Miracle-dz/UniFAR-FTUs huggingface dataset:
Long-term participation 7-8 years after stroke: Experiences of people in working-age

Objective To enhance the understanding of long-term participation in working-aged people 7–8 years after stroke. Methods This study had a qualitative design, using a thematic analysis methodology. Eleven individuals took part in an in depth interview 7–8 years after a first time stroke. They had received care at the Sahlgrenska University Hospital in Gothenburg, and were recruited as a heterogenic sample with respect to age, gender, stroke severity and subtype. Results From the participants’ experiences four themes emerged: “Returning to work after stroke”; “Working life 7–8 years after stroke”; “Social life 7–8 years after stroke”; and “A state of reorientation in life”. Quotes about experienced participation in everyday life were summarized and presented as “Participation after stroke narratives”. Participants chose to emphasize on work- and social life when describing situations of successful participation. Being included in the wider community and having a sense of purpose, when interacting with others, were factors that these narratives had in common. Participants had gradually become accustomed to a somewhat altered life situation. Some consequences after stroke were still considered frustrating in social or work situations. However, the importance of these issues had reduced and were no longer problematized. Conclusions Participants felt content with their everyday life in general, which was a principal and positive result of this study. Reaching a stage of acceptance seemed to be a complex and continuous struggle, and an individual approach in long-term rehabilitation would be valuable to support this personal process. More knowledge about what factors that facilitate participation in people of working-age many years after stroke is needed, so that more people can reach a state of positive identity and participation.
Neuraminidase activity and specificity of influenza A virus are influenced by haemagglutinin-receptor binding

ABSTRACT Influenza virus haemagglutinin (HA) and neuraminidase (NA) are involved in the recognition and modulation of sialic acids on the cell surface as the virus receptor. Although the balance between two proteins functions has been found to be crucial for viral fitness, the interplay between the proteins has not been well established. Herein we present evidence for interplay between influenza HA and NA, which may affect the balance between two glycoprotein functions. NA enzymatic activities against sialoglycans were promoted by the presence of HA, which is in accordance with the level of co-existing HA. Such activity enhancement was lost when the HA-receptor binding properties were abolished by low-pH treatment or by mutations at the HA receptor binding domain. Sialidase activities of NA-containing virus-like particles and native influenza viruses were detected using different NA-assays and sialic acid substrates. Most pronounced HA-mediated NA enhancement was found when intact virions were confronted with multivalent surface-anchored substrates, which mimics the physiological conditions on cell membranes. Using recombinant viruses with altered HA bindings preference between α2,3- and α2,6-linked sialic acids, we also found that NA function against different substrates is correlated with the HA-receptor specificity. The effect of HA-receptor specificities on NA functions, together with the HA-mediated NA enhancement, may play a role in virus evasion of the mucus barrier, as well as in cross-species adaptation. Our data also indicate the importance of using multivalent substrates in future studies of NA functions.
“Inactive” ingredients in oral medications

Inactive ingredients in oral medications are generally poorly appreciated, and many include materials associated with adverse reactions in patients. Oral forms of medications contain “inactive” ingredients to enhance their physical properties. Using data analytics, we characterized the abundance and complexity of inactive ingredients in approved medications. A majority of medications contain ingredients that could cause adverse reactions, underscoring the need to maximize the tolerability and safety of medications and their inactive ingredients.
Aberrant DOCK2, GRASP, HIF3A and PKFP Hypermethylation has Potential as a Prognostic Biomarker for Prostate Cancer

Prostate cancer (PCa) is a clinically heterogeneous disease and currently, accurate diagnostic and prognostic molecular biomarkers are lacking. This study aimed to identify novel DNA hypermethylation markers for PCa with future potential for blood-based testing. Accordingly, to search for genes specifically hypermethylated in PCa tissue samples and not in blood cells or other cancer tissue types, we performed a systematic analysis of genome-wide DNA methylation data (Infinium 450K array) available in the Marmal-aid database for 4072 malignant/normal tissue samples of various types. We identified eight top candidate markers (cg12799885, DOCK2, FBXO30, GRASP, HIF3A, MOB3B, PFKP, and TPM4) that were specifically hypermethylated in PCa tissue samples and hypomethylated in other benign and malignant tissue types, including in peripheral blood cells. Potential as diagnostic and prognostic biomarkers was further assessed by the quantitative methylation specific PCR (qMSP) analysis of 37 nonmalignant and 197 PCa tissue samples from an independent population. Here, all eight hypermethylated candidates showed high sensitivity (75–94%) and specificity (84–100%) for PCa. Furthermore, DOCK2, GRASP, HIF3A and PKFP hypermethylation was significantly associated with biochemical recurrence (BCR) after radical prostatectomy (RP; 197 patients), independent of the routine clinicopathological variables. DOCK2 is the most promising single candidate marker (hazard ratio (HR) (95% confidence interval (CI)): 1.96 (1.24–3.10), adjusted p = 0.016; multivariate cox regression). Further validation studies are warranted and should investigate the potential value of these hypermethylation candidate markers for blood-based testing also.
Calibration of a Multiphase Model Based on a Comprehensive Data Set for a Normal Strength Concrete

Hygro-thermo-chemo-mechanical modelling of time-dependent concrete behavior requires the accurate determination of a large set of parameters. In this paper, the parameters of a multiphase model are calibrated based on a comprehensive set of experiments for a particular concrete of grade C30/37. The experiments include a calorimetry test, tests for age-dependent mechanical properties, tests for determining the water desorption isotherm, shrinkage tests, and compressive creep tests. The latter two were performed on sealed and unsealed specimens with accompanying mass water content measurements. The multiphase model is based on an effective stress formulation. It features a porosity-dependent desorption isotherm, taking into account the time-dependency of the desorption properties. The multiphase model is shown to yield excellent results for the evolutions of the mechanical parameters. The evolution of the autogenous shrinkage strain and evolutions of the creep compliances for loading at concrete ages of 2 days, 7 days, and 28 days are well predicted together with the respective mass water content evolution. This also holds for the evolution of the drying shrinkage strain, at least for moderate drying up to one year. However, it will be demonstrated that for longer drying times further conceptual thoughts concerning the coupled representation of shrinkage and creep are required.
Randomized trial of add‐on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy

To investigate the feasibility, safety, and tolerability of add‐on treatment of the triglycerides of heptanoate (triheptanoin) vs the triglycerides of octanoate and decanoate (medium chain triglycerides [MCTs]) in adults with treatment‐refractory epilepsy.
The exposome and health: Where chemistry meets biology

Despite extensive evidence showing that exposure to specific chemicals can lead to disease, current research approaches and regulatory policies fail to address the chemical complexity of our world. To safeguard current and future generations from the increasing number of chemicals polluting our environment, a systematic and agnostic approach is needed. The “exposome” concept strives to capture the diversity and range of exposures to synthetic chemicals, dietary constituents, psychosocial stressors, and physical factors, as well as their corresponding biological responses. Technological advances such as high-resolution mass spectrometry and network science have allowed us to take the first steps toward a comprehensive assessment of the exposome. Given the increased recognition of the dominant role that nongenetic factors play in disease, an effort to characterize the exposome at a scale comparable to that of the human genome is warranted.
Education level and incident functional disability in elderly Japanese: The Ohsaki Cohort 2006 study

As the factors that link education level with incident functional disability in elderly Japanese have never been investigated, the present study investigated this issue in an elderly Japanese population. A 9-year prospective cohort study (2006–2015) was conducted among 8,680 Japanese individuals (≥65 years), Ohsaki city, Japan. In a baseline survey, we collected data on education level and potential mediators. Data on incident functional disability were retrieved from the Long-term Care Insurance database. The Cox proportional hazards model was used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for incident functional disability by education level (below upper-secondary education (reference), and upper secondary education and above). Mediating effects were estimated using accelerated failure time model and a logistic regression model. During 9-year follow-up period, 2,742 cases (31.6%) of incident functional disability were observed, and education level showed an inverse association with functional disability (P for trend <0.01). Participation in community activities had the largest mediating effect (34.7%) on the relationship between education level and incident functional disability. This effect remained among those aged 65–74 years (19.9%) but became negligible among those aged ≥75 years. Other potential mediators (such as smoking and drinking status) were also tested, but these showed only small mediating effects. The inverse association between education level and the incident risk of functional disability appears to be largely mediated by participation in community activities among elderly Japanese, especially those aged 65–74 years.
Experimental simulation to analyse geomorphological properties of cometary surfaces with outgassing volatiles

We want to study the development of cometary and other outgassing surfaces of airless planetary objects with analog laboratory experiments on Earth. The focus is on the evolution of different morphologies, taking into account the composition of the sample material and variable insolation flux. Our aim is to understand how different cometary materials interact and how the appearance of cracks and boulders develop during insolation and outgassing.
Preclinical Activities of Epigallocatechin Gallate in Signaling Pathways in Cancer

Epigallocatechin gallate (EGCG) is the main bioactive component of catechins predominantly present in various types of tea. EGCG is well known for a wide spectrum of biological activities as an anti-oxidative, anti-inflammatory, and anti-tumor agent. The effect of EGCG on cell death mechanisms via the induction of apoptosis, necrosis, and autophagy has been documented. Moreover, its anti-proliferative action has been demonstrated in many cancer cell lines. It was also involved in the modulation of cyclooxygenase-2, oxidative stress and inflammation of different cellular processes. EGCG has been reported as a promising agent target for plasma membrane proteins, such as epidermal growth factor receptor. In addition, it has been demonstrated a mechanism of action relying on the inhibition of ERK1/2, p38 MAPK, NF-κB, and vascular endothelial growth factor. Furthermore, EGCG and its derivatives were used in proteasome inhibition and they were involved in epigenetic mechanisms. In summary, EGCG is the most predominant and bioactive constituent of tea and may play a role in cancer prevention.
Risk factors, characteristics, and outcomes of acute respiratory distress syndrome in dogs and cats: 54 cases

OBJECTIVE To characterize the clinical features of the acute respiratory distress syndrome (ARDS), risk factors, and outcome in dogs and cats. The study also aimed to evaluate the current veterinary criteria for the diagnosis of ARDS by comparison of clinical diagnostic criteria with necropsy findings. DESIGN Retrospective study. ANIMALS Fifty-four client-owned animals, 46 dogs and 8 cats. INTERVENTIONS Medical records were reviewed for patients with the diagnosis of ARDS based on previously published clinical criteria or necropsy diagnosis. Signalment, clinical findings, and outcome were recorded. MEASUREMENTS AND MAIN RESULTS Animals were grouped according to a clinical or necropsy diagnosis: 43/54 (80%) were diagnosed with ARDS based on clinical criteria (group 1) and 11/54 (20%) were diagnosed with ARDS based on necropsy only (group 2). In group 1, 22/43 (51%) had a necropsy, which confirmed ARDS in 12/22 (54%). Direct (pulmonary) causes of ARDS were more common than indirect causes in dogs, while cats had a similar occurrence of direct and indirect causes. The most common risk factors identified in dogs were aspiration pneumonia (42%), systemic inflammatory response syndrome (SIRS) (29%), and shock (29%). All cats diagnosed clinically with ARDS had SIRS with or without sepsis. Of the animals with a clinical diagnosis of ARDS, 49% received mechanical ventilation and 58% received treatment (with or without mechanical ventilation) for 24 hours or longer. The overall case fatality rate was 84% in dogs and 100% in cats. CONCLUSIONS AND CLINICAL RELEVANCE As described in human literature, pneumonia was the most common risk factor in dogs with ARDS, whereas it was SIRS for the cat population. The high mortality rate and discrepancy between the clinical diagnosis and necropsy findings may highlight limitations in the clinical criteria for the diagnosis of ARDS and treatment in dogs and cats.
NAP (davunetide) preferential interaction with dynamic 3-repeat Tau explains differential protection in selected tauopathies

The microtubule (MT) associated protein Tau is instrumental for the regulation of MT assembly and dynamic instability, orchestrating MT-dependent cellular processes. Aberration in Tau post-translational modifications ratio deviation of spliced Tau isoforms 3 or 4 MT binding repeats (3R/4R) have been implicated in neurodegenerative tauopathies. Activity-dependent neuroprotective protein (ADNP) is vital for brain formation and cognitive function. ADNP deficiency in mice causes pathological Tau hyperphosphorylation and aggregation, correlated with impaired cognitive functions. It has been previously shown that the ADNP-derived peptide NAP protects against ADNP deficiency, exhibiting neuroprotection, MT interaction and memory protection. NAP prevents MT degradation by recruitment of Tau and end-binding proteins to MTs and expression of these proteins is required for NAP activity. Clinically, NAP (davunetide, CP201) exhibited efficacy in prodromal Alzheimer’s disease patients (Tau3R/4R tauopathy) but not in progressive supranuclear palsy (increased Tau4R tauopathy). Here, we examined the potential preferential interaction of NAP with 3R vs. 4R Tau, toward personalized treatment of tauopathies. Affinity-chromatography showed that NAP preferentially interacted with Tau3R protein from rat brain extracts and fluorescence recovery after photobleaching assay indicated that NAP induced increased recruitment of human Tau3R to MTs under zinc intoxication, in comparison to Tau4R. Furthermore, we showed that NAP interaction with tubulin (MTs) was inhibited by obstruction of Tau-binding sites on MTs, confirming the requirement of Tau-MT interaction for NAP activity. The preferential interaction of NAP with Tau3R may explain clinical efficacy in mixed vs. Tau4R pathologies, and suggest effectiveness in Tau3R neurodevelopmental disorders.
Iron Oxide Nanoflowers @ CuS Hybrids for Cancer Tri-Therapy: Interplay of Photothermal Therapy, Magnetic Hyperthermia and Photodynamic Therapy

Innovative synthesis routes revolutionized nanomaterial combination and design possibilities resulting in a new generation of fine-tuned nanoparticles featuring exquisite shape and constitution control. However, there is still room for improvement when it comes to the development of multi-functional nanoparticle agents merging a plurality of therapeutic functions to tackle tumors simultaneously by synergic mechanisms. Herein, we report the design of an optimized nanohybrid for cancer tri-therapy featuring a maghemite (γ-Fe2O3) nanoflower-like multicore nanoparticle conceived for efficient magnetic hyperthermia (MHT) and a spiky copper sulfide shell (IONF@CuS) with a high near-infrared (NIR) absorption coefficient suitable for photothermal (PTT) and photodynamic therapy (PDT). Methods: Spiky-like IONF@CuS nanohybrids were obtained through a straightforward and scalable water-based template sacrificial synthesis, which allows the shell shape control by tuning polyvinylpyrrolidone (PVP) concentration. A comprehensive characterization of nanohybrid size, shape and structural properties was carried out by combining complementary TEM, SEM, HR-TEM, EELS, XRD and NTA. The all-in-one therapeutic multi-functionality was assessed on cancer cells and on tumor-bearing nude mice. Results: Tests carried out on IONF@CuS nanohybrid aqueous dispersion demonstrated their impressive efficiency to convert light (conversion coefficient = 42 ± 6 %) and magnetic stimulation (SAR ~ 350 W g-1) into heat as well as to induce concurrent reactive oxygen species (ROS) formation upon laser irradiation. Such capabilities were further confirmed in cellular environment by in vitro tests and at the organism level by in vivo tests in a murine tumor model. Notably, complete tumor regression was obtained for the PTT mode at low Cu concentration. Overall, these results allowed determining windows of applicability for each therapy individually or in combination. Conclusions: Altogether, the obtained data evidence the successful synthesis of a unique tri-therapeutic nanoparticle featuring highly relevant assets for clinical translation such as reduced nanoparticle administered dose, reduced laser power exposure, reduced magnetic field frequency, and the possibility of serial heating cycles and therapy monitoring by photoacoustic (PA) and magnetic resonance imaging (MRI). Furthermore, the integration of the dual heating capability (MHT + PTT) with the PDT insult offers a unique asset to tackle tumors by multiple cytotoxic strategies in order to improve the therapeutic outcome in a broader spectrum of clinical conditions.
Anemia and iron deficiency in compensated and decompensated cirrhosis: Prevalence and impact on clinical outcomes

Iron deficiency anemia (IDA)is the leading cause of anemia worldwide. Data on prevalence and clinical impact of anemia in cirrhosis are scarce. Aim was to report on the following:(i) prevalence of anemia and IDA in cirrhosis and (ii) its possible impact on clinical outcomes.
Direct Comparison of Odor Responses of Homologous Glomeruli in the Medial and Lateral Maps of the Mouse Olfactory Bulb

Abstract Olfactory sensory neurons (OSNs) expressing same-type odorant receptors typically project to a pair of glomeruli in the medial and lateral sides of the olfactory bulbs (OBs) in rodents. This multiple glomerular representation of homologous inputs is considered to have more important functional roles for odor information processing than the redundant backup system. However, a consensus idea is lacking and this hinders interpretation of the phenomenon. In addition, the shared and unique odorant response properties of the homologous glomeruli remain unclear because the majority of medial glomeruli are hidden in the septal OB, and thus it is difficult to directly compare them. OSNs, which express trace amine-associated odorant receptors (TAARs), were recently identified that project to a pair of glomeruli uniquely located in the dorsal OB. In this study, we measured the odorant-induced calcium responses of homologous pairs of TAAR glomeruli simultaneously in anesthetized mice and directly compared their response patterns. We found that they exhibited similar temporal response patterns and could not find differences in onset latency, rise time, decay time, or response amplitude. However, the medial glomeruli had significantly larger respiration-locked calcium fluctuations than the lateral glomeruli. This trend was observed with/without odorant stimulation in postsynaptic neurons of GABAergic, dopaminergic, and mitral/tufted cells, but not in presynaptic olfactory sensory axon terminals. This indicates that, at least in these TAAR glomeruli, the medial rather than the lateral OB map enhances the respiration-locked rhythm and transfers this information to higher brain centers.
Evolution of cooperation on large networks with community structure

Cooperation is a major factor in the evolution of human societies. The structure of social networks, which affects the dynamics of cooperation and other interpersonal phenomena, have common structural signatures. One of these signatures is the tendency to organize as groups. This tendency gives rise to networks with community structure, which are composed of distinct modules. In this paper, we study analytically the evolutionary game dynamics on large modular networks in the limit of weak selection. We obtain novel analytical conditions such that natural selection favours cooperation over defection. We calculate the transition point for each community to favour cooperation. We find that a critical inter-community link creation probability exists for given group density, such that the overall network supports cooperation even if individual communities inhibit it. As a byproduct, we present solutions for the critical benefit-to-cost ratio which perform with remarkable accuracy for diverse generative network models, including those with community structure and heavy-tailed degree distributions. We also demonstrate the generalizability of the results to arbitrary two-player games.