minimum postmortem interval (PMImin). Many researchers raised necrophagous flies under constant temperature regimes to collect their developmental data. However, in most forensic cases, the ambient temperature fluctuates. In order to investigate a forensically important fly developmental mode (the Isomegalen diagram, Isomorphen diagram and Thermal summation models) and make comparisons of the developmental rate between constant temperatures and fluctuating temperatures, we used Aldrichina grahami (Diptera: Calliphoridae) to investigate the life history parameters at eight constant temperatures ranging from 8 to 36 °C. We also compared developmental rate of A. grahami in three groups of constant versus fluctuating temperatures: 8 °C vs. 6–12 °C, 12 °C vs. 10–16 °C, and 16 °C vs. 14–20 °C. Our data showed that A. grahami is cold tolerant with a mean (±SE) development threshold temperature (D0) of 3.41 ± 0.48 °C and a thermal summation constant (K) of 8125.2 ± 288.4-degree hours. The three groups subjected to fluctuating temperatures took longer to develop compared to those developing in constant temperatures when simulated in a model. These results not only provide detailed developmental data for the use of A. grahami in the estimation of the PMI, but also indicate that ambient temperature fluctuation must be taken into consideration for the use of all necrophagous fly species.
Endothelial-Dependent Vasomotor Dysfunction in Infants After Cardiopulmonary Bypass

Supplemental Digital Content is available in the text. Objectives: Cardiopulmonary bypass–induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants. Design: Single-center prospective observational cohort pilot study. Setting: Pediatric cardiac ICU at a tertiary children’s hospital. Patients: Children less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion. Intervention: None. Measurements and Main Results: Laser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2–4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2–4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R2 = 0.43; p = 0.008). Conclusions: Cutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.