Miracle-dz/UniFAR-FTUs huggingface dataset:
SERIAL-ORDER recall in working memory across the cognitive spectrum of Parkinson's disease and neuroimaging correlates.

We sought to determine if Parkinson's disease (PD) with mild cognitive impairment (MCI) is associated with a greater SERIAL-ORDER (mental manipulation) than ANY-ORDER (auditory span, storage) deficit in working memory (WM). We investigated WM combining neuropsychological measures with the study of brain functional connectivity. A cohort of 160 patients with idiopathic PD, classified as PD-MCI (n = 87) or PD with normal cognition (PD-NC; n = 73), and 70 matched healthy controls were studied. Verbal WM was assessed with the Backward Digit Span Task (BDT; Lamar et al., 2007, Neuropsychologia, 45, 245), measuring SERIAL-ORDER and ANY-ORDER recall. Resting-state MRI data were collected for 15 PD-MCI, 15 PD-NC and 30 controls. Hypothesis-driven seed-based functional connectivity of the dorsolateral prefrontal cortex (DLPFC) was compared between the three groups and correlated with BDT performance. We found the main effect of the test (impairment in SERIAL ORDER > ANY ORDER) and group ((NC = PD-NC) > PD-MCI) in BDT performance that was even more pronounced in SERIAL ORDER when controlling for ANY ORDER variability but not vice versa. Furthermore, PD-MCI compared to other groups were characterized by the functional disconnection between the bilateral DLPFC and the cerebellum. In functional correlations, DLPFC connectivity was positively related to both SERIAL- and ANY-ORDER performance. In conclusion, PD-MCI patients evidenced greater SERIAL-ORDER (manipulation and cognitive control) than ANY-ORDER (storage) working memory impairment than PD-NC and controls with a disrupted DLPFC resting-state connectivity that was also related to the verbal WM performance.
Hypermethylation of the TSPOAP1-AS1 Promoter May Be Associated with Obesity in Overweight/Obese Korean Subjects

Obesity is a major chronic disease associated with the risk of serious cardiovascular or endocrinal diseases, such as hypertension, diabetes, atherosclerosis and stroke. Considerable interest has been directed towards the potential effects of epigenetic variations in obesity. In this study, we evaluated DNA methylation level at the promoter region of the gene encoding TSPO-associated protein 1 antisense RNA 1 (TSPOAP1-AS1) in 80 overweight/obese subjects (body mass index (BMI) > 25) and 104 non-obese subjects who participated in the SOPI-Stroke study in Korea. DNA methylation was measured using bisulfite amplicon sequencing (BSAS). A general linear model or relative correlation was used to determine the effects of DNA methylation on obesity and obese phenotypes. Notably, the mean level of DNA methylation was significantly higher in the overweight/obese group than in the non-obese group (18.62% vs. 17.18%). Further analyses revealed significant positive correlations of the BMI, the serum total cholesterol and low-density lipoprotein cholesterol levels with the DNA methylation level (p = 0.0493, p = 0.003, and p = 0.0094, respectively). The study findings suggest an association between DNA methylation at the TSPOAP1-AS1 promoter and overweight/obesity. Accordingly, methylation in this promoter region might be a potential predictor of obesity.
miRNAs, oxidative stress, and cancer: A comprehensive and updated review

Oxidative stress refers to elevated levels of intracellular reactive oxygen species (ROS). ROS homeostasis functions as a signaling pathway for normal cell survival and appropriate cell signaling. Chronic inflammation induced by imbalanced levels of ROS contributes to many diseases and different types of cancer. ROS can alter the expression of oncogenes and tumor suppressor genes through epigenetic modifications, transcription factors, and non‐coding RNAs. MicroRNAs (miRNAs) are small non‐coding RNAs that play a key role in most biological pathways. Each miRNA regulates hundreds of target genes by inhibiting protein translation and/or promoting messenger RNA degradation. In normal conditions, miRNAs play a physiological role in cell proliferation, differentiation, and apoptosis. However, different factors that can dysregulate cell signaling and cellular homeostasis can also affect miRNA expression. The alteration of miRNA expression can work against disturbing factors or mediate their effects. Oxidative stress is one of these factors. Considering the complex interplay between ROS level and miRNA regulation and both of these with cancer development, we review the role of miRNAs in cancer, focusing on their function in oxidative stress.
Leptin-Mediated Changes in the Human Metabolome

Abstract Context While severe obesity due to congenital leptin deficiency is rare, studies in patients before and after treatment with leptin can provide unique insights into the role that leptin plays in metabolic and endocrine function. Objective The aim of this study was to characterize changes in peripheral metabolism in people with congenital leptin deficiency undergoing leptin replacement therapy, and to investigate the extent to which these changes are explained by reduced caloric intake. Design Ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) was used to measure 661 metabolites in 6 severely obese people with congenital leptin deficiency before, and within 1 month after, treatment with recombinant leptin. Data were analyzed using unsupervised and hypothesis-driven computational approaches and compared with data from a study of acute caloric restriction in healthy volunteers. Results Leptin replacement was associated with class-wide increased levels of fatty acids and acylcarnitines and decreased phospholipids, consistent with enhanced lipolysis and fatty acid oxidation. Primary and secondary bile acids increased after leptin treatment. Comparable changes were observed after acute caloric restriction. Branched-chain amino acids and steroid metabolites decreased after leptin, but not after acute caloric restriction. Individuals with severe obesity due to leptin deficiency and other genetic obesity syndromes shared a metabolomic signature associated with increased BMI. Conclusion Leptin replacement was associated with changes in lipolysis and substrate utilization that were consistent with negative energy balance. However, leptin’s effects on branched-chain amino acids and steroid metabolites were independent of reduced caloric intake and require further exploration.
Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-a]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-3-carboxylates 4a–f and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylates 4g–k have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of Mycobacterium tuberculosis by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8–128 µg/mL against H37Rv. The test compound dimethyl-1-(4-fluorobenzoyl)-5-methylpyrrolo[1,2-a]quinoline-2,3-dicarboxylate 4j emerged as the most promising anti-TB agent against H37Rv and multidrug-resistant strains of Mycobacterium tuberculosis at 8 and 16 µg/mL, respectively. In silico evaluation of pharmacokinetic properties indicated overall drug-likeness for most of the compounds. Docking studies were also carried out to investigate the binding affinities as well as interactions of these compounds with the target proteins.
The phosphorelay BarA/SirA activates the non-cognate regulator RcsB in Salmonella enterica

To survive an environmental stress, organisms must detect the stress and mount an appropriate response. One way that bacteria do so is by phosphorelay systems that respond to a stress by activating a regulator that modifies gene expression. To ensure an appropriate response, a given regulator is typically activated solely by its cognate phosphorelay protein(s). However, we now report that the regulator RcsB is activated by both cognate and non-cognate phosphorelay proteins, depending on the condition experienced by the bacterium Salmonella enterica serovar Typhimurium. The RcsC and RcsD proteins form a phosphorelay that activates their cognate regulator RcsB in response to outer membrane stress and cell wall perturbations, conditions Salmonella experiences during infection. Surprisingly, the non-cognate phosphorelay protein BarA activates RcsB during logarithmic growth in Luria-Bertani medium in three ways. That is, BarA’s cognate regulator SirA promotes transcription of the rcsDB operon; the SirA-dependent regulatory RNAs CsrB and CsrC further increase RcsB-activated gene transcription; and BarA activates RcsB independently of the RcsC, RcsD, and SirA proteins. Activation of a regulator by multiple sensors broadens the spectrum of environments in which a set of genes is expressed without evolving binding sites for different regulators at each of these genes.
Egg Weights, Energy Reserves, and Internal Nest Temperatures in Embryo Nests of Dolichovespula maculata (Hymenoptera: Vespidae)

Eggs of the baldfaced hornet, Dolichovespula maculata (L.), were collected from embryo (spring) nests and summer nests to quantify the energetic contributions provided by the queen. Egg weights were highest in the spring and decreased with progressive nest development. Mean dry weight of eggs in embryo nests was 266. 4µg; August nests had a mean dry egg weight of 179. 6µg. Nutrient reserves of eggs in embryo nests, in order of importance, were lipid (22%), glucose (9.5%), and glycogen (5%). A 10-d egg incubation experiment snowed a mean loss of 83µg in egg dry weight from an initial weight of 282µg. Temperature recordings from an embryo nest indicated that D. maculata queens can increase the temperature within an embryo nest as much as 4°C above ambient. The energetic contributions that a queen provides to the eggs are discussed with respect to environmental influences on development.
Marine Mortality Schedules of Pink Salmon of the Bella Coola River, Central British Columbia

The hypothesis that natural mortality rates of pink salmon during early life are generally much larger than during the later period has been tested for 3 brood-years of the Bella Coola River stock using a two-stage marking technique. Average daily losses to the population during the first 40 days are estimated to vary between 2 and 4%, and for the later 410-day period between 0.4 and 0.8%. These rates produce losses amounting to between 59 and 77% of the initial population during the first 40 days. Of the population surviving at 40 days, further losses of between 78 and 95% occurred. The latter losses are considered to be maximum estimates because of bias introduced by catches of unknown magnitude. Thus, although the early mortality is exceeded by the later, the time period is approximately 10 times as long, and the intensity of the mortality rate is much higher during early sea life.
Phase Modulation Beamforming for Ultrafast Plane-Wave Imaging

In order to improve the spatial resolution for high-frame-rate imaging, a new image formation approach is proposed based on introducing very weak aberration into received data, then combining the multiple results by taking the pixel-wise standard deviation of multiple aberrated images and subtracting the result from the delay-and-sum image. This approach is demonstrated in simulations, tissue-mimicking phantom experiments, and in vivo imaging. Simulations indicate the lateral full-width half-maximum (FWHM) of targets decreases by 38.24% ± 6.38%. In imaging wire targets in a tissue-mimicking phantom at 7.8 MHz, wire target FWHM decreases by 35.91% ± 5.39%. However, contrast was observed to decrease by 1.23 dB and contrast-to-noise ratio (CNR) by 18.5% in phantom studies due to the subtraction of similar images, which increases the number of dark pixels in the image. Finally, the proposed technique is tested in vivo, with images showing improvements similar to those in tissue-mimicking phantoms, including increased separation between closely spaced targets.
Artificial Intelligence and Primary Care Research: A Scoping Review

PURPOSE Rapid increases in technology and data motivate the application of artificial intelligence (AI) to primary care, but no comprehensive review exists to guide these efforts. Our objective was to assess the nature and extent of the body of research on AI for primary care. METHODS We performed a scoping review, searching 11 published or gray literature databases with terms pertaining to AI (eg, machine learning, bayes* network) and primary care (eg, general pract*, nurse). We performed title and abstract and then full-text screening using Covidence. Studies had to involve research, include both AI and primary care, and be published in Eng-lish. We extracted data and summarized studies by 7 attributes: purpose(s); author appointment(s); primary care function(s); intended end user(s); health condition(s); geographic location of data source; and AI subfield(s). RESULTS Of 5,515 unique documents, 405 met eligibility criteria. The body of research focused on developing or modifying AI methods (66.7%) to support physician diagnostic or treatment recommendations (36.5% and 13.8%), for chronic conditions, using data from higher-income countries. Few studies (14.1%) had even a single author with a primary care appointment. The predominant AI subfields were supervised machine learning (40.0%) and expert systems (22.2%). CONCLUSIONS Research on AI for primary care is at an early stage of maturity. For the field to progress, more interdisciplinary research teams with end-user engagement and evaluation studies are needed.
EBC metabolomics for asthma severity

Asthma is a heterogeneous disease with diverse severity and represents a considerable socio-economic burden. Exhaled Breath Condensate (EBC) is a biofluid directly obtained from the airway lining fluid non-invasively. We attempted to discriminate severe from mild-to-moderate asthma using EBC metabolomics based on both NMR and UHPLC-MS techniques. 36 patients were included in this study (15 patients with severe and 21 with mild-to-moderate asthma). EBC was collected and analyzed using both NMR and UHPLC-MS techniques for possible metabolites. Using PLS and oPLS analysis for the UHPLC-MS data, no metabolite was found to be sufficient for the discrimination of asthma severity. However, when another PLS-regression model was applied five metabolites were found to discriminate severe from mild-to-moderate asthma. Amino-acid lysine was the only metabolite that discriminated the two study groups using NMR data (p= 0.04, t-test with Welch’s correction, AUC 0.66). EBC is an easily available biofluid which directly represents the lower airways but difficult-to-use for metabolomic analysis. Our study presents some encouraging findings for the discrimination of asthma severity subgroups using EBC metabolomics but more well-designed studies with a higher number of patients need to be conducted.
Experimental demonstration of dynamic temperature-dependent behaviour of UiO-66 metal-organic-framework: Compaction of hydroxylated and deydroxylated forms of UiO-66 for high pressure hydrogen storage.

High-pressure (700 MPa or ~100 000 psi) compaction of dehydroxylated and hydroxylated UiO-66 for H2 storage applications is reported. The dehydroxylation reaction was found to occur between 150 - 300 oC. The H2 uptake capacity of powdered hydroxylated UiO-66 reaches 4.6 wt% at 77 K and 100 bar, which is 21% higher than that of dehydroxylated UiO-66 (3.8 wt%). On compaction the H2 uptake capacity of dehydroxylated UiO-66 pellets reduces by 66% from 3.8 wt% to 1.3 wt%, while for hydroxylated UiO-66 the pellets show only a 9% reduction in capacity from 4.6 wt% to 4.2 wt%. This implies the H2 uptake capacity of compacted hydroxylated UiO-66 is at least three times higher than that of dehydroxylated UiO-66, and therefore hydroxylated UiO-66 is more promising for hydrogen storage applications. The H2 uptake capacity is closely related to compaction induced changes in the porosity of UiO-66. The effect of compaction is greatest in partially dehydroxylated UiO-66 samples that are thermally treated at 200 and 290 oC. These compacted samples exhibit XRD patterns indicative of an amorphous material, low porosity (surface area reduces from between 700 and 1300 m2/g to ca. 200 m2/g and pore volume from between 0.4 and 0.6 cm3/g to 0.1 and 0.15 cm3/g) and very low hydrogen uptake (0.7 - 0.9 wt% at 77 K and 100 bar). The observed activation temperature-induced dynamic behaviour of UiO-66 is unusual for MOFs and has previously only been reported in computational studies. After compaction at 700 MPa, the structural properties and H2 uptake of hydroxylated UiO-66 remain relatively unchanged, but are extremely compromised upon compaction of dehydroxylated UiO-66. Therefore, UiO-66 responds in a dynamic manner to changes in activation temperature within the range in which it has hitherto been considered stable.
Extensively expanded murine‐induced hepatic stem cells maintain high‐efficient hepatic differentiation potential for repopulation of injured livers

Shortage of donor hepatocytes limits hepatocyte transplantation for clinical application. Induced hepatic stem cells (iHepSCs) have capacities of self‐renewal and bipotential differentiations. Here, we investigated whether iHepSCs could be extensively expanded, and whether they could differentiate into sufficient functional hepatocytes as donors for transplantation therapy after their extensive expansions.
Hydraulic and photosynthetic limitations prevail over root non-structural carbohydrate reserves as drivers of resprouting in two Mediterranean oaks.

Resprouting is an ancestral trait in angiosperms that confers resilience after perturbations. As climate change increases stress, resprouting vigor is declining in many forest regions, but the underlying mechanism is poorly understood. Resprouting in woody plants is thought to be primarily limited by the availability of non-structural carbohydrate reserves (NSC), but hydraulic limitations could also be important. We conducted a multifactorial experiment with two levels of light (ambient, 2-3% of ambient) and three levels of water stress (0, 50 and 80% losses of hydraulic conductivity, PLC) on two Mediterranean oaks (Quercus ilex and Q. faginea) under a rain-out shelter (n = 360). The proportion of resprouting individuals after canopy clipping declined markedly as PLC increased for both species. NSC concentrations affected the response of Q. ilex, the species with higher leaf construction costs, and its effect depended on the PLC. The growth of resprouting individuals was largely dependent on photosynthetic rates for both species, while stored NSC availability and hydraulic limitations played minor and non-significant roles, respectively. Contrary to conventional wisdom, our results indicate that resprouting in oaks may be primarily driven by complex interactions between hydraulics and carbon sources, whereas stored NSC play a significant but secondary role. This article is protected by copyright. All rights reserved.
Marine reserves: patterns of adult movement of the coral trout (Plectropomus leopardus (Serranidae))

Movements of Plectropomus leopardus (Serranidae), a major fisheries species, across marine reserve boundaries were investigated on the Great Barrier Reef, Australia. Mark-release-recapture and ultrasonic telemetry were used to assess movements. Mark-release-recapture used hook and line as the method of capture and underwater visual census (UVC) as the "recapture" tool. Catch rates were significantly higher in zones closed to fishing, despite UVC indicating no significant differences in density between closed and open zones. Of 183 fish marked with numerical freeze brands, 93 estimates of movements of branded fish were obtained. No branded fish was recorded to cross the reserve boundaries during the 2-month study, probably due to the initial decision to allocate capture effort evenly across the study area, rather than concentrating it on reserve boundaries. Fish carrying ultrasonic transmitters, and having home ranges straddling reserve boundaries, crossed boundaries on average 15.3 times•month⁻¹. The mean distance moved by freeze branded specimens between capture and recapture was significantly larger in areas closed to fishing than in those open to fishing. However, mean distance moved per day determined by ultrasonic telemetry did not differ between areas closed and open to fishing. This study suggests low flux rates of adult P. leopardus across marine reserve boundaries.
Going beyond F0: The acquisition of Mandarin tones

Abstract Using a semi-spontaneous speech corpus, we present evidence from computational modelling of tonal productions from Mandarin-speaking children (4- to 11-years old) and adults, showing that children exceed the adult-level tonal distinction at the age of 7 to 8 years using F0 cues, but do not reach the high adult-level distinction using spectral cues even at the age of 10 to 11 years. The difference in the developmental curves of F0 and spectral cues suggests that, in Mandarin tone production, secondary cues continue to develop even after the mastery of primary cues.
The social regulation of emotion: Inconsistencies suggest no mediation through ventromedial prefrontal cortex

ABSTRACT Physical touch in the form of holding a loved one’s hand attenuates the neural response to threat. Speculation regarding the neural mediation of this effect points to the ventromedial prefrontal cortex (vmPFC), which is known to have inhibitory connections with threat responsive brain regions such as the amygdala. Despite the attractiveness of this hypothesis, a link between the vmPFC and diminished threat during handholding has been difficult to demonstrate empirically. Here we report that in a sample of 110 participants no evidence for vmPFC mediation of the handholding effect was obtained. Indeed, results indicated that connectivity patterns between threat responsive salience network structures and the vmPFC were in the opposite direction one would predict if the vmPFC mediated reductions in neural threat-responding caused by partner handholding. Our findings suggest that the vmPFC does not mediate the regulating effect of physical contact on neural threat responses.
New developments in von Willebrand disease

Von Willebrand disease (VWD) constitutes the most common inherited human bleeding disorder. It is associated with a mucocutaneous bleeding phenotype that can significantly impact upon quality of life. Despite its prevalence and associated morbidity, the diagnosis and subclassification of VWD continue to pose significant clinical challenges. This is in part attributable to the fact that plasma von Willebrand factor (VWF) levels vary over a wide range in the normal population, together with the multiple different physiological functions played by VWF in vivo. Over recent years, substantial progress has been achieved in elucidating the biological roles of VWF. Significant advances have also been made into defining the pathophysiological mechanisms underpinning both quantitative and qualitative VWD. In particular, several new laboratory assays have been developed that enable more precise assessment of specific aspects of VWF activity. In the present review, we discuss these recent developments in the field of VWD diagnosis, and consider how these advances can impact upon clinical diagnostic algorithms for use in routine clinical practice. In addition, we review some important recent advances pertaining to the various treatment options available for managing patients with VWD.