Miracle-dz/UniFAR-FTUs huggingface dataset:
Minimal experimental requirements for definition of extracellular vesicles and their functions: a position statement from the International Society for Extracellular Vesicles

Secreted membrane-enclosed vesicles, collectively called extracellular vesicles (EVs), which include exosomes, ectosomes, microvesicles, microparticles, apoptotic bodies and other EV subsets, encompass a very rapidly growing scientific field in biology and medicine. Importantly, it is currently technically challenging to obtain a totally pure EV fraction free from non-vesicular components for functional studies, and therefore there is a need to establish guidelines for analyses of these vesicles and reporting of scientific studies on EV biology. Here, the International Society for Extracellular Vesicles (ISEV) provides researchers with a minimal set of biochemical, biophysical and functional standards that should be used to attribute any specific biological cargo or functions to EVs.
Recent Speciation in Three Closely Related Sympatric Specialists: Inferences Using Multi-Locus Sequence, Post-Mating Isolation and Endosymbiont Data

Shifting between unrelated host plants is relatively rare for phytophagous insects, and distinct host specificity may play crucial roles in reproductive isolation. However, the isolation status and the relationship between parental divergence and post-mating isolation among closely related sympatric specialists are still poorly understood. Here, multi-locus sequence were used to estimate the relationship among three host plant–specific closely related flea beetles, Altica cirsicola, A. fragariae and A. viridicyanea (abbreviated as AC, AF and AV respectively). The tree topologies were inconsistent using different gene or different combinations of gene fragments. The relationship of AF+(AC+AV) was supported, however, by both gene tree and species tree based on concatenated data. Post-mating reproductive data on the results of crossing these three species are best interpreted in the light of a well established phylogeny. Nuclear-induced but not Wolbachia-induced unidirectional cytoplasmic incompatibility, which was detected in AC-AF and AF-AV but not in AC-AV, may also suggest more close genetic affinity between AC and AV. Prevalence of Wolbachia in these three beetles, and the endosymbiont in most individuals of AV and AC sharing a same wsp haplotype may give another evidence of AF+(AC+AV). Our study also suggested that these three flea beetles diverged in a relative short time (0.94 My), which may be the result of shifting between unrelated host plants and distinct host specificity. Incomplete post-mating isolation while almost complete lineage sorting indicated that effective pre-mating isolation among these three species should have evolved.
ARTIST: A fully automated artifact rejection algorithm for single‐pulse TMS‐EEG data

Concurrent single‐pulse TMS‐EEG (spTMS‐EEG) is an emerging noninvasive tool for probing causal brain dynamics in humans. However, in addition to the common artifacts in standard EEG data, spTMS‐EEG data suffer from enormous stimulation‐induced artifacts, posing significant challenges to the extraction of neural information. Typically, neural signals are analyzed after a manual time‐intensive and often subjective process of artifact rejection. Here we describe a fully automated algorithm for spTMS‐EEG artifact rejection. A key step of this algorithm is to decompose the spTMS‐EEG data into statistically independent components (ICs), and then train a pattern classifier to automatically identify artifact components based on knowledge of the spatio‐temporal profile of both neural and artefactual activities. The autocleaned and hand‐cleaned data yield qualitatively similar group evoked potential waveforms. The algorithm achieves a 95% IC classification accuracy referenced to expert artifact rejection performance, and does so across a large number of spTMS‐EEG data sets (n = 90 stimulation sites), retains high accuracy across stimulation sites/subjects/populations/montages, and outperforms current automated algorithms. Moreover, the algorithm was superior to the artifact rejection performance of relatively novice individuals, who would be the likely users of spTMS‐EEG as the technique becomes more broadly disseminated. In summary, our algorithm provides an automated, fast, objective, and accurate method for cleaning spTMS‐EEG data, which can increase the utility of TMS‐EEG in both clinical and basic neuroscience settings.
Novel roles for basement membrane collagens : isoform-specific functions of collagen XVIII in adipogenesis, fat deposition and eye development, and effects of the collagen IV-derived matricryptin arresten on oral carcinoma growth and invasion

Collagen XVIII is an evolutionarily conserved, ubiquitously-expressed basement membrane (BM) proteoglycan produced in three isoforms, the individual roles of which are largely unknown. The physiological in vivo roles of these collagen XVIII isoforms are studied here using novel genetically modified mouse strains deficient in either the short or the medium/long isoforms of the molecule. In addition, the effects of keratin-14-driven overexpression of the thrombospondin-1 (Tsp-1) –like domain, which is common to all three collagen XVIII isoforms, are studied. The findings underline the importance of the short collagen XVIII isoform in the eye, as its absence was sufficient to cause the aberrant vascularisation of the retina previously reported in mice lacking all isoforms of collagen XVIII. In addition, an excess of the collagen XVIII Tsp-1 domain led to serious eye abnormalities, possibly by interfering with the functions of the fulllength collagen XVIII produced in mice. Collagen XVIII was also shown to contribute to adipogenesis in an isoform-specific manner, in that a lack of the medium/long isoforms of collagen XVIII led to impaired adipocyte maturation and the subsequent reduction in the adipocyte number induced liver steatosis and hypertriglyceridaemia. Hence this work establishes a new extracellular matrix (ECM)-directed mechanism contributing to control over the multistep adipogenesis programme and points to the functional consequences of its impairment for ectopic fat deposition. The enzymatic remodelling of ECM components results in molecules with novel biological activities. Arresten is a collagen IV(α1)-derived fragment with anti-angiogenic properties which was originally described as not having any direct anti-tumour effects on cancer cells themselves. The present data revealed novel inhibitory roles for arresten in oral squamous carcinoma cell proliferation, survival, motility and invasion. Since arresten is a potent inhibitor of angiogenesis, the data generated here further underline the possibility for using it as a therapeutic agent in cases of cancer.
Sedentary and Physical Activity Patterns in Adults with Intellectual Disability

Little is known about the patterns of sedentary time (ST) and physical activity (PA) levels throughout the week among adults and older adults with Intellectual Disability (ID). We analyzed ST and PA patterns of adults and older adults with ID. Forty-two adults and 42 older adults with mild to severe ID participated in this study. Height and weight were obtained to calculate Body Mass Index (BMI). Body fat and fat-free mass percentages were also obtained. Patterns of PA levels and ST were assessed with GT3X Actigraph accelerometers. Adults performed higher amounts of total PA and moderate to vigorous PA than older adults during the week, on weekdays and in center time (all p > 0.05). No differences between males and females were found for either PA levels or ST. Only 10.7% of the participants met the global recommendations on PA for health. The participants of the current study showed low PA levels and a high prevalence of ST. Interestingly, when comparing age and/or sex groups, no differences were observed for ST. Our findings provide novel and valuable information to be considered in future interventions aiming to increase PA levels and reduce ST.
Age-Related Impairment on a Forced-Choice Version of the Mnemonic Similarity Task

Previous studies from our lab have indicated that healthy older adults are impaired in their ability to mnemonically discriminate between previously viewed objects and similar lure objects in the Mnemonic Similarity Task (MST). These studies have used either old/similar/new or old/new test formats. The forced-choice test format (e.g., “Did you see object A or object A′ during the encoding phase? ”) relies on different assumptions than the old/new test format (e.g., “Did you see this object during the encoding phase? ”); hence, converging evidence from these approaches would bolster the conclusion that healthy aging is accompanied by impaired performance on the MST. Consistent with our hypothesis, healthy older adults exhibited impaired performance on a forced-choice test format that required discriminating between a target and a similar lure. We also tested the hypothesis that age-related impairments on the MST could be modeled within a global matching computational framework. We found that decreasing the probability of successful feature encoding in the models caused changes that were similar to the empirical data in healthy older adults. Collectively, our behavioral results using the forced-choice format extend the finding that healthy aging is accompanied by an impaired ability to discriminate between targets and similar lures, and our modeling results suggest that a diminished probability of encoding stimulus features is a candidate mechanism for memory changes in healthy aging. We also discuss the ability of global matching models to account for findings in other studies that have used variants on mnemonic similarity tasks.
Plasmid-Mediated OqxAB Is an Important Mechanism for Nitrofurantoin Resistance in Escherichia coli

ABSTRACT Increasing consumption of nitrofurantoin (NIT) for treatment of acute uncomplicated urinary tract infections (UTI) highlights the need to monitor emerging NIT resistance mechanisms. This study investigated the molecular epidemiology of the multidrug-resistant efflux gene oqxAB and its contribution to nitrofurantoin resistance by using Escherichia coli isolates originating from patients with UTI (n = 205; collected in 2004 to 2013) and food-producing animals (n = 136; collected in 2012 to 2013) in Hong Kong. The oqxAB gene was highly prevalent among NIT-intermediate (11.5% to 45.5%) and -resistant (39.2% to 65.5%) isolates but rare (0% to 1.7%) among NIT-susceptible (NIT-S) isolates. In our isolates, the oqxAB gene was associated with IS26 and was carried by plasmids of diverse replicon types. Multilocus sequence typing revealed that the clones of oqxAB-positive E. coli were diverse. The combination of oqxAB and nfsA mutations was found to be sufficient for high-level NIT resistance. Curing of oqxAB-carrying plasmids from 20 NIT-intermediate/resistant UTI isolates markedly reduced the geometric mean MIC of NIT from 168.9 μg/ml to 34.3 μg/ml. In the plasmid-cured variants, 20% (1/5) of isolates with nfsA mutations were NIT-S, while 80% (12/15) of isolates without nfsA mutations were NIT-S (P = 0.015). The presence of plasmid-based oqxAB increased the mutation prevention concentration of NIT from 128 μg/ml to 256 μg/ml and facilitated the development of clinically important levels of nitrofurantoin resistance. In conclusion, plasmid-mediated oqxAB is an important nitrofurantoin resistance mechanism. There is a great need to monitor the dissemination of this transferable multidrug-resistant efflux pump.
Adult brain tissue segmentation in multi-modal images with a HyperDenseNet

Accurate segmentation of brain tissue serves as the first step towards volumetric studies and quantitative analysis, being highly beneficial for diagnosis, treatment and follow up of many neurological diseases. Manual segmentation is the conventional approach in clinical routine, which is time-consuming and prone to interand intraobserver variability. Despite all the efforts devoted to the automation of this task, automatic precise segmentation still remains challenging. We propose a fully convolutional neural network with hyper dense connectivity, called HyperDenseNet, to tackle this problem. One of the main advantages of hyper-dense connections lies on its inherent ability to perform deep supervision and aiding the gradient flow during training due to the long connections. Further, by combining the feature maps of intermediate convolutional layers the architecture also injects multi-scale information into the final segmentation. To validate our network we have employed the MRBrainS dataset for brain segmentation on 3D magnetic resonance (MR) images. We compared the proposed method to well-known state-of-the-art networks outperforming them in the task at hand. Additionally, we have tested the performance of the proposed network with 2, and with 3 modalities to investigate the effect of having more independent streams on the network. Figure 1: A section of the proposed HyperDenseNet. Each gray region represents a convolutional block. Red arrows correspond to convolutions and black arrows indicate dense connections between feature maps.
Adaptive Power monitoring for self-aware embedded systems

Dynamic Thermal and Power Management methods require efficient monitoring techniques. Based on a set of data collected by sensors, embedded models estimate online the power consumption: this task is a real challenge, since models must be both accurate and low cost, but they also have to be robust to variations. In this paper, we investigate a self-aware approach using the performance events and the external temperature. We present a solution (PESel) for the selection of the relevant information. This method is two times faster than existing solutions and provides better results compared to related works. The power models achieve a 96% accuracy with a temporal resolution of 100 ms, and negligible performance/energy overheads (less than 1%). Moreover, we show that our estimations are not sensitive to external temperature variations.
The Application of Positive Psychotherapy in Mental Health Care: A Systematic Review.

OBJECTIVE Positive psychotherapy (PPT) stems from the positive psychology movement and is a multicomponent model promoting therapeutic change by developing engagement, pleasure, and meaning. There is some evidence it is effective for depression. PPT is recommended as a flexible model that can be applied to other patient groups alongside other treatments approaches. However, it remains unclear which of the many components are applied. The study aimed to identify how PPT is applied in mental health care. METHOD We systematically searched online databases, including Medline, Embase, PsycINFO, British Nursing Index, Cumulative Index of Nursing and Applied Health, and Cochrane registers (CENTRAL), and completed complementary hand and citation searches. Narrative synthesis was used for analysis. RESULTS A total of 12 papers (from 9 studies) widely applied some PPT components (e.g., blessings journal, character strengths) and scarcely applied others (e.g., satisficing plan or family strengths tree). However, papers poorly described the intervention and rationale for applying components. CONCLUSION Given the lack of rationale for applying PPT, further research is needed to establish which components are acceptable and feasible for use in different patient groups and settings.
mRNA Expression of Interferon Regulatory Factors during Acute Rejection of Liver Transplants in Patients with Autoimmune Hepatitis

Background: Interferon regulatory factors (IRFs) can play a critical role in the regulation of many facets of innate and adaptive immune responses through transcriptional activation of type I interferons, other proinflammatory cytokines, and chemokines. However, their roles in transplantation immunity still remain to be elucidated. Objective: To evaluate the time course of mRNA expression of all 9 members of IRFs family of transcription factors during liver allograft acute rejection. Methods: Blood samples of 19 patients with autoimmune hepatitis receiving liver transplants were collected on days 1, 3, 5, and 7 post-transplantation. The patients were followed for 6 months after transplantation and divided into two groups of acute rejection (AR) (n=4) and non-acute rejection (non-AR) (n=15). Results: All of the studied transcription factors were down-regulated in AR-group on days 3, 5, and 7 post-transplantation compared to non-AR group. The mean±SEM IRF5 on day 7 post-transplantation was significantly (p=0.005) lower in AR-group than in non-AR group (0.7±0.21 vs. 1.91±0.27, respectively); expression of other IRFs family members was not significantly different between the two groups on days 3, 5, and 7 post-transplantation. Conclusion: IRF5 may have an important role during the acute rejection of liver transplants.
Supporting Acceptance Testing in Distributed Software Projects with Integrated Feedback Systems: Experiences and Requirements

During acceptance testing customers assess whether a system meets their expectations and often identify issues that should be improved. These findings have to be communicated to the developers -- a task we observed to be error prone, especially in distributed teams. Here, it is normally not possible to have developer representatives from every site attend the test. Developers who were not present might misunderstand insufficiently documented findings. This hinders fixing the issues and endangers customer satisfaction. Integrated feedback systems promise to mitigate this problem. They allow to easily capture findings and their context. Correctly applied, this technique could improve feedback, while reducing customer effort. This paper collects our experiences from comparing acceptance testing with and without feedback systems in a distributed project. Our results indicate that this technique can improve acceptance testing -- if certain requirements are met. We identify key requirements feedback systems should meet to support acceptance testing.
Compensatory Development and Costs of Plasticity: Larval Responses to Desiccated Conspecifics

Understanding constraints on phenotypic plasticity is central to explaining its evolution and the evolution of phenotypes in general, yet there is an ongoing debate on the classification and relationships among types of constraints. Since plasticity is often a developmental process, studies that consider the ontogeny of traits and their developmental mechanisms are beneficial. We manipulated the timing and reliability of cues perceived by fire salamander larvae for the future desiccation of their ephemeral pools to determine whether flexibility in developmental rates is constrained to early ontogeny. We hypothesized that higher rates of development, and particularly compensation for contradictory cues, would incur greater endogenous costs. We found that larvae respond early in ontogeny to dried conspecifics as a cue for future desiccation, but can fully compensate for this response in case more reliable but contradictory cues are later perceived. Patterns of mortality suggested that endogenous costs may depend on instantaneous rates of development, and revealed asymmetrical costs of compensatory development between false positive and false negative early information. Based on the results, we suggest a simple model of costs of development that implies a tradeoff between production costs of plasticity and phenotype-environment mismatch costs, which may potentially underlie the phenomenon of ontogenetic windows constraining plasticity.
Identifying Residual Foci of Plasmodium falciparum Infections for Malaria Elimination: The Urban Context of Khartoum, Sudan

Background Identifying the location and size of residual foci of infections is critical where malaria elimination is the primary goal. Here the spatial heterogeneity of Plasmodium falciparum infections within the urban extent of Khartoum state in Sudan is investigated using data from cross-sectional surveys undertaken from 1999 to 2008 to inform the Khartoum Malaria Free Initiative (KMFI). Methods From 1999–2008 the KMFI undertook cross-sectional surveys of 256 clusters across 203 random samples of residential blocks in the urban Khartoum state in September of each year. Within sampled blocks, at least five persons, including at least one child under the age of five years, were selected from each household. Blood smears were collected from the sampled individuals to examine the presence of P. falciparum parasites. Residential blocks were mapped. Data were analysed for spatial clustering using the Bernoulli model and the significance of clusters were tested using the Kulldorff scan statistic. Results A total of 128,510 malaria slide examinations were undertaken during the study period. In 1999, overall prevalence was 2.5%, rising to 3.2% in 2000 and consistently staying below 1% in subsequent years. From 2006, over 90% of all surveyed clusters reported no infections. Spatial clustering of infections was present in each year but not statistically significant in the years 2001, 2002, 2004 and 2008. Spatial clusters of high infection were often located at the junction of the Blue and White Niles. Conclusion Persisting foci of malaria infection in Khartoum are likely to distort wide area assessments and disproportionately affect future transmission within the city limits. Improved investments in surveillance that combines both passive and active case detection linked to a geographic information system and a more detailed analysis of the location and stability of foci should be undertaken to facilitate and track malaria elimination in the state of Khartoum.
The NS1 Glycoprotein Can Generate Dramatic Antibody-Enhanced Dengue Viral Replication in Normal Out-Bred Mice Resulting in Lethal Multi-Organ Disease

Antibody-enhanced replication (AER) of dengue type-2 virus (DENV-2) strains and production of antibody-enhanced disease (AED) was tested in out-bred mice. Polyclonal antibodies (PAbs) generated against the nonstructural-1 (NS1) glycoprotein candidate vaccine of the New Guinea-C (NG-C) or NSx strains reacted strongly and weakly with these antigens, respectively. These PAbs contained the IgG2a subclass, which cross-reacted with the virion-associated envelope (E) glycoprotein of the DENV-2 NSx strain, suggesting that they could generate its AER via all mouse Fcγ-receptor classes. Indeed, when these mice were challenged with a low dose (<0.5 LD50) of the DENV-2 NSx strain, but not the NG-C strain, they all generated dramatic and lethal DENV-2 AER/AED. These AER/AED mice developed life-threatening acute respiratory distress syndrome (ARDS), displayed by diffuse alveolar damage (DAD) resulting from i) dramatic interstitial alveolar septa-thickening with mononuclear cells, ii) some hyperplasia of alveolar type-II pneumocytes, iii) copious intra-alveolar protein secretion, iv) some hyaline membrane-covered alveolar walls, and v) DENV-2 antigen-positive alveolar macrophages. These mice also developed meningo-encephalitis, with greater than 90,000-fold DENV-2 AER titers in microglial cells located throughout their brain parenchyma, some of which formed nodules around dead neurons. Their spleens contained infiltrated megakaryocytes with DENV-2 antigen-positive red-pulp macrophages, while their livers displayed extensive necrosis, apoptosis and macro- and micro-steatosis, with DENV-2 antigen-positive Kuppfer cells and hepatocytes. Their infections were confirmed by DENV-2 isolations from their lungs, spleens and livers. These findings accord with those reported in fatal human “severe dengue” cases. This DENV-2 AER/AED was blocked by high concentrations of only the NG-C NS1 glycoprotein. These results imply a potential hazard of DENV NS1 glycoprotein-based vaccines, particularly against DENV strains that contain multiple mutations or genetic recombination within or between their DENV E and NS1 glycoprotein-encoding genes. The model provides potential for assessing DENV strain pathogenicity and anti-DENV therapies in normal mice.