Miracle-dz/UniFAR-FTUs huggingface dataset:
Prognostic significance of serum albumin in patients with stable coronary artery disease treated by percutaneous coronary intervention

Background Stable coronary artery disease (CAD) is known to have an increased risk of cardiovascular events. Serum albumin (Alb) is reported as a useful risk-stratification tool in cardiovascular diseases such as acute coronary syndrome or heart failure. However, the association between Alb and stable CAD is unclear. Thus, we aimed to investigate the prognostic significance of Alb in patients with stable CAD. Methods and results We analyzed the data of all patients admitted to Shinonoi General Hospital between October 2014 and October 2017 for newly diagnosed stable CAD, treated via elective percutaneous coronary intervention, with the exception of old myocardial infarction. We collected data, including Alb, at admission. The primary endpoint was major adverse cardiac events (MACE; defined as all-cause death, non-fatal myocardial infarction, non-fatal stroke). In 204 enrolled patients (median age, 73 years), during a median follow-up of 783 days, 28 experienced MACE. Alb was significantly lower in patients with MACE than in those without (p<0.001). In Kaplan-Meier analysis, low Alb predicted worse prognosis in MACE (p<0.001). In multivariate Cox regression analysis, low Alb levels independently predicted MACE (p<0.001) after adjusting for age and sex (HR 4.128 [95% CI 1.632–10.440], p = 0.003), or, age and C-reactive protein (HR 3.373 [95% CI 1.289–8.828], p = 0.013). Conclusions Low Alb levels predicted MACE in patients with stable CAD.
Disruption of peripheral nerve development in a zebrafish model of hyperglycemia.

Diabetes mellitus-induced hyperglycemia is associated with a number of pathologies such as retinopathy, nephropathy, delayed wound healing and diabetic peripheral neuropathy (DPN). Approximately 50% of patients with diabetes mellitus will develop DPN, which is characterized by disrupted sensory and/or motor functioning, with treatment limited to pain management. Zebrafish (Danio Rerio) are an emerging animal model used to study a number of metabolic disorders, including diabetes. Diabetic retinopathy, nephropathy, and delayed wound healing have all been demonstrated in zebrafish. Recently, our lab has demonstrated that following the ablation of the insulin producing β-cells of the pancreas (and subsequent hyperglycemia), the peripheral nerves begin to show signs of dysregulation. Here, we take a different approach, taking advantage of the transdermal absorption abilities of zebrafish larvae to extend the period of hyperglycemia. Following 5 days of 60mM D-glucose treatment, we observed motor axon defasciculation, disturbances in perineurial glia sheath formation, decreased myelination of motor axons, and sensory neuron mislocalization. This study extends our understanding of the structural changes of the peripheral nerve following induction of hyperglycemia, and does so in an animal model capable of potential DPN drug discovery in the future.
Cycle-by-cycle analysis of neural oscillations

Neural oscillations are widely studied using methods based on the Fourier transform, which models data as sums of sinusoids. For decades these Fourier-based approaches have successfully uncovered links between oscillations and cognition or disease. However, because of the fundamental sinusoidal basis, these methods might not fully capture neural oscillatory dynamics, because neural data are both nonsinusoidal and non-stationary. Here, we present a new analysis framework, complementary to Fourier analysis, that quantifies cycle-by-cycle time-domain features. For each cycle, the amplitude, period, and waveform symmetry are measured, the latter of which is missed using conventional approaches. Additionally, oscillatory bursts are algorithmically identified, allowing us to investigate the variability of oscillatory features within and between bursts. This approach is validated on simulated noisy signals with oscillatory bursts and outperforms conventional metrics. Further, these methods are applied to real data—including hippocampal theta, motor cortical beta, and visual cortical alpha—and can differentiate behavioral conditions.
The Phenylalanine Requirement of Elderly Men and Women Measured by Direct 13C Carbon Oxidation Method Is Similar to That of Young Adults.

BACKGROUND The phenylalanine requirement of the elderly is not known. Current recommendations are based on studies in young adults and are derived from a combined estimate of the total aromatic amino acids, phenylalanine, and tyrosine. OBJECTIVES The purpose of this study was to determine the dietary phenylalanine requirement of adults aged >65 y, using the direct amino acid oxidation method, by measuring the oxidation of l-[1-13C]phenylalanine to 13CO2 in response to graded phenylalanine intakes in the presence of excess tyrosine. METHODS Twelve subjects (6 men, 6 women), aged 73.8 ± 6.7 y (mean ± SD) and with a BMI (in kg/m2) of 26.4 ± 4.8 and 25.2 ± 4.4 for men and women, respectively, were randomized to phenylalanine intakes ranging from 7.20 to 40.0 mg . kg-1 . d-1 for a total of 66 studies. Study diets were isocaloric and isonitrogenous, providing protein and energy at 1.0 g . kg-1 . d-1 and 1.5 × resting energy expenditure (REE), respectively. Protein was provided as an amino acid mixture patterned after egg protein, with an excess of tyrosine and alanine to balance the nitrogen as phenylalanine intakes were varied. Two days prior to the study day, subjects were adapted to a milkshake diet providing protein at 1.0 g.kg-1 . d-1 and energy at 1.7 × REE. The mean phenylalanine requirement was determined using biphase linear regression analysis, which identified a breakpoint in the F13CO2 in response to graded phenylalanine intakes. RESULTS The mean and upper 95% CIs (approximating the recommended dietary allowance) of phenylalanine requirements were estimated to be 9.03 and 15.9 mg.kg-1 . d-1, respectively. CONCLUSION These results are similar to previously derived estimates of 9.1 and 13.6 mg.kg-1 . d-1 in young adult men and suggest that higher protein needs of the elderly to stimulate similar muscle protein synthesis rates as young adults are not driven by an increased requirement for phenylalanine. This trial was registered at clinicaltrials.gov as NCT02971059.
Simultaneous Detection of 14 Microcystin Congeners from Tissue Samples Using UPLC- ESI-MS/MS and Two Different Deuterated Synthetic Microcystins as Internal Standards

Cyanobacterial microcystins (MCs), potent serine/threonine-phosphatase inhibitors, pose an increasing threat to humans. Current detection methods are optimised for water matrices with only a few MC congeners simultaneously detected. However, as MC congeners are known to differ in their toxicity, methods are needed that simultaneously quantify the congeners present, thus allowing for summary hazard and risk assessment. Moreover, detection of MCs should be expanded to complex matrices, e.g., blood and tissue samples, to verify in situ MC concentrations, thus providing for improved exposure assessment and hazard interpretation. To achieve this, we applied two synthetic deuterated MC standards and optimised the tissue extraction protocol for the simultaneous detection of 14 MC congeners in a single ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) run. This procedure was validated using plasma and liver homogenates of mice (male and female) spiked with deuterated MC standards. For proof of concept, tissue and plasma samples from mice i.p. injected with MC-LR and MC-LF were analysed. While MC-LF was detected in all tissue samples of both sexes, detection of MC-LR was restricted to liver samples of male mice, suggesting different toxicokinetics in males, e.g., transport, conjugation or protein binding. Thus, deconjugation/-proteinisation steps should be employed to improve detection of bound MC.
Effects of Cholesterol on Water Permittivity of Biomimetic Ion Pair Amphiphile Bilayers: Interplay between Membrane Bending and Molecular Packing

Ion pair amphiphile (IPA), a molecular complex composed of a pair of cationic and anionic amphiphiles, is an inexpensive phospholipid substitute to fabricate vesicles with various pharmaceutical applications. Modulating the physicochemical and permeation properties of IPA vesicles are important for carrier designs. Here, we applied molecular dynamics simulations to examine the cholesterol effects on the structures, mechanics, and water permittivity of hexadecyltrimethylammonium-dodecylsulfate (HTMA-DS) and dodecyltrimethylammonium- hexadecylsulfate (DTMA-HS) IPA bilayers. Structural and mechanical analyses indicate that both IPA systems are in gel phase at 298 K. Adding cholesterol induces alkyl chain ordering around the rigid sterol ring and increases the cavity density within the hydrophilic region of both IPA bilayers. Furthermore, the enhanced alkyl chain ordering and the membrane deformation energy induced by cholesterol increase the permeation free energy penalty. In contrast, cholesterol has minor effects on the water local diffusivities within IPA membranes. Overall, the cholesterol reduces the water permittivity of rigid IPA membranes due to the synergistic effects of increased alkyl chain ordering and enhanced membrane mechanical modulus. The results provide molecular insights into the effects of molecular packing and mechanical deformations on the water permittivity of biomimetic IPA membranes, which is critical for designing IPA vesicular carriers.
Molecular Dysfunction and Phenotypic Derangement in Diabetic Cardiomyopathy

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15–20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.
Spinocerebellar ataxia type 7 with RP1L1-negative occult macular dystrophy as retinal manifestation

ABSTRACT Background: Spinocerebellar ataxia Type 7 (SCA7) is an autosomal dominant, progressive neurodegenerative disorder, primarily characterized by cerebellar ataxia. The disease is caused by the expansion of a CAG trinucleotide repeat within the ataxin-7 gene when its CAG repeat sequences are extended beyond 38. The degree of retinopathy can vary from pigment change in the fovea to foveal atrophy and is correlated with the number of CAG repeats. The present study describes a case of SCA7 with a retinal presentation similar to occult macular dystrophy (OMD) which is an inherited macular dystrophy characterized by presenting with a normal fundus and fluorescein angiography but with progressive central visual loss. Materials and Methods: Report of a case. Results: In this case, no specific abnormality was found on fundus examination, fluorescein angiography, full-field electroretinography and infrared autofluorescence. Spectral-domain optical coherence tomography showed foveal thinning, focal disruption of the ellipsoid zone, and central loss of the outer segment–retinal pigment epithelium interdigitation zone that were well matched with the multifocal electroretinography finding. Thirty-nine CAG repeats in ataxin-7 gene were identified through genetic testing. Conclusions: SCA7 can present with a very mild form of retinal degeneration similar to the classic phenotype of RP1L1-negative OMD in case of the lower number of CAG repeats.
Dynamics of a hippocampal neuronal ensemble encoding trace fear memory revealed by in vivo Ca2+ imaging

Although the biochemical signaling events in area CA1 of the hippocampus underlying memory acquisition, consolidation, retrieval, and extinction have been extensively studied, little is known about the activity dynamics of hippocampal neurons in CA1 during Pavlovian fear conditioning. Here, we use fiber-optic confocal microscopy coupled with the calcium indicator GCaMP6m to monitor neuron activity in freely moving mice during trace fear conditioning. We show that the activity of a group of CA1 neurons increases not only after the stimulus presentations, but also during the stimulus-free trace period when the conditioned mice exhibit a high level of freezing behavior. Therefore, we designate these cells “trace cells”. Interestingly, the activity of the trace cells increases in response to the conditioned stimuli during memory retrieval but diminishes during memory extinction. Importantly, the dynamics of neuron activity exhibit a high degree of correlation with the freezing behavior of the mice, suggesting that a neuronal ensemble responsible for encoding the trace fear memory is repeatedly reactivated during memory retrieval and later extinguished during memory extinction.
Load-Carriage Conditioning Elicits Task-Specific Physical and Psychophysical Improvements in Males.

Wills, JA, Saxby, DJ, Glassbrook, DJ, and Doyle, TLA. Load-carriage conditioning elicits task-specific physical and psychophysical improvements in males. J Strength Cond Res XX(X): 000-000, 2019-Load carriage is a requirement of many military roles and is commonly used as an assessment of soldier physical readiness. Loaded, compared with unloaded, walking tasks elicit increased physical demands, particularly around the hip joint, which can exceed the initial capacity of military personnel. This study aimed to identify and characterize physical performance responses to a lower-limb focused physical training program targeted toward load-carriage task demands. Fifteen healthy male civilians (22.6 ± 1.5 years, 1.82 ± 0.06 m, and 84.1 ± 6.9 kg) completed a 10-week physical training program consisting of resistance training and weighted walking. A load-carriage task representing the Australian Army All Corps minimum standard (5 km at 5.5 km·h, wearing a 23-kg torso-borne vest) was completed before and on completion of the 10-week training program. Heart rate and rating of perceived exertion measures were collected throughout the load-carriage task. The performance measures of countermovement and squat jumps, push-ups, sit-ups, and beep test were performed before, mid-way, and on completion (weeks 0, 6, and 11) of the 10-week training program. Psychophysical performance, as measured by rating of perceived exertion, significantly decreased (p < 0.05) during the load-carriage task after training, demonstrating improvements in psychophysical responses. The training program resulted in significant increases in squat jump maximal force, push-ups, sit-ups (p < 0.05), and estimated maximal oxygen uptake (p < 0.05). Physical performance improvements and positive physiological adaptations to a load-carriage task were elicited in males after completing a 10-week training program. Military organizations could use this evidence-based training program to efficiently train soldiers to improve their load-carriage capacity.
An Umbrella Review and Narrative Synthesis of the Effectiveness of Interventions Aimed at Decreasing Food Prices to Increase Food Quality

Background: sustainability of population diet is a public health concern: the high price of healthy food is one of the main causes of diet-related health problems. The aim of this study is to synthesize the evidence produced by systematic reviews that evaluated the effectiveness of decreasing healthy food prices to improve accessibility in order to positively modify the dietary pattern. Methods: We carried out a review of systematic reviews that examined the effects of the interventions, by exploring the online databases PubMed, Embase, Web of Science, Cochrane Library and hand-searching the reference lists. Results: after screening by titles and abstracts, we selected 11 systematic reviews that met the inclusion criteria, plus one that was hand-searched. The review generally presented a good quality. Studies concluded that measures aimed at modifying the prices of targeted healthy food were effective in improving population diet by modifying what people buy. Conclusions: the complexity of the outcome—population diet—as well as the poor transferability of data across populations and geographical areas makes it obligatory to provide clear and universal conclusions. Nonetheless, this should not stop policymakers from adapting them and resorting to food fiscal interventions to improve people’s diet and health.
Synaptic Strengths Dominate Phasing of Motor Circuit: Intrinsic Conductances of Neuron Types Need Not Vary across Animals

Visual Abstract Identified neurons and the networks they compose produce stereotypical, albeit individually unique, activity across members of a species. We propose, for a motor circuit driven by a central pattern generator (CPG), that the uniqueness derives mainly from differences in synaptic strength rather than from differences in intrinsic membrane conductances. We studied a dataset of recordings from six leech (Hirudo sp.) heartbeat control networks, containing complete spiking activity patterns from inhibitory premotor interneurons, motor output spike patterns, and synaptic strength patterns to investigate the source of uniqueness. We used a conductance-based multicompartmental motor neuron model to construct a bilateral motor circuit model, and controlled it by playing recorded input spike trains from premotor interneurons to generate output inhibitory synaptic patterns similar to experimental measurements. By generating different synaptic conductance parameter sets of this circuit model, we found that relative premotor synaptic strengths impinging onto motor neurons must be different across individuals to produce animal-specific output burst phasing. Obtaining unique outputs from each individual’s circuit model did not require different intrinsic ionic conductance parameters. Furthermore, changing intrinsic conductances failed to compensate for modified synaptic strength patterns. Thus, the pattern of synaptic strengths of motor neuron inputs is critical for the phasing of this motor circuit and can explain individual differences. When intrinsic conductances were allowed to vary, they exhibited the same conductance correlations across individuals, suggesting a motor neuron “type” required for proper network function. Our results are general and may translate to other systems and neuronal networks that control output phasing.
The Relationship Between β-cell Function Indices and Sudomotor Function in Chinese Patients with Type 2 Diabetes

Abstract Purpose SUDOSCAN, a new non-invasive, quick, sensitive and quantitative technique, has been developed to detect diabetic peripheral neuropathy, and the latter is believed to be correlated with impaired β-cell function. The purpose of the present study was to investigate the associations between β-cell function indices and sudomotor function in Chinese type 2 diabetes. Methods A total of 266 Chinese patients with type 2 diabetes were enrolled. Sudomotor function was assessed using electrochemical skin conductance of hands and feet. Pancreatic β-cell function was determined by homeostasis model assessment of β-cell function index, early-phase β-cell function indices and total β-cell function indices. Pearson correlation analysis and multiple linear stepwise regression analysis were carried out to explore the associations between β-cell function indices and sudomotor function. Results Patients with lower early-phase β-cell function had lower electrochemical skin conductance levels of hands and feet and higher asymmetry ratio of hands and feet. Both Pearson correlation analysis and multiple linear stepwise regression analysis showed significantly positive relationships between early-phase β-cell function and electrochemical skin conductance levels of hands and feet, after controlling for potential confounders (P<0.05). Conclusions Impaired early-phase β-cell function was positively associated with sudomotor dysfunction in Chinese patients with type 2 diabetes. We speculated that impaired early-phase β-cell function may be associated with the incidence of sudomotor dysfunction in patients with T2DM.
Expression of miR159 Is Altered in Tomato Plants Undergoing Drought Stress

In a scenario of global climate change, water scarcity is a major threat for agriculture, severely limiting crop yields. Therefore, alternatives are urgently needed for improving plant adaptation to drought stress. Among them, gene expression reprogramming by microRNAs (miRNAs) might offer a biotechnologically sound strategy. Drought-responsive miRNAs have been reported in many plant species, and some of them are known to participate in complex regulatory networks via their regulation of transcription factors involved in water stress signaling. We explored the role of miR159 in the response of Solanum lycopersicum Mill. plants to drought stress by analyzing the expression of sly-miR159 and its target SlMYB transcription factor genes in tomato plants of cv. Ailsa Craig grown in deprived water conditions or in response to mechanical damage caused by the Colorado potato beetle, a devastating insect pest of Solanaceae plants. Results showed that sly-miR159 regulatory function in the tomato plants response to distinct stresses might be mediated by differential stress-specific MYB transcription factor targeting. sly-miR159 targeting of SlMYB33 transcription factor transcript correlated with accumulation of the osmoprotective compounds proline and putrescine, which promote drought tolerance. This highlights the potential role of sly-miR159 in tomato plants’ adaptation to water deficit conditions.