Miracle-dz/UniFAR-FTUs huggingface dataset:
Modeling Gliomas Using Two Recombinases.

Development of animal models to investigate the complex ecosystem of malignant gliomas using the Cre/loxP recombination system has significantly contributed to our understanding of the molecular underpinnings of this deadly disease. In these model systems, once the tumor is induced by activation of Cre-recombinase in a tissue-specific manner, further genetic manipulations to explore the progression of tumorigenesis are limited. To expand the application of mouse models for gliomas, we developed glial fibrillary acidic protein (GFAP)-FLP recombinase (FLPo) mice that express FLPo recombinase specifically in GFAP-positive cells. Lentivirus-based in vivo delivery of cancer genes conditioned by FLP/FRT-mediated recombination initiated gliomas in GFAP-FLPo mice. Using the Cre-mediated multifluorescent protein-expressing system, we demonstrated that the GFAP-FLPo mouse model enables the analysis of various stages of gliomagenesis. Collectively, we present a new mouse model that will expand our ability to dissect developmental processes of gliomagenesis and to provide new avenues for therapeutic approaches.Significance: This study presents a new glioma mouse model derived using lentiviral vectors and two recombination systems that will expand the ability to dissect developmental processes of gliomagenesis.
A direct interaction between survivin and myosin II is required for cytokinesis

ABSTRACT An acto-myosin contractile ring, which forms after anaphase onset and is highly regulated in time and space, mediates cytokinesis, the final step of mitosis. The chromosomal passenger complex (CPC), composed of Aurora-B kinase, INCENP, borealin and survivin (also known as BIRC5), regulates various processes during mitosis, including cytokinesis. It is not understood, however, how CPC regulates cytokinesis. We show that survivin binds to non-muscle myosin II (NMII), regulating its filament assembly. Survivin and NMII interact mainly in telophase, and Cdk1 regulates their interaction in a mitotic-phase-specific manner, revealing the mechanism for the specific timing of survivin–NMII interaction during mitosis. The survivin–NMII interaction is indispensable for cytokinesis, and its disruption leads to multiple mitotic defects. We further show that only the survivin homodimer binds to NMII, attesting to the biological importance for survivin homodimerization. We suggest a novel function for survivin in regulating the spatio-temporal formation of the acto-NMII contractile ring during cytokinesis and we elucidate the role of Cdk1 in regulating this process. This article has an associated First Person interview with the first author of the paper. Highlighted Article: Survivin interacts with myosin II regulating myosin II filament assembly. This interaction occurs during telophase, is regulated by Cdk1 and the dimerization state of survivin, and is required for cytokinesis.
Novel ACT-based eHealth psychoeducational intervention for students with mental distress: a study protocol for a mixed-methodology pilot trial

Introduction Recent studies have revealed a high prevalence of depression, anxiety and stress symptoms among university students, highlighting an urgent need for preventative measures at low cost to better support often overwhelmed support services. Objective Here we propose a protocol for assessing the feasibility of a randomised controlled trial (RCT) for an online transdiagnostic psychoeducational intervention called ‘A Bite of ACT’ compared with a waitlist control. Methods and analysis This is an RCT with crossover design involving baseline assessments and two follow-up periods. The primary outcome measure will be the Acceptance Checklist for Clinical Effectiveness Pilot Trials (ACCEPT) for measuring the feasibility of the trial design and methods. Secondary outcomes include measures of well-being, social connectedness, quality of life (EuroQol Five Dimensions), depression, anxiety and stress (Depression Anxiety Stress Scales-21), as well as the process measures: psychological flexibility (Acceptance and Action Questionnaire-Second Version and the Mindful Attention Awareness Scale) and heart rate variability. Analysis will involve calculating descriptive statistics, examining trial feasibility outcomes through ACCEPT, and determining effect size measures to determine the sample size needed in a future trial (if indicated). Qualitative interviews and preliminary health economics analysis will provide additional insights into the feasibility of the intervention and trial methods. Ethics and dissemination This study has been approved by the Department of Psychology Research Ethics Committee in the College of Human and Health Sciences at Swansea University. Dissemination will involve publication in international peer-reviewed journals, presentation of findings at relevant local, national and international conferences, and promotion of study outcomes using social media and other channels for disseminating findings to the wider community. Trial registration number NCT03810131; Pre-results.
On the semantics of nonwords and their lexical category.

Using computational simulations, this work demonstrates that it is possible to learn a systematic relation between words' sound and their meanings. The sound-meaning relation was learned from a corpus of phonologically transcribed child-directed speech by using the linear discriminative learning (LDL) framework (Baayen, Chuang, Shafaei-Bajestan, & Blevins, 2019), which implements linear mappings between words' form vectors and semantic vectors. Presented with the form vectors of 16 nonwords, taken from a study on word learning (Fitneva, Christiansen, & Monaghan, 2009), the network generated the estimated semantic vectors of the nonwords. As half of these nonwords were created to phonologically resemble English nouns and the other half were phonologically similar to English verbs, we assessed whether the estimated semantic vectors for these nonwords reflect this word category difference. In 7 different simulations, linear discriminant analysis (LDA) successfully discriminated between noun-like nonwords and verb-like nonwords, based on their semantic relation to the words in the lexicon. Furthermore, how well LDA categorized a nonword correlated well with a phonological typicality measure (i.e., the degree of its form being noun-like or verb-like) and with children's performance in an entity/action discrimination task. On the one hand, the results suggest that children can infer the implicit meaning of a word directly from its sound. On the other hand, this study shows that nonwords do land in semantic space, such that children can capitalize on their semantic relations with other elements in the lexicon to decide whether a nonword is more likely to denote an entity or an action. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Antioxidative effects of supplementing linseed oil-enriched diets with α-tocopherol, ascorbic acid, selenium, or their combination on carcass and meat quality in broilers

ABSTRACT In a previous study, we examined the synergistic effects of the dietary supranutritional supplementation with vitamin E, vitamin C, and Se on the in vivo antioxidative status of broilers under conditions of dietary oxidative stress induced by feeding a diet high in n-3 PUFA. In this study, we examined the effect of their inclusion on the quality characteristics and oxidative stability of raw or cooked meat, both fresh or after a long-term frozen storage. Four hundred 21-day-old Ross 308 male broilers were allocated to 5 experimental groups fed 5% linseed oil-enriched finisher diets (days 21 to 40): Cont (recommended levels of vitamin E, C, and selenium), +E (200 IU vitamin E/kg feed), +C (250 mg vitamin C/kg feed), +Se (0.2 mg selenium/kg feed), or +ECSe (concentrations as in the sole supplementation, combined). Animal performance and carcass characteristics were monitored at the age of 40 D. Breast meat samples of 12 chickens per group were analysed fresh, fresh after frozen storage, cooked fresh, and cooked after frozen storage (2 × 2 factorial design) for parameters of meat quality (water-holding capacity—WHC, pH, and color) and oxidative stability (concentrations of vitamin E, malondialdehyde—MDA, antioxidant capacity of the water-soluble compounds—ACW, and fatty acid composition). Vitamin E alone (+E) and combined with Se and vitamin C (+ECSe) increased the α-tocopherol concentration in breast muscle, and showed similar protective effects against lipid peroxidation measured as MDA regardless of the frozen storage or cooking. The sole supplementation of vitamin C or selenium showed no effects on the meat quality parameters. In conclusion, the dietary supranutritional inclusion of vitamin E inhibited the lipid peroxidation in fresh, frozen stored, cooked fresh, and frozen stored meat in broilers fed with diets rich in n-3 PUFAs. Even though no clear synergistic effects of the supranutritional supplementation of vitamin C and Se with vitamin E were detected, their dietary inclusion did not negatively affect broilers carcass and meat quality parameters.
Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochrome c oxidase

Experimentally relocating mitochondrial genes to the nucleus for functional expression (allotopic expression) is a challenging process. The high hydrophobicity of mitochondria-encoded proteins seems to be one of the main factors preventing this allotopic expression. We focused on subunit II of cytochrome c oxidase (Cox2) to study which modifications may enable or improve its allotopic expression in yeast. Cox2 can be imported from the cytosol into mitochondria in the presence of the W56R substitution, which decreases the protein hydrophobicity and allows partial respiratory rescue of a cox2-null strain. We show that the inclusion of a positive charge is more favorable than substitutions that only decrease the hydrophobicity. We also searched for other determinants enabling allotopic expression in yeast by examining the COX2 gene in organisms where it was transferred to the nucleus during evolution. We found that naturally occurring variations at within-membrane residues in the legume Glycine max Cox2 could enable yeast COX2 allotopic expression. We also evidence that directing high doses of allotopically synthesized Cox2 to mitochondria seems to be counterproductive because the subunit aggregates at the mitochondrial surface. Our findings are relevant to the design of allotopic expression strategies and contribute to the understanding of gene retention in organellar genomes.
Establishment of BALB/C mouse models of influenza A H1N1 aerosol inhalation

Influenza A (H1N1) is a rapidly spreading acute respiratory illness that remains a worldwide burden on public health. To simulate natural infection routes, BALB/C mice were challenged with the H1N1 virus by aerosol and intranasal instillation routes. We compared the weight change and survival of the mice for 14 consecutive days after infection. The infected mice were euthanized at days 3, 5, 7, and 9 to perform necropsies, lung pathological analyses, viral titers measurement, and lung cytokines examination. The aerosol‐treated mice showed clinical symptoms on day 4, obvious lung lesions on day 5, rapid weight loss on day 7, peak virus replication in the lungs on days 7 to 9, and bronchial epithelial hyperplasia on day 9. However, after intranasal instillation, the mice exhibited clinical signs on day 2, rapid weight loss and obvious lung lesions on day 3, and peak virus replication in the lungs on days 3 to 5; no bronchial epithelial hyperplasia was detected. High levels of proinflammatory cytokines and chemokines were detected in the lungs of infected mice by both two routes. Disease and lung lesion progressions were slower in the mice that inhaled H1N1‐containing aerosols than in those treated by intranasal instillation, and lung lesions were homogeneous in the aerosol group and heterogeneous in the intranasal group. In this study, BALB/C mouse models of H1N1 virus aerosol inhalation were successfully established and compared with mouse models of intranasal inoculation, aerosol mouse models had an infection route and lung pathology characteristics that more closely resembled those observed in humans.
ESR1 mutations in breast cancer

The acquisition of ligand‐independent ESR1 mutations during aromatase inhibitor therapy in metastatic estrogen receptor (ER)‐positive breast cancer is a common mechanism of hormonal therapy resistance. Preclinical and clinical studies have demonstrated that ESR1 mutations can preexist in primary tumors and can be enriched during metastasis. Furthermore, ESR1 mutations express a unique transcriptional profile that favors tumor progression, suggesting that selected ESR1 mutations may influence metastasis. Several groups have used sensitive detection methods using patient liquid biopsies to track ESR1 or truncal somatic mutations to predict treatment outcome and tumor progression, and some of these techniques may eventually be used to guide sequential treatment options in patients. Further development and standardization of mutation tracking in circulating tumor DNA is ongoing. Clinically, patients with ESR1 mutations derive clinical benefit when treated with fulvestrant and CDK4/6‐targeted therapies, but the development of more potent selective ER degraders and/or new targeted biotherapies are needed to overcome the endocrine‐resistant phenotype of ESR1 mutant–bearing tumors. In this review, we discuss the mechanisms of resistance and dissemination of ESR1 mutations as well as the detection methods for ESR1 mutation tracking, newly discovered potential therapeutic targets, and the clinical implications and treatment options for treating patients with ESR1 mutant–bearing tumors.
Platelets Are Critical Key Players in Sepsis

Host defense against infection is based on two crucial mechanisms: the inflammatory response and the activation of coagulation. Platelets are involved in both hemostasis and immune response. These mechanisms work together in a complex and synchronous manner making the contribution of platelets of major importance in sepsis. This is a summary of the pathophysiology of sepsis-induced thrombocytopenia, microvascular consequences, platelet-endothelial cells and platelet–pathogens interactions. The critical role of platelets during sepsis and the therapeutic implications are also reviewed.
Characterization of the Fouling Layer on the Membrane Surface in a Membrane Bioreactor: Evolution of the Foulants’ Composition and Aggregation Ability

In this study, the characteristics of membrane foulants were analyzed with regard to morphology, composition, and aggregation ability during the three stages of transmembrane pressure (TMP) development (fast–slow–fast rise in TMP) in a steady operational membrane bioreactor (MBR). The results obtained show that the fouling layer at the slow TMP-increase stage possessed a higher average roughness (71.27 nm) and increased fractal dimension (2.33), which resulted in a low membrane fouling rate (0.87 kPa/d). A higher extracellular DNA (eDNA) proportion (26.12%) in the extracellular polymeric substances (EPS) resulted in both higher zeta potential (-23.3 mV) and higher hydrophobicity (82.3%) for initial foulants, which induced and increased the protein proportion in the subsequent fouling layer (74.11%). Furthermore, the main composition of the EPS shifted from protein toward polysaccharide dominance in the final fouling layer. The aggregation test confirmed that eDNA was essential for foulant aggregation in the initial fouling layer, whereas ion interaction significantly affected foulant aggregation in the final fouling layer.
Posterior reversible encephalopathy syndrome as a complication of pre-eclampsia in the early postpartum period

We present the case of a 30-year-old woman with posterior reversible encephalopathy syndrome (PRES) as a complication of pre-eclampsia in the early postpartum period. PRES is a rare neurological disorder which causes non-specific neurological symptoms such as headache, seizures and visual disturbances. It generally has a good prognosis, but severe complications can arise. Therefore, early recognition and treatment are paramount. Pre-eclampsia is a multiorgan disease and is associated with both maternal and foetal morbidity and mortality. Neurological symptoms occurring in the postpartum period indicate pre-eclampsia until proven otherwise. This case report was written to stress the attention on this rare complication of pre-eclampsia. When a patient in the postpartum period presents with a combination of seizures, disturbed vision and headache, PRES should always be kept in mind.
Unique cardiovascular risk factors in women

Despite an overall reduction in cardiovascular disease (CVD) mortality in the USA, the rate of coronary heart disease and CVD mortality is on the rise in younger women aged 35 to 54 years. This has been attributed to an increasing prevalence of CVD risk factors, which can portend disparate outcomes in women versus men. Women with diabetes and those who smoke have an excess relative risk of CVD when compared with their male counterparts. In addition to these discrepancies in traditional risk factors, a number of clinical conditions unique to women have been shown to increase CVD risks such as pre-eclampsia, gestational diabetes, polycystic ovary syndrome, early menopause and autoimmune diseases. The majority of these sex-specific risk factors can be identified at an early age, allowing for aggressive risk factor modification through lifestyle changes and, in certain patients, medications. The recently published 2018 American College of Cardiology and American Heart Association (ACC/AHA) hypercholesterolaemia and 2019 ACC/AHA primary prevention guidelines reflect this, citing pre-eclampsia, early menopause and autoimmune diseases as ‘risk enhancers’ that if present may favour initiation of statin therapy in borderline or intermediate risk patients. This comprehensive review addresses both traditional and unique risk factors of CVD in women, as well as sex-specific risk stratification and management options.
An Emergency Seamless Positioning Technique Based on ad hoc UWB Networking Using Robust EKF

In this paper, a new emergency positioning technique is proposed based on ad hoc GNSS/UWB (Global Navigation Satellite System/Ultra-Wideband) network. The main innovations of the program are reflected in two aspects. First of all, a unified coordinate frame for indoor and outdoor environments is constructed dynamically with GNSS/UWB integration. In the outdoor environments, the high accuracy positioning can be achieved with GNSS/UWB equipment. The high-accuracy indoor coordinate is obtained by measuring the range observations between adjacent network nodes and outdoor GNSS/UWB nodes, and the range information of the UWB network is transmitted to the cloud server center. A network adjustment algorithm is proposed to improve the positioning accuracy of the UWB network. Secondly, a UWB indoor location algorithm based on robust EKF (Extended Kalman Filter) is proposed. By analyzing the transfer characteristics of gross error in EKF model, a new robust EKF model is established. The model is constructed based on the statistical characteristics of redundant observation components and prediction residual. The robust equivalent gain matrix is constructed, and the robust positioning solution of UWB is obtained with iteration. The global test is carried out first to further improve the real-time operation efficiency. Finally, a field indoor and outdoor seamless positioning experiment was carried out to verify the effectiveness of the proposed algorithm. The results show that the positioning accuracy of UWB emergency network nodes (anchors) can reach 0.35 m. Based on the network, the positioning accuracy of the tag can reach 0.38 m by applying the improved robust EKF positioning algorithm, which is improved by 20.83% and 73.43% compared with standard EKF and least square method, respectively.
Sex disparities in premature adult mortality in Estonia 1995–2016: a national register-based study

Objectives To quantify sex disparities in cause-specific premature adult mortality in Estonia, to determine the causes of death with the largest differences, to provide insight into related behaviours and to offer some guidance to public health policy-makers based on the results of the study. Design A national register-based study. Setting Estonia. Data Individual records of deaths at ages 20–69 years in 1995–2016 from the Estonian causes of death register; data on tobacco smoking and alcohol consumption in the adult population in 1996–2016 from the biennial postal survey of health behaviour. Main outcome measures Overall and cause-specific age-standardised mortality rates, average annual percentage changes in mortality, and cause-specific men-to-women mortality rate ratios were calculated. In addition, the age-standardised prevalence proportions of tobacco smoking and alcohol consumption and men-to-women prevalence rate ratios were determined. Results Overall premature adult mortality decreased considerably during 1995–2016, but no reduction was observed with respect to the large relative sex disparities. In circulatory disease mortality, the disparities widened significantly over time. Extremely high mortality rate ratios were observed for cancer of the upper aerodigestive tract and for lung cancer. There was a stable, more than fivefold male excess mortality from external causes. A fourfold male disadvantage was evident for alcohol poisoning, mental disorders due to alcohol and alcohol-related degeneration of the nervous system as a group. The prevalence of tobacco smoking and harmful alcohol consumption among men exceeded that among women by factors of two and six, respectively. Conclusions Even though premature adult mortality has markedly decreased over time, there has been no success in diminishing the large sex differences in the mortality patterns, mostly associated with smoking and excessive alcohol consumption, both more prevalent among men. Estonia needs a comprehensive and consistent alcohol policy while maintaining and further developing antitobacco measures.
Proteogenomics: advances in cancer antigen research

Abstract T cells recognize antigen peptides displayed by HLA molecules and specifically eliminate their target cells. Identification of responsible antigens as well as understanding the mechanism by which antigens are produced inside cells are equally crucial for cancer immunology. In this review, we introduce proteogenomics and its applications in cancer antigen research, which leverages mass spectrometry and next-generation sequencing. The approach comprehensively captures immunopeptidome displayed by HLA, revealing new classes of antigens, such as mutation-derived neoantigens, spliced peptides, and non-coding region derived peptides. These antigens may serve as therapeutic targets or biomarkers. Thus, proteogenomics is a promising approach for cancer antigen research and contributes to immunotherapy development.