Miracle-dz/UniFAR-FTUs huggingface dataset:
The NP protein of Newcastle disease virus dictates its oncolytic activity by regulating viral mRNA translation efficiency

Newcastle disease virus (NDV) has been extensively studied as a promising oncolytic virus for killing tumor cells in vitro and in vivo in clinical trials. However, the viral components that regulate the oncolytic activity of NDV remain incompletely understood. In this study, we systematically compared the replication ability of different NDV genotypes in various tumor cells and identified NP protein determines the oncolytic activity of NDV. On the one hand, NDV strains with phenylalanine (F) at the 450th amino acid position of the NP protein (450th-F-NP) exhibit a loss of oncolytic activity. This phenotype is predominantly associated with genotype VII NDVs. In contrast, the NP protein with a leucine amino acid at this site in other genotypes (450th-L-NP) can facilitate the loading of viral mRNA onto ribosomes more effectively than 450th-F-NP. On the other hand, the NP protein from NDV strains that exhibit strong oncogenicity interacts with eIF4A1 within its 366–489 amino acid region, leading to the inhibition of cellular mRNA translation with a complex 5’ UTR structure. Our study provide mechanistic insights into how highly oncolytic NDV strains selectively promote the translation of viral mRNA and will also facilitate the screening of oncolytic strains for oncolytic therapy.
Report on trawling and other investigations carried out in the Bays on the South-East Coast of Devon during 1901 and 1902

Section 1. The Brixham fishing-grounds and fishery statistics. Section 2. Distribution and migrations of food-fishes. Section 3. The reproduction of the flat-fishes. Appendix 1. Preliminary Report on the Trawling Experiments in the Bays on the South Coast of Devon.
Aberrant PRDM2 methylation as an early event in serrated lesions destined to evolve into microsatellite‐instable colorectal cancers

Abstract Up to 30% of colorectal cancers (CRCs) develop from sessile serrated lesions (SSLs). Within the serrated neoplasia pathway, at least two principally distinct oncogenetic routes exist generating microsatellite‐stable and microsatellite‐instable CRCs, respectively. Aberrant DNA methylation (DNAm) is found early in the serrated pathway and might play a role in both oncogenetic routes. We studied a cohort of 23 SSLs with a small focus (<10 mm) of dysplasia or cancer, 10 of which were MLH1 deficient and 13 MLH1 proficient. By comparing, for each SSL, the methylation status of (1) the region of dysplasia or cancer (SSL‐D), (2) the nondysplastic SSL (SSL), and (3) adjacent normal mucosa, differentially methylated probes (DMPs) and regions (DMRs) were assessed both genome‐wide as well as in a tumor‐suppressor gene‐focused approach. By comparing DNAm of MLH1‐deficient SSL‐Ds with their corresponding SSLs, we identified five DMRs, including those annotating for PRDM2 and, not unexpectedly, MLH1. PRDM2 gene promotor methylation was associated with MLH1 expression status, as it was largely hypermethylated in MLH1‐deficient SSL‐Ds and hypomethylated in MLH1‐proficient SSL‐Ds. Significantly increased DNAm levels of PRDM2 and MLH1, in particular at ‘critical’ MLH1 probe sites, were to some extent already visible in SSLs as compared to normal mucosa (p = 0.02, p = 0.01, p < 0.0001, respectively). No DMRs, nor DMPs, were identified for SSLs destined to evolve into MLH1‐proficient SSL‐Ds. Our data indicate that, within both arms of the serrated CRC pathway, the majority of the epigenetic alterations are introduced early during SSL formation. Promoter hypermethylation of PRDM2 and MLH1 on the other hand specifically initiates in SSLs destined to transform into MLH1‐deficient CRCs suggesting that the fate of SSLs may not necessarily result from a stochastic process but possibly is already imprinted and predisposed.
Fabrication of gradient hydrogels using a thermophoretic approach in microfluidics.

The extracellular matrix presents spatially varying physical cues that can influence cell behavior in many processes. Physical gradients within hydrogels that mimic the heterogenous mechanical microenvironment are useful to study the impact of these cues on cellular responses. Therefore, simple and reliable techniques to create such gradient hydrogels are highly desirable. This work demonstrates the fabrication of stiffness gradient Gellan gum hydrogels by applying a temperature gradient across a microchannel containing hydrogel precursor solution. Thermophoretic migration of components within the precursor solution generates a concentration gradient that mirrors the temperature gradient profile, which translates into mechanical gradients upon crosslinking. Using this technique, Gellan gum hydrogels with stiffness gradients ranging from 20 to 90 kPa over 600µm are created, covering the elastic moduli typical of moderately hard to hard tissues. MC3T3 osteoblast cells are then cultured on these gradient substrates, which exhibit preferential migration and enhanced osteogenic potential toward the stiffest region on the gradient. Overall, the thermophoretic approach provides a non-toxic and effective method to create hydrogels with defined mechanical gradients at the micron scale suitable for in vitro biological studies and potentially tissue engineering applications.
Evaluating the implementation of personalised outcomes forecasts to optimise supervised exercise therapy in patients with intermittent claudication in the Netherlands: a multimethods study

Background To support the optimisation of supervised exercise therapy (SET) in patients with intermittent claudication, we developed personalised outcomes forecasts (POFs), which visualise estimated walking distance and quality of life for individual patients. The POFs may enable healthcare professionals, such as physical and exercise therapists, to improve shared decision-making and patient outcomes. Objectives To assess differences in patient outcomes (functional walking distance, maximal walking distance and health-related quality of life) and the level of shared decision-making before and after the implementation of POFs in the conservative treatment of patients with intermittent claudication. Methods An interrupted time series design was used to compare preimplementation and postimplementation differences on patient outcomes. Using routinely collected data, differences from baseline to 6 months were compared between patients before and patients after the implementation. To compare levels of shared decision-making, we conducted observations of initial consults within a sample of physical or exercise therapists both before and after the implementation. Audiorecords of observations were scored on shared decision-making using the OPTION-5 instrument. Results Differences in improvements between patients with whom POFs were discussed (n=317) and patients before the implementation of POFs (n=721) did not reach statistical significance for both functional walking distance (experimental vs. control=+23%, p=0.11) and maximal walking distance (experimental vs. control=+21%, p=0.08). For health-related quality of life, the POFs-informed patients showed a statistically significant greater improvement of 4% (p=0.04). Increased levels of shared decision-making were observed in postimplementation consults (n=20) when compared with preimplementation consults (n=36), as the median OPTION-5 total score showed a statistically significant increase from 45 to 55 points (p=0.01). Conclusions Integrating POFs into daily practice of SET for patients with intermittent claudication could assist in improving health-related quality of life and enhancing patient involvement. Using POFs did not result in statistically significant different improvements between groups on walking distances. Trial registration number NL8838.
Overlapping representations of observed actions and action‐related features

Abstract The lateral occipitotemporal cortex (LOTC) has been shown to capture the representational structure of a smaller range of actions. In the current study, we carried out an fMRI experiment in which we presented human participants with images depicting 100 different actions and used representational similarity analysis (RSA) to determine which brain regions capture the semantic action space established using judgments of action similarity. Moreover, to determine the contribution of a wide range of action‐related features to the neural representation of the semantic action space we constructed an action feature model on the basis of ratings of 44 different features. We found that the semantic action space model and the action feature model are best captured by overlapping activation patterns in bilateral LOTC and ventral occipitotemporal cortex (VOTC). An RSA on eight dimensions resulting from principal component analysis carried out on the action feature model revealed partly overlapping representations within bilateral LOTC, VOTC, and the parietal lobe. Our results suggest spatially overlapping representations of the semantic action space of a wide range of actions and the corresponding action‐related features. Together, our results add to our understanding of the kind of representations along the LOTC that support action understanding.
Modification of the Paediatric Gastro-oesophageal Reflux Disease Symptom and Quality of Life Questionnaire (PGSQ) for children with cerebral palsy: a preliminary study

Objective Gastro-oesophageal reflux disease (GORD) is a common condition affecting children, characterised by the passage of gastric contents into the oesophagus causing pain, vomiting and regurgitation. Children with neurodisability (such as cerebral palsy; CP) are predisposed to more severe GORD due to coexisting gut dysmotility and exclusive/supplementary liquid diet; however, there are no existing tools or outcome measures to assess the severity of GORD in this patient group. For children without CP, the ‘Paediatric Gastro-oesophageal Symptom and Quality of Life Questionnaire’ (PGSQ) assesses symptoms and response to treatment, but the questions are not suitable for children with significant cognitive impairment. We aimed to adapt the existing PGSQ assessment tool to enable use in evaluating children with CP and GORD. Patients/interventions Cognitive interviews were conducted by the research team with six parents/carers of children (aged 3–15) with CP (Gross Motor Function Classification System level V) who have current or past symptoms of reflux. They were asked to interpret the questionnaire using a ‘think-aloud technique,’ and offer suggestions on alterations to questions. Reasons for changing questions included confusing/difficult to understand questions, differing interpretations of questions and response choices not applying to the patient group. Results The PGSQ was modified iteratively following each interview. Overall, parents/carers reported that it was acceptable to recall information over the past 7 days. In the final version, it was felt the questions were relevant, useful and related to symptoms that they observed. It was easy to comprehend with no uncomfortable questions. Suggestions for future work included a section specifically focusing on the school day answered by school staff and home life answered by carers who assist them in the home. Conclusions We have adapted the PGSQ to improve relevance and acceptability for families/carers of children with symptoms of GORD and neurodisability. Further work is needed to validate the questionnaire for this patient group.
Petrogenesis of the EET 92023 achondrite and implications for early impact events

We report petrology and geochemistry of an achondrite EET 92023 and compare it with normal and anomalous eucrites. EET 92023 is an unbrecciated achondrite and shows a granular texture mainly composed of low‐Ca pyroxene and plagioclase, petrologically similar to normal cumulate eucrites such as Moore County. However, this rock contains a significant amount of kamacite and taenite not common in unbrecciated, crystalline eucrites. EET 92023 contains a significant amount of platinum group elements (PGEs) (ca. 10% of CI), several orders of magnitude higher than those of monomict eucrites. We suggest that the metallic phases carrying PGEs were incorporated by a projectile during or before igneous crystallization and thermal metamorphism. The projectile was likely to be an iron meteorite rather than chondritic materials, as indicated by the lack of olivine and the presence of free silica. Therefore, the oxygen isotopic signature is indigenous, rather than due to contamination of the projectile material with different oxygen isotopic compositions. A significant thermal event involving partial melting and metamorphism after the impact event indicates that EET 92023 records early impact events which took place shortly after the crust formation on a differentiated protoplanet when the crust was still hot.
Urbanization drives biotic homogenization of the avian community in China.

Urbanization-driven biotic homogenization has been recorded in various ecosystems on local and global scales; however, it is largely unexplored in developing countries. Empirical studies on different taxa and bioregions show conflicting results (i.e. biotic homogenization vs. biotic differentiation); the extent to which the community composition changes in response to anthropogenic disturbances and the factors governing this process, therefore, require elucidation. Here, we used a compiled database of 760 bird species in China to quantify the multiple-site β-diversity and fitted distance decay in pairwise β-diversities between natural and urban assemblages to assess whether urbanization had driven biotic homogenization. We used generalized dissimilarity models (GDM) to elucidate the roles of spatial and environmental factors in avian community dissimilarities before and after urbanization. The multiple-site β-diversities among urban assemblages were markedly lower than those among natural assemblages, and the distance decays in pairwise similarities in natural assemblages were more rapid. These results were consistent among taxonomic, phylogenetic, and functional aspects, supporting a general biotic homogenization driven by urbanization. The GDM results indicated that geographical distance and temperature were the dominant predictors of avian community dissimilarity. However, the contribution of geographical distance and climatic factors decreased in explaining compositional dissimilarities in urban assemblages. Geographical and environmental distances accounted for much lower variations in compositional dissimilarities in urban than in natural assemblages, implying a potential risk of uncertainty in model predictions under further climate change and anthropogenic disturbances. Our study concludes that taxonomic, phylogenetic, and functional dimensions elucidate urbanization-driven biotic homogenization in China.
Sulfur reduction in sediments of marine and evaporite environments

Transformations of sulfur in sediments of ponds ranging in salinities from that of normal seawater to those of brines saturated with sodium chloride were examined. The chemistry of the sediment and pore waters were focused on with emphasis on the fate of sulfate reduction. The effects of increasing salinity on both forms of sulfur and microbial activity were determined. A unique set of chemical profiles and sulfate-reducing activity was found for the sediments of each of the sites examined. The quantity of organic matter in the salt pond sediments was significantly greater than that occurring in the adjacent intertidal site. The total quantitative and qualitative distribution of volatile fatty acids was also greater in the salt ponds. Volatile fatty acids increased with salinity.
Nutrient enhanced coastal ocean productivity in the north Gulf of Mexico: understanding the effects of nutrients on a coastal ecosystem

The continental shelf adjacent to the Mississippi River is a highly productive system, often referred to as the fertile fisheries crescent. This productivity is attributed to the effects of the river, especially nutrient delivery. In the later decades of the 2oth century, though, changes in the system were becoming evident. Nutrient loads were seen to be increasing and reports of hypoxia were becoming more frequent. During most recent summers, a broad area (up to 20,000 krn2) of near bottom, inner shelf waters immediately west of the Mississippi River delta becomes hypoxic (dissolved oxygen concentrations less than 2 mgll). In 1990, the Coastal Ocean Program of the National Oceanic and Atmospheric Administration initiated the Nutrient Enhanced Coastal Ocean Productivity (NECOP) study of this area to test the hypothesis that anthropogenic nutrient addition to the coastal ocean has contributed to coastal eutrophication with a significant impact on water quality. Three major goals of the study were to determine the degree to which coastal productivity in the region is enhanced by terrestrial nutrient input, to determine the impact of enhanced productivity on water quality, and to determine the fate of fixed carbon and its impact on living marine resources. The study involved 49 federal and academic scientists from 14 institutions and cost $9.7 million. Field work proceeded from 1990 through 1993 and analysis through 1996, although some analyses continue to this day. The Mississippi River system delivers, on average, 19,000 m3/s of water to the northern Gulf of Mexico. The major flood of the river system occurs in spring following snow melt in the upper drainage basin. This water reaches the Gulf of Mexico through the Mississippi River birdfoot delta and through the delta of the Atchafalaya River. Much of this water flows westward along the coast as a highly stratified coastal current, the Louisiana Coastal Current, isolated from the bottom by a strong halocline and from mid-shelf waters by a strong salinity front. This stratification maintains dissolved and particulate matter from the rivers, as well as recycled material, in a well-defined flow over the inner shelf. It also inhibits the downward mixing of oxygenated surface waters from the surface layer to the near bottom waters. This highly stratified flow is readily identifiable by its surface turbidity, as it carries much of the fine material delivered with the river discharge and resuspended by nearshore wave activity. A second significant contribution to the turbidity of the surface waters is due to phytoplankton in these waters. This turbidity reduces the solar radiation penetrating to depth through the water column. These two aspects of the coastal current, isolation of the inner shelf surface waters and maintenance of a turbid surface layer, precondition the waters for the development of near bottom summer hypoxia.
Environmental, social and economic aptitudes for sustainable viability of sheep farming systems in northern Spain.

Overall assessment of farming systems is an issue necessary to take into account due to multiple interactions in agriculture sector. Several studies have appeared the latest years trying to measure sustainability in one of its dimensions (environmental, social, and economic), or all together in order to give an answer to society demands for one hand and farmer’s needs for the other. The main objective of this study is to find strengths and weaknesses of traditional milk sheep production in the Basque Country comparing with intensive farms that have emerged recent years, as well as trying to trace correlations between different indicators of sustainability. Economic, social and environmental indicators have been studied, in different categories. These indicators have been combined into a single index of sustainability (numerical integration) to every dimension, to present together into three diagrams (visual integration). This study shows preliminary results of an integrated study of environmental, social and economic aptitudes of sheep farms in the Basque County (Northern Spain) through a set of indicators and possible interactions between them. A holistic view of farms will improve viability options for survival of farms, as well as seeing correlations between social, economic and environmental aptitudes to adapt farms and farmers to new challenges.
Injectable Alginate Complex Hydrogel Loaded with Dual-Drug Nanovectors Offers Effective Photochemotherapy against Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC), accounting for approximately 20% of breast cancer cases, is a particular subtype that lacks tumor-specific targets and is difficult to treat due to its high aggressiveness and poor prognosis. Chemotherapy remains the major systemic treatment for TNBC. However, its applicability and efficacy in the clinic are usually concerning due to a lack of targeting, adverse side effects, and occurrence of multidrug resistance, suggesting that the development of effective therapeutics is still highly demanded nowadays. In this study, an injectable alginate complex hydrogel loaded with indocyanine green (ICG)-entrapped perfluorocarbon nanoemulsions (IPNEs) and camptothecin (CPT)-doped chitosan nanoparticles (CCNPs), named IPECCNAHG, was developed for photochemotherapy against TNBC. IPNEs with perfluorocarbon can induce hyperthermia and generate more singlet oxygen than an equal dose of free ICG upon near-infrared (NIR) irradiation to achieve photothermal and photodynamic therapy. CCNPs with positive charge may facilitate cellular internalization and provide sustained release of CPT to carry out chemotherapy. Both nanovectors can stabilize agents in the same hydrogel system without interactions. IPECCNAHG integrating IPNEs and CCNPs enables stage-wise combinational therapeutics that may overcome the issues described above. With 60 s of NIR irradiation, IPECCNAHG significantly inhibited the growth of MDA-MB-231 tumors in the mice without systemic toxicity within the 21 day treatment. We speculate that such anticancer efficacy was accomplished by phototherapy followed by chemotherapy, where cancer cells were first destroyed by IPNE-derived hyperthermia and singlet oxygen, followed by sustained damage with CPT after internalization of CCNPs; a two-stage tumoricidal process. Taken together, the developed IPECCNAHG is anticipated to be a feasible tool for TNBC treatment in the clinic.
A Simple and Yet Fairly Effective Defense for Graph Neural Networks

Graph Neural Networks (GNNs) have emerged as the dominant approach for machine learning on graph-structured data. However, concerns have arisen regarding the vulnerability of GNNs to small adversarial perturbations. Existing defense methods against such perturbations suffer from high time complexity and can negatively impact the model's performance on clean graphs. To address these challenges, this paper introduces NoisyGNNs, a novel defense method that incorporates noise into the underlying model's architecture. We establish a theoretical connection between noise injection and the enhancement of GNN robustness, highlighting the effectiveness of our approach. We further conduct extensive empirical evaluations on the node classification task to validate our theoretical findings, focusing on two popular GNNs: the GCN and GIN. The results demonstrate that NoisyGNN achieves superior or comparable defense performance to existing methods while minimizing added time complexity. The NoisyGNN approach is model-agnostic, allowing it to be integrated with different GNN architectures. Successful combinations of our NoisyGNN approach with existing defense techniques demonstrate even further improved adversarial defense results. Our code is publicly available at: https://github.com/Sennadir/NoisyGNN.