Miracle-dz/UniFAR-FTUs huggingface dataset:
Seeing a Page in a Flipbook: Shorter Visual Temporal Integration Windows in 2‐Year‐Old Toddlers with Autism Spectrum Disorder

Individuals with autism spectrum disorder (ASD) experience differences in visual temporal processing, the part of vision responsible for parsing continuous input into discrete objects and events. Here we investigated temporal processing in 2‐year‐old toddlers diagnosed with ASD and age‐matched typically developing (TD) toddlers. We used a visual search task where the visibility of the target was determined by the pace of a display sequence. On integration trials, each display viewed alone had no visible target, but if integrated over time, the target became visible. On segmentation trials, the target became visible only when displays were perceptually segmented. We measured the percent of trials when participants fixated the target as a function of the stimulus onset asynchrony (SOA) between displays. We computed the crossover point of the integration and segmentation performance functions for each group, an estimate of the temporal integration window (TIW), the period in which visual input is combined. We found that both groups of toddlers had significantly longer TIWs (125 ms) than adults (65 ms) from previous studies using the same paradigm, and that toddlers with ASD had significantly shorter TIWs (108 ms) than chronologically age‐matched TD controls (142 ms).
Evidence of nickel and other trace elements and their relationship to clinical findings in acute Mesoamerican Nephropathy: A case-control analysis

Background Although there are several hypothesized etiologies of Mesoamerican Nephropathy (MeN), evidence has not yet pointed to the underlying cause. Exposure to various trace elements can cause the clinical features observed in MeN. Methods and findings We measured 15 trace elements, including heavy metals, in renal case-patients (n = 18) and healthy controls (n = 36) in a MeN high-risk region of Nicaragua. Toenails clippings from study participants were analyzed using inductively coupled plasma mass spectrometry. A case-control analysis was performed, and concentrations were also analyzed over participant characteristics and clinical parameters. Nickel (Ni) concentrations were significantly higher in toenails from cases (1.554 mg/kg [0.176–42.647]) than controls (0.208 mg/kg [0.055–51.235]; p<0.001). Ni concentrations correlated positively with serum creatinine levels (p = 0.001) and negatively with eGFR (p = 0.001). Greater Ni exposure was also associated with higher leukocyte (p = 0.001) and neutrophil (p = 0.003) counts, fewer lymphocytes (p = 0.003), and lower hemoglobin (p = 0.004) and hematocrit (p = 0.011). Conclusions Low-dose, chronic environmental exposure to Ni is a possible health risk in this setting. Ni intoxication and resulting systemic and renal effects could explain the clinical signs observed during early MeN. This study provides compelling evidence for a role of Ni in the acute renal impairment observed in this MeN high-risk population. Additional work to assess exposure levels in a larger and heterogeneous population, identify environmental sources of Ni and exposure pathways, and evaluate the link between Ni and MeN pathogenesis are urgently needed.
Mesenchymal stromal cells for acute respiratory distress syndrome (ARDS), sepsis, and COVID-19 infection: optimizing the therapeutic potential

ABSTRACT Introduction: Mesenchymal stromal (stem) cell (MSC) therapies are emerging as a promising therapeutic intervention in patients with Acute Respiratory Distress Syndrome (ARDS) and sepsis due to their reparative, immunomodulatory, and antimicrobial properties. Areas covered: This review provides an overview of Mesenchymal stromal cells (MSCs) and their mechanisms of effect in ARDS and sepsis. The preclinical and clinical evidence to support MSC therapy in ARDS and sepsis is discussed. The potential for MSC therapy in COVID-19 ARDS is discussed with insights from respiratory viral models and early clinical reports of MSC therapy in COVID-19. Strategies to optimize the therapeutic potential of MSCs in ARDS and sepsis are considered including preconditioning, altered gene expression, and alternative cell-free MSC-derived products, such as extracellular vesicles and conditioned medium. Expert opinion: MSC products present considerable therapeutic promise for ARDS and sepsis. Preclinical investigations report significant benefits and early phase clinical studies have not highlighted safety concerns. Optimization of MSC function in preclinical models of ARDS and sepsis has enhanced their beneficial effects. MSC-derived products, as cell-free alternatives, may provide further advantages in this field. These strategies present opportunity for the clinical development of MSCs and MSC-derived products with enhanced therapeutic efficacy.
Is Routine Prophylaxis Against Pneumocystis jirovecii Needed in Liver Transplantation? A Retrospective Single-Centre Experience and Current Prophylaxis Strategies in Spain

In liver transplant (LT) recipients, Pneumocystis jirovecii pneumonia (PJP) is most frequently reported before 1992 when immunosuppressive regimens were more intense. It is uncertain whether universal PJP prophylaxis is still applicable in the contemporary LT setting. We aimed to examine the incidence of PJP in LT recipients followed at our institution where routine prophylaxis has never been practiced and to define the prophylaxis strategies currently employed among LT units in Spain. All LT performed from 1990 to October 2019 were retrospectively reviewed and Spanish LT units were queried via email to specify their current prophylaxis strategy. During the study period, 662 LT procedures were carried out on 610 patients. Five cases of PJP were identified, with only one occurring within the first 6 months. The cumulative incidence and incidence rate were 0.82% and 0.99 cases per 1000 person transplant years. All LT units responded, the majority of which provide prophylaxis (80%). Duration of prophylaxis, however, varied significantly. The low incidence of PJP in our unprophylaxed cohort, with most cases occurring beyond the usual recommended period of prophylaxis, questions a one-size-fits-all approach to PJP prophylaxis. A significant heterogeneity in prophylaxis strategies exists among Spanish LT centres.
Conditioned pain modulation affects the N2/P2 complex but not the N1 wave: A pilot study with laser‐evoked potentials

The ‘pain‐inhibits‐pain’ effect stems from neurophysiological mechanisms involving endogenous modulatory systems termed diffuse noxious inhibitory controls (DNIC) or conditioned pain modulation (CPM). Laser‐evoked potentials (LEPs) components, the N2/P2 complex, and the N1 wave, reflect the medial and lateral pain pathway, respectively: anatomically, the lateral thalamic nuclei (LT) project mainly to the somatosensory cortex (N1 generator), while the medial thalamic nuclei (MT) are bound to the limbic cortices (N2/P2 generators).
A comparison of two remotely operated vehicle (ROV) survey methods used to estimate fish assemblages and densities around a California oil platform

Offshore oil and gas platforms have a finite life of production operations. Once production ceases, decommissioning options for the platform are assessed. The role that a platform’s jacket plays as fish habitat can inform the decommissioning decision. In this study, conducted along the crossbeams of a California platform jacket and using an ROV, we compared estimates of fish diversity and densities determined from a targeted “biological” survey with those from a replicated “structural” survey. We found that the water column fish species assemblages characterized by the two methods were similar. By contrast, the two survey methods yielded different species assemblages inhabiting the crossbeam at the platform jacket base. This difference occurred because, at least off California, the platform jacket base species diversity tends to be highest where the bottom crossbeam is undercut, creating sheltering sites for many species. Because the structural method inadequately imaged the seafloor-crossbeam interface, particularly where a gap occurred between crossbeam and seafloor, substantial numbers of fishes were not visible. While we cannot extrapolate from this study to all platforms’ worldwide, it is clear that routine platform structural integrity surveys may be a valuable source for opportunistic marine community surveys. Intentional planning of the structural survey to incorporate relatively minor variations (e.g., maintaining fixed ROV distance from the infrastructure and consistent 90° camera angle) coupled with a deliberate consideration of the platform ecology (e.g., positioning the ROV to capture the seafloor-crossbeam interface) can substantially improve the effects on fish assemblage assessments from routine structural surveys without compromising the integrity assessment. We suggest that these biases should be both acknowledged and, understood when using routine structural surveys to inform platform ecology assessment. Additional consideration may be given to structural surveys that incorporate incremental adjustments to provide better data applicability to biological assessments.
Ensemble-Based Analysis of the Dynamic Allostery in the PSD-95 PDZ3 Domain in Relation to the General Variability of PDZ Structures

PDZ domains are abundant interaction hubs found in a number of different proteins and they exhibit characteristic differences in their structure and ligand specificity. Their internal dynamics have been proposed to contribute to their biological activity via changes in conformational entropy upon ligand binding and allosteric modulation. Here we investigate dynamic structural ensembles of PDZ3 of the postsynaptic protein PSD-95, calculated based on previously published backbone and side-chain S2 order parameters. We show that there are distinct but interdependent structural rearrangements in PDZ3 upon ligand binding and the presence of the intramolecular allosteric modulator helix α3. We have also compared these rearrangements in PDZ1-2 of PSD-95 and the conformational diversity of an extended set of PDZ domains available in the PDB database. We conclude that although the opening-closing rearrangement, occurring upon ligand binding, is likely a general feature for all PDZ domains, the conformer redistribution upon ligand binding along this mode is domain-dependent. Our findings suggest that the structural and functional diversity of PDZ domains is accompanied by a diversity of internal motional modes and their interdependence.
Analysis of Vancomycin-Resistant Enterococci in Hemato-Oncological Patients

Enterococci are important bacterial pathogens, and their significance is even greater in the case of vancomycin-resistant enterococci (VRE). The study analyzed the presence of VRE in the gastrointestinal tract (GIT) of hemato-oncological patients. Active screening using selective agars yielded VRE for phenotypic and genotypic analyses. Isolated strains were identified with MALDI-TOF MS, (Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry) their susceptibility to antibiotics was tested, and resistance genes (vanA, vanB, vanC-1, vanC2-C3) and genes encoding virulence factors (asa1, gelE, cylA, esp, hyl) were detected. Pulsed-field gel electrophoresis was used to assess the relationship of the isolated strains. Over a period of three years, 103 VanA-type VRE were identified in 1405 hemato-oncological patients. The most frequently detected virulence factor was extracellular surface protein (84%), followed by hyaluronidase (40%). Unique restriction profiles were observed in 33% of strains; clonality was detected in 67% of isolates. The study found that 7% of hemato-oncological patients carried VRE in their GIT. In all cases, the species identified was Enterococcus faecium. No clone persisted for the entire 3-year study period. However, genetically different clusters were observed for shorter periods of time, no longer than eight months, with identical VRE spreading among patients.
Tetrapodal Anion Transporters

Synthetic anion transporters that facilitate chloride transport are promising candidates for channelopathy treatments. However, most anion transporters exhibit an undesired side effect of facilitating proton transport via interacting with fatty acids present in the membrane. To address the limitation, we here report the use of a new tetrapodal scaffold to maximize the selective interaction with spherical chloride over binding the carboxylate headgroup of fatty acids. One of the new transporters demonstrated a high selectivity for chloride uniport over fatty acid-induced proton transport while being >10 times more active in chloride uniport than strapped calixpyrroles that were previously the only class of compounds known to possess similar selectivity properties.
Shifting seas, shifting boundaries: Dynamic marine protected area designs for a changing climate

Marine protected areas (MPAs) are valuable tools for marine conservation that aim to limit human impacts on marine systems and protect valuable species or habitats. However, as species distributions shift due to ocean warming, acidification, and oxygen depletion from climate change, the areas originally designated under MPAs may bear little resemblance to their past state. Different approaches have been suggested for coping with species on the move in conservation. Here, we test the effectiveness of different MPA designs, including dynamic, network, and different directional orientations on protecting shifting species under climate change through ecosystem modeling in a theoretical ecosystem. Our findings suggest that dynamic MPAs may benefit some species (e.g., whiting and anchovy) and fishing fleets, and these benefits can inform the design or adaptation of MPAs worldwide. In addition, we find that it is important to design MPAs with specific goals and to account for the effects of released fishing pressure and species interactions in MPA design.
Genome-wide assessment of diversity and differentiation between original and modern Brown cattle populations.

Identifying genomic regions involved in the differences between breeds can provide information on genes that are under the influence of both artificial and natural selection. The aim of this study was to assess the genetic diversity and differentiation among four different Brown cattle populations (two original vs. two modern populations) and to characterize the distribution of runs of homozygosity (ROH) islands using the Illumina Bovine SNP50 BeadChip genotyping data. After quality control, 34 735 SNPs and 106 animals were retained for the analyses. Larger heterogeneity was highlighted for the original populations. Patterns of genetic differentiation, multidimensional scaling, and the neighboring joining tree distinguished the modern from the original populations. The FST -outlier identified several genes putatively involved in the genetic differentiation between the two groups, such as stature and growth, behavior, and adaptability to local environments. The ROH islands within both the original and the modern populations overlapped with QTL associated with relevant traits. In modern Brown (Brown Swiss and Italian Brown), ROH islands harbored candidate genes associated with milk production traits, in evident agreement with the artificial selection conducted to improve this trait in these populations. In original Brown (Original Braunvieh and Braunvieh), we identified candidate genes related with fat deposition, confirming that breeding strategies for the original Brown populations aimed to produce dual-purpose animals. Our study highlighted the presence of several genomic regions that vary between Brown populations, in line with their different breeding histories.
Image Segmentation of the Ventricular Septum in Fetal Cardiac Ultrasound Videos Based on Deep Learning Using Time-Series Information

Image segmentation is the pixel-by-pixel detection of objects, which is the most challenging but informative in the fundamental tasks of machine learning including image classification and object detection. Pixel-by-pixel segmentation is required to apply machine learning to support fetal cardiac ultrasound screening; we have to detect cardiac substructures precisely which are small and change shapes dynamically with fetal heartbeats, such as the ventricular septum. This task is difficult for general segmentation methods such as DeepLab v3+, and U-net. Hence, here we proposed a novel segmentation method named Cropping-Segmentation-Calibration (CSC) that is specific to the ventricular septum in ultrasound videos in this study. CSC employs the time-series information of videos and specific section information to calibrate the output of U-net. The actual sections of the ventricular septum were annotated in 615 frames from 421 normal fetal cardiac ultrasound videos of 211 pregnant women who were screened. The dataset was assigned a ratio of 2:1, which corresponded to a ratio of the training to test data, and three-fold cross-validation was conducted. The segmentation results of DeepLab v3+, U-net, and CSC were evaluated using the values of the mean intersection over union (mIoU), which were 0.0224, 0.1519, and 0.5543, respectively. The results reveal the superior performance of CSC.
In well-differentiated primary human bronchial epithelial cells, TGF-β1 and TGF-β2 induce expression of furin

The COVID-19 pandemic is an ongoing threat to public health. Since the identification of COVID-19, the disease caused by SARS-CoV-2, no drugs have been developed to specifically target SARS-CoV-2. To develop effective and safe treatment options, a better understanding of cellular mechanisms underlying SARS-CoV-2 infection is required. To fill this knowledge gap, researchers require reliable experimental systems that express the host factor proteins necessary for the cellular entry of SARS-CoV-2. These proteins include the viral receptor, angiotensin-converting enzyme 2 (ACE2), and the proteases, transmembrane serine protease 2 (TMPRSS2) and furin. A number of studies have reported cell-type-specific expression of the genes encoding these molecules. However, less is known about the protein expression of these molecules. We assessed the suitability of primary human bronchial epithelial (HBE) cells maintained in an air-liquid interface (ALI) as an experimental system for studying SARS-CoV-2 infection in vitro. During cellular differentiation, we measured the expression of ACE2, TMPRSS2, and furin over progressive ALI days by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence staining. We also explored the effect of the fibrotic cytokine TGF-β on the expression of these proteins in well-differentiated HBE cells. Like ACE2, TMPRSS2 and furin proteins are localized in differentiated ciliated cells, as confirmed by immunofluorescence staining. These data suggest that well-differentiated HBE cells maintained in ALI are a reliable in vitro system for investigating cellular mechanisms of SARS-CoV-2 infection. We further identified that the profibrotic mediators, TGF-β1 and TGF-β2, increase the expression of furin, which is a protease required for the cellular entry of SARS-CoV-2.
Age‐related electrophysiological changes in mouse taste receptor cells

What is the central question of this study? Loss of taste or inability to distinguish between different tastes progresses with age. The purpose was to evaluate the age‐dependent changes in taste by studying the electrophysiological properties of taste receptor cells. What is the main finding and its importance? Ageing decreased the voltage‐gated Na+ and K+ current densities of type III cells (sour and/or salt receptor cells) but did not affect the current densities in type II cells. At the peripheral levels, the excitability of type III cells was reduced due to ageing, which may affect the signal transduction to taste nerves.
Transcriptional Effects of Psychoactive Drugs on Genes Involved in Neurogenesis

Although neurogenesis is affected in several psychiatric diseases, the effects and mechanisms of action of psychoactive drugs on neurogenesis remain unknown and/or controversial. This study aims to evaluate the effects of psychoactive drugs on the expression of genes involved in neurogenesis. Neuronal-like cells (NT2-N) were treated with amisulpride (10 µM), aripiprazole (0.1 µM), clozapine (10 µM), lamotrigine (50 µM), lithium (2.5 mM), quetiapine (50 µM), risperidone (0.1 µM), or valproate (0.5 mM) for 24 h. Genome wide mRNA expression was quantified and analysed using gene set enrichment analysis, with the neurogenesis gene set retrieved from the Gene Ontology database and the Mammalian Adult Neurogenesis Gene Ontology (MANGO) database. Transcription factors that are more likely to regulate these genes were investigated to better understand the biological processes driving neurogenesis. Targeted metabolomics were performed using gas chromatography-mass spectrometry. Six of the eight drugs decreased the expression of genes involved in neurogenesis in both databases. This suggests that acute treatment with these psychoactive drugs negatively regulates the expression of genes involved in neurogenesis in vitro. SOX2 and three of its target genes (CCND1, BMP4, and DKK1) were also decreased after treatment with quetiapine. This can, at least in part, explain the mechanisms by which these drugs decrease neurogenesis at a transcriptional level in vitro. These results were supported by the finding of increased metabolite markers of mature neurons following treatment with most of the drugs tested, suggesting increased proportions of mature relative to immature neurons consistent with reduced neurogenesis.
Dynamic Knee Valgus in Single-Leg Movement Tasks. Potentially Modifiable Factors and Exercise Training Options. A Literature Review

Dynamic knee valgus (DKV) as an incorrect movement pattern is recognized as a risk factor for lower limb injuries. Therefore, it is important to find the reasons behind this movement to select effective preventive procedures. There is a limited number of publications focusing on specific tasks, separating the double-leg from the single-leg tasks. Test patterns commonly used for DKV assessment, such as single-leg squat (SLS) or single leg landings (SLL), may show different results. The current review presents the modifiable factors of knee valgus in squat and landing single-leg tests in healthy people, as well as exercise training options. The authors used the available literature from PubMed, Scopus, PEDro and clinicaltrials.gov databases, and reviewed physiotherapy journals and books. For the purpose of the review, studies were searched for using 2D or 3D motion analysis methods only in the SLL and SLS tasks among healthy active people. Strengthening and activating gluteal muscles, improving trunk lateral flexion strength, increasing ROM dorsiflexion ankle and midfoot mobility should be taken into account when planning training programs aimed at reducing DKV occurring in SLS. In addition, knee valgus during SLL may occur due to decreased hip abductors, extensors, external rotators strength and higher midfoot mobility. Evidence from several studies supports the addition of biofeedback training exercises to reduce the angles of DKV.