Miracle-dz/UniFAR-FTUs huggingface dataset:
Alterations in Brain Network Topology and Structural-Functional Connectome Coupling Relate to Cognitive Impairment

According to the network-based neurodegeneration hypothesis, neurodegenerative diseases target specific large-scale neural networks, such as the default mode network, and may propagate along the structural and functional connections within and between these brain networks. Cognitive impairment no dementia (CIND) represents an early prodromal stage but few studies have examined brain topological changes within and between brain structural and functional networks. To this end, we studied the structural networks [diffusion magnetic resonance imaging (MRI)] and functional networks (task-free functional MRI) in CIND (61 mild, 56 moderate) and healthy older adults (97 controls). Structurally, compared with controls, moderate CIND had lower global efficiency, and lower nodal centrality and nodal efficiency in the thalamus, somatomotor network, and higher-order cognitive networks. Mild CIND only had higher nodal degree centrality in dorsal parietal regions. Functional differences were more subtle, with both CIND groups showing lower nodal centrality and efficiency in temporal and somatomotor regions. Importantly, CIND generally had higher structural-functional connectome correlation than controls. The higher structural-functional topological similarity was undesirable as higher correlation was associated with poorer verbal memory, executive function, and visuoconstruction. Our findings highlighted the distinct and progressive changes in brain structural-functional networks at the prodromal stage of neurodegenerative diseases.
Adaptation over time of intestinal fermentation in the growing pig is influenced by the amount of kiwifruit consumed.

The effect of kiwi fruit at two dietary levels on the adaptation of intestinal fermentation over time in the growing pig was studied. A semi-synthetic fibre-free diet and two semi-synthetic diets containing kiwi fruit as a model fibre source (133 or 266 g/kg (DM basis); 28 or 48 g fibre/kg) were formulated and the diets contained titanium dioxide as an indigestible marker. A total of fourteen ileal cannulated pigs (41 kg body weight) were fed the fibre-free diet for 7 d followed by either the low or high kiwi fruit-containing diets (n 7/diet) for a further 44 d. Ileal digesta and faeces were collected at five times throughout the study. Ileal digesta were fermented (in vitro) with a standard pooled human faecal inoculum, while fresh pig faeces were used as inocula to ferment in vitro a standard purified fibre. Observations were normalised for diet DM intake using the marker. The 16S ribosomal RNA gene copy number of ileal and total faecal bacteria were high for the high-kiwi fruit level diet (P<0·05). The ileal bacteria tended to decrease over time (P<0·1), while the faecal bacteria increased (P<0·05), at the same rate for both diets. The amounts of crude protein and insoluble dietary fibre entering the hindgut changed over time similarly for both diets, whereas for starch it changed only for the low kiwi fruit-containing diet (P<0·05). Changes over time were also observed for the predicted hindgut valeric acid production and butyric acid absorption (P<0·05). In conclusion, adaptational changes over time of some characteristics of intestinal fermentation depended on the dietary level of kiwi fruit.
Sensitivity analyses for effect modifiers not observed in the target population when generalizing treatment effects from a randomized controlled trial: Assumptions, models, effect scales, data scenarios, and implementation details

Background Randomized controlled trials are often used to inform policy and practice for broad populations. The average treatment effect (ATE) for a target population, however, may be different from the ATE observed in a trial if there are effect modifiers whose distribution in the target population is different that from that in the trial. Methods exist to use trial data to estimate the target population ATE, provided the distributions of treatment effect modifiers are observed in both the trial and target population—an assumption that may not hold in practice. Methods The proposed sensitivity analyses address the situation where a treatment effect modifier is observed in the trial but not the target population. These methods are based on an outcome model or the combination of such a model and weighting adjustment for observed differences between the trial sample and target population. They accommodate several types of outcome models: linear models (including single time outcome and pre- and post-treatment outcomes) for additive effects, and models with log or logit link for multiplicative effects. We clarify the methods’ assumptions and provide detailed implementation instructions. Illustration We illustrate the methods using an example generalizing the effects of an HIV treatment regimen from a randomized trial to a relevant target population. Conclusion These methods allow researchers and decision-makers to have more appropriate confidence when drawing conclusions about target population effects.
Haemophagocytic lymphohistiocytosis associated with leishmaniasis reactivation: a potential adverse event to anti-tumour necrosis factor-α therapy

Department of Haematology, Herlev and Gentofte University Hospital, Herlev, Denmark Department of Nephrology, Herlev and Gentofte University Hospital, Herlev, Denmark Department of Anesthesiology, Herlev and Gentofte University Hospital, Herlev, Denmark Department of Pathology, Herlev and Gentofte University Hospital, Herlev, Denmark Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Copenhagen, Denmark Department of Rheumatology, Institute for Inflammation Research, Copenhagen, Denmark
Lack of a Dose Response from 7 Days of Ischemic Preconditioning in Moderately trained Cyclists

Abstract Ischemic preconditioning (IP) has a small benefit on exercise performance, but differences in the IP method, performance tasks and exercise modality have made providing practical coach guidelines difficult. We investigated the performance-enhancing effects of IP on cyclists by comparing the frequency of IP application over a 7-day period. Using a randomized, sham-controlled, single-blinded experiment, 24 competitive age-group track cyclists (38±12 years) were assigned to one of three twice-daily (sham: 20 and 20 mmHg; once-a-day: 20 and 220 mmHg; twice-a-day: 220 and 220 mmHg) IP leg protocols (4 × 5 min ischemia/5 min reperfusion alternating between legs) over seven consecutive days. A 4000-m cycling-ergometer time trial was completed before, immediately following and one week after the protocols. Neither mean power, nor 4000-m performance time nor VO2 were significantly affected by either of the IP protocols compared to the sham at any time point following treatment. Repeated application of IP over seven days did not enhance the performance of trained cyclists in a 4000-m laboratory time trial. More research is required to understand how changes to methodological variables can improve the chances of IP successfully enhancing athlete performance.
The role of fork stalling and DNA structures in causing chromosome fragility

Alternative non‐B form DNA structures, also called secondary structures, can form in certain DNA sequences under conditions that produce single‐stranded DNA, such as during replication, transcription, and repair. Direct links between secondary structure formation, replication fork stalling, and genomic instability have been found for many repeated DNA sequences that cause disease when they expand. Common fragile sites (CFSs) are known to be AT‐rich and break under replication stress, yet the molecular basis for their fragility is still being investigated. Over the past several years, new evidence has linked both the formation of secondary structures and transcription to fork stalling and fragility of CFSs. How these two events may synergize to cause fragility and the role of nuclease cleavage at secondary structures in rare and CFSs are discussed here. We also highlight evidence for a new hypothesis that secondary structures at CFSs not only initiate fragility but also inhibit healing, resulting in their characteristic appearance.
Identification, Molecular Cloning, and Functional Characterization of a Wheat UDP-Glucosyltransferase Involved in Resistance to Fusarium Head Blight and to Mycotoxin Accumulation

Plant uridine diphosphate (UDP)-glucosyltransferases (UGT) catalyze the glucosylation of xenobiotic, endogenous substrates and phytotoxic agents produced by pathogens such as mycotoxins. The Bradi5g03300 UGT-encoding gene from the model plant Brachypodium distachyon was previously shown to confer tolerance to the mycotoxin deoxynivalenol (DON) through glucosylation into DON 3-O-glucose (D3G). This gene was shown to be involved in early establishment of quantitative resistance to Fusarium Head Blight, a major disease of small-grain cereals. In the present work, using a translational biology approach, we identified and characterized a wheat candidate gene, Traes_2BS_14CA35D5D, orthologous to Bradi5g03300 on the short arm of chromosome 2B of bread wheat (Triticum aestivum L.). We showed that this UGT-encoding gene was highly inducible upon infection by a DON-producing Fusarium graminearum strain while not induced upon infection by a strain unable to produce DON. Transformation of this wheat UGT-encoding gene into B. distachyon revealed its ability to confer FHB resistance and root tolerance to DON as well as to potentially conjugate DON into D3G in planta and its impact on total DON reduction. In conclusion, we provide a UGT-encoding candidate gene to include in selection process for FHB resistance.
Negative Effects of Copper Oxide Nanoparticles on Carbon and Nitrogen Cycle Microbial Activities in Contrasting Agricultural Soils and in Presence of Plants

Metal-oxide nanoparticles (NPs) such as copper oxide (CuO) NPs offer promising perspectives for the development of novel agro-chemical formulations of pesticides and fertilizers. However, their potential impact on agro-ecosystem functioning still remains to be investigated. Here, we assessed the impact of CuO-NPs (0.1, 1, and 100 mg/kg dry soil) on soil microbial activities involved in the carbon and nitrogen cycles in five contrasting agricultural soils in a microcosm experiment over 90 days. Additionally, in a pot experiment, we evaluated the influence of plant presence on the toxicity of CuO-NPs on soil microbial activities. CuO-NPs caused significant reductions of the three microbial activities measured (denitrification, nitrification, and soil respiration) at 100 mg/kg dry soil, but the low concentrations (0.1 and 1 mg/kg) had limited effects. We observed that denitrification was the most sensitive microbial activity to CuO-NPs in most soil types, while soil respiration and nitrification were mainly impacted in coarse soils with low organic matter content. Additionally, large decreases in heterotrophic microbial activities were observed in soils planted with wheat, even at 1 mg/kg for soil substrate-induced respiration, indicating that plant presence did not mitigate or compensate CuO-NP toxicity for microorganisms. These two experiments show that CuO-NPs can have detrimental effects on microbial activities in soils with contrasting physicochemical properties and previously exposed to various agricultural practices. Moreover, we observed that the negative effects of CuO-NPs increased over time, indicating that short-term studies (hours, days) may underestimate the risks posed by these contaminants in soils.
Decrease in membrane phospholipids unsaturation correlates with myocardial diastolic dysfunction

Increase in saturated fatty acid (SFA) content in membrane phospholipids dramatically affects membrane properties and cellular functioning. We sought to determine whether exogenous SFA from the diet directly affects the degree of membrane phospholipid unsaturation in adult hearts and if these changes correlate with contractile dysfunction. Although both SFA-rich high fat diets (HFDs) and monounsaturated FA (MUFA)-rich HFDs cause the same degree of activation of myocardial FA uptake, triglyceride turnover, and mitochondrial FA oxidation and accumulation of toxic lipid intermediates, the former induced more severe diastolic dysfunction than the latter, which was accompanied with a decrease in membrane phospholipid unsaturation, induction of unfolded protein response (UPR), and a decrease in the expression of Sirt1 and stearoyl-CoA desaturase-1 (SCD1), catalyzing the conversion of SFA to MUFA. When the SFA supply in the heart overwhelms the cellular capacity to use it for energy, excess exogenous SFA channels to membrane phospholipids, leading to UPR induction, and development of diastolic dysfunction.
Diversity and Phylogenetic Analyses Reveal Horizontal Transmission of Endosymbionts Between Whiteflies and Their Parasitoids

Abstract Endosymbionts are widely distributed among insects via intraspecific vertical transmission and interspecific horizontal transmission. Parasitoids have attracted considerable interest due to their possible role in the horizontal transmission of endosymbionts. Horizontal transmission of endosymbionts between whiteflies via parasitoids has been revealed in the laboratory. However, whether this occurs under field conditions remains unknown. Here, the diversity and phylogenetic relationships of endosymbionts in 1,350 whiteflies and 36 parasitoids that emerged from whitefly nymphs collected from three locations in Jiangsu Province of China were investigated. Only Rickettsia and Wolbachia were identified in both whiteflies and parasitoids, with an overall infection frequency of 22.67% in whiteflies and 16.67% in parasitoids for Wolbachia and of 12.15% in whiteflies and 25% in parasitoids for Rickettsia. Despite the distant relationship between whiteflies and their parasitoids, phylogenetic analyses revealed that the Rickettsia and Wolbachia individuals collected from the two types of organisms were grouped together. Furthermore, shared haplotypes were also identified, which was consistent with the horizontal transmission of endosymbionts between parasitoids and whiteflies. In addition, a parasitoid resistance-related symbiont, Hamiltonella, was detected in whiteflies at a 100% infection frequency, probably accounting for the relatively low parasitism of the whiteflies in the field. The factors affecting the infection frequency of the four secondary endosymbionts in whiteflies were also examined.
Shared and Unique Variances of Interpersonal Callousness and Low Prosocial Behavior

Although low prosocial behavior (LPB) items have been incorporated into youth measures of callousness, it remains unclear from current factor analytic findings whether callous traits and LPB are best operationalized as a common construct, or distinct dimensions. Using data from a population-representative birth cohort (N = 5,463), this study compared 4 latent factor structures for interpersonal callousness (IC; 6 items) and LPB (5 items) at age 13: (a) unidimensional; (b) two-factor; (c) higher-order (with 2 subfactors); and (d) bifactor (1 general and 2 specific residual factors). Alternative models distinguishing positively and negatively worded items were tested for comparative purposes. To assess the external validity of the factors that emerged from the best-fitting model, associations with early parenting styles and psychiatric comorbidities were examined. A bifactor model, achieving invariance for males and females, offered the best fit for these data. However, additional bifactor-specific indices suggested that the specific IC factor did not offer a unique contribution to the total variance over and above the general factor (IC/LPB). Of the remaining factors, IC/LPB was associated with higher levels of harsh parenting, externalizing and internalizing disorder, and social–cognitive difficulties, and lower levels of warm parenting. The LPB factor, meanwhile, was associated with greater social–cognitive difficulties and externalizing disorder, and lower maternal warmth, evoking a phenotype that may be more indicative of the autism spectrum than IC. These findings suggest that the shared variance underlying IC and LPB taps a severe psychiatric phenotype, while the residual variance for LPB may represent a distinct profile of social–cognitive dysfunction.
Factorial design based curcumin ethosomal nanocarriers for the skin cancer delivery: in vitro evaluation

Abstract Melanoma is the most deadly and life-threatening form of skin cancer with progressively higher rates of incidence worldwide. The objective of the present investigation is to develop and to statistically optimize and characterize curcumin (CUR) loaded ethosomes for treatment of melanoma. A two factor, three level (32) factorial design approach was employed for the optimization of ethosomes. The prepared ethosomes were evaluated for size, zeta potential, entrapment efficiency, in vitro skin permeation and deposition ability. The optimized ethosomal formulation was evaluated for in vitro cytotoxicity and cellular uptake studies using A375 human melanoma cells. The optimized formulation has imperfect round shaped unilamellar structures with a mean vesicle size of 247 ± 5.25 nm and an entrapment efficiency of 92.24 ± 0.20%. The in vitro skin permeation studies proved the superiority of ethosomes over the traditional liposomes in terms of the amount of drug permeated and deposited in skin layers. Fluorescence microscopy showed the enhanced penetration of ethosomes into the deeper layers of the skin. In vitro cytotoxicity and cellular uptake studies revealed that curcumin ethosomes have significantly improved cytotoxicity and cellular uptake in A375 human melanoma cell lines. The colony formation assay results showed that curcumin ethosomes have a superior antiproliferative effect as they effectively inhibit the clonogenic ability of A375 cells. The flow cytometry results indicate that curcumin ethosomes induce cell death in A375 cells by apoptosis mechanism. The present study provides a strong rationale and motivation for further investigation of newly developed curcumin ethosomes as a potential therapeutic strategy for melanoma treatment.
Impact of Intervals on the Emotional Effect in Western Music

Every art form ultimately aims to invoke an emotional response over the audience, and music is no different. While the precise perception of music is a highly subjective topic, there is an agreement in the "feeling" of a piece of music in broad terms. Based on this observation, in this study, we aimed to determine the emotional feeling associated with short passages of music; specifically by analyzing the melodic aspects. We have used the dataset put together by Eerola et. al. which is comprised of labeled short passages of film music. Our initial survey of the dataset indicated that other than "happy" and "sad" labels do not possess a melodic structure. We transcribed the main melody of the happy and sad tracks and used the intervals between the notes to classify them. Our experiments have shown that treating a melody as a bag-of-intervals do not possess any predictive power whatsoever, whereas counting intervals with respect to the key of the melody yielded a classifier with 85% accuracy.
Neighbourhood Watch: Referring Expression Comprehension via Language-Guided Graph Attention Networks

The task in referring expression comprehension is to localize the object instance in an image described by a referring expression phrased in natural language. As a language-to-vision matching task, the key to this problem is to learn a discriminative object feature that can adapt to the expression used. To avoid ambiguity, the expression normally tends to describe not only the properties of the referent itself, but also its relationships to its neighbourhood. To capture and exploit this important information we propose a graph-based, language-guided attention mechanism. Being composed of node attention component and edge attention component, the proposed graph attention mechanism explicitly represents inter-object relationships, and properties with a flexibility and power impossible with competing approaches. Furthermore, the proposed graph attention mechanism enables the comprehension decision to be visualizable and explainable. Experiments on three referring expression comprehension datasets show the advantage of the proposed approach.
An experimental investigation into the surface and hydrodynamic characteristics of marine coatings with mimicked hull roughness ranges

Abstract There are limited scientific data on contributors to the added drag of in-service ships, represented by modern-day coating roughness and biofouling, either separately or combined. This study aimed to gain an insight into roughness and hydrodynamic performance of typical coatings under in-service conditions of roughened ships’ hull surfaces. Comprehensive and systematic experimental data on the boundary layer and drag characteristics of antifouling coating systems with different finishes are presented. The coating types investigated were linear-polishing polymers, foul-release and controlled-depletion polymers. The data were collected through state-of-the-art equipment, including a 2-D laser Doppler velocimetry (LDV) system for hydrodynamic data in a large circulating water tunnel. Three coating systems were first applied on flat test panels with ‘normal’ finishes in the first test campaign to represent coating applications under idealised laboratory conditions. In order to address more realistic roughness conditions, as typically observed on ships’ hulls, ‘low’ and ‘high’ roughness densities were introduced into the same types of coating, in the second test campaign. The data collected from the first test campaign served as the baseline to demonstrate the effect on the surface roughness and hydrodynamic drag characteristics of these coating types as a result of ‘in-service’ or ‘severely flawed’ coating application scenarios. Data collected on coatings with a range of in-service surface conditions provided a basis to establish correlation between the surface roughness characteristics and hydrodynamic performance (roughness function). The findings of the study indicate that the estimations of drag penalties based on well-applied, relatively smooth coating conditions underestimate the importance of hull roughness, which although undesirable, is commonplace in the world’s commercial fleet.