Miracle-dz/UniFAR-FTUs huggingface dataset:
Occupational experiences of college students with ADHD: A qualitative study

Abstract Background College students with attention deficit hyperactivity disorder (ADHD) face difficulties with occupational performance in many functional domains. Despite the broad literature on academic and psychosocial functions, there is a gap in knowledge regarding how these students experience participation in their various daily functions. Objective Gaining a deeper understanding of the occupational experiences of college students with ADHD and exploring factors that facilitate or impede their occupational performance. Method Twenty college students with ADHD were interviewed using the Occupational Performance History Interview (OPHI-II). Qualitative content analysis was employed. Results Six themes were found in relation to varied occupational domains: (1) Eating and meal preparation: Too little or too much; (2) Sleep: Not enough to ‘recharge batteries’; (3) Medication management: Intense ambivalence; (4) Studying: Too hard, too effortful (5) Work: Need it and love it; and (6) Leisure: Desired yet absent. Each theme contained categories related to factors that influenced performance. Impeding factors included occupational demands, ADHD biological attributes, and personal beliefs. Facilitating factors included self-awareness, executive strategies, adaptive routines, and enabling social context. Conclusions College students with ADHD experience profound difficulties in occupational performance, yet variation occurs across domains, attributable to occupational, biological, psychological, and social factors. Results can inform tailored interventions supporting occupational performance in this population.
EHD2 Overexpression Suppresses the Proliferation, Migration, and Invasion in Human Colon Cancer

Abstract Background: To investigate how EHD2 influences the development of colon cancer. Methods: Immunohistochemistry of 90 colon cancer tissue specimens were determined the expression of EHD2. The lentivirus-EHD2-transfected colon cancer cells were conducted to evaluate the biological behaviors. Results: EHD2 was closely associated with clinic pathological parameters (p < 0.001). EHD2 upregulation was relative with a longer overall survival. The results of the univariate and multivariate analyses indicated that EHD2 could be an independent prognosis marker. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest. Conclusions: EHD2 might represent a therapeutic target of colon cancer. IMPACT STATEMENT What is already known on this subject? Membrane trafficking is crucial for cell proliferation, differentiation and apoptosis, especially tumorigenesis and development. EHD2 proteins play an important role in the regulation of membrane trafficking in endocytosis. EHD2 has been suggested to participate in the occurrence of some malignancies. What are the new findings? EHD2 could be an independent prognosis marker in colon cancer. EHD2 overexpression suppressed cell invasion and proliferation, but enhanced cell apoptosis and cell cycle arrest in vitro. EHD2 overexpression markedly increased the expression of EMT marker E-cadherin in colon cancer. How might it impact on clinical practice in the foreseeable future? EHD2 overexpression may inhibit tumorigenesis in colon cancer through the modulation of E-cadherin, the critical marker of EMT which is closely related to invasion and distant metastasis of tumor cells.
Differential activation mechanisms of two isoforms of Gcr1 transcription factor generated from spliced and un-spliced transcripts in Saccharomyces cerevisiae

Abstract Gcr1, an important transcription factor for glycolytic genes in Saccharomyces cerevisiae, was recently revealed to have two isoforms, Gcr1U and Gcr1S, produced from un-spliced and spliced transcripts, respectively. In this study, by generating strains expressing only Gcr1U or Gcr1S using the CRISPR/Cas9 system, we elucidate differential activation mechanisms of these two isoforms. The Gcr1U monomer forms an active complex with its coactivator Gcr2 homodimer, whereas Gcr1S acts as a homodimer without Gcr2. The USS domain, 55 residues at the N-terminus existing only in Gcr1U, inhibits dimerization of Gcr1U and even acts in trans to inhibit Gcr1S dimerization. The Gcr1S monomer inhibits the metabolic switch from fermentation to respiration by directly binding to the ALD4 promoter, which can be restored by overexpression of the ALD4 gene, encoding a mitochondrial aldehyde dehydrogenase required for ethanol utilization. Gcr1U and Gcr1S regulate almost the same target genes, but show unique activities depending on growth phase, suggesting that these isoforms play differential roles through separate activation mechanisms depending on environmental conditions.
Fractional exhaled nitric oxide and asthma treatment adherence

Purpose of review Despite increased clinician awareness, nonadherence to inhaled corticosteroid treatment presents a major challenge to successful asthma management and risks inappropriate treatment escalation, particularly in severe disease. In patients with Type-2 mediated biology, fractional exhaled nitric oxide (FeNO) has a role in assessment and monitoring of adherence to inhaled corticosteroids. Recent findings Asthmatic patients with elevated FeNO are at an increased risk of exacerbation. High FeNO is often secondary to suboptimal adherence to inhaled corticosteroid treatment, whether intentional or nonintentional. FENO-suppression can ‘unmask’ underlying adherence issues and is a useful test in the presence of Type-2 biology in the ‘difficult-to-control’ asthma population. Identification of nonadherence can improve asthma control and prevent inappropriate commencement of costly biologic therapies. Summary Assessment of adherence and FeNO response to monitored inhaled corticosteroid in Type-2 biomarker high asthmatic individuals may prevent unnecessary escalation to biologic therapy. Establishing an ‘optimised’ FeNO may alert clinicians to the possibility of underlying nonadherence at future clinical assessments.
Recruitment of pro-IL-1α to mitochondrial cardiolipin, via shared LC3 binding domain, inhibits mitophagy and drives maximal NLRP3 activation

Significance The NLRP3 inflammasome is a critical component of the innate immune response to infectious agents, but its overactivation is implicated in numerous pathologies, including atherosclerosis, Alzheimer’s Disease, gout, inflammatory bowel disease, and type 2 diabetes. Our study reveals a mechanism by which cells modulate NLRP3 inflammasome activation and identifies potential therapeutic targets to treat pathologies associated with NLRP3 inflammasome activation. The balance between NLRP3 inflammasome activation and mitophagy is essential for homeostasis and cellular health, but this relationship remains poorly understood. Here we found that interleukin-1α (IL-1α)–deficient macrophages have reduced caspase-1 activity and diminished IL-1β release, concurrent with reduced mitochondrial damage, suggesting a role for IL-1α in regulating this balance. LPS priming of macrophages induced pro-IL-1α translocation to mitochondria, where it directly interacted with mitochondrial cardiolipin (CL). Computational modeling revealed a likely CL binding motif in pro-IL-1α, similar to that found in LC3b. Thus, binding of pro-IL-1α to CL in activated macrophages may interrupt CL-LC3b–dependent mitophagy, leading to enhanced Nlrp3 inflammasome activation and more robust IL-1β production. Mutation of pro-IL-1α residues predicted to be involved in CL binding resulted in reduced pro-IL-1α–CL interaction, a reduction in NLRP3 inflammasome activity, and increased mitophagy. These data identify a function for pro-IL-1α in regulating mitophagy and the potency of NLRP3 inflammasome activation.
Identification of a miRNA based model to detect prognostic subgroups in patients with aggressive B-cell lymphoma

Abstract In order to differentiate prognostic subgroups of patients with aggressive B-cell lymphoma, we analyzed the expression of 800 miRNAs with the NanoString nCounter human miRNA assay on a cohort of 228 FFPE samples of patients enrolled in the RICOVER-60 and MegaCHOEP trials. We identified significant miRNA signatures for overall survival (OS) and progression-free survival (PFS) by LASSO-penalized linear Cox-regression. High expression levels of miR-130a-3p and miR-423-5p indicate a better prognosis, whereas high levels of miR-374b-5p, miR-590-5p, miR-186-5p, and miR-106b-5p increase patients’ risk levels for OS. Regarding PFS high expression of miR-365a-5p in addition to the other two miRNAs improves the prognosis and high levels of miR374a-5p, miR-106b-5p, and miR-590-5p, connects with increased risk and poor prognosis. We identified miRNA signatures to subdivide patients into two different risk groups. These prognostic models may be used in risk stratification in future clinical trials and help making personalized therapy decisions.
Automatic hip abductor muscle fat fraction estimation and association with early OA cartilage degeneration biomarkers

The aim of this study was to develop an automatic segmentation method for hip abductor muscles and find their fat fraction associations with early stage hip osteoarthritis (OA) cartilage degeneration biomarkers. This Institutional Review Board approved, Health Insurance Portability and Accountability Act compliant prospective study recruited 61 patients with evidence of hip OA or Femoroacetabular Impingement (FAI). Magnetic resonance (MR) images were acquired for cartilage segmentation, T1ρ and T2 relaxation times computation and grading of cartilage lesion scores. A 3D V‐Net (Dice loss, Adam optimizer, learning rate = 1e−4, batch size = 3) was trained to segment the three muscles (gluteus medius, gluteus minimus, and tensor fascia latae). The V‐Net performance was measured using Dice, distance maps between manual and automatic masks, and Bland‐Altman plots of the fat fractions and volumes. Associations between muscle fat fraction and T1ρ, T2 relaxation times values were found using voxel based relaxometry (VBR). A p < 0.05 was considered significant. The V‐Net had a Dice of 0.90, 0.88, and 0.91 (GMed, GMin, and TFL). The VBR results found associations of fat fraction of all three muscles in early stage OA and FAI patients with T1ρ, T2 relaxation times. Using an automatic, validated segmentation model, the associations derived between OA biomarkers and muscle fat fractions provide insight into early changes that occur in OA, and show that hip abductor muscle fat is associated with markers of cartilage degeneration.
Privacy Accountability and Penalties for IoT Firms

Internet of things (IoT) business partnership are formed by technological partners and traditional manufacturers. IoT sensors and devices capture data from manufacturers' products. Data enforce product/service innovation thanks to data sharing among companies. However, data sharing among firms increases the risk of data breaches. The latter is due to two phenomena: information linkage and privacy interdependency. Data Protection Authorities (DPA) protect data users' rights and fine firms if there is an infringement of privacy laws. DPA sanction the responsible for the infringement of privacy laws. We present two different business scenarios: the first occurs when each firm is a data owner; the second occurs when only the manufacturer is the data owner. For both scenarios, we present two fair penalty schemes that suggest the following: total amount of the fine; and how to share the fine among participants. Penalties critically vary at how innovation networks are structured in IoT industries. Our penalties provide incentives to data sharing since they redistribute firms' responsibility against data breaches. Our penalties may mitigate the risk on the manufacturer if is the unique responsible for data handling.
Imaging slow brain activity during neocortical and hippocampal epileptiform events with electrical impedance tomography

Objective. Electrical impedance tomography (EIT) is an imaging technique that produces tomographic images of internal impedance changes within an object using surface electrodes. It can be used to image the slow increase in cerebral tissue impedance that occurs over seconds during epileptic seizures, which is attributed to cell swelling due to disturbances in ion homeostasis following hypersynchronous neuronal firing and its associated metabolic demands. In this study, we characterised and imaged this slow impedance response during neocortical and hippocampal epileptiform events in the rat brain and evaluated its relationship to the underlying neural activity. Approach. Neocortical or hippocampal seizures, comprising repeatable series of high-amplitude ictal spikes, were induced by electrically stimulating the sensorimotor cortex or perforant path of rats anaesthetised with fentanyl-isoflurane. Transfer impedances were measured during ≥30 consecutive seizures, by applying a sinusoidal current through independent electrode pairs on an epicortical array, and combined to generate an EIT image of slow activity. Main results. The slow impedance responses were consistently time-matched to the end of seizures and EIT images of this activity were reconstructed reproducibly in all animals (p < 0.03125, N = 5). These displayed foci of activity that were spatially confined to the facial somatosensory cortex and dentate gyrus for neocortical and hippocampal seizures, respectively, and encompassed a larger volume as the seizure progressed. Centre-of-mass analysis of reconstructions revealed that this activity corresponded to the true location of the epileptogenic zone, as determined by EEG recordings and fast neural EIT measurements which were obtained simultaneously. Significance. These findings suggest that the slow impedance response presents a reliable marker of hypersynchronous neuronal activity during epileptic seizures and can thus be utilised for investigating the mechanisms of epileptogenesis in vivo and for aiding localisation of the epileptogenic zone during presurgical evaluation of patients with refractory epilepsies.
Redesigning walking brochures using behaviour change theory: implications for walking intentions in natural environments

Summary Natural environments can be used to promote health through facilitating recreational walking. However, efforts to encourage this often neglect messages identified in psychological research that are effective at influencing intentions to walk. This is despite the National Institute for Health and Care Excellence stating that promotional efforts should utilize theoretical frameworks of behaviour change and be targeted towards less active adults. As an illustrative example, this experiment compared a prototypical recreational walking brochure with an “enhanced” version including such persuasive messages on people’s intentions to walk for recreation in natural environments. The enhanced brochure heightened intentions for inexperienced recreational walkers through our hypothesized mechanisms, but appeared to dissuade already-experienced walkers. Optimal messaging strategies in recreational walking brochures require tailoring to more and less active readerships. Guidelines are provided for authors of recreational walking brochures, though the principles and techniques could easily be extended to other means of outdoor walking promotion.
RIPK3-mediated inflammation is a conserved β cell response to ER stress.

Islet inflammation is an important etiopathology of type 2 diabetes; however, the underlying mechanisms are not well defined. Using complementary experimental models, we discovered RIPK3-dependent IL1B induction in β cells as an instigator of islet inflammation. In cultured β cells, ER stress activated RIPK3, leading to NF-kB-mediated proinflammatory gene expression. In a zebrafish muscle insulin resistance model, overnutrition caused islet inflammation, β cell dysfunction, and loss in an ER stress-, ripk3-, and il1b-dependent manner. In mouse islets, high-fat diet triggered the IL1B expression in β cells before macrophage recruitment in vivo, and RIPK3 inhibition suppressed palmitate-induced β cell dysfunction and Il1b expression in vitro. Furthermore, in human islets grafted in hyperglycemic mice, a marked increase in ER stress, RIPK3, and NF-kB activation in β cells were accompanied with murine macrophage infiltration. Thus, RIPK3-mediated induction of proinflammatory mediators is a conserved, previously unrecognized β cell response to metabolic stress and a mediator of the ensuing islet inflammation.
ENDOCRINE REGULATION OF ERYTHROID LINEAGE OF HEMATOPOIESIS IN CHILDREN LIVING UNDER A LOW-DOSE RADIATION EXPOSURE AFTER THE CHORNOBYL NPP ACCIDENT.

OBJECTIVE Elucidation of relationship between the levels of thyroid-stimulating hormone (TSH), free serum thyroxine, serum and urine cortisol and parameters of erythroid lineage of hematopoiesis to estimate the thyroid functionin children of prepubertal, pubertal, and postpubertal age permanently residing under a low-dose radiation exposureto determine the premorbid state of thyroid function. MATERIALS AND METHODS Children aged 3 to 18 years old (n = 203) living in the most intensively radionuclide-contaminated regions of Kyiv, Zhytomyr and Chornihiv oblasts of Ukraine after the Chornobyl NPP accident wereenrolled. Complaints of ossalgia, arthralgia, fatigue, bone fractures in the history, bone dysembryogenetic stigmata,hypermobility syndrome degree, and types of somatic diseases were taken into account. Peripheral blood countparameters, biochemical indices of blood serum were studied, namely the levels of total protein, cholesterol, creatinine and alkaline phosphatase activity. Levels of the free thyroxine, pituitary TSH, serum and daily urine cortisol, anddoses of radiation exposure were determined. RESULTS The radiation dose values in children ranged from (0.35 ± 0.09) mSv to (0.54 ± 0.12) mSv. There was nodifference between the parameters of erythroid lineage of hematopoiesis depending on radiation dose. At the levels of serum TSH up to 1.0 μIU/ml no correlation was found with cortisol levels; at TSH levels of 1.0-3.0 μIU/ml thecorrelation coefficient was r = 0.31; at TSH levels higher than 3.0 μIU/ml the correlation coefficient was r = 0.61probably indicating a compensatory role of adrenal cortex in children at risk of thyroid disease development. In children with joint hypermobility grade II there was a higher incidence of dentofacial anomalies (χ2 = 6.9), deformitiesof lower extremities (χ2 = 6.9), and dental caries (χ2 = 4.3) (p < 0.05). There was a direct correlation between theserum TSH level (over 3 μIU/ml) and micrognathia (brachygnathia) (r = 0.62) indicating the impact of thyroid disease on dentofacial development. The TSH at a level of upper limit of the reference range values may contribute toa decreased RBC count in peripheral blood, increased average volume and hemoglobin content in erythrocyte beingassociated with the initial manifestations of thyroid dysfunction. CONCLUSIONS Abnormal endocrine regulation of hematopoiesis affects the connective tissue, stromal microenvironment of bone marrow, and accordingly the erythroid branch of hematopoiesis in children, which may be relevant inthe development and course of oncohematological diseases.
Prediction of Transporter-Mediated Drug-Drug Interactions and Phenotyping of Hepatobiliary Transporters Involved in the Clearance of E7766, a Novel Macrocycle-Bridged Dinucleotide

E7766 represents a novel class of macrocycle-bridged dinucleotides and is under clinical development for immuno-oncology. In this report, we identified mechanism of systemic clearance E7766 and investigated the hepatobiliary transporters involved in the disposition of E7766 and potential drug interactions of E7766 as a victim of organic anion–transporting polypeptide (OATP) inhibitors. In bile-duct cannulated rats and dogs, E7766 was mainly excreted unchanged in bile (>80%) and to a lesser extent in urine (<20%). Sandwich-cultured human hepatocytes (SCHHs), transfected cells, and vesicles were used to phenotype the hepatobiliary transporters involved in the clearance of E7766. SCHH data showed temperature-dependent uptake of E7766 followed by active biliary secretion. In vitro transport assays using transfected cells and membrane vesicles confirmed that E7766 was a substrate of OATP1B1, OATP1B3, and multidrug resistance–associated protein 2. Phenotyping studies suggested predominant contribution of OATP1B3 over OATP1B1 in the hepatic uptake of E7766. Studies in OATP1B1/1B3 humanized mice showed that plasma exposure of E7766 increased 4.5-fold when coadministered with Rifampicin. Physiologically based pharmacokinetic models built upon two independent bottom-up approaches predicted elevation of E7766 plasma exposure when administered with Rifampicin, a clinical OATP inhibitor. In conclusion, we demonstrate that OATP-mediated hepatic uptake is the major contributor to the clearance of E7766, and inhibition of OATP1B may increase its systemic exposure. Predominant contribution of OATP1B3 in the hepatic uptake of E7766 was observed, suggesting polymorphisms in OATP1B1 would be unlikely to cause variability in the exposure of E7766. SIGNIFICANCE STATEMENT Understanding the clearance mechanisms of new chemical entities is critical to predicting human pharmacokinetics and drug interactions. A physiologically based pharmacokinetic model that incorporated parameters from mechanistic in vitro and in vivo experiments was used to predict pharmacokinetics and drug interactions of E7766, a novel dinucleotide drug. The findings highlighted here may shed a light on the pharmacokinetic profile and transporter-mediated drug interaction propensity of other dinucleotide drugs.
Daily associations among aging perceptions, perceived health, and perceived stress in older adults

Abstract Objectives Daily perceived stress is a key indicator of well-being across adulthood, but particularly for those experiencing age-linked challenges. Understanding how day-level factors most salient to the aging process are associated with daily stress levels can further elucidate the mechanisms involved. Here, we investigate two such age-salient factors—daily perceived health and day-level aging perceptions—on daily perceived stress in later life, with a particular interest in the potential role of aging perceptions as an emotion-focused coping resource. Method 127 older adults (mean age 79) completed daily surveys reporting aging perceptions, perceived health, and perceived stress for 14 days, along with a global questionnaire. Multilevel models assessed the between-person and within-person influences of both daily aging perceptions and daily perceived health on day-level perceived stress. Results Key findings: (a) days of worse perceived health are also days of higher perceived stress; (b) days of more negative aging perceptions are days of higher perceived stress; (c) these individual effects maintain significance when the other is controlled, and (d) these effects interact, so that perceived health is more strongly associated with perceived stress on days when aging perceptions are below a person’s mean. Conclusion The moderating effect identifies aging perceptions as a potentially important resource for emotion-focused coping in later life, particularly for older adults experiencing stress associated with poorer perceived health.